P



Pulmonary cryptococcosis: a review of biological and clinical aspectsFindra Setianingrum1,2, Riina Rautemaa-Richardson 1,3,4, David W. Denning1,4,5Institutions and Affiliations:1Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK2Parasitology Department, Universitas Indonesia, Jakarta, Indonesia3Mycology Reference Centre Manchester, ECMM Centre of Excellence in Clinical and Laboratory Mycology and Clinical Studies, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK4Department of Infectious Diseases, Wythenshawe Hospital Manchester University NHS Foundation Trust, Manchester, UK5National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UKCorrespondence: Riina.Richardson@manchester.ac.ukKeywords:Cryptococcal pneumonia; cryptococcal infection of lungs; Cryptococcus neoformans; Cryptococcus gattiiAbstractPulmonary cryptococcosis is an important opportunistic invasive mycosis in immunocompromised patients but it is also increasingly seen in immunocompetent patients. The main human pathogens are Cryptococcus neoformans and C. gattii which have a world-wide distribution. In contrast to cryptococcal meningitis, pulmonary cryptococcosis is still underdiagnosed because of limitations in diagnostic tools. It can mimic lung cancer, pulmonary tuberculosis, bacterial pneumonia and other pulmonary mycoses both clinically and radiologically. Pulmonary nodules are the most common radiological feature, but these are not specific to pulmonary cryptococcosis. The sensitivity of culture of respiratory samples for Cryptococcus is poor and a positive result may also reflect colonisation. Cryptococcal antigen (CrAg) with lateral flow device is a fast and sensitive test and widely used on serum and cerebrospinal fluid, but sera from patients with pulmonary cryptococcosis is rarely positive in the absence of disseminated disease. Detection of CrAg from respiratory specimens might assist the diagnosis of pulmonary cryptococcosis but there are very few data. Molecular detection techniques such as multiplex RT PCR could also provide better sensitivity but these still require validation for respiratory specimens. The first line treatment for pulmonary cryptococcosis is fluconazole, or amphotericin B and flucytosine for those with central nervous system involvement. Pulmonary cryptococcosis worsens the prognosis of cryptococcal meningitis. In this review, we summarise the biological aspects of Cryptococcus and provide an update on the diagnosis and management of pulmonary cryptococcosis.231/250 wordsIntroductionPulmonary cryptococcosis is commonly seen in immunocompromised patients and it has become an emerging disease in immunocompetent patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/524738", "ISSN" : "1058-4838", "author" : [ { "dropping-particle" : "", "family" : "Singh", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alexander", "given" : "B. 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We performed a retrospective review of 76 patients diagnosed with tissue-confirmed pulmonary cryptococcosis at the Shanghai Pulmonary Hospital (Shanghai, China) during a 10-yr period (2001-2010). Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic. Approximately 80% of the patients had histories suspicious of environmental fungal exposure. Radiological (computed tomography) findings showed predominantly peripheral findings (85.53%, 65 out of 76 patients) including nodular masses (55.26%, 42 out of 76), pneumonic infiltrates (23.68%, 18 out of 76) and mixed type (21.05%, 16 out of 76). 43.42% (33 out of 76) were initially misdiagnosed, often as cancer by false-positive (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) (28 out of 46 cases). 51 patients received antifungal therapy, 25 patients were clinically observed without treatment. As of December 31, 2010, 71 cases showed total recovery and four cases showed improvement (efficacy rate of 98.68%, 75 out of 76). One HIV-positive case died of cryptococcal meningitis. Incidence of pulmonary cryptococcosis in China may be related to environmental fungal exposures. Most presented as asymptomatic peripheral lung lesions. False-positive (18)FDG-PET examinations often lead to initial clinical misdiagnosis of cancer. Unlike immunocompromised or clinically symptomatic patients, all immunocompetent patients had a good response, either to fluconazole monotherapy or observation, with a tendency for spontaneous remissions in the asymptomatic immunocompetent subjects.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Yuxuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Huiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Xueyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Shanmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rongxuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jinfu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "Jingyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yung", "given" : "Rex C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Respiratory Journal", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1191-1200", "title" : "Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1258/ar.2012.110612", "ISSN" : "1600-0455", "PMID" : "22798384", "abstract" : "BACKGROUND: Discrepancies still exist in the diagnosis of primary pulmonary cryptococcosis in immunocompetent patients.\\n\\nPURPOSE: To describe and evaluate radiological manifestations of pulmonary cryptococcosis in immunocompetent patients.\\n\\nMATERIAL AND METHODS: Twenty-six histopathologically confirmed cases of pulmonary cryptococcosis were analyzed for clinical, pathological, and CT characteristics. Necessary statistical tests for differences in CT presentations and correlation analysis between clinical and CT characteristics were performed.\\n\\nRESULTS: The patients' ages ranged from 24 to 79 years, with 20 men and six women. Eighteen patients were symptomatic, with cough as the most common symptom (n = 14, 53.8%). Nodules (n = 21, 80.8%) were the most common CT findings. Eight cases presented with solitary and nine with multiple nodules, while 13 cases presented with irregular and 19 with ill-defined nodules. The halo sign was demonstrated, encompassing nodules in 14 of the 21 patients. Lesions were mainly localized in the lower lobes of the lungs (n = 15, 57.7%) with peripheral distribution (n = 18, 69.2%). Ground-glass opacities (GGOs) were more easily detected in older patients (66.7%, P <0.01). No significant differences in CT abnormalities were found between male and female patients.\\n\\nCONCLUSION: Primary pulmonary cryptococcosis in immunocompetent patients exhibits certain CT characteristics. The typical presentation includes multiple nodules with the halo sign scattered in the peripheral field in the lower lobes of the bilateral lungs. This could contribute to diagnosis of the disease entity. However, vigilance should be exercised when facing GGOs, with or without nodules, in older patients.", "author" : [ { "dropping-particle" : "", "family" : "Qu", "given" : "Yanjuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Guobing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghimire", "given" : "Prasanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Meiyan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "Heshui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Guifang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Liying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Guanliang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta radiologica (Stockholm, Sweden : 1987)", "id" : "ITEM-5", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "668-74", "title" : "Primary pulmonary cryptococcosis: evaluation of CT characteristics in 26 immunocompetent Chinese patients.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1007/s00408-011-9362-8", "ISSN" : "1432-1750", "PMID" : "22246551", "abstract" : "Pulmonary cryptococcosis typically occurs in immunocompromised patients, but it can also occur in immunocompetent patients. Our objective was to describe the clinical manifestations, diagnosis, and management of primary pulmonary cryptococcosis in immunocompetent patients.", "author" : [ { "dropping-particle" : "", "family" : "Ye", "given" : "Feng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Jia-xing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeng", "given" : "Qing-si", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Guo-qin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Shu-qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Nan-shan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lung", "id" : "ITEM-6", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "339-46", "title" : "Retrospective analysis of 76 immunocompetent patients with primary pulmonary cryptococcosis.", "type" : "article-journal", "volume" : "190" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1007/s12281-009-0006-x", "ISSN" : "19363761", "abstract" : "Pulmonary cryptococcosis occurs primarily in immunocompromised hosts as an isolated infection or as a precursor to disseminated disease. Recent studies indicate that patients with isolated pulmonary cryptococcosis may be asymptomatic or, if symptomatic, will often have very low serum cryptococcal antigen, distinguishing them from patients with disseminated disease. Amphotericin B plus fl ucytosine is the initial treatment for disseminated cryptococcosis or severe symptomatic pulmonary cryptococcosis, followed by fl uconazole once symptoms have improved. Fluconazole is recommended for asymptomatic or mild disease. Targeted immunotherapies and vaccines are being studied and offer exciting new prevention and treatment strategies.", "author" : [ { "dropping-particle" : "", "family" : "Willenburg", "given" : "Kara S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadley", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Fungal Infection Reports", "id" : "ITEM-7", "issue" : "1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "40-44", "title" : "Pulmonary cryptococcosis: A rare but emerging disease", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^1\u20137", "plainTextFormattedCitation" : "1\u20137", "previouslyFormattedCitation" : "^1\u20137" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1–7 A study from Uganda reported that 11% of hospitalised HIV patients had pulmonary cryptococcosis as a secondary infection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/QAI.0b013e3181ce6b19.The", "author" : [ { "dropping-particle" : "", "family" : "Yoo", "given" : "Samuel D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Worodria", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Med", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cattamanchi", "given" : "Adithya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Den", "family" : "Boon", "given" : "Saskia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyeyune", "given" : "Rachel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kisembo", "given" : "Harriet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Laurence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Acquir Immune Defic Syndr", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "269-274", "title" : "The prevalence and clinical course of HIV-associated pulmonary cryptococcosis in Uganda", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸", "plainTextFormattedCitation" : "8", "previouslyFormattedCitation" : "⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }8 Recent research from Thailand noted that 13% of HIV patients with pneumonia had cryptococcal antigen present in their serum, although a third of this population did not have cryptococcal meningitis or a history of it.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/cid/cir903", "ISBN" : "1058-4838", "ISSN" : "10584838", "PMID" : "22198791", "abstract" : "BACKGROUND: Cryptococcal meningitis (CM) is a major cause of death among HIV-infected patients. Cryptococcal antigenemia (CrAg+) in the absence of CM can represent early-stage cryptococcosis during which antifungal treatment might improve outcomes. However, patients without meningitis are rarely tested for cryptococcal infection. We evaluated Cryptococcus species as a cause of acute respiratory infection in hospitalized patients in Thailand and evaluated clinical characteristics associated with CrAg+.\\n\\nMETHODS: We tested banked serum samples from 704 human immunodeficiency virus (HIV)-infected and 730 HIV-uninfected patients hospitalized with acute respiratory infection from 2004 through 2009 in 2 rural provinces in Thailand for the presence of CrAg+. Retrospective chart reviews were conducted for CrAg+ patients to distinguish meningeal and nonmeningeal cryptococcosis and to identify clinical characteristics associated with CrAg+ in patients with and without evidence of CM.\\n\\nRESULTS: CrAg+ was found in 92 HIV-infected patients (13.1%); only tuberculosis (19.3%) and rhinovirus (16.5%) were identified more frequently. No HIV-uninfected patients were CrAg+. Of 70 CrAg+ patients with medical charts available, 37 (52.9%) had no evidence of past or existing CM at hospitalization; 30 of those patients (42.9% of all CrAg+) had neither past nor existing CM, nor any alternate etiology of infection identified. Dyspnea was more frequent among CrAg+ patients without CM than among CrAg- patients (P = .0002).\\n\\nCONCLUSIONS: Cryptococcus species were the most common pathogens detected in HIV-infected patients hospitalized with acute respiratory infection in Thailand. Few clinical differences were found between antigenemic and nonantigenemic HIV-infected patients. Health care providers in Thailand should evaluate HIV-infected patients hospitalized with acute respiratory infection for cryptococcal antigenemia, even in the absence of meningitis.", "author" : [ { "dropping-particle" : "", "family" : "Harris", "given" : "Julie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindsley", "given" : "Mark D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henchaichon", "given" : "Sununta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poonwan", "given" : "Natteewan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naorat", "given" : "Sathapana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prapasiri", "given" : "Prabda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chantra", "given" : "Somrak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruamcharoen", "given" : "Fuangrak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Loretta S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chittaganpitch", "given" : "Malinee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehta", "given" : "Nanthawan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peruski", "given" : "Leonard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maloney", "given" : "Susan A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Benjamin J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baggett", "given" : "Henry C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Infectious Diseases", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "43-50", "title" : "High prevalence of cryptococcal infection among HIV-infected patients hospitalized with pneumonia in Thailand", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹", "plainTextFormattedCitation" : "9", "previouslyFormattedCitation" : "⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }9 It is probable that the respiratory infections in these patients are cryptococcal. A retrospective review from China revealed that 60% of pulmonary cryptococcosis cases were diagnosed in immunocompetent non-HIV patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.21037/jtd.2016.10.36", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Kaixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Haibo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Ruixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qichang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qu", "given" : "Jieming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Thoracic Disease", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "2813-2821", "title" : "Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "¹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10 Pulmonary cryptococcosis may also disseminate and lead to fatal complications.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.5152/dir.2013.13049", "author" : [ { "dropping-particle" : "", "family" : "Suwatanapongched", "given" : "Thitiporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sangsatra", "given" : "Wasinan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boonsarngsuk", "given" : "Viboon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Incharoen", "given" : "Pimpin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diagnostic Interv Radiol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "438-446", "title" : "Clinical and radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients and their outcomes after treatment", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1159/000357715", "ISBN" : "0025-7931", "ISSN" : "14230356", "PMID" : "24525662", "abstract" : "Cryptococcosis causes significant morbidity and mortality in the world. Pulmonary cryptococcosis is a kind of subacute or chronic pulmonary fungal disease. We present a case of pulmonary cryptococcosis with a trachea wall invasion-like malignant tumor in an immunocompetent patient and a literature review. The 44-year-old man, a nonsmoker, suffered from mild dyspnea and white sputum with intermittent blood streaks. A computed tomography (CT) scan of his chest showed two possibly malignant lesions in the right hilum and upper-right field of his lung, which have higher uptake values of fluorodeoxyglucose on positron emission tomography (PET)/CT. Lung biopsy pathology showed scattered fungal spores and positive periodic acid-Schiff (PAS) staining. The immune status and blood tumor markers were all normal in this patient. The titer of Cryptococcus antigen latex agglutination test was 1:1,280. Under fiberoptic bronchoscopy, a prominent new mass on the right wall of the trachea blocked most of the right main bronchus. To reduce the symptoms of airway obstruction, treatment by bronchoscopy, i.e. ablation and endotracheal stent, was used. As his symptoms were aggravated by the use of itraconazole, amphotericin B liposome was used as antifungal treatment. All these methods led to a better prognosis. We conclude that pulmonary cryptococcosis may mimic lung neoplasms radiologically and bronchoscopically, even in immunocompetent patients.", "author" : [ { "dropping-particle" : "", "family" : "Sun", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shao", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bai", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Respiration", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "324-328", "title" : "Pulmonary cryptococcosis with trachea wall invasion in an immunocompetent patient: a case report and literature review", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1186/s12879-017-2450-5", "ISSN" : "1471-2334", "PMID" : "28532447", "abstract" : "Background: Disseminated cryptococcosis is a rare and fatal disease, and limited data exist regarding it in children. This study aimed to investigate the clinical characteristics of disseminated cryptococcosis in previously healthy children in China. Methods: Hospitalized patients with disseminated cryptococcosis were enrolled during January 1996 to December 2015 in Beijing Children\u2019s Hospital, Capital Medical University, China. Data on clinical manifestations, laboratory tests, treatment, and prognosis were evaluated. Results: A total of 52 pediatric patients with no underlying disease were enrolled, including 38 boys and 14 girls. Only 10 cases had a history of exposure to pigeon droppings. Fever, cough, and hepatomegaly were 3 main manifestations of disseminated cryptococcosis. However, headache was more common in patients with central nervous system (CNS) invasion than in patients with non-CNS invasion (P\u00a0<\u00a00.05). Lung (96.2%, 50/52) was the most commonly invaded organ, but only 9.6% (5/52) of patients had respiratory signs. The most common findings on chest imaging were hilar or mediastinal lymphadenopathy (46.8%, 22/47), and nodules (44.7%, 21/47), including small nodules in a scattered distribution (57.1%, 12/21) or miliary distribution (42.9%, 9/25), especially localized in subpleural area. Subsequent invasion occurred in the CNS, abdomen lymph nodes, liver, spleen, peripheral lymph nodes, and skin. In all patients, 42.3% (22/52) and 51.9% (27/52) had elevated eosinophils or IgE, respectively. The positive rate of serum cryptococcal antigen was higher, especially in patients with CNS invasion (approximately 83.3%), than with other primary methods used for pathogen detection, including cerebrospinal fluid (CSF) cryptococcal antigen, cultures of blood, bone marrow, or CSF, and CSF ink staining. The overall mortality rate of pediatric patients in our study was 11.5% (6/52). Some cases had long-term sequela, including hydrocephalus, cirrhosis, or blindness. Conclusions: Disseminated cryptococcosis can occur in previously healthy or immunocompetent children in China. Lung and CNS were most commonly invaded by this disease. Furthermore, most cases usually showed no obvious or specific symptoms or signs, and therefore pediatricians should pay more careful attention to identify this disease.", "author" : [ { "dropping-particle" : "", "family" : "Gao", "given" : "Li-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiao", "given" : "An-Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Xi-Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Shun-Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ma", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Gang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Ju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bao-Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Kun-Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Infectious Diseases", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "359", "publisher" : "BMC Infectious Diseases", "title" : "Clinical characteristics of disseminated cryptococcosis in previously healthy children in China", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^11\u201313", "plainTextFormattedCitation" : "11\u201313", "previouslyFormattedCitation" : "^11\u201313" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11–13 A previous study reported that 67% of pulmonary cryptococcosis in immunocompetent patients disseminated into the central nervous system causing cryptococcal meningitis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.5152/dir.2013.13049", "author" : [ { "dropping-particle" : "", "family" : "Suwatanapongched", "given" : "Thitiporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sangsatra", "given" : "Wasinan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boonsarngsuk", "given" : "Viboon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Incharoen", "given" : "Pimpin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diagnostic Interv Radiol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "438-446", "title" : "Clinical and radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients and their outcomes after treatment", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹", "plainTextFormattedCitation" : "11", "previouslyFormattedCitation" : "¹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11 Patients with pulmonary cryptococcosis concomitantly with cryptococcal meningitis showed inadequate treatment response and poor clinical outcome compare to cryptococcal meningitis alone.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11046-018-0263-8", "ISSN" : "1573-0832", "author" : [ { "dropping-particle" : "", "family" : "Cao", "given" : "Wenhao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jian", "given" : "Cui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Huojun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Shuyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycopathologia", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2018" ] ] }, "publisher" : "Springer Netherlands", "title" : "Comparison of Clinical Features and Prognostic Factors of Cryptococcal Meningitis Caused by Cryptococcus neoformans in Patients With and Without Pulmonary Nodules", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "¹⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14 The spectrum of fungal diseases seen in critically ill patients and immunocompetent patients is broadening and the role of pulmonary cryptococcosis may be increasingly important.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1513/pats.200906-049AL", "ISSN" : "1943-5665", "PMID" : "20463243", "abstract" : "Fungal lung infections are being diagnosed with increasing frequency. This is related to the increased numbers of immune-compromised and other susceptible patient groups. This article will focus on the evolving epidemiology of fungal lung infections and clinical manifestations that should prompt the clinician to consider the possibility of fungal lung infection. In addition, current approaches for the diagnosis of these infection are also reviewed. Heightened awareness of fungal lung infection, and appropriate use of the available diagnostic modalities, will permit appropriate treatment of these important clinical infections in immune-compromised individuals.", "author" : [ { "dropping-particle" : "", "family" : "Limper", "given" : "Andrew H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the American Thoracic Society", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "163-168", "title" : "The changing spectrum of fungal infections in pulmonary and critical care practice: clinical approach to diagnosis.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s11684-017-0601-0", "ISBN" : "2095-0217", "ISSN" : "20950225", "PMID" : "29380297", "abstract" : "With the increasing number of immunocompromised hosts, the epidemiological characteristics of fungal infections have undergone enormous changes worldwide, including in China. In this paper, we reviewed the existing data on mycosis across China to summarize available epidemiological profiles. We found that the general incidence of superficial fungal infections in China has been stable, but the incidence of tinea capitis has decreased and the transmission route has changed. By contrast, the overall incidence of invasive fungal infections has continued to rise. The occurrence of candidemia caused by Candida species other than C. albicans and including some uncommon Candida species has increased recently in China. Infections caused by Aspergillus have also propagated in recent years, particularly with the emergence of azole-resistant Aspergillus fumigatus. An increasing trend of cryptococcosis has been noted in China, with Cryptococcus neoformans var. grubii ST 5 genotype isolates as the predominant pathogen. Retrospective studies have suggested that the epidemiological characteristics of Pneumocystis pneumonia in China may be similar to those in other developing countries. Endemic fungal infections, such as sporotrichosis in Northeastern China, must arouse research, diagnostic, and treatment vigilance. Currently, the epidemiological data on mycosis in China are variable and fragmentary. Thus, a nationwide epidemiological research on fungal infections in China is an important need for improving the country's health.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Yali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lei", "given" : "Wenzhi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Du", "given" : "Lin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jingjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lei", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xiong", "given" : "Lin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Langqi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers of Medicine", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "58-75", "title" : "Epidemiology of fungal infections in China", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1007/s11046-011-9398-6", "ISBN" : "0301-486X", "ISSN" : "0301486X", "PMID" : "21509517", "abstract" : "This epidemiological survey was a retrospective study on three nodes during the past three decades on fungal infections representing the China, including Taiwan. Owing to rare publications reporting on dynamic epidemiological trends in the pathogen epidemiology in China, we surveyed the isolation rates and pathogenic fungi from 8 representative districts in China using uniform identification with uniform methodology. The pathogenic fungi isolation rates and species obtained from 1986 (n=9,096), 1996 (n=19,009), and 2006 (n=33,022) suggested that Trichophyton rubrum was the commonest organism cultured in 1980s (45.4%) and 1990s (34.5%), but Candida albicans increased significantly and reaching to its peak (26.9%) in 2006s' survey, and has become the most common isolate of fungal infections in China currently. In addition, Candida glabrata became the most common non-albicans species of Candida in 2006s' survey. At the same time, the incidence of molds also gradually increased. According to comparative analysis of the results of these three surveys, we found apparent differences in the isolation rates of different pathogenic fungi and the forefront 10 species in China varied significantly, and the dermatophytes decreased markedly, while yeasts, especially the Candida species and the molds, increased gradually during the past three decades. Less dermatophytic infections may suggest better access to healthcare or increase in Candida species indicated higher incidence of hospital acquired infections.", "author" : [ { "dropping-particle" : "", "family" : "Wu", "given" : "S. X.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guo", "given" : "N. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "X. F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "W. Q.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Q. Q.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "C. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "R. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulmer", "given" : "G. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "D. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xi", "given" : "L. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Y. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ran", "given" : "Y. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuan", "given" : "Y. Z.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycopathologia", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "387-393", "title" : "Human pathogenic fungi in China-emerging trends from ongoing national survey for 1986, 1996, and 2006", "type" : "article-journal", "volume" : "171" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Chau", "given" : "Tran T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mai", "given" : "Nguyen H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phu", "given" : "Nguyen H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nghia", "given" : "Ho D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Chuong", "given" : "Ly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinh", "given" : "Dinh X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duong", "given" : "Van A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diep", "given" : "Pham T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hien", "given" : "Tran T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lalloo", "given" : "David G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farrar", "given" : "Jeremy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Jeremy N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Infect Dis", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "2-9", "title" : "A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam - high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^15\u201318", "plainTextFormattedCitation" : "15\u201318", "previouslyFormattedCitation" : "^15\u201318" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }15–18 We elected to review this topic, with a focus on pulmonary cryptococcosis.MethodsA literature search of all published articles in the English language within the last 50 years (1968-2018) was conducted using the PubMed database. Key search terms included ‘pulmonary cryptococcosis’, ‘cryptococcal pneumonia’, ‘cryptococcal infection of lungs’, ‘Cryptococcus neoformans’ and ‘Cryptococcus gattii’. Additional references were obtained by a thorough manual scanning of the bibliographies listed in the selected articles. All relevant articles (n=249) have been included into this review. CryptococcusCryptococcus is a genus of encapsulated yeasts belonging to the Basidiomycota phylum and is widely distributed around the world.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/EC.00039-10", "ISBN" : "1535-9786 (Electronic)\\r1535-9786 (Linking)", "ISSN" : "15359778", "PMID" : "20382758", "abstract" : "Opportunistic pathogens have become of increasing medical importance over the last decade due to the AIDS pandemic. Not only is cryptococcosis the fourth-most-common fatal infectious disease in sub-Saharan Africa, but also Cryptococcus is an emerging pathogen of immunocompetent individuals. The interaction between Cryptococcus and the host's immune system is a major determinant for the outcome of disease. Despite initial infection in early childhood with Cryptococcus neoformans and frequent exposure to C. neoformans within the environment, immunocompetent individuals are generally able to contain the fungus or maintain the yeast in a latent state. However, immune deficiencies lead to disseminating infections that are uniformly fatal without rapid clinical intervention. This review will discuss the innate and adaptive immune responses to Cryptococcus and cryptococcal strategies to evade the host's defense mechanisms. It will also address the importance of these strategies in pathogenesis and the potential of immunotherapy in cryptococcosis treatment.", "author" : [ { "dropping-particle" : "", "family" : "Voelz", "given" : "Kerstin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "Robin C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "835-846", "title" : "Cryptococcal interactions with the host immune system", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/nrmicro.2015.6", "ISSN" : "1740-1526", "PMID" : "26685750", "abstract" : "Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development.", "author" : [ { "dropping-particle" : "", "family" : "May", "given" : "Robin C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stone", "given" : "Neil R.H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiesner", "given" : "Darin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bicanic", "given" : "Tihana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Reviews Microbiology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "106-117", "publisher" : "Nature Publishing Group", "title" : "<i> Cryptococcus </i> : from environmental saprophyte to global pathogen", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaneda", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wanke", "given" : "Bodo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lazera", "given" : "Marcia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "237-260", "publisher" : "ASM Press", "title" : "Enviromental niches for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^19\u201322", "plainTextFormattedCitation" : "19\u201322", "previouslyFormattedCitation" : "^19\u201322" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19–22 The most common environmental niches of Cryptococcus are lignaceous environments such as hollows in trees, flowering plants and bird faeces.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/1040841X.2011.606426", "ISBN" : "1549-7828 (Electronic)\\r1040-841X (Linking)", "ISSN" : "1549-7828", "PMID" : "22133016", "abstract" : "An overview of work done to-date in India on environmental prevalence, population structure, seasonal variations and antifungal susceptibility of Cryptococcus neoformans and Cryptococcus gattii is presented. The primary ecologic niche of both pathogens is decayed wood in trunk hollows of a wide spectrum of host trees, representing 18 species. Overall, C. neoformans showed a higher environmental prevalence than that of C. gattii which was not found in the avian habitats. Apart from their arboreal habitat, both species were demonstrated in soil and air in close vicinity of their tree hosts. In addition, C. neoformans showed a strong association with desiccated avian excreta. An overwhelming number of C. neoformans strains belonged to genotype AFLP1/VNI, var. grubii (serotype A), whereas C. gattii strains were genotype AFLP4/VGI, serotype B. All of the environmental strains of C. neoformans and C. gattii were mating type \u03b1 (MAT\u03b1). Contrary to the Australian experience, Eucalyptus trees were among the epidemiologically least important and, therefore, the hypothesis of global spread of C. gattii through Australian export of infected Eucalyptus seeds is rebutted. Reference is made to long-term colonization of an abandoned, old timber beam of sal wood (Shorea robusta) by a melanin positive (Mel(+)) variant of Cryptococcus laurentii that was pathogenic to laboratory mice.", "author" : [ { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Anuradha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhandhawa", "given" : "Harbans S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "Anupam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meis", "given" : "Jacques F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical reviews in microbiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1-16", "title" : "Environmental prevalence of <i> Cryptococcus neoformans</i> and <i>Cryptococcus gattii </i> in India: an update.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.ppat.1004285", "ISSN" : "1553-7374", "PMID" : "25144534", "author" : [ { "dropping-particle" : "", "family" : "Springer", "given" : "Deborah J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Billmyre", "given" : "R. Blake", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filler", "given" : "Elan E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voelz", "given" : "Kerstin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pursall", "given" : "Rhiannon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mieczkowski", "given" : "Piotr A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "Robert A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dietrich", "given" : "Fred S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "Robin C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filler", "given" : "Scott G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Pathogens", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "e1004285", "title" : "<i>Cryptococcus gattii </i> VGIII isolates causing infections in HIV/AIDS patients in southern California: identification of the local environmental source as arboreal", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1111/j.1567-1364.2007.00218.x", "ISBN" : "1567-1356", "ISSN" : "15671356", "PMID" : "17346260", "abstract" : "Here we report on the results of a survey of the yeast populations occurring on submerged leaves (alder, eucalyptus and oak) in a natural mountain stream, during different phases of their decomposition and through two consecutive years. Leaf litter mass loss, total yeast counts, Shannon-Weiner index (H'), yeast community structure and physiologic abilities were analyzed to evaluate the dynamics of yeast communities during decay. Seventy-two yeast taxa were recorded, and in all litter types, species of basidiomycetous affinity predominated over ascomycetous ones. Discriminant analysis of presence/absence data (yeast species) showed significant differences both among substrate types (P<0.0026) and with decomposition time (P<0.0001). Carbon and nitrogen source utilization by yeast strains also varied with the substrate (P<0.0001) and decomposition time (P<0.0001). Further conclusions were that: (1) all litter types have in common ubiquitous yeast species, such as Cryptococcus albidus, Debaryomyces hansenii and Rhodotorula glutinis, among the common 20 yeast species; (2) only a few species were dominant, and most species were rare, being recorded once or twice throughout decomposition; and (3) the order of yeast appearance, and their substrate assimilation patterns, strongly suggest a succession phenomenon. Finally, explanations for the distribution patterns and variations in yeast communities are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Sampaio", "given" : "Ana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampaio", "given" : "Jos\u00e9 Paulo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Le\u00e3o", "given" : "Cec\u00edlia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "595-603", "title" : "Dynamics of yeast populations recovered from decaying leaves in a nonpolluted stream: A 2-year study on the effects of leaf litter type and decomposition time", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^23\u201325", "plainTextFormattedCitation" : "23\u201325", "previouslyFormattedCitation" : "^23\u201325" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }23–25 In addition, Cryptococcus has been found in arctic climates and under conditions of extremes of pH (Table 1). ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "/S0036-46652006000200003", "ISBN" : "0036-4665", "ISSN" : "00364665", "PMID" : "16699626", "abstract" : "Cryptococcosis has been a significant cause of morbidity and mortality in patients with Aids. Many reservoirs of the agent Cryptococcus neoformans have been reported, but the ecology of this yeast must be elucidated in order to establish surveillance programs and to prevent infections. The objective of this study was to evaluate the presence of C. neoformans in Rio de Janeiro City, RJ, Brazil. Ten churches were selected for sampling and detection of the yeast collecting pigeon dropping, air samples from church towers and neighboring areas during one year. The data demonstrated that C. neoformans has been present in every church selected and was present in 37.8% of 219 pigeon dropping samples. As well as, the yeast was isolated from soil, insects, eggs, pigeon nests and feathers. Fifteen air samples (4.9%) were positive. The growth on C.G.B. medium showed that all strains belonged to C. neoformans var. neoformans, with 98.8% of the strains belonging to serotype A.", "author" : [ { "dropping-particle" : "", "family" : "Baroni", "given" : "Francisco De Assis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paula", "given" : "Claudete Rodrigues", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "\u00c9riques Gon\u00e7alves", "non-dropping-particle" : "Da", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viani", "given" : "Fl\u00e1vio Cesar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "Irma N G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira", "given" : "Maria Tereza Barreto", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gambale", "given" : "Walderez", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "71-75", "title" : "<i> Cryptococcus neoformans</i> strains isolated from church towers in Rio de Janeiro City, RJ, Brazil", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Ergin", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ilkit", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaftanog", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycoses", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "431-434", "title" : "Detection of <i>Cryptococcus neoformans var.grubii</i> in honeybee (<i>Apis mellifera</i>) colonies", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1111/j.1574-6941.2008.00514.x", "ISBN" : "0168-6496 (Print)\\r0168-6496 (Linking)", "ISSN" : "01686496", "PMID" : "18537834", "abstract" : "The Rio Agrio and Lake Caviahue system (RAC), in Northwestern Patagonia, is a natural acidic environment. The aims of this study were to characterize the yeast community and to provide the first ecological assessment of yeast diversity of this extreme aquatic environment. Yeast occurrence and diversity were studied at seven sites where the water pH varied between 1.8 and 6.7. Yeast CFU counts in the river ranged from 30 to 1200 CFU L(-1), but in the Lake the values were lower (30-60 CFU L(-1)). A total of 25 different yeast species were found, 11 of which belonged to undescribed taxa. Among these was an unusual strongly acidophilic Cryptococcus species. The RAC yeast community resembles that of acidic aquatic environments resulting from anthropic activities such as the S\u00e3o Domingos mines in Portugal and the Rio Tinto in Spain, respectively. The isolated yeast species were organized into different grades of adaptation to the RAC aquatic system. Based on the proposed grades, Rhodotorula mucilaginosa, Rhodosporidium toruloides and two novel Cryptococcus species were the most adapted species. These Cryptococcus species are apparently specialists of acidic aquatic environments, and might bear physiological features that possibly account for their ability to thrive in such extreme environments.", "author" : [ { "dropping-particle" : "", "family" : "Russo", "given" : "Gabriel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Libkind", "given" : "Diego", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampaio", "given" : "Jos\u00e9 P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broock", "given" : "Maria R.", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Microbiology Ecology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "415-424", "title" : "Yeast diversity in the acidic Rio Agrio-Lake Caviahue volcanic environment (Patagonia, Argentina)", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1111/j.1574-6941.2006.00239.x", "ISBN" : "0168-6496", "ISSN" : "01686496", "PMID" : "17313582", "abstract" : "The occurrence of culturable yeasts in glacial meltwater from the Fr\u00edas, Casta\u00f1o Overo and R\u00edo Manso glaciers, located on Mount Tronador in the Nahuel Huapi National Park (Northwestern Patagonia, Argentina) is presented. Subsurface water samples were filtered for colony counting and yeast isolation. The total yeast count ranged between 6 and 360 CFU L(-1). Physiologic and molecular methods were employed to identify 86 yeast isolates. In agreement with yeast diversity data from studies for Antarctic and Alpine glaciers, the genera Cryptococcus, Leucosporidiella, Dioszegia, Rhodotorula, Rhodosporidium, Mrakia, Sporobolomyces, Udeniomyces and Candida were found. Cryptococcus and Leucosporidiella accounted for 50% and 20% of the total number of strains, respectively. Among 21 identified yeast species, Cryptococcus sp. 1 and Leucosporidiella fragaria were the most frequent. The typically psychrophilic Mrakia yeast strain and three new yeast species, yet to be described, were also isolated. All yeast strains were able to grow at 5, 10, and 15 degrees C. Among yeast strains expressing extracellular enzymatic activity, higher proteolytic and lipolytic activities were obtained at 4 degrees C than at 20 degrees C.", "author" : [ { "dropping-particle" : "", "family" : "Garc\u00eda", "given" : "Virginia", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brizzio", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Libkind", "given" : "Diego", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buzzini", "given" : "Pietro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broock", "given" : "Mar\u00eda", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Microbiology Ecology", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "331-341", "title" : "Biodiversity of cold-adapted yeasts from glacial meltwater rivers in Patagonia, Argentina", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaneda", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wanke", "given" : "Bodo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lazera", "given" : "Marcia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "237-260", "publisher" : "ASM Press", "title" : "Enviromental niches for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{21,22,26\u201329}", "plainTextFormattedCitation" : "21,22,26\u201329", "previouslyFormattedCitation" : "^{21,22,26\u201329}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21,22,26–29 Some Cryptococcus species are pathogenic to humans and some animals and typically cause meningitis and infections in the airways. The portal of entry is normally in the respiratory tract.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrmicro2522", "ISBN" : "1740-1534 (Electronic)\\r1740-1526 (Linking)", "ISSN" : "1740-1526", "PMID" : "21326274", "abstract" : "Cryptococcus neoformans is generally considered to be an opportunistic fungal pathogen because of its tendency to infect immunocompromised individuals, particularly those infected with HIV. However, this view has been challenged by the recent discovery of specialized interactions between the fungus and its mammalian hosts, and by the emergence of the related species Cryptococcus gattii as a primary pathogen of immunocompetent populations. In this Review, we highlight features of cryptococcal pathogens that reveal their adaptation to the mammalian environment. These features include not only remarkably sophisticated interactions with phagocytic cells to promote intracellular survival, dissemination to the central nervous system and escape, but also surprising morphological and genomic adaptations such as the formation of polyploid giant cells in the lung.", "author" : [ { "dropping-particle" : "", "family" : "Kronstad", "given" : "J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Attarian", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cadieux", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Souza", "given" : "C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffiths", "given" : "E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geddes", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jung", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kretschmer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saikia", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Rev Microbiol", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "193-203", "publisher" : "Nature Publishing Group", "title" : "Expanding fungal pathogenesis: <i>Cryptococcus</i> breaks out of the opportunistic box", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁰", "plainTextFormattedCitation" : "30", "previouslyFormattedCitation" : "³⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }30 Cryptococcus infections have been reported in a broad range of animals, including cats, dogs, horses, birds and koala bears.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Malik", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krockenberger", "given" : "Mark B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brien", "given" : "Carolyn R O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carter", "given" : "D E E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canfield", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "489-502", "publisher" : "ASM Press", "title" : "Veterinary insights into cryptococcosis caused by <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³¹", "plainTextFormattedCitation" : "31", "previouslyFormattedCitation" : "³¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31 Cryptococcal rhinosinusitis in dogs and cats, lower respiratory tract cryptococcosis in koala and cryptococcal mastitis in cattle are examples of cryptococcosis in animals. In contrast, many birds are carriers of Cryptococcus and contribute to its spread but rarely become infected themselves.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaneda", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wanke", "given" : "Bodo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lazera", "given" : "Marcia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "237-260", "publisher" : "ASM Press", "title" : "Enviromental niches for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1146/annurev.micro.60.080805.142102", "ISBN" : "0066-4227 (Print)\\n0066-4227 (Linking)", "ISSN" : "0066-4227", "PMID" : "16704346", "abstract" : "Cryptococcus neoformans is a major cause of fungal meningoencephalitis in immunocompromised patients. Despite recent advances in the genetics and molecular biology of C. neoformans, and improved techniques for molecular epidemiology, aspects of the ecology, population structure, and mode of reproduction of this environmental pathogen remain to be established. Application of recent insights into the life cycle of C. neoformans and its different ways of engaging in sexual reproduction under laboratory conditions has just begun to affect research on the ecology and epidemiology of this human pathogenic fungus. The melding of these disparate disciplines should yield rich dividends in our understanding of the evolution of microbial pathogens, providing insights relevant to diagnosis, treatment, and prevention", "author" : [ { "dropping-particle" : "", "family" : "Lin", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annu.Rev.Microbiol.", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "69-105", "title" : "The biology of the <i> Cryptococcus neoformans</i> species complex", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Sethi", "given" : "KK", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randhawa", "given" : "HS", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Infectious Diseases", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "1968" ] ] }, "page" : "135-138", "title" : "Survival of <i> Cryptococcus neoformans</i> in the gastrointestinal tract of pigeons following ingestion of the organism", "type" : "article-journal", "volume" : "118" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^21,32,33", "plainTextFormattedCitation" : "21,32,33", "previouslyFormattedCitation" : "^21,32,33" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21,32,33 The genus Cryptococcus consists of more than 70 species which exhibit significant biodiversity between them.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/B978-0-444-52149-1.00138-5", "ISBN" : "9780444521491", "abstract" : "This chapter discusses the genus Cryptococcus. In the determination of the asexual reproduction it is seen that cells are spheroidal, ovoid, ellipsoidal, or elongate. A polysaccharide capsule is present in most species. Reproduction is by multilateral or polar, enteroblastic budding; pseudohyphae or true hyphae may develop. In species with true hyphae, septa have dolipores with or without parenthesomes. In the sexual reproduction it is found that some species are anamorphic states of teleomorphic genera in the Cystofilobasidiales, Filobasidiales, and Tremellales. The chapter also discusses physiology/biochemistry and phylogenetic placement of the genus. The type species taken is Cryptococcus neoformans. In the systematic discussion of the species phylogenetic placement, growth on malt extract, soytone, yeast extract (MYP) agar, growth in YM broth, Dalmau plate culture on corn meal agar, gene sequence accession numbers, type strain, origin of the strains studied, and systematics are determined. \u00a9 2011 Copyright \u00a9 2011 Elsevier B.V. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Fonseca", "given" : "\u00c1lvaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fell", "given" : "Jack W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Yeasts", "id" : "ITEM-1", "issue" : "1901", "issued" : { "date-parts" : [ [ "2011" ] ] }, "number-of-pages" : "1661-1737", "publisher" : "Elsevier B.V.", "title" : "Cryptococcus Vuillemin (1901)", "type" : "book", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kwon Chung", "given" : "KJ", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickes", "given" : "BL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fell", "given" : "JW", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "3-15", "publisher" : "ASM Press", "title" : "Systematics of the genus <i>Cryptococcus</i> and its type species <i>C. neoformans</i>.", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1128/mBio.00311-15", "ISSN" : "2150-7511", "abstract" : "Cryptococcus neoformans is a human opportunistic fungal pathogen causing severe disseminated meningoencephalitis, mostly in patients with cellular immune defects. This species is divided into three serotypes: A, D, and the AD hybrid. Our objectives were to compare population structures of serotype A and D clinical isolates and to assess whether infections with AD hybrids differ from infections with the other serotypes. For this purpose, we analyzed 483 isolates and the corresponding clinical data from 234 patients enrolled during the CryptoA/D study or the nationwide survey on cryptococcosis in France. Isolates were characterized in terms of ploidy, serotype, mating type, and genotype, utilizing flow cytometry, serotype- and mating type-specific PCR amplifications, and multilocus sequence typing (MLST) methods. Our results suggest that C. neoformans serotypes A and D have different routes of multiplication (primarily clonal expansion versus recombination events for serotype A and serotype D, respectively) and important genomic differences. Cryptococcosis includes a high proportion of proven or probable infections (21.5%) due to a mixture of genotypes, serotypes, and/or ploidies. Multivariate analysis showed that parameters independently associated with failure to achieve cerebrospinal fluid (CSF) sterilization by week 2 were a high serum antigen titer, the lack of flucytosine during induction therapy, and the occurrence of mixed infection, while infections caused by AD hybrids were more likely to be associated with CSF sterilization. Our study provides additional evidence for the possible speciation of C. neoformans var. neoformans and grubii and highlights the importance of careful characterization of causative isolates. IMPORTANCE: Cryptococcus neoformans is an environmental fungus causing severe disease, estimated to be responsible for 600,000 deaths per year worldwide. This species is divided into serotypes A and D and an AD hybrid, and these could be considered two different species and an interspecies hybrid. The objectives of our study were to compare population structures of serotype A and serotype D and to assess whether infections with AD hybrids differ from infections with serotype A or D isolates in terms of clinical presentation and outcome. For this purpose, we used clinical data and strains from patients diagnosed with cryptococcosis in France. Our results suggest that, according to the serotype, isolates have different routes of multipli\u2026", "author" : [ { "dropping-particle" : "", "family" : "Desnos-Ollivier", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patel", "given" : "Sweta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raoux-Barbot", "given" : "Doroth\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Fran\u00e7oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "mBio", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "e00311-15", "title" : "Cryptococcosis serotypes impact outcome and provide evidence of <i> Cryptococcus neoformans</i> speciation", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^34\u201336", "plainTextFormattedCitation" : "34\u201336", "previouslyFormattedCitation" : "^34\u201336" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }34–36 The two main pathogenic cryptococcal species for humans and animals are C. neoformans and C. gattii that belong to the C. neoformans species complex.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/yea.2997.Cryptococcus", "author" : [ { "dropping-particle" : "", "family" : "Deepa", "given" : "Srikanta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Felipe H", "given" : "Santiago-Tirado", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tamara L", "given" : "Doering", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NIH Public Access. Yeast", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "47-60", "title" : "<i>Cryptococcus neoformans</i>: Historical curiosity to modern pathogen", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁷", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37 Non- C. neoformans species, such as C. laurentii, C. uniguttulatus and C. albidus may cause infections.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s15010-007-6142-8", "ISBN" : "0300-8126", "ISSN" : "03008126", "PMID" : "17401707", "abstract" : "Non-neoformans cryptococci have been generally regarded as saprophytes and rarely reported as human pathogens. However, the incidence of infection due to these organisms has increased over the past 40 years, with Cryptococcus laurentii and Cryptococcus albidus, together, responsible for 80% of reported cases. Conditions associated with impaired cell-mediated immunity are important risks for non-neoformans cryptococcal infections and prior azole prophylaxis has been associated with antifungal resistance. The presence of invasive devices was a significant risk factor for Cryptococcus laurentii infection (adjusted OR = 8.7; 95% CI = 1.48-82.9; p = 0.003), while predictors for mortality included age > or =45 years (aOR = 8.4; 95% CI = 1.18-78.82; p = 0.004) and meningeal presentation (aOR = 7.0; 95% CI = 1.85-60.5; p= 0.04). Because clinical manifestations of non-neoformans cryptococcal infections are most often indistinguishable from Cryptococcus neoformans, a high index of suspicion remains important to facilitate early diagnosis and prompt treatment for such infections.", "author" : [ { "dropping-particle" : "", "family" : "Khawcharoenporn", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Apisarnthanarak", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mundy", "given" : "L. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "51-58", "title" : "Non-neoformans cryptococcal infections: A systematic review", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁸", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "³⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38 Other Cryptococcus spp. are less pathogenic probably because of a weaker capsular structure although can be fatal in humans as observed in C. liquefaciens.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0065-2164(08)01005-8", "ISBN" : "9780123748027", "ISSN" : "00652164", "PMID" : "19245939", "abstract" : "Cryptococcus neoformans and Cryptococcus gattii are the cause of life-threatening meningoencephalitis in immunocompromised and immunocompetent individuals respectively. The increasing incidence of cryptococcal infection as a result of the AIDS epidemic, the recent emergence of a hypervirulent cryptococcal strain in Canada and the fact that mortality from cryptococcal disease remains high have stimulated intensive research into this organism. Here we outline recent advances in our understanding of C. neoformans and C. gattii, including intraspecific complexity, virulence factors, and key signaling pathways. We discuss the molecular basis of cryptococcal virulence and the interaction between these pathogens and the host immune system. Finally, we discuss future challenges in the study and treatment of cryptococcosis. ?? 2009 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Ma", "given" : "Hansong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "Robin C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Advances in Applied Microbiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "131-190", "publisher" : "Elsevier", "title" : "Virulence in <i> Cryptococcus </i> species", "type" : "chapter", "volume" : "67" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0029561", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "22253734", "abstract" : "Capsule production is common among bacterial species, but relatively rare in eukaryotic microorganisms. Members of the fungal Cryptococcus genus are known to produce capsules, which are major determinants of virulence in the highly pathogenic species Cryptococcus neoformans and Cryptococcus gattii. Although the lack of virulence of many species of the Cryptococcus genus can be explained solely by the lack of mammalian thermotolerance, it is uncertain whether the capsules from these organisms are comparable to those of the pathogenic cryptococci. In this study, we compared the characteristic of the capsule from the non-pathogenic environmental yeast Cryptococcus liquefaciens with that of C. neoformans. Microscopic observations revealed that C. liquefaciens has a capsule visible in India ink preparations that was also efficiently labeled by three antibodies generated to specific C. neoformans capsular antigens. Capsular polysaccharides of C. liquefaciens were incorporated onto the cell surface of acapsular C. neoformans mutant cells. Polysaccharide composition determinations in combination with confocal microscopy revealed that C. liquefaciens capsule consisted of mannose, xylose, glucose, glucuronic acid, galactose and N-acetylglucosamine. Physical chemical analysis of the C. liquefaciens polysaccharides in comparison with C. neoformans samples revealed significant differences in viscosity, elastic properties and macromolecular structure parameters of polysaccharide solutions such as rigidity, effective diameter, zeta potential and molecular mass, which nevertheless appeared to be characteristics of linear polysaccharides that also comprise capsular polysaccharide of C. neoformans. The environmental yeast, however, showed enhanced susceptibility to the antimicrobial activity of the environmental phagocytes, suggesting that the C. liquefaciens capsular components are insufficient in protecting yeast cells against killing by amoeba. These results suggest that capsular structures in pathogenic Cryptococcus species and environmental species share similar features, but also manifest significant difference that could influence their potential to virulence.", "author" : [ { "dropping-particle" : "", "family" : "Araujo", "given" : "Glauber S.", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fonseca", "given" : "Fernanda L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pontes", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torres", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordero", "given" : "Radames J B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zancop??-Oliveira", "given" : "Rosely M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viana", "given" : "Nathan B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nimrichter", "given" : "Leonardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodrigues", "given" : "Marcio L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garcia", "given" : "Eloi S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Wanderley", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frases", "given" : "Susana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Capsules from pathogenic and non-pathogenic <i> Cryptococcus </i> spp. manifest significant differences in structure and ability to protect against phagocytic cells", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jiac.2014.11.007", "ISSN" : "1341-321X", "author" : [ { "dropping-particle" : "", "family" : "Takemura", "given" : "Hiromu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohno", "given" : "Hideaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miura", "given" : "Ikuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takagi", "given" : "Taeko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Infection and Chemotherapy", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "392-394", "publisher" : "Elsevier Ltd", "title" : "The first reported case of central venous catheter-related fungemia caused by Cryptococcus liquefaciens", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1128/JCM.00840-15", "author" : [ { "dropping-particle" : "", "family" : "Conde-Pereira", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodas-Rodriguez", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz-Paz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palacios-Rivera", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Firacative", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alcazar-Castillo", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-4", "issue" : "8", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2753-2755", "title" : "Fatal Case of Polymicrobial Meningitis Caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis Complex in a Human Immunodeficiency Virus-Infected Patient", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^39\u201342", "plainTextFormattedCitation" : "39\u201342", "previouslyFormattedCitation" : "^39\u201342" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39–42 C. neoformans is commonly found in pigeon droppings, whereas C. gattii is more likely to be found in vegetation, such as eucalyptus trees.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaneda", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wanke", "given" : "Bodo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lazera", "given" : "Marcia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "237-260", "publisher" : "ASM Press", "title" : "Enviromental niches for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3109/1040841X.2011.606426", "ISBN" : "1549-7828 (Electronic)\\r1040-841X (Linking)", "ISSN" : "1549-7828", "PMID" : "22133016", "abstract" : "An overview of work done to-date in India on environmental prevalence, population structure, seasonal variations and antifungal susceptibility of Cryptococcus neoformans and Cryptococcus gattii is presented. The primary ecologic niche of both pathogens is decayed wood in trunk hollows of a wide spectrum of host trees, representing 18 species. Overall, C. neoformans showed a higher environmental prevalence than that of C. gattii which was not found in the avian habitats. Apart from their arboreal habitat, both species were demonstrated in soil and air in close vicinity of their tree hosts. In addition, C. neoformans showed a strong association with desiccated avian excreta. An overwhelming number of C. neoformans strains belonged to genotype AFLP1/VNI, var. grubii (serotype A), whereas C. gattii strains were genotype AFLP4/VGI, serotype B. All of the environmental strains of C. neoformans and C. gattii were mating type \u03b1 (MAT\u03b1). Contrary to the Australian experience, Eucalyptus trees were among the epidemiologically least important and, therefore, the hypothesis of global spread of C. gattii through Australian export of infected Eucalyptus seeds is rebutted. Reference is made to long-term colonization of an abandoned, old timber beam of sal wood (Shorea robusta) by a melanin positive (Mel(+)) variant of Cryptococcus laurentii that was pathogenic to laboratory mice.", "author" : [ { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Anuradha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhandhawa", "given" : "Harbans S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "Anupam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meis", "given" : "Jacques F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical reviews in microbiology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1-16", "title" : "Environmental prevalence of <i> Cryptococcus neoformans</i> and <i>Cryptococcus gattii </i> in India: an update.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^21,23", "plainTextFormattedCitation" : "21,23", "previouslyFormattedCitation" : "^21,23" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21,23 The predisposing factors that support the survival and the growth of C. neoformans in pigeon droppings are an acidic pH, a high concentration of glucose, and minimal competition with bacterial species compared to other animal excreta. The worldwide migration of many bird species supports the ubiquitous spread of C. neoformans whereas C. gattii is confined to endemic pockets.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10096-013-1915-8", "ISSN" : "0934-9723", "author" : [ { "dropping-particle" : "", "family" : "Gullo", "given" : "F. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossi", "given" : "S. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sardi", "given" : "J. de C. O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teodoro", "given" : "V. L. I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mendes-Giannini", "given" : "M. J. 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M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Clinical Microbiology & Infectious Diseases", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1377-1391", "title" : "Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaneda", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wanke", "given" : "Bodo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lazera", "given" : "Marcia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "237-260", "publisher" : "ASM Press", "title" : "Enviromental niches for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^21,43", "plainTextFormattedCitation" : "21,43", "previouslyFormattedCitation" : "^21,43" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21,43 Serotype grouping is based on capsular polysaccharide agglutination patterns, and the two main species of Cryptococcus (C. neoformans and C. gattii) have been serotyped as A, B, C and D. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kwon Chung", "given" : "KJ", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickes", "given" : "BL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fell", "given" : "JW", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "3-15", "publisher" : "ASM Press", "title" : "Systematics of the genus <i>Cryptococcus</i> and its type species <i>C. neoformans</i>.", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Ikeda", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shinoda", "given" : "Takako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fukazawa", "given" : "Yoshimura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaufman", "given" : "L E O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "1982" ] ] }, "page" : "22-29", "title" : "Antigenic characterization of <i> Cryptococcus neoformans</i> serotypes and its application to serotyping of clinical isolates.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^35,44", "plainTextFormattedCitation" : "35,44", "previouslyFormattedCitation" : "^35,44" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }35,44 Each serotype or their combination represents a specific variety within C. neoformans species (Table. 1).ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0095-1137 (Print)\\r0095-1137 (Linking)", "ISSN" : "00951137", "PMID" : "9986871", "abstract" : "Cryptococcus neoformans var. neoformans presently includes isolates which have been determined by the immunologic reactivity of their capsular polysaccharides to be serotype A and those which have been determined to be serotype D. However, recent analyses of the URA5 sequences and DNA fingerprinting patterns suggest significant genetic differences between the two serotypes. Therefore, we propose to recognize these genotypic distinctions, as well as previously reported phenotypic differences, by restricting C. neoformans var. neoformans to isolates which are serotype D and describing a new variety, C. neoformans var. grubii, for serotype A isolates.", "author" : [ { "dropping-particle" : "", "family" : "Franzot", "given" : "Sarah P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salkin", "given" : "Ira F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "838-840", "title" : "<i>Cryptococcus neoformans var. grubii</i> : Separate varietal status for <i>Cryptococcus neoformans</i> serotype A isolates", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kwon Chung", "given" : "KJ", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickes", "given" : "BL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fell", "given" : "JW", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "3-15", "publisher" : "ASM Press", "title" : "Systematics of the genus <i>Cryptococcus</i> and its type species <i>C. neoformans</i>.", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-3", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^22,35,45,46", "plainTextFormattedCitation" : "22,35,45,46", "previouslyFormattedCitation" : "^22,35,45,46" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22,35,45,46 Common varieties of C. neoformans are grubii (serotype A) and neoformans (serotype D). In contrast, C. gattii serotypes are not classified into varieties and they all belong to serotypes B or C ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0095-1137 (Print)\\r0095-1137 (Linking)", "ISSN" : "00951137", "PMID" : "9986871", "abstract" : "Cryptococcus neoformans var. neoformans presently includes isolates which have been determined by the immunologic reactivity of their capsular polysaccharides to be serotype A and those which have been determined to be serotype D. However, recent analyses of the URA5 sequences and DNA fingerprinting patterns suggest significant genetic differences between the two serotypes. Therefore, we propose to recognize these genotypic distinctions, as well as previously reported phenotypic differences, by restricting C. neoformans var. neoformans to isolates which are serotype D and describing a new variety, C. neoformans var. grubii, for serotype A isolates.", "author" : [ { "dropping-particle" : "", "family" : "Franzot", "given" : "Sarah P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salkin", "given" : "Ira F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "838-840", "title" : "<i>Cryptococcus neoformans var. grubii</i> : Separate varietal status for <i>Cryptococcus neoformans</i> serotype A isolates", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kwon-chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fell", "given" : "Jack W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "TAXON", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "804-806", "title" : "Proposal to conserve the name <i>Cryptococcus gattii </i> against <i>C . hondurianus</i> and <i>C. bacillisporus</i> (Basidiomycota, Hymenomycetes, Tremellomycetidae)", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kwon-chung", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycologia", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1975" ] ] }, "page" : "1197-1200", "title" : "A new genus, Filobasidiella, the perfect state of <i>Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^45,47,48", "plainTextFormattedCitation" : "45,47,48", "previouslyFormattedCitation" : "^45,47,48" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }45,47,48. One shortfall of the serotype classification system is antigenic evolution.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1567-1364.2006.00088.x", "ISBN" : "1567-1356 (Print)\\r1567-1356 (Linking)", "ISSN" : "15671356", "PMID" : "16696653", "abstract" : "Cryptococcus neoformans, the agent of cryptococcosis, had been considered a homogeneous species until 1949 when the existence of four serotypes was revealed based on the antigenic properties of its polysaccharide capsule. Such heterogeneity of the species, however, remained obscure until the two morphologically distinct teleomorphs of C. neoformans were discovered during the mid 1970s. The teleomorph Filobasidiella neoformans was found to be produced by strains of serotype A and D, and Filobasidiella bacillispora was found to be produced by strains of serotype B and C. Ensuing studies revealed numerous differences between the anamorphs of the two Filobasidiella species with regard to their ecology, epidemiology, pathobiology, biochemistry and genetics. At present, the etiologic agent of cryptococcosis is classified into two species, C. neoformans (serotypes A and D) and Cryptococcus gattii (serotypes B and C). Intraspecific genetic diversity has also been revealed as more genotyping methods have been applied for each serotype. As a result, the number of scientifically valid species within C. neoformans has become a controversial issue because of the differing opinions among taxonomists as to the appropriate definition of a species. There are three major species concepts that govern classification of organisms: phenetic (morphologic, phenotypic), biologic (interbreeding) and cladistic (evolutionary, phylogenetic). Classification of the two C. neoformans species has been based on the phenetic as well as the biologic species concept, which is also supported by the cladistic species concept. In this paper, we review and attest to the validity of the current two-species system in light of the three major species concepts.", "author" : [ { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "574-587", "title" : "Do major species concepts support one, two or more species within <i> Cryptococcus neoformans</i> ?", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁴⁹", "plainTextFormattedCitation" : "49", "previouslyFormattedCitation" : "⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }49 For example, the CBS 132T type strain of C. neoformans was initially identified as serotype D but more recently has been found as an AD hybrid.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.fgb.2015.02.009", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10960937", "PMID" : "25721988", "abstract" : "Phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic Cryptococcus gattii/. Cryptococcus neoformans species complex. Genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. Consequently, we propose to recognize the current C. neoformans var. grubii and C. neoformans var. neoformans as separate species, and five species within C. gattii. The type strain of C. neoformans CBS132 represents a serotype AD hybrid and is replaced. The newly delimited species differ in aspects of pathogenicity, prevalence for patient groups, as well as biochemical and physiological aspects, such as susceptibility to antifungals. MALDI-TOF mass spectrometry readily distinguishes the newly recognized species.", "author" : [ { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theelen", "given" : "Bart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolecka", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polacheck", "given" : "Itzhack", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sionov", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falk", "given" : "Rama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parnmen", "given" : "Sittiporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lumbsch", "given" : "H. Thorsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "16-48", "publisher" : "Elsevier Inc.", "title" : "Recognition of seven species in the <i>Cryptococcus gattii </i>/<i> Cryptococcus neoformans</i> species complex", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁰", "plainTextFormattedCitation" : "50", "previouslyFormattedCitation" : "⁵⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }50 C. neoformans var. grubii is estimated to be the pathogen in 90% of cryptococcosis cases worldwide and causes more severe infection than other species.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pmed.0040021", "ISBN" : "1549-1676", "ISSN" : "15491277", "PMID" : "17284154", "abstract" : "BACKGROUND: Cryptococcosis is a life-threatening opportunistic fungal infection in both HIV-positive and -negative patients. Information on clinical presentation and therapeutic guidelines, derived mostly from clinical trials performed before introduction of highly active antiretroviral therapy in patients with cryptococcal meningoencephalitis, is missing data on extrameningeal involvement and infections by serotype D as opposed to serotype A of Cryptococcus neoformans. METHODS AND FINDINGS: The prospective multicenter study CryptoA/D was designed in France (1997-2001) to analyse the factors influencing clinical presentation and outcome without the bias of inclusion into therapeutic trials. Of the 230 patients enrolled, 177 (77%) were HIV-positive, 50 (22%) were female, and 161 (72.5%) were infected with serotype A. Based on culture results at baseline, cryptococcosis was more severe in men, in HIV-positive patients, and in patients infected with serotype A. Factors independently associated with mycological failure at week 2 independent of HIV status were initial dissemination (OR, 2.4 [95% confidence interval (CI), 1.2-4.9]), high (>1:512) serum antigen titre (OR, 2.6 [1.3-5.4]), and lack of flucytosine during induction therapy (OR, 3.8 [1.9-7.8]). The three-month survival was shorter in patients with abnormal neurology or brain imaging at baseline, and in those with haematological malignancy. CONCLUSIONS: Thus sex, HIV status, and infecting serotype are major determinants of presentation and outcome during cryptococcosis. We propose a modification of current guidelines for the initial management of cryptococcosis based on systematic fungal burden evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Dromer", "given" : "Fran\u00e7oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathoulin-P\u00e9lissier", "given" : "Simone", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launay", "given" : "Odile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Achard", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chabasse", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bland", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bru", "given" : "J. 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P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delzant", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kac", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trivalle", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "0297-0308", "title" : "Determinants of disease presentation and outcome during cryptococcosis: The CryptoA/D study", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jinf.2004.07.013", "ISBN" : "0163-4453", "ISSN" : "01634453", "PMID" : "15979484", "abstract" : "Objectives. To characterize the pathogenicity of 15 strains of Cryptococcus neoformans belonging to several serotype/mating type allele patterns (D??, Da, A??, Aa, A??/Da and D??/Aa) in experimental models of murine cryptococcosis. Methods. CD1-infected mice were examined for survival and fungal loads in either brain or lung during the course of infection. Results. All strains, with the exception of one Da strain, produced melanin in vitro. Similarly, all strains were encapsulated and produced phospholipase. When CD1 mice were challenged intravenously (i.v.) with 5??105 CFU/mouse and observed for 60 days post-infection, a significant variation of mortality rate was observed among mice infected with different strains. A?? and A??/Da strains all produced 100% mortality within the study period with mean survivals significantly shorter than those of mice infected with strains belonging to any other allele type (P<0.0001). A wide range of pathogenicity was shown by haploid and diploid strains presenting D?? allele. This finding was confirmed by an intranasal model of challenge. To investigate the progression of infection, the mice were challenged i.v. with 5??104 CFU/mouse and tissue burden experiments (brain and lung) were performed on days 6 and 12 post-infection. Only the mice infected with A?? and A??/Da strains showed a >1 log10 increase of CFU/g in both tissues throughout the study period. Conclusions. Our results suggest that the presence of the A?? mating type allele in either haploid or diploid strains is correlated with virulence, while the presence of the Aa or Da allele in haploid strains is associated with moderate or no virulence. Finally, either haploid or diploid strains presenting D?? allele vary in virulence. ?? 2004 The British Infection Society. Published by Elsevier Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Barchiesi", "given" : "F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cogliati", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esposto", "given" : "M. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spreghini", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schimizzi", "given" : "A. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickes", "given" : "B. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scalise", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viviani", "given" : "M. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Infection", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "10-16", "title" : "Comparative analysis of pathogenicity of <i> Cryptococcus neoformans</i> serotypes A, D and AD in murine cryptococcosis", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/S0190-9622(97)80336-2", "ISBN" : "0893-8512 (Print)\\r0893-8512 (Linking)", "ISSN" : "0893-8512", "PMID" : "8665468", "abstract" : "Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the advent of the AIDS pandemic, cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality and a frequently life-threatening opportunistic mycosis among patients with AIDS. Both basic and clinical research have accelerated in the 1990s, and this review attempts to highlight some of these advances. The discussion covers recent findings, current concepts, controversies, and unresolved issues related to the ecology and genetics of C. neoformans; the surface structure of the yeast; and the mechanisms of host defense. Regarding cell-mediated immunity, CD4+ T cells are crucial for successful resistance, but CD8+ T cells may also participate significantly in the cytokine-mediated activation of anticryptococcal effector cells. In addition to cell-mediated immunity, monoclonal antibodies to the major capsular polysaccharide, the glucuronoxylomannan, offer some protection in murine models of cryptococcosis. Clinical concepts are presented that relate to the distinctive features of cryptococcosis in patients with AIDS and the diagnosis, treatment, and prevention of cryptococcosis in AIDS patients.", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "T G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "515-48", "title" : "Cryptococcosis in the era of AIDS--100 years after the discovery of <i> Cryptococcus neoformans</i> .", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1128/mBio.00311-15", "ISSN" : "2150-7511", "abstract" : "Cryptococcus neoformans is a human opportunistic fungal pathogen causing severe disseminated meningoencephalitis, mostly in patients with cellular immune defects. This species is divided into three serotypes: A, D, and the AD hybrid. Our objectives were to compare population structures of serotype A and D clinical isolates and to assess whether infections with AD hybrids differ from infections with the other serotypes. For this purpose, we analyzed 483 isolates and the corresponding clinical data from 234 patients enrolled during the CryptoA/D study or the nationwide survey on cryptococcosis in France. Isolates were characterized in terms of ploidy, serotype, mating type, and genotype, utilizing flow cytometry, serotype- and mating type-specific PCR amplifications, and multilocus sequence typing (MLST) methods. Our results suggest that C. neoformans serotypes A and D have different routes of multiplication (primarily clonal expansion versus recombination events for serotype A and serotype D, respectively) and important genomic differences. Cryptococcosis includes a high proportion of proven or probable infections (21.5%) due to a mixture of genotypes, serotypes, and/or ploidies. Multivariate analysis showed that parameters independently associated with failure to achieve cerebrospinal fluid (CSF) sterilization by week 2 were a high serum antigen titer, the lack of flucytosine during induction therapy, and the occurrence of mixed infection, while infections caused by AD hybrids were more likely to be associated with CSF sterilization. Our study provides additional evidence for the possible speciation of C. neoformans var. neoformans and grubii and highlights the importance of careful characterization of causative isolates. IMPORTANCE: Cryptococcus neoformans is an environmental fungus causing severe disease, estimated to be responsible for 600,000 deaths per year worldwide. This species is divided into serotypes A and D and an AD hybrid, and these could be considered two different species and an interspecies hybrid. The objectives of our study were to compare population structures of serotype A and serotype D and to assess whether infections with AD hybrids differ from infections with serotype A or D isolates in terms of clinical presentation and outcome. For this purpose, we used clinical data and strains from patients diagnosed with cryptococcosis in France. Our results suggest that, according to the serotype, isolates have different routes of multipli\u2026", "author" : [ { "dropping-particle" : "", "family" : "Desnos-Ollivier", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patel", "given" : "Sweta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raoux-Barbot", "given" : "Doroth\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Fran\u00e7oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "mBio", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "e00311-15", "title" : "Cryptococcosis serotypes impact outcome and provide evidence of <i> Cryptococcus neoformans</i> speciation", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{36,51\u201353}", "plainTextFormattedCitation" : "36,51\u201353", "previouslyFormattedCitation" : "^{36,51\u201353}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }36,51–53Genetic diversity of Cryptococcus Molecular genotyping methods have revealed a wide genetic diversity of Cryptococcus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/13693780902953886", "ISSN" : "1369-3786", "PMID" : "19462334", "author" : [ { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aanensen", "given" : "David M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cogliati", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esposto", "given" : "Maria Carmela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilgado", "given" : "Felix", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaocharoen", "given" : "Sirada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Litvintseva", "given" : "Anastasia P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simwami", "given" : "Sitali P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilles", "given" : "Luciana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viviani", "given" : "Maria Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "June", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "561-570", "title" : "Consensus multi-locus sequence typing scheme for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁴", "plainTextFormattedCitation" : "54", "previouslyFormattedCitation" : "⁵⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }54 There are wide genotype and phenotype divergences between C. neoformans and C. gattii. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.fgb.2015.02.009", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10960937", "PMID" : "25721988", "abstract" : "Phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic Cryptococcus gattii/. Cryptococcus neoformans species complex. Genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. Consequently, we propose to recognize the current C. neoformans var. grubii and C. neoformans var. neoformans as separate species, and five species within C. gattii. The type strain of C. neoformans CBS132 represents a serotype AD hybrid and is replaced. The newly delimited species differ in aspects of pathogenicity, prevalence for patient groups, as well as biochemical and physiological aspects, such as susceptibility to antifungals. MALDI-TOF mass spectrometry readily distinguishes the newly recognized species.", "author" : [ { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theelen", "given" : "Bart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolecka", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polacheck", "given" : "Itzhack", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sionov", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falk", "given" : "Rama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parnmen", "given" : "Sittiporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lumbsch", "given" : "H. Thorsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "16-48", "publisher" : "Elsevier Inc.", "title" : "Recognition of seven species in the <i>Cryptococcus gattii </i>/<i> Cryptococcus neoformans</i> species complex", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁰", "plainTextFormattedCitation" : "50", "previouslyFormattedCitation" : "⁵⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }50 The main methods used have been deoxyribonucleic acid?(DNA) and polymerase chain reaction (PCR) fingerprinting, multi-locus sequence typing (MLST), amplified fragment length polymorphism (AFLP) analysis and multigene and intergenic spacer (IGS) sequences of the ribosomal DNA analysis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1534/genetics.105.046672", "ISBN" : "0016-6731 (Print)\\n0016-6731 (Linking)", "ISSN" : "00166731", "PMID" : "16322524", "abstract" : "We applied multilocus sequence typing (MLST) to investigate the population structure and mode of reproduction of Cryptococcus neoformans var. grubii (serotype A). This MLST system utilizes 12 unlinked polymorphic loci, which are dispersed on nine different chromosomes, and allows the unambiguous identification of closely related strains of serotype A. We compared MLST analyses with the conventional genotyping method of detecting amplified fragment length polymorphisms (AFLPs), and there was excellent correlation between the MLST and AFLP results. However, MLST differentiated a larger number of strains. We analyzed a global collection of isolates of serotype A using both methods, and the results identified at least three genetically distinct subpopulations, designated groups VNI, VNII, and VNB. Groups VNI and VNII are widespread, dominated by isolates with the MATalpha mating type, and predominantly clonal. Conversely, isolates of group VNB are unique to Botswana, include a significant proportion of fertile strains with the MATa mating type, and manifest compelling evidence of recombination. We have AFLP genotyped >1000 strains of serotype A from different parts of the world, including isolates from several African countries, and, to date, haploid serotype A isolates of group VNB have been found only in Botswana.", "author" : [ { "dropping-particle" : "", "family" : "Litvintseva", "given" : "Anastasia P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thakur", "given" : "Rameshwari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilgalys", "given" : "Rytas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "2223-2238", "title" : "Multilocus sequence typing reveals three genetic subpopulations of <i> Cryptococcus neoformans var. grubii (serotype </i> A), including a unique population in Botswana", "type" : "article-journal", "volume" : "172" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.femsyr.2005.05.005", "ISSN" : "15671356", "PMID" : "16061425", "abstract" : "Cryptococcus neoformans is an opportunistic basidiomycete responsible for the high incidence of cryptococcosis in patients with AIDS and in other immune-compromised individuals. This study, which focused on the molecular structure and genetic variability of the two varieties in the C. neoformans and Cryptococcus gattii species complex, employed sequence analysis of the intergenic spacer regions, IGSI and IGSII. The IGS region is the most rapidly evolving region of the rDNA families. The IGSI displayed the most genetic variability represented by nucleotide base substitutions and the presence of long insertions/deletions (indels). In contrast, the IGSII region exhibited less heterogeneity and the indels were not as extensive as those displayed in the IGSI region. Both intergenic spacers contained short, interspersed repeat motifs, which can be related to length polymorphisms observed between sequences. Phylogenetic analysis undertaken in the IGSI, IGSII and IGSI + 5S rRNA + IGSII regions revealed the presence of six major phylogenetic lineages, some of which segregated into subgroups. The major lineages are represented by genotypes 1 (C. neoformans var. grubii), genotype 2 (C. neoformans var. neoformans), and genotypes 3, 4, 5 and 6 represented by C. gattii. Genotype 6 is a newly described IGS genotypic group within the C. neoformans species complex. With the inclusion of IGS subgenotypic groups, our sequence analysis distinguished 12 different lineages. Sequencing of clones, which was performed to determine the presence of multiple alleles at the IGS locus in several hybrid strains, yielded a single IGS sequence type per isolate, thus suggesting that the selected group of cloned strains was mono-allelic at this locus. IGS sequence analyses proved to be a powerful technique for the delineation of the varieties of C. neoformans and C. gattii at genotypic and subgenotypic levels. ?? 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiesling", "given" : "Traci", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fell", "given" : "Jack W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "1129-1140", "title" : "Comparative analysis of the intergenic spacer regions and population structure of the species complex of the pathogenic yeast <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.fgb.2007.12.004", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10871845", "PMID" : "18261945", "abstract" : "Cryptococcus neoformans and Cryptococcus gattii are closely related pathogenic basidiomycetous yeasts in which six haploid genotypic groups have been distinguished. The two haploid genotypic groups of C. neoformans have been described as variety grubii and variety neoformans. The four C. gattii genotypic groups have, however, not been described as separate taxa. One hundred and seventeen isolates representing all six haploid genotypic groups were selected for multi-locus sequence typing using six loci to investigate if the isolates consistently formed monophyletic lineages. Two monophyletic lineages, corresponding to varieties grubii and neoformans, were consistently present within C. neoformans, supporting the current classification. In addition, four monophyletic lineages corresponding to the previously described genotypic groups were consistently found within C. gattii, indicating that these lineages should be considered different taxa as well. ?? 2007 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Bovers", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuramae", "given" : "E. E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "400-421", "title" : "Six monophyletic lineages identified within <i> Cryptococcus neoformans</i> and <i>Cryptococcus gattii </i> by multi-locus sequence typing", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Meyer", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lieckfeldt", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuhls", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "EZ", "given" : "Freedman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6rner", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "TG", "given" : "Mitchell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "DNA Fingerprinting: State of the Science", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "311-320", "publisher" : "Birkh\u00e4user Basel", "title" : "DNA and PCR fingerprinting in fungi.", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Spitzer", "given" : "E D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spitzer", "given" : "S G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical microbiology", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "1094-1097", "title" : "Use of a dispersed repetitive DNA element to distinguish clinical isolates of <i> Cryptococcus </i> use of a dispersed repetitive DNA element to distinguish clinical isolates of <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^55\u201359", "plainTextFormattedCitation" : "55\u201359", "previouslyFormattedCitation" : "^55\u201359" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }55–59 Inter-laboratory reproducibility using PCR fingerprinting and AFLP analysis is poor. MLST types have been shown to associate more closely with the virulence and patterns of infection than serotyping in both immunocompetent and immunocompromised hosts.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/IAI.00296-09", "ISBN" : "1098-5522 (Electronic)\\r0019-9567 (Linking)", "ISSN" : "00199567", "PMID" : "19487475", "abstract" : "Most cases of cryptococcosis are caused by Cryptococcus neoformans var. grubii (serotype A), which is widespread in the environment, where it is primarily associated with pigeon excreta. A number of molecular epidemiological studies indicate that many environmental and clinical isolates of serotype A are indistinguishable. However, the murine virulence of environmental strains of C. neoformans has not been thoroughly evaluated. We used the murine intranasal model of cryptococcosis to compare the lethality of clinical and environmental strains of serotype A that possessed identical genotypes as determined by amplified fragment length polymorphisms (AFLP) and multilocus sequence typing (MLST). Eleven environmental strains were tested, and only one caused disease within 60 days postinfection, at which time the experiments were terminated. Conversely, 7 of 10 clinical isolates were lethal for mice at median times of 19 to 40 days. Passing environmental isolates in mice (up to three times) did not significantly increase their lethality. In follow-up studies, we developed a new genotyping technique based on hybridization with TCN2 and TCN4 retrotransposon-specific probes. Although the retrotransposon banding patterns were unstable after prolonged incubation in the laboratory, this method was able to differentiate clinical and environmental strains that had the same AFLP/MLST genotypes.", "author" : [ { "dropping-particle" : "", "family" : "Litvintseva", "given" : "Anastasia P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "3188-3195", "title" : "Most environmental isolates of <i>Cryptococcus neoformans var. grubii</i> (serotype A) are not lethal for mice", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pntd.0003847", "ISBN" : "1935-2727", "ISSN" : "19352735", "PMID" : "26110902", "abstract" : "Cryptococcal meningitis is a major cause of mortality throughout the developing world, yet little is known about the genetic markers underlying Cryptococcal virulence and patient outcome. We studied a cohort of 230 Cryptococcus neoformans (Cn) isolates from HIV-positive South African clinical trial patients with detailed clinical follow-up using multi-locus sequence typing and in vitro phenotypic virulence assays, correlating these data with clinical and fungal markers of disease in the patient. South African Cn displayed high levels of genetic diversity and locus variability compared to globally distributed types, and we identified 50 sequence types grouped within the main molecular types VNI, VNII and VNB, with 72% of isolates typed into one of seven 'high frequency' sequence types. Spatial analysis of patients' cryptococcal genotype was not shown to be clustered geographically, which might argue against recent local acquisition and in favour of reactivation of latent infection. Through comparison of MLST genotyping data with clinical parameters, we found a relationship between genetic lineage and clinical outcome, with patients infected with the VNB lineage having significantly worse survival (n=8, HR 3.35, CI 1.51-7.20, p=0.003), and this was maintained even after adjustment for known prognostic indicators and treatment regimen. Comparison of fungal genotype with in vitro phenotype (phagocytosis, laccase activity and CSF survival) performed on a subset of 89 isolates revealed evidence of lineage-associated virulence phenotype, with the VNII lineage displaying increased laccase activity (p=0.001) and ex vivo CSF survival (p=0.0001). These findings show that Cryptococcus neoformans is a phenotypically heterogeneous pathogen, and that lineage plays an important role in cryptococcal virulence during human infection. Furthermore, a detailed understanding of the genetic diversity in Southern Africa will support further investigation into how genetic diversity is structured across African environments, allowing assessment of the risks different ecotypes pose to infection.", "author" : [ { "dropping-particle" : "", "family" : "Beale", "given" : "Mathew A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sabiiti", "given" : "Wilber", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Emma J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fuentes-Cabrejo", "given" : "Karen M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hanlon", "given" : "Simon J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loyse", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meintjes", "given" : "Graeme", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "Robin C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Matthew C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bicanic", "given" : "Tihana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Neglected Tropical Diseases", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-18", "title" : "Genotypic diversity is associated with clinical outcome and phenotype in cryptococcal meningitis across Southern Africa", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1128/mBio.00196-12", "ISBN" : "2150-7511", "ISSN" : "21612129", "PMID" : "23015735", "abstract" : "UNLABELLED: In sub-Saharan Africa, cryptococcal meningitis (CM) continues to be a predominant cause of AIDS-related mortality. Understanding virulence and improving clinical treatments remain important. To characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 Cryptococcus isolates from 111 Ugandans with AIDS and CM. Isolates consisted of 107 nonredundant Cryptococcus neoformans var. grubii strains and 8 C. neoformans var. grubii/neoformans hybrid strains. Multilocus sequence typing (MLST) was used to characterize genotypes, yielding 15 sequence types and 4 clonal clusters. The largest clonal cluster consisted of 74 isolates. The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). Patient mortality was differentially associated with the different evolutionary groups (P = 0.04), with the highest mortality observed among Burst group 1, Burst group 2, and hybrid strains. Compared to Burst group 3 strains, Burst group 1 strains were associated with higher mortality (P = 0.02), exhibited increased capsule shedding (P = 0.02), and elicited a more pronounced Th(2) response during ex vivo cytokine release assays with strain-specific capsule stimulation (P = 0.02). The results of these analyses suggest that cryptococcal strain variation can be an important determinant of human immune responses and mortality.\\n\\nIMPORTANCE: Cryptococcus neoformans is a common life-threatening human fungal pathogen that is responsible for an estimated 1 million cases of meningitis in HIV-infected patients annually. Virulence factors that are important in human disease have been identified, yet the impacts of the fungal strain genotype on virulence and outcomes of human infection remain poorly understood. Using an analysis of strain variation based on in vitro assays and clinical data from Ugandans living with AIDS and cryptococcal infection, we report that strain genotype predicts the type of immune response and mortality risk. These studies suggest that knowledge of the strain genotype during human infections could be used to predict disease outcomes and lead to improved treatment approaches aimed at targeting the specific combination of pathogen virulence and host response.", "author" : [ { "dropping-particle" : "", "family" : "Wiesner", "given" : "Darin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moskalenko", "given" : "Oleksandr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corcoran", "given" : "Jennifer M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mcdonald", "given" : "Tami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolfes", "given" : "Melissa A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meya", "given" : "David B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kajumbula", "given" : "Henry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kambugu", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bohjanen", "given" : "Paul R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Joseph F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boulware", "given" : "David R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "mBio", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1-10", "title" : "Cryptococcal genotype influences immunologic response and human clinical outcome after meningitis", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1371/journal.pone.0072222", "ISBN" : "1932-6203", "ISSN" : "19326203", "PMID" : "24019866", "abstract" : "Cryptococcosis is an important fungal disease in Asia with an estimated 140,000 new infections annually the majority of which occurs in patients suffering from HIV/AIDS. Cryptococcus neoformans variety grubii (serotype A) is the major causative agent of this disease. In the present study, multilocus sequence typing (MLST) using the ISHAM MLST consensus scheme for the C. neoformans/C. gattii species complex was used to analyse nucleotide polymorphisms among 476 isolates of this pathogen obtained from 8 Asian countries. Population genetic analysis showed that the Asian C. neoformans var. grubii population shows limited genetic diversity and demonstrates a largely clonal mode of reproduction when compared with the global MLST dataset. HIV-status, sequence types and geography were found to be confounded. However, a correlation between sequence types and isolates from HIV-negative patients was observed among the Asian isolates. Observations of high gene flow between the Middle Eastern and the Southeastern Asian populations suggest that immigrant workers in the Middle East were originally infected in Southeastern Asia.", "author" : [ { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simwami", "given" : "Sitali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Matthew C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahyuningsih", "given" : "Retno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Arunaloke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Anuradha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikeda", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taj-Aldeen", "given" : "Saad J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Ziauddin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ip", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imran", "given" : "Darma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sjam", "given" : "Ridhawati", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sriburee", "given" : "Pojana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaicumpar", "given" : "Kunyaluk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vuddhakul", "given" : "Varaporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilles", "given" : "Luciana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iersel", "given" : "Leo J J", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meis", "given" : "Jacques F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klaassen", "given" : "Corn?? H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-4", "issue" : "9", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-14", "title" : "Geographically structured populations of <i> Cryptococcus neoformans variety grubii</i> in Asia correlate with HIV status and show a clonal population structure", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^60\u201363", "plainTextFormattedCitation" : "60\u201363", "previouslyFormattedCitation" : "^60\u201363" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }60–63 Therefore, the Cryptococcal Working Group 1 (Genotyping of C. neoformans and C. gattii) of the International Society for Human and Animal Mycology (ISHAM) has recommended MLST as the primary method for cryptococcal strain typing.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/13693780902953886", "ISSN" : "1369-3786", "PMID" : "19462334", "author" : [ { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aanensen", "given" : "David M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cogliati", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esposto", "given" : "Maria Carmela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilgado", "given" : "Felix", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaocharoen", "given" : "Sirada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Litvintseva", "given" : "Anastasia P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simwami", "given" : "Sitali P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilles", "given" : "Luciana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viviani", "given" : "Maria Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "June", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "561-570", "title" : "Consensus multi-locus sequence typing scheme for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁴", "plainTextFormattedCitation" : "54", "previouslyFormattedCitation" : "⁵⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }54 This working group also promotes the use of VNI-VNIV and VGI-VGIV nomenclature for Cryptococcus isolates ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3201/eid0902.020246", "ISBN" : "1080-6040 (Print)\\r1080-6040 (Linking)", "ISSN" : "10806040", "PMID" : "12603989", "abstract" : "A network was established to acquire basic knowledge of Cryptococcus neoformans in IberoAmerican countries. To this effect, 340 clinical, veterinary, and environmental isolates from Argentina, Brazil, Chile, Colombia, Mexico, Peru, Venezuela, Guatemala, and Spain were typed by using M13 polymerase chain reaction-fingerprinting and orotidine monophosphate pyrophosphorylase (URA5) gene restriction fragment length polymorphism analysis with HhaI and Sau96I in a double digest. Both techniques grouped all isolates into eight previously established molecular types. The majority of the isolates, 68.2% (n=232), were VNI (var. grubii, serotype A), which accords with the fact that this variety causes most human cryptococcal infections worldwide. A smaller proportion, 5.6% (n=19), were VNII (var. grubii, serotype A); 4.1% (n=14), VNIII (AD hybrid), with 9 isolates having a polymorphism in the URA5 gene; 1.8% (n=6), VNIV (var. neoformans, serotype D); 3.5% (n=12), VGI; 6.2% (n=21), VGII; 9.1% (n=31), VGIII, and 1.5% (n=5) VGIV, with all four VG types containing var. gatii serotypes B and C isolates.", "author" : [ { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaneda", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huynh", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaneda", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "the IberoAmerican Cryptococcal Study Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Emerging Infectious Diseases", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "189-195", "title" : "Molecular typing of IberoAmerican <i> Cryptococcus neoformans</i> isolates", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1080/13693780902953886", "ISSN" : "1369-3786", "PMID" : "19462334", "author" : [ { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aanensen", "given" : "David M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cogliati", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esposto", "given" : "Maria Carmela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilgado", "given" : "Felix", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaocharoen", "given" : "Sirada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Litvintseva", "given" : "Anastasia P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simwami", "given" : "Sitali P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilles", "given" : "Luciana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viviani", "given" : "Maria Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "June", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "561-570", "title" : "Consensus multi-locus sequence typing scheme for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^54,64", "plainTextFormattedCitation" : "54,64", "previouslyFormattedCitation" : "^54,64" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }54,64 (Table 1).Genetic variations are linked to biochemical and physiological differences including serotypes, the profile of matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS), pathophysiology and clinical manifestations.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0034258", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "22479580", "abstract" : "Two members of the Cryptococcus neoformans-gattii species complex, the etiologic agents of cryptococcosis, can be differentiated by biological, biochemical, serological and molecular typing techniques. Based on their differences in carbon and nitrogen utilization patterns, cost effective and very specific diagnostic tests using D-proline and canvanine-glycine-bromthymol blue (CGB) media have been formulated and are widely used for identification of the two species. However, these methods have yet to be tested for strains with confirmed molecular types to assess the degree of specificity for each molecular type in the two species. We collected global isolates of every major molecular type available and tested their patterns of nitrogen utilization. We confirmed specificity of the CGB test to be 100% regardless of molecular type while the D-proline test yielded 8-38% false negative results in three of the four C. gattii molecular types, VGI-VGIII. The utilization pattern of a new set of amino acids: D-alanine, L-tryptophan and L-phenylalanine, showed species specificity comparable to that of D-proline. We discovered that the transcription factor Gat1 (Are1) regulates the utilization of nitrogen differently between C. neoformans and C. gattii strains. Unlike in C. neoformans, expression of the genes encoding glycine decarboxylase complex in C. gatti was only partially suppressed by nitrogen catabolite repression in the presence of ammonium. GAT1 in C. neoformans controlled the induction of three of the four genes encoding the glycine decarboxylase complex when glycine was used as the sole nitrogen source while in C. gattii its regulation of these genes was less stringent. Moreover, while virulence of C. neoformans strains in mice was not affected by Gat1, the transcription factor positively influenced the virulence of C. gattii strain.", "author" : [ { "dropping-particle" : "", "family" : "Ngamskulrungroj", "given" : "Popchai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roh", "given" : "Jamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Differences in nitrogen metabolism between <i> Cryptococcus neoformans</i> and <i>C. gattii </i>, the two etiologic agents of cryptococcosis", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.femsyr.2005.05.005", "ISSN" : "15671356", "PMID" : "16061425", "abstract" : "Cryptococcus neoformans is an opportunistic basidiomycete responsible for the high incidence of cryptococcosis in patients with AIDS and in other immune-compromised individuals. This study, which focused on the molecular structure and genetic variability of the two varieties in the C. neoformans and Cryptococcus gattii species complex, employed sequence analysis of the intergenic spacer regions, IGSI and IGSII. The IGS region is the most rapidly evolving region of the rDNA families. The IGSI displayed the most genetic variability represented by nucleotide base substitutions and the presence of long insertions/deletions (indels). In contrast, the IGSII region exhibited less heterogeneity and the indels were not as extensive as those displayed in the IGSI region. Both intergenic spacers contained short, interspersed repeat motifs, which can be related to length polymorphisms observed between sequences. Phylogenetic analysis undertaken in the IGSI, IGSII and IGSI + 5S rRNA + IGSII regions revealed the presence of six major phylogenetic lineages, some of which segregated into subgroups. The major lineages are represented by genotypes 1 (C. neoformans var. grubii), genotype 2 (C. neoformans var. neoformans), and genotypes 3, 4, 5 and 6 represented by C. gattii. Genotype 6 is a newly described IGS genotypic group within the C. neoformans species complex. With the inclusion of IGS subgenotypic groups, our sequence analysis distinguished 12 different lineages. Sequencing of clones, which was performed to determine the presence of multiple alleles at the IGS locus in several hybrid strains, yielded a single IGS sequence type per isolate, thus suggesting that the selected group of cloned strains was mono-allelic at this locus. IGS sequence analyses proved to be a powerful technique for the delineation of the varieties of C. neoformans and C. gattii at genotypic and subgenotypic levels. ?? 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiesling", "given" : "Traci", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fell", "given" : "Jack W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "1129-1140", "title" : "Comparative analysis of the intergenic spacer regions and population structure of the species complex of the pathogenic yeast <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0037566", "ISBN" : "1932-6203", "ISSN" : "19326203", "PMID" : "22666368", "abstract" : "BACKGROUND: The Cryptococcus neoformans/C. gattii species complex comprises two sibling species that are divided into eight major molecular types, C. neoformans VNI to VNIV and C. gattii VGI to VGIV. These genotypes differ in host range, epidemiology, virulence, antifungal susceptibility and geographic distribution. The currently used phenotypic and molecular identification methods for the species/molecular types are time consuming and expensive. As Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS) offers an effective alternative for the rapid identification of microorganisms, the objective of this study was to examine its potential for the identification of C. neoformans and C. gattii strains at the intra- and inter-species level.METHODOLOGY: Protein extracts obtained via the formic acid extraction method of 164 C. neoformans/C. gattii isolates, including four inter-species hybrids, were studied.RESULTS: The obtained mass spectra correctly identified 100% of all studied isolates, grouped each isolate according to the currently recognized species, C. neoformans and C. gattii, and detected potential hybrids. In addition, all isolates were clearly separated according to their major molecular type, generating greater spectral differences among the C. neoformans molecular types than the C. gattii molecular types, most likely reflecting a closer phylogenetic relationship between the latter. The number of colonies used and the incubation length did not affect the results. No spectra were obtained from intact yeast cells. An extended validated spectral library containing spectra of all eight major molecular types was established.CONCLUSIONS: MALDI-TOF MS is a rapid identification tool for the correct recognition of the two currently recognized human pathogenic Cryptococcus species and offers a simple method for the separation of the eight major molecular types and the detection of hybrid strains within this species complex in the clinical laboratory. The obtained mass spectra provide further evidence that the major molecular types warrant variety or even species status.", "author" : [ { "dropping-particle" : "", "family" : "Firacative", "given" : "Carolina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilles", "given" : "Luciana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "MALDI-TOF MS enables the rapid identification of the major molecular types within the <i>Cryptococcus neoformans /C. gattii</i> species complex", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.7883/yoken.66.216", "ISBN" : "8133767156", "ISSN" : "13446304", "PMID" : "23698482", "abstract" : "Although Cryptococcus gattii can cause life-threatening complications, putative virulence factors of C. gattii remain controversial. Therefore, we conducted the present study to elucidate the virulence factors of the yeast and found that the mortality rate of mice infected with C. gattii R265 was significantly higher than that of those infected with C. gattii 5815; however, no difference was found in the mortality rates between mice infected with C. gattii R265 and Cryptococcus neoformans H99. In contrast, we found a significant difference in histopathological findings of the lungs between mice infected with C. gattii R265 and C. neoformans H99. The former showed alveolar expansion due to yeast proliferation with much lesser macrophage response, whereas the latter showed numerous nodules in the alveolar space consisting of macrophages and multinucleated giant cells. Furthermore, alveolar expansion was more enhanced in mice infected with C. gattii R265 than in those infected with C. gattii 5815. Our study confirmed that there is a different pathophysiology leading to death during C. gattii and C. neoformans infections. The result can provide two characteristics of C. gattii: one includes some mechanisms to escape from host recognition via macrophage and another includes a high performance of pulmonary structural alteration. These characteristics may be associated with the high virulence of C. gattii.", "author" : [ { "dropping-particle" : "", "family" : "Okubo", "given" : "Yoichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wakayama", "given" : "Megumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohno", "given" : "Hideaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Shuhei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tochigi", "given" : "Naobumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanabe", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaneko", "given" : "Yukihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamagoe", "given" : "Satoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umeyama", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shinozaki", "given" : "Minoru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nemoto", "given" : "Tetsuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakayama", "given" : "Haruo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sasai", "given" : "Daisuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishiwatari", "given" : "Takao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimodaira", "given" : "Kayoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamei", "given" : "Katsuhiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shibuya", "given" : "Kazutoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Japanese Journal of Infectious Diseases", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "216-221", "title" : "Histopathological study of murine pulmonary cryptococcosis induced by <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1128/mBio.00103-12.Editor", "author" : [ { "dropping-particle" : "", "family" : "Ngamskulrungroj", "given" : "Popchai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sionov", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "mBio American Society of Microbiology", "id" : "ITEM-5", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1-9", "title" : "The primary target organ of <i>Cryptococcus gattii </i> is different from that of <i> Cryptococcus neoformans</i> in a murine model", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{56,65\u201368}", "plainTextFormattedCitation" : "56,65\u201368", "previouslyFormattedCitation" : "^{56,65\u201368}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }56,65–68 Using phylogenetic analysis on IGSI, IGSII and IGSI + 5S ribosomal ribonucleic acid? (rRNA) + IGSII regions of Cryptococcus found at least six genotypes of Cryptococcus, each of them with various subgroups.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.femsyr.2005.05.005", "ISSN" : "15671356", "PMID" : "16061425", "abstract" : "Cryptococcus neoformans is an opportunistic basidiomycete responsible for the high incidence of cryptococcosis in patients with AIDS and in other immune-compromised individuals. This study, which focused on the molecular structure and genetic variability of the two varieties in the C. neoformans and Cryptococcus gattii species complex, employed sequence analysis of the intergenic spacer regions, IGSI and IGSII. The IGS region is the most rapidly evolving region of the rDNA families. The IGSI displayed the most genetic variability represented by nucleotide base substitutions and the presence of long insertions/deletions (indels). In contrast, the IGSII region exhibited less heterogeneity and the indels were not as extensive as those displayed in the IGSI region. Both intergenic spacers contained short, interspersed repeat motifs, which can be related to length polymorphisms observed between sequences. Phylogenetic analysis undertaken in the IGSI, IGSII and IGSI + 5S rRNA + IGSII regions revealed the presence of six major phylogenetic lineages, some of which segregated into subgroups. The major lineages are represented by genotypes 1 (C. neoformans var. grubii), genotype 2 (C. neoformans var. neoformans), and genotypes 3, 4, 5 and 6 represented by C. gattii. Genotype 6 is a newly described IGS genotypic group within the C. neoformans species complex. With the inclusion of IGS subgenotypic groups, our sequence analysis distinguished 12 different lineages. Sequencing of clones, which was performed to determine the presence of multiple alleles at the IGS locus in several hybrid strains, yielded a single IGS sequence type per isolate, thus suggesting that the selected group of cloned strains was mono-allelic at this locus. IGS sequence analyses proved to be a powerful technique for the delineation of the varieties of C. neoformans and C. gattii at genotypic and subgenotypic levels. ?? 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiesling", "given" : "Traci", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fell", "given" : "Jack W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "1129-1140", "title" : "Comparative analysis of the intergenic spacer regions and population structure of the species complex of the pathogenic yeast <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁵⁶", "plainTextFormattedCitation" : "56", "previouslyFormattedCitation" : "⁵⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }56 In recent years, there has been increasing interest in proposing C. neoformans var. neoformans (serotype D) as a different species from C. neoformans var. grubii (serotype A).ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.fgb.2015.02.009", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10960937", "PMID" : "25721988", "abstract" : "Phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic Cryptococcus gattii/. Cryptococcus neoformans species complex. Genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. Consequently, we propose to recognize the current C. neoformans var. grubii and C. neoformans var. neoformans as separate species, and five species within C. gattii. The type strain of C. neoformans CBS132 represents a serotype AD hybrid and is replaced. The newly delimited species differ in aspects of pathogenicity, prevalence for patient groups, as well as biochemical and physiological aspects, such as susceptibility to antifungals. MALDI-TOF mass spectrometry readily distinguishes the newly recognized species.", "author" : [ { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theelen", "given" : "Bart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolecka", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polacheck", "given" : "Itzhack", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sionov", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falk", "given" : "Rama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parnmen", "given" : "Sittiporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lumbsch", "given" : "H. Thorsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "16-48", "publisher" : "Elsevier Inc.", "title" : "Recognition of seven species in the <i>Cryptococcus gattii </i>/<i> Cryptococcus neoformans</i> species complex", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1128/mBio.00311-15", "ISSN" : "2150-7511", "abstract" : "Cryptococcus neoformans is a human opportunistic fungal pathogen causing severe disseminated meningoencephalitis, mostly in patients with cellular immune defects. This species is divided into three serotypes: A, D, and the AD hybrid. Our objectives were to compare population structures of serotype A and D clinical isolates and to assess whether infections with AD hybrids differ from infections with the other serotypes. For this purpose, we analyzed 483 isolates and the corresponding clinical data from 234 patients enrolled during the CryptoA/D study or the nationwide survey on cryptococcosis in France. Isolates were characterized in terms of ploidy, serotype, mating type, and genotype, utilizing flow cytometry, serotype- and mating type-specific PCR amplifications, and multilocus sequence typing (MLST) methods. Our results suggest that C. neoformans serotypes A and D have different routes of multiplication (primarily clonal expansion versus recombination events for serotype A and serotype D, respectively) and important genomic differences. Cryptococcosis includes a high proportion of proven or probable infections (21.5%) due to a mixture of genotypes, serotypes, and/or ploidies. Multivariate analysis showed that parameters independently associated with failure to achieve cerebrospinal fluid (CSF) sterilization by week 2 were a high serum antigen titer, the lack of flucytosine during induction therapy, and the occurrence of mixed infection, while infections caused by AD hybrids were more likely to be associated with CSF sterilization. Our study provides additional evidence for the possible speciation of C. neoformans var. neoformans and grubii and highlights the importance of careful characterization of causative isolates. IMPORTANCE: Cryptococcus neoformans is an environmental fungus causing severe disease, estimated to be responsible for 600,000 deaths per year worldwide. This species is divided into serotypes A and D and an AD hybrid, and these could be considered two different species and an interspecies hybrid. The objectives of our study were to compare population structures of serotype A and serotype D and to assess whether infections with AD hybrids differ from infections with serotype A or D isolates in terms of clinical presentation and outcome. For this purpose, we used clinical data and strains from patients diagnosed with cryptococcosis in France. Our results suggest that, according to the serotype, isolates have different routes of multipli\u2026", "author" : [ { "dropping-particle" : "", "family" : "Desnos-Ollivier", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patel", "given" : "Sweta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raoux-Barbot", "given" : "Doroth\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Fran\u00e7oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "mBio", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "e00311-15", "title" : "Cryptococcosis serotypes impact outcome and provide evidence of <i> Cryptococcus neoformans</i> speciation", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^36,50", "plainTextFormattedCitation" : "36,50", "previouslyFormattedCitation" : "^36,50" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }36,50 Similarly, another suggestion is to divide C. gattii into five different species because of their apparent differences of phylogenetic analysis and population structure.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.fgb.2015.02.009", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10960937", "PMID" : "25721988", "abstract" : "Phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic Cryptococcus gattii/. Cryptococcus neoformans species complex. Genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. Consequently, we propose to recognize the current C. neoformans var. grubii and C. neoformans var. neoformans as separate species, and five species within C. gattii. The type strain of C. neoformans CBS132 represents a serotype AD hybrid and is replaced. The newly delimited species differ in aspects of pathogenicity, prevalence for patient groups, as well as biochemical and physiological aspects, such as susceptibility to antifungals. MALDI-TOF mass spectrometry readily distinguishes the newly recognized species.", "author" : [ { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theelen", "given" : "Bart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolecka", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polacheck", "given" : "Itzhack", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sionov", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falk", "given" : "Rama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parnmen", "given" : "Sittiporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lumbsch", "given" : "H. 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Distinction between the two species is based on phenotypic and genotypic characteristics. Recently, it was proposed that C. neoformans be divided into two species and C. gattii into five species based on a phylogenetic analysis of 115 isolates. While this proposal adds to the knowledge about the genetic diversity and population structure of cryptococcosis agents, the published genotypes of 2,606 strains have already revealed more genetic diversity than is encompassed by seven species. Naming every clade as a separate species at this juncture will lead to continuing nomenclatural instability. In the absence of biological differences between clades and no consensus about how DNA sequence alone can delineate a species, we recommend using \u201c Cryptococcus neoformans species complex\u201d and \u201c C. gattii species complex\u201d as a practical intermediate step, rather than creating more species. This strategy recognizes genetic diversity without creating confusion.", "author" : [ { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "John E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickes", "given" : "Brian L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuomo", "given" : "Christina A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wollenburg", "given" : "Kurt R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bicanic", "given" : 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C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Thomas J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williamson", "given" : "Peter R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jianping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelazny", "given" : "Adrian M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "mSphere American Society for Microbiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "e00357-16", "title" : "The case for adopting the \u201cspecies complex\u201d nomenclature for the etiologic agents of cryptococcosis", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶⁹", "plainTextFormattedCitation" : "69", "previouslyFormattedCitation" : "⁶⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }69 However, no consensus has yet been reached on nomenclature. Global epidemiology of Cryptococcus C. neoformans and C. gattii has a worldwide distribution with their specific areas for different serotypesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev.micro.60.080805.142102", "ISBN" : "0066-4227 (Print)\\n0066-4227 (Linking)", "ISSN" : "0066-4227", "PMID" : "16704346", "abstract" : "Cryptococcus neoformans is a major cause of fungal meningoencephalitis in immunocompromised patients. Despite recent advances in the genetics and molecular biology of C. neoformans, and improved techniques for molecular epidemiology, aspects of the ecology, population structure, and mode of reproduction of this environmental pathogen remain to be established. Application of recent insights into the life cycle of C. neoformans and its different ways of engaging in sexual reproduction under laboratory conditions has just begun to affect research on the ecology and epidemiology of this human pathogenic fungus. The melding of these disparate disciplines should yield rich dividends in our understanding of the evolution of microbial pathogens, providing insights relevant to diagnosis, treatment, and prevention", "author" : [ { "dropping-particle" : "", "family" : "Lin", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annu.Rev.Microbiol.", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "69-105", "title" : "The biology of the <i> Cryptococcus neoformans</i> species complex", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³²", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32 (Table 1). In the ARTEMIS DISK global antifungal surveillance project (1999-2007) C. neoformans was the most common yeast isolated after Candida.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/JCM.01747-08", "ISSN" : "0095-1137", "abstract" : "Fluconazole in vitro susceptibility test results determined by the CLSI M44-A disk diffusion method for 11,240 isolates of noncandidal yeasts were collected from 134 study sites in 40 countries from June 1997 through December 2007. Data were collected for 8,717 yeast isolates tested with voriconazole from 2001 through 2007. A total of 22 different species/organism groups were isolated, of which Cryptococcus neoformans was the most common (31.2% of all isolates). Overall, Cryptococcus (32.9%), Saccharomyces (11.7%), Tricho-sporon (10.6%), and Rhodotorula (4.1%) were the most commonly identified genera. The overall percentages of isolates in each category (susceptible, susceptible dose dependent, and resistant) were 78.0%, 9.5%, and 12.5% and 92.7%, 2.3%, and 5.0% for fluconazole and voriconazole, respectively. Less than 30% of fluconazole-resistant isolates of Cryptococcus spp., Cryptococcus albidus, Cryptococcus laurentii, Trichosporon beigelii/Tricho-sporon cutaneum, Rhodotorula spp., Rhodotorula rubra/Rhodotorula mucilaginosa, and Rhodotorula glutinis remained susceptible to voriconazole. Emerging resistance to fluconazole was documented among isolates of C. neoformans from the Asia-Pacific, Africa/Middle East, and Latin American regions but not among isolates from Europe or North America. This survey documents the continuing broad spectrum of activity of voriconazole against opportunistic yeast pathogens but identifies several of the less common species with decreased azole susceptibility. These organisms may pose a future threat to optimal antifungal therapy and emphasize the importance of prompt and accurate species identification. Copyright \u00a9 2009, American Society for Microbiology. All Rights Reserved.", "author" : [ { "dropping-particle" : "", "family" : "Pfaller", "given" : "M.A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diekema", "given" : "D.J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gibbs", "given" : "D.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Newell", "given" : "V.A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijie", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dzierzanowska", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klimko", "given" : "N.N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Letscher-Bru", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lisalova", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muehlethaler", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rennison", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaidi", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "The Global Antifungal Surveillance Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "117-123", "title" : "Results from the ARTEMIS DISK global antifungal surveillance study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1080/13693780801972490", "ISSN" : "1369-3786", "PMID" : "19180725", "abstract" : "The emergence of less common fungal pathogens has been increasingly reported in the last decade. We describe 25 cases of Rhodotorula spp. isolated from blood cultures at a large Brazilian tertiary teaching hospital from 1996-2004. We also investigated the in vitro activity of four antifungal drugs, using a standardized method. The median age of patients was 43 years. The majority of patients (88%) had a central venous catheter (CVC) and 10 (40%) were recipients of a bone marrow transplant. The episode was classified as a bloodstream infection (BSI) in 80% of the patients. Amphotericin B deoxycholate was the most common antifungal used and CVC was removed in 89.5% of the patients. Death occurred in four patients (17.4%), all classified as BSI. All strains were identified as R. mucilaginosa by conventional methods. Misidentification of the species was observed in 20% and 5% of the strains with the Vitek Yeast Biochemical Card and API 20C AUX systems, respectively. Amphotericin B demonstrated good in vitro activity (MIC50/90, 0.5 microg/ml) and the MICs for fluconazole were high for all strains (MIC50/90, >64 microg/ml).", "author" : [ { "dropping-particle" : "", "family" : "Almeida", "given" : "Gisele M Duboc", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costa", "given" : "Silvia Figueiredo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melhem", "given" : "Marcia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Motta", "given" : "Adriana L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szeszs", "given" : "Maria Walderez", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyashita", "given" : "Fumiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pierrotti", "given" : "Ligia C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossi", "given" : "Fl\u00e1via", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burattini", "given" : "Marcelo N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "547-56", "title" : "<i>Rhodotorula</i> spp. isolated from blood cultures: clinical and microbiological aspects.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^70,71", "plainTextFormattedCitation" : "70,71", "previouslyFormattedCitation" : "^70,71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }70,71 Of the clinical non-Candida yeast isolates, 31% were identified as C. neoformans and 1% as C. gattii.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/JCM.01747-08", "ISSN" : "0095-1137", "abstract" : "Fluconazole in vitro susceptibility test results determined by the CLSI M44-A disk diffusion method for 11,240 isolates of noncandidal yeasts were collected from 134 study sites in 40 countries from June 1997 through December 2007. Data were collected for 8,717 yeast isolates tested with voriconazole from 2001 through 2007. A total of 22 different species/organism groups were isolated, of which Cryptococcus neoformans was the most common (31.2% of all isolates). Overall, Cryptococcus (32.9%), Saccharomyces (11.7%), Tricho-sporon (10.6%), and Rhodotorula (4.1%) were the most commonly identified genera. The overall percentages of isolates in each category (susceptible, susceptible dose dependent, and resistant) were 78.0%, 9.5%, and 12.5% and 92.7%, 2.3%, and 5.0% for fluconazole and voriconazole, respectively. Less than 30% of fluconazole-resistant isolates of Cryptococcus spp., Cryptococcus albidus, Cryptococcus laurentii, Trichosporon beigelii/Tricho-sporon cutaneum, Rhodotorula spp., Rhodotorula rubra/Rhodotorula mucilaginosa, and Rhodotorula glutinis remained susceptible to voriconazole. Emerging resistance to fluconazole was documented among isolates of C. neoformans from the Asia-Pacific, Africa/Middle East, and Latin American regions but not among isolates from Europe or North America. This survey documents the continuing broad spectrum of activity of voriconazole against opportunistic yeast pathogens but identifies several of the less common species with decreased azole susceptibility. These organisms may pose a future threat to optimal antifungal therapy and emphasize the importance of prompt and accurate species identification. Copyright \u00a9 2009, American Society for Microbiology. All Rights Reserved.", "author" : [ { "dropping-particle" : "", "family" : "Pfaller", "given" : "M.A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diekema", "given" : "D.J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gibbs", "given" : "D.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Newell", "given" : "V.A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijie", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dzierzanowska", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klimko", "given" : "N.N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Letscher-Bru", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lisalova", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muehlethaler", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rennison", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaidi", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "The Global Antifungal Surveillance Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "117-123", "title" : "Results from the ARTEMIS DISK global antifungal surveillance study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁰", "plainTextFormattedCitation" : "70", "previouslyFormattedCitation" : "⁷⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }70 However, C. gattii is an emerging pathogen responsible, for example, for an ongoing epidemic in North America and Vancouver Island in immunocompetent patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1073/pnas.0402981101", "ISBN" : "0027-8424 (Print)\\n0027-8424 (Linking)", "ISSN" : "0027-8424", "PMID" : "15572442", "abstract" : "Cryptococcus gattii causes life-threatening infection of the pulmonary and central nervous systems in hosts with normal immunity and traditionally has been considered to be restricted geographically to tropical and subtropical climates. The recent outbreak of C. gattii in the temperate climate of Vancouver Island, BC, Canada, led to a collaborative investigation. The objectives of the current study were to ascertain the environmental source of the outbreak infections, survey the molecular types of the outbreak and environmental cryptococcal isolates, and determine the extent of genetic diversity among the isolates. PCR-fingerprinting and amplified fragment length polymorphism (AFLP) were used to examine the genotypes, and mating assays were performed to determine the mating type of the isolates. All outbreak and environmental isolates belonged to C. gattii. Concordant results were obtained by using PCR-fingerprinting and AFLP analysis. The vast majority of clinical and veterinary infections were caused by isolates of the molecular type VGII/AFLP6, but two were caused by molecular type VGI/AFLP4. All environmental isolates belonged to molecular type VGII/AFLP6. Two or three subtypes were observed within VGII/AFLP6 among outbreak and environmental isolates. All mating-competent isolates were of the alpha-mating type. The emergence of this usually tropical pathogen on Vancouver Island highlights the changing distribution of this genotype and emphasizes the importance of an ongoing collaborative effort to monitor the global epidemiology of this yeast.", "author" : [ { "dropping-particle" : "", "family" : "Kidd", "given" : "S E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tscharke", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huynh", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartlett", "given" : "K H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fyfe", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Macdougall", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the National Academy of Sciences of the United States of America", "id" : "ITEM-1", "issue" : "49", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "17258-17263", "title" : "A rare genotype of <i>Cryptococcus gattii </i> caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada).", "type" : "article-journal", "volume" : "101" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1155/2009/840452", "ISBN" : "1687-708X (Print)\\r1687-708X (Linking)", "ISSN" : "1687-708X", "PMID" : "19503836", "abstract" : "During the latter half of the twentieth century, fungal pathogens such as Cryptococcus neoformans were increasingly recognized as a significant threat to the health of immune compromised populations throughout the world. Until recently, the closely related species C. gattii was considered to be a low-level endemic pathogen that was confined to tropical regions such as Australia. Since 1999, C. gattii has emerged in the Pacific Northwest region of North America and has been responsible for a large disease epidemic among generally healthy individuals. The changing epidemiology of C. gattii infection is likely to be a consequence of alterations in fungal ecology and biology and illustrates its potential to cause serious human disease. This review summarizes selected biological and clinical aspects of C. gattii that are particularly relevant to the recent North American outbreak and compares these to the Australian and South American experience.", "author" : [ { "dropping-particle" : "", "family" : "Dixit", "given" : "Ashwin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carroll", "given" : "Scott F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qureshi", "given" : "Salman T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Interdisciplinary perspectives on infectious diseases", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "840452", "title" : "<i>Cryptococcus gattii</i>: an emerging cause of fungal disease in North America.", "type" : "article-journal", "volume" : "2009" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^72,73", "plainTextFormattedCitation" : "72,73", "previouslyFormattedCitation" : "^72,73" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72,73 There is also evidence of its spread outside the original endemic area.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/13693786.2011.607854", "ISBN" : "0844743208", "ISSN" : "1369-3786", "author" : [ { "dropping-particle" : "", "family" : "Harris", "given" : "Julie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lockhart", "given" : "Shawn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiller", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "113-129", "title" : "<i>Cryptococcus gattii</i> : where do we go from here?", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3201/eid1607.100106", "ISBN" : "1080-6059 (Electronic)\\r1080-6040 (Linking)", "ISSN" : "10806059", "PMID" : "20587194", "abstract" : "We report a patient in Japan infected with Cryptococcus gattii genotype VGIIa who had no recent history of travel to disease-endemic areas. This strain was identical to the Vancouver Island outbreak strain R265. Our results suggest that this virulent strain has spread to regions outside North America.", "author" : [ { "dropping-particle" : "", "family" : "Okamoto", "given" : "Koh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatakeyama", "given" : "Shuji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Itoyama", "given" : "Satoru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nukui", "given" : "Yoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshino", "given" : "Yusuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitazawa", "given" : "Takatoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yotsuyanagi", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikeda", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugita", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koike", "given" : "Kazuhiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Emerging Infectious Diseases", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1155-1157", "title" : "<i>Cryptococcus gattii </i> genotype VGIIa infection in man, Japan, 2007", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jiac.2017.12.014", "ISSN" : "14377780", "PMID" : "29352650", "abstract" : "A 71-year-old Japanese man with travel history to the Vancouver Island, Canada was diagnosed the pulmonary and central nervous system infections caused by Cryptococcus gattii genotype VGIIa. This is the first imported case of Cryptococcus gattii genotype VGIIa infection from endemic area of North America to Japan. He was recovery with no residual neurological dysfunction by early resection of brain mass and antifungal therapy. Early surgical resection of cerebellar cryptococcoma may shorten the length of induction therapy with antifungal drugs.", "author" : [ { "dropping-particle" : "", "family" : "Kitaura", "given" : "Tsuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takahashi", "given" : "Masamichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umeyama", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeshita", "given" : "Nozomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katanami", "given" : "Yuichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takaya", "given" : "Saho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Kei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kutsuna", "given" : "Satoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayakawa", "given" : "Kayoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Yasuyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Takahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narita", "given" : "Yoshitaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohmagari", "given" : "Norio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Infection and Chemotherapy", "id" : "ITEM-3", "issue" : "2017", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "12-14", "publisher" : "Elsevier Taiwan LLC", "title" : "<i>Cryptococcus gattii</i> genotype VGIIa infection imported from Vancouver Island to Japan", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^74\u201376", "plainTextFormattedCitation" : "74\u201376", "previouslyFormattedCitation" : "^74\u201376" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }74–76 A recent epidemiological study covering Asia, Africa, America, Europe and Oceania and analyses of 68,811 isolates of C. neoformans and C. gattii revealed that C. neoformans var. grubii molecular type VN1 is the most common type except in Oceania.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2013/675213", "ISSN" : "2090-908X", "PMID" : "24278784", "abstract" : "Cryptococcosis is a fungal disease affecting more than one million people per year worldwide. The main etiological agents of cryptococcosis are the two sibling species Cryptococcus neoformans and Cryptococcus gattii that present numerous differences in geographical distribution, ecological niches, epidemiology, pathobiology, clinical presentation and molecular characters. Genotyping of the two Cryptococcus species at subspecies level supplies relevant information to understand how this fungus has spread worldwide, the nature of its population structure, and how it evolved to be a deadly pathogen. At present, nine major molecular types have been recognized: VNI, VNII, VNB, VNIII, and VNIV among C. neoformans isolates, and VGI, VGII, VGIII, and VGIV among C. gattii isolates. In this paper all the information available in the literature concerning the isolation of the two Cryptococcus species has been collected and analyzed on the basis of their geographical origin, source of isolation, level of identification, species, and molecular type. A detailed analysis of the geographical distribution of the major molecular types in each continent has been described and represented on thematic maps. This study represents a useful tool to start new epidemiological surveys on the basis of the present knowledge.", "author" : [ { "dropping-particle" : "", "family" : "Cogliati", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scientifica", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-23", "title" : "Global molecular epidemiology of <i> Cryptococcus neoformans</i> and <i>Cryptococcus gattii </i>: an atlas of the molecular types.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1469-0691.2009.02930.x", "ISBN" : "1469-0691 (Electronic)\\r1198-743X (Linking)", "ISSN" : "1198743X", "PMID" : "19694765", "abstract" : "This study investigated the microbiological characteristics of 100 clinical isolates of Cryptococcus neoformans species complex, including serotypes, mating types, molecular types, antifungal susceptibility and virulence. The isolates were collected at National Taiwan University Hospital from 1999 to 2004. Eight isolates of C. neoformans from pigeon droppings were also evaluated. Among these isolates, 99 were C. neoformans var. grubii serotype A and one was C. neoformans var. gattii serotype B. All of these isolates were alpha mating types. PCR fingerprinting, generated by primers M13 and (GACA)(4), and URA5 gene restriction fragment length polymorphism analysis revealed that C. neoformans var. grubii isolates belonged to the VNI (98 isolates) and the VNII (one isolate) types, and the single C. neoformans var. gattii was VGI type. The similar profiles of clinical and environmental isolates suggest that patients might acquire these yeasts from the environment. The MIC(90) for fluconazole, itraconazole, 5-flucytosine, voriconazole and amphotericin B against all C. neoformans isolates were 8, 0.5, 4, 0.125 and 0.5 mg/L, respectively. All clinical isolates produced urease, phospholipase, capsule and melanin, but these activities varied with individual isolates. Analysis of six clinical and two environmental isolates with various levels of phospholipase activity indicated a correlation between phospholipase activity and the ability to adhere to the lung epithelial cell line, A549. The extent of cell damage, as indicated by lactate dehydrogenase release, also paralleled the phospholipase activity of these isolates. In addition, production of melanin contributed significant protection against amphotericin B killing of the isolates tested.", "author" : [ { "dropping-particle" : "", "family" : "Liaw", "given" : "S. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "H. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsueh", "given" : "P. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "696-703", "title" : "Microbiological characteristics of clinical isolates of <i>Cryptococcus neoformans</i> in Taiwan: serotypes, mating types, molecular types, virulence factors, and antifungal susceptibility", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.fgb.2014.10.017", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10871845", "PMID" : "25445309", "abstract" : "a b s t r a c t Cryptococcosis is a significant invasive fungal infection with noteworthy morbidity and mortality, pri-marily caused by Cryptococcus neoformans and Cryptococcus gattii. In China, C. neoformans var. grubii (especially molecular type VNI) is the most common variety in the environment and responsible for the majority of cryptococcal infections. C. gattii infections are quite rare in China and the primary molec-ular type is VGI, which is closely related to C. gattii isolates in Australia. Interestingly, the majority of cryptococcosis in China were reported in the HIV-uninfected patients (especially immunocompetent hosts). This unique phenomenon may be attributed to multiple polymorphisms in the genes encoding mannose-binding lectin (MBL) and Fc-gamma receptor 2B (FCGR2B) in the Han population, the major eth-nic group in China. Compared to immunocompromised patients, immunocompetent patients with cryp-tococcal meningitis often presented with more intense inflammatory responses and more severe neurological complications, but less fungal burdens and disseminated infection. The overall prognosis, which is independently associated with amphotericin B-based initial therapy, is similar between immunocompetent and immunocompromised patients. In addition, intrathecal administration of amphotericin B has been proved to be an effective adjunctive treatment for cryptococcosis in China.", "author" : [ { "dropping-particle" : "", "family" : "Fang", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fa", "given" : "Zhenzong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "7-15", "publisher" : "Elsevier Inc.", "title" : "Epidemiology of <i>Cryptococcus</i> and cryptococcosis in China", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1111/j.1567-1364.2006.00081.x", "ISBN" : "1567-1356 (Print)\\r1567-1356 (Linking)", "ISSN" : "15671356", "PMID" : "16696657", "abstract" : "During a European Confederation of Medical Mycology (ECMM) prospective survey of cryptococcosis in Europe (from July 1997 to December 1999) 655 cases were reported from 17 countries; 565 of the completed questionnaires were evaluable. Cryptococcosis was associated with HIV infection in 77% of cases (range 57.5-94%). Assessment of the laboratory data highlighted the lack of defined standard procedures for the diagnosis of cryptococcosis: the antigen test was not usually used for screening, the disease was mainly recognised when meningitis occurred (65% of patients) and, with the exception of a few cases, the extent of the infection was not investigated. Cryptococcus neoformans was the etiological agent in all of the cases except for six caused by C. gattii and four by other Cryptococcus species. A total of 311 C. neoformans strains were serotyped by Crypto Check latex agglutination, genotyped by PCR-fingerprinting using the (GACA)4 oligonucleotide as a single primer, and their mating type was determined by PCR of the STE20 alleles. Serotype A was the most represented (51% of the isolates), followed by serotype D (30%) and serotype AD (19%). PCR-fingerprinting analysis significantly increased the percentage of hybrid strains to 30%, as 6% of the serotype A and 28% of the serotype D isolates were of the VN3 or VN4 hybrid genotype. In addition, the mating type determinations revealed the MATa serotype A allele in one haploid strain and 28 hybrids, and hybrid isolates with a single mating type (four Aalpha and two Dalpha) were also identified. This is the first prospective survey to be carried out in Europe which has attempted to investigate the epidemiology of cryptococcosis and the population structure of C. neoformans, and the results obtained thus far show the widespread involvement of AD hybrid strains in C. neoformans infections.", "author" : [ { "dropping-particle" : "", "family" : "Viviani", "given" : "Maria Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cogliati", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esposto", "given" : "Maria Carmela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemmer", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tintelnot", "given" : "Kathrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valiente", "given" : "Maria Francisca Colom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swinne", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Velegraki", "given" : "Aristea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Velho", "given" : "Rosa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoepelman", "given" : "A. I M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kouzmanov", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nowicka", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petrini", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polachek", "given" : "I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polak", "given" : "A. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radka", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sc\u1e27ar", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vasilyeva", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "614-619", "title" : "Molecular analysis of 311 <i> Cryptococcus neoformans</i> isolates from a 30-month ECMM survey of cryptococcosis in Europe", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^77\u201380", "plainTextFormattedCitation" : "77\u201380", "previouslyFormattedCitation" : "^77\u201380" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }77–80 There (Australia, New Zealand, Papua New Guinea, and Hawaii), C. gattii type VG1 was the most common types representing 39% of the total isolates, consistent with the endemicity of C. gattii.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2013/675213", "ISSN" : "2090-908X", "PMID" : "24278784", "abstract" : "Cryptococcosis is a fungal disease affecting more than one million people per year worldwide. The main etiological agents of cryptococcosis are the two sibling species Cryptococcus neoformans and Cryptococcus gattii that present numerous differences in geographical distribution, ecological niches, epidemiology, pathobiology, clinical presentation and molecular characters. Genotyping of the two Cryptococcus species at subspecies level supplies relevant information to understand how this fungus has spread worldwide, the nature of its population structure, and how it evolved to be a deadly pathogen. At present, nine major molecular types have been recognized: VNI, VNII, VNB, VNIII, and VNIV among C. neoformans isolates, and VGI, VGII, VGIII, and VGIV among C. gattii isolates. In this paper all the information available in the literature concerning the isolation of the two Cryptococcus species has been collected and analyzed on the basis of their geographical origin, source of isolation, level of identification, species, and molecular type. A detailed analysis of the geographical distribution of the major molecular types in each continent has been described and represented on thematic maps. This study represents a useful tool to start new epidemiological surveys on the basis of the present knowledge.", "author" : [ { "dropping-particle" : "", "family" : "Cogliati", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scientifica", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-23", "title" : "Global molecular epidemiology of <i> Cryptococcus neoformans</i> and <i>Cryptococcus gattii </i>: an atlas of the molecular types.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁷⁷", "plainTextFormattedCitation" : "77", "previouslyFormattedCitation" : "⁷⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }77 These conclusions were based on a combination of clinical and environmental isolates, with a dominance of clinical isolates (83%). Another study showed similarly that C. neoformans var. grubii serotype A represents 81% of all Cryptococcus isolated from all over the world.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2013/471363", "ISBN" : "2090-939x", "ISSN" : "2090-939X", "PMID" : "24052889", "abstract" : "Cryptococcal meningitis is a life-threatening opportunistic fungal infection in both HIV-infected and HIV-uninfected patients. According to the most recent taxonomy, the responsible fungus is classified into a complex that contains two species (Cryptococcus neoformans and C. gattii), with eightmajormolecular types.HIV infection is recognizedworldwide as themain underlying disease responsible for the development of cryptococcal meningitis (accounting for 80\u201390% of cases). In several areas of sub-Saharan Africa with the highest HIV prevalence despite the recent expansion of antiretroviral (ARV) therapy programme, cryptococcal meningitis is the leading cause of community-acquired meningitiswith a highmortality burden.Although cryptococcalmeningitis should be considered a neglected disease, a large body of knowledge has been developed by several studies performed in recent years. This paper will focus especially on newclinical aspects such as immune reconstitution inflammatory syndrome, advances on management, and strategies for the prevention of clinical disease.", "author" : [ { "dropping-particle" : "", "family" : "Antinori", "given" : "Spinello", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "ISRN AIDS", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-22", "title" : "New insights into HIV / AIDS-associated Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸¹", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "⁸¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81 Different levels of genetic diversity have been reported in different countries in Asia.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0072222", "ISBN" : "1932-6203", "ISSN" : "19326203", "PMID" : "24019866", "abstract" : "Cryptococcosis is an important fungal disease in Asia with an estimated 140,000 new infections annually the majority of which occurs in patients suffering from HIV/AIDS. Cryptococcus neoformans variety grubii (serotype A) is the major causative agent of this disease. In the present study, multilocus sequence typing (MLST) using the ISHAM MLST consensus scheme for the C. neoformans/C. gattii species complex was used to analyse nucleotide polymorphisms among 476 isolates of this pathogen obtained from 8 Asian countries. Population genetic analysis showed that the Asian C. neoformans var. grubii population shows limited genetic diversity and demonstrates a largely clonal mode of reproduction when compared with the global MLST dataset. HIV-status, sequence types and geography were found to be confounded. However, a correlation between sequence types and isolates from HIV-negative patients was observed among the Asian isolates. Observations of high gene flow between the Middle Eastern and the Southeastern Asian populations suggest that immigrant workers in the Middle East were originally infected in Southeastern Asia.", "author" : [ { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simwami", "given" : "Sitali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Matthew C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahyuningsih", "given" : "Retno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Arunaloke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Anuradha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikeda", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taj-Aldeen", "given" : "Saad J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Ziauddin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ip", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imran", "given" : "Darma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sjam", "given" : "Ridhawati", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sriburee", "given" : "Pojana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaicumpar", "given" : "Kunyaluk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vuddhakul", "given" : "Varaporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilles", "given" : "Luciana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iersel", "given" : "Leo J J", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meis", "given" : "Jacques F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klaassen", "given" : "Corn?? H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-14", "title" : "Geographically structured populations of <i> Cryptococcus neoformans variety grubii</i> in Asia correlate with HIV status and show a clonal population structure", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0032868", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "22427900", "abstract" : "BACKGROUND: Cryptococcus neoformans is a pathogenic yeast that causes cryptococcosis, a life threatening disease. The prevalence of cryptococcosis in Asia has been rising after the onset of the AIDS epidemic and estimates indicate more than 120 cases per 1,000 HIV-infected individuals per year. Almost all cryptococcal disease cases in both immunocompromised and immunocompetent patients in Asia are caused by C. neoformans var. grubii. Epidemiological studies on C. neoformans in pan-Asia have not been reported. The present work studies the genetic diversity of the fungus by microsatellite typing and susceptibility analysis of approximately 500 isolates from seven Asian countries.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Genetic diversity of Asian isolates of C. neoformans was determined using microsatellite analysis with nine microsatellite markers. The analysis revealed eight microsatellite complexes (MCs) which showed different distributions among geographically defined populations. A correlation between MCs and HIV-status was observed. Microsatellite complex 2 was mainly associated with isolates from HIV-negative patients, whereas MC8 was associated with those from HIV-positive patients. Most isolates were susceptible to amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole, but 17 (3.4%) and 10 (2%) were found to be resistant to 5-flucytosine and fluconazole, respectively. Importantly, five Indonesian isolates (approximately 12.5% from all Indonesian isolates investigated and 1% from the total studied isolates) were resistant to both antifungals. The majority of 5-flucytosine resistant isolates belonged to MC17.\\n\\nCONCLUSIONS: The findings showed a different distribution of genotypes of C. neoformans var. grubii isolates from various countries in Asia, as well as a correlation of the microsatellite genotypes with the original source of the strains and resistance to 5-flucytosine.", "author" : [ { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahyuningsih", "given" : "Retno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Arunaloke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Anuradha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikeda", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taj-Aldeen", "given" : "Saad J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Ziauddin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imran", "given" : "Darma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sjam", "given" : "Ridhawati", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sriburee", "given" : "Pojana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaicumpar", "given" : "Kunyaluk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingviya", "given" : "Natnicha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mouton", "given" : "Johan W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curfs-Breuker", "given" : "Ilse", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meis", "given" : "Jacques F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klaassen", "given" : "Corn\u00e9 H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "e32868", "title" : "Resistance of Asian <i> Cryptococcus neoformans</i> serotype a is confined to few microsatellite genotypes", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^63,82", "plainTextFormattedCitation" : "63,82", "previouslyFormattedCitation" : "^63,82" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }63,82 Those of Southeast Asia (Indonesia, India and Thailand) appear to have more cryptococcal polymorphisms than those of East Asia (China, Hong Kong, Japan). A rare type (ST93) has been reported to be predominant in Indonesian and Indian isolates.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0072222", "ISBN" : "1932-6203", "ISSN" : "19326203", "PMID" : "24019866", "abstract" : "Cryptococcosis is an important fungal disease in Asia with an estimated 140,000 new infections annually the majority of which occurs in patients suffering from HIV/AIDS. Cryptococcus neoformans variety grubii (serotype A) is the major causative agent of this disease. In the present study, multilocus sequence typing (MLST) using the ISHAM MLST consensus scheme for the C. neoformans/C. gattii species complex was used to analyse nucleotide polymorphisms among 476 isolates of this pathogen obtained from 8 Asian countries. Population genetic analysis showed that the Asian C. neoformans var. grubii population shows limited genetic diversity and demonstrates a largely clonal mode of reproduction when compared with the global MLST dataset. HIV-status, sequence types and geography were found to be confounded. However, a correlation between sequence types and isolates from HIV-negative patients was observed among the Asian isolates. Observations of high gene flow between the Middle Eastern and the Southeastern Asian populations suggest that immigrant workers in the Middle East were originally infected in Southeastern Asia.", "author" : [ { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simwami", "given" : "Sitali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Matthew C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahyuningsih", "given" : "Retno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Arunaloke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Anuradha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikeda", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taj-Aldeen", "given" : "Saad J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Ziauddin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ip", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imran", "given" : "Darma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sjam", "given" : "Ridhawati", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sriburee", "given" : "Pojana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaicumpar", "given" : "Kunyaluk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vuddhakul", "given" : "Varaporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trilles", "given" : "Luciana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iersel", "given" : "Leo J J", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meis", "given" : "Jacques F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klaassen", "given" : "Corn?? H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-14", "title" : "Geographically structured populations of <i> Cryptococcus neoformans variety grubii</i> in Asia correlate with HIV status and show a clonal population structure", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁶³", "plainTextFormattedCitation" : "63", "previouslyFormattedCitation" : "⁶³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }63,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0032868", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "22427900", "abstract" : "BACKGROUND: Cryptococcus neoformans is a pathogenic yeast that causes cryptococcosis, a life threatening disease. The prevalence of cryptococcosis in Asia has been rising after the onset of the AIDS epidemic and estimates indicate more than 120 cases per 1,000 HIV-infected individuals per year. Almost all cryptococcal disease cases in both immunocompromised and immunocompetent patients in Asia are caused by C. neoformans var. grubii. Epidemiological studies on C. neoformans in pan-Asia have not been reported. The present work studies the genetic diversity of the fungus by microsatellite typing and susceptibility analysis of approximately 500 isolates from seven Asian countries.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Genetic diversity of Asian isolates of C. neoformans was determined using microsatellite analysis with nine microsatellite markers. The analysis revealed eight microsatellite complexes (MCs) which showed different distributions among geographically defined populations. A correlation between MCs and HIV-status was observed. Microsatellite complex 2 was mainly associated with isolates from HIV-negative patients, whereas MC8 was associated with those from HIV-positive patients. Most isolates were susceptible to amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole, but 17 (3.4%) and 10 (2%) were found to be resistant to 5-flucytosine and fluconazole, respectively. Importantly, five Indonesian isolates (approximately 12.5% from all Indonesian isolates investigated and 1% from the total studied isolates) were resistant to both antifungals. The majority of 5-flucytosine resistant isolates belonged to MC17.\\n\\nCONCLUSIONS: The findings showed a different distribution of genotypes of C. neoformans var. grubii isolates from various countries in Asia, as well as a correlation of the microsatellite genotypes with the original source of the strains and resistance to 5-flucytosine.", "author" : [ { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khayhan", "given" : "Kantarawee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahyuningsih", "given" : "Retno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Arunaloke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Anuradha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikeda", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taj-Aldeen", "given" : "Saad J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Ziauddin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imran", "given" : "Darma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sjam", "given" : "Ridhawati", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sriburee", "given" : "Pojana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaicumpar", "given" : "Kunyaluk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingviya", "given" : "Natnicha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mouton", "given" : "Johan W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curfs-Breuker", "given" : "Ilse", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meis", "given" : "Jacques F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klaassen", "given" : "Corn\u00e9 H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "e32868", "title" : "Resistance of Asian <i> Cryptococcus neoformans</i> serotype a is confined to few microsatellite genotypes", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸²", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "⁸²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82Pathogenesis of pulmonary cryptococcosisCryptococcus and the host responseThe most common means of Cryptococcus causing infection in human is via inhalation.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MCP.0b013e328329268d", "ISBN" : "1070-5287", "ISSN" : "1070-5287", "PMID" : "19352182", "abstract" : "PURPOSE OF REVIEW: Cryptococcosis is an important opportunistic fungal infection, especially in the immunocompromised patient. Meningitis is the most common manifestation of cryptococcosis; however, cryptococcal lung disease is probably underdiagnosed, and knowledge of epidemiology, diagnosis, and treatment is necessary. RECENT FINDINGS: Cryptococcal lung disease ranges from asymptomatic colonization or infection to severe pneumonia with respiratory failure. Clinical presentation of pulmonary cryptococcosis is highly variable and often is related to the immune status of the patient. There have been many important clinical trials outlining treatment of cryptococcal meningitis in patients with AIDS, but there is a lack of treatment data available for patients with cryptococcal lung disease. Treatment recommendations for cryptococcal lung disease are made on the basis of host immune status and severity of clinical illness. For less severe disease, fluconazole therapy is recommended. In immunocompromised patients, or those with severe disease, induction therapy with an amphotericin B preparation and flucytosine, followed by fluconazole as consolidation and maintenance therapy, is recommended. SUMMARY: Cryptococcal lung disease is an important and probably underdiagnosed infection. Knowledge of the epidemiology, diagnostic methodologies, and treatment is needed to ensure good patient outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Shirley", "given" : "Rhett M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baddley", "given" : "John W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current opinion in pulmonary medicine", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "254-260", "title" : "Cryptococcal lung disease.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0095-1137 (Print)\\r0095-1137 (Linking)", "ISSN" : "00951137", "PMID" : "8586730", "abstract" : "We examined clinical (pulmonary cryptococcosis and cryptococcal meningitis) and environmental (pigeon excreta) isolates of Cryptococcus neoformans var. neoformans (serotype A) in the southern Japanese prefecture of Nagasaki. The random amplified polymorphic DNA profiles obtained by using three primers revealed six patterns among 21 clinical isolates and three patterns among 8 environmental isolates. Pattern I was the most common (18 of 29 isolates) and was found among isolates obtained throughout the entire Nagasaki Prefecture. Patterns I, III, and IV were found among both clinical and environmental isolates. Patterns I and IV had a characteristic distribution, and in particular, pattern IV was isolated exclusively (five of six isolates) from isolates from Nagasaki City. Two environmental isolates from two locations associated strongly with two patients revealed identical random amplified polymorphic DNA patterns (patterns I and IV) for isolates from each patient. Our results suggest that clinical and environmental isolates belong to the same pool of C. neoformans isolates and that these isolates have certain geographic locations, although the number of isolated strains was limited.", "author" : [ { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koga", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomono", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaku", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamazaki", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arisawa", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "3328-3332", "title" : "Random amplified polymorphic DNA analysis of clinically and environmentally isolated <i> Cryptococcus neoformans</i> in Nagasaki", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0095-1137 (Print)\\r0095-1137 (Linking)", "ISSN" : "00951137", "PMID" : "8727912", "abstract" : "Sixty-one clinical and forty-nine environmental isolates of Cryptococcus neoformans var. gattii from Australia and the United States were analyzed by random amplification of polymorphic DNA (RAPD), using 12- to 22-mer primers in pairs, and/or PCR fingerprinting with a single primer derived from the microsatellite core sequence of the wild-type phage M13 (5' GAGGGTGGCGGTTCT 3'). Three major genetic profiles were identified by both typing techniques. A single RAPD profile (VGI) predominated among clinical isolates (44 of 48, 92%) and isolates from host eucalypts (45 of 45, 100%) from Australia. Of the 94 Australian isolates, 4 (3 clinical and 1 environmental) were assigned to profile VGII; 2 of these were recovered from patients and one was recovered from plant debris from Western Australia. Only one Australian clinical isolate was assigned to profile VGIII. A different distribution of RAPD profiles (four VGIII, two VGII, and one VGI) was found among four clinical and three environmental isolates from the United States. RAPD profiles of 8 of the 101 isolates studied revealed minor genetic variants, 4 of profile VGI and 4 of profile VGII. Genetic concordance between the majority of clinical and environmental isolates in Australia is consistent with the hypothesis that human disease is acquired from exposure to host eucalypts. Profiles of clinical isolates were independent of body site of infection, and profiles of all isolates were stable over time. Analysis by PCR fingerprinting confirmed the RAPD results. A second RAPD profile (VGII) was associated with infection in southwest Western Australia, where the two host eucalypts do not occur naturally. This raises the possibility of an alternative and as yet unidentified natural habitat of C. neoformans var. gattii. Our results indicate that RAPD analysis is a sensitive and useful method for investigating environmental sources of human infection with this biotype.", "author" : [ { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Sharon C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruma", "given" : "Patricia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Tania J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellis", "given" : "David H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brownlee", "given" : "Alan G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "1253-1260", "title" : "Concordance of clinical and environmental isolates of <i> Cryptococcus neoformans var. gattii</i> by random amplification of polymorphic DNA analysis and PCR fingerprinting", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^83\u201385", "plainTextFormattedCitation" : "83\u201385", "previouslyFormattedCitation" : "^83\u201385" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }83–85 Spores and small desiccated yeast cells (approximately 1-5 ?m in diameter) of Cryptococcus may reach the lower airways and pulmonary alveoli.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/IAI.00542-09", "ISBN" : "1098-5522 (Electronic)\\r0019-9567 (Linking)", "ISSN" : "00199567", "PMID" : "19620339", "abstract" : "Cryptococcus neoformans and Cryptococcus gattii are closely related pathogenic fungi that cause pneumonia and meningitis in both immunocompromised and immunocompetent hosts and are a significant global infectious disease risk. Both species are found in the environment and are acquired via inhalation, leading to an initial pulmonary infection. The infectious propagule is unknown but is hypothesized to be small desiccated yeast cells or spores produced by sexual reproduction (opposite- or same-sex mating). Here we characterize the morphology, germination properties, and virulence of spores. A comparative morphological analysis of hyphae and spores produced by opposite-sex mating, same-sex mating, and self-fertile diploid strains was conducted by scanning electron microscopy, yielding insight into hyphal/basidial morphology and spore size, structure, and surface properties. Spores isolated by microdissection were found to readily germinate even on water agarose medium. Thus, nutritional signals do not appear to be required to stimulate spore germination, and as-yet-unknown environmental factors may normally constrain germination in nature. As few as 500 CFU of a spore-enriched infectious inoculum (approximately 95% spores) of serotype A C. neoformans var. grubii were fully virulent (100% lethal infection) in both a murine inhalation virulence model and the invertebrate model host Galleria mellonella. In contrast to a previous report on C. neoformans var. neoformans, spores of C. neoformans var. grubii were not more infectious than yeast cells. Molecular analysis of isolates recovered from tissues of infected mice (lung, spleen, and brain) provides evidence for infection and dissemination by recombinant spore products. These studies provide a detailed morphological and physiological analysis of the spore and document that spores can serve as infectious propagules.", "author" : [ { "dropping-particle" : "", "family" : "Velagapudi", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsueh", "given" : "Yen Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geunes-Boyer", "given" : "Scarlett", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Jo Rae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "4345-4355", "title" : "Spores as infectious propagules of <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸⁶", "plainTextFormattedCitation" : "86", "previouslyFormattedCitation" : "⁸⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86 Respiratory defences such as mucociliary transport, airflow turbulence, physical epithelial mucosal barrier and mucus trapping system do not prevent these small infectious propagules reaching the distal lung.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/IAI.00542-09", "ISBN" : "1098-5522 (Electronic)\\r0019-9567 (Linking)", "ISSN" : "00199567", "PMID" : "19620339", "abstract" : "Cryptococcus neoformans and Cryptococcus gattii are closely related pathogenic fungi that cause pneumonia and meningitis in both immunocompromised and immunocompetent hosts and are a significant global infectious disease risk. Both species are found in the environment and are acquired via inhalation, leading to an initial pulmonary infection. The infectious propagule is unknown but is hypothesized to be small desiccated yeast cells or spores produced by sexual reproduction (opposite- or same-sex mating). Here we characterize the morphology, germination properties, and virulence of spores. A comparative morphological analysis of hyphae and spores produced by opposite-sex mating, same-sex mating, and self-fertile diploid strains was conducted by scanning electron microscopy, yielding insight into hyphal/basidial morphology and spore size, structure, and surface properties. Spores isolated by microdissection were found to readily germinate even on water agarose medium. Thus, nutritional signals do not appear to be required to stimulate spore germination, and as-yet-unknown environmental factors may normally constrain germination in nature. As few as 500 CFU of a spore-enriched infectious inoculum (approximately 95% spores) of serotype A C. neoformans var. grubii were fully virulent (100% lethal infection) in both a murine inhalation virulence model and the invertebrate model host Galleria mellonella. In contrast to a previous report on C. neoformans var. neoformans, spores of C. neoformans var. grubii were not more infectious than yeast cells. Molecular analysis of isolates recovered from tissues of infected mice (lung, spleen, and brain) provides evidence for infection and dissemination by recombinant spore products. These studies provide a detailed morphological and physiological analysis of the spore and document that spores can serve as infectious propagules.", "author" : [ { "dropping-particle" : "", "family" : "Velagapudi", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsueh", "given" : "Yen Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geunes-Boyer", "given" : "Scarlett", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Jo Rae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "4345-4355", "title" : "Spores as infectious propagules of <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mib.2010.05.003.Dueling", "author" : [ { "dropping-particle" : "", "family" : "Botts", "given" : "Michael R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hull", "given" : "Christina M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Opin Microbiol.", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "437-442", "title" : "Dueling in the lung: How <i> Cryptococcus </i> spores race the host for survival", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "1180-2332", "PMID" : "22346380", "abstract" : "OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.\\n\\nDATA SOURCES: English articles from 1966 to present were identified from a MEDLINE search.\\n\\nSTUDY SELECTION: Articles were identified by a MEDLINE search of 'exp lung/' or 'exp lung diseases/' and 'exp fungi/'. The titles and abstracts were screened to identify articles that contained salient information pertaining to host defense of respiratory mycoses.\\n\\nDATA EXTRACTION: Information was summarized from the articles pertaining to host defense of pulmonary mycosis that had been identified by the MEDLINE search.\\n\\nDATA SYNTHESIS: Fungi represent a unique and highly diverse group of pathogenic organisms that have become an increasingly prevalent cause of life-threatening illness. A worldwide increase in persons with immunodeficiency has been a major contributing factor to the increase in fungal disease. As a result, clinicians are faced with an expanding array of fungal infections that pose diagnostic and therapeutic challenges. The respiratory tract is the route of acquisition for many important fungal infections; thus, understanding the host defense in the lung is an essential component of understanding host defense to fungal disease. With this understanding, fungi may be divided on the basis of the predilection of certain mycosis for specific immune defects.\\n\\nCONCLUSIONS: By separating fungi based on the host immune defects that predispose to disease, in conjunction with traditional divisions based on the geographic distribution of fungi, clinicians are able to focus their diagnostic efforts and to identify fungal pathogens better. In addition, an understanding of the normal host defense mechanisms that serve to control fungal infections is essential to the development of novel antifungal therapies.", "author" : [ { "dropping-particle" : "", "family" : "Mody", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warren", "given" : "P W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Canadian journal of infectious diseases = Journal canadien des maladies infectieuses", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "147-55", "title" : "Host defence to pulmonary mycosis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Zimmer", "given" : "B.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hempel", "given" : "H.O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodman", "given" : "N.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycopathologia", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "1984" ] ] }, "page" : "149-153", "title" : "Pathogenicity o f the basidiospores of <i>Filobasidiella neoformans</i>", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^86\u201389", "plainTextFormattedCitation" : "86\u201389", "previouslyFormattedCitation" : "^86\u201389" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86–89 Both innate and adaptive immune systems are involved in host response against Cryptococcus infection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.fgb.2014.11.006", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10960937", "PMID" : "25498576", "abstract" : "The vast majority of infection with cryptococcal species occurs with Cryptococcus neoformans in the severely immunocompromised. A significant exception to this is the infections of those with apparently normal immune systems by Cryptococcus gattii. Susceptibility to cryptococcosis can be broadly categorised as a defect in adaptive immune responses, especially in T cell immunity. However, innate immune cells such as macrophages play a key role and are likely the primary effector cell in the killing and ultimate clearance of cryptococcal infection. In this review we discuss the current state of our understanding of how the immune system responds to cryptococcal infection in health and disease, with reference to the work communicated at the 9th International Conference on Cryptococcus and Cryptococcosis (ICCC9). We have focussed on cell mediated responses, particularly early in infection, but with the aim of presenting a broad overview of our understanding of immunity to cryptococcal infection, highlighting some recent advances and offering some perspectives on future directions.", "author" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Josie F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "Simon A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "76-86", "publisher" : "Elsevier Inc.", "title" : "Immunity to <i> Cryptococcus neoformans</i> and <i>C. gattii </i> during cryptococcosis", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1128/EC.00039-10", "ISBN" : "1535-9786 (Electronic)\\r1535-9786 (Linking)", "ISSN" : "15359778", "PMID" : "20382758", "abstract" : "Opportunistic pathogens have become of increasing medical importance over the last decade due to the AIDS pandemic. Not only is cryptococcosis the fourth-most-common fatal infectious disease in sub-Saharan Africa, but also Cryptococcus is an emerging pathogen of immunocompetent individuals. The interaction between Cryptococcus and the host's immune system is a major determinant for the outcome of disease. Despite initial infection in early childhood with Cryptococcus neoformans and frequent exposure to C. neoformans within the environment, immunocompetent individuals are generally able to contain the fungus or maintain the yeast in a latent state. However, immune deficiencies lead to disseminating infections that are uniformly fatal without rapid clinical intervention. This review will discuss the innate and adaptive immune responses to Cryptococcus and cryptococcal strategies to evade the host's defense mechanisms. It will also address the importance of these strategies in pathogenesis and the potential of immunotherapy in cryptococcosis treatment.", "author" : [ { "dropping-particle" : "", "family" : "Voelz", "given" : "Kerstin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "Robin C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "835-846", "title" : "Cryptococcal interactions with the host immune system", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^19,90", "plainTextFormattedCitation" : "19,90", "previouslyFormattedCitation" : "^19,90" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19,90 Innate immune responses including lung surfactant, complement, dendritic cells (DCs), eosinophils and alveolar macrophages (AMs) are activated in the initial step of Cryptococcus invasion.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.fgb.2014.11.006", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10960937", "PMID" : "25498576", "abstract" : "The vast majority of infection with cryptococcal species occurs with Cryptococcus neoformans in the severely immunocompromised. A significant exception to this is the infections of those with apparently normal immune systems by Cryptococcus gattii. Susceptibility to cryptococcosis can be broadly categorised as a defect in adaptive immune responses, especially in T cell immunity. However, innate immune cells such as macrophages play a key role and are likely the primary effector cell in the killing and ultimate clearance of cryptococcal infection. In this review we discuss the current state of our understanding of how the immune system responds to cryptococcal infection in health and disease, with reference to the work communicated at the 9th International Conference on Cryptococcus and Cryptococcosis (ICCC9). We have focussed on cell mediated responses, particularly early in infection, but with the aim of presenting a broad overview of our understanding of immunity to cryptococcal infection, highlighting some recent advances and offering some perspectives on future directions.", "author" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Josie F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "Simon A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "76-86", "publisher" : "Elsevier Inc.", "title" : "Immunity to <i> Cryptococcus neoformans</i> and <i>C. gattii </i> during cryptococcosis", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹⁰", "plainTextFormattedCitation" : "90", "previouslyFormattedCitation" : "⁹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }90 DCs, AMs, and eosinophils have a role as phagocytic cells against Cryptococcus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/IAI.00317-06", "ISSN" : "00199567", "PMID" : "16790753", "abstract" : "Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from na\u00efve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Wozniak", "given" : "Karen L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vyas", "given" : "Jatin M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levitz", "given" : "Stuart M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "3817-3824", "title" : "In vivo role of dendritic cells in a murine model of pulmonary cryptococcosis", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1128/IAI.00855-13", "ISSN" : "00199567", "PMID" : "24478083", "abstract" : "Cryptococcus neoformans is an opportunistic fungal pathogen that initiates infection following inhalation. As a result, the pulmonary immune response provides a first line of defense against C. neoformans. Surfactant protein D (SP-D) is an important regulator of pulmonary immune responses and is typically host protective against bacterial and viral respiratory infections. However, SP-D is not protective against C. neoformans. This is evidenced by previous work from our laboratory demonstrating that SP-D-deficient mice infected with C. neoformans have a lower fungal burden and live longer than wild-type (WT) control animals. We hypothesized that SP-D alters susceptibility to C. neoformans by dysregulating the innate pulmonary immune response following infection. Thus, inflammatory cells and cytokines were compared in the bronchoalveolar lavage fluid from WT and SP-D(-/-) mice after C. neoformans infection. Postinfection, mice lacking SP-D have reduced eosinophil infiltration and interleukin-5 (IL-5) in lung lavage fluid. To further explore the interplay of SP-D, eosinophils, and IL-5, mice expressing altered levels of eosinophils and/or IL-5 were infected with C. neoformans to assess the role of these innate immune mediators. IL-5-overexpressing mice have increased pulmonary eosinophilia and are more susceptible to C. neoformans infection than WT mice. Furthermore, susceptibility of SP-D(-/-) mice to C. neoformans infection could be restored to the level of WT mice by increasing IL-5 and eosinophils by crossing the IL-5-overexpressing mice with SP-D(-/-) mice. Together, these studies support the conclusion that SP-D increases susceptibility to C. neoformans infection by promoting C. neoformans-driven pulmonary IL-5 and eosinophil infiltration.", "author" : [ { "dropping-particle" : "", "family" : "Holmer", "given" : "Stephanie M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "Kathy S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asfaw", "given" : "Yohannes G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saini", "given" : "Divey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schell", "given" : "Wiley A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ledford", "given" : "Julie G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frothingham", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Jo Rae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sempowski", "given" : "Gregory D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "683-693", "title" : "Impact of surfactant protein D, interleukin-5, and eosinophilia on cryptococcosis", "type" : "article-journal", "volume" : "82" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.fgb.2014.11.006", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10960937", "PMID" : "25498576", "abstract" : "The vast majority of infection with cryptococcal species occurs with Cryptococcus neoformans in the severely immunocompromised. A significant exception to this is the infections of those with apparently normal immune systems by Cryptococcus gattii. Susceptibility to cryptococcosis can be broadly categorised as a defect in adaptive immune responses, especially in T cell immunity. However, innate immune cells such as macrophages play a key role and are likely the primary effector cell in the killing and ultimate clearance of cryptococcal infection. In this review we discuss the current state of our understanding of how the immune system responds to cryptococcal infection in health and disease, with reference to the work communicated at the 9th International Conference on Cryptococcus and Cryptococcosis (ICCC9). We have focussed on cell mediated responses, particularly early in infection, but with the aim of presenting a broad overview of our understanding of immunity to cryptococcal infection, highlighting some recent advances and offering some perspectives on future directions.", "author" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Josie F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "Simon A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "76-86", "publisher" : "Elsevier Inc.", "title" : "Immunity to <i> Cryptococcus neoformans</i> and <i>C. gattii </i> during cryptococcosis", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^90\u201392", "plainTextFormattedCitation" : "90\u201392", "previouslyFormattedCitation" : "^90\u201392" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }90–92 Lung surfactant contains SP-D protein that likely binds with Cryptococcus and attracts eosinophils.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2567.2010.03351.x", "ISBN" : "1365-2567 (Electronic)\\r0019-2805 (Linking)", "ISSN" : "00192805", "PMID" : "21039463", "abstract" : "Experimental Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, revealing a strong granulomatous response and a low susceptibility to dissemination. Moreover, it has been shown that eosinophils are components of the inflammatory response to C. neoformans infections. In this in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of C. neoformans, and that the phenomenon involves the engagement of Fc\u03b3RII and CD18. Moreover, our results showed that the phagocytosis of opsonized C. neoformans triggers eosinophil activation, as indicated by (i) the up-regulation of major histocompatibility complex (MHC) class I, MHC class II and costimulatory molecules, and (ii) an increase in interleukin (IL)-12, tumour necrosis factor-\u03b1 (TNF-\u03b1) and interferon-\u03b3 (IFN-\u03b3) production. However, nitric oxide (NO) and hydrogen peroxide (H(2) O(2) ) synthesis by eosinophils was down-regulated after interaction with C. neoformans. Furthermore, this work demonstrated that CD4(+) and CD8(+) T lymphocytes isolated from spleens of infected rats and cultured with C. neoformans-pulsed eosinophils proliferate in an MHC class II- and class I-dependent manner, respectively, and produce important amounts of T-helper 1 (Th1) type cytokines, such as TNF-\u03b1 and IFN-\u03b3, in the absence of T-helper 2 (Th2) cytokine synthesis. In summary, the present study demonstrates that eosinophils act as fungal antigen-presenting cells and suggests that C. neoformans-loaded eosinophils might participate in the adaptive immune response.", "author" : [ { "dropping-particle" : "", "family" : "Garro", "given" : "Ana P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiapello", "given" : "Laura S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baronetti", "given" : "Jos\u00e9 L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masih", "given" : "Diana T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Immunology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "174-187", "title" : "Rat eosinophils stimulate the expansion of <i>Cryptococcus neoformans</i>-specific CD4+ and CD8+ T cells with a T-helper 1 profile", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹³", "plainTextFormattedCitation" : "93", "previouslyFormattedCitation" : "⁹³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }93 In alveolar spaces, AMs phagocytose Cryptococcus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/IAI.00341-08", "author" : [ { "dropping-particle" : "", "family" : "Guillot", "given" : "Loic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carroll", "given" : "Scott F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Homer", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qureshi", "given" : "Salman T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "4745-4756", "title" : "Enhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection", "type" : "article-journal", "volume" : "76" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1099/mic.0.045989-0", "author" : [ { "dropping-particle" : "", "family" : "McQuiston", "given" : "Travis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luberto", "given" : "Chiara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Del", "family" : "Poeta", "given" : "Maurizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Microbiology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1416-1427", "title" : "Role of sphingosine-1-phosphate ( S1P ) and S1P receptor 2 in the phagocytosis of Cryptococcus neoformans by alveolar macrophages", "type" : "article-journal", "volume" : "157" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^94,95", "plainTextFormattedCitation" : "94,95", "previouslyFormattedCitation" : "^94,95" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94,95 A granulomatous immune response may follow with the formation of a sub-pleural nodule or primary lymph node complex.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0002-9173", "ISSN" : "00029173", "abstract" : "Such a condition has been seen at autopsy or after thoracotomy in 1% of Cryptococcus neoformans infections. This paper reports 9 such cases, 4 of which developed in apparently normal people, and 5 in those hypersusceptible to infection. The complexes in the 4 were circumscribed granulomas and represented 1st infection cryptocococcosis similar to 1st infection tuberculosis. There was a chronic course and a good prognosis with surgical resection. The complexes in the other 5 were predominantly acute diffuse pneumonias and large diffuse lesions of the lymph nodes and were interpreted as 1st infection cryptococcosis with massive spread facilitated by the comprised state. All 5 died.", "author" : [ { "dropping-particle" : "", "family" : "Baker", "given" : "R. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Clinical Pathology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1976" ] ] }, "page" : "83-92", "title" : "The primary pulmonary lymph node complex of cryptococcosis", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Salyer", "given" : "William R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salyer", "given" : "Diane C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Roger D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Infectious Diseases", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "1974" ] ] }, "page" : "74-77", "title" : "Primary complex of <i> Cryptococcus </i> and pulmonary lymph nodes", "type" : "article-journal", "volume" : "130" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^96,97", "plainTextFormattedCitation" : "96,97", "previouslyFormattedCitation" : "^96,97" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }96,97 Murine models support this sequence of events, as C. neoformans infection results in hilar lymph node infection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/IAI.72.4.2229", "author" : [ { "dropping-particle" : "", "family" : "Santangelo", "given" : "Rosemary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zoellner", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Christabel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donald", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Djordjevic", "given" : "Julianne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Lesley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shounan", "given" : "Yi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "2229-2239", "title" : "Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹⁸", "plainTextFormattedCitation" : "98", "previouslyFormattedCitation" : "⁹⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98 Pulmonary nodules are a common manifestation on radiologic examination.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.inf.0000101916.33855.06", "ISBN" : "0891-3668 (Print)\\r0891-3668 (Linking)", "ISSN" : "08913668", "PMID" : "14688572", "abstract" : "Pulmonary cryptococcosis is an uncommonly recognized disease of childhood. Among immunocompetent and non-HIV-infected individuals, pulmonary cryptococcosis may be asymptomatic or present with chronic, nondescript symptomatology. In this report we describe a 10-year-old with malignant fibrous histiocytoma of bone and a pulmonary nodule secondary to Cryptococcus neoformans. We use this case as a background to review the pediatric literature regarding pulmonary cryptococcosis and to discuss the utility of immunohistochemistry for diagnosis of this clinical entity.", "author" : [ { "dropping-particle" : "", "family" : "Sweeney", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caserta", "given" : "M T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korones", "given" : "D N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "D L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatr Infect Dis J", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "1089-1093", "title" : "A ten-year-old boy with a pulmonary nodule secondary to <i> Cryptococcus neoformans</i>: case report and review of the literature", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁹⁹", "plainTextFormattedCitation" : "99", "previouslyFormattedCitation" : "⁹⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }99 Finally, DCs also stimulate T lymphocytes (T cells) as the key adaptive immune response. CD4+ T cells have a central role in the defence against cryptococcal infection. CD4+, CD8+ and natural killer (NK) cells act as fungistatic agents for Cryptococcus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "abstract" : "Lymphocytes constitute a critical component of host defenses against cryptococcosis. Previously, we demonstrated that human lymphocytes cultured with interleukin-2 formed conjugates with, and directly inhibited the growth of, Cryptococcus neoformans. Here, we explore the anticryptococcal activity of freshly isolated, highly purified populations of human peripheral blood lymphocytes. Lymphocytes were incubated with encapsulated C. neoformans for 24 h, after which the lymphocytes were lysed, dilutions and spread plates were made, and CFU were counted. Fungistasis was determined by comparing growth in wells with and without lymphocytes. Nylon wool-nonadherent peripheral blood mononuclear cells (NWNA PBMC) were highly fungistatic, even if either T cells or natural killer (NK) cells were depleted by panning. A mixed population of T cells and NK cells, obtained by rosetting NWNA PBMC with sheep erythrocytes, completely inhibited cryptococcal growth, whereas the nonrosetting cells had little fungistatic activity. CD4+, CD8+, and CD16/56+ lymphocytes, isolated by positive immunoselection, had potent growth-inhibitory activity. In contrast, purified B cells had no activity. Fungistasis was seen even in the absence of opsonins. Antifungal activity was markedly diminished when surface receptors on NWNA PBMC were cleaved by treatment with trypsin or bromelain. Supernatants from stimulated lymphocytes or concentrated lymphocyte sonicates were not active. Lymphocyte-mediated fungistasis was seen with two different strains of C. neoformans. CD4+, CD8+, and CD16/56+ lymphocytes formed conjugates with C. neoformans, as observed under Nomarski differential interference contrast microscopy and videomicroscopy. These data demonstrate that freshly isolated peripheral blood T cells and NK cells have the capacity to bind and directly inhibit the growth of C. neoformans.", "author" : [ { "dropping-particle" : "", "family" : "Levitz", "given" : "Stuart M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupont", "given" : "Michele P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smail", "given" : "Edwin H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and immunity", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "194-202", "title" : "Direct activity of human T lymphocytes and natural killer cells against <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁰", "plainTextFormattedCitation" : "100", "previouslyFormattedCitation" : "¹⁰⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }100 The release of granulysin by cytotoxic CD4+ and CD8+ cells and perforin by NK cells probably has a role in the effective killing of Cryptococcus. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1182/blood-2006-03-009720", "ISBN" : "0006-4971 (Print)\\r0006-4971 (Linking)", "ISSN" : "00064971", "PMID" : "17038537", "abstract" : "An important mechanism of host defense to Cryptococcus neoformans involves the direct microbicidal activity of lymphocytes. The importance of CD4+ T cells is illustrated by the incidence of this infection in the acquired immunodeficiency syndrome (AIDS) patients; however, the relative activity of microbicidal CD4+ T cells compared with CD8+ T cells and natural killer (NK) cells has not been established. Further, although NK cells and CD8+ T cells use perforin or granulysin, respectively, to kill C neoformans, the effector molecule used by CD4+ T cells is not known. Experiments demonstrated that IL-2-activated peripheral blood lymphocytes from healthy adults acquire anticryptococcal activity, and surprisingly, that CD4+ T cells had the most profound effect on this activity. Using SrCl(2)induced degranulation and siRNA knockdown, granulysin was shown to be the effector molecule. Although activation by anti-CD3 + IL-2 resulted in the additional expression of perforin, this did not improve the anticryptococcal activity. Cryptococcal killing by CD4+ T cells was defective in human immunodeficiency virus (HIV)-infected patients due to dysregulated granulysin and perforin production in response to IL-2 or anti-CD3 + IL-2. In conclusion, CD4+ T cells are the major subset of cells responsible for killing C neoformans in peripheral blood. These cells use granulysin as the effector molecule, and priming is dysregulated in HIV-infected patients, which results in defective microbicidal activity.", "author" : [ { "dropping-particle" : "", "family" : "Chun", "given" : "Fu Zheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ling", "given" : "Ling Ma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Gareth J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gill", "given" : "M. John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krensky", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubes", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mody", "given" : "Christopher H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Blood Journal American Society of Hematology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "2049-2057", "title" : "Cytotoxic CD4+ T cells use granulysin to kill <i> Cryptococcus neoformans</i>, and activation of this pathway is defective in HIV patients", "type" : "article-journal", "volume" : "109" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/S0065-2164(08)01005-8", "ISBN" : "9780123748027", "ISSN" : "00652164", "PMID" : "19245939", "abstract" : "Cryptococcus neoformans and Cryptococcus gattii are the cause of life-threatening meningoencephalitis in immunocompromised and immunocompetent individuals respectively. The increasing incidence of cryptococcal infection as a result of the AIDS epidemic, the recent emergence of a hypervirulent cryptococcal strain in Canada and the fact that mortality from cryptococcal disease remains high have stimulated intensive research into this organism. Here we outline recent advances in our understanding of C. neoformans and C. gattii, including intraspecific complexity, virulence factors, and key signaling pathways. We discuss the molecular basis of cryptococcal virulence and the interaction between these pathogens and the host immune system. Finally, we discuss future challenges in the study and treatment of cryptococcosis. ?? 2009 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Ma", "given" : "Hansong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "Robin C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Advances in Applied Microbiology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "131-190", "publisher" : "Elsevier", "title" : "Virulence in <i> Cryptococcus </i> species", "type" : "chapter", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^39,101", "plainTextFormattedCitation" : "39,101", "previouslyFormattedCitation" : "^39,101" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39,101 In the mouse model, allergic response and airway reactivity were observed related to pulmonary cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/501363", "ISBN" : "0022-1899 (Print)\\r0022-1899 (Linking)", "ISSN" : "0022-1899", "PMID" : "16544260", "abstract" : "Although Cryptococcus neoformans is recognized for its ability to cause meningoencephalitis and pneumonia among immunocompromised persons, subclinical pulmonary infection is also common among immunocompetent persons. The significance of this infection is unknown. Using a rat model, we explored the potential for pulmonary cryptococcosis to modify allergic responses and airway reactivity. Our findings indicate that localized pulmonary cryptococcal infection (but not disseminated infection) can exacerbate allergic responses to respiratory challenge with ovalbumin, as measured by total immunoglobulin E levels, ovalbumin-specific immunoglobulin E titers, and eosinophil content of bronchoalveolar lavage fluid. Infection-associated enhancement of allergic responses was not dependent on cryptococcal encapsulation and was partially ameliorated by the administration of fluconazole. Increases in both the number of goblet cells and airway responsiveness, which are also features of reactive airway disease, were also present with pulmonary infection. An examination of lung cytokine levels in the context of active pulmonary infection revealed increased expression of interleukin (IL)-10, tumor necrosis factor- alpha , and IL-13, but not IL-12 or interferon- gamma . In contrast, systemic infection was associated with higher levels of interferon- gamma but lower levels of IL-13. Our studies highlight the potential for localized pulmonary C. neoformans infection to potentiate allergic responses and airway reactivity and suggest a potential role for subclinical pulmonary cryptococcosis in the pathogenesis of asthma.", "author" : [ { "dropping-particle" : "", "family" : "Goldman", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bommarito", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shao", "given" : "Xiuping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of infectious diseases", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "1178-86", "title" : "Enhanced allergic inflammation and airway responsiveness in rats with chronic <i> Cryptococcus neoformans</i> infection: potential role for fungal pulmonary infection in the pathogenesis of asthma.", "type" : "article-journal", "volume" : "193" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰²", "plainTextFormattedCitation" : "102", "previouslyFormattedCitation" : "¹⁰²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }102 C. neoformans specific serum IgG titres are increased in the serum of some asthma patients in urban areas of Germany, a provocative finding implicating C. neoformans in asthma.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/mmy/myv024", "ISSN" : "14602709", "abstract" : "Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised patients but is also able to asymptomatically infect immunocompetent individuals. C. neoformans is found ubiquitously especially in urban areas where it is spread by pigeons, and fungal exposure may predispose for asthma development already at an early age, as soon as confronted with pigeon droppings. In the study presented here, we investigated the presence of specific immunoglobulin G (IgG) against C. neoformans in sera from patients suffering from asthma in comparison to a healthy control cohort, accrued from the Leipzig Research Centre for Civilization Diseases (LIFE). For serological analysis we developed a flow cytometry (FACS) based assay specific for an acapsular strain of C. neoformans to comprehensively analyze different cryptococcal serotypes. Compared with the non-asthmatic cohort, asthmatics exhibited, as expected, an elevated level of total serum immunoglobulin E (IgE), whereas the IgG seroreactivity against C. neoformans was not significantly different among the two groups (P = .118). Nevertheless, there was a trend toward increased Cryptococcus-specific IgG antibodies in the serum of asthmatics. Additionally, in male asthmatics an increased IgG-mediated seroreactivity compared to female asthmatics was found. This points to a higher prevalence of subclinical C. neoformans infection in male asthmatics and may support the hypothesis of C. neoformans as a risk factor for the development of asthma in urban areas.", "author" : [ { "dropping-particle" : "", "family" : "Grahnert", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muller", "given" : "Uwe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buttlar", "given" : "Heiner", "non-dropping-particle" : "Von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treudler", "given" : "Regina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alber", "given" : "Gottfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "576-586", "title" : "Analysis of asthma patients for cryptococcal seroreactivity in an urban German area", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰³", "plainTextFormattedCitation" : "103", "previouslyFormattedCitation" : "¹⁰³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }103 However, whether pulmonary cryptococcosis is related to either the pathogenesis or exacerbation of asthma is unknown and requires further study. The fate of Cryptococcus within macrophages is determined by the host immune status.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11908-007-0070-8", "ISBN" : "1523-3847 (Print)\\r1523-3847 (Linking)", "ISSN" : "15233847", "PMID" : "17999881", "abstract" : "Disseminated cryptococcosis begins with infection of the lungs via inhalation. This is followed by escape from the lungs and entry into the bloodstream allowing dissemination to the brain and central nervous system. We discuss the steps involved in dissemination and the host and microbial factors that influence each step. For the host, containment in the lung is accomplished with a combination of cell-mediated and antibody responses. Dissemination occurs when these systems fail and/or when phagocytic cells that fail to kill the yeast instead act as a niche for replication. One of the main microbial factors affecting dissemination is the polysaccharide capsule, a major virulence factor that promotes dissemination at every step. Secreted enzymes are important, including laccase and phospholipase B, which promote escape from the lungs, and urease, which contributes to crossing the blood-brain barrier. Lastly, a number of regulatory factors contribute, especially to growth of Cryptococcus neoformans in the brain.", "author" : [ { "dropping-particle" : "", "family" : "Eisenman", "given" : "Helene C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McClelland", "given" : "Erin E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Infectious Disease Reports", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "457-464", "title" : "New insights on the pathogenesis of invasive <i> Cryptococcus neoformans</i> infection", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁴", "plainTextFormattedCitation" : "104", "previouslyFormattedCitation" : "¹⁰⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }104 Cryptococcus cells may be destroyed resulting in the elimination of infection in most immunocompetent people. Alternatively, Cryptococcus may persist in granuloma as sequestrations and establishe latent infection in those with alterated immune status or in the presence of specific risk factors.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S1473-3099(11)70140-2", "ISBN" : "9781603272384", "ISSN" : "14733099", "abstract" : "When one hears that there is a new 620 page textbook on the fungus Cryptococcus neoformans , the uninitiated might wonder if there really is that much of interest that could be written about just one yeast. Yet Cryptococcus is not just a yeast, it is a deadly yeast. For each page of the textbook there have been 1000 deaths worldwide annually attributable to this yeast. For the organism that causes the most deadly fungal infection worldwide, one might wonder why there is not more written.\\nThe editors ...", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "number-of-pages" : "534", "publisher" : "ASM Press", "title" : "Cryptococcus: from human pathogen to model yeast", "type" : "book", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁰⁵", "plainTextFormattedCitation" : "105", "previouslyFormattedCitation" : "¹⁰⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }105 In addition, Cryptococcus may colonise the respiratory tract without any symptoms, indicative of incomplete elimination by macrophages.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev.micro.60.080805.142102", "ISBN" : "0066-4227 (Print)\\n0066-4227 (Linking)", "ISSN" : "0066-4227", "PMID" : "16704346", "abstract" : "Cryptococcus neoformans is a major cause of fungal meningoencephalitis in immunocompromised patients. Despite recent advances in the genetics and molecular biology of C. neoformans, and improved techniques for molecular epidemiology, aspects of the ecology, population structure, and mode of reproduction of this environmental pathogen remain to be established. Application of recent insights into the life cycle of C. neoformans and its different ways of engaging in sexual reproduction under laboratory conditions has just begun to affect research on the ecology and epidemiology of this human pathogenic fungus. The melding of these disparate disciplines should yield rich dividends in our understanding of the evolution of microbial pathogens, providing insights relevant to diagnosis, treatment, and prevention", "author" : [ { "dropping-particle" : "", "family" : "Lin", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitman", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annu.Rev.Microbiol.", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "69-105", "title" : "The biology of the <i> Cryptococcus neoformans</i> species complex", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³²", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32 Significantly reduced immunity, especially the CD4 T-helper system, allows Cryptococcus to escape from the lung and disseminate.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/EC.00039-10", "ISBN" : "1535-9786 (Electronic)\\r1535-9786 (Linking)", "ISSN" : "15359778", "PMID" : "20382758", "abstract" : "Opportunistic pathogens have become of increasing medical importance over the last decade due to the AIDS pandemic. Not only is cryptococcosis the fourth-most-common fatal infectious disease in sub-Saharan Africa, but also Cryptococcus is an emerging pathogen of immunocompetent individuals. The interaction between Cryptococcus and the host's immune system is a major determinant for the outcome of disease. Despite initial infection in early childhood with Cryptococcus neoformans and frequent exposure to C. neoformans within the environment, immunocompetent individuals are generally able to contain the fungus or maintain the yeast in a latent state. However, immune deficiencies lead to disseminating infections that are uniformly fatal without rapid clinical intervention. This review will discuss the innate and adaptive immune responses to Cryptococcus and cryptococcal strategies to evade the host's defense mechanisms. It will also address the importance of these strategies in pathogenesis and the potential of immunotherapy in cryptococcosis treatment.", "author" : [ { "dropping-particle" : "", "family" : "Voelz", "given" : "Kerstin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "Robin C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "835-846", "title" : "Cryptococcal interactions with the host immune system", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "", "ISSN" : "1806-3756", "PMID" : "20011850", "abstract" : "neoforman Cryptococcosis is a systemic mycosis caused by two species of the encapsulated basidiomycetes, s s and C. gattii , which, respectively, cause infection in immunocompromised individuals and in immunologically normal hosts. Patients with T-cell deficiencies are more susceptible to this infection. The spectrum Cryptococcu of the disease ranges from asymptomatic pulmonary lesions to disseminated infection with meningoencephalitis. The medical relevance of cryptococcosis increased dramatically as a consequence of the AIDS epidemic and organ transplants.", "author" : [ { "dropping-particle" : "", "family" : "Cec\u00edlia Bittencourt Severo, Alexandra Fl\u00e1via Gazzoni", "given" : "Luiz Carlos Severo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Bras Pneumol.", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1136-1144", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.fgb.2014.11.006", "ISBN" : "1096-0937 (Electronic)\\r1087-1845 (Linking)", "ISSN" : "10960937", "PMID" : "25498576", "abstract" : "The vast majority of infection with cryptococcal species occurs with Cryptococcus neoformans in the severely immunocompromised. A significant exception to this is the infections of those with apparently normal immune systems by Cryptococcus gattii. Susceptibility to cryptococcosis can be broadly categorised as a defect in adaptive immune responses, especially in T cell immunity. However, innate immune cells such as macrophages play a key role and are likely the primary effector cell in the killing and ultimate clearance of cryptococcal infection. In this review we discuss the current state of our understanding of how the immune system responds to cryptococcal infection in health and disease, with reference to the work communicated at the 9th International Conference on Cryptococcus and Cryptococcosis (ICCC9). We have focussed on cell mediated responses, particularly early in infection, but with the aim of presenting a broad overview of our understanding of immunity to cryptococcal infection, highlighting some recent advances and offering some perspectives on future directions.", "author" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Josie F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "Simon A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "76-86", "publisher" : "Elsevier Inc.", "title" : "Immunity to <i> Cryptococcus neoformans</i> and <i>C. gattii </i> during cryptococcosis", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^19,90,106", "plainTextFormattedCitation" : "19,90,106", "previouslyFormattedCitation" : "^19,90,106" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19,90,106Virulence factors of CryptococcusC. neoformans and C. gattii share many virulence factors that allow infection in the human.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrmicro2522", "ISBN" : "1740-1534 (Electronic)\\r1740-1526 (Linking)", "ISSN" : "1740-1526", "PMID" : "21326274", "abstract" : "Cryptococcus neoformans is generally considered to be an opportunistic fungal pathogen because of its tendency to infect immunocompromised individuals, particularly those infected with HIV. However, this view has been challenged by the recent discovery of specialized interactions between the fungus and its mammalian hosts, and by the emergence of the related species Cryptococcus gattii as a primary pathogen of immunocompetent populations. In this Review, we highlight features of cryptococcal pathogens that reveal their adaptation to the mammalian environment. These features include not only remarkably sophisticated interactions with phagocytic cells to promote intracellular survival, dissemination to the central nervous system and escape, but also surprising morphological and genomic adaptations such as the formation of polyploid giant cells in the lung.", "author" : [ { "dropping-particle" : "", "family" : "Kronstad", "given" : "J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Attarian", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cadieux", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Souza", "given" : "C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffiths", "given" : "E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geddes", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jung", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kretschmer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saikia", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Rev Microbiol", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "193-203", "publisher" : "Nature Publishing Group", "title" : "Expanding fungal pathogenesis: <i>Cryptococcus</i> breaks out of the opportunistic box", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁰", "plainTextFormattedCitation" : "30", "previouslyFormattedCitation" : "³⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }30 These virulence factors include polysaccharide capsule, melanin pigments in the cell walls, ability to grow at 37°C, and extracellular enzymes.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0065-2164(09)01204-0.The", "author" : [ { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodrigues", "given" : "Marcio L", "non-dropping-particle" : "", "parse-names" : 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"parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crta", "given" : "I I I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Advances in Applied Microbiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1-64", "title" : "The capsule of the fungal pathogen The capsule of the fungal pathogen <i> Cryptococcus neoformans</i> .", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1128/AAC.00545-06", "ISBN" : "0066-4804 (Print)", "ISSN" : "00664804", "PMID" : "17065617", "abstract" : "10.1128/AAC.00545-06", "author" : [ { "dropping-particle" : "", "family" : "Nosanchuk", "given" : "Joshua D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Antimicrobial Agents and Chemotherapy", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "3519-3528", "title" : "Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1111/j.1567-1364.2006.00051.x", "ISBN" : "1567-1356 (Print)\\r1567-1356 (Linking)", "ISSN" : "15671356", "PMID" : "16696642", "abstract" : "The ability of fungi to grow well at mammalian body temperatures is a fundamental characteristic of invasive human fungal pathogens. Cryptococcus neoformans, with its genetics, molecular biology, robust animal models and clinical importance, has become a premier fungal model system for molecular fungal pathogenesis studies. There has been over a half century of study into how C. neoformans grows at high temperatures. However, recently the understanding of high-temperature growth at a molecular level has dramatically accelerated. Many strategies have been used to identify genes and over a dozen genes have already been identified to be necessary for high-temperature growth. It is likely that there are many more to discover. It is clear that, as further studies understand how this encapsulated yeast is able to withstand the stresses of high temperature at a genetic and molecular basis, we will also know more about how it and other fungal pathogens have evolved into well-established human pathogens.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "463-468", "title" : "<i> Cryptococcus neoformans</i> : The yeast that likes it hot", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1128/EC.00370-07", "ISBN" : "1535-9786 (Electronic)\\r1535-9786 (Linking)", "ISSN" : "15359778", "PMID" : "18039940", "abstract" : "Cryptococcus neoformans produces vesicles containing its major virulence factor, the capsular polysaccharide glucuronoxylomannan (GXM). These vesicles cross the cell wall to reach the extracellular space, where the polysaccharide is supposedly used for capsule growth or delivered into host tissues. In the present study, we characterized vesicle morphology and protein composition by a combination of techniques including electron microscopy, proteomics, enzymatic activity, and serological reactivity. Secretory vesicles in C. neoformans appear to be correlated with exosome-like compartments derived from multivesicular bodies. Extracellular vesicles manifested various sizes and morphologies, including electron-lucid membrane bodies and electron-dense vesicles. Seventy-six proteins were identified by proteomic analysis, including several related to virulence and protection against oxidative stress. Biochemical tests indicated laccase and urease activities in vesicles. In addition, different vesicle proteins were recognized by sera from patients with cryptococcosis. These results reveal an efficient and general mechanism of secretion of pathogenesis-related molecules in C. neoformans, suggesting that extracellular vesicles function as \"virulence bags\" that deliver a concentrated payload of fungal products to host effector cells and tissues.", "author" : [ { "dropping-particle" : "", "family" : "Rodrigues", "given" : "Marcio L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakayasu", "given" : "Ernesto S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira", "given" : "Debora L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nimrichter", "given" : "Leonardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nosanchuk", "given" : "Joshua D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almeida", "given" : "Igor C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "58-67", "title" : "Extracellular vesicles produced by <i> Cryptococcus neoformans</i> contain protein components associated with virulence", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^107\u2013110", "plainTextFormattedCitation" : "107\u2013110", "previouslyFormattedCitation" : "^107\u2013110" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }107–110 The polysaccharide capsule may disturb T-cell responses in the lung resulting in reduced macrophage functions.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1567-1364.2006.00071.x", "ISBN" : "1567-1356 (Print)\\r1567-1356 (Linking)", "ISSN" : "15671356", "PMID" : "16696647", "abstract" : "T-cell-mediated immunity is necessary for effective host defenses against infections caused by Cryptococcus neoformans. Clinical and experimental studies have identified a heterogeneous family of mannoproteins as critical cryptococcal antigens responsible for stimulating T-cell responses. The archetypal mannoprotein has a signal sequence, a functional domain, a serine/threonine-rich region and a site for attachment of a glycosylphosphatidylinositol anchor. Extensive O-mannosylation, which occurs at the serine/threonine region, facilitates recognition by mannose receptors on antigen-presenting cells, particularly dendritic cells. This results in efficient antigen uptake, processing and presentation to T cells. Inhibition of mannose receptors or deglycosylation of mannoproteins profoundly inhibits T-cell responses, demonstrating the crucial contribution of mannosylation to immunogenicity.", "author" : [ { "dropping-particle" : "", "family" : "Levitz", "given" : "Stuart M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Specht", "given" : "Charles A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "513-524", "title" : "The molecular basis for the immunogenicity of <i> Cryptococcus neoformans</i> mannoproteins", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0009-9104 (Print)\\n0009-9104", "PMID" : "7955525", "abstract" : "Our previous studies have shown that unstimulated alveolar macrophages (AM) play a predominant role as antigen-presenting cells in Cryptococcus neoformans infections, while the function as effector cells seems to be of minor relevance. The present study focuses on the role of encapsulation of C. neoformans on fungicidal activity and the antigen presentation process of AM. Fungicidal activity in unstimulated AM occurs to a higher degree when the acapsular strain is employed, but this is impaired compared with other natural effectors, such as peripheral blood monocytes (PBM) and polymorphonuclear (PMN) cells. Cryptococcus-laden AM also induce a higher proliferative response in autologous CD4+ lymphocytes when the acapsular strain is used compared with encapsulated yeast. The enhanced blastogenic response is, in part, ascribed to an augmented IL-2 production by T cells. In addition, higher levels of interferon-gamma (IFN-gamma), but not IL-4, are produced by the responding T cells, when the acapsular strain is used compared with the encapsulated yeast. Moreover, IFN-gamma is able to induce fungicidal activity in AM against the encapsulated yeast and augments killing activity of the acapsular strain. This phenomenon is not mediated by nitric oxide production, but is correlated with an enhancement of fungicidal activity of cytoplasmic cationic proteases. We speculate that encapsulation of C. neoformans could down-regulate the development of the immune response mediated by Cryptococcus-laden AM at lung level.", "author" : [ { "dropping-particle" : "", "family" : "Vecchiarelli", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietrella", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dottorini", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monari", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Retini", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todisco", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bistoni", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clin Exp Immunol", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "217-223", "title" : "Encapsulation of <i> Cryptococcus neoformans</i> regulates fungicidal activity and the antigen presentation process in human alveolar macrophages", "type" : "article-journal", "volume" : "98" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^111,112", "plainTextFormattedCitation" : "111,112", "previouslyFormattedCitation" : "^111,112" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }111,112 Oxidative killing of the immune cells against Cryptococcus is diminished by melanin with the redox buffer mechanism.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/AAC.00545-06", "ISBN" : "0066-4804 (Print)", "ISSN" : "00664804", "PMID" : "17065617", "abstract" : "10.1128/AAC.00545-06", "author" : [ { "dropping-particle" : "", "family" : "Nosanchuk", "given" : "Joshua D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Antimicrobial Agents and Chemotherapy", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "3519-3528", "title" : "Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0021-9193 (Print)\\r0021-9193 (Linking)", "ISSN" : "00219193", "PMID" : "8226653", "abstract" : "Polyphenols have been implicated in the virulence and oxidant resistance of Cryptococcus neoformans. Although monomeric polyphenols did not protect against the prooxidant, plumbagin, polymeric dopamine-melanin conferred resistance both to hypochlorite and to permanganate. The physiologic antioxidant capacity conferred by melanin was found to be 21.3 x 10(-15) mole-equivalents per cell, a value which approximates oxidant production by stimulated macrophages.", "author" : [ { "dropping-particle" : "", "family" : "Jacobson", "given" : "E. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tinnell", "given" : "S. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Bacteriology", "id" : "ITEM-2", "issue" : "21", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "7102-7104", "title" : "Antioxidant function of fungal melanin", "type" : "article-journal", "volume" : "175" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^108,113", "plainTextFormattedCitation" : "108,113", "previouslyFormattedCitation" : "^108,113" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }108,113 The survival of Cryptococcus at body temperature is critically supported by superoxide dismutase (SOD2), as the null mutant of this gene is both avirulent and loses the ability to grow at 37°C.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/EC.4.1.46-54.2005", "ISBN" : "1535-9778 (Print)\\r1535-9786 (Linking)", "ISSN" : "15359778", "PMID" : "15643059", "abstract" : "Manganese superoxide dismutase is an essential component of the mitochondrial antioxidant defense system of most eukaryotes. In the present study, we used a reverse-genetics approach to assess the contribution of the Cryptococcus neoformans manganese superoxide dismutase (Sod2) for antioxidant defense. Strains with mutations in the SOD2 gene exhibited increased susceptibility to oxidative stress as well as poor growth at elevated temperatures compared to isogenic wild-type strains. The sod2Delta mutants were also avirulent in a murine model of inhaled cryptococcosis. Reconstitution of a sod2Delta mutant restored Sod2 activity, eliminated the oxidative stress and temperature-sensitive (ts) phenotypes, and complemented the virulence phenotype. Characterization of the ts phenotype revealed a dependency between Sod2 antioxidant activity and the ability of C. neoformans cells to adapt to growth at elevated temperatures. The ts phenotype could be suppressed by the addition of either ascorbic acid (10 mM) or Mn salen (200 muM) at 30 degrees C, but not at 37 degrees C. Furthermore, sod2Delta mutant cells that were incubated for 24 h at 37 degrees C under anaerobic, but not aerobic, conditions were viable when shifted to the permissive conditions of 25 degrees C in the presence of air. These data suggest that the C. neoformans Sod2 is a major component of the antioxidant defense system in this human fungal pathogen and that adaptation to growth at elevated temperatures is also dependent on Sod2 activity.", "author" : [ { "dropping-particle" : "", "family" : "Giles", "given" : "Steven S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batinic-Haberle", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Gary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "46-54", "title" : "<i> Cryptococcus neoformans</i> mitochondrial superoxide dismutase: An essential link between antioxidant function and high-temperature growth", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1567-1364.2006.00051.x", "ISBN" : "1567-1356 (Print)\\r1567-1356 (Linking)", "ISSN" : "15671356", "PMID" : "16696642", "abstract" : "The ability of fungi to grow well at mammalian body temperatures is a fundamental characteristic of invasive human fungal pathogens. Cryptococcus neoformans, with its genetics, molecular biology, robust animal models and clinical importance, has become a premier fungal model system for molecular fungal pathogenesis studies. There has been over a half century of study into how C. neoformans grows at high temperatures. However, recently the understanding of high-temperature growth at a molecular level has dramatically accelerated. Many strategies have been used to identify genes and over a dozen genes have already been identified to be necessary for high-temperature growth. It is likely that there are many more to discover. It is clear that, as further studies understand how this encapsulated yeast is able to withstand the stresses of high temperature at a genetic and molecular basis, we will also know more about how it and other fungal pathogens have evolved into well-established human pathogens.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEMS Yeast Research", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "463-468", "title" : "<i> Cryptococcus neoformans</i> : The yeast that likes it hot", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^109,114", "plainTextFormattedCitation" : "109,114", "previouslyFormattedCitation" : "^109,114" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }109,114 One substantial difference between C. neoformans and C. gattii is the diminished ability of C. gattii to grow inside macrophages.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ncomms6194", "ISBN" : "2041-1723 (Electronic)\\r2041-1723 (Linking)", "ISSN" : "2041-1723", "PMID" : "25323068", "abstract" : "Cryptococcus gattii is an emerging intracellular pathogen and the cause of the largest primary outbreak of a life-threatening fungal disease in a healthy population. Outbreak strains share a unique mitochondrial gene expression profile and an increased ability to tubularize their mitochondria within host macrophages. However, the underlying mechanism that causes this lineage of C. gattii to be virulent in immunocompetent individuals remains unexplained. Here we show that a subpopulation of intracellular C. gattii adopts a tubular mitochondrial morphology in response to host reactive oxygen species. These fungal cells then facilitate the rapid growth of neighbouring C. gattii cells with non-tubular mitochondria, allowing for effective establishment of the pathogen within a macrophage intracellular niche. Thus, host reactive oxygen species, an essential component of the innate immune response, act as major signalling molecules to trigger a 'division of labour' in the intracellular fungal population, leading to increased pathogenesis within this outbreak lineage.", "author" : [ { "dropping-particle" : "", "family" : "Voelz", "given" : "Kerstin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "Simon A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Leanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Rebecca A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Idnurm", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "Robin C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature communications", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "5194", "publisher" : "Nature Publishing Group", "title" : "'Division of labour' in response to host oxidative burst drives a fatal <i>Cryptococcus gattii </i> outbreak.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁵", "plainTextFormattedCitation" : "115", "previouslyFormattedCitation" : "¹¹⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }115 During pulmonary cryptococcosis caused by C. neoformans, cryptococcal titan cells (giant cells) probably play a significant role in host immune evasion.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrmicro2522", "ISBN" : "1740-1534 (Electronic)\\r1740-1526 (Linking)", "ISSN" : "1740-1526", "PMID" : "21326274", "abstract" : "Cryptococcus neoformans is generally considered to be an opportunistic fungal pathogen because of its tendency to infect immunocompromised individuals, particularly those infected with HIV. However, this view has been challenged by the recent discovery of specialized interactions between the fungus and its mammalian hosts, and by the emergence of the related species Cryptococcus gattii as a primary pathogen of immunocompetent populations. In this Review, we highlight features of cryptococcal pathogens that reveal their adaptation to the mammalian environment. These features include not only remarkably sophisticated interactions with phagocytic cells to promote intracellular survival, dissemination to the central nervous system and escape, but also surprising morphological and genomic adaptations such as the formation of polyploid giant cells in the lung.", "author" : [ { "dropping-particle" : "", "family" : "Kronstad", "given" : "J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Attarian", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cadieux", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Souza", "given" : "C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffiths", "given" : "E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geddes", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jung", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kretschmer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saikia", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Rev Microbiol", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "193-203", "publisher" : "Nature Publishing Group", "title" : "Expanding fungal pathogenesis: <i>Cryptococcus</i> breaks out of the opportunistic box", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "³⁰", "plainTextFormattedCitation" : "30", "previouslyFormattedCitation" : "³⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }30 Titan cells are C. neoformans cells with an extreme increase in size (25-30 ?m in diameter) that leverage the virulence of C. neoformans mostly during initial pulmonary infection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/EC.00121-12", "ISBN" : "1535-9786 (Electronic)\\n1535-9786 (Linking)", "ISSN" : "15359778", "PMID" : "22544904", "abstract" : "The human fungal pathogen Cryptococcus neoformans produces an enlarged \"titan\" cell morphology when exposed to the host pulmonary environment. Titan cells exhibit traits that promote survival in the host. Previous studies showed that titan cells are not phagocytosed and that increased titan cell production in the lungs results in reduced phagocytosis of cryptococcal cells by host immune cells. Here, the effect of titan cell production on host-pathogen interactions during early stages of pulmonary cryptococcosis was explored. The relationship between titan cell production and phagocytosis was found to be nonlinear; moderate increases in titan cell production resulted in profound decreases in phagocytosis, with significant differences occurring within the first 24 h of the infection. Not only were titan cells themselves protected from phagocytosis, but titan cell formation also conferred protection from phagocytosis to normal-size cryptococcal cells. Large particles introduced into the lungs were not phagocytosed, suggesting the large size of titan cells protects against phagocytosis. The presence of large particles was unable to protect smaller particles from phagocytosis, revealing that titan cell size alone is not sufficient to provide the observed cross-protection of normal-size cryptococcal cells. These data suggest that titan cells play a critical role in establishment of the pulmonary infection by promoting the survival of the entire population of cryptococcal cells.", "author" : [ { "dropping-particle" : "", "family" : "Okagaki", "given" : "Laura H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "820-826", "title" : "Titan cells confer protection from phagocytosis in <i> Cryptococcus neoformans</i> infections", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1350-0872", "author" : [ { "dropping-particle" : "", "family" : "Feldmesser", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kress", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Microbiology", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "2355-2365", "title" : "Dynamic changes in the morphology of <i> Cryptococcus neoformans</i> during murine pulmonary infection", "type" : "article-journal", "volume" : "147" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.mib.2013.03.006", "ISBN" : "1369-5274", "ISSN" : "13695274", "PMID" : "23588027", "abstract" : "Cryptococcus neoformans is a pathogenic yeast that commonly infects immunocompromised individuals, yet has developed multiple adaptation mechanisms to the host. Several virulence factors (capsule and melanin) have been known for many years. However, this yeast also possesses a morphogenetic program that is still not well characterized. C. neoformans has the ability to dramatically enlarge its size during infection to form 'titan cells' that can reach up to 100. ??m in cell body diameter, in contrast to typical size cells of 5-7. ??m. These titan cells pose a problem for the host because they contribute to fungal survival, dissemination to the central nervous system, and possibly even latency. In this review, we will provide an overview of these cells, covering current knowledge about their phenotypic features, mechanism of formation, and their significance during infection. ?? 2013 Elsevier Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Microbiology", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "409-413", "publisher" : "Elsevier Ltd", "title" : "Titan cells in <i> Cryptococcus neoformans</i>: Cells with a giant impact", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^116\u2013118", "plainTextFormattedCitation" : "116\u2013118", "previouslyFormattedCitation" : "^116\u2013118" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }116–118 Mouse models of pulmonary cryptococcosis have shown cryptococcal titan cells can be seen in lung parenchyma after three weeks of infection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.ppat.1000945", "ISSN" : "15537366", "PMID" : "20585557", "abstract" : "The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.", "author" : [ { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocio", "given" : "Garcia-Rodas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nosanchuk", "given" : "Joshua D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuenca-Estrella", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriguez-Tudela", "given" : "Juan Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Pathogens", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "title" : "Fungal cell gigantism during mammalian infection", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁹", "plainTextFormattedCitation" : "119", "previouslyFormattedCitation" : "¹¹⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }119 Titan cells are not killed by phagocytic activity and exhibit higher resistance to oxidative stress, resulting in a decreased rate of phagocytosis, with reduced pulmonary clearance and possibly dissemination.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/EC.00121-12", "ISBN" : "1535-9786 (Electronic)\\n1535-9786 (Linking)", "ISSN" : "15359778", "PMID" : "22544904", "abstract" : "The human fungal pathogen Cryptococcus neoformans produces an enlarged \"titan\" cell morphology when exposed to the host pulmonary environment. Titan cells exhibit traits that promote survival in the host. Previous studies showed that titan cells are not phagocytosed and that increased titan cell production in the lungs results in reduced phagocytosis of cryptococcal cells by host immune cells. Here, the effect of titan cell production on host-pathogen interactions during early stages of pulmonary cryptococcosis was explored. The relationship between titan cell production and phagocytosis was found to be nonlinear; moderate increases in titan cell production resulted in profound decreases in phagocytosis, with significant differences occurring within the first 24 h of the infection. Not only were titan cells themselves protected from phagocytosis, but titan cell formation also conferred protection from phagocytosis to normal-size cryptococcal cells. Large particles introduced into the lungs were not phagocytosed, suggesting the large size of titan cells protects against phagocytosis. The presence of large particles was unable to protect smaller particles from phagocytosis, revealing that titan cell size alone is not sufficient to provide the observed cross-protection of normal-size cryptococcal cells. These data suggest that titan cells play a critical role in establishment of the pulmonary infection by promoting the survival of the entire population of cryptococcal cells.", "author" : [ { "dropping-particle" : "", "family" : "Okagaki", "given" : "Laura H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "820-826", "title" : "Titan cells confer protection from phagocytosis in <i> Cryptococcus neoformans</i> infections", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.ppat.1000945", "ISSN" : "15537366", "PMID" : "20585557", "abstract" : "The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.", "author" : [ { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocio", "given" : "Garcia-Rodas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nosanchuk", "given" : "Joshua D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuenca-Estrella", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriguez-Tudela", "given" : "Juan Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Pathogens", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "title" : "Fungal cell gigantism during mammalian infection", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1128/IAI.00507-12", "ISBN" : "0019-9567", "ISSN" : "00199567", "PMID" : "22890995", "abstract" : "Infection with Cryptococcus neoformans begins when desiccated yeast cells or spores are inhaled and lodge in the alveoli of the lungs. A subset of cryptococcal cells in the lungs differentiate into enlarged cells, referred to as titan cells. Titan cells can be as large as 50 to 100 \u03bcm in diameter and exhibit a number of features that may affect interactions with host immune defenses. To characterize the effect of titan cell formation on the host-pathogen interaction, we utilized a previously described C. neoformans mutant, the gpr4\u0394 gpr5\u0394 mutant, which has minimal titan cell production in vivo. The gpr4\u0394 gpr5\u0394 mutant strain had attenuated virulence, a lower CFU, and reduced dissemination compared to the wild-type strain. Titan cell production by the wild-type strain also resulted in increased eosinophil accumulation and decreased phagocytosis in the lungs compared to those with the gpr4\u0394 gpr5\u0394 mutant strain. Phagocytosed cryptococcal cells exhibited less viability than nonphagocytosed cells, which potentially explains the reduced cell survival and overall attenuation of virulence in the absence of titan cells. These data show that titan cell formation is a novel virulence factor in C. neoformans that promotes establishment of the initial pulmonary infection and plays a key role in disease progression.", "author" : [ { "dropping-particle" : "", "family" : "Crabtree", "given" : "Juliet N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okagaki", "given" : "Laura H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiesner", "given" : "Darin L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strain", "given" : "Anna K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Judith N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-3", "issue" : "11", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "3776-3785", "title" : "Titan cell production enhances the virulence of <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^116,119,120", "plainTextFormattedCitation" : "116,119,120", "previouslyFormattedCitation" : "^116,119,120" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }116,119,120 Titan cells are a potential novel target cell for therapy of pulmonary cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.mib.2013.03.006", "ISBN" : "1369-5274", "ISSN" : "13695274", "PMID" : "23588027", "abstract" : "Cryptococcus neoformans is a pathogenic yeast that commonly infects immunocompromised individuals, yet has developed multiple adaptation mechanisms to the host. Several virulence factors (capsule and melanin) have been known for many years. However, this yeast also possesses a morphogenetic program that is still not well characterized. C. neoformans has the ability to dramatically enlarge its size during infection to form 'titan cells' that can reach up to 100. ??m in cell body diameter, in contrast to typical size cells of 5-7. ??m. These titan cells pose a problem for the host because they contribute to fungal survival, dissemination to the central nervous system, and possibly even latency. In this review, we will provide an overview of these cells, covering current knowledge about their phenotypic features, mechanism of formation, and their significance during infection. ?? 2013 Elsevier Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Microbiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "409-413", "publisher" : "Elsevier Ltd", "title" : "Titan cells in <i> Cryptococcus neoformans</i>: Cells with a giant impact", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹¹⁸", "plainTextFormattedCitation" : "118", "previouslyFormattedCitation" : "¹¹⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }118 The published literature is silent on whether titan cells are involved in the pathogenesis of C. gatti infection. Laccase is one of the enzymes contained in the extracellular vesicles of both C. neoformans and C. gattii and associated with virulence.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/EC.00370-07", "ISBN" : "1535-9786 (Electronic)\\r1535-9786 (Linking)", "ISSN" : "15359778", "PMID" : "18039940", "abstract" : "Cryptococcus neoformans produces vesicles containing its major virulence factor, the capsular polysaccharide glucuronoxylomannan (GXM). These vesicles cross the cell wall to reach the extracellular space, where the polysaccharide is supposedly used for capsule growth or delivered into host tissues. In the present study, we characterized vesicle morphology and protein composition by a combination of techniques including electron microscopy, proteomics, enzymatic activity, and serological reactivity. Secretory vesicles in C. neoformans appear to be correlated with exosome-like compartments derived from multivesicular bodies. Extracellular vesicles manifested various sizes and morphologies, including electron-lucid membrane bodies and electron-dense vesicles. Seventy-six proteins were identified by proteomic analysis, including several related to virulence and protection against oxidative stress. Biochemical tests indicated laccase and urease activities in vesicles. In addition, different vesicle proteins were recognized by sera from patients with cryptococcosis. These results reveal an efficient and general mechanism of secretion of pathogenesis-related molecules in C. neoformans, suggesting that extracellular vesicles function as \"virulence bags\" that deliver a concentrated payload of fungal products to host effector cells and tissues.", "author" : [ { "dropping-particle" : "", "family" : "Rodrigues", "given" : "Marcio L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakayasu", "given" : "Ernesto S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira", "given" : "Debora L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nimrichter", "given" : "Leonardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nosanchuk", "given" : "Joshua D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almeida", "given" : "Igor C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "58-67", "title" : "Extracellular vesicles produced by <i> Cryptococcus neoformans</i> contain protein components associated with virulence", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0016076", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "21249145", "abstract" : "Human and animal cryptococcosis due to an unusual molecular type of Cryptococcus gattii (VGII) emerged recently on Vancouver Island, Canada. Unlike C. neoformans, C. gattii causes disease mainly in immunocompetent hosts, despite producing a similar suite of virulence determinants. To investigate a potential relationship between the regulation of expression of a virulence gene composite and virulence, we took advantage of two subtypes of VGII (a and b), one highly virulent (R265) and one less virulent (R272), that were identified from the Vancouver outbreak. By expression microarray analysis, 202 genes showed at least a 2-fold difference in expression with 108 being up- and 94 being down-regulated in strain R265 compared with strain R272. Specifically, expression levels of genes encoding putative virulence factors (e.g. LAC1, LAC2, CAS3 and MPK1) and genes encoding proteins involved in cell wall assembly, carbohydrate and lipid metabolism were increased in strain R265, whereas genes involved in the regulation of mitosis and ergosterol biosynthesis were suppressed. In vitro phenotypic studies and transcription analysis confirmed the microarray results. Gene disruption of LAC1 and MPK1 revealed defects in melanin synthesis and cell wall integrity, respectively, where CAS3 was not essential for capsule production. Moreover, MPK1 also controls melanin and capsule production and causes a severe attenuation of the virulence in a murine inhalational model. Overall, this study provides the basis for further genetic studies to characterize the differences in the virulence composite of strains with minor evolutionary divergences in gene expression in the primary pathogen C. gattii, that have led to a major invasive fungal infection outbreak.", "author" : [ { "dropping-particle" : "", "family" : "Ngamskulrungroj", "given" : "Popchai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "title" : "<i>Cryptococcus gattii </i> virulence composite: Candidate genes revealed by microarray analysis of high and less virulent Vancouver Island outbreak strains", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^110,121", "plainTextFormattedCitation" : "110,121", "previouslyFormattedCitation" : "^110,121" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }110,121 Laccase reduces macrophage activity in the lung and produces melanin pigments, prostaglandin E2 and iron oxidation products.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0019-9567 (Print)\\r0019-9567 (Linking)", "ISSN" : "00199567", "PMID" : "10531264", "abstract" : "While laccase of Cryptococcus neoformans is implicated in the virulence of the organism, our recent studies showing absence of melanin in the infected mouse brain has led us to a search for alternative roles for laccase in cryptococcosis. We investigated the role of laccase in protection of C. neoformans against murine alveolar macrophage (AM)-mediated antifungal activity by using a pair of congenic laccase-positive (2E-TUC) and laccase-deficient (2E-TU) strains. The laccase-positive cells with laccase derepression were more resistant to the antifungal activity of AM than a laccase-deficient strain ([28.9 \u060e 1.2]% versus [40.2 \u060e 2.6]% killing). Addition of L-dopa to Cryptococcus to produce melanin in a laccase-positive strain resulted in a slight increase in protection of C. neoformans from the antifungal activity of macrophages ([25.4 \u060e 3.4]% versus [28.9 \u060e 1.2]% killing). Recombinant cryptococcal laccase exhibited iron oxidase activity in converting Fe(II) to Fe(III). Moreover, recombinant laccase inhibited killing of C. neoformans by hydroxyl radicals catalyzed by iron in a cell-free system. Addition of the hydroxyl radical scavenger mannitol or dimethyl sulfoxide to AMs prior to the introduction of cryptococcal cells decreased killing of both strains and reduced the difference in susceptibility between the laccase-positive and laccase-deficient strains. Furthermore, laccase-mediated protection from AM killing was inhibited by the addition of Fe(II), presumably by overcoming the effects of the iron oxidase activity of cryptococcal laccase. These results suggest that the iron oxidase activity of laccase may protect C. neoformans from macrophages by oxidation of phagosomal iron to Fe(III) with a resultant decrease in hydroxyl radical formation.", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Lide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tewari", "given" : "Ram P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williamson", "given" : "Peter R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "6034-6039", "title" : "Laccase protects <i> Cryptococcus neoformans</i> from antifungal activity of alveolar macrophages", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1099/mic.0.2007/011049-0", "ISBN" : "1350-0872", "ISSN" : "13500872", "PMID" : "18048910", "abstract" : "The human fungal pathogen Cryptococcus neoformans produces melanin in the presence of various substrates, including the L enantiomer of 3,4-dihydroxyphenylalanine (DOPA). The enzyme laccase catalyses the formation of melanin by oxidizing L-DOPA, initiating a series of presumably spontaneous reactions that ultimately leads to the polymerization of the pigment in the yeast cell wall. There, melanin protects the cell from a multitude of environmental and host assaults. Thus, the ability of C. neoformans to produce pigments from a variety of available substrates is likely to confer a survival advantage. A number of C. neoformans isolates of different serotypes produced pigments from D-DOPA, the stereoisomer of L-DOPA. Acid-resistant particles were isolated from pigmented C. neoformans cells grown in the presence of D-DOPA. Biophysical characterization showed the particles had a stably detectable free-radical signal by EPR, and negative zeta potential, similar to L-DOPA-derived particles. No major differences were found between L- and D-DOPA ghosts in terms of binding to anti-melanin antibodies, or in overall architecture when imaged by electron microscopy. C. neoformans cells utilized L- and D-DOPA at a similar rate. Overall, our results indicate that C. neoformans shows little stereoselectivity for utilizing DOPA in melanin synthesis. The ability of C. neoformans to use both L and D enantiomers for melanization implies that this organism has access to a greater potential pool of substrates for melanin synthesis, and this could potentially be exploited in the design of therapeutic inhibitors of laccase.", "author" : [ { "dropping-particle" : "", "family" : "Eisenman", "given" : "Helene C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mues", "given" : "Mascha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Sarah E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frases", "given" : "Susana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaskes", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerfen", "given" : "Gary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Microbiology", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "3954-3962", "title" : "<i> Cryptococcus neoformans</i> laccase catalyses melanin synthesis from both D- and L-DOPA", "type" : "article-journal", "volume" : "153" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1111/j.1365-2958.2008.06245.x", "ISBN" : "1365-2958 (Electronic)\\r0950-382X (Linking)", "ISSN" : "0950382X", "PMID" : "18410494", "abstract" : "Recently, it has been demonstrated that the opportunistic fungal pathogen Cryptococcus neoformans can synthesize authentic immunomodulatory prostaglandins. The mechanism by which this takes place is unclear as there is no cyclooxygenase homologue in the cryptococcal genome. In this study, we show that cryptococcal production of both PGE(2) and PGF(2 alpha) can be chemically inhibited by caffeic acid, resveratrol and nordihydroguaiaretic acid. These polyphenolic molecules are frequently used as inhibitors of lipoxygenase enzymes; however, blast searches of the cryptococcal genome were unable to identify any homologues of mammalian, plant or fungal lipoxygenases. Next we investigated cryptococcal laccase, an enzyme known to bind polyphenols, and found that either antibody depletion or genetic deletion of the primary cryptococcal laccase (lac1 Delta) resulted in a loss of cryptococcal prostaglandin production. To determine how laccase is involved, we tested recombinant laccase activity on the prostaglandin precursors, arachidonic acid (AA), PGG(2) and PGH(2). Using mass spectroscopy we determined that recombinant Lac1 does not modify AA or PGH(2), but does have a marked activity toward PGG(2) converting it to PGE(2) and 15-keto-PGE(2). These data demonstrate a critical role for laccase in cryptococcal prostaglandin production, and provides insight into a new and unique fungal prostaglandin pathway.", "author" : [ { "dropping-particle" : "", "family" : "Erb-Downward", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noggle", "given" : "Rachael M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williamson", "given" : "Peter R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huffnagle", "given" : "Gary B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular Microbiology", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1428-1437", "title" : "The role of laccase in prostaglandin production by <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^122\u2013124", "plainTextFormattedCitation" : "122\u2013124", "previouslyFormattedCitation" : "^122\u2013124" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }122–124 These laccase products alter host defences with a decrease in the pulmonary virulence of Cryptococcus as observed in a murine study.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0047853", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "23110112", "abstract" : "C. neoformans is a leading cause of fatal mycosis linked to CNS dissemination. Laccase, encoded by the LAC1 gene, is an important virulence factor implicated in brain dissemination yet little is known about the mechanism(s) accounting for this observation. Here, we investigated whether the presence or absence of laccase altered the local immune response in the lungs by comparing infections with the highly virulent strain, H99 (which expresses laccase) and mutant strain of H99 deficient in laccase (lac1\u0394) in a mouse model of pulmonary infection. We found that LAC1 gene deletion decreased the pulmonary fungal burden and abolished CNS dissemination at weeks 2 and 3. Furthermore, LAC1 deletion lead to: 1) diminished pulmonary eosinophilia; 2) increased accumulation of CD4+ and CD8+ T cells; 3) increased Th1 and Th17 cytokines yet decreased Th2 cytokines; and 4) lung macrophage shifting of the lung macrophage phenotype from M2- towards M1-type activation. Next, we used adoptively transferred CD4+ T cells isolated from pulmonary lymph nodes of mice infected with either lac1\u0394 or H99 to evaluate the role of laccase-induced immunomodulation on CNS dissemination. We found that in comparison to PBS treated mice, adoptively transferred CD4+ T cells isolated from lac1\u0394-infected mice decreased CNS dissemination, while those isolated from H99-infected mice increased CNS dissemination. Collectively, our findings reveal that immune modulation away from Th1/Th17 responses and towards Th2 responses represents a novel mechanism through which laccase can contribute to cryptococcal virulence. Furthermore, our data support the hypothesis that laccase-induced changes in polarization of CD4+ T cells contribute to CNS dissemination.", "author" : [ { "dropping-particle" : "", "family" : "Qiu", "given" : "Yafeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "Michael J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dayrit", "given" : "Jeremy K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadd", "given" : "Zachary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meister", "given" : "Daniel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Osterholzer", "given" : "John J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williamson", "given" : "Peter R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olszewski", "given" : "Michal A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Immune modulation mediated by cryptococcal laccase promotes pulmonary growth and brain dissemination of virulent <i> Cryptococcus neoformans</i> in mice", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²⁵", "plainTextFormattedCitation" : "125", "previouslyFormattedCitation" : "¹²⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }125 Cryptococcal laccase leads to a significant decrease in lymphocytes and increase pulmonary eosinophils disturbing the proper adaptive immune response in infected lungs.120Risk factors for pulmonary cryptococcosisMost patients with pulmonary cryptococcosis (> 50%) have no risk factor or immune disorder.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1183/09031936.00168011", "ISBN" : "0903-1936", "ISSN" : "09031936", "PMID" : "22408204", "abstract" : "The aim of the present study was to investigate the clinical characteristics of pulmonary cryptococcosis patients in China, with analysis of immunocompetent and immunocompromised subjects. We performed a retrospective review of 76 patients diagnosed with tissue-confirmed pulmonary cryptococcosis at the Shanghai Pulmonary Hospital (Shanghai, China) during a 10-yr period (2001-2010). Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic. Approximately 80% of the patients had histories suspicious of environmental fungal exposure. Radiological (computed tomography) findings showed predominantly peripheral findings (85.53%, 65 out of 76 patients) including nodular masses (55.26%, 42 out of 76), pneumonic infiltrates (23.68%, 18 out of 76) and mixed type (21.05%, 16 out of 76). 43.42% (33 out of 76) were initially misdiagnosed, often as cancer by false-positive (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) (28 out of 46 cases). 51 patients received antifungal therapy, 25 patients were clinically observed without treatment. As of December 31, 2010, 71 cases showed total recovery and four cases showed improvement (efficacy rate of 98.68%, 75 out of 76). One HIV-positive case died of cryptococcal meningitis. Incidence of pulmonary cryptococcosis in China may be related to environmental fungal exposures. Most presented as asymptomatic peripheral lung lesions. False-positive (18)FDG-PET examinations often lead to initial clinical misdiagnosis of cancer. Unlike immunocompromised or clinically symptomatic patients, all immunocompetent patients had a good response, either to fluconazole monotherapy or observation, with a tendency for spontaneous remissions in the asymptomatic immunocompetent subjects.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Yuxuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Huiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Xueyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Shanmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rongxuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jinfu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "Jingyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yung", "given" : "Rex C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Respiratory Journal", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1191-1200", "title" : "Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.chest.2016.02.129", "ISSN" : "00123692", "author" : [ { "dropping-particle" : "", "family" : "Huang", "given" : "Jinbao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lan", "given" : "Chang-qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Hong-yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qing-hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jia-fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Heng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "A124", "publisher" : "American College of Chest Physicians", "title" : "Retrospective analysis of 117 chinese patients with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "149" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1128/CMR.00126-13", "ISBN" : "1098-6618 (Electronic)\\r0893-8512 (Linking)", "ISSN" : "10986618", "PMID" : "25278580", "abstract" : "Understanding of the taxonomy and phylogeny of Cryptococcus gattii has been advanced by modern molecular techniques. C. gattii probably diverged from Cryptococcus neoformans between 16 million and 160 million years ago, depending on the dating methods applied, and maintains diversity by recombining in nature. South America is the likely source of the virulent C. gattii VGII molecular types that have emerged in North America. C. gattii shares major virulence determinants with C. neoformans, although genomic and transcriptomic studies revealed that despite similar genomes, the VGIIa and VGIIb subtypes employ very different transcriptional circuits and manifest differences in virulence phenotypes. Preliminary evidence suggests that C. gattii VGII causes severe lung disease and death without dissemination, whereas C. neoformans disseminates readily to the central nervous system (CNS) and causes death from meningoencephalitis. Overall, currently available data indicate that the C. gattii VGI, VGII, and VGIII molecular types more commonly affect nonimmunocompromised hosts, in contrast to VGIV. New, rapid, cheap diagnostic tests and imaging modalities are assisting early diagnosis and enabling better outcomes of cerebral cryptococcosis. Complications of CNS infection include increased intracranial pressure, severe neurological sequelae, and development of immune reconstitution syndrome, although the mortality rate is low. C. gattii VGII isolates may exhibit higher fluconazole MICs than other genotypes. Optimal therapeutic regimens are yet to be determined; in most cases, initial therapy with amphotericin B and 5-flucytosine is recommended.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Sharon C.A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "980-1024", "title" : "<i>Cryptococcus gattii </i> infections", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1007/s00408-011-9362-8", "ISSN" : "1432-1750", "PMID" : "22246551", "abstract" : "Pulmonary cryptococcosis typically occurs in immunocompromised patients, but it can also occur in immunocompetent patients. Our objective was to describe the clinical manifestations, diagnosis, and management of primary pulmonary cryptococcosis in immunocompetent patients.", "author" : [ { "dropping-particle" : "", "family" : "Ye", "given" : "Feng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Jia-xing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeng", "given" : "Qing-si", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Guo-qin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Shu-qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Nan-shan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lung", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "339-46", "title" : "Retrospective analysis of 76 immunocompetent patients with primary pulmonary cryptococcosis.", "type" : "article-journal", "volume" : "190" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.2169/internalmedicine.55.7175", "ISSN" : "1349-7235", "PMID" : "27746442", "abstract" : "A 39-year-old man presented to our hospital with a four-week history of headache and a two-week history of low-grade fever. Chest X-rays showed a tumor of approximately 50 mm in size in the right lower field. A histopathological examination of a transbronchial lung biopsy specimen from the right S9/10 revealed numerous fungal elements that appeared as encapsulated yeast with clear halos. Gadolinium-enhanced brain magnetic resonance images showed multiple cerebral nodules. Cryptococcus gattii (Genotype VGIIa) was isolated from the bronchial lavage and cerebrospinal fluid specimens. The patient was an immunocompetent Japanese man who had not recently traveled to a C. gattii-endemic area.", "author" : [ { "dropping-particle" : "", "family" : "Nakao", "given" : "Makoto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muramatsu", "given" : "Hideki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takahashi", "given" : "Tetsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niwa", "given" : "Shunsuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kagawa", "given" : "Yusuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurokawa", "given" : "Ryota", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sone", "given" : "Kazuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uozumi", "given" : "Yuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohkusu", "given" : "Misako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamei", "given" : "Katsuhiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koga", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Internal medicine (Tokyo, Japan)", "id" : "ITEM-5", "issue" : "20", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "3021-3024", "title" : "<i>Cryptococcus gattii </i> genotype VGIIa infection in an immunocompetent Japanese patient: a case report and mini-review.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1155/2012/652351", "ISSN" : "2090-6781", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "Bin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Xiu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Shengyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Clin Exp Pathol", "id" : "ITEM-6", "issue" : "9", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "9798-9801", "title" : "Pulmonary cryptococcosis in an immunocompetent patient : a case report", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1177/1179555717722962", "ISSN" : "1179-5557", "author" : [ { "dropping-particle" : "", "family" : "Kanjanapradit", "given" : "Kanet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kosjerina", "given" : "Zdravko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanomkiat", "given" : "Wiwatana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keeratichananont", "given" : "Warangkana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puntuwong", "given" : "Siripen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Medicine Insights: Pathology", "id" : "ITEM-7", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-5", "title" : "Pulmonary cryptococcosis presenting with lung mass: Report of 7 cases and review of literature", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1186/s12879-017-2459-9", "ISSN" : "1471-2334", "abstract" : "Background: Cryptococcus neoformans is frequently present as an opportunistic pathogen mainly affecting immunocompromised populations. Disseminated C. neoformans infection in immunocompetent population is rare and usually involves lung and central nerve system. Cryptococcus from biologic samples can easily grow on routine fungal and bacterial culture media. Besides, cryptococcal latex agglutination test has been established as a reliable diagnostic tool with overall sensitivities of 93-100%. Case presentation: We report a rare disseminated cryptococcosis case which presented with chronic recurrent multiple abscess in an immunocompetent male involving skin, lung, spine and iliac fossa without evidence of central nerve system involving. The results of serum cryptococcal latex agglutination tests and standard microbial cultures were negative. The patient underwent empirical anti-bacterial and anti-tuberculosis therapy which turned out to be effectless. Finally, bedside inoculation of the pus was carried out and revealed Cryptococcus neoformans, which was confirmed by polymerase chain reaction. After the administration of anti-fungal drugs including liposomal amphotericin B, the patient recovered from fever and paraplegia. Conclusions: This case reveals an uncommon pattern of disseminated C. neoformans infection in immunocompetent population presented with chronic multiple abscess and without central nerve system involving. Negative routine microbial cultures may not necessarily rule out cryptococcosis, especially in early stage. Besides, cryptococcal latex agglutination test does have a chance of false negative, which might be related with \"capsule-deficiency\". Moreover, this phenomenon could be related with low-grade virulence and relative long illness duration.", "author" : [ { "dropping-particle" : "", "family" : "Ruan", "given" : "Qiaoling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Yimin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Shu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Liping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Shu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Wenhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Infectious Diseases", "id" : "ITEM-8", "issue" : "1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369", "publisher" : "BMC Infectious Diseases", "title" : "Disseminated cryptococcosis with recurrent multiple abscesses in an immunocompetent patient: a case report and literature review", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{4,6,126\u2013131}", "plainTextFormattedCitation" : "4,6,126\u2013131", "previouslyFormattedCitation" : "^{4,6,126\u2013131}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4,6,126–131 Additionally, approximately 60% of pulmonary cryptococcosis cases in the HIV-negative population have no underlying disease.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.21037/jtd.2016.10.36", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Kaixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Haibo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Ruixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qichang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qu", "given" : "Jieming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Thoracic Disease", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "2813-2821", "title" : "Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Xie", "given" : "Xiaona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Botao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Chang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Mayun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Dan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Xiaomei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Xueding", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Clin Exp Med", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "3114-3119", "title" : "Clinical analysis of pulmonary cryptococcosis in non-HIV patients in south China", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^10,132,133", "plainTextFormattedCitation" : "10,132,133", "previouslyFormattedCitation" : "^10,132,133" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10,132,133 A report from Thailand of cases collected over 17 years found pulmonary cryptococcosis occurs more frequently in non-immunocompromised patients than in immunocompromised patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ijid.2004.12.004", "ISBN" : "1201-9712 (Print)\\n1201-9712", "ISSN" : "12019712", "PMID" : "16288998", "abstract" : "Objective: To describe the clinical characteristics, treatment, and outcomes of cryptococcosis in HIV-negative patients. Methods: HIV-negative adult patients with positive culture for Cryptococcus neoformans who attended Ramathibodi Hospital between 1987 and 2003 were retrospectively reviewed. Results: During the 17 year review period, 40 HIV-negative patients with cryptococcosis were identified. Of these, 37 patients had medical records available for study. The mean age was 49 ?? 18 (range 16-83) years and 73% were female. Twenty-four patients (65%) had associated underlying conditions. The most common associated conditions included immunosuppressive drug treatment (41%), presence of systemic lupus erythematosus (16%), malignancies (16%), and diabetes mellitus (14%). C. neoformans was mainly recovered from cerebrospinal fluid (32%), blood (28%), and sputum/bronchoalveolar lavage/lung tissue (28%). Twenty-three patients (62%) had disseminated cryptococcosis. Six of 14 patients with cryptococcal meningitis were asymptomatic. About half of the patients were treated with amphotericin B and subsequent fluconazole. Five patients (14%) were initially misdiagnosed and treated for tuberculosis or bacterial infection. The overall mortality rate was 27%. Conclusions: Cryptococcosis is not rare in HIV-negative patients. The mortality rate is high. Early recognition of cryptococcosis and use of appropriate antifungal therapy in these patients may improve clinical outcomes. ?? 2005 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Kiertiburanakul", "given" : "Sasisopin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wirojtananugoon", "given" : "Sirirat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pracharktam", "given" : "Roongnapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sungkanuparph", "given" : "Somnuek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Infectious Diseases", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "72-78", "title" : "Cryptococcosis in human immunodeficiency virus-negative patients", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³⁴", "plainTextFormattedCitation" : "134", "previouslyFormattedCitation" : "¹³⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }134 There were also several reports of co-infection between pulmonary cryptococcosis and tuberculosis in the immunocompetent host, suggestive of some shared, ill-defined risk factor.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ijtb.2016.09.016", "ISSN" : "00195707", "abstract" : "Coexistence of pulmonary cryptococcosis with other infections has commonly been described in immuno-suppressed individuals. In immuno-competent hosts, such coexistence is rare and mostly described in disseminated disease or uncommonly involving different sites. The simultaneous coinfection of cryptococcosis and tuberculosis of lung in an immuno-competent host is extremely rare with only one previously reported case in the literature. This is the second such case and the first to be reported in India. We describe a case of a 36-year-old immuno-competent male who presented with haemoptysis and cough. Computed tomography showed a sub-pleural lung nodule. Diagnostic thoracoscopic wedge resection of the right lung nodule revealed granulomatous inflammation with cryptococcus on histopathology. Coexistent tuberculosis was diagnosed by microbiological culture study on lung tissue. The patient responded clinically to fluconazole and anti-tubercular therapy. This case shows that although rare, coexistent infections can occur in immuno-competent persons and highlights the importance of careful evaluation and tissue microbiological culture examination.", "author" : [ { "dropping-particle" : "", "family" : "Jain", "given" : "Sunila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Vrushali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Arvind", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Indian Journal of Tuberculosis", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "228-231", "publisher" : "Tuberculosis Association of India", "title" : "Unusual case of coexistent pulmonary cryptococcosis and tuberculosis in an immuno-competent host", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/s12890-018-0578-8", "ISSN" : "14712466", "PMID" : "29338706", "abstract" : "BACKGROUND: Tuberculosis and cryptococcosis co-infection usually occurs in immunosuppressed patients with impaired cell-mediated immunity. However, there are few reports about such co-infection in non-HIV patients without underlying diseases. Here, we report a case of miliary tuberculosis with co-existing pulmonary cryptococcosis in non-HIV patient without underlying diseases. CASE PRESENTATION: An 84-year-old Asian female presented to our hospital with complaints of a 1-week history of abdominal pain and appetite loss. Chest computed tomography (CT) showed diffuse micronodules in random patterns in both lung fields. Liver, skin and bone marrow biopsies showed epithelioid cell granuloma. Polymerase chain reaction of gastric aspirate was positive for Mycobacterium tuberculosis. According to these findings, miliary tuberculosis was suspected and antimycobacterial therapy was initiated. After a 6-month treatment course, chest radiograph showed new multiple nodules in the right middle lung field. Chest CT showed that a right S6 small nodule was increased and new multiple nodules appeared in the right lower lobe. Flexible fiberoptic bronchoscopy was subsequently perfomed. Cytology of the bronchial lavage showed a small number of Periodic acid-Schiff-positive bodies, suggesting Cryptococcus species. Moreover, serum cryptococcal antigen testing was positive. According to these findings, pulmonary cryptococcosis was diagnosed, although the culture was negative. Oral fluconazole therapy was subsequently initiated. After a 6-month treatment course, chest radiograph showed gradual improvement. CONCLUSION: Although tuberculosis and cryptococcosis co-infection is relatively rare in immunocompromised hosts, such as those with acquired immunodeficiency syndrome, clinicians should be aware that these infections can co-exist even in non-HIV patients without underlying diseases.", "author" : [ { "dropping-particle" : "", "family" : "Sawai", "given" : "Toyomitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakao", "given" : "Takumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koga", "given" : "Satoru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ide", "given" : "Shotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshioka", "given" : "Sumako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsuo", "given" : "Nobuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukae", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Pulmonary Medicine", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "1-5", "publisher" : "BMC Pulmonary Medicine", "title" : "Miliary tuberculosis with co-existing pulmonary cryptococcosis in non-HIV patient without underlying diseases: a case report", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "00375675", "abstract" : "INTRODUCTION Cryptococcus neoformans is a ubiquitous pathogen that can cause infections after being acquired through the inhalational route. The virulence and pathogenic spectrum depends on the cell mediated immunity of the host. Pulmonary cryptococcosis can have a varied clinical and radiographic presentation. Concomitant pulmonary infection with Mycobacterium tuberculosis in an immunocompetent host is exceedingly rare with very few cases reported in the medical literature. CASE DESCRIPTION A 60 year old Vietnamese immigrant presented to the emergency department with a one month history of cough with mild hemoptysis. She also noted a six month histoyr of mild weight loss. The patient's admission chest roentgenogram demonstrated an elongated right middle lobe opacity. A subsequent computerized tomography (CT) scan showed a consolidation in the lateral segment of the right middle lobe with occlusion of the segmental bronchus (see figure). The patient was isolated and sputum samples were sent for acid fast staining and culture. Subsequently, the patient underwent a bronchoscopy which demonstrated a hyper pigmented, non-occlusive mucosal lesion in the affected segment. The lesion was not biopsied for fear of causing severe bleeding. Lavage cultures came back positive for Cryptococcus neoformans at 3 weeks. Subsequent cultures also grew Mycobacterium tuberculosis at 8 weeks. The patient was started on rifampin, isoniazid, ethambutol, pyrazinamide therapy. Her serum cryptococcal antigen titer was negative therefore antifungal therapy was withheld. The patient's symptoms subsequently resolved. Discussion: Coinfection with Cryptococcus in patients infected with Mycobacterium tuberculosis usually has a more severe presentation. Patients often have positive antigen titers and early dissemination with central nervous system involvement. Primary pulmonary presentation of Cryptococcus neoformans alone in an immunocompetent host is relatively uncommon. The CT findings of pulmonary cryptococcosis includes pulmonary nodules of varying sizes. Consolidations, ground glass opacities and pleural effusions can also be found in more severe cases. The focal, lobar consolidation as seen in our patient may have represented her mycobacterial disease rather than cryptococcal pneumonia. There appears to be controversy regarding the treatment of pulmonary cryptococcosis in an immunocompetent host. It seems that it is reasonable to observe these patients off treatment. Our patient \u2026", "author" : [ { "dropping-particle" : "", "family" : "Thomas", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christopher", "given" : "DJ", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balamugesh", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Singapore Med J", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "32-34", "title" : "Coexisting pulmonary cryptococcosis and pulmonary tuberculosis in an immunocompetent host", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1093/qjmed/hct211", "ISBN" : "1460-2725\\n1460-2393", "ISSN" : "14602725", "PMID" : "24149279", "author" : [ { "dropping-particle" : "", "family" : "Huang", "given" : "C. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "C. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "S. W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "T. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Q J Med", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "223-224", "title" : "Simultaneous coinfection with <i>Cryptococcus neoformans and Mycobacterium tuberculosis</i> in an adult", "type" : "article-journal", "volume" : "107" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Nabaei", "given" : "Ghaemeh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afhami", "given" : "Shirin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-5", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "174-176", "title" : "Disseminated cryptococcosis and active pulmonary tuberculosis co- infection in an otherwise healthy adult", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1378/chest.50.2.214", "ISSN" : "00960217", "author" : [ { "dropping-particle" : "", "family" : "Chomicki", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST Journal", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "1966" ] ] }, "page" : "1-3", "publisher" : "The American College of Chest Physicians", "title" : "Coexistence of pulmonary tuberculosis with pulmonary and meningeal cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1038/emi.2017.61", "ISSN" : "22221751", "PMID" : "28831193", "abstract" : "Cases of tuberculosis/cryptococcosis co-infection are rapidly increasing in China. However, most studies addressing this co-infection have been published in Chinese journals, and this publication strategy has obscured this disease trend for scientists in other parts of the world. Our investigation found that 62.9% of all co-infection cases worldwide were reported in the Chinese population (n=197) between 1965 and 2016, and 56.3% of these Chinese cases were reported after 2010. Nearly all cases originated from the warm and wet monsoon regions of China. HIV-positive subjects tended to correlate with more severe manifestations of a tuberculosis/cryptococcosis co-infection than those without HIV. Notablely, dual tubercular/cryptococcal meningitis was the most frequent (54.0%) and most easily misdiagnosed (95.2%, n=40/42) co-infection. We also found that the combined use of cerebrospinal fluid pressure and concentrations of glucose, protein and chlorine might be an inexpensive and effective indicator to differentiate tubercular/cryptococcal co-infection meningitis from tubercular meningitis and cryptococcal meningitis.", "author" : [ { "dropping-particle" : "", "family" : "Fang", "given" : "Wenjie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Denning", "given" : "David W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiang", "given" : "Weiwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Shuwen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lei", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Danqi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jianping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Emerging microbes & infections", "id" : "ITEM-7", "issue" : "8", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "e73", "publisher" : "Nature Publishing Group", "title" : "Tuberculosis/cryptococcosis co-infection in China between 1965 and 2016", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1136/bcr-2015-213380", "ISBN" : "1757-790x", "ISSN" : "1757790X", "PMID" : "26917794", "abstract" : "A 61-year-old man living in rural Rwanda presented with a 2-month history of fevers, headaches, dry cough, weight loss and confusion. A cerebrospinal fluid analysis revealed neutrophilic pleocytosis, yeast and a positive cryptococcal antigen (CrAg). An HIV antibody test was negative. The patient's cough worsened while on antifungal induction therapy with intravenous conventional amphotericin B and high-dose oral fluconazole. Computerised tomography (CT) scan of the chest showed extensive miliary infiltrates. Bronchoalveolar lavage revealed acid-fast bacilli on smear and a positive GeneXpert test without rifampicin resistance. The patient improved with the addition of antitubercular therapy. In this case report, we describe an unusual presentation of two opportunistic infections occurring together in an HIV-negative man with no other known immunocompromising conditions. The case highlights the fact that, in disease endemic areas, multiple disseminated infections can occur in individuals without obvious immunocompromise.", "author" : [ { "dropping-particle" : "", "family" : "Musabende", "given" : "Marcellin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukabatsinda", "given" : "Constance", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riviello", "given" : "Elisabeth D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogbuagu", "given" : "Onyema", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ Case Reports", "id" : "ITEM-8", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-4", "title" : "Concurrent cryptococcal meningitis and disseminated tuberculosis occurring in an immunocompetent male", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^135\u2013142", "plainTextFormattedCitation" : "135\u2013142", "previouslyFormattedCitation" : "^135\u2013142" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }135–142 However, some patients with pulmonary cryptococcosis have a defect in their immune system.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-1", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Rigby", "given" : "Amy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glanville", "given" : "Allan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Respiratory and Critical Care Medicine", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "200-201", "title" : "Miliary pulmonary cryptococcosis in an HIV-positive patient", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^3,46", "plainTextFormattedCitation" : "3,46", "previouslyFormattedCitation" : "^3,46" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }3,46 Hu et al. found the genetic polymorphism in Dectin-2 to be more frequent in those with pulmonary cryptococcosis in an HIV-negative population in China.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/mmy/myv043", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Xiu-ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Rui-ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Ya-hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yan-qiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Hua-zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ji-qin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weng", "given" : "Xin-hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gao", "given" : "Xin-hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Ren-hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Li-ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "810-816", "title" : "Dectin-2 polymorphism associated with pulmonary cryptococcosis in HIV-uninfected Chinese patients", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴³", "plainTextFormattedCitation" : "143", "previouslyFormattedCitation" : "¹⁴³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }143 Immunocompromised conditions such as HIV infection, organ transplantation, diabetes mellitus, corticosteroid or immunosuppressive therapy, and malignancy are all conditions linked with pulmonary cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hajjeh", "given" : "Rana A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conn", "given" : "Laura A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stephens", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baughman", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graviss", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pappas", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Carolynn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reingold", "given" : "Arthur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rothrock", "given" : "Gretchen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hutwagner", "given" : "Lori C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schuchat", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandt", "given" : "Mary E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinner", "given" : "Robert W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Infectious Diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "449-454", "title" : "Cryptococcosis : population-based multistate active surveillance and risk factors in Human immunodeficiency Virus \u2013 infected persons", "type" : "article-journal", "volume" : "179" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0065-7778 (Print)\\r0065-7778", "ISSN" : "0065-7778", "PMID" : "23874010", "abstract" : "Infections due to Cryptococcus species occur globally and in a wide variety of hosts, ranging from those who are severely immunosuppressed to those who have phenotypically \"normal\" immune systems. Approximately 1 million cases of cryptococcosis occur throughout the world, and is it estimated that there are 650,000 associated deaths annually. Most of these cases occur among patients with advanced HIV disease, but a growing number occur among solid organ transplant recipients and others receiving exogenous immunosuppression, patients with innate and acquired immunodeficiency, and otherwise immunologically normal hosts. Much of our recent knowledge is solely derived from clinical experience over the last 2 to 3 decades of cryptococcosis among HIV-infected patients. However, based on recent observations, it is clear that there are substantial differences in the epidemiology, clinical features, approaches to therapy, and outcome when comparing HIV-infected to non-HIV-infected individuals who have cryptococcosis. If one carefully examines cryptococcosis in the three largest subgroups of patients based on host immune status, specifically, those with HIV, solid organ transplant recipients, and those who are non-HIV, non-transplant (NHNT) infected persons, then one can observe very different risks for infection, varied clinical presentations, long-term complications, mortality, and approaches to therapy. This article focuses on cryptococcosis in the non-HIV-infected patient, including a brief review of ongoing events in the Pacific Northwest of the United States and Canada relative to the outbreak of Cryptococcus gattii infections among a largely immunologically normal population, and highlights some of the key insights and questions which have emerged as a result of these important new observations.", "author" : [ { "dropping-particle" : "", "family" : "Pappas", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Transactions of the American Clinical and Climatological Association", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "61-79", "title" : "Cryptococcal infections in non-HIV-infected patients.", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.bjid.2012.07.004", "ISBN" : "1413-8670", "ISSN" : "1678-4391", "PMID" : "23154046", "abstract" : "OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients.\\n\\nMETHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied.\\n\\nRESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2\u00b111.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients.\\n\\nCONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Jin-Quan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Ke-Jing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing-Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Can-Mao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Light", "given" : "Richard W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "531-9", "publisher" : "Elsevier Editora Ltda", "title" : "Pulmonary cryptococcosis in non-AIDS patients.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{22,144\u2013146}", "plainTextFormattedCitation" : "22,144\u2013146", "previouslyFormattedCitation" : "^{22,144\u2013146}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22,144–146 HIV infectionA remarkable histopathology autopsy study of 8,421 miners who died revealed the incidence of pulmonary cryptococcosis to be 7%, whereas the ante-mortem incidence was only 2.7%: the estimated HIV-prevalence was 24%.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1027-3719", "ISSN" : "1027-3719", "PMID" : "17439676", "abstract" : "SETTING: Deceased miners from South Africa whose cardiorespiratory organs were submitted for autopsy for compensation for occupational lung diseases from 1996 to 2000. OBJECTIVES: To 1) calculate the prevalence of cryptococcal pneumonia in 8421 autopsied miners, a population with a high prevalence of human immunodeficiency virus (HIV) infection; 2) document the association of cryptococcal pneumonia with other pulmonary infection; 3) document the association of cryptococcal pneumonia with a clinical diagnosis of cryptococcal meningitis; and 4) determine the accuracy of the clinical diagnosis of cryptococcal pneumonia. DESIGN: Case series of 589 black miners with histological evidence of cryptococcal pneumonia at autopsy, defined as the presence of cryptococcal organisms in the lung parenchyma, identified by staining of the mucinous capsule. RESULTS: The incidence of cryptococcal pneumonia at autopsy was 7%. Ninety-seven of the 589 cases (16.5%) had a concomitant respiratory infection, most commonly Pneumocystis jirovecii pneumonia (51.5%), followed by mycobacterial infection (42.3%). In life, cryptococcal meningitis was diagnosed in 46.9% and cryptococcal pneumonia in only 2.7%. CONCLUSION: Although tuberculosis remains the most common HIV-associated respiratory disease in Africa, it is important to consider the diagnosis of cryptococcal pneumonia in acquired immune-deficiency syndrome (AIDS) patients, and to bear in mind the possibility of dual pathology. 2007 The Union.", "author" : [ { "dropping-particle" : "", "family" : "Wong", "given" : "M. L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Back", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Candy", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nelson", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murray", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Tuberculosis and Lung Disease", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "528-533", "title" : "Cryptococcal pneumonia in African miners at autopsy", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁷", "plainTextFormattedCitation" : "147", "previouslyFormattedCitation" : "¹⁴⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }147 Most of the missed cases were misdiagnosed as pulmonary tuberculosis. Cryptococcus was detected from induced sputum in 2.7% pneumonia patients (81% HIV-infected) in Botswana.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1027-3719 (Print)\r1027-3719 (Linking)", "ISSN" : "1027-3719", "PMID" : "19105896", "author" : [ { "dropping-particle" : "", "family" : "Houston", "given" : "Stan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "149", "title" : "Who determines the 'standard of care' in research in resource poor countries?", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁸", "plainTextFormattedCitation" : "148", "previouslyFormattedCitation" : "¹⁴⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }148 A study by Park based on global data from United Nations Program on HIV/AIDS 2007 estimated 55% of cryptococcal meningitis patients also have pulmonary cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/QAD.0b013e328322ffac", "ISBN" : "1473-5571 (Electronic)\\r0269-9370 (Linking)", "ISSN" : "0269-9370", "PMID" : "19182676", "abstract" : "OBJECTIVE: Cryptococcal meningitis is one of the most important HIV-related opportunistic infections, especially in the developing world. In order to help develop global strategies and priorities for prevention and treatment, it is important to estimate the burden of cryptococcal meningitis. DESIGN: Global burden of disease estimation using published studies. METHODS: We used the median incidence rate of available studies in a geographic region to estimate the region-specific cryptococcal meningitis incidence; this was multiplied by the 2007 United Nations Programme on HIV/AIDS HIV population estimate for each region to estimate cryptococcal meningitis cases. To estimate deaths, we assumed a 9% 3-month case-fatality rate among high-income regions, a 55% rate among low-income and middle-income regions, and a 70% rate in sub-Saharan Africa, based on studies published in these areas and expert opinion. RESULTS: Published incidence ranged from 0.04 to 12% per year among persons with HIV. Sub-Saharan Africa had the highest yearly burden estimate (median incidence 3.2%, 720 000 cases; range, 144 000-1.3 million). Median incidence was lowest in Western and Central Europe and Oceania (</=0.1% each). Globally, approximately 957 900 cases (range, 371 700-1 544 000) of cryptococcal meningitis occur each year, resulting in 624 700 deaths (range, 125 000-1 124 900) by 3 months after infection. CONCLUSION: This study, the first attempt to estimate the global burden of cryptococcal meningitis, finds the number of cases and deaths to be very high, with most occurring in sub-Saharan Africa. Further work is needed to better define the scope of the problem and track the epidemiology of this infection, in order to prioritize prevention, diagnosis, and treatment strategies.", "author" : [ { "dropping-particle" : "", "family" : "Park", "given" : "B J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wannemuehler", "given" : "K A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marston", "given" : "B J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Govender", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pappas", "given" : "P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiller", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Aids", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "525-530", "title" : "Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁹", "plainTextFormattedCitation" : "149", "previouslyFormattedCitation" : "¹⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }149 These studies provide evidence that pulmonary cryptococcosis in HIV patients is underdiagnosed.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1046/j.1468-1293.2001.00079.x", "ISBN" : "1464-2662", "ISSN" : "14642662", "PMID" : "11737408", "abstract" : "Objective. Although India has a high prevalence of HIV/AIDS, the associated pathologies responsible for morbidity have not been evaluated previously in a representative study. Hence, an autopsy study was carried out to analyse the spectrum of pulmonary lesions in patients with HIV/AIDS. Methods. A retrospective and prospective autopsy study was carried out during 1988-2000 at Mumbai, India. Lungs from 143 adults, with at least 10 sections from each case, were examined using routine and special stains. Results. The risk factors for 97 men (68%) and 38 women (27%) included: heterosexual sex with multiple partners (135 cases, 95%); blood transfusions (three cases; 2%); sex between men (two cases; 1%); and unknown risk factors (three cases, 2%). Pulmonary pathology was observed in 126 (88%) cases. The lesions identified were tuberculosis (85 cases, 59%), bacterial pneumonia (26 cases, 18%), cytomegalovirus (CMV) infection (10 cases, 7%), cryptococcosis (eight cases, 6%), Pneumocystis carinii pneumonia (seven cases, 5%), aspergillosis (four cases, 3%), toxoplasmosis (two cases, 1%), Kaposi's sarcoma (one case, 1%), squamous cell carcinoma (one case, 1%). Two or more infections were observed in 18 (13%) cases. Conclusions. Pulmonary diseases and risk factors among patients with AIDS in India differ from those reported in industrialized countries. Tuberculosis was the most frequently observed pulmonary infection, followed by bacterial pneumonia and CMV pneumonitis. In contrast with industrialized countries, PCP remains less common in our patients. The information on opportunistic infections obtained in this study will be useful for managing HIV/AIDS cases at district level hospitals where diagnosing specific HIV-associated diseases is not always possible.", "author" : [ { "dropping-particle" : "", "family" : "Lanjewar", "given" : "D. N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duggal", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "HIV Medicine", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "266-271", "title" : "Pulmonary pathology in patients with AIDS: An autopsy study from Mumbai", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/00000441-199605000-00004", "ISSN" : "00029629", "PMID" : "8615396", "abstract" : "The authors set out to evaluate the use of the autopsy in an urban public teaching hospital setting during the AIDS era. Demographic and length of hospital stay data were obtained from weekly mortality review reports on all patients dying on the medicine service between 1/1/92 and 12/31/93. Clinical and autopsy diagnoses were compared for those patients who had autopsies. The autopsy rate was 16% (152/974). Significant, unsuspected diagnoses were found in 35% (53/152) of the cases, with infections, pulmonary emboli, and myocardial infarctions being most common. Human immunodeficiency virus-infected patients had a greater percentage of unsuspected findings (55%, 23/42), and many of these also were from an infectious etiology. The authors conclude that valuable, unsuspected information frequently can be obtained from autopsies in this clinical setting.", "author" : [ { "dropping-particle" : "", "family" : "Bernicker", "given" : "E H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atmar", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schaffner", "given" : "D L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenberg", "given" : "S B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of the medical sciences", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "215-220", "title" : "Unanticipated diagnoses found at autopsy in an urban public teaching hospital.", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "1027-3719 (Print)\r1027-3719 (Linking)", "ISSN" : "1027-3719", "PMID" : "19105896", "author" : [ { "dropping-particle" : "", "family" : "Houston", "given" : "Stan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "149", "title" : "Who determines the 'standard of care' in research in resource poor countries?", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^148,150,151", "plainTextFormattedCitation" : "148,150,151", "previouslyFormattedCitation" : "^148,150,151" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }148,150,151 There was no significant difference in 90-day and 1-year mortality among HIV patients, organ transplant patients and non-HIV non-organ transplant (NHNT) patients in a cohort study of cryptococcal disease.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0065-7778 (Print)\\r0065-7778", "ISSN" : "0065-7778", "PMID" : "23874010", "abstract" : "Infections due to Cryptococcus species occur globally and in a wide variety of hosts, ranging from those who are severely immunosuppressed to those who have phenotypically \"normal\" immune systems. Approximately 1 million cases of cryptococcosis occur throughout the world, and is it estimated that there are 650,000 associated deaths annually. Most of these cases occur among patients with advanced HIV disease, but a growing number occur among solid organ transplant recipients and others receiving exogenous immunosuppression, patients with innate and acquired immunodeficiency, and otherwise immunologically normal hosts. Much of our recent knowledge is solely derived from clinical experience over the last 2 to 3 decades of cryptococcosis among HIV-infected patients. However, based on recent observations, it is clear that there are substantial differences in the epidemiology, clinical features, approaches to therapy, and outcome when comparing HIV-infected to non-HIV-infected individuals who have cryptococcosis. If one carefully examines cryptococcosis in the three largest subgroups of patients based on host immune status, specifically, those with HIV, solid organ transplant recipients, and those who are non-HIV, non-transplant (NHNT) infected persons, then one can observe very different risks for infection, varied clinical presentations, long-term complications, mortality, and approaches to therapy. This article focuses on cryptococcosis in the non-HIV-infected patient, including a brief review of ongoing events in the Pacific Northwest of the United States and Canada relative to the outbreak of Cryptococcus gattii infections among a largely immunologically normal population, and highlights some of the key insights and questions which have emerged as a result of these important new observations.", "author" : [ { "dropping-particle" : "", "family" : "Pappas", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Transactions of the American Clinical and Climatological Association", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "61-79", "title" : "Cryptococcal infections in non-HIV-infected patients.", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁵", "plainTextFormattedCitation" : "145", "previouslyFormattedCitation" : "¹⁴⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }145 Pulmonary cryptococcosis was also diagnosed along with other fungal pneumonia such as pulmonary aspergillosis and Pneumocystis jirovecii (carinii) lung infections in HIV-positive patients; mixed infection might occur in certain cases. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.7860/JCDR/2017/24219.9277", "ISBN" : "2249-782X", "ISSN" : "0973709X", "PMID" : "28384860", "abstract" : "INTRODUCTION Opportunistic pneumonias are a major cause of mortality and morbidity in Human Immunodeficiency Virus (HIV) reactive patients. Despite the significant role that fungi play in causation of this opportunistic mycoses, very few Indian studies have attempted to investigate the burden and aetiological spectrum of HIV/AIDS-associated fungal pneumonias. AIM To document the prevalence of fungal aetiology in HIV/AIDS-related opportunistic pneumonias in an Indian setting; and to elucidate the various fungal opportunists responsible for the same. MATERIALS AND METHODS The present study was a prospective, cross-sectional analysis conducted at Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi from October 2008 to September 2011. Expectorated sputa were collected from 71 HIV reactive patients with a clinical diagnosis of pneumonia and subjected to direct microscopic examination employing Gram stain, 10% KOH wet mount and India ink preparation. In addition, direct immunofluorescence of sputum samples was performed for detection of cysts and trophozoites of Pneumocystis carinii. Also, each sputum sample was inoculated in duplicate onto Sabouraud Dextrose Agar (SDA) for culture. A blood sample was drawn from each patient and a battery of serological tests was performed, including Cryptococcal Antigen Latex Agglutination System (CALAS(TM)) for detection of cryptococcal capsular polysaccharide antigen; Platelia\u2122 Aspergillus EIA for detection of Aspergillus galactomannan antigen; SERION ELISA antigenCandida for detection of Candida antigen and Histoplasma DxSelect\u2122 for detecting antibodies to Histoplasma species. Descriptive statistics were employed to depict results as proportions and figures. Further, arithmetic mean and standard deviation were calculated for central tendencies and median for non-normal/skewed distributions. RESULTS A definite fungal aetiology was established in 25 (35.2%) of 71 HIV reactive patients with pneumonic involvement. Of these, sputa of 21 patients yielded single fungal isolates, while mixed fungal isolates were reported in four patients. Pneumocystis carinii was the predominant fungal pathogen isolated in our study and was reported in 14 (19.7%) patients. Pulmonary aspergillosis was reported in 7 (9.9%) patients, with Aspergillus flavus (4), Aspergillus fumigatus (2) and Aspergillus niger (1) being the commonly recovered Aspergillus species. Candida pneumonia was documented in 6 (8.5%) patients and the Cand\u2026", "author" : [ { "dropping-particle" : "", "family" : "Kaur", "given" : "Ravinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Bhanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhakad", "given" : "Megh Singh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goyal", "given" : "Ritu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhalla", "given" : "Preena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dewan", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical and Diagnostic Research", "id" : 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Another study reported that pulmonary cryptococcosis was more likely to occur in SOT recipients from the most recent cohort (2001 – 2008) than in the previous decades (1960-2000).ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/598936", "ISSN" : "1058-4838", "author" : [ { "dropping-particle" : "", "family" : "Sun", "given" : "Hsin\u2010Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagener", "given" : "Marilyn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Infectious Diseases", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1566-1576", "title" : "Cryptococcosis in solid\u2010organ, hematopoietic stem cell, and tissue transplant recipients: Evidence\u2010based evolving trends", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁵⁷", "plainTextFormattedCitation" : "157", "previouslyFormattedCitation" : "¹⁵⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }157 This study also found nine cryptococcal infections associated with haematological stem cell transplant patients.Corticosteroid or immunosuppressive therapy Long-term corticosteroid or immunosuppressive therapy is a risk factor for developing pulmonary cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.21037/jtd.2016.10.36", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Kaixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Haibo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Ruixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qichang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qu", "given" : "Jieming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Thoracic Disease", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "2813-2821", "title" : "Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Xie", "given" : "Xiaona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Botao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Chang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Mayun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Dan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Xiaomei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Xueding", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Clin Exp Med", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "3114-3119", "title" : "Clinical analysis of pulmonary cryptococcosis in non-HIV patients in south China", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. 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A 64-year-old man, who had been taking corticosteroids for interstitial pneumonia, was diagnosed with disseminated cryptococcal infection. While the patient was receiving anticryptococcal therapy, pulmonary tuberculosis also emerged. The patient developed acute exacerbation of interstitial pneumonia and passed away. Based on the patient's clinical course, serial computed tomography images, and autopsy results, we believe that the preceding several months of corticosteroid treatment might have contributed to these coinfections in the lungs already vulnerable due to underlying fibrosis.;", "author" : [ { "dropping-particle" : "", "family" : "Kuroda", "given" : "Aoi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tasaka", "given" : "Sadatomo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yagi", "given" : "Kazuma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mochimaru", "given" : "Takao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tani", "given" : "Tetsuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Namkoong", "given" : "Ho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Kyuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "Yusuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatano", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasegawa", "given" : "Naoki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okada", "given" : "Yasunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Betsuyaku", "given" : "Tomoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Case Reports In Pulmonology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-6", "title" : "A case of disseminated cryptococcal infection and concurrent lung tuberculosis in a patient under steroid therapy for interstitial pneumonia.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1155/2013/807197", "ISBN" : "2090-6781 (Print)\\n2090-679x", "ISSN" : "2090-6781 (Print)", "PMID" : "23936710", "abstract" : "A case of autoimmune hepatitis complicated with pulmonary and meningeal cryptococcosis during long-term treatment with corticosteroid is reported. An 84-year-old woman who received long-term corticosteroid therapy (40 mg/day prednisolone for two years) for autoimmune hepatitis developed a headache, slight fever, and anorexia and was diagnosed with cryptococcal meningitis two months prior to hospital admission. Due to deterioration of her condition, the patient was transferred to our university hospital. After admission, a pulmonary nodule 1 cm in diameter was noticed in the patient's right lower lobe. Cryptococcal meningitis was diagnosed as positive for cryptococcal antigen from both serum and cerebrospinal fluid (CSF) as well as the growth of Cryptococcus neoformans (C. neoformans) in fungal culture. A combination therapy of amphotericin B and flucytosine was started, and the corticosteroid therapy was gradually reduced and finally discontinued. In addition to continuous cryptococcal infection, complications of Pseudomonas aeruginosa and methicillin-resistance Staphylococcus aureus infection caused death after a 2-month hospitalization. Autopsy disclosed encapsulated yeast in the lungs and subarachnoid space characteristic of Cryptococcus. 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M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husain", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Infectious Diseases", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "e12-e18", "title" : "Pulmonary cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹", "plainTextFormattedCitation" : "1", "previouslyFormattedCitation" : "¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1MalignanciesA recent literature survey found pulmonary cryptococcosis in 26% and 48% in patients with a C. neoformans infection associated either with underlying disease haematological malignancy or solid organ tumours, respectively.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/myc.12496", "ISSN" : "14390507", "author" : [ { "dropping-particle" : "", "family" : "Schmalzle", "given" : "Sarah A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchwald", "given" : "Ulrike K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilliam", "given" : "Bruce L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riedel", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycoses", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "542-552", "title" : "<i> Cryptococcus neoformans</i> infection in malignancy", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁰", "plainTextFormattedCitation" : "160", "previouslyFormattedCitation" : "¹⁶⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }160 The most common haematological malignancy linked to cryptococcal infection was lymphoma. The case series of cryptococcosis in haematological malignancies revealed the lungs as the infection site in most of the patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s12879-017-2561-z", "ISSN" : "1471-2334", "PMID" : "28673256", "abstract" : "BACKGROUND Cryptococcal infection has become a public health challenge globally. However, information about cryptococcal infection in patients with hematological diseases remains relatively rare. METHODS HIV-uninfected cryptococcosis cases with hematological diseases admitted to Huashan Hospital from January 2001 to December 2014 were reviewed. RESULTS In total, 33 cryptococcosis patients were enrolled, including 12 malignant and 21 non-malignant hematological cases. Twenty-six patients had central nervous system (CNS) involvement, which was observed more often in patients with non-malignancies than with malignancies (20/21 vs. 6/12, P\u00a0=\u00a00.001) Most patients (25/26) with CNS infection were confirmed by cerebrospinal fluid (CSF) culture or smear, and 100% (20/20) of them tested positive for the CSF cryptococcal antigen test. Eighteen out of 26 cryptococcal meningitis patients were treated with amphotericin B (AmB)-based therapy, 16 of them with AmB deoxycholate (d-AmB) and 2 patients with liposomal AmB. The clinical success rate was 55.6%. D-AmB was well-tolerated at 0.35-0.59\u00a0mg/kg/d (median 0.43\u00a0mg/kg/d) and only 12 patients had mild adverse events. CONCLUSIONS CNS cryptococcal infection was more frequent in patients with hematological non-malignancies, and cryptococcal antigen test as well as the CSF fungal culture or smear are suggested for early diagnosis. D-AmB could be used as an alternative therapy for CNS-infected patients with hematological diseases.", "author" : [ { "dropping-particle" : "", "family" : "Wang", "given" : "Rui-ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yan-qiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ji-qin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Ya-hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Hua-zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Li-ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Infectious Diseases", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "463", "publisher" : "BMC Infectious Diseases", "title" : "Cryptococcosis in patients with hematological diseases: a 14-year retrospective clinical analysis in a Chinese tertiary hospital", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶¹", "plainTextFormattedCitation" : "161", "previouslyFormattedCitation" : "¹⁶¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }161 The management of lymphoma with T-cell depleting agents and cancer-related immune alteration are probably responsible. Other reports of HIV-negative patients showed 7.3% and 10.2% of this group had malignancies as risk factors for developing pulmonary cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.21037/jtd.2016.10.36", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Kaixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Haibo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Ruixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qichang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qu", "given" : "Jieming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Thoracic Disease", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "2813-2821", "title" : "Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^10,132", "plainTextFormattedCitation" : "10,132", "previouslyFormattedCitation" : "^10,132" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10,132 Diabetes mellitusSevere diabetes mellitus with organ damage appeared as a major risk factor (31.7%) for pulmonary cryptococcosis among HIV-negative patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Xie", "given" : "Xiaona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Botao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Chang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Mayun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Dan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Xiaomei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Xueding", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Clin Exp Med", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "3114-3119", "title" : "Clinical analysis of pulmonary cryptococcosis in non-HIV patients in south China", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/bcr-2016-214453", "ISSN" : "1757-790X", "PMID" : "26917800", "abstract" : "Cryptococcosis is a fungal infection that usually occurs in immunocompromised individuals. Meningitis is the most frequent presentation; uncommonly, a disseminated form occurs. Cryptococcosis can sometimes occur in immunocompetent individuals with certain predisposing conditions such as diabetes mellitus. However, disseminated cryptococcosis is exceedingly rare in these individuals. A 48-year-old man presented with a lung mass and was initially suspected to have bronchogenic carcinoma. However, on further evaluation, it turned out to be disseminated cryptococcosis due to Cryptococcus gattii, with pulmonary, pleural and meningeal involvement.", "author" : [ { "dropping-particle" : "", "family" : "Prasad", "given" : "Kuruswamy Thurai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehgal", "given" : "Inderpaul Singh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shivaprakash", "given" : "M R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhooria", "given" : "Sahajal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ case reports", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-4", "title" : "Uncommon mycosis in a patient with diabetes.", "type" : "article-journal", "volume" : "2016" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^133,162", "plainTextFormattedCitation" : "133,162", "previouslyFormattedCitation" : "^133,162" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }133,162 Another confirmatory study from Japan confirmed diabetes mellitus as a common underlying disease in the same population, with 32.1% affected among all the cryptococcosis cases.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³²", "plainTextFormattedCitation" : "132", "previouslyFormattedCitation" : "¹³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }132 A large study in diabetes mellitus population with cryptococcosis in China revealed 12 of 16 (75%) were pulmonary cases. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/myc.12645", "ISSN" : "09337407", "PMID" : "28857298", "abstract" : "Diabetes mellitus II (DM II) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. This retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in Chinese DM II patients. This study included 30 cases of cryptococcosis with DM II occurring from 1993 to 2015 in mainland China. The hospital-based prevalence of cryptococcosis in DM II was 0.21%. The mean age of the patients was 56.1 years (95% confidence interval: 51.5, 60.6), and 93% of the patients were older than 40 years. Sixty-two per cent of the patients experienced untreated or poorly controlled blood glucose before infection. Multilocus sequence typing analysis categorised all cultured strains as Cryptococcus neoformans and sequence type 5. Sixty-nine per cent of pulmonary cryptococcosis patients experienced misdiagnoses and treatment delays. Sixty per cent of cryptococcal meningitis patients received substandard antifungal therapy. The overall death rate was 33%. Considering the large population size of DM II patients in China, improved attention should be paid to the high prevalence of cryptococcosis as revealed by us. We also emphasised the importance of blood glucose control for infection prevention, especially among the elderly.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "Yingfang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Wenjie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiang", "given" : "Weiwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", 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Infection", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "608-614", "publisher" : "Elsevier Ltd", "title" : "Diabetes mellitus is associated with acquisition and increased mortality in HIV-uninfected patients with cryptococcosis: A population-based study", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁴", "plainTextFormattedCitation" : "164", "previouslyFormattedCitation" : "¹⁶⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }164 The mortality rate is higher in cryptococcosis patients with diabetes compare to matched controls.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0119090", "ISSN" : "19326203", "PMID" : "25747471", "abstract" : "BACKGROUND: Cryptococcus neoformans is a ubiquitous environmental fungus that can cause life-threatening meningitis and fungemia, often in the presence of acquired immunodeficiency syndrome (AIDS), liver cirrhosis, diabetes mellitus, or other medical conditions. To distinguish risk factors from comorbidities, we performed a hospital-based, density-sampled, matched case-control study.\\n\\nMETHODS: All new-onset cryptococcal meningitis cases and cryptococcemia cases at a university hospital in Taiwan from 2002-2010 were retrospectively identified from the computerized inpatient registry and were included in this study. Controls were selected from those hospitalized patients not experiencing cryptococcal meningitis or cryptococcemia. Controls and cases were matched by admission date, age, and gender. Conditional logistic regression was used to analyze the risk factors.\\n\\nRESULTS: A total of 101 patients with cryptococcal meningitis (266 controls) and 47 patients with cryptococcemia (188 controls), of whom 32 patients had both cryptococcal meningitis and cryptococcemia, were included in this study. Multivariate regression analysis showed that AIDS (adjusted odds ratio [aOR] = 181.4; p < 0.001), decompensated liver cirrhosis (aOR = 8.5; p = 0.008), and cell-mediated immunity (CMI)-suppressive regimens without calcineurin inhibitors (CAs) (aOR = 15.9; p < 0.001) were independent risk factors for cryptococcal meningitis. Moreover, AIDS (aOR = 216.3, p < 0.001), decompensated liver cirrhosis (aOR = 23.8; p < 0.001), CMI-suppressive regimens without CAs (aOR = 7.3; p = 0.034), and autoimmune diseases (aOR = 9.3; p = 0.038) were independent risk factors for developing cryptococcemia. On the other hand, diabetes mellitus and other medical conditions were not found to be risk factors for cryptococcal meningitis or cryptococcemia.\\n\\nCONCLUSIONS: The findings confirm AIDS, decompensated liver cirrhosis, CMI-suppressive regimens without CAs, and autoimmune diseases are risk factors for invasive C. neoformans diseases.", "author" : [ { "dropping-particle" : "", "family" : "Lin", "given" : "Ying Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiau", "given" : "Stephanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Chi Tai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-13", "title" : "Risk factors for invasive Cryptococcus neoformans diseases: A case-control study", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁵", "plainTextFormattedCitation" : "165", "previouslyFormattedCitation" : "¹⁶⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }165 Other immunological disorders that co-exist with diabetes mellitus increases the vulnerability of patients to Cryptococcus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1378/chest.119.6.1865", "author" : [ { "dropping-particle" : "", "family" : "Vilchez", "given" : "Regis A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linden", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacomis", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costello", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "1865-1869", "title" : "Acute respiratory failure associated with pulmonary cryptococcosis in non- AIDS patients", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2169/internalmedicine.56.7438", "ISSN" : "0918-2918", "author" : [ { "dropping-particle" : "", "family" : "Inaba", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okada", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshida", "given" : "Taiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Itoyama", "given" : "Satoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakai", "given" : "Tatsuro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hisada", "given" : "Tetsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takano", "given" : "Hideki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Internal Medicine", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "377-380", "title" : "Disseminated cryptococcosis with rapidly growing lung nodules in an end-stage renal disease patient", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^166,167", "plainTextFormattedCitation" : "166,167", "previouslyFormattedCitation" : "^166,167" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }166,167CirrhosisCirrhosis was reported as a risk factor for cryptococcosis with proportion of pulmonary cryptococcosis in the study population ranged between 18-37.5%.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.md.0000126760.45299.69", "ISBN" : "0025-7974", "ISSN" : "0025-7974", "PMID" : "15118545", "abstract" : "We reviewed the cases of patients with cirrhosis, including liver transplant candidates, at our institution in the last 3 years (n = 5) and those individually described in the literature (n = 28), to assess unique characteristics and outcome of cryptococcosis in these patients. Sixty-four percent (21/33) of the patients had no other recognized immunosuppression. Peritonitis (in 45%, 15/33 of the patients) with modest pleocytosis in the ascitic fluid, was the most common presenting feature. Median time to detection of Cryptococcus in the ascitic fluid cultures was 6 days. Overall mortality rate was 81% (26/32); death was deemed attributable to cryptococcosis in 24/26 patients who died. Evaluation of culture-negative neutrocytic ascites in febrile cirrhotic patients warrants consideration of cryptococcal peritonitis.", "author" : [ { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husain", "given" : "Shahid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vera", "given" : "Michael", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gayowski", "given" : "Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Cacciarelli", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "188-192", "title" : "<i> Cryptococcus neoformans</i> infection in patients with cirrhosis, including liver transplant candidates.", "type" : "article-journal", "volume" : "83" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/TP.0000000000000690", "ISBN" : "0000000000000", "ISSN" : "00411337", "PMID" : "25806406", "abstract" : "BACKGROUND: The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known., METHODS: We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care., RESULTS: In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%., CONCLUSIONS: Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.", "author" : [ { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sifri", "given" : "Costi D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Fernanda P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Rachel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregg", "given" : "Kevin S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huprikar", "given" : "Shirish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lease", "given" : "Erika D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmer", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stephen Dummer", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spak", "given" : "Cedric W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koval", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banach", "given" : "David B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shroff", "given" : "Miloni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Le", "given" : "Jade", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ostrander", "given" : "Darin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avery", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eid", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Razonable", "given" : "Raymund R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montero", "given" : "Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blumberg", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alynbiawi", "given" : "Ahlaam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Michele I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Henry B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alangaden", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tessier", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagener", "given" : "Marilyn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Hsin Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Transplantation", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2132-2141", "title" : "Cryptococcosis in patients with cirrhosis of the liver and posttransplant outcomes", "type" : "article-journal", "volume" : "99" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/ofid/ofv197", "ISSN" : "23288957", "PMID" : "26835475", "abstract" : "Background. \u2003Cryptococcosis in the setting of end-stage liver disease (ESLD) has been associated with high mortality. We sought to compare the outcome of cryptococcal disease in patients with ESLD to that of human immunodeficiency virus (HIV)-positive patients and to those patients without HIV or ESLD. Methods. \u2003We assembled a retrospective cohort of 232 consecutive cases of cryptococcosis in our institution, from 2002 to 2014, inclusively. We analyzed the cases for comorbidities, type of infection, and survival. Data were analyzed with t tests, Fishers Exact test, and Kaplan-Meyer analysis. Results. \u2003Twenty-five (10.8%) patients with cryptococcal infection had concomitant ESLD; of these, 5 (20%) presented with peritonitis. Most (17 of 25, 68%) did not have any other cause of immunocompromise that has been more classically associated with cryptococcosis. Patients with ESLD had a significantly higher mortality than HIV-positive patients and HIV-negative patients without ESLD (HIVNE) (80% vs 13.6% and 22.7%, respectively; P < .001). In addition, fatal outcome in ESLD patients occurred more rapidly than in HIVNE patients, with a median survival of 6 days (vs 17), despite a comparable time to diagnosis (6.2 vs 6.6 days). Conclusions. \u2003Cryptococcosis is an important morbidity in patients with ESLD. Patients with ESLD who are infected with Cryptococcus have a high and rapid mortality. This suggests that a high level of vigilance for cryptococcal infection should be kept in patients with ESLD.", "author" : [ { "dropping-particle" : "", "family" : "Spec", "given" : "Andrej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raval", "given" : "Krunal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powderly", "given" : "William G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Open Forum Infectious Diseases", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-5", "title" : "End-stage liver disease is a strong predictor of early mortality in cryptococcosis", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^168\u2013170", "plainTextFormattedCitation" : "168\u2013170", "previouslyFormattedCitation" : "^168\u2013170" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }168–170 The 90-days mortality is high at 57.1% with 54.6% of the death is associated with cryptoccosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/TP.0000000000000690", "ISBN" : "0000000000000", "ISSN" : "00411337", "PMID" : "25806406", "abstract" : "BACKGROUND: The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known., METHODS: We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care., RESULTS: In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%., CONCLUSIONS: Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.", "author" : [ { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sifri", "given" : "Costi D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Fernanda P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Rachel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregg", "given" : "Kevin S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huprikar", "given" : 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"parse-names" : false, "suffix" : "" } ], "container-title" : "Transplantation", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "2132-2141", "title" : "Cryptococcosis in patients with cirrhosis of the liver and posttransplant outcomes", "type" : "article-journal", "volume" : "99" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁹", "plainTextFormattedCitation" : "169", "previouslyFormattedCitation" : "¹⁶⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }169 Although there are case reports of pulmonary cryptococcosis with cirrhosis the correlation between these two diseases is still unknown.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2015/358926", "ISSN" : "2090-6846", "abstract" : "Both disseminated cryptococcal infection and tuberculosis occur in hosts with impaired cell-mediated immunity, but there have been few reports about the concurrent infections in patients without 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A 64-year-old man, who had been taking corticosteroids for interstitial pneumonia, was diagnosed with disseminated cryptococcal infection. While the patient was receiving anticryptococcal therapy, pulmonary tuberculosis also emerged. The patient developed acute exacerbation of interstitial pneumonia and passed away. Based on the patient's clinical course, serial computed tomography images, and autopsy results, we believe that the preceding several months of corticosteroid treatment might have contributed to these coinfections in the lungs already vulnerable due to underlying fibrosis.;", "author" : [ { "dropping-particle" : "", "family" : "Kuroda", "given" : "Aoi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tasaka", "given" : "Sadatomo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yagi", "given" : "Kazuma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mochimaru", "given" : "Takao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tani", "given" : "Tetsuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Namkoong", "given" : "Ho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Kyuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "Yusuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatano", "given" : "Mami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasegawa", "given" : "Naoki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okada", "given" : "Yasunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Betsuyaku", "given" : "Tomoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Case Reports In Pulmonology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-6", "title" : "A case of disseminated cryptococcal infection and concurrent lung tuberculosis in a patient under steroid therapy for interstitial pneumonia.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2169/internalmedicine.49.3785", "ISBN" : "0918-2918\\r1349-7235", "ISSN" : "1349-7235", "PMID" : "20720361", "abstract" : "A 58-year-old woman with an 18-year history of primary biliary cirrhosis was admitted because of pneumococcal pneumonia. She was treated with antibiotics and mechanical ventilation. After the pneumonia improved, she developed severe watery diarrhea. Although vancomycin was administered enterally, the diarrhea persisted. She died of multiple organ failure within 16 days of the onset of diarrhea. An autopsy showed intracapillary cryptococci in the systemic organs, especially in the intestinal tract. The cause of diarrhea was considered to be extensive intestinal mucosal necrosis due to disseminated cryptococcosis. This is a rare case of cryptococcal infection manifesting as acute diarrhea.", "author" : [ { "dropping-particle" : "", "family" : "Hokari", "given" : "Satoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsukada", "given" : "Hiroki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ito", "given" : "Kazuhisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shibuya", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Internal medicine (Tokyo, Japan)", "id" : "ITEM-2", "issue" : "16", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1793-6", "title" : "An autopsy case of disseminated cryptococcosis manifesting as acute diarrhea in a patient with primary biliary cirrhosis.", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "4126486399", "ISSN" : "0025-7974", "PMID" : "11552084", "author" : [ { "dropping-particle" : "", "family" : "Vilchez", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Irish", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacomis", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costello", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fung", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kusne", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medicine", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "308-312", "title" : "The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a tertiary care medical center.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^158,171,172", "plainTextFormattedCitation" : "158,171,172", "previouslyFormattedCitation" : "^158,171,172" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }158,171,172Clinical manifestation of pulmonary cryptococcosisThe central nervous system and the lung are the two organs that comprise the main sites of Cryptococcus infection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2013/471363", "ISBN" : "2090-939x", "ISSN" : "2090-939X", "PMID" : "24052889", "abstract" : "Cryptococcal meningitis is a life-threatening opportunistic fungal infection in both HIV-infected and HIV-uninfected patients. According to the most recent taxonomy, the responsible fungus is classified into a complex that contains two species (Cryptococcus neoformans and C. gattii), with eightmajormolecular types.HIV infection is recognizedworldwide as themain underlying disease responsible for the development of cryptococcal meningitis (accounting for 80\u201390% of cases). In several areas of sub-Saharan Africa with the highest HIV prevalence despite the recent expansion of antiretroviral (ARV) therapy programme, cryptococcal meningitis is the leading cause of community-acquired meningitiswith a highmortality burden.Although cryptococcalmeningitis should be considered a neglected disease, a large body of knowledge has been developed by several studies performed in recent years. This paper will focus especially on newclinical aspects such as immune reconstitution inflammatory syndrome, advances on management, and strategies for the prevention of clinical disease.", "author" : [ { "dropping-particle" : "", "family" : "Antinori", "given" : "Spinello", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "ISRN AIDS", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-22", "title" : "New insights into HIV / AIDS-associated Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "⁸¹", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "⁸¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81 However, skin, soft tissue, joint, bone, kidney, muscle, liver, kidney and other organs may also be infected by this fungus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/313992", "ISBN" : "1058-4838 (Print)\\r1058-4838 (Linking)", "ISSN" : "1058-4838", "PMID" : "10987712", "abstract" : "A prospective population-based study was conducted in Australia and New Zealand during 1994-1997 to elucidate the epidemiology of cryptococcosis due to Cryptococcus neoformans var. neoformans (CNVN) and C. neoformans var. gattii (CNVG) and to relate clinical manifestations to host immune status and cryptococcal variety. The mean annual incidence per 10(6) population was 6.6 in Australia and 2.2 in New Zealand. Of 312 episodes, CNVN caused 265 (85%; 98% of the episodes in immunocompromised hosts) and CNVG caused 47 (15%; 44% of the episodes in immunocompetent hosts). The incidence of AIDS-associated cases in Australia declined annually (P<.001). Aborigines in rural or semirural locations (P<.001) and immunocompetent males (P<.001) were at increased risk of CNVG infection. Cryptococcomas in lung or brain were more common in immunocompetent hosts (P< or =.03) in whom there was an association only between lung cryptococcomas and CNVG. An AIDS-associated genetic profile of CNVN serotype A was confirmed by random amplification of polymorphic DNA analysis. Resistance to antifungal drugs was uncommon. The epidemiology of CNVN infection has changed substantially. Clinical manifestations of disease are influenced more strongly by host immune status than by cryptococcal variety.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nimmo", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speed", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Currie", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellis", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marriott", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parr", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Byth", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "499-508", "title" : "Epidemiology and host- and variety-dependent characteristics of infection due to <i> Cryptococcus neoformans</i> in Australia and New Zealand. Australasian Cryptococcal Study Group.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/0002-9343(72)90174-X", "ISSN" : "00029343", "PMID" : "5054723", "abstract" : "The records of thirty-two patients with cryptococcosis admitted to the University of Iowa Hospitals were reviewed. The organ system clinically involved most frequently was the central nervous system. The next most frequently infected system was the lung. However, in postmortem studies Cryptococcus neoformans was present in the lung and central nervous system with equal frequency. The organism was found in many other organs including the kidney, heart, spleen, pancreas, adrenals, ovaries, lymph nodes, skeletal muscle, liver, gastrointestinal tract and skin. A clinical diagnosis was made in a greater percentage of patients with central nervous system involvement than in patients with other organ system involvement. The most common signs and symptoms of cryptococcal meningitis were headache, nausea, vomiting, disturbance of consciousness, meningeal signs, pathologic reflexes and cranial nerve involvement. In most patients lumbar puncture revealed a high initial pressure as well as leukocytosis, low sugar level and high protein level in the cerebrospinal fluid. Fourteen patients died on the first admission. Eight patients with central nervous system cryptococcosis were alive and well two months to seven years after discharge. The usual therapy was administration of amphotericin B. The patients with central nervous system involvement who were most likely to survive were those who had received amphotericin B for four weeks or more and whose cultures of the cerebrospinal fluid converted from positive to negative. ?? 1972.", "author" : [ { "dropping-particle" : "", "family" : "Lewis", "given" : "Jerry L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rabinovich", "given" : "Sergio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Medicine", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1972" ] ] }, "page" : "315-322", "title" : "The wide spectrum of cryptococcal infections", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Behrman", "given" : "Rachel E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masci", "given" : "Joseph R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nicholas", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Reviews of Infectious Diseases", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "181-190", "title" : "Cryptococcal skeletal infections : Case report and review", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1111/j.1399-3062.2006.00149.x", "ISBN" : "1398-2273 (Print)\\n1398-2273", "ISSN" : "13982273", "PMID" : "17313467", "abstract" : "Rabbit anti-thymocyte globulin (ATG) and alemtuzumab have been used for induction or preconditioning and for the treatment of acute rejection in organ transplant recipients in many centers. Such regimens may lead to a substantial decline in the CD4 lymphocyte count to levels seen in other population groups at high risk of cryptococcosis. In view of this, we examined the impact of such therapy on the cumulative incidence of cryptococcosis among liver and kidney recipients. A total of 834 liver and 727 kidney transplants were performed during the study period. Seven hundred and eighty-one patients did not receive ATG or alemtuzumab; 646 received 1 dose of either drug, and 134 patients received 2 doses of either drug. The cumulative incidence of cryptococcosis was 0.26% (2/781) among those who did not receive ATG or alemtuzumab; 0.3% (2/646) among those who received only 1 dose, and 2.24% (3/134) among those who received 2 doses (P=0.03). There were 5 cases of cryptococcosis in liver recipients and 2 in kidney recipients. There were 3 cases of cryptococcal meningitis, 3 of pneumonia, and 1 of disseminated disease. The 2 kidney recipients had meningitis. Diagnosis occurred at a median of 255 days (range 7-517) after transplantation. The mortality rate was 14.2%. We conclude that the use of 1 dose of ATG or alemtuzumab is not associated with an increased cumulative incidence of cryptococcosis, but that those patients receiving 2 doses are at increased risk.", "author" : [ { "dropping-particle" : "", "family" : "Silveira", "given" : "F. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husain", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwak", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linden", "given" : "P. K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcos", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shapiro", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontes", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marsh", "given" : "J. W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vera", "given" : "M.", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tom", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thai", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "H. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soltys", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paterson", "given" : "D. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Transplant Infectious Disease", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "22-27", "title" : "Cryptococcosis in liver and kidney transplant recipients receiving anti-thymocyte globulin or alemtuzumab", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^173\u2013176", "plainTextFormattedCitation" : "173\u2013176", "previouslyFormattedCitation" : "^173\u2013176" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }173–176 Among non-HIV patients, pulmonary cryptococcosis is the most common non-CNS location.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1378/chest.115.3.734", "ISSN" : "0012-3692", "author" : [ { "dropping-particle" : "", "family" : "Aberg", "given" : "Judith A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mundy", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powderly", "given" : "William G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST Journal", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "734-740", "title" : "Pulmonary cryptococcosis in patients without HIV infection", "type" : "article-journal", "volume" : "115" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷⁷", "plainTextFormattedCitation" : "177", "previouslyFormattedCitation" : "¹⁷⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }177 Pulmonary cryptococcosis usually presents with non-specific symptoms such as cough, dyspnea, chest pain and fever both in adults and children.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-2", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wei-Chou Chang, Ching Tzao, Hsian-He Hsu, Shih-Chun Lee, Kun-Lun Huang, Ho-Jui Tung", "given" : "and Cheng-Yu Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "333-340", "title" : "Pulmonary cryptococcosis * Comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1186/s12879-017-2450-5", "ISSN" : "1471-2334", "PMID" : "28532447", "abstract" : "Background: Disseminated cryptococcosis is a rare and fatal disease, and limited data exist regarding it in children. This study aimed to investigate the clinical characteristics of disseminated cryptococcosis in previously healthy children in China. Methods: Hospitalized patients with disseminated cryptococcosis were enrolled during January 1996 to December 2015 in Beijing Children\u2019s Hospital, Capital Medical University, China. Data on clinical manifestations, laboratory tests, treatment, and prognosis were evaluated. Results: A total of 52 pediatric patients with no underlying disease were enrolled, including 38 boys and 14 girls. Only 10 cases had a history of exposure to pigeon droppings. Fever, cough, and hepatomegaly were 3 main manifestations of disseminated cryptococcosis. However, headache was more common in patients with central nervous system (CNS) invasion than in patients with non-CNS invasion (P\u00a0<\u00a00.05). Lung (96.2%, 50/52) was the most commonly invaded organ, but only 9.6% (5/52) of patients had respiratory signs. The most common findings on chest imaging were hilar or mediastinal lymphadenopathy (46.8%, 22/47), and nodules (44.7%, 21/47), including small nodules in a scattered distribution (57.1%, 12/21) or miliary distribution (42.9%, 9/25), especially localized in subpleural area. Subsequent invasion occurred in the CNS, abdomen lymph nodes, liver, spleen, peripheral lymph nodes, and skin. In all patients, 42.3% (22/52) and 51.9% (27/52) had elevated eosinophils or IgE, respectively. The positive rate of serum cryptococcal antigen was higher, especially in patients with CNS invasion (approximately 83.3%), than with other primary methods used for pathogen detection, including cerebrospinal fluid (CSF) cryptococcal antigen, cultures of blood, bone marrow, or CSF, and CSF ink staining. The overall mortality rate of pediatric patients in our study was 11.5% (6/52). Some cases had long-term sequela, including hydrocephalus, cirrhosis, or blindness. Conclusions: Disseminated cryptococcosis can occur in previously healthy or immunocompetent children in China. Lung and CNS were most commonly invaded by this disease. Furthermore, most cases usually showed no obvious or specific symptoms or signs, and therefore pediatricians should pay more careful attention to identify this disease.", "author" : [ { "dropping-particle" : "", "family" : "Gao", "given" : "Li-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiao", "given" : "An-Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Xi-Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Shun-Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ma", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Gang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yin", "given" : "Ju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bao-Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Kun-Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Infectious Diseases", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "359", "publisher" : "BMC Infectious Diseases", "title" : "Clinical characteristics of disseminated cryptococcosis in previously healthy children in China", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISBN" : "9702216400", "ISSN" : "0149-2195", "PMID" : "20651643", "abstract" : "This article reports some details regarding the dengue epidemic in Puerto Rico in 1-15 July 2010. During the period, a total of 6321 suspected dengue cases were reported to the Puerto Rico Department of Health (PRDH) and Centre for Disease Control and Prevention (CDC). Of the suspected cases, 2831 (45%) have been laboratory-confirmed; the incidence of confirmed cases was 74.3 cases per 100 000 population, with 35% of patients hospitalized and five deaths reported, all adults. The incidence of confirmed cases was highest among children aged 10-14 years (165 cases per 100 000); 15-19 years (163), 5-9 years (91), infants (83), adults aged 20-24 years (77). 72 of the 78 municipalities of Puerto Rico were affected. PRDH and the CDC are working with municipal leadership to raise awareness about dengue prevention measures and eliminate mosquito production sites, and are providing continuing medical education on dengue clinical management and educational materials for patients.", "author" : [ { "dropping-particle" : "", "family" : "Feliciano", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deseda", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomashek", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munoz-Jordan", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunsperger", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Padro", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santiago", "given" : "L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soto", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perez", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriguez", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seda", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arguello", "given" : "D F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Margolis", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Morbidity and Mortality Weekly Report, CDC", "id" : "ITEM-5", "issue" : "28", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "865-893", "title" : "Emergence of <i>Cryptococcus gattii </i>-Pacific Northwest, 2004-2010", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1093/clinids/13.1.64", "ISSN" : "1058-4838", "author" : [ { "dropping-particle" : "", "family" : "Cameron", "given" : "M. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartlett", "given" : "J. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gallis", "given" : "H. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waskin", "given" : "H. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Infectious Diseases", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "64-67", "title" : "Manifestations of pulmonary cryptococcusis in patients with acquired immunodeficiency syndrome", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1378/chest.98.5.1060", "ISBN" : "0012-3692 (Print)\\n0012-3692", "ISSN" : "00123692", "PMID" : "2225944", "abstract" : "Forty-eight patients with disseminated cryptococcosis and AIDS were retrospectively studied to define the pulmonary manifestations. Cryptococcus neoformans (CN) was first isolated from a pulmonary site in 12 patients. Disseminated disease was subsequently documented in all these patients. Symptoms and roentgenographic manifestations (normal, nodular/circumscribed infiltrates, pleural effusions, lobar consolidation) were diverse. Interstitial infiltrates predicted the presence of another opportunistic lung infection besides cryptococcosis in five patients (three untreated and two treated patients). Infectious causes other than cryptococcosis were established by culture and clinical course in five of the ten patients who developed chest roentgenographic abnormalities during amphotericin B therapy. Endobronchial abnormalities were identified in four patients at bronchoscopy. Bronchoalveolar lavage (9/9) and pleural fluid (3/3) cultures were sensitive tests for detection of pulmonary involvement with CN.", "author" : [ { "dropping-particle" : "", "family" : "Chechani", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamholz", "given" : "S. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-7", "issue" : "5", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "1060-1066", "title" : "Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS", "type" : "article-journal", "volume" : "98" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1086/322597", "ISBN" : "1058-4838 (Print)\\n1058-4838", "ISSN" : "1058-4838", "PMID" : "11477526", "abstract" : "We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.", "author" : [ { "dropping-particle" : "", "family" : "Pappas", "given" : "P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cloud", "given" : "G a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankey", "given" : "G a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lancaster", "given" : "D J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauffman", "given" : "C a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haas", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saccente", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holloway", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warren", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "W E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-8", "issue" : "5", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "690-699", "title" : "Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1007/s00408-011-9362-8", "ISSN" : "1432-1750", "PMID" : "22246551", "abstract" : "Pulmonary cryptococcosis typically occurs in immunocompromised patients, but it can also occur in immunocompetent patients. Our objective was to describe the clinical manifestations, diagnosis, and management of primary pulmonary cryptococcosis in immunocompetent patients.", "author" : [ { "dropping-particle" : "", "family" : "Ye", "given" : "Feng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Jia-xing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeng", "given" : "Qing-si", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Guo-qin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Shu-qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Nan-shan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lung", "id" : "ITEM-9", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "339-46", "title" : "Retrospective analysis of 76 immunocompetent patients with primary pulmonary cryptococcosis.", "type" : "article-journal", "volume" : "190" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1128/AAC.01299-15.Address", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "Kyle D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Achan", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hullsiek", "given" : "Kathy Huppler", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mcdonald", "given" : "Tami R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okagaki", "given" : "Laura H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alhadab", "given" : "Ali A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akampurira", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhein", "given" : "Joshua R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meya", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boulware", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Antimicrobial Agents and Chemotherapy", "id" : "ITEM-10", "issue" : "12", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "7197-7204", "title" : "Increased antifungal drug resistance in clinical isolates of <i> Cryptococcus neoformans</i> in Uganda", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-11", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "DOI" : "10.1016/j.bjid.2012.07.004", "ISBN" : "1413-8670", "ISSN" : "1678-4391", "PMID" : "23154046", "abstract" : "OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients.\\n\\nMETHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied.\\n\\nRESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2\u00b111.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients.\\n\\nCONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Jin-Quan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Ke-Jing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing-Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Can-Mao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Light", "given" : "Richard W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases", "id" : "ITEM-12", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "531-9", "publisher" : "Elsevier Editora Ltda", "title" : "Pulmonary cryptococcosis in non-AIDS patients.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{6,13,182,183,22,46,132,146,178\u2013181}", "plainTextFormattedCitation" : "6,13,182,183,22,46,132,146,178\u2013181", "previouslyFormattedCitation" : "^{6,13,22,46,132,146,178\u2013183}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6,13,182,183,22,46,132,146,178–181 However, it may be totally asymptomatic, or may present with respiratory failureADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-2", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wei-Chou Chang, Ching Tzao, Hsian-He Hsu, Shih-Chun Lee, Kun-Lun Huang, Ho-Jui Tung", "given" : "and Cheng-Yu Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "333-340", "title" : "Pulmonary cryptococcosis * Comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/ccr3.337", "ISSN" : "20500904", "PMID" : "26401280", "abstract" : "Pulmonary cryptococcosis is a common condition in HIV-infected patients which is frequently missed or misdiagnosed in resource-limited countries. We report a case of HIV/AIDS patient who was misdiagnosed with a fatal outcome. There is a need to implement screening tools to be used where the diagnosis may not be confirmed.", "author" : [ { "dropping-particle" : "", "family" : "Gunda", "given" : "Daniel W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakshi", "given" : "Fatma A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rambau", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kilonzo", "given" : "Semvua B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Case Reports", "id" : "ITEM-4", "issue" : "9", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "749-752", "title" : "Pulmonary cryptococcosis presenting as acute severe respiratory distress in a newly diagnosed HIV patient in Tanzania: a case report", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1016/j.mmcr.2017.02.004", "ISBN" : "2211-7539", "ISSN" : "22117539", "PMID" : "29379704", "abstract" : "We present a 27-year-old lady with HIV-1 infection who died due to rapidly worsening respiratory failure one day after commencing amphotericin B deoxycholate therapy for cryptococcal meningitis. Chest x-ray appearances were consistent with pneumocystis pneumonia but post mortem examination showed evidence of severe necrotizing cryptococcal pneumonia. Cryptococcal pneumonia is an underrecognized condition and should be considered in the differential of patients with HIV-1 infection and low CD4 count who develop respiratory symptoms.", "author" : [ { "dropping-particle" : "", "family" : "Scriven", "given" : "James E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Botha", "given" : "Francois CJ", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schutz", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lalloo", "given" : "David G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wainwright", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meintjes", "given" : "Graeme", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology Case Reports", "id" : "ITEM-5", "issue" : "November 2016", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "38-40", "publisher" : "Elsevier B.V.", "title" : "Paradoxical respiratory failure due to cryptococcal pneumonia after amphotericin B treatment for HIV-associated cryptococcal meningitis", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{22,46,178,184,185}", "plainTextFormattedCitation" : "22,46,178,184,185", "previouslyFormattedCitation" : "^{22,46,180,184,185}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22,46,178,184,185 (Table 2). The non-specific symptoms of this disease are likely to cause delays in diagnosis and proper treatment resulting in further dissemination of Cryptococcus infection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wei-Chou Chang, Ching Tzao, Hsian-He Hsu, Shih-Chun Lee, Kun-Lun Huang, Ho-Jui Tung", "given" : "and Cheng-Yu Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "333-340", "title" : "Pulmonary cryptococcosis * Comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.chest.2016.02.119", "ISSN" : "0012-3692", "author" : [ { "dropping-particle" : "", "family" : "Liang", "given" : "Yi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Jianquan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Xiaoning", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "114A", "publisher" : "American College of Chest Physicians", "title" : "Pulmonary cryptococcosis among 3 immunocompetent patients misdiagnosed as bacterial pneumonia and pulmonary tuberculosis", "type" : "article-journal", "volume" : "149" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1111/myc.12645", "ISSN" : "09337407", "PMID" : "28857298", "abstract" : "Diabetes mellitus II (DM II) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. This retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in Chinese DM II patients. This study included 30 cases of cryptococcosis with DM II occurring from 1993 to 2015 in mainland China. The hospital-based prevalence of cryptococcosis in DM II was 0.21%. The mean age of the patients was 56.1 years (95% confidence interval: 51.5, 60.6), and 93% of the patients were older than 40 years. Sixty-two per cent of the patients experienced untreated or poorly controlled blood glucose before infection. Multilocus sequence typing analysis categorised all cultured strains as Cryptococcus neoformans and sequence type 5. Sixty-nine per cent of pulmonary cryptococcosis patients experienced misdiagnoses and treatment delays. Sixty per cent of cryptococcal meningitis patients received substandard antifungal therapy. The overall death rate was 33%. Considering the large population size of DM II patients in China, improved attention should be paid to the high prevalence of cryptococcosis as revealed by us. We also emphasised the importance of blood glucose control for infection prevention, especially among the elderly.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "Yingfang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Wenjie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiang", "given" : "Weiwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Xiaoguang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lei", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Danqi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jianping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycoses", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "706-713", "title" : "Cryptococcosis in patients with diabetes mellitus II in mainland China: 1993-2015", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^163,178,186", "plainTextFormattedCitation" : "163,178,186", "previouslyFormattedCitation" : "^163,180,186" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }163,178,186 Physical examination may reveal reduced breath sounds, crackles, and/or dullness to percussion indicated pleural effusion.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁷", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "¹⁸⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187 Cryptococcus leads to differing clinical manifestations in immunocompromised and immunocompetent people.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wei-Chou Chang, Ching Tzao, Hsian-He Hsu, Shih-Chun Lee, Kun-Lun Huang, Ho-Jui Tung", "given" : "and Cheng-Yu Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "333-340", "title" : "Pulmonary cryptococcosis * Comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷⁸", "plainTextFormattedCitation" : "178", "previouslyFormattedCitation" : "¹⁸⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }178 Approximately half of immunocompetent patients with pulmonary cryptococcosis are asymptomatic, the infection accidentally detected during a routine chest X-ray (CXR) or follow-up of other diseases.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bjid.2012.07.004", "ISBN" : "1413-8670", "ISSN" : "1678-4391", "PMID" : "23154046", "abstract" : "OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients.\\n\\nMETHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied.\\n\\nRESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2\u00b111.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients.\\n\\nCONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Jin-Quan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Ke-Jing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing-Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Can-Mao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Light", "given" : "Richard W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "531-9", "publisher" : "Elsevier Editora Ltda", "title" : "Pulmonary cryptococcosis in non-AIDS patients.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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pulmonary cryptococcosis,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wei-Chou Chang, Ching Tzao, Hsian-He Hsu, Shih-Chun Lee, Kun-Lun Huang, Ho-Jui Tung", "given" : "and Cheng-Yu Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "333-340", "title" : "Pulmonary cryptococcosis * Comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁷⁸", "plainTextFormattedCitation" : "178", "previouslyFormattedCitation" : "¹⁸⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }178 apart from the rare asymptomatic solitary pulmonary nodules in HIV patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1058-4838 (Print)\\r1058-4838 (Linking)", "PMID" : "8909849", "abstract" : "We report the cases of three HIV-positive patients with solitary pulmonary nodules caused by Cryptococcus neoformans. Although human infection with C. neoformans occurs via the respiratory tract, isolated pulmonary infection in HIV-positive patients, in contrast with HIV-negative patients, has been thought to be relatively rare. When isolated pulmonary disease in HIV-infected patients, has been described, most of the patients have been symptomatic (symptoms have included fever, cough, and dyspnea). In addition, these patients have had diffuse interstitial infiltrates, alveolar infiltrates, or nodular infiltrates that have often been associated with hilar adenopathy and occasionally with pleural effusions. None of the patients in the previously reported series have had lesions described as small, asymptomatic, isolated pulmonary nodules.", "author" : [ { "dropping-particle" : "", "family" : "Miller", "given" : "K D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mican", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davey", "given" : "R T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clin Infect Dis", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "810-812", "title" : "Asymptomatic solitary pulmonary nodules due to <i> Cryptococcus neoformans</i> in patients infected with human immunodeficiency virus", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁸", "plainTextFormattedCitation" : "188", "previouslyFormattedCitation" : "¹⁸⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }188 Acute respiratory failure was the presentation in 33% of pulmonary cryptococcosis cases reported without HIV, most of whom had a solid organ transplant as their underlying condition.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1378/chest.119.6.1865", "author" : [ { "dropping-particle" : "", "family" : "Vilchez", "given" : "Regis A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linden", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacomis", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costello", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "1865-1869", "title" : "Acute respiratory failure associated with pulmonary cryptococcosis in non- AIDS patients", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁶", "plainTextFormattedCitation" : "166", "previouslyFormattedCitation" : "¹⁶⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }166 In all probability many other factors affect the clinical appearance of pulmonary cryptococcosis such as geography, virulence of different Cryptococcus strains, and possibly immunogenetic variations among patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/CMR.00126-13", "ISBN" : "1098-6618 (Electronic)\\r0893-8512 (Linking)", "ISSN" : "10986618", "PMID" : "25278580", "abstract" : "SUMMARY: Understanding of the taxonomy and phylogeny of Cryptococcus gattii has been advanced by modern molecular techniques. C. gattii probably diverged from Cryptococcus neoformans between 16 million and 160 million years ago, depending on the dating methods applied, and maintains diversity by recombining in nature. South America is the likely source of the virulent C. gattii VGII molecular types that have emerged in North America. C. gattii shares major virulence determinants with C. neoformans, although genomic and transcriptomic studies revealed that despite similar genomes, the VGIIa and VGIIb subtypes employ very different transcriptional circuits and manifest differences in virulence phenotypes. Preliminary evidence suggests that C. gattii VGII causes severe lung disease and death without dissemination, whereas C. neoformans disseminates readily to the central nervous system (CNS) and causes death from meningoencephalitis. Overall, currently available data indicate that the C. gattii VGI, VGII, and VGIII molecular types more commonly affect nonimmunocompromised hosts, in contrast to VGIV. New, rapid, cheap diagnostic tests and imaging modalities are assisting early diagnosis and enabling better outcomes of cerebral cryptococcosis. Complications of CNS infection include increased intracranial pressure, severe neurological sequelae, and development of immune reconstitution syndrome, although the mortality rate is low. C. gattii VGII isolates may exhibit higher fluconazole MICs than other genotypes. Optimal therapeutic regimens are yet to be determined; in most cases, initial therapy with amphotericin B and 5-flucytosine is recommended.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Sharon C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "980-1024", "title" : "<i>Cryptococcus gattii </i> infections", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pmed.0040021", "ISBN" : "1549-1676", "ISSN" : "15491277", "PMID" : "17284154", "abstract" : "BACKGROUND: Cryptococcosis is a life-threatening opportunistic fungal infection in both HIV-positive and -negative patients. Information on clinical presentation and therapeutic guidelines, derived mostly from clinical trials performed before introduction of highly active antiretroviral therapy in patients with cryptococcal meningoencephalitis, is missing data on extrameningeal involvement and infections by serotype D as opposed to serotype A of Cryptococcus neoformans. METHODS AND FINDINGS: The prospective multicenter study CryptoA/D was designed in France (1997-2001) to analyse the factors influencing clinical presentation and outcome without the bias of inclusion into therapeutic trials. Of the 230 patients enrolled, 177 (77%) were HIV-positive, 50 (22%) were female, and 161 (72.5%) were infected with serotype A. Based on culture results at baseline, cryptococcosis was more severe in men, in HIV-positive patients, and in patients infected with serotype A. Factors independently associated with mycological failure at week 2 independent of HIV status were initial dissemination (OR, 2.4 [95% confidence interval (CI), 1.2-4.9]), high (>1:512) serum antigen titre (OR, 2.6 [1.3-5.4]), and lack of flucytosine during induction therapy (OR, 3.8 [1.9-7.8]). The three-month survival was shorter in patients with abnormal neurology or brain imaging at baseline, and in those with haematological malignancy. CONCLUSIONS: Thus sex, HIV status, and infecting serotype are major determinants of presentation and outcome during cryptococcosis. 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METHODS: In this retrospective study, we reviewed clinical and computed tomography (CT) findings from 27 patients who presented with suspicion of thoracic malignancy who were ultimately diagnosed with fungal disease. RESULTS: Patients' median age was 55.7 (range 31-78) years. The most common clinical findings were cough (48.1 %), expectoration (33.3 %), chest pain (25.9 %), weakness (25.9 %), weight loss (18.5 %), and hemoptysis, dyspnea, and fever (7.4 % each). The median lesion size was 35.5 (range 10-85) mm. CT findings included a solid nodule (51.9 %), solid mass (37 %), or both (11.1 %). Nodule and mass margins were lobulated in 9 (33.3 %) patients, ill-defined in 5 (18.5 %), spiculated in 4 (14.8 %), and smooth in 4 (14.8 %) patients. Additional findings included consolidation in 4 (14.8 %) patients, cavitation in 3 (11.1 %), pleural effusion in 2 (7.4 %), and lymphadenopathy in 11 (40.7 %) patients. In all patients, specific diagnoses were made and confirmed by histopathology; final diagnoses were histoplasmosis (25.9 %), coccidiomycosis (22.2 %), cryptococcosis (22.2 %), aspergillosis (14.8 %), North American blastomycosis (7.4 %), mucormycosis (3.75 %), and paracoccidioidomycosis (3.75 %). CONCLUSIONS: Fungal infection can present with clinical and radiological features that are indistinguishable from thoracic malignancy, such as lung nodules or masses. Because the management and outcomes of fungal infection and malignancy are entirely distinct, the establishment of a specific diagnosis is critical to provide appropriate therapy.", "author" : [ { "dropping-particle" : "", "family" : "Guimaraes", "given" : "Marcos Duarte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchiori", "given" : "Edson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza Portes Meirelles", "given" : "Gustavo", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hochhegger", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santana", "given" : "Pablo Rydz Pinheiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gross", "given" : "Jefferson Luiz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bitencourt", "given" : "Almir Galvao Vieira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boonsirikamchai", "given" : "Piyaporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godoy", "given" : "Myrna Corbos Barco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lung", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "655-662", "title" : "Fungal infection mimicking pulmonary malignancy: Clinical and radiological characteristics", "type" : "article-journal", "volume" : "191" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.21037/jtd.2017.02.11", "author" : [ { "dropping-particle" : "", "family" : "Choi", "given" : "Hye Won", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chong", "given" : "Semin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Mi Kyung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "In Won", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Thorac Dis", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "E138-E141", "title" : "Pulmonary cryptococcosis manifesting as diffuse air-space consolidations in an immunocompetent patient", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jocn.2016.09.016", "ISSN" : "09675868", "PMID" : "27769644", "author" : [ { "dropping-particle" : "", "family" : "Ang", "given" : "Samantha Y.L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Victor W.L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Shree Dinesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Low", "given" : "Sharon Y.Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Neuroscience", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "10-12", "publisher" : "Elsevier Ltd", "title" : "Cryptococcosis mimicking lung carcinoma with brain metastases in an immunocompetent patient", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1007/s11046-017-0233-6", "ISBN" : "1104601702", "ISSN" : "15730832", "abstract" : "Cryptococcus gattii is an endemic fungus predominantly isolated in the tropical and subtropical regions, causing predominantly pulmonary disease with a predilection for the central nervous system. Herein, we report a case of rapidly progressing C. gattii pneumonia in an immune-deficient but virologically suppressed host with underlying human immunodeficiency viral (HIV) infection, exhibiting various fungal morphologies from bronchoalveolar lavage (BAL) cytological specimens. A 51-year-old Chinese male with known HIV disease was admitted to the Singapore General Hospital for evaluation of functional decline, febrile episodes, and a left hilar mass on chest radiograph. Computed tomography (CT) showed consolidation in the apical segment of the left lower lobe. He underwent bronchoscopy and BAL. Positron emission tomography-computed tomography done 10 days after the initial CT showed approximate doubling of the pulmonary lesion. Cytological examination of the fluid revealed yeasts of varying sizes. Subsequent fungal culture from BAL fluid grew C. gattii 10 days later. \u00a9 2017 Springer Science+Business Media B.V., part of Springer Nature", "author" : [ { "dropping-particle" : "", "family" : "Zheng", "given" : "Shuwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "Thuan Tong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chien", "given" : "Jaime Mei Fong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycopathologia", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-6", "publisher" : "Springer Netherlands", "title" : "<i>Cryptococcus gattii</i> infection presenting as an aggressive lung mass", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^190\u2013193", "plainTextFormattedCitation" : "190\u2013193", "previouslyFormattedCitation" : "^190\u2013193" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }190–193 Nodules, especially located in the peripheral area of the lung, were the most commonly diagnosed finding on CXR and computed tomography (CT) scan of non-compromised patients with proven pulmonary cryptococcosisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Godwin", "given" : "J David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ravin", "given" : "Carl E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gallis", "given" : "Harry A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Putman", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Roentgenol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1984" ] ] }, "page" : "893-896", "title" : "Thoracic cryptococcosis: Immunologic competence and radiologic appearance", "type" : "article-journal", "volume" : "141" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.21037/jtd.2016.10.36", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Kaixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Haibo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Ruixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qichang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qu", "given" : "Jieming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Thoracic Disease", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "2813-2821", "title" : "Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1183/09031936.00168011", "ISBN" : "0903-1936", "ISSN" : "09031936", "PMID" : "22408204", "abstract" : "The aim of the present study was to investigate the clinical characteristics of pulmonary cryptococcosis patients in China, with analysis of immunocompetent and immunocompromised subjects. We performed a retrospective review of 76 patients diagnosed with tissue-confirmed pulmonary cryptococcosis at the Shanghai Pulmonary Hospital (Shanghai, China) during a 10-yr period (2001-2010). Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic. Approximately 80% of the patients had histories suspicious of environmental fungal exposure. Radiological (computed tomography) findings showed predominantly peripheral findings (85.53%, 65 out of 76 patients) including nodular masses (55.26%, 42 out of 76), pneumonic infiltrates (23.68%, 18 out of 76) and mixed type (21.05%, 16 out of 76). 43.42% (33 out of 76) were initially misdiagnosed, often as cancer by false-positive (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) (28 out of 46 cases). 51 patients received antifungal therapy, 25 patients were clinically observed without treatment. 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"22798384", "abstract" : "BACKGROUND: Discrepancies still exist in the diagnosis of primary pulmonary cryptococcosis in immunocompetent patients.\\n\\nPURPOSE: To describe and evaluate radiological manifestations of pulmonary cryptococcosis in immunocompetent patients.\\n\\nMATERIAL AND METHODS: Twenty-six histopathologically confirmed cases of pulmonary cryptococcosis were analyzed for clinical, pathological, and CT characteristics. Necessary statistical tests for differences in CT presentations and correlation analysis between clinical and CT characteristics were performed.\\n\\nRESULTS: The patients' ages ranged from 24 to 79 years, with 20 men and six women. Eighteen patients were symptomatic, with cough as the most common symptom (n = 14, 53.8%). Nodules (n = 21, 80.8%) were the most common CT findings. Eight cases presented with solitary and nine with multiple nodules, while 13 cases presented with irregular and 19 with ill-defined nodules. The halo sign was demonstrated, encompassing nodules in 14 of the 21 patients. Lesions were mainly localized in the lower lobes of the lungs (n = 15, 57.7%) with peripheral distribution (n = 18, 69.2%). Ground-glass opacities (GGOs) were more easily detected in older patients (66.7%, P <0.01). No significant differences in CT abnormalities were found between male and female patients.\\n\\nCONCLUSION: Primary pulmonary cryptococcosis in immunocompetent patients exhibits certain CT characteristics. The typical presentation includes multiple nodules with the halo sign scattered in the peripheral field in the lower lobes of the bilateral lungs. This could contribute to diagnosis of the disease entity. However, vigilance should be exercised when facing GGOs, with or without nodules, in older patients.", "author" : [ { "dropping-particle" : "", "family" : "Qu", "given" : "Yanjuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Guobing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghimire", "given" : "Prasanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Meiyan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "Heshui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Guifang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Liying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Guanliang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta radiologica (Stockholm, Sweden : 1987)", "id" : "ITEM-7", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "668-74", "title" : "Primary pulmonary cryptococcosis: evaluation of CT characteristics in 26 immunocompetent Chinese patients.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{4,5,10,126,130,194,195}", "plainTextFormattedCitation" : "4,5,10,126,130,194,195", "previouslyFormattedCitation" : "^{4,5,10,126,130,194,195}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4,5,10,126,130,194,195 (Figure. 3). Nodules may be single or multiple.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.rmcr.2018.01.011", "ISSN" : "2213-0071", "author" : [ { "dropping-particle" : "", "family" : "Basnayake", "given" : "Thilini L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Aijye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Currie", "given" : "Bart J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Respiratory Medicine Case Reports", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "122-124", "publisher" : "Elsevier", "title" : "Respiratory Medicine Case Reports Pulmonary cryptococcal infection presenting with multiple lung nodules", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹⁶", "plainTextFormattedCitation" : "196", "previouslyFormattedCitation" : "¹⁹⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }196 Pulmonary cryptococcosis has often been initially misdiagnosed as lung cancer as some nodules also were positive on F-fluorodeoxyglucose positron emission tomography (FDG-PET).ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1183/09031936.00168011", "ISBN" : "0903-1936", "ISSN" : "09031936", "PMID" : "22408204", "abstract" : "The aim of the present study was to investigate the clinical characteristics of pulmonary cryptococcosis patients in China, with analysis of immunocompetent and immunocompromised subjects. We performed a retrospective review of 76 patients diagnosed with tissue-confirmed pulmonary cryptococcosis at the Shanghai Pulmonary Hospital (Shanghai, China) during a 10-yr period (2001-2010). Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic. Approximately 80% of the patients had histories suspicious of environmental fungal exposure. Radiological (computed tomography) findings showed predominantly peripheral findings (85.53%, 65 out of 76 patients) including nodular masses (55.26%, 42 out of 76), pneumonic infiltrates (23.68%, 18 out of 76) and mixed type (21.05%, 16 out of 76). 43.42% (33 out of 76) were initially misdiagnosed, often as cancer by false-positive (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) (28 out of 46 cases). 51 patients received antifungal therapy, 25 patients were clinically observed without treatment. As of December 31, 2010, 71 cases showed total recovery and four cases showed improvement (efficacy rate of 98.68%, 75 out of 76). One HIV-positive case died of cryptococcal meningitis. Incidence of pulmonary cryptococcosis in China may be related to environmental fungal exposures. Most presented as asymptomatic peripheral lung lesions. False-positive (18)FDG-PET examinations often lead to initial clinical misdiagnosis of cancer. Unlike immunocompromised or clinically symptomatic patients, all immunocompetent patients had a good response, either to fluconazole monotherapy or observation, with a tendency for spontaneous remissions in the asymptomatic immunocompetent subjects.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Yuxuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Huiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Xueyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Shanmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rongxuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jinfu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "Jingyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yung", "given" : "Rex C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Respiratory Journal", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1191-1200", "title" : "Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1258/ar.2012.110612", "ISSN" : "1600-0455", "PMID" : "22798384", "abstract" : "BACKGROUND: Discrepancies still exist in the diagnosis of primary pulmonary cryptococcosis in immunocompetent patients.\\n\\nPURPOSE: To describe and evaluate radiological manifestations of pulmonary cryptococcosis in immunocompetent patients.\\n\\nMATERIAL AND METHODS: Twenty-six histopathologically confirmed cases of pulmonary cryptococcosis were analyzed for clinical, pathological, and CT characteristics. 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No significant differences in CT abnormalities were found between male and female patients.\\n\\nCONCLUSION: Primary pulmonary cryptococcosis in immunocompetent patients exhibits certain CT characteristics. The typical presentation includes multiple nodules with the halo sign scattered in the peripheral field in the lower lobes of the bilateral lungs. This could contribute to diagnosis of the disease entity. However, vigilance should be exercised when facing GGOs, with or without nodules, in older patients.", "author" : [ { "dropping-particle" : "", "family" : "Qu", "given" : "Yanjuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Guobing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghimire", "given" : "Prasanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Meiyan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "Heshui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Guifang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Liying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Guanliang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta radiologica (Stockholm, Sweden : 1987)", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "668-74", "title" : "Primary pulmonary cryptococcosis: evaluation of CT characteristics in 26 immunocompetent Chinese patients.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "(01)00916-2", "ISBN" : "4349242007", "author" : [ { "dropping-particle" : "", "family" : "Farias", "given" : "Lucas de Padua Gomes", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Padilha", "given" : "Igor Gomes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemos", "given" : "Marcia Rosana Lelte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santos", "given" : "Carla Jotta Justo", "non-dropping-particle" : "Dos", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miranda", "given" : "Christiana Maria NR", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiol Bras", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "1-4", "title" : "Pulmonary cryptococcosis mimicking neoplasm in trems of uptake PET/CT", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^4,5,197", "plainTextFormattedCitation" : "4,5,197", "previouslyFormattedCitation" : "^4,5,197" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4,5,197 Rarer appearances of pulmonary cryptococcosis include calcification, “tree in bud” appearances, lymphadenopathies and pleural effusions.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1258/ar.2012.110612", "ISSN" : "1600-0455", "PMID" : "22798384", "abstract" : "BACKGROUND: Discrepancies still exist in the diagnosis of primary pulmonary cryptococcosis in immunocompetent patients.\\n\\nPURPOSE: To describe and evaluate radiological manifestations of pulmonary cryptococcosis in immunocompetent patients.\\n\\nMATERIAL AND METHODS: Twenty-six histopathologically confirmed cases of pulmonary cryptococcosis were analyzed for clinical, pathological, and CT characteristics. 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Miliary pulmonary infiltrates are an exceptionally rare presentation.", "author" : [ { "dropping-particle" : "", "family" : "Kelly", "given" : "Shane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marriott", "given" : "Deborah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology Case Reports", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "22-24", "publisher" : "Elsevier", "title" : "Miliary pulmonary cryptococcosis", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.ejrad.2017.02.008", "ISSN" : "0720-048X", "author" : [ { "dropping-particle" : "", "family" : "Si-yun", "given" : "Wang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gang", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, 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"volume" : "89" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISBN" : "1111111111", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Zhiliang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xiong", "given" : "Qingfang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Yandan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Yongfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Chuanjun", 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"10.1016/j.chest.2016.02.129", "ISSN" : "00123692", "author" : [ { "dropping-particle" : "", "family" : "Huang", "given" : "Jinbao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lan", "given" : "Chang-qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Hong-yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qing-hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jia-fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Heng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "A124", "publisher" : "American College of Chest Physicians", "title" : "Retrospective analysis of 117 chinese patients with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "149" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1183/09031936.00168011", "ISBN" : "0903-1936", "ISSN" : "09031936", "PMID" : "22408204", "abstract" : "The aim of the present study was to investigate the clinical characteristics of pulmonary cryptococcosis patients in China, with analysis of immunocompetent and immunocompromised subjects. We performed a retrospective review of 76 patients diagnosed with tissue-confirmed pulmonary cryptococcosis at the Shanghai Pulmonary Hospital (Shanghai, China) during a 10-yr period (2001-2010). Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic. Approximately 80% of the patients had histories suspicious of environmental fungal exposure. Radiological (computed tomography) findings showed predominantly peripheral findings (85.53%, 65 out of 76 patients) including nodular masses (55.26%, 42 out of 76), pneumonic infiltrates (23.68%, 18 out of 76) and mixed type (21.05%, 16 out of 76). 43.42% (33 out of 76) were initially misdiagnosed, often as cancer by false-positive (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) (28 out of 46 cases). 51 patients received antifungal therapy, 25 patients were clinically observed without treatment. As of December 31, 2010, 71 cases showed total recovery and four cases showed improvement (efficacy rate of 98.68%, 75 out of 76). One HIV-positive case died of cryptococcal meningitis. Incidence of pulmonary cryptococcosis in China may be related to environmental fungal exposures. Most presented as asymptomatic peripheral lung lesions. False-positive (18)FDG-PET examinations often lead to initial clinical misdiagnosis of cancer. Unlike immunocompromised or clinically symptomatic patients, all immunocompetent patients had a good response, either to fluconazole monotherapy or observation, with a tendency for spontaneous remissions in the asymptomatic immunocompetent subjects.", "author" : [ { "dropping-particle" : "", "family" : "Zhang", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Yuxuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Huiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Xueyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Shanmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rongxuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jinfu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "Jingyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yung", "given" : "Rex C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Respiratory Journal", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1191-1200", "title" : "Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.21037/jtd.2016.10.36", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Kaixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Haibo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Ruixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qichang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qu", "given" : "Jieming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Thoracic Disease", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "2813-2821", "title" : "Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^4,10,126", "plainTextFormattedCitation" : "4,10,126", "previouslyFormattedCitation" : "^4,10,126" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }4,10,126 Immunocompetent patients more often appeared with solitary and well-defined nodules.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.21037/jtd.2016.10.36", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Kaixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Haibo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "You", "given" : "Ruixiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xing", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qichang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qu", "given" : "Jieming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Thoracic Disease", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "2813-2821", "title" : "Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1148/radiol.2361040460", "ISSN" : "0033-8419", "PMID" : "15987984", "abstract" : "PURPOSE: To evaluate retrospectively the computed tomographic (CT) findings in immunocompetent patients with pulmonary cryptococcosis. MATERIALS AND METHODS: Institutional review board approval was obtained with a waiver of informed consent, and the study complied with requirements of the Health Insurance Portability and Accountability Act. Chest CT scans of 10 immunocompetent patients with clinically proved pulmonary cryptococcosis were retrospectively reviewed by four reviewers in consensus. Criterion for diagnosis of pulmonary cryptococcosis was (a) the histopathologic presence of the organism at lung biopsy or (b) a positive culture of a respiratory specimen or positive serum cryptococcal antigen test with clinical or radiographic evidence of active pulmonary infection. Patients included six women and four men ranging in age from 46 to 73 years (mean, 59 years). Scans were evaluated for nodules, masses, areas of ground-glass attenuation or of hazy increased attenuation, areas of consolidation, areas of cavitation, pleural effusions, linear opacities, septal thickening, lymphadenopathy, extent of parenchymal involvement, and distribution. RESULTS: The most common CT finding was pulmonary nodules (n = 9). Multiple nodules (n = 7) were more common than solitary nodules (n = 2). Nodules most commonly occupied less than 10% of the pulmonary parenchyma (n = 7), measured less than 10 mm in diameter (n = 7), and had middle and upper lung predominance (n = 6). The majority of the nodules were well defined with smooth margins (n = 7). Multiple nodules were usually bilaterally distributed (n = 5). Masses (n = 2), lymphadenopathy (n = 2), areas of consolidation (n = 2), areas of hazy increased attenuation (n = 1), pleural effusion (n = 1), and areas of cavitation (n = 1) were uncommon. CONCLUSION: CT most commonly demonstrated pulmonary nodules in immunocompetent patients with pulmonary cryptococcosis. The nodules were most often multiple, small, well defined, and smoothly marginated with middle and upper lung predominance.", "author" : [ { "dropping-particle" : "", "family" : "Lindell", "given" : "Rebecca M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartman", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nadrous", "given" : "Hassan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryu", "given" : "Jay H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "326-331", "title" : "Pulmonary cryptococcosis: CT findings in immunocompetent patients.", "type" : "article-journal", "volume" : "236" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1080/00365540903036212", "ISBN" : "0036554090303", "ISSN" : "00365548", "PMID" : "19513938", "abstract" : "Pulmonary cryptococcosis tends to occur commonly in immunocompromized patients. However, as more individuals are undergoing regular medical examinations, the number of cases of pulmonary cryptococcosis detected incidentally in immunocompetent individuals is increasing. The aim of the present study was to evaluate the radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients with no significant symptoms. The clinical records and radiographic findings of 7 immunocompetent subjects with isolated pulmonary cryptococcosis who were diagnosed by pathological examinations, were reviewed. The mean age of patients was 68.4 y (range 58-80 y), and 6 of them were female. The radiographic manifestations in all patients were 1 or more nodules. Computed tomography (CT) demonstrated 22 pulmonary nodules with diameter from 3 mm to 22 mm, and multiple nodules were more frequent than solitary nodules (5 cases versus 2 cases). Axial analysis of patients showed that an involvement of the upper lobe was observed in all patients. Most nodules were well defined and smoothly marginated (21 nodules) and cavitations were infrequent findings (2 nodules). Lymphadenopathies were found in 2 patients. The most common imaging finding of pulmonary cryptococcosis in asymptomatic immunocompetent hosts was the presence of multiple nodules marginated smoothly with upper lobe predominance.", "author" : [ { "dropping-particle" : "", "family" : "Choe", "given" : "Yeong Hun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moon", "given" : "Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Seoung Ju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "So Ri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Hyo Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Kyung Sun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Yong Chul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian Journal of Infectious Diseases", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "602-607", "title" : "Pulmonary cryptococcosis in asymptomatic immunocompetent hosts", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^10,200,201", "plainTextFormattedCitation" : "10,200,201", "previouslyFormattedCitation" : "^10,200,201" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10,200,201 Laboratory diagnosis of pulmonary cryptococcosisGiven the complexities surrounding the diagnosis and identification of pulmonary cryptococcosis, the diagnosis of pulmonary cryptococcosis is usually based on a combination of clinical and radiological suspicion and laboratory confirmation.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1590/S0036-46652009000500004", "ISSN" : "00364665", "PMID" : "19893977", "abstract" : "Cryptococcosis is one of the most common opportunistic fungal infections in patients with acquired immunodeficiency syndrome (AIDS). We report 13 cases of cryptococcal infection based on histopathology, serology and cultures. Epidemiological analysis, histochemical techniques of hematoxilin and eosin (HE) and Grocot's silver (GMS), as well special histochemical techniques such as Mayer's mucicarmine (MM) and Fontana-Masson (FM), cryptococcal antigen test (CrAg) and isolation on fungal media: Sabouraud's (SAB), brain-heart infusion agar (BHI) and canavanine-glycine-bromothymol blue (CGB) agar were analyzed. Unsatisfactory staining results by MM stain associated to negative titers by CrAg test, which FM stain confirmed that capsule-deficient Cryptococcus infections were observed in four cases. Eight isolated cases were identified as follows: six cases were infection with Cryptococcus neoformans and two cases were Cryptococcus gattii.", "author" : [ { "dropping-particle" : "", "family" : "Gazzoni", "given" : "Alexandra Fl\u00e1via", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Cec\u00edlia Bittencourt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salles", "given" : "Emily Ferreira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Luiz Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "255-259", "title" : "Histopathology, serology and cultures in the diagnosis of cryptococcosis", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1086/588660.Revised", "ISBN" : "1537-6591 (Electronic)\\r1058-4838 (Linking)", "ISSN" : "1537-6591", "PMID" : "18462102", "abstract" : "Background\u2014Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods\u2014After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results\u2014The revised definitions retain the original classifications of \u201cproven,\u201d \u201cprobable,\u201d and \u201cpossible\u201d invasive fungal disease, but the definition of \u201cprobable\u201d has been expanded, whereas the scope of the category \u201cpossible\u201d has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions\u2014These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high- risk patients. In", "author" : [ { "dropping-particle" : "", "family" : "Pauw", "given" : "Ben", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Thomas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donnelly", "given" : "J. 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Infect. Dis", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1813-1821", "title" : "Revised definitions of invasive fungal disease from the European Organization for Research & Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses (EORTC/MSG) Consensus Group", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1513/pats.200906-049AL", "ISSN" : "1943-5665", "PMID" : "20463243", "abstract" : "Fungal lung infections are being diagnosed with increasing frequency. This is related to the increased numbers of immune-compromised and other susceptible patient groups. This article will focus on the evolving epidemiology of fungal lung infections and clinical manifestations that should prompt the clinician to consider the possibility of fungal lung infection. In addition, current approaches for the diagnosis of these infection are also reviewed. Heightened awareness of fungal lung infection, and appropriate use of the available diagnostic modalities, will permit appropriate treatment of these important clinical infections in immune-compromised individuals.", "author" : [ { "dropping-particle" : "", "family" : "Limper", "given" : "Andrew H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the American Thoracic Society", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "163-168", "title" : "The changing spectrum of fungal infections in pulmonary and critical care practice: clinical approach to diagnosis.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1111/myc.12645", "ISSN" : "09337407", "PMID" : "28857298", "abstract" : "Diabetes mellitus II (DM II) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. This retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in Chinese DM II patients. This study included 30 cases of cryptococcosis with DM II occurring from 1993 to 2015 in mainland China. The hospital-based prevalence of cryptococcosis in DM II was 0.21%. The mean age of the patients was 56.1 years (95% confidence interval: 51.5, 60.6), and 93% of the patients were older than 40 years. Sixty-two per cent of the patients experienced untreated or poorly controlled blood glucose before infection. Multilocus sequence typing analysis categorised all cultured strains as Cryptococcus neoformans and sequence type 5. Sixty-nine per cent of pulmonary cryptococcosis patients experienced misdiagnoses and treatment delays. Sixty per cent of cryptococcal meningitis patients received substandard antifungal therapy. The overall death rate was 33%. Considering the large population size of DM II patients in China, improved attention should be paid to the high prevalence of cryptococcosis as revealed by us. We also emphasised the importance of blood glucose control for infection prevention, especially among the elderly.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "Yingfang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Wenjie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiang", "given" : "Weiwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Xiaoguang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lei", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Danqi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jianping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycoses", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "706-713", "title" : "Cryptococcosis in patients with diabetes mellitus II in mainland China: 1993-2015", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-5", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1007/s00408-013-9506-0", "ISBN" : "0341-2040", "ISSN" : "03412040", "PMID" : "24043490", "abstract" : "OBJECTIVE: The purpose of this study was to evaluate the clinical and radiological features of patients with fungal infection mimicking thoracic malignancy and to establish a diagnostic approach for both clinicians and radiologists to avoid misdiagnosis. METHODS: In this retrospective study, we reviewed clinical and computed tomography (CT) findings from 27 patients who presented with suspicion of thoracic malignancy who were ultimately diagnosed with fungal disease. RESULTS: Patients' median age was 55.7 (range 31-78) years. The most common clinical findings were cough (48.1 %), expectoration (33.3 %), chest pain (25.9 %), weakness (25.9 %), weight loss (18.5 %), and hemoptysis, dyspnea, and fever (7.4 % each). The median lesion size was 35.5 (range 10-85) mm. CT findings included a solid nodule (51.9 %), solid mass (37 %), or both (11.1 %). Nodule and mass margins were lobulated in 9 (33.3 %) patients, ill-defined in 5 (18.5 %), spiculated in 4 (14.8 %), and smooth in 4 (14.8 %) patients. Additional findings included consolidation in 4 (14.8 %) patients, cavitation in 3 (11.1 %), pleural effusion in 2 (7.4 %), and lymphadenopathy in 11 (40.7 %) patients. In all patients, specific diagnoses were made and confirmed by histopathology; final diagnoses were histoplasmosis (25.9 %), coccidiomycosis (22.2 %), cryptococcosis (22.2 %), aspergillosis (14.8 %), North American blastomycosis (7.4 %), mucormycosis (3.75 %), and paracoccidioidomycosis (3.75 %). CONCLUSIONS: Fungal infection can present with clinical and radiological features that are indistinguishable from thoracic malignancy, such as lung nodules or masses. Because the management and outcomes of fungal infection and malignancy are entirely distinct, the establishment of a specific diagnosis is critical to provide appropriate therapy.", "author" : [ { "dropping-particle" : "", "family" : "Guimaraes", "given" : "Marcos Duarte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchiori", "given" : "Edson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza Portes Meirelles", "given" : "Gustavo", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hochhegger", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santana", "given" : "Pablo Rydz Pinheiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gross", "given" : "Jefferson Luiz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bitencourt", "given" : "Almir Galvao Vieira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boonsirikamchai", "given" : "Piyaporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godoy", "given" : "Myrna Corbos Barco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lung", "id" : "ITEM-6", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "655-662", "title" : "Fungal infection mimicking pulmonary malignancy: Clinical and radiological characteristics", "type" : "article-journal", "volume" : "191" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1128/CMR.00053-10", "ISBN" : "1098-6618 (Electronic)\\r0893-8512 (Linking)", "ISSN" : "08938512", "PMID" : "21482725", "abstract" : "Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.", "author" : [ { "dropping-particle" : "", "family" : "Guarner", "given" : "Jeannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandt", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-7", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "247-280", "title" : "Histopathologic diagnosis of fungal infections in the 21st century", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "ISSN" : "1726-426X", "abstract" : "Atypical organisms such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila are implicated in up to 40 percent of cases of community-acquired pneumonia. Antibiotic treatment is empiric and includes coverage for both typical and atypical organisms. Doxycycline, a fluoroquinolone with enhanced activity against Streptococcus pneumoniae, or a macrolide is appropriate for outpatient treatment of immunocompetent adult patients. Hospitalised adults should be treated with cefotaxime or ceftriaxone plus a macrolide, or with a fluoroquinolone alone. The same agents can be used in adult patients in intensive care units, although fluoroquinolone monotherapy is not recommended; ampicillin-sulbactam or piperacillin-tazobactam can be used instead of cefotaxime or ceftriaxone. Outpatient treatment of children two months to five years of age consists of high-dose amoxicillin given for seven to 10 days. A single dose of ceftriaxone can be used in infants when the first dose of antibiotic is likely to be delayed or not absorbed. Older children can be treated with a macrolide. Hospitalised children should be treated with a macrolide plus a beta-lactam inhibitor. In a bioterrorist attack, pulmonary illness may result from the organisms that cause anthrax, plague, or tularaemia. Sudden acute respiratory syndrome begins with a flu-like illness, followed two to seven days later by cough, dyspnoea and, in some instances, acute respiratory distress. Copyright\u00a9 2004 American Academy of Family Physicians.", "author" : [ { "dropping-particle" : "", "family" : "Thibodeau", "given" : "Kristopher P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viera", "given" : "Anthony J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Academy of Family Physicians", "id" : "ITEM-8", "issue" : "8", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "14-19", "title" : "Atypical pathogens and challenges in community-acquired pneumonia", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1016/S1201-9712(01)90030-X", "ISSN" : "12019712", "PMID" : "11468102", "abstract" : "OBJECTIVE: To gain insight into the histopathologic characteristics of fungal infection in acquired immunodeficiency syndrome (AIDS). METHODS: A review was conducted of the histopathology for 162 patients with evident fungal infection. RESULTS: The microscopic appearance of esophageal candidiasis that was common in patients with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida infection. Eighteen patients had generalized cryptococcosis, representing the commonest generalized fungal disease. The essential histologic features of the disease consisted of yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from the manifestations of both Candida and Aspergillus infections. The two histologic patterns recognized in the pulmonary cryptococcal lesions could be graded with respect to the degree and type of inflammatory reaction. The milder one consisted of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which might be simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in all 18 patients.", "author" : [ { "dropping-particle" : "", "family" : "Shibuya", "given" : "Kazutoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coulson", "given" : "Walter F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wollman", "given" : "Jerome S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wakayama", "given" : "Megumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ando", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oharaseki", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takahashi", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naoe", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of infectious diseases", "id" : "ITEM-9", "issue" : "2", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "78-85", "title" : "Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{15,163,187,190,202\u2013206}", "plainTextFormattedCitation" : "15,163,187,190,202\u2013206", "previouslyFormattedCitation" : "^{15,163,187,190,202\u2013206}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }15,163,187,190,202–206 The methods used to confirm the infection are culture, direct microscopic, histopathology, serology and molecular detection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1590/S0036-46652009000500004", "ISSN" : "00364665", "PMID" : "19893977", "abstract" : "Cryptococcosis is one of the most common opportunistic fungal infections in patients with acquired immunodeficiency syndrome (AIDS). We report 13 cases of cryptococcal infection based on histopathology, serology and cultures. Epidemiological analysis, histochemical techniques of hematoxilin and eosin (HE) and Grocot's silver (GMS), as well special histochemical techniques such as Mayer's mucicarmine (MM) and Fontana-Masson (FM), cryptococcal antigen test (CrAg) and isolation on fungal media: Sabouraud's (SAB), brain-heart infusion agar (BHI) and canavanine-glycine-bromothymol blue (CGB) agar were analyzed. Unsatisfactory staining results by MM stain associated to negative titers by CrAg test, which FM stain confirmed that capsule-deficient Cryptococcus infections were observed in four cases. Eight isolated cases were identified as follows: six cases were infection with Cryptococcus neoformans and two cases were Cryptococcus gattii.", "author" : [ { "dropping-particle" : "", "family" : "Gazzoni", "given" : "Alexandra Fl\u00e1via", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Cec\u00edlia Bittencourt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salles", "given" : "Emily Ferreira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Luiz Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "255-259", "title" : "Histopathology, serology and cultures in the diagnosis of cryptococcosis", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1099/jmm.0.007328-0", "ISBN" : "0022-2615 (Print)\\n0022-2615", "ISSN" : "00222615", "PMID" : "19528182", "abstract" : "The rising incidence of cryptococcosis in India is posing a serious threat. Due to lack of sensitive methods for diagnosis, high morbidity and mortality are associated with the disease. Early diagnosis is essential to prevent serious complications. Therefore, we attempted to find highly sensitive and specific detection methods. A comparative evaluation of the detection of cryptococcosis was done by conventional (direct microscopy and culture) and rapid diagnostic [latex agglutination test (LAT), enzyme immunoassay (EIA) and PCR] methods. The study was done on 359 samples from 52 positive patients and 30 negative controls in an Indian set-up. Evaluation was done for cerebrospinal fluid (CSF), serum and urine separately. The diagnostic value of the tests was assessed in pre-treatment samples, and follow-up tests were also done on samples obtained after initiation of treatment. PCR had the highest sensitivity, followed by EIA and LAT, both before and after treatment. The positive detection by LAT, EIA and PCR was the longest in CSF (>90 days), followed by serum ( approximately 65 days) then urine ( approximately 45 days) after initiation of treatment. Our results indicated that the sensitivity and specificity of PCR and EIA were comparable in urine, CSF and serum for diagnosis of cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Saha", "given" : "Dolan Champa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xess", "given" : "Immaculata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biswas", "given" : "Ashutosh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhowmik", "given" : "Dipankar M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Padma", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Medical Microbiology", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1098-1105", "title" : "Detection of Cryptococcus by conventional, serological and molecular methods", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/S1201-9712(01)90030-X", "ISSN" : "12019712", "PMID" : "11468102", "abstract" : "OBJECTIVE: To gain insight into the histopathologic characteristics of fungal infection in acquired immunodeficiency syndrome (AIDS). METHODS: A review was conducted of the histopathology for 162 patients with evident fungal infection. RESULTS: The microscopic appearance of esophageal candidiasis that was common in patients with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida infection. Eighteen patients had generalized cryptococcosis, representing the commonest generalized fungal disease. The essential histologic features of the disease consisted of yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from the manifestations of both Candida and Aspergillus infections. The two histologic patterns recognized in the pulmonary cryptococcal lesions could be graded with respect to the degree and type of inflammatory reaction. The milder one consisted of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which might be simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in all 18 patients.", "author" : [ { "dropping-particle" : "", "family" : "Shibuya", "given" : "Kazutoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coulson", "given" : "Walter F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wollman", "given" : "Jerome S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wakayama", "given" : "Megumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ando", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oharaseki", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takahashi", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naoe", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of infectious diseases", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "78-85", "title" : "Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1086/588660.Revised", "ISBN" : "1537-6591 (Electronic)\\r1058-4838 (Linking)", "ISSN" : "1537-6591", "PMID" : "18462102", "abstract" : "Background\u2014Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods\u2014After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results\u2014The revised definitions retain the original classifications of \u201cproven,\u201d \u201cprobable,\u201d and \u201cpossible\u201d invasive fungal disease, but the definition of \u201cprobable\u201d has been expanded, whereas the scope of the category \u201cpossible\u201d has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions\u2014These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high- risk patients. 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Infect. Dis", "id" : "ITEM-5", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1813-1821", "title" : "Revised definitions of invasive fungal disease from the European Organization for Research & Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses (EORTC/MSG) Consensus Group", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{187,202,203,206,207}", "plainTextFormattedCitation" : "187,202,203,206,207", "previouslyFormattedCitation" : "^{187,202,203,206,207}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187,202,203,206,207 We propose diagnostic criteria for pulmonary cryptococcosis in Figure 1. Identifying a positive culture of Cryptococcus from bronchoalveolar lavage (BAL) or pleural fluid, together with appropriate clinical symptoms and/or radiology findings are the key diagnostic approaches.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-1", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1468-1293.2011.00944_1.x", "ISBN" : "9783924774509", "ISSN" : "1468-1293", "PMID" : "21851517", "author" : [ { "dropping-particle" : "", "family" : "Jos\u00e9", "given" : "Ian Gatell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jurgen", "given" : "Rocktroh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlomo", "given" : "Staszewski", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "HIV Medicine", "id" : "ITEM-2", "issue" : "September", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "supp 2", "title" : "British HIV Association and British Infection Association Guidelines for the Treatment of Opportunistic Infection in HIV-seropositive Individuals 2011 HIV MEDICINE EDITORS", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^46,208", "plainTextFormattedCitation" : "46,208", "previouslyFormattedCitation" : "^46,208" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }46,208 These findings may be discovered in parallel with, or without, positive antigen tests or direct microscopy from serum, BAL or pleural fluid.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1468-1293.2011.00944_1.x", "ISBN" : "9783924774509", "ISSN" : "1468-1293", "PMID" : "21851517", "author" : [ { "dropping-particle" : "", "family" : "Jos\u00e9", "given" : "Ian Gatell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jurgen", 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"Geneva: World Health Organization", "id" : "ITEM-2", "issue" : "December", "issued" : { "date-parts" : [ [ "2011" ] ] }, "title" : "Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children: December 2011", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^208,209", "plainTextFormattedCitation" : "208,209", "previouslyFormattedCitation" : "^208,209" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }208,209 Antigen tests from serum or blood or culture are rarely positive unless there is disseminated cryptococcal infection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1590/S0036-46652010000300006", "ISBN" : "1678-9946 (Electronic)\\r0036-4665 (Linking)", "ISSN" : "00364665", "PMID" : "20602024", "abstract" : "Ten cases of cryptococcosis due to unusual microscopic forms of Cryptococcus sp. observed over a twenty-eight year period (1981-2009) are presented. The most important clinicopathological and laboratory data are tabulated. The uncommon forms of cryptococcal cells given are: structures resembling germ tube (one case), chains of budding yeasts (one case), pseudohyphae (two cases) and nonencapsulated yeast-like organisms (eight cases). The diagnosis was based on the histopathological findings. The causative organism was isolated and identified in seven cases; five were due to C. neoformans, and two to C. gattii. In addition, the importance of using staining histochemical techniques - Grocott's silver stain (GMS), Mayer's mucicarmine stain (MM) and Fontana-Masson stain (FM) - in the diagnosis of cryptococcosis is argued.", "author" : [ { "dropping-particle" : "", "family" : "Gazzoni", "given" : "Alexandra Fl??via", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira", "given" : "Fl??vio de Mattos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salles", "given" : "Emily Ferreira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayayo", "given" : "Emilio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guarro", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Capilla", "given" : "Javier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Luiz Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "145-149", "title" : "Unusual morphologies of <i>Cryptococcus</i> spp. in tissue specimens: Report of 10 cases", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹⁰", "plainTextFormattedCitation" : "210", "previouslyFormattedCitation" : "²¹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }210 The use of lysis centrifugation of the buffy coat from blood may increase detection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/B978-1-4160-4390-4.00084-9", "author" : [ { "dropping-particle" : "", "family" : "Dromer", "given" : "Fran\u00e7oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hunter's Tropical Medicine and Emerging Infectious Disease", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "641-643", "title" : "Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹¹", "plainTextFormattedCitation" : "211", "previouslyFormattedCitation" : "²¹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }211 Once a diagnosis of pulmonary cryptococcosis is made, a lumbar puncture and cerebrospinal fluid (CSF) examination (including antigen) are recommended in all patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/649858", "ISBN" : "1537-6591 (Electronic)\\r1058-4838 (Linking)", "ISSN" : "1537-6591", "PMID" : "20047480", "abstract" : "Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Francoise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graybill", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "Richard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "Minh-Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pappas", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powderly", "given" : "William G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sobel", "given" : "Jack D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "291-322", "title" : "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹²", "plainTextFormattedCitation" : "212", "previouslyFormattedCitation" : "²¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }212 The differential diagnosis of pulmonary cryptococcosis is summarised in Table 3.Microscopy and cultureSputum, BAL, pleural fluid, or tissue from a lung biopsy is collected for microscopy to visualise yeasts and fungal culture may grow Cryptococcus spp.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/B978-1-4160-4390-4.00084-9", "author" : [ { "dropping-particle" : "", "family" : "Dromer", "given" : "Fran\u00e7oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hunter's Tropical Medicine and Emerging Infectious Disease", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "641-643", "title" : "Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^22,211", "plainTextFormattedCitation" : "22,211", "previouslyFormattedCitation" : "^22,211" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22,211 A lung biopsy from nodules of uncertain aetiology requires a fungal culture to be done, in addition to histopathology examination. The laboratory procedure for handling sputum from suspected cases is not standardised, due to different culture conditions and media used by local laboratories.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "²²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22 The pellet from pleural fluid or BAL can be mixed with India ink and observed under a microscope. The distinctive structure for Cryptococcus spp. is narrow budding encapsulated yeasts. Samples for culture should be placed on Sabouraud dextrose agar at 30°C for seven days, in aerobic conditions, and observed daily.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^22,187", "plainTextFormattedCitation" : "22,187", "previouslyFormattedCitation" : "^22,187" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22,187 Cultures from patients receiving systemic antifungal therapy might need longer to grow Cryptococcus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁷", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "¹⁸⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187 Cryptococcus appears as mucoid creamy colonies. C. neoformans are identified generally as smooth colonies while C. gattii mostly appears as mucoid colonies. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11046-008-9137-9.Phenotypic", "author" : [ { "dropping-particle" : "", "family" : "Jain", "given" : "Neena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fries", "given" : "Bettina C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycopathologia", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "181-188", "title" : "Phenotypic switching of <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "article-journal", "volume" : "166" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1128/JCM.43.11.5733", "ISBN" : "0095-1137 (Print)\\r0095-1137 (Linking)", "ISSN" : "00951137", "PMID" : "16272511", "author" : [ { "dropping-particle" : "", "family" : "Jain", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickes", "given" : "B L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keller", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fu", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ragan", "given" : "M a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fries", "given" : "B C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jain", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Microbiol", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "5733-5742", "title" : "Molecular epidemiology of clinical <i> Cryptococcus neoformans</i> strains from India", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^213,214", "plainTextFormattedCitation" : "213,214", "previouslyFormattedCitation" : "^213,214" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }213,214 Canavanine-glycine-bromothymol blue (CGB) agar can be used to differentiate between C. neoformans and C. gattii. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/B978-1-4160-4390-4.00084-9", "author" : [ { "dropping-particle" : "", "family" : "Dromer", "given" : "Fran\u00e7oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hunter's Tropical Medicine and Emerging Infectious Disease", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "641-643", "title" : "Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-2", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^46,211", "plainTextFormattedCitation" : "46,211", "previouslyFormattedCitation" : "^46,211" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }46,211 Colonies of C. neoformans will not cause changes in CGB agar. On the other hand, C. gattii produces a blue colour in CGB agar. Unlike other types of specimens, there are many variations in the culture media and culture conditions for sputum. One study reported that birdseed extract (BSE) agar may increase Cryptococcus detection in sputum and urine samples in HIV patients,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0095-1137 (Print)\\r0095-1137 (Linking)", "ISSN" : "0095-1137", "PMID" : "2254431", "abstract" : "Growth of Cryptococcus neoformans from the sputum of patients with acquired immunodeficiency syndrome may be obscured by oral contamination with Candida albicans on conventional media. We prospectively compared direct plating of sputum and urine onto birdseed agar and compared birdseed agar plating with plating onto Mycosel and Sabouraud dextrose agar cultures. Thirty-two sputum and three urine specimens were compared. C. neoformans was isolated from five specimens. In two specimens, one of sputum and one of urine, C. neoformans was detected only on the birdseed agar plate because of overgrowth on the conventional media by C. albicans. C. neoformans produced dark colonies on birdseed agar, unlike C. albicans, which produces white colonies. The use of birdseed agar as the primary culture medium for sputum and urine specimens from patients with acquired immunodeficiency syndrome increases sensitivity for C. neoformans.", "author" : [ { "dropping-particle" : "", "family" : "Denning", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamilton", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical microbiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "2565-7", "title" : "Comparison of <i>Guizotia abyssinica</i> seed extract (birdseed) agar with conventional media for selective identification of <i>Cryptococcus neoformans</i> in patients with acquired immunodeficiency syndrome.", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹⁵", "plainTextFormattedCitation" : "215", "previouslyFormattedCitation" : "²¹⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }215 partly because white colonies on Sabouraud dextrose agar may be indistinguishable from Candida spp. The addition of benomyl to BSE agar has been shown to likely increase detection of Cryptococcus from environmental isolates when the samples are highly contaminated with other moulds.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/mmy/myt028", "ISSN" : "14602709", "PMID" : "24782104", "abstract" : "One of the difficulties of isolating Cryptococcus neoformans and Cryptococcus gattii from environmental samples is the abundant overgrowth of other yeast and mold species that occurs on the plates. Here we report the application of benomyl to Guizotia abyssinica seed extract growth medium to improve the isolation of C. neoformans and C. gattii from environmental samples. We validated this medium by recovering C. neoformans and C. gattii from convenience soils and swabs from a region of the United States where these yeasts are endemic.", "author" : [ { "dropping-particle" : "", "family" : "Pham", "given" : "Cau D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahn", "given" : "Stacey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turner", "given" : "Lance A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wohrle", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lockhart", "given" : "Shawn R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "417-421", "title" : "Development and validation of benomyl birdseed agar for the isolation of <i> Cryptococcus neoformans</i> and <i>Cryptococcus gattii </i> from environmental samples", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹⁶", "plainTextFormattedCitation" : "216", "previouslyFormattedCitation" : "²¹⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }216 Benomyl is a fungicide that inhibits ascomycetes but has no effect on basidiomycetes including C. neoformans and C. gattii. Positive results for C. neoformans and C. gattii cultures from any types of specimens should be followed by clinical investigation.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "²²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22 HistopathologyA lung biopsy is the best diagnostic option when sputum or bronchoscopy specimens are unavailable or negative.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "²²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22 There are several methods of lung biopsy including percutaneous lung biopsy, trans-bronchial lung biopsy, video-assisted thoracoscopic (VAT) biopsy, and open lung biopsy. The most appropriate method to use for the biopsy depends on the skills available and the location of the lung lesion. Histological staining with hematoxylin and eosin (H&E), Grocott or Gomori methenamine silver (GMS), and periodic acid-Schiff (PAS) are used to detect Cryptococcus that present as narrow-based budding yeasts (4-10 ?m), usually surrounded by thick capsules in the lung tissue.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/CMR.00053-10", "ISBN" : "1098-6618 (Electronic)\\r0893-8512 (Linking)", "ISSN" : "08938512", "PMID" : "21482725", "abstract" : "Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.", "author" : [ { "dropping-particle" : "", "family" : "Guarner", "given" : "Jeannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandt", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "247-280", "title" : "Histopathologic diagnosis of fungal infections in the 21st century", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-2", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^46,204", "plainTextFormattedCitation" : "46,204", "previouslyFormattedCitation" : "^46,204" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }46,204 Tissue sections can be processed with alcian blue or mucicarmine to display the capsuleADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/B978-1-4160-4390-4.00084-9", "author" : [ { "dropping-particle" : "", "family" : "Dromer", "given" : "Fran\u00e7oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hunter's Tropical Medicine and Emerging Infectious Disease", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "641-643", "title" : "Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹¹", "plainTextFormattedCitation" : "211", "previouslyFormattedCitation" : "²¹¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }211 (Figure. 2). Mucicarmine can differentiate Cryptococcus from other yeast-like structures such as those of Coccidioides, Histoplasma, or Candida, but only stain Blastomyces weakly. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "M Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "547-564", "title" : "Diagnostic approach based on capsular antigen, capsule detection, Beta-glucan, and DNA analysis", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹⁷", "plainTextFormattedCitation" : "217", "previouslyFormattedCitation" : "²¹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }217 Occasionally, Cryptococcus infection with a capsule-deficient strain is present and not detected with mucicarmine.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1590/S0036-46652010000300006", "ISBN" : "1678-9946 (Electronic)\\r0036-4665 (Linking)", "ISSN" : "00364665", "PMID" : "20602024", "abstract" : "Ten cases of cryptococcosis due to unusual microscopic forms of Cryptococcus sp. observed over a twenty-eight year period (1981-2009) are presented. The most important clinicopathological and laboratory data are tabulated. The uncommon forms of cryptococcal cells given are: structures resembling germ tube (one case), chains of budding yeasts (one case), pseudohyphae (two cases) and nonencapsulated yeast-like organisms (eight cases). The diagnosis was based on the histopathological findings. The causative organism was isolated and identified in seven cases; five were due to C. neoformans, and two to C. gattii. In addition, the importance of using staining histochemical techniques - Grocott's silver stain (GMS), Mayer's mucicarmine stain (MM) and Fontana-Masson stain (FM) - in the diagnosis of cryptococcosis is argued.", "author" : [ { "dropping-particle" : "", "family" : "Gazzoni", "given" : "Alexandra Fl??via", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira", "given" : "Fl??vio de Mattos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salles", "given" : "Emily Ferreira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayayo", "given" : "Emilio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guarro", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Capilla", "given" : "Javier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Luiz Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "145-149", "title" : "Unusual morphologies of <i>Cryptococcus</i> spp. in tissue specimens: Report of 10 cases", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cheon", "given" : "Won Seok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eom", "given" : "Kwang-seok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoo", "given" : "Byoung Kwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Dong-gyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jung", "given" : "Ki-suck", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Korean Journal of Internal Medicine", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "83-87", "title" : "A case of pulmonary cryptococcosis by capsule-deficient <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^210,218", "plainTextFormattedCitation" : "210,218", "previouslyFormattedCitation" : "^210,218" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }210,218 In this instance, Fontana-Masson stain should be used to detect Cryptococcus because it stains melanin and other silver-reducing granules in the Cryptococcus cell walls.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "00039985", "abstract" : "We describe light and electron microscopic findings in three cases of pulmonary infection caused by capsule-deficient Cryptococcus neoformans (CDCN) and emphasize the value of the Fontana-Masson silver (FMS) stain in diagnosing cryptococcosis. Capsule-deficient C neoformans infections, including coccidioidomycosis, histoplasmosis, typical cryptococcosis, blastomycosis, candidiasis, and pneumocystosis were used as controls. Several stains including mucicarmine, alcian blue, and FMS were done on tissue sections from all of the above mentioned infections. It was found that while the FMS stain was positive only in the organisms of CDCN and typical C neoformans, the mucicarmine was positive only in typical C neoformans. The negativity of the mucicarmine in the organisms of CDCN reflected the absence of capsular material as demonstrated by ultrastructural study. Therefore, when fungal cultures are not available or are negative, and tissue mucicarmine is negative, the FMS stain is a valuable alternative for use on tissue sections. It may be used, along with routine fungal stains, when a yeast-forming fungal infection is suspected.", "author" : [ { "dropping-particle" : "", "family" : "Ro", "given" : "J. Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ayala", "given" : "A. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Pathology and Laboratory Medicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1987" ] ] }, "page" : "53-57", "title" : "Advantage of Fontana-Masson stain in capsule-deficient cryptococcal infection", "type" : "article-journal", "volume" : "111" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "", "ISSN" : "1806-3756", "PMID" : "20011850", "abstract" : "neoforman Cryptococcosis is a systemic mycosis caused by two species of the encapsulated basidiomycetes, s s and C. gattii , which, respectively, cause infection in immunocompromised individuals and in immunologically normal hosts. Patients with T-cell deficiencies are more susceptible to this infection. The spectrum Cryptococcu of the disease ranges from asymptomatic pulmonary lesions to disseminated infection with meningoencephalitis. The medical relevance of cryptococcosis increased dramatically as a consequence of the AIDS epidemic and organ transplants.", "author" : [ { "dropping-particle" : "", "family" : "Cec\u00edlia Bittencourt Severo, Alexandra Fl\u00e1via Gazzoni", "given" : "Luiz Carlos Severo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Bras Pneumol.", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1136-1144", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^106,219", "plainTextFormattedCitation" : "106,219", "previouslyFormattedCitation" : "^106,219" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }106,219 Several studies have reported that the majority of the Cryptococcus samples revealed a lack of capsule and instead unusual structures (for Cryptococcus) such as pseudohyphae, germ tubes and chains of budding yeasts.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1590/S0036-46652010000300006", "ISBN" : "1678-9946 (Electronic)\\r0036-4665 (Linking)", "ISSN" : "00364665", "PMID" : "20602024", "abstract" : "Ten cases of cryptococcosis due to unusual microscopic forms of Cryptococcus sp. observed over a twenty-eight year period (1981-2009) are presented. The most important clinicopathological and laboratory data are tabulated. The uncommon forms of cryptococcal cells given are: structures resembling germ tube (one case), chains of budding yeasts (one case), pseudohyphae (two cases) and nonencapsulated yeast-like organisms (eight cases). The diagnosis was based on the histopathological findings. The causative organism was isolated and identified in seven cases; five were due to C. neoformans, and two to C. gattii. In addition, the importance of using staining histochemical techniques - Grocott's silver stain (GMS), Mayer's mucicarmine stain (MM) and Fontana-Masson stain (FM) - in the diagnosis of cryptococcosis is argued.", "author" : [ { "dropping-particle" : "", "family" : "Gazzoni", "given" : "Alexandra Fl??via", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira", "given" : "Fl??vio de Mattos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salles", "given" : "Emily Ferreira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayayo", "given" : "Emilio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guarro", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Capilla", "given" : "Javier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Luiz Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "145-149", "title" : "Unusual morphologies of <i>Cryptococcus</i> spp. in tissue specimens: Report of 10 cases", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0001-5547", "ISSN" : "0001-5547 (Print)", "PMID" : "8629428", "abstract" : "BACKGROUND: Cryptococcus neoformans is not generally recognized as producing pseudohyphae. Although atypical morphologic forms have been described in the microbiology literature, we believe this is the first complete cytologic report describing this uncommon and unusual cytologic appearance of cryptococcal infection. CASES: In five cases of cryptococcal infection, C neoformans formed chains of budding yeasts, pseudohyphae and germ tube-like structures. The atypical forms of C neoformans were seen in cerebrospinal fluid, imprints and in histopathologic sections from multiple organs from two human immunodeficiency virus (HIV)-positive patients; in pleural fluid from a patient with non-Hodgkin's lymphoma; in crush smears from a stereotactic biopsy of the brain; and in a fine needle aspirate of a lung nodule in two patients with no known risk factors for HIV infection. CONCLUSION: Recognition of atypical cytomorphologic variants of C neoformans is important since there are potential diagnostic pitfalls for confusing these atypical-appearing organisms with a Candida-type species or fungal contaminants. Special stains for capsular material and culture can be helpful in making a correct diagnosis.", "author" : [ { "dropping-particle" : "", "family" : "Williamson", "given" : "J D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silverman", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mallak", "given" : "C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christie", "given" : "J D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta cytologica", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "363-370", "title" : "Atypical cytomorphologic appearance of <i> Cryptococcus neoformans</i>: a report of five cases.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^210,220", "plainTextFormattedCitation" : "210,220", "previouslyFormattedCitation" : "^210,220" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }210,220 In addition, titan cells were identified in 10% of pulmonary cryptococcosis cases. A wide variety of inflammatory reactions are observed in pulmonary cryptococcal infection from well-formed granulomas to minimal inflammation.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1590/S0036-46652009000500004", "ISSN" : "00364665", "PMID" : "19893977", "abstract" : "Cryptococcosis is one of the most common opportunistic fungal infections in patients with acquired immunodeficiency syndrome (AIDS). We report 13 cases of cryptococcal infection based on histopathology, serology and cultures. Epidemiological analysis, histochemical techniques of hematoxilin and eosin (HE) and Grocot's silver (GMS), as well special histochemical techniques such as Mayer's mucicarmine (MM) and Fontana-Masson (FM), cryptococcal antigen test (CrAg) and isolation on fungal media: Sabouraud's (SAB), brain-heart infusion agar (BHI) and canavanine-glycine-bromothymol blue (CGB) agar were analyzed. Unsatisfactory staining results by MM stain associated to negative titers by CrAg test, which FM stain confirmed that capsule-deficient Cryptococcus infections were observed in four cases. Eight isolated cases were identified as follows: six cases were infection with Cryptococcus neoformans and two cases were Cryptococcus gattii.", "author" : [ { "dropping-particle" : "", "family" : "Gazzoni", "given" : "Alexandra Fl\u00e1via", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Cec\u00edlia Bittencourt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salles", "given" : "Emily Ferreira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Severo", "given" : "Luiz Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "255-259", "title" : "Histopathology, serology and cultures in the diagnosis of cryptococcosis", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁰²", "plainTextFormattedCitation" : "202", "previouslyFormattedCitation" : "²⁰²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }202 A complete granuloma complex is built from aggregates of macrophages, lymphocytes, plasma cells, and multi-nucleated giant cells.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1043/1543-2165-134.5.667", "ISSN" : "1543-2165", "PMID" : "21794667", "abstract" : "Inflammatory myopathies are a group of idiopathic diseases characterized by an inflammatory infiltrate of the skeletal muscles that includes Polymyositis, Dermatomyositis, and Inclusion Body Myositis, each one displaying distinctive histopathological, immunological, and pathogenic features. The diagnosis of Inflammatory Myopathies is suspected on the basis of clinical features and supported by evidence obtained from laboratory tests, plasma levels of muscle enzymes, detection of autoantibodies, electromyography and, recently, magnetic resonance and ultrasonographic image studies have been included into the diagnostic arsenal. A definitive diagnosis relies on the findings in the muscle biopsy, performed before treatment and preferably before severe muscle atrophy has developed. Precision in diagnosis plays a fundamental role in the evaluation of these patients, allowing conclusions to be drawn regarding the response to treatment and prognosis.", "author" : [ { "dropping-particle" : "", "family" : "Nava", "given" : "Arnulfo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orozco-Barocio", "given" : "Gerardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Pathology and Laboratory Medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "667-690", "title" : "Granulomatous lung disease an approach to the differential diagnosis", "type" : "article-journal", "volume" : "134" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²¹", "plainTextFormattedCitation" : "221", "previouslyFormattedCitation" : "²²¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }221 The presence and architecture of granulomas or other lesions are likely related to Cryptococcus species (and capsule characteristics) and host immune status.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/CMR.00053-10", "ISBN" : "1098-6618 (Electronic)\\r0893-8512 (Linking)", "ISSN" : "08938512", "PMID" : "21482725", "abstract" : "Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.", "author" : [ { "dropping-particle" : "", "family" : "Guarner", "given" : "Jeannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandt", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "247-280", "title" : "Histopathologic diagnosis of fungal infections in the 21st century", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-2", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^46,204", "plainTextFormattedCitation" : "46,204", "previouslyFormattedCitation" : "^46,204" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }46,204 Post-mortem studies of HIV patients with pulmonary cryptococcosis have revealed abundant organism in distended alveoli, submucosa and peribronchial tissue without any sign of an inflammatory response,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ijid.2010.02.2255", "ISBN" : "1201-9712", "ISSN" : "12019712", "PMID" : "20932485", "abstract" : "HIV-associated pulmonary cryptococcosis is under diagnosed, and may progress to fatal meningoencephalitis. We present a case of HIV-associated pulmonary Cryptococcus neoformans infection, initially mis-diagnosed as smear-negative pulmonary TB, which progressed to fatal cryptococcal meningitis. Autopsy series suggest that pulmonary cryptococcosis is common in African AIDS patients, and, due to limited diagnostic capacity, often mis-diagnosed as smear negative TB. Serum cryptococcal antigen testing may facilitate diagnosis in such cases. ?? 2010 International Society for Infectious Diseases.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wainwright", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rebe", "given" : "Kevin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meintjes", "given" : "Graeme", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Infectious Diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "e310-e312", "publisher" : "International Society for Infectious Diseases", "title" : "Pulmonary cryptococcosis misdiagnosed as smear-negative pulmonary tuberculosis with fatal consequences", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²²", "plainTextFormattedCitation" : "222", "previouslyFormattedCitation" : "²²²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }222 whereas typical granulomas and other inflammatory cells comprised the majority of the histopathology findings from immunocompetent patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2008-1063853.", "author" : [ { "dropping-particle" : "", "family" : "Jarvis", "given" : "Joseph N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Care", "id" : "ITEM-1", "issue" : "212", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "141-150", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s10156-005-0387-x", "ISBN" : "8133767156", "author" : [ { "dropping-particle" : "", "family" : "Shibuya", "given" : "Kazutoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirata", "given" : "Akiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Omuta", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugamata", "given" : "Miho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katori", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Norihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murata", "given" : "Nozomu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morita", "given" : "Ayako", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takahashi", "given" : "Keiji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Infect Chemother", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "115-122", "title" : "Granuloma and cryptococcosis", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^46,223", "plainTextFormattedCitation" : "46,223", "previouslyFormattedCitation" : "^46,223" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }46,223 Positive histopathology does not always correlate with the culture result. A negative culture might be caused by nonviable organisms in the sample. Immune responses in the lungs, especially granuloma formation, may render Cryptococcus non-viable.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ofid/ofw167", "author" : [ { "dropping-particle" : "", "family" : "Fisher", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valencia-rey", "given" : "Paula A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "William B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Open Forum Infectious Diseases", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-6", "title" : "Pulmonary cryptococcosis in the immunocompetent patient \u2014 many questions, some answers", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Feldmesser", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kress", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novikoff", "given" : "Phyllis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "4225-4237", "title" : "<i> Cryptococcus neoformans</i> is a facultative intracellular pathogen in murine pulmonary infection", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "K Kawakami S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "N Morikawa J Kadota A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clin Exp Immunol", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "230-237", "title" : "Activation of macrophages and expansion of specific T lymphocytes in the lungs of mice intratracheally inoculated with <i> Cryptococcus neoformans</i>", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^2,224,225", "plainTextFormattedCitation" : "2,224,225", "previouslyFormattedCitation" : "^2,224,225" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2,224,225 Antigen detection testsCapsular polysaccharides of Cryptococcus can be detected and quantified from body fluids such as serum, CSF, BAL and urine using specific anti-C. neoformans antisera.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/CMR.00126-13", "ISBN" : "1098-6618 (Electronic)\\r0893-8512 (Linking)", "ISSN" : "10986618", "PMID" : "25278580", "abstract" : "SUMMARY: Understanding of the taxonomy and phylogeny of Cryptococcus gattii has been advanced by modern molecular techniques. C. gattii probably diverged from Cryptococcus neoformans between 16 million and 160 million years ago, depending on the dating methods applied, and maintains diversity by recombining in nature. South America is the likely source of the virulent C. gattii VGII molecular types that have emerged in North America. C. gattii shares major virulence determinants with C. neoformans, although genomic and transcriptomic studies revealed that despite similar genomes, the VGIIa and VGIIb subtypes employ very different transcriptional circuits and manifest differences in virulence phenotypes. Preliminary evidence suggests that C. gattii VGII causes severe lung disease and death without dissemination, whereas C. neoformans disseminates readily to the central nervous system (CNS) and causes death from meningoencephalitis. Overall, currently available data indicate that the C. gattii VGI, VGII, and VGIII molecular types more commonly affect nonimmunocompromised hosts, in contrast to VGIV. New, rapid, cheap diagnostic tests and imaging modalities are assisting early diagnosis and enabling better outcomes of cerebral cryptococcosis. Complications of CNS infection include increased intracranial pressure, severe neurological sequelae, and development of immune reconstitution syndrome, although the mortality rate is low. C. gattii VGII isolates may exhibit higher fluconazole MICs than other genotypes. Optimal therapeutic regimens are yet to be determined; in most cases, initial therapy with amphotericin B and 5-flucytosine is recommended.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Sharon C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "980-1024", "title" : "<i>Cryptococcus gattii </i> infections", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁹", "plainTextFormattedCitation" : "189", "previouslyFormattedCitation" : "¹⁸⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }189 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "M Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "547-564", "title" : "Diagnostic approach based on capsular antigen, capsule detection, Beta-glucan, and DNA analysis", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹⁷", "plainTextFormattedCitation" : "217", "previouslyFormattedCitation" : "²¹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }217 Three formats of cryptococcal antigen (CrAg) detection tests are currently available: the latex agglutination test (LAT), the enzyme-linked immunoassay (EIA), and the lateral flow immunoassay (LFA).ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/CMR.00126-13", "ISBN" : "1098-6618 (Electronic)\\r0893-8512 (Linking)", "ISSN" : "10986618", "PMID" : "25278580", "abstract" : "SUMMARY: Understanding of the taxonomy and phylogeny of Cryptococcus gattii has been advanced by modern molecular techniques. C. gattii probably diverged from Cryptococcus neoformans between 16 million and 160 million years ago, depending on the dating methods applied, and maintains diversity by recombining in nature. South America is the likely source of the virulent C. gattii VGII molecular types that have emerged in North America. C. gattii shares major virulence determinants with C. neoformans, although genomic and transcriptomic studies revealed that despite similar genomes, the VGIIa and VGIIb subtypes employ very different transcriptional circuits and manifest differences in virulence phenotypes. Preliminary evidence suggests that C. gattii VGII causes severe lung disease and death without dissemination, whereas C. neoformans disseminates readily to the central nervous system (CNS) and causes death from meningoencephalitis. Overall, currently available data indicate that the C. gattii VGI, VGII, and VGIII molecular types more commonly affect nonimmunocompromised hosts, in contrast to VGIV. New, rapid, cheap diagnostic tests and imaging modalities are assisting early diagnosis and enabling better outcomes of cerebral cryptococcosis. Complications of CNS infection include increased intracranial pressure, severe neurological sequelae, and development of immune reconstitution syndrome, although the mortality rate is low. C. gattii VGII isolates may exhibit higher fluconazole MICs than other genotypes. Optimal therapeutic regimens are yet to be determined; in most cases, initial therapy with amphotericin B and 5-flucytosine is recommended.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Sharon C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "980-1024", "title" : "<i>Cryptococcus gattii </i> infections", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0049541", "ISBN" : "1932-6203", "ISSN" : "19326203", "PMID" : "23166705", "abstract" : "BACKGROUND: Cryptococcus neoformans causes life-threatening meningitis. A recently introduced lateral flow immunoassay (LFA) to detect cryptococcal antigen (CRAG) is reportedly more rapid and convenient than standard latex agglutination (LA), but has not yet been evaluated in a diagnostic laboratory setting.\\n\\nMETHODS: One hundred and six serum, 42 cerebrospinal fluid (CSF), and 20 urine samples from 92 patients with known or suspected cryptococcosis were tested by LA and LFA, and titres were compared. Results were correlated with laboratory-confirmed cryptococcosis. Serial samples were tested in nine treated patients.\\n\\nRESULTS: Twenty-five of 92 patients had confirmed cryptococcosis; all sera (n = 56) from these patients were positive by LFA (sensitivity 100%, 95% confidence interval (CI) 93.6-100%) compared with 51/56 positive by LA (sensitivity 91.1%, 95% CI 80.7-96.1%). Fifty sera from 67 patients without cryptococcosis tested negative in both assays. While LA yielded more false negative results (5/56) this did not reach statistical significance (p = 0.063). Nine CSF samples from patients with cryptococcal meningitis yielded positive results using both assays while 17/18 urine samples from patients with cryptococcosis were positive by the LFA. The LFA detected CRAG in C. gattii infection (n = 4 patients). Agreement between titres obtained by both methods (n = 38 samples) was imperfect; correlation between log-transformed titres (r) was 0.84. Turn-around-time was 20 minutes for the LFA and 2 h for LA. The cost per qualitative sample was 18USD and 91 USD, respectively and per quantitative sample was 38USD and 144USD, respectively.\\n\\nCONCLUSIONS: Qualitative agreement between the LFA and LA assays performed on serum and CSF was good but agreement between titres was imperfect. Ease of performance of the LFA and the capacity for testing urine suggest it has a role in the routine laboratory as a rapid diagnostic test or point-of-care test.", "author" : [ { "dropping-particle" : "", "family" : "McMullan", "given" : "Brendan J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halliday", "given" : "Catriona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Judd", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sleiman", "given" : "Sue", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marriott", "given" : "Debbie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olma", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Sharon C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1-6", "title" : "Clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jinf.2010.03.015", "ISBN" : "0163-4453", "ISSN" : "01634453", "PMID" : "20347868", "abstract" : "Objective: To determine the role of serum cryptococcal antigen (SCA) for the screening of cryptococcosis in HIV-infected patients with different ranges of CD4 cell counts. Methods: A retrospective cohort study was conducted in antiretroviral-na??ve HIV-infected patients who had no symptom and had been screened with SCA in a tertiary-care hospital. Prevalence of positive SCA at different ranges of CD4 cell counts, risk factor of positive SCA, and incidence of cryptococcosis during one-year follow-up period after negative SCA were determined. Results: There were 131 patients with a mean age of 38.5 years; 61.8% were male. Median (range) CD4 was 62 (3-590) cells/mm3. The overall prevalence of positive SCA was 9.2%. This prevalence in patients with CD4 < 100, 100-199, and ???200 cells/mm3 were 12.9%, 3.6%, and 0%, respectively (P = 0.041). In multivariate analysis, CD4 < 100 cells/mm3 was associated with positive SCA (OR = 6.69; 95% CI, 1.03-23.56). Four (33.3%) of 12 patients with positive SCA had cryptococcosis whereas one (0.8%) of 119 patients with negative SCA developed meningitis at one-year follow-up. Conclusions: SCA screening has a substantial role for the early detection of cryptococcal infection in HIV-infected patients with low CD4 cell counts. Routine screening with SCA should be performed in patients with CD4 < 100 cells/mm3. ?? 2010 The British Infection Society.", "author" : [ { "dropping-particle" : "", "family" : "Pongsai", "given" : "Pannee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atamasirikul", "given" : "Kalayanee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sungkanuparph", "given" : "Somnuek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Infection", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "474-477", "publisher" : "Elsevier Ltd", "title" : "The role of serum cryptococcal antigen screening for the early diagnosis of cryptococcosis in HIV-infected patients with different ranges of CD4 cell counts", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^189,226,227", "plainTextFormattedCitation" : "189,226,227", "previouslyFormattedCitation" : "^189,226,227" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }189,226,227 These methods are rapid, sensitive and specific but have not been standardised for respiratory specimens such as BAL, pleural fluid or sputum. The sensitivity of serum CrAg for cryptococcal meningitis and disseminated disease is 93-100% and the specificity is 93-98%.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁷", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "¹⁸⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187 The sensitivity and specificity of CSF CrAg are even higher. False negative serum CrAg is commonly associated with pulmonary cryptococcal infection, probably because of the low fungal burden outside the lung or the capsule-deficient strain of Cryptococcus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s12879-017-2459-9", "ISSN" : "1471-2334", "abstract" : "Background: Cryptococcus neoformans is frequently present as an opportunistic pathogen mainly affecting immunocompromised populations. Disseminated C. neoformans infection in immunocompetent population is rare and usually involves lung and central nerve system. Cryptococcus from biologic samples can easily grow on routine fungal and bacterial culture media. Besides, cryptococcal latex agglutination test has been established as a reliable diagnostic tool with overall sensitivities of 93-100%. Case presentation: We report a rare disseminated cryptococcosis case which presented with chronic recurrent multiple abscess in an immunocompetent male involving skin, lung, spine and iliac fossa without evidence of central nerve system involving. The results of serum cryptococcal latex agglutination tests and standard microbial cultures were negative. The patient underwent empirical anti-bacterial and anti-tuberculosis therapy which turned out to be effectless. Finally, bedside inoculation of the pus was carried out and revealed Cryptococcus neoformans, which was confirmed by polymerase chain reaction. After the administration of anti-fungal drugs including liposomal amphotericin B, the patient recovered from fever and paraplegia. Conclusions: This case reveals an uncommon pattern of disseminated C. neoformans infection in immunocompetent population presented with chronic multiple abscess and without central nerve system involving. Negative routine microbial cultures may not necessarily rule out cryptococcosis, especially in early stage. Besides, cryptococcal latex agglutination test does have a chance of false negative, which might be related with \"capsule-deficiency\". Moreover, this phenomenon could be related with low-grade virulence and relative long illness duration.", "author" : [ { "dropping-particle" : "", "family" : "Ruan", "given" : "Qiaoling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Yimin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Shu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Liping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Shu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Wenhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Infectious Diseases", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "369", "publisher" : "BMC Infectious Diseases", "title" : "Disseminated cryptococcosis with recurrent multiple abscesses in an immunocompetent patient: a case report and literature review", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³¹", "plainTextFormattedCitation" : "131", "previouslyFormattedCitation" : "¹³¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }131 However, it may be positive in disseminated cryptococcosis with lung involvement.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1468-1293.2011.00944_1.x", "ISBN" : "9783924774509", "ISSN" : "1468-1293", "PMID" : "21851517", "author" : [ { "dropping-particle" : "", "family" : "Jos\u00e9", "given" : "Ian Gatell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Margaret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jurgen", "given" : "Rocktroh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlomo", "given" : "Staszewski", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "HIV Medicine", "id" : "ITEM-2", "issue" : "September", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "supp 2", "title" : "British HIV Association and British Infection Association Guidelines for the Treatment of Opportunistic Infection in HIV-seropositive Individuals 2011 HIV MEDICINE EDITORS", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^132,187,208", "plainTextFormattedCitation" : "132,187,208", "previouslyFormattedCitation" : "^132,187,208" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }132,187,208 False-positive results are seen in the presence of rheumatoid factors or infections by Klebsiella pneumonia, Trichosporon beigelii, Stomatococcus mucilaginosus, or Capnocytophaga canimorsus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁷", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "¹⁸⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187 The median titre of serum CrAg in pulmonary cryptococcosis in non–HIV patients is 1:16 in patients without any underlying diseases, and 1:32 in those with some form of immunocompromised state.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹³²", "plainTextFormattedCitation" : "132", "previouslyFormattedCitation" : "¹³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }132 In a 12-month follow-up, serum CrAg titres decrease slowly on therapy from >1:32 to negative in most (76%) immunocompetent patients suffering from pulmonary cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ofid/ofw167", "author" : [ { "dropping-particle" : "", "family" : "Fisher", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valencia-rey", "given" : "Paula A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "William B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Open Forum Infectious Diseases", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-6", "title" : "Pulmonary cryptococcosis in the immunocompetent patient \u2014 many questions, some answers", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²", "plainTextFormattedCitation" : "2", "previouslyFormattedCitation" : "²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2 However, the decrease is also seen in untreated survivors although the CrAg rarely becomes negative. At the same time, CrAg may persist for months after successful therapy. Therefore, serum CrAg cannot be used as a prognostic tool or for assessing response to treatment for pulmonary cryptococcosis. Several studies report the use of BAL and percutaneous pulmonary aspirates for CrAg detection.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Baughman", "given" : "Robert P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohn", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frame", "given" : "Peter T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Review of Respiratory Diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "1226-1229", "title" : "Detection of cryptococcal antigen in roncbhoalveolar lavage fluid: A prospective study of diagnostic utility", "type" : "article-journal", "volume" : "145" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kralovic", "given" : "Stephen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhodes", "given" : "Judith C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "3088-3089", "title" : "Utility of routine testing of bronchoalveolar lavage fluid for cryptococcal antigen", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0095-1137 (Print)\\n0095-1137", "ISSN" : "00951137", "PMID" : "7650192", "abstract" : "Pulmonary cryptococcosis causes significant morbidity and mortality in immunocompromised patients. Definitive diagnosis of pulmonary cryptococcosis is usually difficult. The use of direct determination of cryptococcal antigen in transthoracic needle aspirate to diagnose pulmonary cryptococcosis was investigated. Over a 2-year period, we studied a total of 41 patients with respiratory symptoms and pulmonary infiltrates of unknown etiology who were suspected of having pulmonary cryptococcosis. Twenty-two patients were immunocompetent patients and 19 patients were immunocompromised. A diagnosis of pulmonary cryptococcosis was based on cytological examination, culture for Cryptococcus neoformans, histopathologic examination, and clinical response to antifungal therapy. All patients underwent chest ultrasound and ultrasound-guided percutaneous transthoracic needle aspiration to obtain specimens for cryptococcal antigen determination. The presence of cryptococcal antigen was determined by the latex agglutination system (CALAS; Meridian Diagnostics, Cincinnati, Ohio). An antigen titer equal to or greater than 1:8 was considered positive. The specimens were also sent for cytological examination, fungal culture, and/or histopathologic examination. A final diagnosis of pulmonary cryptococcosis was made in eight patients. Direct determinations of cryptococcal antigen in lung aspirate were positive in all eight patients with pulmonary cryptococcosis (100% sensitivity, 97% specificity, a positive predictive value of 89%, and negative value of 100%), and there was only one false-positive in noncryptococcosis patients. The diagnostic accuracy was 97.5%. Serum cryptococcal antigen was positive in only three patients with pulmonary cryptococcosis (sensitivity, 37.5%). This study showed that direct measurement of cryptococcal antigen in lung aspirate can be a rapid and useful test for diagnosis of pulmonary cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Liaw", "given" : "Y. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "P. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "C. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "D. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "H. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "L. N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo -", "given" : "S. H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luh", "given" : "K. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "1588-1591", "title" : "Direct determination of cryptococcal antigen in transthoracic needle aspirate for diagnosis of pulmonary cryptococcosis", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1093/mmy/myx092", "ISSN" : "1369-3786", "author" : [ { "dropping-particle" : "", "family" : "Senghor", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guitard", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Angoulvant", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hennequin", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-4", "title" : "Cryptococcal antigen detection in broncho-alveolar lavage fluid", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^228\u2013231", "plainTextFormattedCitation" : "228\u2013231", "previouslyFormattedCitation" : "^228\u2013231" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }228–231 A CrAg titre of >1:8 in BAL samples of HIV-infected patients resulted in 100% sensitivity and 98% specificity.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Baughman", "given" : "Robert P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohn", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "Harold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frame", "given" : "Peter T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Review of Respiratory Diseases", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "1226-1229", "title" : "Detection of cryptococcal antigen in roncbhoalveolar lavage fluid: A prospective study of diagnostic utility", "type" : "article-journal", "volume" : "145" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²⁸", "plainTextFormattedCitation" : "228", "previouslyFormattedCitation" : "²²⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }228 This is in line with findings from immunocompetent patient lung aspirates showing 100% sensitivity and 97% specificity.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0095-1137 (Print)\\n0095-1137", "ISSN" : "00951137", "PMID" : "7650192", "abstract" : "Pulmonary cryptococcosis causes significant morbidity and mortality in immunocompromised patients. Definitive diagnosis of pulmonary cryptococcosis is usually difficult. The use of direct determination of cryptococcal antigen in transthoracic needle aspirate to diagnose pulmonary cryptococcosis was investigated. Over a 2-year period, we studied a total of 41 patients with respiratory symptoms and pulmonary infiltrates of unknown etiology who were suspected of having pulmonary cryptococcosis. Twenty-two patients were immunocompetent patients and 19 patients were immunocompromised. A diagnosis of pulmonary cryptococcosis was based on cytological examination, culture for Cryptococcus neoformans, histopathologic examination, and clinical response to antifungal therapy. All patients underwent chest ultrasound and ultrasound-guided percutaneous transthoracic needle aspiration to obtain specimens for cryptococcal antigen determination. The presence of cryptococcal antigen was determined by the latex agglutination system (CALAS; Meridian Diagnostics, Cincinnati, Ohio). An antigen titer equal to or greater than 1:8 was considered positive. The specimens were also sent for cytological examination, fungal culture, and/or histopathologic examination. A final diagnosis of pulmonary cryptococcosis was made in eight patients. Direct determinations of cryptococcal antigen in lung aspirate were positive in all eight patients with pulmonary cryptococcosis (100% sensitivity, 97% specificity, a positive predictive value of 89%, and negative value of 100%), and there was only one false-positive in noncryptococcosis patients. The diagnostic accuracy was 97.5%. Serum cryptococcal antigen was positive in only three patients with pulmonary cryptococcosis (sensitivity, 37.5%). This study showed that direct measurement of cryptococcal antigen in lung aspirate can be a rapid and useful test for diagnosis of pulmonary cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Liaw", "given" : "Y. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "P. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "C. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "D. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "H. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "L. N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo -", "given" : "S. H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luh", "given" : "K. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "1588-1591", "title" : "Direct determination of cryptococcal antigen in transthoracic needle aspirate for diagnosis of pulmonary cryptococcosis", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁰", "plainTextFormattedCitation" : "230", "previouslyFormattedCitation" : "²³⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }230 False negatives may be caused by dilution of the sample in the process of bronchial washing. A recent study with 23 HIV-negative pulmonary cryptococcosis patients revealed 82.6% sensitivity of CrAg detection in BAL while the serum CrAg sensitivity was only 73.9%.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/mmy/myx010", "ISBN" : "1460-2709 (Electronic) 1369-3786 (Linking)", "ISSN" : "1369-3786", "PMID" : "28419364", "author" : [ { "dropping-particle" : "", "family" : "Oshima", "given" : "Kazuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takazono", "given" : "Takahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saijo", "given" : "Tomomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Masato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurihara", "given" : "Shintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Kazuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imamura", "given" : "Yoshifumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsukamoto", "given" : "Misuzu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukae", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-7", "title" : "Examination of cryptococcal glucuronoxylomannan antigen in bronchoalveolar lavage fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³²", "plainTextFormattedCitation" : "232", "previouslyFormattedCitation" : "²³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }232 Latex agglutination methods have been used for the detection of CrAg in respiratory samples in all published studies. The performance of the LFA in the diagnosis of pulmonary cryptococcosis has not been evaluated. Although BAL and lung aspirate have potential as a diagnostic tool, bronchoscopy is an invasive method. It is unlikely bronchoscopy will be performed unless the patient presents with nodules and there is a suspicion of malignancy or the clinical presentation is severe. Sputum may prove to be an alternative sample type for early diagnosis of pulmonary cryptococcosis as Cryptococcus cells can be detected both in sputum and lung aspirates by cytology.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jmii.2014.02.005", "ISSN" : "16841182", "PMID" : "24767416", "author" : [ { "dropping-particle" : "", "family" : "Jan", "given" : "I. Shiow", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Wern Cherng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lo", "given" : "Shyh Chyi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weng", "given" : "Ming Hsiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Li Na", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Microbiology, Immunology and Infection", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "463-464", "publisher" : "Elsevier Taiwan LLC", "title" : "<i> Cryptococcus neoformans</i> in sputum and lung aspiration cytology smears", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³³", "plainTextFormattedCitation" : "233", "previouslyFormattedCitation" : "²³³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }233 Molecular detection Molecular detection of Cryptococcus is required in specific conditions where other diagnostic tools have failed to confirm a diagnosis of cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Diaz", "given" : "Mara R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "M Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "547-564", "title" : "Diagnostic approach based on capsular antigen, capsule detection, Beta-glucan, and DNA analysis", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹⁷", "plainTextFormattedCitation" : "217", "previouslyFormattedCitation" : "²¹⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }217 One of the circumstances is when there is positive result from histological examination but the culture presents a negative result. These molecular methods include pan-fungal PCR, DNA sequencing for identification, multiplex PCR, isothermal amplification method and probe-based microarrays.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/JCM.02895-13", "ISBN" : "0095-1137", "ISSN" : "1098660X", "PMID" : "24478409", "abstract" : "A molecular diagnostic technique based on real-time PCR was developed for the simultaneous detection of three of the most frequent causative agents of fungal opportunistic pneumonia in AIDS patients: Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii. This technique was tested in cultured strains and in clinical samples from HIV-positive patients. The methodology used involved species-specific molecular beacon probes targeted to the internal transcribed spacer regions of the rDNA. An internal control was also included in each assay. The multiplex real-time PCR assay was tested in 24 clinical strains and 43 clinical samples from AIDS patients with proven fungal infection. The technique developed showed high reproducibility (r(2) of >0.98) and specificity (100%). For H. capsulatum and Cryptococcus spp., the detection limits of the method were 20 and 2 fg of genomic DNA/20 \u03bcl reaction mixture, respectively, while for P. jirovecii the detection limit was 2.92 log10 copies/20 \u03bcl reaction mixture. The sensitivity in vitro was 100% for clinical strains and 90.7% for clinical samples. The assay was positive for 92.5% of the patients. For one of the patients with proven histoplasmosis, P. jirovecii was also detected in a bronchoalveolar lavage sample. No PCR inhibition was detected. This multiplex real-time PCR technique is fast, sensitive, and specific and may have clinical applications.", "author" : [ { "dropping-particle" : "", "family" : "Gago", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esteban", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valero", "given" : "Clara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "La Bellacasa", "given" : "Jorge Puig", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buitrago", "given" : "Maria Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1168-1176", "title" : "A multiplex real-time PCR assay for identification of <i>Pneumocystis jirovecii</i>, <i>Histoplasma capsulatum</i>,and <i>Cryptococcus neoformans</i>/<i>Cryptococcus gattii</i> in samples from AIDS patients with opportunistic pneumonia", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1128/JCM.00064-13", "ISBN" : "0095-1137", "ISSN" : "00951137", "PMID" : "23536400", "abstract" : "A singleplex PCR assay using a single primer pair targeting the putative sugar transporter gene was developed here to distinguish Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, and Cryptococcus gattii according to the distinct size of the amplicon. The interspecies and intravarietal hybrids were also characterized on the basis of distinct combined profiles of amplicons. This PCR assay is a rapid, simple, and reliable approach suitable for laboratory diagnoses and large-scale epidemiologic studies.", "author" : [ { "dropping-particle" : "", "family" : "Feng", "given" : "Xiaobo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fu", "given" : "Xiaohua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ling", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Zhirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1920-1923", "title" : "Development of a singleplex PCR assay for rapid identification and differentiation of <i>Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, Cryptococcus gattii</i>, and hybrids.", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.bjid.2014.09.004", "ISSN" : "16784391", "PMID" : "25523072", "abstract" : "Aim: This study evaluated the use of polymerase chain reaction for cryptococcal meningitis diagnosis in clinical samples. Materials and methods: The sensitivity and specificity of the methodology were evaluated using eight Cryptococcus neoformans/C. gattii species complex reference strains and 165 cerebrospinal fluid samples from patients with neurological diseases divided into two groups: 96 patients with cryptococcal meningitis and AIDS; and 69 patients with other neurological opportunistic diseases (CRL/AIDS). Two primer sets were tested (CN4-CN5 and the multiplex CNa70S-CNa70A/CNb49S-CNb-49A that amplify a specific product for C. neoformans and another for C. gattii). Results: CN4-CN5 primer set was positive in all Cryptococcus standard strains and in 94.8% in DNA samples from cryptococcal meningitis and AIDS group. With the multiplex, no 448-bp product of C. gattii was observed in the clinical samples of either group. The 695. bp products of C. neoformans were observed only in 64.6% of the cryptococcal meningitis and AIDS group. This primer set was negative for two standard strains. The specificity based on the negative samples from the CTL/AIDS group was 98.5% in both primer sets. Conclusions: These data suggest that the CN4/CN5 primer set was highly sensitive for the identification of C. neoformans/C. gattii species complex in cerebrospinal fluid samples from patients with clinical suspicion of cryptococcal meningitis.", "author" : [ { "dropping-particle" : "", "family" : "Martins", "given" : "Marilena dos Anjos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brighente", "given" : "Kate Bastos Santos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matos", "given" : "Terezinha Aparecida", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vidal", "given" : "Jose Ernesto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hipolito", "given" : "Daise Damaris Carnietto", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira-Chioccola", "given" : "Vera Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brazilian Journal of Infectious Diseases", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "62-67", "publisher" : "Elsevier Editora Ltda", "title" : "Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: Comparison of primer sets for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> species complex", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^234\u2013236", "plainTextFormattedCitation" : "234\u2013236", "previouslyFormattedCitation" : "^234\u2013236" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }234–236The conventional method for Cryptococcus species differentiation is a CGB test. However, studies revealed that CGB test is inferior than PCR in distinguishing species of Cryptococcus in 4.58% of samples.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/13693780701824429", "ISBN" : "1369-3786 (Print)\\r1369-3786 (Linking)", "ISSN" : "13693786", "PMID" : "18415847", "abstract" : "Members of the Cryptococcus species complex are encapsulated basidiomycetous yeasts, which can affect the central nervous system (CNS) and if untreated may cause meningitis. Cryptococcus neoformans is an opportunistic pathogen causing infections mainly in immunocompromised individuals. Cryptococcus gattii is a primary pathogen responsible for a high incidence of cryptococcomas in the lung and brain and shows a delayed response to antifungal therapy. The differentiation between the two species is primarily based on their growth on and color change of canavanine - glycine-bromothymol blue agar (CGB). Since this test is not always reliable, a multiplex PCR to identify both Cryptococcus species using more than 130 samples was standardized and the results obtained compared to those with the CGB test, using the Crypto Check serotyping kit as the standard. The multiplex PCR was shown to be more specific than the CGB test, in that results obtained with it were in agreement with those from serotyping all the samples, while the data from the CGB test disagreed with 6 out of 131 samples.", "author" : [ { "dropping-particle" : "", "family" : "Leal", "given" : "Ana Lusia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faganello", "given" : "Josiane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassanesi", "given" : "Maria Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vainstein", "given" : "Marilene H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical mycology : official publication of the International Society for Human and Animal Mycology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "377-383", "title" : "<i>Cryptococcus</i> species identification by multiplex PCR.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.vetmic.2011.06.038", "ISBN" : "1873-2542 (Electronic)\\r0378-1135 (Linking)", "ISSN" : "03781135", "PMID" : "21802868", "abstract" : "The extraordinary ability of Cryptococcus species to cause disease has focused the attention of scientists on finding ways to improve their identification methods. In this study, PCR-REA, manual methods (morphological and biochemical characteristics), API 20C and VITEK 2 were used to test identify a total of 30 Cryptococcus spp. from human and veterinary sources. PCR-REA was performed using the capsular region as amplification target followed by restriction with the enzymes AgeI, BsmFI and HpaII. PCR-REA identified the strains as C. neoformans var. grubii (n=19) and C. gattii (n=8). There was no significant difference between the API 20C AUX and VITEK 2 when compared to manual methods for the identification of Cryptococcus spp. However, none of these non-manual methods were able to detect C. gattii samples. PCR-REA showed a greater level of concordance with the manual method, besides being faster and more sensitive than the other methods. Therefore, it is indicated for routine identification of Cryptococcus spp. strains. \u00a9 2011 Elsevier B.V.", "author" : [ { "dropping-particle" : "", "family" : "Cordeiro", "given" : "Rossana Aguiar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costa", "given" : "Ana Karoline Freire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brilhante", "given" : "Raimunda S\u00e2mia Nogueira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lima", "given" : "Rita Amanda Chaves", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castelo-Branco", "given" : "D\u00e9bora de Souza Collares Maia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ribeiro", "given" : "Joyce Fonteles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monteiro", "given" : "Andr\u00e9 Jalles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocha", "given" : "Francisco Airton Castro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sidrim", "given" : "Jos\u00e9 J\u00falio Costa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocha", "given" : "Marcos F\u00e1bio Gadelha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Veterinary Microbiology", "id" : "ITEM-2", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "180-184", "title" : "PCR-REA as an important tool for the identification of <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> from human and veterinary sources", "type" : "article-journal", "volume" : "154" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^237,238", "plainTextFormattedCitation" : "237,238", "previouslyFormattedCitation" : "^237,238" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }237,238 Moreover, it provides rapid identification and may identify mating-type profiles via amplification of the STE (sterile) gene sequences.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-0691.2004.00972.x", "ISBN" : "1198-743X (Print)\\r1198-743X (Linking)", "ISSN" : "1198743X", "PMID" : "15606637", "abstract" : "Mating type plays an important role in the epidemiology and virulence of Cryptococcus neoformans. The present study designed a multiplex PCR method to distinguish the six mating type patterns (Aa, Da, Aalpha, Dalpha, Aa/Dalpha, and Aalpha/Da) of C. neoformans var. neoformans. PCR amplification identified one fragment for Aa (860 bp), Dalpha (413 bp) and Da (645 bp) strains, two fragments for Aalpha (320 and 400 bp) and Aa/Dalpha (860 and 413 bp) strains, and three fragments (645, 400, 320 bp) for an Aalpha/Da strain. The method appears to be a valid, simple and relatively inexpensive tool for epidemiological and virulence studies.", "author" : [ { "dropping-particle" : "", "family" : "Esposto", "given" : "M. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cogliati", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tortorano", "given" : "A. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viviani", "given" : "Marianna A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1092-1094", "publisher" : "European Society of Clinical Infectious Diseases", "title" : "Determination of <i>Cryptococcus neoformans var. neoformans</i> mating type by multiplex PCR", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁹", "plainTextFormattedCitation" : "239", "previouslyFormattedCitation" : "²³⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }239 There are several studies that have used PCR for the direct detection of Cryptococcus spp. in respiratory samples (Table 4).ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/13693780701824429", "ISBN" : "1369-3786 (Print)\\r1369-3786 (Linking)", "ISSN" : "13693786", "PMID" : "18415847", "abstract" : "Members of the Cryptococcus species complex are encapsulated basidiomycetous yeasts, which can affect the central nervous system (CNS) and if untreated may cause meningitis. Cryptococcus neoformans is an opportunistic pathogen causing infections mainly in immunocompromised individuals. Cryptococcus gattii is a primary pathogen responsible for a high incidence of cryptococcomas in the lung and brain and shows a delayed response to antifungal therapy. The differentiation between the two species is primarily based on their growth on and color change of canavanine - glycine-bromothymol blue agar (CGB). Since this test is not always reliable, a multiplex PCR to identify both Cryptococcus species using more than 130 samples was standardized and the results obtained compared to those with the CGB test, using the Crypto Check serotyping kit as the standard. The multiplex PCR was shown to be more specific than the CGB test, in that results obtained with it were in agreement with those from serotyping all the samples, while the data from the CGB test disagreed with 6 out of 131 samples.", "author" : [ { "dropping-particle" : "", "family" : "Leal", "given" : "Ana Lusia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faganello", "given" : "Josiane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassanesi", "given" : "Maria Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vainstein", "given" : "Marilene H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical mycology : official publication of the International Society for Human and Animal Mycology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "377-383", "title" : "<i>Cryptococcus</i> species identification by multiplex PCR.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1128/JCM.02895-13", "ISBN" : "0095-1137", "ISSN" : "1098660X", "PMID" : "24478409", "abstract" : "A molecular diagnostic technique based on real-time PCR was developed for the simultaneous detection of three of the most frequent causative agents of fungal opportunistic pneumonia in AIDS patients: Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii. This technique was tested in cultured strains and in clinical samples from HIV-positive patients. The methodology used involved species-specific molecular beacon probes targeted to the internal transcribed spacer regions of the rDNA. An internal control was also included in each assay. The multiplex real-time PCR assay was tested in 24 clinical strains and 43 clinical samples from AIDS patients with proven fungal infection. The technique developed showed high reproducibility (r(2) of >0.98) and specificity (100%). For H. capsulatum and Cryptococcus spp., the detection limits of the method were 20 and 2 fg of genomic DNA/20 \u03bcl reaction mixture, respectively, while for P. jirovecii the detection limit was 2.92 log10 copies/20 \u03bcl reaction mixture. The sensitivity in vitro was 100% for clinical strains and 90.7% for clinical samples. The assay was positive for 92.5% of the patients. For one of the patients with proven histoplasmosis, P. jirovecii was also detected in a bronchoalveolar lavage sample. No PCR inhibition was detected. This multiplex real-time PCR technique is fast, sensitive, and specific and may have clinical applications.", "author" : [ { "dropping-particle" : "", "family" : "Gago", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esteban", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valero", "given" : "Clara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "La Bellacasa", "given" : "Jorge Puig", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buitrago", "given" : "Maria Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1168-1176", "title" : "A multiplex real-time PCR assay for identification of <i>Pneumocystis jirovecii</i>, <i>Histoplasma capsulatum</i>,and <i>Cryptococcus neoformans</i>/<i>Cryptococcus gattii</i> in samples from AIDS patients with opportunistic pneumonia", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1128/JCM.00064-13", "ISBN" : "0095-1137", "ISSN" : "00951137", "PMID" : "23536400", "abstract" : "A singleplex PCR assay using a single primer pair targeting the putative sugar transporter gene was developed here to distinguish Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, and Cryptococcus gattii according to the distinct size of the amplicon. The interspecies and intravarietal hybrids were also characterized on the basis of distinct combined profiles of amplicons. This PCR assay is a rapid, simple, and reliable approach suitable for laboratory diagnoses and large-scale epidemiologic studies.", "author" : [ { "dropping-particle" : "", "family" : "Feng", "given" : "Xiaobo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fu", "given" : "Xiaohua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ling", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Zhirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1920-1923", "title" : "Development of a singleplex PCR assay for rapid identification and differentiation of <i>Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, Cryptococcus gattii</i>, and hybrids.", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1136/jclinpath-2014-202790", "author" : [ { "dropping-particle" : "", "family" : "Ogundeji", "given" : "Adepemi O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albertyn", "given" : "Jacobus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pohl", "given" : "Carolina H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sebolai", "given" : "Olihile M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Pathol", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-6", "title" : "Method for identification of <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> useful in resource-limited settings", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISBN" : "0095-1137", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hossain", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-5", "issue" : "11", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "2826-2828", "title" : "Detection of <i>Cryptococcus neoformans</i> gene in patients with pulmonary crptococcosis", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1590/S0036-46652007000400002", "ISBN" : "0036-4665 (Print)\\r0036-4665 (Linking)", "ISSN" : "00364665", "PMID" : "17823747", "abstract" : "Cryptococcus neoformans is an encapsulated yeast, etiological agent of cryptococcosis. The species is commonly associated with pigeon droppings and plant materials. The aim of the present work was to verify the presence of the yeast in pigeon droppings, and to identify the isolates obtained in serotypes and mating types (MAT). Ten samples of pigeon droppings were collected in the rural area of the city of Alfenas, Brazil. Samples were inoculated in agar Niger medium for fungal isolation and 22 isolates with characteristics of C. neoformans were obtained. The serotypes and MAT were determined by multiplex PCR using specific primers. Serotypes were also determined by using the Kit Crypto Check. Among the 22 samples evaluated, eight were identified as C. neoformans by classic identification tests. These samples were characterized as serotype A by the Kit Crypto check and as serotype A MAT alpha by the multiplex PCR. The present study reinforces the evidence that pigeon droppings are a reservoir for C. neoformans and confirms the prevalence of C. neoformans var. grubii (A alpha) among environmental isolates. It also demonstrates that multiplex PCR is an acceptable alternative for serotype analysis because it reduces the costs for each reaction and analyses serotype and MAT simultaneously.", "author" : [ { "dropping-particle" : "", "family" : "Carvalho", "given" : "Vivian Goncalves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Terceti", "given" : "Mateus Souza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dias", "given" : "Amanda Latercia Tranches", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paula", "given" : "Claudete Rodrigues", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyon", "given" : "Juliana Pereira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siqueira", "given" : "Antonio Martins", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franco", "given" : "Marilia Caixeta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-6", "issue" : "4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "207-210", "title" : "Serotype and mating type characterization of <i>Cryptococcus neoformans</i> by multiplex PCR", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1128/CDLI.9.2.461", "ISBN" : "1071-412X (Print)\\r1071-412X (Linking)", "ISSN" : "1071-412X", "PMID" : "11874894", "abstract" : "Two PCR protocols targeting the 18S rRNA gene of Cryptococcus neoformans were established, compared, and evaluated in murine cryptococcal meningitis. One protocol was designed as a nested PCR to be performed in conventional block thermal cyclers. The other protocol was designed as a quantitative single-round PCR adapted to LightCycler technology. One hundred brain homogenates and dilutions originating from 20 ICR mice treated with different azoles were examined. A fungal burden of 3 x 10(1) to 2.9 x 10(4) CFU per mg of brain tissue was determined by quantitative culture. Specific PCR products were amplified by the conventional and the LightCycler methods in 86 and 87 samples, respectively, with products identified by DNA sequencing and real-time fluorescence detection. An analytical sensitivity of 1 CFU of C. neoformans per mg of brain tissue and less than 10 CFU per volume used for extraction was observed for both PCR protocols, while homogenates of 70 organs from mice infected with other fungi were PCR negative. Specificity testing was performed with genomic DNA from 31 hymenomycetous fungal species and from the ustilaginomycetous yeast Malassezia furfur, which are phylogenetically related to C. neoformans. Twenty-four strains, including species of human skin flora like M. furfur and Trichosporon spp., were PCR negative. Amplification was observed with Cryptococcus amylolentus, Filobasidiella depauperata, Cryptococcus laurentii, and five species unrelated to clinical specimens. LightCycler PCR products from F. depauperata and Trichosporon faecale could be clearly discriminated by melting curve analysis. The sensitive and specific nested PCR assay as well as the rapid and quantitative LightCycler PCR assay might be useful for the diagnosis and monitoring of human cryptococcal infections.", "author" : [ { "dropping-particle" : "", "family" : "Bialek", "given" : "Ralf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bekure-Nemariam", "given" : "Kubrom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Najvar", "given" : "Laura K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alberdi", "given" : "Maria B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graybill", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reischl", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and diagnostic laboratory immunology", "id" : "ITEM-7", "issue" : "2", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "461-9", "title" : "Detection of <i>Cryptococcus neoformans</i> DNA in tissue samples by nested and real-time PCR assays.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "ISSN" : "0095-1137", "PMID" : "9774618", "abstract" : "We report the development of a nested-PCR-based assay for the detection of Cryptococcus neoformans in cerebrospinal fluid. The specificity and sensitivity of the test were assessed. The technique was then applied to 40 cerebrospinal fluid samples. We obtained positive reactions for all 21 clinical samples from patients who had been previously diagnosed as having cryptococcal meningitis by conventional techniques and negative reactions for all 19 negative controls. Nested PCR is here compared with other diagnostic methods currently used in patients' follow-up exams during anticryptococcal therapy.", "author" : [ { "dropping-particle" : "", "family" : "Rappelli", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Are", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fiori", "given" : "P L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappuccinelli", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aceti", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical microbiology", "id" : "ITEM-8", "issue" : "11", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "3438-40", "title" : "Development of a nested PCR for detection of <i>Cryptococcus neoformans</i> cerebrospinal fluid.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1016/j.bjid.2014.09.004", "ISSN" : "16784391", "PMID" : "25523072", "abstract" : "Aim: This study evaluated the use of polymerase chain reaction for cryptococcal meningitis diagnosis in clinical samples. Materials and methods: The sensitivity and specificity of the methodology were evaluated using eight Cryptococcus neoformans/C. gattii species complex reference strains and 165 cerebrospinal fluid samples from patients with neurological diseases divided into two groups: 96 patients with cryptococcal meningitis and AIDS; and 69 patients with other neurological opportunistic diseases (CRL/AIDS). Two primer sets were tested (CN4-CN5 and the multiplex CNa70S-CNa70A/CNb49S-CNb-49A that amplify a specific product for C. neoformans and another for C. gattii). Results: CN4-CN5 primer set was positive in all Cryptococcus standard strains and in 94.8% in DNA samples from cryptococcal meningitis and AIDS group. With the multiplex, no 448-bp product of C. gattii was observed in the clinical samples of either group. The 695. bp products of C. neoformans were observed only in 64.6% of the cryptococcal meningitis and AIDS group. This primer set was negative for two standard strains. The specificity based on the negative samples from the CTL/AIDS group was 98.5% in both primer sets. Conclusions: These data suggest that the CN4/CN5 primer set was highly sensitive for the identification of C. neoformans/C. gattii species complex in cerebrospinal fluid samples from patients with clinical suspicion of cryptococcal meningitis.", "author" : [ { "dropping-particle" : "", "family" : "Martins", "given" : "Marilena dos Anjos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brighente", "given" : "Kate Bastos Santos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matos", "given" : "Terezinha Aparecida", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vidal", "given" : "Jose Ernesto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hipolito", "given" : "Daise Damaris Carnietto", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira-Chioccola", "given" : "Vera Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brazilian Journal of Infectious Diseases", "id" : "ITEM-9", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "62-67", "publisher" : "Elsevier Editora Ltda", "title" : "Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: Comparison of primer sets for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> species complex", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{234\u2013237,240\u2013244}", "plainTextFormattedCitation" : "234\u2013237,240\u2013244", "previouslyFormattedCitation" : "^{234\u2013237,240\u2013244}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }234–237,240–244 Respiratory samples from proven pulmonary cryptococcocosis processed with multiplex RT PCR showed 90.7% sensitivity and 100% specificity to detect C. neoformans.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/JCM.02895-13", "ISBN" : "0095-1137", "ISSN" : "1098660X", "PMID" : "24478409", "abstract" : "A molecular diagnostic technique based on real-time PCR was developed for the simultaneous detection of three of the most frequent causative agents of fungal opportunistic pneumonia in AIDS patients: Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii. This technique was tested in cultured strains and in clinical samples from HIV-positive patients. The methodology used involved species-specific molecular beacon probes targeted to the internal transcribed spacer regions of the rDNA. An internal control was also included in each assay. The multiplex real-time PCR assay was tested in 24 clinical strains and 43 clinical samples from AIDS patients with proven fungal infection. The technique developed showed high reproducibility (r(2) of >0.98) and specificity (100%). For H. capsulatum and Cryptococcus spp., the detection limits of the method were 20 and 2 fg of genomic DNA/20 \u03bcl reaction mixture, respectively, while for P. jirovecii the detection limit was 2.92 log10 copies/20 \u03bcl reaction mixture. The sensitivity in vitro was 100% for clinical strains and 90.7% for clinical samples. The assay was positive for 92.5% of the patients. For one of the patients with proven histoplasmosis, P. jirovecii was also detected in a bronchoalveolar lavage sample. No PCR inhibition was detected. This multiplex real-time PCR technique is fast, sensitive, and specific and may have clinical applications.", "author" : [ { "dropping-particle" : "", "family" : "Gago", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esteban", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valero", "given" : "Clara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "La Bellacasa", "given" : "Jorge Puig", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buitrago", "given" : "Maria Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1168-1176", "title" : "A multiplex real-time PCR assay for identification of <i>Pneumocystis jirovecii</i>, <i>Histoplasma capsulatum</i>,and <i>Cryptococcus neoformans</i>/<i>Cryptococcus gattii</i> in samples from AIDS patients with opportunistic pneumonia", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁴", "plainTextFormattedCitation" : "234", "previouslyFormattedCitation" : "²³⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }234 PCR may also distinguish different species of Cryptococcus spp. using STR1F and STR1R as the target genes.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/JCM.00064-13", "ISBN" : "0095-1137", "ISSN" : "00951137", "PMID" : "23536400", "abstract" : "A singleplex PCR assay using a single primer pair targeting the putative sugar transporter gene was developed here to distinguish Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, and Cryptococcus gattii according to the distinct size of the amplicon. The interspecies and intravarietal hybrids were also characterized on the basis of distinct combined profiles of amplicons. This PCR assay is a rapid, simple, and reliable approach suitable for laboratory diagnoses and large-scale epidemiologic studies.", "author" : [ { "dropping-particle" : "", "family" : "Feng", "given" : "Xiaobo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fu", "given" : "Xiaohua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ling", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Zhirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1920-1923", "title" : "Development of a singleplex PCR assay for rapid identification and differentiation of <i>Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, Cryptococcus gattii</i>, and hybrids.", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁵", "plainTextFormattedCitation" : "235", "previouslyFormattedCitation" : "²³⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }235 Management of pulmonary cryptococcosisThe comprehensive management of pulmonary cryptococcosis depends on the host-immune status and the predilection of the disease, whether present as a sole disease in the lung, spread to CNS, or generally disseminated (Table 5).ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "978 92 4 150297 9", "author" : [ { "dropping-particle" : "", "family" : "WHO", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Geneva: World Health Organization", "id" : "ITEM-1", "issue" : "December", "issued" : { "date-parts" : [ [ "2011" ] ] }, "title" : "Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children: December 2011", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1164/rccm.2008-740ST", "ISBN" : "1535-4970 (Electronic)\\r1073-449X (Linking)", "ISSN" : "1073449X", "PMID" : "21193785", "abstract" : "With increasing numbers of immune-compromised patients with malignancy, hematologic disease, and HIV, as well as those receiving immunosupressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, the incidence of fungal infections has dramatically increased over recent years. Definitive diagnosis of pulmonary fungal infections has also been substantially assisted by the development of newer diagnostic methods and techniques, including the use of antigen detection, polymerase chain reaction, serologies, computed tomography and positron emission tomography scans, bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. At the same time, the introduction of new treatment modalities has significantly broadened options available to physicians who treat these conditions. While traditionally antifungal therapy was limited to the use of amphotericin B, flucytosine, and a handful of clinically available azole agents, current pharmacologic treatment options include potent new azole compounds with extended antifungal activity, lipid forms of amphotericin B, and newer antifungal drugs, including the echinocandins. In view of the changing treatment of pulmonary fungal infections, the American Thoracic Society convened a working group of experts in fungal infections to develop a concise clinical statement of current therapeutic options for those fungal infections of particular relevance to pulmonary and critical care practice. This document focuses on three primary areas of concern: the endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections of special concern for immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections.", "author" : [ { "dropping-particle" : "", "family" : "Limper", "given" : "Andrew H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knox", "given" : "Kenneth S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarosi", "given" : "George A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ampel", "given" : "Neil M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "John E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Catanzaro", "given" : "Antonino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "Scott F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hage", "given" : "Chadi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marr", "given" : "Kieren A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mody", "given" : "Christopher H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "David A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Respiratory and Critical Care Medicine", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "96-128", "title" : "An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients", "type" : "article-journal", "volume" : "183" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1086/649858", "ISBN" : "1537-6591 (Electronic)\\r1058-4838 (Linking)", "ISSN" : "1537-6591", "PMID" : "20047480", "abstract" : "Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Francoise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graybill", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "Richard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "Minh-Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pappas", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powderly", "given" : "William G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sobel", "given" : "Jack D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "291-322", "title" : "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^209,212,245", "plainTextFormattedCitation" : "209,212,245", "previouslyFormattedCitation" : "^209,212,245" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }209,212,245 Both immunocompromised and immunocompetent patients with cryptococcal pneumonia should have blood culture, CSF examination via lumbar puncture, and serum cryptococcal antigen testing.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "²²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22 Whenever CNS involvement is identified, this requires induction amphotericin B or fluconazole combined with flucytosine, and the adjustment of the dosage and duration of antifungal therapy, compared to pulmonary involvement alone.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1164/rccm.2008-740ST", "ISBN" : "1535-4970 (Electronic)\\r1073-449X (Linking)", "ISSN" : "1073449X", "PMID" : "21193785", "abstract" : "With increasing numbers of immune-compromised patients with malignancy, hematologic disease, and HIV, as well as those receiving immunosupressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, the incidence of fungal infections has dramatically increased over recent years. Definitive diagnosis of pulmonary fungal infections has also been substantially assisted by the development of newer diagnostic methods and techniques, including the use of antigen detection, polymerase chain reaction, serologies, computed tomography and positron emission tomography scans, bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. At the same time, the introduction of new treatment modalities has significantly broadened options available to physicians who treat these conditions. While traditionally antifungal therapy was limited to the use of amphotericin B, flucytosine, and a handful of clinically available azole agents, current pharmacologic treatment options include potent new azole compounds with extended antifungal activity, lipid forms of amphotericin B, and newer antifungal drugs, including the echinocandins. In view of the changing treatment of pulmonary fungal infections, the American Thoracic Society convened a working group of experts in fungal infections to develop a concise clinical statement of current therapeutic options for those fungal infections of particular relevance to pulmonary and critical care practice. This document focuses on three primary areas of concern: the endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections of special concern for immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections.", "author" : [ { "dropping-particle" : "", "family" : "Limper", "given" : "Andrew H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knox", "given" : "Kenneth S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarosi", "given" : "George A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ampel", "given" : "Neil M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "John E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Catanzaro", "given" : "Antonino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "Scott F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hage", "given" : "Chadi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marr", "given" : "Kieren A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mody", "given" : "Christopher H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "David A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Respiratory and Critical Care Medicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "96-128", "title" : "An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients", "type" : "article-journal", "volume" : "183" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1086/649858", "ISBN" : "1537-6591 (Electronic)\\r1058-4838 (Linking)", "ISSN" : "1537-6591", "PMID" : "20047480", "abstract" : "Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Francoise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graybill", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : 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cryptococcosis without CNS involvement.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1058-4838 (Print)\\n1058-4838", "ISSN" : "1058-4838", "PMID" : "8722844", "abstract" : "We retrospectively analyzed clinical outcome of meningeal and extrameningeal cryptococcosis in HIV-negative patients treated with amphotericin B (43 patients) or fluconazole (40 patients). Amphotericin B and fluconazole were prescribed equally to patients with neoplastic diseases and no risk factor, but organ transplant recipients and patients with other diseases were mostly given fluconazole and amphotericin B, respectively. Patients with more severe infections (i.e., meningitis, neurological disorders, or higher levels of antigen in cerebrospinal fluid) were more frequently treated with amphotericin B. A cure rate of > 70% was achieved regardless of the initial treatment and the severity of the infection. A Cox regression analysis showed that age of > 60 years, neoplastic disease, abnormal mental status, disseminated infection at the time of diagnosis, and therapeutic failure were independent predictors of death. Although fluconazole appears to be as effective as amphotericin B, only a prospective multicenter study will determine the best treatment regimen for patients with cryptococcal meningitis who do not have AIDS.", "author" : [ { "dropping-particle" : "", "family" : "Dromer", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathoulin", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupont", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brugiere", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Letenneur", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "S154-S160", "title" : "Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. French Cryptococcosis Study Group.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴⁷", "plainTextFormattedCitation" : "247", "previouslyFormattedCitation" : "²⁴⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }247 One study reported that eight of 25 (32%) non-immunocompromised patients experienced spontaneous recovery from isolated pulmonary cryptococcosis without antifungal treatment.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1378/chest.124.6.2143", "ISSN" : "0012-3692", "author" : [ { "dropping-particle" : "", "family" : "Nadrous", "given" : "Hassan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antonius", "given" : "Vera S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Terrell", "given" : "Christine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryu", "given" : "Jay H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST Journal", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "2143-2147", "title" : "Pulmonary cryptococcosis in nonimmunocompromised patients", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴⁸", "plainTextFormattedCitation" : "248", "previouslyFormattedCitation" : "²⁴⁸" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }248 A recent literature review of immunocompetent patients recommends fluconazole 400 mg/day orally for six to twelve months in either symptomatic or asymptomatic conditions.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ofid/ofw167", "author" : [ { "dropping-particle" : "", "family" : "Fisher", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valencia-rey", "given" : "Paula A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "William B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Open Forum Infectious Diseases", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-6", "title" : "Pulmonary cryptococcosis in the immunocompetent patient \u2014 many questions, some answers", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²", "plainTextFormattedCitation" : "2", "previouslyFormattedCitation" : "²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2 This is because antifungal therapy prevents or diminishes the risk of disease progression. Oral itraconazole or voriconazole 200 mg twice daily may be substituted if fluconazole is not available or contraindicated.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1164/rccm.2008-740ST", "ISBN" : "1535-4970 (Electronic)\\r1073-449X (Linking)", "ISSN" : "1073449X", "PMID" : "21193785", "abstract" : "With increasing numbers of immune-compromised patients with malignancy, hematologic disease, and HIV, as well as those receiving immunosupressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, the incidence of fungal infections has dramatically increased over recent years. Definitive diagnosis of pulmonary fungal infections has also been substantially assisted by the development of newer diagnostic methods and techniques, including the use of antigen detection, polymerase chain reaction, serologies, computed tomography and positron emission tomography scans, bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. At the same time, the introduction of new treatment modalities has significantly broadened options available to physicians who treat these conditions. While traditionally antifungal therapy was limited to the use of amphotericin B, flucytosine, and a handful of clinically available azole agents, current pharmacologic treatment options include potent new azole compounds with extended antifungal activity, lipid forms of amphotericin B, and newer antifungal drugs, including the echinocandins. In view of the changing treatment of pulmonary fungal infections, the American Thoracic Society convened a working group of experts in fungal infections to develop a concise clinical statement of current therapeutic options for those fungal infections of particular relevance to pulmonary and critical care practice. This document focuses on three primary areas of concern: the endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections of special concern for immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections.", "author" : [ { "dropping-particle" : "", "family" : "Limper", "given" : "Andrew H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knox", "given" : "Kenneth S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarosi", "given" : "George A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ampel", "given" : "Neil M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "John E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Catanzaro", "given" : "Antonino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "Scott F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hage", "given" : "Chadi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marr", "given" : "Kieren A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mody", "given" : "Christopher H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "David A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Respiratory and Critical Care Medicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "96-128", "title" : "An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients", "type" : "article-journal", "volume" : "183" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴⁵", "plainTextFormattedCitation" : "245", "previouslyFormattedCitation" : "²⁴⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }245 It may be necessary to add corticosteroid in cases of acute respiratory distress syndrome.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/649858", "ISBN" : "1537-6591 (Electronic)\\r1058-4838 (Linking)", "ISSN" : "1537-6591", "PMID" : "20047480", "abstract" : "Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Francoise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graybill", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "Richard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "Minh-Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pappas", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powderly", "given" : "William G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sobel", "given" : "Jack D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "291-322", "title" : "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹²", "plainTextFormattedCitation" : "212", "previouslyFormattedCitation" : "²¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }212 A recent study described a 10.6% mean fluconazole resistance from 4995 Cryptococcus isolates from HIV-positive patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/myc.12747", "ISBN" : "0000000154871", "ISSN" : "14390507", "PMID" : "29377368", "abstract" : "Fluconazole is the most commonly used antifungal agent for both the treatment of cryptococcal meningitis, and for prophylaxis against the disease. However, its prolonged use has the potential to exert selection pressure in favour of fluconazole-resistant strains. We evaluated the prevalence of fluconazole resistance in Cryptococcus spp. clinical isolates in 29 studies from 1988 to May 2017 included in EMBASE and MEDLINE databases. A total of 4995 Cryptococcus isolates from 3210 patients constituted this study; 248 (5.0%) of the isolates from relapsed episodes of cryptococcosis were included in this analysis. Eleven (38%) of the studies used minimum inhibitory concentrations (MICs) breakpoints of \u226564 \u03bcg/mL to define fluconazole resistance, 6 (21%) used \u226532 \u03bcg/mL, 11 (38%) used \u226516 \u03bcg/mL and 1 (3%) used \u226420 \u03bcg/mL. Overall, mean prevalence of fluconazole resistance was 12.1% (95% confidence interval [CI]: 6.7-17.6) for all isolates (n = 4995). Mean fluconazole resistance was 10.6% (95% CI: 5.5-15.6) for the incident isolates (n = 4747) and 24.1% (95% CI: -3.1-51.2) for the relapse isolates (n = 248). Of the 4995 isolates, 936 (18.7%) had MICs above the ecological cut-off value. Fluconazole resistance appears to be an issue in Cryptococcus isolates from patients with relapses. It remains unclear whether relapses occur due to resistance or other factors. There is an urgent need to establish antifungal breakpoints for Cryptococcus spp.", "author" : [ { "dropping-particle" : "", "family" : "Bongomin", "given" : "Felix", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oladele", "given" : "Rita O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gago", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moore", "given" : "Caroline B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richardson", "given" : "Malcolm D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycoses", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "290-297", "title" : "A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴⁹", "plainTextFormattedCitation" : "249", "previouslyFormattedCitation" : "²⁴⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }249 The rate of fluconazole resistance is increasing over time which is an alarming rate for cryptococcosis management.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/AAC.01299-15.Address", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "Kyle D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Achan", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hullsiek", "given" : "Kathy Huppler", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mcdonald", "given" : "Tami R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okagaki", "given" : "Laura H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alhadab", "given" : "Ali A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akampurira", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhein", "given" : "Joshua R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meya", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boulware", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Antimicrobial Agents and Chemotherapy", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "7197-7204", "title" : "Increased antifungal drug resistance in clinical isolates of <i> Cryptococcus neoformans</i> in Uganda", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/s12879-015-1023-8", "ISBN" : "1471-2334", "ISSN" : "14712334", "PMID" : "26194004", "abstract" : "BACKGROUND This study aimed to investigate the rate of fluconazole-non-susceptible Cryptococcus neoformans in Southern Taiwan for the period 2001-2012 and analyze the risk factors for acquiring it among patients with invasive cryptococcosis. METHODS All enrolled strains were isolated from blood or cerebrospinal fluid samples of the included patients. If a patient had multiple positive results for C. neoformans, only the first instance was enrolled. Susceptibility testing was performed using the Clinical and Laboratory Standards Institutes M27-A3 broth micro-dilution method. The MIC interpretative criteria for susceptibility to fluconazole were \u2264 8 \u03bcg/ml. A total of 89 patients were included. Patients (n = 59) infected by fluconazole-susceptible strains were compared with those (n = 30) infected by non-susceptible strains. The patients' demographic and clinical characteristics were analyzed. RESULTS The rate of fluconazole-non-susceptible C. neoformans in the study period significantly increased over time (p < 0.001). The C. neoformans isolated in 2011-2012 (odds ratio: 10.68; 95 % confidence interval: 2.87-39.74; p < 0.001) was an independent predictive factor for the acquisition of fluconazole-non-susceptible C. neoformans. CONCLUSIONS The rate of fluconazole-non-susceptible C. neoformans has significantly increased recently. Continuous and large-scale anti-fungal susceptibility tests for C. neoformans are warranted to confirm this trend.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Yi Chun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Tzu Yao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jien Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Fang Ju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chien", "given" : "Chun Chih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Chen Hsiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Cheng Hsien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Infectious Diseases", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-7", "publisher" : "BMC Infectious Diseases", "title" : "Increasing trend of fluconazole-non-susceptible Cryptococcus neoformans in patients with invasive cryptococcosis: A 12-year longitudinal study", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^183,250", "plainTextFormattedCitation" : "183,250", "previouslyFormattedCitation" : "^179,250" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }183,250 There is an urgent need for novel antifungal to counter the resistance strains of Cryptococcus.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/nyas.13739", "author" : [ { "dropping-particle" : "", "family" : "Geddes-McAlister", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shapiro", "given" : "Rebecca S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "1-22", "title" : "New pathogens , new tricks : emerging , drug-resistant fungal pathogens and future prospects for antifungal therapeutics", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵¹", "plainTextFormattedCitation" : "251", "previouslyFormattedCitation" : "²⁵¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }251 APX001A, VT-1129, and T-2307 are being developed as the new therapeutic options for cryptococcosis. APX001A already completed phase II clinical trial while VT-1129 and T-2307 developed passed phase I clinical trial.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/AAC.00523-18", "author" : [ { "dropping-particle" : "", "family" : "Shaw", "given" : "Karen J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schell", "given" : "Wiley A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Covel", "given" : "Jonathan.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duboc", "given" : "Gisele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giamberardino", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moloney", "given" : "Molly.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soltow", "given" : "Quinlyn A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tenor", "given" : "Jennifer L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toffaletti", "given" : "Dena L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trzoss", "given" : "Michael.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Webb", "given" : "Peter.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Antimicrobial Agents and Chemotherapy", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2018" ] ] }, "page" : "1-36", "title" : "In vitro and in vivo evaluation of APX001A/APX001 and other Gwt1 inhibitors against Cryptococcus", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/jac/dkx020", "ISBN" : "0081764318389", "ISSN" : "14602091", "PMID" : "28201509", "abstract" : "Objectives: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against the majority of fungal pathogens. In this study, the antifungal activity of T-2307 against Cryptococcus gattii was evaluated in comparison with those of amphotericin B, fluconazole and voriconazole in vitro and in vivo.Methods: The MICs for 15 clinical isolates were determined according to CLSI guidelines and time\u2013kill studies were performed using C. gattii YF2784. In a murine model for intranasal pulmonary infection caused by C. gattii YF2784, the test compounds were administered once daily for 7 days from 2\u2009h or 14 days post-infection. The viable counts in the lungs and brain were determined at 21 days post-infection.Results: The MIC range, MIC50, MIC90 and geometric mean MIC of T-2307 were 0.0078\u20130.0625, 0.0313, 0.0625 and 0.0394\u2009mg/L, respectively. The MIC of T-2307 was significantly lower than those of fluconazole, voriconazole and amphotericin B. T-2307 showed concentration-dependent fungicidal activity at 4 times the MIC or higher. Administration of T-2307 at 2\u2009mg/kg/day, amphotericin B at 1\u2009mg/kg/day and fluconazole at 160\u2009mg/kg/day from 2\u2009h post-infection significantly reduced viable counts in the lungs and brain. However, when the administration was started 14 days post-infection, only T-2307 significantly reduced the viable counts in both the lungs and the brain at 1\u2009mg/kg/day.Conclusions: T-2307 shows excellent in vitro and in vivo antifungal activities against C. gattii and would be a promising new candidate for the treatment of cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Nishikawa", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fukuda", "given" : "Yoshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsuyama", "given" : "Junichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Masato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Akitaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takazono", "given" : "Takahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saijo", "given" : "Tomomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Kazuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Shigeki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imamura", "given" : "Yoshifumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukae", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Antimicrobial Chemotherapy", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1709-1713", "title" : "In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: An emerging fungal pathogen", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/mmy/myw089", "ISSN" : "14602709", "PMID" : "27664991", "abstract" : "Although antifungal drug resistance in the human fungal pathogen Cryptococcus neoformans is relatively uncommon, fluconazole-resistant strains are problematic for preemptive treatment of cryptococcal antigenemia or during cryptococcal meningitis consolidation therapy. We analyzed activity of the experimental antifungal VT-1129 on 51 clinical Cryptococcus neoformans isolates previously screened for fluconazole resistance; with an emphasis on fluconazole dose-dependent (MIC 16-32\u00a0\u03bcg/ml) or resistant (MIC \u2265 64\u00a0\u03bcg/ml) isolates. Overall, the VT-1129 geometric mean MIC was 0.027\u00a0\u03bcg/ml. The VT-1129 MIC50 was 0.05\u00a0\u03bcg/ml and 0.25\u00a0\u03bcg/ml for dose-dependent (n = 27) and resistant isolates (n = 6), respectively. These data suggest VT-1129 shows potential for use against fluconazole-resistant Cryptococcus.", "author" : [ { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vedula", "given" : "Priya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Kyle D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meya", "given" : "David B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garvey", "given" : "Edward P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoekstra", "given" : "William J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schotzinger", "given" : "Robert J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boulware", "given" : "David R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical mycology", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "453-456", "title" : "Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^252\u2013254", "plainTextFormattedCitation" : "252\u2013254", "previouslyFormattedCitation" : "^252\u2013254" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }252–254 T-2307 may have value in pulmonary cryptococcosis as in a murine model as it prevents alveolar collapse while this important activity is not observed with fluconazole and amphotericin B.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/jac/dkx020", "ISBN" : "0081764318389", "ISSN" : "14602091", "PMID" : "28201509", "abstract" : "Objectives: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against the majority of fungal pathogens. In this study, the antifungal activity of T-2307 against Cryptococcus gattii was evaluated in comparison with those of amphotericin B, fluconazole and voriconazole in vitro and in vivo.Methods: The MICs for 15 clinical isolates were determined according to CLSI guidelines and time\u2013kill studies were performed using C. gattii YF2784. In a murine model for intranasal pulmonary infection caused by C. gattii YF2784, the test compounds were administered once daily for 7 days from 2\u2009h or 14 days post-infection. The viable counts in the lungs and brain were determined at 21 days post-infection.Results: The MIC range, MIC50, MIC90 and geometric mean MIC of T-2307 were 0.0078\u20130.0625, 0.0313, 0.0625 and 0.0394\u2009mg/L, respectively. The MIC of T-2307 was significantly lower than those of fluconazole, voriconazole and amphotericin B. T-2307 showed concentration-dependent fungicidal activity at 4 times the MIC or higher. Administration of T-2307 at 2\u2009mg/kg/day, amphotericin B at 1\u2009mg/kg/day and fluconazole at 160\u2009mg/kg/day from 2\u2009h post-infection significantly reduced viable counts in the lungs and brain. However, when the administration was started 14 days post-infection, only T-2307 significantly reduced the viable counts in both the lungs and the brain at 1\u2009mg/kg/day.Conclusions: T-2307 shows excellent in vitro and in vivo antifungal activities against C. gattii and would be a promising new candidate for the treatment of cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Nishikawa", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fukuda", "given" : "Yoshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsuyama", "given" : "Junichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Masato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Akitaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takazono", "given" : "Takahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saijo", "given" : "Tomomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Kazuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Shigeki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imamura", "given" : "Yoshifumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukae", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Antimicrobial Chemotherapy", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1709-1713", "title" : "In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: An emerging fungal pathogen", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵³", "plainTextFormattedCitation" : "253", "previouslyFormattedCitation" : "²⁵³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }253 Furthermore, established therapeutic drugs such as sertraline, amiodarone, thioridazine and tamoxifene are repurposed as anti-cryptococcal agents. Sertraline, a selective serotonin reuptake inhibitor, is under phase III clinical trial for adjuvant therapy of cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrd.2017.46", "ISBN" : "1474-1784 (Electronic)\r1474-1776 (Linking)", "ISSN" : "14741784", "PMID" : "28496146", "abstract" : "Invasive fungal infections continue to appear in record numbers as the immunocompromised population of the world increases, owing partially to the increased number of individuals who are infected with HIV and partially to the successful treatment of serious underlying diseases. The effectiveness of current antifungal therapies - polyenes, flucytosine, azoles and echinocandins (as monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or specific therapies) - in the management of these infections has plateaued. Although these drugs are clinically useful, they have several limitations, such as off-target toxicity, and drug-resistant fungi are now emerging. New antifungals are therefore needed. In this Review, I discuss the robust and dynamic antifungal pipeline, including results from preclinical academic efforts through to pharmaceutical industry products, and describe the targets, strategies, compounds and potential outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Reviews Drug Discovery", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "603-616", "title" : "The antifungal pipeline: A reality check", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵⁵", "plainTextFormattedCitation" : "255", "previouslyFormattedCitation" : "²⁵⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }255 Amiodarone and thioridazine show active killing of intraphagocyte C. neoformans in the lungs known as an inaccessible location for fluconazole and amphotericin B.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/EC.00314-12", "author" : [ { "dropping-particle" : "", "family" : "Butts", "given" : "Arielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Didone", "given" : "Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koselny", "given" : "Kristy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baxter", "given" : "Bonnie K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chabrier-rosello", "given" : "Yeissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wellington", "given" : "Melanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krysan", "given" : "Damian J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eukaryotic Cell", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "278-287", "title" : "A Repurposing Approach Identifies Off-Patent Drugs with Fungicidal Cryptococcal Activity , a Common Structural Chemotype , and Pharmacological Properties Relevant to the Treatment of", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵⁶", "plainTextFormattedCitation" : "256", "previouslyFormattedCitation" : "²⁵⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }256 Prognosis of pulmonary cryptococcosisPulmonary cryptococcosis lead to no deaths, relapses or dissemination amongst non-HIV patients in China, with a follow-up of two to eleven years.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bjid.2012.07.004", "ISBN" : "1413-8670", "ISSN" : "1678-4391", "PMID" : "23154046", "abstract" : "OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients.\\n\\nMETHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied.\\n\\nRESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2\u00b111.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients.\\n\\nCONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Jin-Quan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Ke-Jing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing-Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Can-Mao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Light", "given" : "Richard W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "531-9", "publisher" : "Elsevier Editora Ltda", "title" : "Pulmonary cryptococcosis in non-AIDS patients.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁴⁶", "plainTextFormattedCitation" : "146", "previouslyFormattedCitation" : "¹⁴⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }146 However, acute severe respiratory distress is a possible outcome of pulmonary cryptococcosis both in HIV or non-HIV patients.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ccr3.337", "ISSN" : "20500904", "PMID" : "26401280", "abstract" : "Pulmonary cryptococcosis is a common condition in HIV-infected patients which is frequently missed or misdiagnosed in resource-limited countries. We report a case of HIV/AIDS patient who was misdiagnosed with a fatal outcome. There is a need to implement screening tools to be used where the diagnosis may not be confirmed.", "author" : [ { "dropping-particle" : "", "family" : "Gunda", "given" : "Daniel W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakshi", "given" : "Fatma A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rambau", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kilonzo", "given" : "Semvua B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Case Reports", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "749-752", "title" : "Pulmonary cryptococcosis presenting as acute severe respiratory distress in a newly diagnosed HIV patient in Tanzania: a case report", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1378/chest.119.6.1865", "author" : [ { "dropping-particle" : "", "family" : "Vilchez", "given" : "Regis A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linden", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacomis", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costello", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "1865-1869", "title" : "Acute respiratory failure associated with pulmonary cryptococcosis in non- AIDS patients", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "1226-3303", "ISSN" : "12263303", "PMID" : "16646563", "abstract" : "A 36-year-old homosexual Mexican man was admitted to our hospital, with a 30-day history of fever and headache. Upon cerebrospinal fluid examination, the patient's white blood cell count was 1,580/L, total protein was 26 mg/dL, sugar was 17 mg/dL, and his intracranial pressure was 23 cmH2O. The patient was diagnosed with HIV (Human Immunodeficiency Virus) infection by serum Western blotting. Cryptococcus neoformans was isolated in cultures of the patient's blood and cerebrospinal fluids. Chest computerized tomography revealed diffuse reticulonodular infiltration and a ground-glass appearance in both perihilar regions, suggestive of either Pneumocystis carinii pneumonia or cryptococcal pneumonia. On the patient's 6th day in our hospital, bronchoalveolar lavage and transbronchial lung biopsy were conducted via bronchoscopy, and a pathologic examination of lung biopsy specimens revealed signs of cryptococcal pneumonia. This patient died on his 14th day in our hospital, as the result of acute respiratory failure, associated with cryptococcal pneumonia and disseminated cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "Kyoung Hwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "U. Im", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hyung Wook", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Guilsun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Sung Kyoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoo", "given" : "Jinyoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wie", "given" : "Seong Heon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Korean Journal of Internal Medicine", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "39-42", "title" : "Acute respiratory failure associated with cryptococcal pneumonia and disseminated cryptococcosis in an AIDS patient", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Visnegarwala", "given" : "Fehmida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graviss", "given" : "Edward A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacke", "given" : "Christine E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dural", "given" : "A Tarkan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Philip C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atmar", "given" : "Robert L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "Richard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Infectious Diseases", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "1231-1237", "title" : "Acute respiratory failure associated with cryptococcosis in patients with AIDS : Analysis of predictive factors", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{166,184,257,258}", "plainTextFormattedCitation" : "166,184,257,258", "previouslyFormattedCitation" : "^{166,184,257,258}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }166,184,257,258 A 10-year retrospective study concerning non-HIV pulmonary cryptococcosis reported that 33% of patients developed respiratory failure, with a 55% mortality rate.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1378/chest.119.6.1865", "author" : [ { "dropping-particle" : "", "family" : "Vilchez", "given" : "Regis A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linden", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacomis", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costello", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "1865-1869", "title" : "Acute respiratory failure associated with pulmonary cryptococcosis in non- AIDS patients", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶⁶", "plainTextFormattedCitation" : "166", "previouslyFormattedCitation" : "¹⁶⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }166 All cases of respiratory failures occurred within twenty-four hours of the patient arriving at the hospital. The mortality rate of pulmonary cryptococcosis in HIV patients in one study was 74% over the first year following diagnosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1058-4838 (Print)\\n1058-4838", "ISSN" : "10584838", "PMID" : "8527555", "abstract" : "We reviewed the records of 85 patients infected with both human immunodeficiency virus and Cryptococcus neoformans. Twenty-seven patients (32%) had pulmonary cryptococcosis. C. neoformans was cultured from bronchoalveolar lavage (BAL) or pleural fluid in 25 cases; the remaining two patients had cryptococcal antigen (CA) detected in BAL fluid and C. neoformans cultured from other sites. All but one of the 27 patients had detectable CA in serum. The CD4+ lymphocyte count was low in all cases (median, 24/mm3). Clinical manifestations of pulmonary cryptococcosis included fever (94%), cough (71%), dyspnea (7%), expectoration (4%), chest pain (2%), and hemoptysis (1%). Diffuse interstitial opacities (70.5%), focal interstitial abnormalities, alveolar opacities, adenopathies, cavitary lesions, and pleural effusions were evident. Outcome was poor (mean survival time, 23 weeks) despite treatment. Patients with localized pulmonary cryptococcosis appeared to have a higher CD4+ lymphocyte count, an earlier diagnosis, lower serum CA titers, fewer previous or concomitant infections, and a better prognosis than patients with disseminated cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Meyohas", "given" : "M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roux", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bollens", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chouaid", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rozenbaum", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meynard", "given" : "J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poirot", "given" : "J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frottier", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayaud", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "628-633", "title" : "Pulmonary cryptococcosis: localized and disseminated infections in 27 patients with AIDS.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁵⁹", "plainTextFormattedCitation" : "259", "previouslyFormattedCitation" : "²⁵⁹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }259 All of the patients who did not survive had disseminated infection. A recent study of pulmonary cryptococcosis in both immunocompromised and non-compromise patients showed 70.3% (n=71) were successfully treated.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.chest.2016.02.129", "ISSN" : "00123692", "author" : [ { "dropping-particle" : "", "family" : "Huang", "given" : "Jinbao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lan", "given" : "Chang-qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Hong-yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Qing-hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jia-fu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Heng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "A124", "publisher" : "American College of Chest Physicians", "title" : "Retrospective analysis of 117 chinese patients with pulmonary cryptococcosis", "type" : "article-journal", "volume" : "149" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹²⁶", "plainTextFormattedCitation" : "126", "previouslyFormattedCitation" : "¹²⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }126 Prevention of pulmonary cryptococcosisPrimary antifungal prophylaxis for cryptococcosis in HIV patients is only recommended for regions with a high rate of disease, high levels of antiretroviral drugs resistance, and restricted availability of highly active antiretroviral therapy (HAART).ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/649858", "ISBN" : "1537-6591 (Electronic)\\r1058-4838 (Linking)", "ISSN" : "1537-6591", "PMID" : "20047480", "abstract" : "Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Francoise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graybill", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "Richard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "Minh-Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pappas", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powderly", "given" : "William G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sobel", "given" : "Jack D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "291-322", "title" : "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹²", "plainTextFormattedCitation" : "212", "previouslyFormattedCitation" : "²¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }212 Randomised controlled trial studies found fluconazole as a first line prophylaxis, or itraconazole as a second line prophylaxis, for HIV patients with low CD4 counts effective.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S1473-3099(11)70245-6", "ISBN" : "1473-3099", "ISSN" : "14733099", "PMID" : "21982529", "abstract" : "Background: Cryptococcal disease remains an important cause of morbidity and mortality in HIV-infected individuals in sub-Saharan Africa, despite the introduction of antiretroviral therapy. We studied fluconazole as primary prophylaxis against cryptococcal disease in patients awaiting or starting antiretroviral therapy in Uganda. Methods: In this prospective, double-blind randomised controlled trial, we enrolled HIV-positive adults with CD4 counts less than 200 cells per ??L, cryptococcal antigen (CrAg)-negative, naive for antiretroviral therapy, and coming from five local AIDS organisations in Masaka district, Uganda. Enrolment took place between Sept 14, 2004, and Feb 1, 2008. Participants were randomly allocated to placebo or 200 mg fluconazole three times per week (1:1) in blocks of 40. Randomisation was done with ralloc procedure in Stata. Participants were reviewed after 4 weeks and referred for antiretroviral therapy, then seen every 8 weeks. Participants discontinued trial treatment when CD4 counts reached 200 cells per ??L (median 197 days). Primary endpoints were invasive cryptococcal disease and all-cause mortality. Secondary endpoints were time to first episode and incidence of oesophageal candidosis, time to first episode and incidence of oropharyngeal or vaginal candidosis, and time to first hospital admission or death. The primary safety endpoint was cessation of trial drug because of transaminase concentrations higher than five times the upper limit of normal (ULN), or other major adverse events. Analyses were done by intention to treat and included all participants enrolled in the trial. Participants and researchers were masked to group assignment. This trial is registered with controlled-, number ISRCTN 76481529. Results: Of 1519 individuals enrolled, 760 participants received fluconazole and 759 received placebo. 19 developed cryptococcal disease, one in the fluconazole group and 18 in the placebo group (p=0??0001); adjusted HR (aHR) 18??7 (95% CI 2??5-140??7). One case of cryptococcal disease could be prevented by treating 44??6 patients with baseline CD4 counts lower than 200 cells per ??L. Fluconazole was effective against cryptococcal disease both before (aHR=11??0 [1??4-85??3]) and after start of antiretroviral therapy (no cases in fluconazole vs seven cases on placebo). Seven participants died from cryptococcal disease, none in the fluconazole group. All-cause mortality (n=189) did not differ between the two groups (p=\u2026", "author" : [ { "dropping-particle" : "", "family" : "Parkes-Ratanshi", "given" : "Rosalind", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wakeham", "given" : "Katie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levin", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Namusoke", "given" : "Deodata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitworth", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coutinho", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mugisha", "given" : "Nathan Kenya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grosskurth", "given" : "Heiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamali", "given" : "Anatoli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lalloo", "given" : "David G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet Infectious Diseases", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "933-941", "publisher" : "Elsevier Ltd", "title" : "Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: A double-blind, randomised, placebo-controlled trial", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1086/514744", "ISBN" : "1058-4838", "PMID" : "884", "abstract" : "In a prospective, randomized, double-blind trial, 149 patients with advanced human immunodeficiency virus (HIV) infection were randomized to receive itraconazole capsules (200 mg daily) and 146 to receive a matched placebo. Both groups were monitored for evidence of fungal infections. Baseline characteristics of the two groups were similar. Failure of prophylaxis occurred in 29 (19%) of the itraconazole recipients and 42 (29%) of the placebo recipients (P = .004; log-rank test). There were 6 invasive fungal infections in the itraconazole group (4, histoplasmosis; 1, cryptococcosis; 1, aspergillosis) and 19 in the placebo group (10, histoplasmosis; 8, cryptococcosis; 1, aspergillosis) (P = .0007; log-rank test). Itraconazole significantly delayed time to onset of histoplasmosis (P = .03; log-rank test) and cryptococcosis (P = .0005; log-rank test). Prophylaxis failure due to recurrent or refractory mucosal candidiasis occurred with similar frequency in the two groups (itraconazole, 15%; placebo, 16%). A survival benefit was not demonstrated. Itraconazole generally was well tolerated. Primary prophylaxis with itraconazole capsules prevents histoplasmosis and cryptococcosis in patients with HIV infection", "author" : [ { "dropping-particle" : "", "family" : "McKinsey", "given" : "D S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheat", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cloud", "given" : "G A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pierce", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Black", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bamberger", "given" : "D M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutsch", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moskovitz", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "W E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauffman", "given" : "C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Infectious Diseases", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "1049-1056", "title" : "Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. National Institute of Allergy and Infectious Diseases Mycoses Study Group", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Powderly", "given" : "William G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finkelstein", "given" : "Dianne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feinberg", "given" : "Judith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frame", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "He", "given" : "Weili", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Host", "given" : "Charles", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hooton", "given" : "Thomas M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hyslop", "given" : "Newton", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "stephen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bozette", "given" : "Samuel A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "NIAID AIDS Clinical Trial Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England Journal of Medicine", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "700-705", "title" : "A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced Human Immunodeficiency Virus infection", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^260\u2013262", "plainTextFormattedCitation" : "260\u2013262", "previouslyFormattedCitation" : "^260\u2013262" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }260–262 Other prevention methods might include the Cryptococcus vaccines, although none are yet licensed.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fmicb.2012.00291", "ISBN" : "1664-302X (Electronic)\r1664-302X (Linking)", "ISSN" : "1664302X", "PMID" : "22973262", "abstract" : "Cryptococcus neoformans and C. gattii, the predominant etiological agents of cryptococcosis, can cause life-threatening infections of the central nervous system in immunocompromised and immunocompetent individuals. Cryptococcal meningoencephalitis is the most common disseminated fungal infection in AIDS patients, and C. neoformans remains the third most common invasive fungal infection among organ transplant recipients. Current anti-fungal drug therapies are oftentimes rendered ineffective due to drug toxicity, the emergence of drug resistant organisms, and/or the inability of the host's immune defenses to assist in eradication of the yeast. Therefore, there remains an urgent need for the development of immune-based therapies and/or vaccines to combat cryptococcosis. Studies in animal models have demonstrated the efficacy of various vaccination strategies and immune therapies to induce protection against cryptococcosis. This review will summarize the lessons learned from animal models supporting the feasibility of developing immunotherapeutics and vaccines to prevent cryptococcosis.", "author" : [ { "dropping-particle" : "", "family" : "Hole", "given" : "Camaron R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wormley", "given" : "Floyd L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers in Microbiology", "id" : "ITEM-1", "issue" : "AUG", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1-7", "title" : "Vaccine and immunotherapeutic approaches for the prevention of cryptococcosis: Lessons learned from animal models", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.ppat.1004843", "ISBN" : "1553-7366\\r1553-7374", "ISSN" : "1553-7374", "author" : [ { "dropping-particle" : "", "family" : "Leopold Wager", "given" : "Chrissy M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wormley", "given" : "Floyd L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLOS Pathogens", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "e1004843", "title" : "Is development of a vaccine against <i>Cryptococcus neoformans</i> feasible?", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1128/CVI.00130-08", "ISBN" : "1556-6811", "ISSN" : "15566811", "PMID" : "18524882", "abstract" : "Vaccination with P13, a peptide mimotope of the cryptococcal capsular polysaccharide glucuronoxylomannan (GXM), has been shown to confer protection against a subsequent lethal Cryptococcus neoformans challenge. In this study, we sought to investigate whether P13-based vaccines could be effective in an already-established infection. To address this question, we developed a systemic chronic cryptococcal infection model. We vaccinated chronically infected mice with P13-protein conjugates and monitored their survival. Compared to the controls, the conjugates prolonged the survival of chronically infected mice. The degree of protection was a function of the mouse strain (BALB/c or C57BL/6), the carrier protein (tetanus toxoid or diphtheria toxoid), and the route of infection (intraperitoneal or intravenous). Serum GXM levels were correlated with the day of death, but the correlation was driven by the carrier protein and mouse strain. The passive transfer of heat-treated sera from P13 conjugate-vaccinated mice conferred protection to na\u00efve BALB/c mice, indicating that antibody immunity could contribute to protection. The measurement of peripheral blood cytokine (gamma interferon [IFN-gamma], interleukin-10 [IL-10], and IL-6) gene expression showed that P13 conjugate-vaccinated BALB/c and C57BL/6 mice mounted a strong Th2 (IL-10)-like response relative to the Th1 (IFN-gamma)-like response, with the degree depending on the mouse strain and carrier protein. Taken together, our data suggest that a vaccine could hold promise in the setting of chronic cryptococcosis, and that vaccine efficacy could depend on immunomodulation and augmentation of the natural immune response of the host.", "author" : [ { "dropping-particle" : "", "family" : "Datta", "given" : "Kausik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lees", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pirofski", "given" : "Liise Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and Vaccine Immunology", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1176-1187", "title" : "Therapeutic efficacy of a conjugate vaccine containing a peptide mimotope of cryptococcal capsular polysaccharide glucuronoxylomannan", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1128/mBio.01905-15", "ISSN" : "21507511", "PMID" : "26695631", "abstract" : "UNLABELLED: A vaccine capable of protecting at-risk persons against infections due to Cryptococcus neoformans and Cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. Vaccine development has been hampered though, by lack of knowledge as to which antigens are immunoprotective and the need for an effective vaccine delivery system. We made alkaline extracts from mutant cryptococcal strains that lacked capsule or chitosan. The extracts were then packaged into glucan particles (GPs), which are purified Saccharomyces cerevisiae cell walls composed primarily of \u03b2-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of C. neoformans and C. gattii. The alkaline extract derived from the acapsular strain was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the most abundant proteins were identified. Separation of the alkaline extract by size exclusion chromatography revealed fractions that conferred protection when loaded in GP-based vaccines. Robust Th1- and Th17-biased CD4(+) T cell recall responses were observed in the lungs of vaccinated and infected mice. Thus, our preclinical studies have indicated promising cryptococcal vaccine candidates in alkaline extracts delivered in GPs. Ongoing studies are directed at identifying the individual components of the extracts that confer protection and thus would be promising candidates for a human vaccine.\\n\\nIMPORTANCE: The encapsulated yeast Cryptococcus neoformans and its closely related sister species, Cryptococcus gattii, are major causes of morbidity and mortality, particularly in immunocompromised persons. This study reports on the preclinical development of vaccines to protect at-risk populations from cryptococcosis. Antigens were extracted from Cryptococcus by treatment with an alkaline solution. The extracted antigens were then packaged into glucan particles, which are hollow yeast cell walls composed mainly of \u03b2-glucans. The glucan particle-based vaccines elicited robust T cell immune responses and protected mice from otherwise-lethal challenge with virulent strains of C. neoformans and C. gattii. The technology used for antigen extraction and subsequent loading into the glucan particle delivery system is relatively simple and can be applied to vaccine development against other pathogens.", "author" : [ { "dropping-particle" : "", "family" : "Specht", "given" : "Charles A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Chrono K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Haibin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tipper", "given" : "Donald J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Zu T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lodge", "given" : "Jennifer K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leszyk", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ostroff", "given" : "Gary R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levitz", "given" : "Stuart M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "mBio", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-11", "title" : "Protection against experimental cryptococcosis following vaccination with glucan particles containing cryptococcus alkaline extracts", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^263\u2013266", "plainTextFormattedCitation" : "263\u2013266", "previouslyFormattedCitation" : "^263\u2013266" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }263–266 This approach has potential value because of the high risk of the antifungal toxicity, the rise of antifungal resistances in Cryptococcus, and immune defects that hamper the Cryptococcus eradication.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s12981-016-0106-y", "ISBN" : "1298101601267", "ISSN" : "17426405", "PMID" : "27182275", "abstract" : "Tuberculosis (TB) has been the most common opportunistic infection and cause of mortality among HIV-infected patients, especially in resource-limited countries. Clinical manifestations of TB vary and depend on the degree of immunodeficiency. Sputum microscopy and culture with drug-susceptibility testing are recommended as a standard method for diagnosing active TB. TB-related mortality in HIV-infected patients is high especially during the first few months of treatment. Integrated therapy of both HIV and TB is feasible and efficient to control the diseases and yield better survival. Randomized clinical trials have shown that early initiation of antiretroviral therapy (ART) improves survival of HIV-infected patients with TB. A delay in initiating ART is common among patients referred from TB to HIV separate clinics and this delay may be associated with increased mortality risk. Integration of care for both HIV and TB using a single facility and a single healthcare provider to deliver care for both diseases is a successful model. For TB treatment, HIV-infected patients should receive at least the same regimens and duration of TB treatment as HIV-uninfected patients. Currently, a 2-month initial intensive phase of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 4 months of continuation phase of isoniazid and rifampin is considered as the standard treatment of drug-susceptible TB. ART should be initiated in all HIV-infected patients with TB, irrespective of CD4 cell count. The optimal timing to initiate ART is within the first 8 weeks of starting antituberculous treatment and within the first 2 weeks for patients who have CD4 cell counts <50 cells/mm3. Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART remains a first-line regimen for HIV-infected patients with TB in resource-limited settings. Although a standard dose of both efavirenz and nevirapine can be used, efavirenz is preferred because of more favorable treatment outcomes. In the settings where raltegravir is accessible, doubling the dose to 800 mg twice daily is recommended. Adverse reactions to either antituberculous or antiretroviral drugs, as well as immune reconstitution inflammatory syndrome, are common in patients receiving integrated therapy. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with TB.", "author" : [ { "dropping-particle" : "", "family" : "Srichatrapimuk", "given" : "Sirawat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sungkanuparph", "given" : "Somnuek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AIDS Research and Therapy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-15", "publisher" : "BioMed Central", "title" : "Integrated therapy for HIV and cryptococcosis", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.fgb.2014.10.003", "ISSN" : "1087-1845", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bicanic", "given" : "Tihana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Fungal Genetics and Biology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "49-54", "publisher" : "Elsevier Inc.", "title" : "Cryptococcosis diagnosis and treatment : What do we know now", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1128/AAC.01299-15.Address", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "Kyle D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Achan", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hullsiek", "given" : "Kathy Huppler", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mcdonald", "given" : "Tami R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okagaki", "given" : "Laura H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alhadab", "given" : "Ali A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akampurira", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhein", "given" : "Joshua R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meya", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boulware", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Antimicrobial Agents and Chemotherapy", "id" : "ITEM-3", "issue" : "12", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "7197-7204", "title" : "Increased antifungal drug resistance in clinical isolates of <i> Cryptococcus neoformans</i> in Uganda", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^183,267,268", "plainTextFormattedCitation" : "183,267,268", "previouslyFormattedCitation" : "^179,267,268" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }183,267,268 A recent preclinical study in mice utilising vaccines from the antigen extracts of Cryptococcus coated with glucan particles indicated potential advantages with a 60% 50 day survival rate.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/mBio.01905-15", "ISSN" : "21507511", "PMID" : "26695631", "abstract" : "UNLABELLED: A vaccine capable of protecting at-risk persons against infections due to Cryptococcus neoformans and Cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. Vaccine development has been hampered though, by lack of knowledge as to which antigens are immunoprotective and the need for an effective vaccine delivery system. We made alkaline extracts from mutant cryptococcal strains that lacked capsule or chitosan. The extracts were then packaged into glucan particles (GPs), which are purified Saccharomyces cerevisiae cell walls composed primarily of \u03b2-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of C. neoformans and C. gattii. The alkaline extract derived from the acapsular strain was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the most abundant proteins were identified. Separation of the alkaline extract by size exclusion chromatography revealed fractions that conferred protection when loaded in GP-based vaccines. Robust Th1- and Th17-biased CD4(+) T cell recall responses were observed in the lungs of vaccinated and infected mice. Thus, our preclinical studies have indicated promising cryptococcal vaccine candidates in alkaline extracts delivered in GPs. Ongoing studies are directed at identifying the individual components of the extracts that confer protection and thus would be promising candidates for a human vaccine.\\n\\nIMPORTANCE: The encapsulated yeast Cryptococcus neoformans and its closely related sister species, Cryptococcus gattii, are major causes of morbidity and mortality, particularly in immunocompromised persons. This study reports on the preclinical development of vaccines to protect at-risk populations from cryptococcosis. Antigens were extracted from Cryptococcus by treatment with an alkaline solution. The extracted antigens were then packaged into glucan particles, which are hollow yeast cell walls composed mainly of \u03b2-glucans. The glucan particle-based vaccines elicited robust T cell immune responses and protected mice from otherwise-lethal challenge with virulent strains of C. neoformans and C. gattii. The technology used for antigen extraction and subsequent loading into the glucan particle delivery system is relatively simple and can be applied to vaccine development against other pathogens.", "author" : [ { "dropping-particle" : "", "family" : "Specht", "given" : "Charles A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Chrono K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Haibin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tipper", "given" : "Donald J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Zu T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lodge", "given" : "Jennifer K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leszyk", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ostroff", "given" : "Gary R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levitz", "given" : "Stuart M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "mBio", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-11", "title" : "Protection against experimental cryptococcosis following vaccination with glucan particles containing cryptococcus alkaline extracts", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁶⁶", "plainTextFormattedCitation" : "266", "previouslyFormattedCitation" : "²⁶⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }266 Other studies using different models of Cryptococcus vaccines also support this approach as part of pulmonary cryptococcosis prevention methods.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/CVI.00130-08", "ISBN" : "1556-6811", "ISSN" : "15566811", "PMID" : "18524882", "abstract" : "Vaccination with P13, a peptide mimotope of the cryptococcal capsular polysaccharide glucuronoxylomannan (GXM), has been shown to confer protection against a subsequent lethal Cryptococcus neoformans challenge. In this study, we sought to investigate whether P13-based vaccines could be effective in an already-established infection. To address this question, we developed a systemic chronic cryptococcal infection model. We vaccinated chronically infected mice with P13-protein conjugates and monitored their survival. Compared to the controls, the conjugates prolonged the survival of chronically infected mice. The degree of protection was a function of the mouse strain (BALB/c or C57BL/6), the carrier protein (tetanus toxoid or diphtheria toxoid), and the route of infection (intraperitoneal or intravenous). Serum GXM levels were correlated with the day of death, but the correlation was driven by the carrier protein and mouse strain. The passive transfer of heat-treated sera from P13 conjugate-vaccinated mice conferred protection to na\u00efve BALB/c mice, indicating that antibody immunity could contribute to protection. The measurement of peripheral blood cytokine (gamma interferon [IFN-gamma], interleukin-10 [IL-10], and IL-6) gene expression showed that P13 conjugate-vaccinated BALB/c and C57BL/6 mice mounted a strong Th2 (IL-10)-like response relative to the Th1 (IFN-gamma)-like response, with the degree depending on the mouse strain and carrier protein. Taken together, our data suggest that a vaccine could hold promise in the setting of chronic cryptococcosis, and that vaccine efficacy could depend on immunomodulation and augmentation of the natural immune response of the host.", "author" : [ { "dropping-particle" : "", "family" : "Datta", "given" : "Kausik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lees", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pirofski", "given" : "Liise Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and Vaccine Immunology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1176-1187", "title" : "Therapeutic efficacy of a conjugate vaccine containing a peptide mimotope of cryptococcal capsular polysaccharide glucuronoxylomannan", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1128/IAI.00274-06", "ISBN" : "0019-9567 (Print)\\r0019-9567 (Linking)", "ISSN" : "00199567", "PMID" : "17210668", "abstract" : "We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with a Cryptococcus neoformans strain engineered to produce the Th1-type cytokine gamma interferon (IFN-gamma). Mice given a pulmonary infection with an IFN-gamma-producing C. neoformans strain were able to resolve the primary infection and demonstrated complete (100%) protection against a second pulmonary challenge with a pathogenic C. neoformans strain. Pulmonary cytokine analyses showed that Th1-type/proinflammatory cytokine and chemokine expression were significantly higher and Th2-type cytokine expression was significantly lower in mice infected with the IFN-gamma-producing C. neoformans strain compared to wild-type-infected mice. This increased pulmonary Th1-type cytokine expression was also associated with significantly lower pulmonary fungal burden and significantly higher pulmonary leukocyte and T-lymphocyte recruitment in mice infected with the IFN-gamma-producing C. neoformans strain compared to wild-type-infected mice. Our results demonstrate that pulmonary infection of mice with a C. neoformans strain expressing IFN-gamma results in the stimulation of local Th1-type anti-cryptococcal CMI responses and the development of protective host immunity against future pulmonary cryptococcal infections. The use of fungi engineered to produce host cytokines is a novel method to study immune responses to infection and may be useful in developing vaccine strategies in humans.", "author" : [ { "dropping-particle" : "", "family" : "Wormley", "given" : "Floyd L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steele", "given" : "Chad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Gary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "1453-1462", "title" : "Protection against cryptococcosis by using a murine gamma interferon-producing <i>Cryptococcus neoformans</i> strain", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0019-9567 (Print)\\r0019-9567 (Linking)", "ISSN" : "00199567", "PMID" : "1716613", "abstract" : "We synthesized Cryptococcus neoformans serotype A glucuronoxylomannan (GXM) conjugate vaccines under conditions suitable for human use to prevent disseminated cryptococcosis. The purified, sonicated GXM was derivatized with adipic acid dihydrazide through either hydroxyl or carboxyl groups and then covalently bound to tetanus toxoid (TT) or Pseudomonas aeruginosa exoprotein A (rEPA). The immunogenicity of these conjugates was evaluated in BALB/c and general purpose mice by subcutaneous injection in saline. The conjugates elicited higher GXM antibody responses than GXM alone. Booster immunoglobulin G (IgG) and IgM responses were elicited by all conjugates in BALB/c mice. The conjugates prepared through hydroxyl activation (GXM-TT2 and GXM-rEPA) were more immunogenic than the one prepared through carboxyl activation (GXM-TT1). GXM antibody response was enhanced by the administration of monophosphoryl lipid A 2 days following the injection of GXM-TT2 (P less than 0.03). The conjugates also elicited IgG antibodies to the carrier proteins. Gel diffusion tests using conjugate-induced hyperimmune sera and chemically modified GXMs suggested that the specificity of GXM-TT1-induced antibodies was conferred by the O-acetyl groups. Hyperimmune sera generated by GXM-TT2 precipitated with the chemically unmodified and the de-O-acetylated GXMs but not with the carboxyl-reduced and de-O-acetylated GXM. GXM-TT2-induced hyperimmune serum also precipitated with the capsular polysaccharides of C. neoformans serotypes D, B, and C. The conjugate vaccines prepared through hydroxyl activation of the GXM are sufficiently immunogenic and appear to be suitable for clinical evaluation.", "author" : [ { "dropping-particle" : "", "family" : "Devi", "given" : "S. J N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneerson", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ulrich", "given" : "T. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bryla", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robbins", "given" : "J. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "J. E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection and Immunity", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "3700-3707", "title" : "<i>Cryptococcus neoformans</i> serotype A glucuronoxylomannan-protein conjugate vaccines: Synthesis, characterization, and immunogenicity", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.4049/jimmunol.166.2.1087", "ISBN" : "0022-1767", "ISSN" : "0022-1767", "PMID" : "11145689", "abstract" : "Defined Abs to the Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM) have been shown to be protective against experimental cryptococcosis. This suggests that if a vaccine could induce similar Abs it might protect against infection. However, the potential use of a GXM-based vaccine has been limited by evidence that GXM is a poor immunogen that can induce nonprotective and deleterious, as well as protective, Abs, and that the nature of GXM oligosaccharide epitopes that can elicit a protective response is unknown. In this study, we investigated whether a peptide surrogate for a GXM epitope could induce an Ab response to GXM in mice. The immunogenicity of peptide-protein conjugates produced by linking a peptide mimetic of GXM, P13, to either BSA, P13-BSA, or tetanus toxoid, P13-tetanus toxoid, was examined in BALB/c and CBA/n mice that received four s.c. injections of the conjugates at 14- to 30-day intervals. All mice immunized with conjugate produced IgM and IgG to P13 and GXM. Challenge of conjugate-immunized mice with C. neoformans revealed longer survival and lower serum GXM levels than control mice. These results indicate that 1) P13 is a GXM mimotope and 2) that it induced a protective response against C. neoformans in mice. P13 is the first reported mimotope of a C. neoformans Ag. Therefore, the P13 conjugates are vaccine candidates for C. neoformans and their efficacy in this study suggests that peptide mimotopes selected by protective Abs deserve further consideration as vaccine candidates for encapsulated pathogens.", "author" : [ { "dropping-particle" : "", "family" : "Fleuridor", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lees", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pirofski", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "the journal of immunology", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "1087-96", "title" : "A cryptococcal capsular polysaccharide mimotope prolongs the survival of mice with <i>Cryptococcus neoformans</i> infection.", "type" : "article-journal", "volume" : "166" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{265,269\u2013271}", "plainTextFormattedCitation" : "265,269\u2013271", "previouslyFormattedCitation" : "^{265,269\u2013271}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }265,269–271 ConclusionPulmonary cryptococcosis is probably one of the most common pulmonary fungal infections both in immunocompromised and immunocompetent patients. There has been increasing interest in the field of genetic diversity, environmental niches and the pathogenesis of this disease, especially since the outbreak of C. gattii in several areas. However, most of the studies are small; hence, caution must be applied as the findings may not be transferable to different geographical areas or patient risk groups. The development of diagnostic tools or point of care test that can detect CrAg in respiratory specimens is the substantial part of research gap in pulmonary cryptococcosis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/mmy/myx010", "ISBN" : "1460-2709 (Electronic) 1369-3786 (Linking)", "ISSN" : "1369-3786", "PMID" : "28419364", "author" : [ { "dropping-particle" : "", "family" : "Oshima", "given" : "Kazuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takazono", "given" : "Takahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saijo", "given" : "Tomomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Masato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurihara", "given" : "Shintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Kazuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Imamura", "given" : "Yoshifumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsukamoto", "given" : "Misuzu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukae", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Mycology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-7", "title" : "Examination of cryptococcal glucuronoxylomannan antigen in bronchoalveolar lavage fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³²", "plainTextFormattedCitation" : "232", "previouslyFormattedCitation" : "²³²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }232 The interpretation of CrAg in respiratory specimens required support from clinical appearance as colonisation is frequently occurs in respiratory tracts.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1378/chest.72.1.13", "ISBN" : "0012-3692 (Print)\\n0012-3692", "ISSN" : "00123692", "PMID" : "326497", "abstract" : "Cryptococcus neoformans was isolated from 65 patients: 11 had meningitis, 11 had disseminated cryptococcosis without meningitis, and 43 had C neoformans isolated from the respiratory tract. Predisposing conditions and the diagnostic value of cultures from various sites and of the latex agglutination test on cerebrospinal fluid and serum are analyzed for patients with extrapulmonary disease. Nine patients had pleural effusions; the effusion was cultured in six and yielded C neoformans in four. None of 11 deaths among 43 patients with respiratory tract isolates could be attributed to cryptococosis. The 32 survivors were nor treated with antifungal agents. Twenty-six of 43 patients with respiratory isolates had various bronchopulmonary disorders, with chronic obstructive pulmonary diseases and asthma the most common (28 percent). Seven of 28 patients (25 percent) with roentgenographically detected lung lesions had carcinoma of the lung. Roentgenographic evidence of a lung lesion and C neoformans grown from the respiratory tract warrant a further search for carcinoma of the lung.", "author" : [ { "dropping-particle" : "", "family" : "Duperval", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hermans", "given" : "P. E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brewer", "given" : "N. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roberts", "given" : "G. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1977" ] ] }, "page" : "13-19", "publisher" : "AMERICAN COLLEGE OF CHEST PHYSICIANS", "title" : "Cryptococcosis, with emphasis on the significance of isolation of Cryptococcus neoformans from the respiratory tract", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁷²", "plainTextFormattedCitation" : "272", "previouslyFormattedCitation" : "²⁷²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }272 Further research is needed to account for the varying risk factors, including genetic risk factors, embracing a greater sample size, especially in relation to immunocompetent populations. There is also limited clinical research involving patients with isolated pulmonary cryptococcosis. Thus, further research is required to determine the best strategy for rapid diagnosis of pulmonary cryptococcosis to pre-empt dissemination and acute respiratory failure. AcknowledgementWe would like to thank Lembaga Pengelola Dana Pendidikan (LPDP), Republik Indonesia for awarding scholarship to support the studies of the corresponding author.Conflicts of interestDWD and family hold Founder shares in F2G Ltd., a University of Manchester spin-out antifungal discovery company. He acts or has recently acted as a consultant to Astellas, Sigma Tau, Basilea, Scynexis, Cidara, Biosergen, Quintiles, Pulmatrix, Pulmocide and Zambon. In the last 3 years, he has been paid for talks on behalf of Astellas, Dynamiker, Gilead, Merck and Pfizer. He is a longstanding member of the Infectious Disease Society of America Aspergillosis Guidelines group, the European Society for Clinical Microbiology and Infectious Diseases Aspergillosis Guidelines group and the British Society for Medical Mycology Standards of Care committee. RR-R reports personal fees from Gilead Sciences and Astellas. FS declare no conflicts of interest.References:ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. Singh N, Alexander BD, Lortholary O, et al. Pulmonary cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen. Clin Infect Dis. 2008; 46:e12-e18.2. Fisher JF, Valencia-rey PA, Davis WB. Pulmonary cryptococcosis in the immunocompetent patient — many questions, some answers. Open Forum Infect Dis. 2016; 3:1-6.3. Rigby AL, Glanville AR. Miliary pulmonary cryptococcosis in an HIV-positive patient. Am J Respir Crit Care Med. 2012; 186:200-201.4. Zhang Y, Li N, Zhang Y, et al. Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis. Eur Respir J. 2012; 40:1191-1200.5. Qu Y, Liu G, Ghimire P, et al. Primary pulmonary cryptococcosis: evaluation of CT characteristics in 26 immunocompetent Chinese patients. Acta Radiol. 2012; 53:668-674.6. Ye F, Xie J, Zeng Q, Chen G, Zhong S, Zhong N. Retrospective analysis of 76 immunocompetent patients with primary pulmonary cryptococcosis. Lung. 2012; 190:339-346.7. Willenburg KS, Hadley S. Pulmonary cryptococcosis: A rare but emerging disease. Curr Fungal Infect Rep. 2009; 3:40-44.8. Yoo SD, Worodria W, Med M, et al. The prevalence and clinical course of HIV-associated pulmonary cryptococcosis in Uganda. J Acquir Immune Defic Syndr. 2011; 54:269-274.9. Harris JR, Lindsley MD, Henchaichon S, et al. High prevalence of cryptococcal infection among HIV-infected patients hospitalized with pneumonia in Thailand. Clin Infect Dis. 2012; 54:43-50.10. Liu K, Ding H, Xu B, et al. Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis. J Thorac Dis. 2016; 8:2813-2821.11. Suwatanapongched T, Sangsatra W, Boonsarngsuk V, Incharoen P. Clinical and radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients and their outcomes after treatment. Diagnostic Interv Radiol. 2013; 19:438-446.12. Sun L, Chen H, Shao C, Song Y, Bai C. Pulmonary cryptococcosis with trachea wall invasion in an immunocompetent patient: a case report and literature review. Respiration. 2014; 87:324-328.13. Gao L-W, Jiao A-X, Wu X-R, et al. Clinical characteristics of disseminated cryptococcosis in previously healthy children in China. BMC Infect Dis. 2017; 17:359.14. Cao W, Jian C, Zhang H, Xu S. Comparison of Clinical Features and Prognostic Factors of Cryptococcal Meningitis Caused by Cryptococcus neoformans in Patients With and Without Pulmonary Nodules. Mycopathologia. 2018.15. Limper AH. The changing spectrum of fungal infections in pulmonary and critical care practice: clinical approach to diagnosis. Proc Am Thorac Soc. 2010; 7:163-168.16. Chen M, Xu Y, Hong N, et al. Epidemiology of fungal infections in China. Front Med. 2018; 12:58-75.17. Wu SX, Guo NR, Li XF, et al. Human pathogenic fungi in China-emerging trends from ongoing national survey for 1986, 1996, and 2006. Mycopathologia. 2011; 171:387-393.18. Chau TTH, Mai NH, Phu NH, et al. A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam - high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease. BMC Infect Dis. 2010:2-9.19. Voelz K, May RC. Cryptococcal interactions with the host immune system. Eukaryot Cell. 2010; 9:835-846.20. May RC, Stone NRH, Wiesner DL, Bicanic T, Nielsen K. Cryptococcus ?: from environmental saprophyte to global pathogen. Nat Rev Microbiol. 2015; 14:106-117.21. Mitchell TG, Castaneda E, Nielsen K, Wanke B, Lazera MS. Enviromental niches for Cryptococcus neoformans and Cryptococcus gattii. In: Heitman J, Kozel T, Kwon-Chung KJ, Perfect JR, Casadevall A, eds. Cryptococcus: From Human Pathogen to Model Yeast. ASM Press, 2011:237-260.22. Chang CC, Sorrell TC, Chen SCA. Pulmonary cryptococcosis. Sem Respir Crit Care Med. 2015; 36:681-691.23. Chowdhary A, Rhandhawa HS, Prakash A, Meis JF. Environmental prevalence of Cryptococcus neoformans and Cryptococcus gattii in India: an update. Crit Rev Microbiol. 2012; 38:1-16.24. Springer DJ, Billmyre RB, Filler EE, et al. Cryptococcus gattii VGIII isolates causing infections in HIV/AIDS patients in southern California: identification of the local environmental source as arboreal. PLoS Pathog. 2014; 10:e1004285.25. Sampaio A, Sampaio JP, Le?o C. Dynamics of yeast populations recovered from decaying leaves in a nonpolluted stream: A 2-year study on the effects of leaf litter type and decomposition time. FEMS Yeast Res. 2007; 7:595-603.26. Baroni FDA, Paula CR, Da Silva ?G, et al. Cryptococcus neoformans strains isolated from church towers in Rio de Janeiro City, RJ, Brazil. Rev Inst Med Trop Sao Paulo. 2006; 48:71-75.27. Ergin C, Ilkit M, Kaftanog O. Detection of Cryptococcus neoformans var.grubii in honeybee (Apis mellifera) colonies. Mycoses. 2004; 47:431-434.28. Russo G, Libkind D, Sampaio JP, Van Broock MR. Yeast diversity in the acidic Rio Agrio-Lake Caviahue volcanic environment (Patagonia, Argentina). FEMS Microbiol Ecol. 2008; 65:415-424.29. De García V, Brizzio S, Libkind D, Buzzini P, Van Broock M. Biodiversity of cold-adapted yeasts from glacial meltwater rivers in Patagonia, Argentina. FEMS Microbiol Ecol. 2007; 59:331-341.30. Kronstad JW, Attarian R, Cadieux B, et al. Expanding fungal pathogenesis: Cryptococcus breaks out of the opportunistic box. Nat Rev Microbiol. 2011; 9:193-203.31. Malik R, Krockenberger MB, Brien CRO, Carter DEEA, Meyer W, Canfield PJ. Veterinary insights into cryptococcosis caused by Cryptococcus neoformans and Cryptococcus gattii. In: Heitman J, Kozel T, Kwon-Chung KJ, Perfect JR, Casadevall A, eds. Cryptococcus: From Human Pathogen to Model Yeast. ASM Press, 2011:489-502.32. Lin X, Heitman J. The biology of the Cryptococcus neoformans species complex. AnnuRevMicrobiol. 2006; 60:69-105.33. Sethi K, Randhawa H. Survival of Cryptococcus neoformans in the gastrointestinal tract of pigeons following ingestion of the organism. J Infect Dis. 1968; 118:135-138.34. Fonseca ?, Boekhout T, Fell JW. Cryptococcus Vuillemin (1901). Vol 3. Elsevier B.V., 2011.35. Kwon Chung K, Boekhout T, Wickes B, Fell J. Systematics of the genus Cryptococcus and its type species C. neoformans. In: Heitman J, Kozel T, Kwon-Chung KJ, Perfect JR, Casadevall A, eds. Cryptococcus: From Human Pathogen to Model Yeast. ASM Press, 2011:3-15.36. Desnos-Ollivier M, Patel S, Raoux-Barbot D, Heitman J, Dromer F. Cryptococcosis serotypes impact outcome and provide evidence of Cryptococcus neoformans speciation. MBio. 2015; 6:e00311-15.37. Deepa S, Felipe H S-T, Tamara L D. Cryptococcus neoformans: Historical curiosity to modern pathogen. NIH Public Access Yeast. 2014; 31:47-60.38. Khawcharoenporn T, Apisarnthanarak A, Mundy LM. Non-neoformans cryptococcal infections: A systematic review. Infection. 2007; 35:51-58.39. Ma H, May RC. Virulence in Cryptococcus species. In: Advances in Applied Microbiology. Vol 67. Elsevier, 2009:131-190.40. de Araujo GS, Fonseca FL, Pontes B, et al. Capsules from pathogenic and non-pathogenic Cryptococcus spp. manifest significant differences in structure and ability to protect against phagocytic cells. PLoS One. 2012; 7.41. Takemura H, Ohno H, Miura I, Takagi T. The first reported case of central venous catheter-related fungemia caused by Cryptococcus liquefaciens. J Infect Chemother. 2015; 21:392-394.42. Conde-Pereira C, Rodas-Rodriguez L, Diaz-Paz M, et al. Fatal Case of Polymicrobial Meningitis Caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis Complex in a Human Immunodeficiency Virus-Infected Patient. J Clin Microbiol. 2015; 53:2753-2755.43. Gullo FP, Rossi SA, Sardi J de CO, Teodoro VLI, Mendes-Giannini MJS, Fusco-Almeida AM. Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment. Eur J Clin Microbiol Infect Dis. 2013; 32:1377-1391.44. Ikeda R, Shinoda T, Fukazawa Y, Kaufman LEO. Antigenic characterization of Cryptococcus neoformans serotypes and its application to serotyping of clinical isolates. J Clin Microbiol. 1982; 16:22-29.45. Franzot SP, Salkin IF, Casadevall A. Cryptococcus neoformans var. grubii?: Separate varietal status for Cryptococcus neoformans serotype A isolates. J Clin Microbiol. 1999; 37:838-840.46. Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Crit Care. 2008; 1:141-150.47. Kwon-chung KJ, Boekhout T, Fell JW, Diaz M. Proposal to conserve the name Cryptococcus gattii against C . hondurianus and C. bacillisporus (Basidiomycota, Hymenomycetes, Tremellomycetidae). Taxon. 2002; 51:804-806.48. Kwon-chung KJ. A new genus, Filobasidiella, the perfect state of Cryptococcus neoformans. Mycologia. 1975; 67:1197-1200.49. Kwon-Chung KJ, Varma A. Do major species concepts support one, two or more species within Cryptococcus neoformans?? FEMS Yeast Res. 2006; 6:574-587.50. Hagen F, Khayhan K, Theelen B, et al. Recognition of seven species in the Cryptococcus gattii / Cryptococcus neoformans species complex. Fungal Genet Biol. 2015; 78:16-48.51. Dromer F, Mathoulin-Pélissier S, Launay O, et al. Determinants of disease presentation and outcome during cryptococcosis: The CryptoA/D study. PLoS Med. 2007; 4:0297-0308.52. Barchiesi F, Cogliati M, Esposto MC, et al. Comparative analysis of pathogenicity of Cryptococcus neoformans serotypes A, D and AD in murine cryptococcosis. J Infect. 2005; 51:10-16.53. Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans . Clin Microbiol Rev. 1995; 8:515-548.54. Meyer W, Aanensen DM, Boekhout T, et al. Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii. Med Mycol. 2009; 47:561-570.55. Litvintseva AP, Thakur R, Vilgalys R, Mitchell TG. Multilocus sequence typing reveals three genetic subpopulations of Cryptococcus neoformans var. grubii (serotype A), including a unique population in Botswana. Genetics. 2006; 172:2223-2238.56. Diaz MR, Boekhout T, Kiesling T, Fell JW. Comparative analysis of the intergenic spacer regions and population structure of the species complex of the pathogenic yeast Cryptococcus neoformans. FEMS Yeast Res. 2005; 5:1129-1140.57. Bovers M, Hagen F, Kuramae EE, Boekhout T. Six monophyletic lineages identified within Cryptococcus neoformans and Cryptococcus gattii by multi-locus sequence typing. Fungal Genet Biol. 2008; 45:400-421.58. Meyer W, Lieckfeldt E, Kuhls K, EZ F, B?rner T, TG M. DNA and PCR fingerprinting in fungi. In: DNA Fingerprinting: State of the Science. Birkh?user Basel, 1993:311-320.59. Spitzer ED, Spitzer SG. Use of a dispersed repetitive DNA element to distinguish clinical isolates of Cryptococcus use of a dispersed repetitive DNA element to distinguish clinical isolates of Cryptococcus neoformans. J Clin Microbiol. 1992; 30:1094-1097.60. Litvintseva AP, Mitchell TG. Most environmental isolates of Cryptococcus neoformans var. grubii (serotype A) are not lethal for mice. Infect Immun. 2009; 77:3188-3195.61. Beale MA, Sabiiti W, Robertson EJ, et al. Genotypic diversity is associated with clinical outcome and phenotype in cryptococcal meningitis across Southern Africa. PLoS Negl Trop Dis. 2015; 9:1-18.62. Wiesner DL, Moskalenko O, Corcoran JM, et al. Cryptococcal genotype influences immunologic response and human clinical outcome after meningitis. MBio. 2012; 3:1-10.63. Khayhan K, Hagen F, Pan W, et al. Geographically structured populations of Cryptococcus neoformans variety grubii in Asia correlate with HIV status and show a clonal population structure. PLoS One. 2013; 8:1-14.64. Meyer W, Castaneda A, Jackson S, Huynh M, Castaneda E, the IberoAmerican Cryptococcal Study Group. Molecular typing of IberoAmerican Cryptococcus neoformans isolates. Emerg Infect Dis. 2003; 9:189-195.65. Ngamskulrungroj P, Chang Y, Roh J, Kwon-Chung KJ. Differences in nitrogen metabolism between Cryptococcus neoformans and C. gattii , the two etiologic agents of cryptococcosis. PLoS One. 2012; 7.66. Firacative C, Trilles L, Meyer W. MALDI-TOF MS enables the rapid identification of the major molecular types within the Cryptococcus neoformans /C. gattii species complex. PLoS One. 2012; 7.67. Okubo Y, Wakayama M, Ohno H, et al. Histopathological study of murine pulmonary cryptococcosis induced by Cryptococcus neoformans and Cryptococcus gattii. Jpn J Infect Dis. 2013; 66:216-221.68. Ngamskulrungroj P, Chang Y, Sionov E, Kwon-chung KJ. The primary target organ of Cryptococcus gattii is different from that of Cryptococcus neoformans in a murine model. mBio Am Soc Microbiol. 2012; 3:1-9.69. Kwon-Chung KJ, Bennett JE, Wickes BL, et al. The case for adopting the “species complex” nomenclature for the etiologic agents of cryptococcosis. Msph Am Soc Microbiol. 2017; 2:e00357-16.70. Pfaller M., Diekema D., Gibbs D., et al. Results from the ARTEMIS DISK global antifungal surveillance study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing. J Clin Microbiol. 2009; 47:117-123.71. De Almeida GMD, Costa SF, Melhem M, et al. Rhodotorula spp. isolated from blood cultures: clinical and microbiological aspects. Med Mycol. 2008; 46:547-556.72. Kidd SE, Hagen F, Tscharke RL, et al. A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci U S A. 2004; 101:17258-17263.73. Dixit A, Carroll SF, Qureshi ST. Cryptococcus gattii: an emerging cause of fungal disease in North America. Interdiscip Perspect Infect Dis. 2009; 2009:840452.74. Harris J, Lockhart S, Chiller T. Cryptococcus gattii?: where do we go from here? Med Mycol. 2012; 50:113-129.75. Okamoto K, Hatakeyama S, Itoyama S, et al. Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007. Emerg Infect Dis. 2010; 16:1155-1157.76. Kitaura T, Takahashi M, Umeyama T, et al. Cryptococcus gattii genotype VGIIa infection imported from Vancouver Island to Japan. J Infect Chemother. 2018:12-14.77. Cogliati M. Global molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii : an atlas of the molecular types. Scientifica (Cairo). 2013:1-23.78. Liaw SJ, Wu HC, Hsueh PR. Microbiological characteristics of clinical isolates of Cryptococcus neoformans in Taiwan: serotypes, mating types, molecular types, virulence factors, and antifungal susceptibility. Clin Microbiol Infect. 2010; 16:696-703.79. Fang W, Fa Z, Liao W. Epidemiology of Cryptococcus and cryptococcosis in China. Fungal Genet Biol. 2015; 78:7-15.80. Viviani MA, Cogliati M, Esposto MC, et al. Molecular analysis of 311 Cryptococcus neoformans isolates from a 30-month ECMM survey of cryptococcosis in Europe. FEMS Yeast Res. 2006; 6:614-619.81. Antinori S. New insights into HIV / AIDS-associated Cryptococcosis. ISRN AIDS. 2013:1-22.82. Pan W, Khayhan K, Hagen F, et al. Resistance of Asian Cryptococcus neoformans serotype a is confined to few microsatellite genotypes. PLoS One. 2012; 7:e32868.83. Shirley RM, Baddley JW. Cryptococcal lung disease. Curr Opin Pulm Med. 2009; 15:254-260.84. Yamamoto Y, Kohno S, Koga H, et al. Random amplified polymorphic DNA analysis of clinically and environmentally isolated Cryptococcus neoformans in Nagasaki. J Clin Microbiol. 1995; 33:3328-3332.85. Sorrell TC, Chen SCA, Ruma P, et al. Concordance of clinical and environmental isolates of Cryptococcus neoformans var. gattii by random amplification of polymorphic DNA analysis and PCR fingerprinting. J Clin Microbiol. 1996; 34:1253-1260.86. Velagapudi R, Hsueh YP, Geunes-Boyer S, Wright JR, Heitman J. Spores as infectious propagules of Cryptococcus neoformans. Infect Immun. 2009; 77:4345-4355.87. Botts MR, Hull CM. Dueling in the lung: How Cryptococcus spores race the host for survival. Curr Opin Microbiol. 2010; 13:437-442.88. Mody CH, Warren PW. Host defence to pulmonary mycosis. Can J Infect Dis. 1999; 10:147-155.89. Zimmer B., Hempel H., Goodman N. Pathogenicity o f the basidiospores of Filobasidiella neoformans. Mycopathologia. 1984:149-153.90. Gibson JF, Johnston SA. Immunity to Cryptococcus neoformans and C. gattii during cryptococcosis. Fungal Genet Biol. 2015; 78:76-86.91. Wozniak KL, Vyas JM, Levitz SM. In vivo role of dendritic cells in a murine model of pulmonary cryptococcosis. Infect Immun. 2006; 74:3817-3824.92. Holmer SM, Evans KS, Asfaw YG, et al. Impact of surfactant protein D, interleukin-5, and eosinophilia on cryptococcosis. Infect Immun. 2014; 82:683-693.93. Garro AP, Chiapello LS, Baronetti JL, Masih DT. Rat eosinophils stimulate the expansion of Cryptococcus neoformans-specific CD4+ and CD8+ T cells with a T-helper 1 profile. Immunology. 2011; 132:174-187.94. Guillot L, Carroll SF, Homer R, Qureshi ST. Enhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection. Infect Immun. 2008; 76:4745-4756.95. McQuiston T, Luberto C, Poeta M Del. Role of sphingosine-1-phosphate ( S1P ) and S1P receptor 2 in the phagocytosis of Cryptococcus neoformans by alveolar macrophages. Microbiology. 2011; 157:1416-1427.96. Baker RD. The primary pulmonary lymph node complex of cryptococcosis. Am J Clin Pathol. 1976; 65:83-92.97. Salyer WR, Salyer DC, Baker RD. Primary complex of Cryptococcus and pulmonary lymph nodes. J Infect Dis. 1974; 130:74-77.98. Santangelo R, Zoellner H, Sorrell T, et al. Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model. Infect Immun. 2004; 72:2229-2239.99. Sweeney DA, Caserta MT, Korones DN, Casadevall A, Goldman DL. A ten-year-old boy with a pulmonary nodule secondary to Cryptococcus neoformans: case report and review of the literature. Pediatr Infect Dis J. 2003; 22:1089-1093.100. Levitz SM, Dupont MP, Smail EH. Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans. Infect Immun. 1994; 62:194-202.101. Chun FZ, Ling LM, Jones GJ, et al. Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and activation of this pathway is defective in HIV patients. Blood J Am Soc Hematol. 2007; 109:2049-2057.102. Goldman DL, Davis J, Bommarito F, Shao X, Casadevall A. Enhanced allergic inflammation and airway responsiveness in rats with chronic Cryptococcus neoformans infection: potential role for fungal pulmonary infection in the pathogenesis of asthma. J Infect Dis. 2006; 193:1178-1186.103. Grahnert A, Muller U, Von Buttlar H, Treudler R, Alber G. Analysis of asthma patients for cryptococcal seroreactivity in an urban German area. Med Mycol. 2015; 53:576-586.104. Eisenman HC, Casadevall A, McClelland EE. New insights on the pathogenesis of invasive Cryptococcus neoformans infection. Curr Infect Dis Rep. 2007; 9:457-464.105. Heitman J, Kozel T, Kwon-Chung KJ, Perfect JR, Casadevall A, eds. Cryptococcus: From Human Pathogen to Model Yeast. Vol 11. ASM Press, 2011.106. Cecília Bittencourt Severo, Alexandra Flávia Gazzoni LCS. Pulmonary cryptococcosis. J Bras Pneumol. 2009; 35:1136-1144.107. Zaragoza O, Rodrigues ML, Jesus M De, et al. The capsule of the fungal pathogen The capsule of the fungal pathogen Cryptococcus neoformans . Adv Appl Microbiol. 2009; 68:1-64.108. Nosanchuk JD, Casadevall A. Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds. Antimicrob Agents Chemother. 2006; 50:3519-3528.109. Perfect JR. Cryptococcus neoformans?: The yeast that likes it hot. FEMS Yeast Res. 2006; 6:463-468.110. Rodrigues ML, Nakayasu ES, Oliveira DL, et al. Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence. Eukaryot Cell. 2008; 7:58-67.111. Levitz SM, Specht CA. The molecular basis for the immunogenicity of Cryptococcus neoformans mannoproteins. FEMS Yeast Res. 2006; 6:513-524.112. Vecchiarelli A, Pietrella D, Dottorini M, et al. Encapsulation of Cryptococcus neoformans regulates fungicidal activity and the antigen presentation process in human alveolar macrophages. Clin Exp Immunol. 1994; 98:217-223.113. Jacobson ES, Tinnell SB. Antioxidant function of fungal melanin. J Bacteriol. 1993; 175:7102-7104.114. Giles SS, Batinic-Haberle I, Perfect JR, Cox GM. Cryptococcus neoformans mitochondrial superoxide dismutase: An essential link between antioxidant function and high-temperature growth. Eukaryot Cell. 2005; 4:46-54.115. Voelz K, Johnston SA, Smith LM, Hall RA, Idnurm A, May RC. “Division of labour” in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak. Nat Commun. 2014; 5:5194.116. Okagaki LH, Nielsen K. Titan cells confer protection from phagocytosis in Cryptococcus neoformans infections. Eukaryot Cell. 2012; 11:820-826.117. Feldmesser M, Kress Y, Casadevall A. Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection. Microbiology. 2001; 147:2355-2365.118. Zaragoza O, Nielsen K. Titan cells in Cryptococcus neoformans: Cells with a giant impact. Curr Opin Microbiol. 2013; 16:409-413.119. Zaragoza O, Rocio G-R, Nosanchuk JD, Cuenca-Estrella M, Rodriguez-Tudela JL, Casadevall A. Fungal cell gigantism during mammalian infection. PLoS Pathog. 2010; 6.120. Crabtree JN, Okagaki LH, Wiesner DL, Strain AK, Nielsen JN, Nielsen K. Titan cell production enhances the virulence of Cryptococcus neoformans. Infect Immun. 2012; 80:3776-3785.121. Ngamskulrungroj P, Price J, Sorrell T, Perfect JR, Meyer W. Cryptococcus gattii virulence composite: Candidate genes revealed by microarray analysis of high and less virulent Vancouver Island outbreak strains. PLoS One. 2011; 6.122. Liu L, Tewari RP, Williamson PR. Laccase protects Cryptococcus neoformans from antifungal activity of alveolar macrophages. Infect Immun. 1999; 67:6034-6039.123. Eisenman HC, Mues M, Weber SE, et al. Cryptococcus neoformans laccase catalyses melanin synthesis from both D- and L-DOPA. Microbiology. 2007; 153:3954-3962.124. Erb-Downward JR, Noggle RM, Williamson PR, Huffnagle GB. The role of laccase in prostaglandin production by Cryptococcus neoformans. Mol Microbiol. 2008; 68:1428-1437.125. Qiu Y, Davis MJ, Dayrit JK, et al. Immune modulation mediated by cryptococcal laccase promotes pulmonary growth and brain dissemination of virulent Cryptococcus neoformans in mice. PLoS One. 2012; 7.126. Huang J, Lan C, Li H, Lin Q, Liu J, Wen H. Retrospective analysis of 117 chinese patients with pulmonary cryptococcosis. Chest. 2016; 149:A124.127. Chen SCA, Meyer W, Sorrell TC. Cryptococcus gattii infections. Clin Microbiol Rev. 2014; 27:980-1024.128. Nakao M, Muramatsu H, Takahashi T, et al. Cryptococcus gattii genotype VGIIa infection in an immunocompetent Japanese patient: a case report and mini-review. Intern Med. 2016; 55:3021-3024.129. Zhang B, Cao W, Wu X, Wang S. Pulmonary cryptococcosis in an immunocompetent patient?: a case report. Int J Clin Exp Pathol. 2017; 10:9798-9801.130. Kanjanapradit K, Kosjerina Z, Tanomkiat W, Keeratichananont W, Puntuwong S. Pulmonary cryptococcosis presenting with lung mass: Report of 7 cases and review of literature. Clin Med Insights Pathol. 2017; 10:1-5.131. Ruan Q, Zhu Y, Chen S, Zhu L, Zhang S, Zhang W. Disseminated cryptococcosis with recurrent multiple abscesses in an immunocompetent patient: a case report and literature review. BMC Infect Dis. 2017; 17:369.132. Kohno S, Kakeya H, Izumikawa K, et al. Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan. J Infect Chemother. 2015; 21:23-30.133. Xie X, Xu B, Yu C, et al. Clinical analysis of pulmonary cryptococcosis in non-HIV patients in south China. Int J Clin Exp Med. 2015; 8:3114-3119.134. Kiertiburanakul S, Wirojtananugoon S, Pracharktam R, Sungkanuparph S. Cryptococcosis in human immunodeficiency virus-negative patients. Int J Infect Dis. 2006; 10:72-78.135. Jain S, Mahajan V, Kumar A. Unusual case of coexistent pulmonary cryptococcosis and tuberculosis in an immuno-competent host. Indian J Tuberc. 2017; 64:228-231.136. Sawai T, Nakao T, Koga S, et al. Miliary tuberculosis with co-existing pulmonary cryptococcosis in non-HIV patient without underlying diseases: a case report. BMC Pulm Med. 2018; 18:1-5.137. Thomas R, Christopher D, Balamugesh T, James P, Thomas M. Coexisting pulmonary cryptococcosis and pulmonary tuberculosis in an immunocompetent host. Singapore Med J. 2012; 53:32-34.138. Huang CL, Chen CT, Wu SW, Lin TY. Simultaneous coinfection with Cryptococcus neoformans and Mycobacterium tuberculosis in an adult. Q J Med. 2014; 107:223-224.139. Nabaei G, Afhami S. Disseminated cryptococcosis and active pulmonary tuberculosis co- infection in an otherwise healthy adult. 2015; 14:174-176.140. Chomicki J. Coexistence of pulmonary tuberculosis with pulmonary and meningeal cryptococcosis. CHEST J. 1966:1-3.141. Fang W, Zhang L, Liu J, et al. Tuberculosis/cryptococcosis co-infection in China between 1965 and 2016. Emerg Microbes Infect. 2017; 6:e73.142. Musabende M, Mukabatsinda C, Riviello ED, Ogbuagu O. Concurrent cryptococcal meningitis and disseminated tuberculosis occurring in an immunocompetent male. BMJ Case Rep. 2016:1-4.143. Hu X, Wang R, Wang X, et al. Dectin-2 polymorphism associated with pulmonary cryptococcosis in HIV-uninfected Chinese patients. Med Mycol. 2015; 53:810-816.144. Hajjeh RA, Conn LA, Stephens DS, et al. Cryptococcosis?: population-based multistate active surveillance and risk factors in Human immunodeficiency Virus – infected persons. J Infect Dis. 1999; 179:449-454.145. Pappas PG. Cryptococcal infections in non-HIV-infected patients. Trans Am Clin Climatol Assoc. 2013; 124:61-79.146. Yu J-Q, Tang K-J, Xu B-L, Xie C-M, Light RW. Pulmonary cryptococcosis in non-AIDS patients. Braz J Infect Dis. 2012; 16:531-539.147. Wong ML, Back P, Candy G, Nelson G, Murray J. Cryptococcal pneumonia in African miners at autopsy. Int J Tuberc Lung Dis. 2007; 11:528-533.148. Houston S. Who determines the “standard of care” in research in resource poor countries? Int J Tuberc Lung Dis. 2009; 13:149.149. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. Aids. 2009; 23:525-530.150. Lanjewar DN, Duggal R. Pulmonary pathology in patients with AIDS: An autopsy study from Mumbai. HIV Med. 2001; 2:266-271.151. Bernicker EH, Atmar RL, Schaffner DL, Greenberg SB. Unanticipated diagnoses found at autopsy in an urban public teaching hospital. Am J Med Sci. 1996; 311:215-220.152. Kaur R, Mehra B, Dhakad MS, Goyal R, Bhalla P, Dewan R. Fungal opportunistic pneumonias in HIV/AIDS patients: An Indian tertiary care experience. J Clin Diagnostic Res. 2017; 11:DC14-DC19.153. Pappas PG, Alexander BD, Andes DR, et al. Invasive Fungal Infections among Organ Transplant Recipients?: Results of the Transplant-Associated Infection Surveillance Network ( TRANSNET ). Clin Infect Dis. 2010:1101-1111.154. Ponzio V, Fernando L, José C, Robert J, Arnaldo P, Colombo L. Outcomes of cryptococcosis in renal transplant recipients in a resourced health care system. Transpl Infect Dis. 2018:1-9.155. Singh N, Alexander BD, Lortholary O, et al. Cryptococcus neoformans in organ transplant recipients: Impact of calcineurin-inhibitor agents on mortality. J Infect Dis. 2007; 195:756-764.156. George I, Santos C, Powderly W, Olsen M. Epidemiology of cryptococcosis and cryptococcal meningitis in a large retrospective cohort of patients following solid organ transplantation. Open Forum Infect Dis. 2017:1-7.157. Sun H, Wagener MM, Singh N. Cryptococcosis in solid‐organ, hematopoietic stem cell, and tissue transplant recipients: Evidence‐based evolving trends. Clin Infect Dis. 2009; 48:1566-1576.158. Kuroda A, Tasaka S, Yagi K, et al. A case of disseminated cryptococcal infection and concurrent lung tuberculosis in a patient under steroid therapy for interstitial pneumonia. Case Rep Pulmonol. 2015:1-6.159. Yuri T, Kimura A, Yoshizawa K, Emoto Y, Kinoshita Y, Tsubura A. Pulmonary and meningeal cryptococcosis after corticosteroid therapy for autoimmune hepatitis: Coexistence of cryptococci within pulmonary cancer nodule. Case Rep Pathol. 2013:1-4.160. Schmalzle SA, Buchwald UK, Gilliam BL, Riedel DJ. Cryptococcus neoformans infection in malignancy. Mycoses. 2016; 59:542-552.161. Wang R, Chen Y, Wu J, et al. Cryptococcosis in patients with hematological diseases: a 14-year retrospective clinical analysis in a Chinese tertiary hospital. BMC Infect Dis. 2017; 17:463.162. Prasad KT, Sehgal IS, Shivaprakash MR, Dhooria S. Uncommon mycosis in a patient with diabetes. BMJ Case Rep. 2016; 2016:1-4.163. Li Y, Fang W, Jiang W, et al. Cryptococcosis in patients with diabetes mellitus II in mainland China: 1993-2015. Mycoses. 2017:706-713.164. Lin K-H, Chen C-M, Chen T-L, et al. Diabetes mellitus is associated with acquisition and increased mortality in HIV-uninfected patients with cryptococcosis: A population-based study. J Infect. 2016; 72:608-614.165. Lin YY, Shiau S, Fang CT. Risk factors for invasive Cryptococcus neoformans diseases: A case-control study. PLoS One. 2015; 10:1-13.166. Vilchez RA, Linden P, Lacomis J, Costello P. Acute respiratory failure associated with pulmonary cryptococcosis in non- AIDS patients. Chest. 2001; 119:1865-1869.167. Inaba A, Okada A, Yoshida T, et al. Disseminated cryptococcosis with rapidly growing lung nodules in an end-stage renal disease patient. Intern Med. 2017; 56:377-380.168. Singh N, Husain S, De Vera M, Gayowski T, Cacciarelli T V. Cryptococcus neoformans infection in patients with cirrhosis, including liver transplant candidates. Medicine (Baltimore). 2004; 83:188-192.169. Singh N, Sifri CD, Silveira FP, et al. Cryptococcosis in patients with cirrhosis of the liver and posttransplant outcomes. Transplantation. 2015; 99:2132-2141.170. Spec A, Raval K, Powderly WG. End-stage liver disease is a strong predictor of early mortality in cryptococcosis. Open Forum Infect Dis. 2016; 3:1-5.171. Hokari S, Tsukada H, Ito K, Shibuya H. An autopsy case of disseminated cryptococcosis manifesting as acute diarrhea in a patient with primary biliary cirrhosis. Intern Med. 2010; 49:1793-1796.172. Vilchez R a, Irish W, Lacomis J, Costello P, Fung J, Kusne S. The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a tertiary care medical center. Medicine (Baltimore). 2001; 80:308-312.173. Chen S, Sorrell T, Nimmo G, et al. Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group. Clin Infect Dis. 2000; 31:499-508.174. Lewis JL, Rabinovich S. The wide spectrum of cryptococcal infections. Am J Med. 1972; 53:315-322.175. Behrman RE, Masci JR, Nicholas P. Cryptococcal skeletal infections?: Case report and review. Rev Infect Dis. 1990; 12:181-190.176. Silveira FP, Husain S, Kwak EJ, et al. Cryptococcosis in liver and kidney transplant recipients receiving anti-thymocyte globulin or alemtuzumab. Transpl Infect Dis. 2007; 9:22-27.177. Aberg JA, Mundy LM, Powderly WG. Pulmonary cryptococcosis in patients without HIV infection. CHEST J. 1999; 115:734-740.178. Wei-Chou Chang, Ching Tzao, Hsian-He Hsu, Shih-Chun Lee, Kun-Lun Huang, Ho-Jui Tung and C-YC. Pulmonary cryptococcosis * Comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients. Chest. 2006; 129:333-340.179. Feliciano LG, Deseda C, Rivera A, et al. Emergence of Cryptococcus gattii -Pacific Northwest, 2004-2010. Morb Mortal Wkly Report, CDC. 2010; 59:865-893.180. Cameron ML, Bartlett JA, Gallis HA, Waskin HA. Manifestations of pulmonary cryptococcusis in patients with acquired immunodeficiency syndrome. Clin Infect Dis. 1990; 13:64-67.181. Chechani V, Kamholz SL. Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS. Chest. 1990; 98:1060-1066.182. Pappas PG, Perfect JR, Cloud G a, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis. 2001; 33:690-699.183. Smith KD, Achan B, Hullsiek KH, et al. Increased antifungal drug resistance in clinical isolates of Cryptococcus neoformans in Uganda. Antimicrob Agents Chemother. 2015; 59:7197-7204.184. Gunda DW, Bakshi FA, Rambau P, Kilonzo SB. Pulmonary cryptococcosis presenting as acute severe respiratory distress in a newly diagnosed HIV patient in Tanzania: a case report. Clin Case Reports. 2015; 3:749-752.185. Scriven JE, Botha FC, Schutz C, Lalloo DG, Wainwright H, Meintjes G. Paradoxical respiratory failure due to cryptococcal pneumonia after amphotericin B treatment for HIV-associated cryptococcal meningitis. Med Mycol Case Rep. 2018; 19:38-40.186. Liang Y, Shen Y, Zhang J, Zhong X. Pulmonary cryptococcosis among 3 immunocompetent patients misdiagnosed as bacterial pneumonia and pulmonary tuberculosis. Chest. 2016; 149:114A.187. Riha RL, Pataka AD. BMJ Best Practice: Cryptococcosis. Br Med Journals. 2014.188. Miller KD, Mican JA, Davey RT. Asymptomatic solitary pulmonary nodules due to Cryptococcus neoformans in patients infected with human immunodeficiency virus. Clin Infect Dis. 1996; 23:810-812.189. Chen SCA, Meyer W, Sorrell TC. Cryptococcus gattii infections. Clin Microbiol Rev. 2014; 27:980-1024.190. Guimaraes MD, Marchiori E, De Souza Portes Meirelles G, et al. Fungal infection mimicking pulmonary malignancy: Clinical and radiological characteristics. Lung. 2013; 191:655-662.191. Choi HW, Chong S, Kim MK, Park IW. Pulmonary cryptococcosis manifesting as diffuse air-space consolidations in an immunocompetent patient. J Thorac Dis. 2017; 9:E138-E141.192. Ang SYL, Ng VWL, Kumar SD, Low SYY. Cryptococcosis mimicking lung carcinoma with brain metastases in an immunocompetent patient. J Clin Neurosci. 2016; 35:10-12.193. Zheng S, Tan TT, Chien JMF. Cryptococcus gattii infection presenting as an aggressive lung mass. Mycopathologia. 2017:1-6.194. Godwin JD, Ravin CE, Gallis HA, Putman E. Thoracic cryptococcosis: Immunologic competence and radiologic appearance. Am J Roentgenol. 1984; 141:893-896.195. Si-yun W, Gang C, Dong-lan L, et al. F-FDG PET / CT and contrast-enhanced CT findings of pulmonary cryptococcosis. Eur J Radiol. 2017; 89:140-148.196. Basnayake TL, Lim A, Currie BJ. Respiratory Medicine Case Reports Pulmonary cryptococcal infection presenting with multiple lung nodules. Respir Med Case Reports. 2018; 23:122-124.197. de Farias L de PG, Padilha IG, Lemos MRL, Dos Santos CJJ, de Miranda CMN. Pulmonary cryptococcosis mimicking neoplasm in trems of uptake PET/CT. Radiol Bras. 2018; 51:1-4.198. Kelly S, Marriott D. Miliary pulmonary cryptococcosis. Med Mycol Case Rep. 2014; 6:22-24.199. Hu Z, Chen J, Wang J, et al. Radiological characteristics of pulmonary cryptococcosis in HIV-infected patients. PLoS One. 2017; 12:1-9.200. Lindell RM, Hartman TE, Nadrous HF, Ryu JH. Pulmonary cryptococcosis: CT findings in immunocompetent patients. Radiology. 2005; 236:326-331.201. Choe YH, Moon H, Park SJ, et al. Pulmonary cryptococcosis in asymptomatic immunocompetent hosts. Scand J Infect Dis. 2009; 41:602-607.202. Gazzoni AF, Severo CB, Salles EF, Severo LC. Histopathology, serology and cultures in the diagnosis of cryptococcosis. Rev Inst Med Trop Sao Paulo. 2009; 51:255-259.203. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research & Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008; 46:1813-1821.204. Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev. 2011; 24:247-280.205. Thibodeau KP, Viera AJ. Atypical pathogens and challenges in community-acquired pneumonia. Am Acad Fam Physicians. 2005; 47:14-19.206. Shibuya K, Coulson WF, Wollman JS, et al. Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome. Int J Infect Dis. 2001; 5:78-85.207. Saha DC, Xess I, Biswas A, Bhowmik DM, Padma M V. Detection of Cryptococcus by conventional, serological and molecular methods. J Med Microbiol. 2009; 58:1098-1105.208. José IG, Johnson M, Jurgen R, Schlomo S, Williams. British HIV Association and British Infection Association Guidelines for the Treatment of Opportunistic Infection in HIV-seropositive Individuals 2011 HIV MEDICINE EDITORS. HIV Med. 2011; 12:supp 2.209. WHO. Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children: December 2011. Geneva World Heal Organ. 2011.210. Gazzoni AF, Oliveira F de M, Salles EF, et al. Unusual morphologies of Cryptococcus spp. in tissue specimens: Report of 10 cases. Rev Inst Med Trop Sao Paulo. 2010; 52:145-149.211. Dromer F, Lortholary O. Cryptococcosis. Hunter’s Trop Med Emerg Infect Dis. 2013:641-643.212. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010; 50:291-322.213. Jain N, Fries BC. Phenotypic switching of Cryptococcus neoformans and Cryptococcus gattii. Mycopathologia. 2008; 166:181-188.214. Jain N, Wickes BL, Keller SM, et al. Molecular epidemiology of clinical Cryptococcus neoformans strains from India. J Clin Microbiol. 2005; 43:5733-5742.215. Denning DW, Stevens DA, Hamilton JR. Comparison of Guizotia abyssinica seed extract (birdseed) agar with conventional media for selective identification of Cryptococcus neoformans in patients with acquired immunodeficiency syndrome. J Clin Microbiol. 1990; 28:2565-2567.216. Pham CD, Ahn S, Turner LA, Wohrle R, Lockhart SR. Development and validation of benomyl birdseed agar for the isolation of Cryptococcus neoformans and Cryptococcus gattii from environmental samples. Med Mycol. 2014; 52:417-421.217. Diaz MR, Nguyen MH. Diagnostic approach based on capsular antigen, capsule detection, Beta-glucan, and DNA analysis. In: Cryptococcus: From Human Pathogen to Model Yeast. , 2011:547-564.218. Cheon WS, Eom K, Yoo BK, Kim D, Jung K. A case of pulmonary cryptococcosis by capsule-deficient Cryptococcus neoformans. Korean J Intern Med. 2006; 21:83-87.219. Ro JY, Lee SS, Ayala AG. Advantage of Fontana-Masson stain in capsule-deficient cryptococcal infection. Arch Pathol Lab Med. 1987; 111:53-57.220. Williamson JD, Silverman JF, Mallak CT, Christie JD. Atypical cytomorphologic appearance of Cryptococcus neoformans: a report of five cases. Acta Cytol. 1996; 40:363-370.221. Nava A, Orozco-Barocio G. Granulomatous lung disease an approach to the differential diagnosis. Arch Pathol Lab Med. 2010; 134:667-690.222. Jarvis JN, Wainwright H, Harrison TS, Rebe K, Meintjes G. Pulmonary cryptococcosis misdiagnosed as smear-negative pulmonary tuberculosis with fatal consequences. Int J Infect Dis. 2010; 14:e310-e312.223. Shibuya K, Hirata A, Omuta J, et al. Granuloma and cryptococcosis. J Infect Chemother. 2005; 11:115-122.224. Feldmesser M, Kress Y, Novikoff P. Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection. Infect Immun. 2000; 68:4225-4237.225. Kohno KKS, Saito NMJKA, Hara K. Activation of macrophages and expansion of specific T lymphocytes in the lungs of mice intratracheally inoculated with Cryptococcus neoformans. Clin Exp Immunol. 1994; 96:230-237.226. McMullan BJ, Halliday C, Sorrell TC, et al. Clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory. PLoS One. 2012; 7:1-6.227. Pongsai P, Atamasirikul K, Sungkanuparph S. The role of serum cryptococcal antigen screening for the early diagnosis of cryptococcosis in HIV-infected patients with different ranges of CD4 cell counts. J Infect. 2010; 60:474-477.228. Baughman RP, Dohn MN, Henderson H, Frame PT. Detection of cryptococcal antigen in roncbhoalveolar lavage fluid: A prospective study of diagnostic utility. Am Rev Respir Dis. 1992; 145:1226-1229.229. Kralovic SM, Rhodes JC. Utility of routine testing of bronchoalveolar lavage fluid for cryptococcal antigen. J Clin Microbiol. 1998; 36:3088-3089.230. Liaw YS, Yang PC, Yu CJ, et al. Direct determination of cryptococcal antigen in transthoracic needle aspirate for diagnosis of pulmonary cryptococcosis. J Clin Microbiol. 1995; 33:1588-1591.231. Senghor Y, Guitard J, Angoulvant A, Hennequin C. Cryptococcal antigen detection in broncho-alveolar lavage fluid. Med Mycol. 2017:1-4.232. Oshima K, Takazono T, Saijo T, et al. Examination of cryptococcal glucuronoxylomannan antigen in bronchoalveolar lavage fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients. Med Mycol. 2017:1-7.233. Jan IS, Cheng WC, Lo SC, Weng MH, Lee LN. Cryptococcus neoformans in sputum and lung aspiration cytology smears. J Microbiol Immunol Infect. 2014; 48:463-464.234. Gago S, Esteban C, Valero C, Zaragoza O, De La Bellacasa JP, Buitrago MJ. A multiplex real-time PCR assay for identification of Pneumocystis jirovecii, Histoplasma capsulatum,and Cryptococcus neoformans/Cryptococcus gattii in samples from AIDS patients with opportunistic pneumonia. J Clin Microbiol. 2014; 52:1168-1176.235. Feng X, Fu X, Ling B, Wang L, Liao W, Yao Z. Development of a singleplex PCR assay for rapid identification and differentiation of Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, Cryptococcus gattii, and hybrids. J Clin Microbiol. 2013; 51:1920-1923.236. Martins M dos A, Brighente KBS, de Matos TA, Vidal JE, de Hipolito DDC, Pereira-Chioccola VL. Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: Comparison of primer sets for Cryptococcus neoformans and Cryptococcus gattii species complex. Brazilian J Infect Dis. 2015; 19:62-67.237. Leal AL, Faganello J, Bassanesi MC, Vainstein MH. Cryptococcus species identification by multiplex PCR. Med Mycol. 2008; 46:377-383.238. Cordeiro RA, Costa AKF, Brilhante RSN, et al. PCR-REA as an important tool for the identification of Cryptococcus neoformans and Cryptococcus gattii from human and veterinary sources. Vet Microbiol. 2011; 154:180-184.239. Esposto MC, Cogliati M, Tortorano AM, Viviani MA. Determination of Cryptococcus neoformans var. neoformans mating type by multiplex PCR. Clin Microbiol Infect. 2004; 10:1092-1094.240. Ogundeji AO, Albertyn J, Pohl CH, Sebolai OM. Method for identification of Cryptococcus neoformans and Cryptococcus gattii useful in resource-limited settings. J Clin Pathol. 2015:1-6.241. Tanaka K, Miyazaki T, Maesaki S, et al. Detection of Cryptococcus neoformans gene in patients with pulmonary crptococcosis. J Clin Microbiol. 1996; 34:2826-2828.242. Carvalho VG, Terceti MS, Dias ALT, et al. Serotype and mating type characterization of Cryptococcus neoformans by multiplex PCR. Rev Inst Med Trop Sao Paulo. 2007; 49:207-210.243. Bialek R, Weiss M, Bekure-Nemariam K, et al. Detection of Cryptococcus neoformans DNA in tissue samples by nested and real-time PCR assays. Clin Diagn Lab Immunol. 2002; 9:461-469.244. Rappelli P, Are R, Casu G, Fiori PL, Cappuccinelli P, Aceti A. Development of a nested PCR for detection of Cryptococcus neoformans cerebrospinal fluid. J Clin Microbiol. 1998; 36:3438-3440.245. Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011; 183:96-128.246. Molloy SF, Kanyama C, Heyderman RS, et al. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa. N Engl J Med. 2018; 378:1004-1017.247. Dromer F, Mathoulin S, Dupont B, Brugiere O, Letenneur L. Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. French Cryptococcosis Study Group. Clin Infect Dis. 1996; 22:S154-S160.248. Nadrous HF, Antonius VS, Terrell CL, Ryu JH. Pulmonary cryptococcosis in nonimmunocompromised patients. CHEST J. 2003; 124:2143-2147.249. Bongomin F, Oladele RO, Gago S, Moore CB, Richardson MD. A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species. Mycoses. 2018; 61:290-297.250. Chen YC, Chang TY, Liu JW, et al. Increasing trend of fluconazole-non-susceptible Cryptococcus neoformans in patients with invasive cryptococcosis: A 12-year longitudinal study. BMC Infect Dis. 2015; 15:1-7.251. Geddes-McAlister J, Shapiro RS. New pathogens , new tricks?: emerging , drug-resistant fungal pathogens and future prospects for antifungal therapeutics. Ann N Y Acad Sci. 2018:1-22.252. Shaw KJ, Schell WA, Covel J, et al. In vitro and in vivo evaluation of APX001A/APX001 and other Gwt1 inhibitors against Cryptococcus. Antimicrob Agents Chemother. 2018:1-36.253. Nishikawa H, Fukuda Y, Mitsuyama J, et al. In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: An emerging fungal pathogen. J Antimicrob Chemother. 2017; 72:1709-1713.254. Nielsen K, Vedula P, Smith KD, et al. Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs. Med Mycol. 2017; 55:453-456.255. Perfect JR. The antifungal pipeline: A reality check. Nat Rev Drug Discov. 2017; 16:603-616.256. Butts A, Didone L, Koselny K, et al. A Repurposing Approach Identifies Off-Patent Drugs with Fungicidal Cryptococcal Activity , a Common Structural Chemotype , and Pharmacological Properties Relevant to the Treatment of. Eukaryot Cell. 2013; 12:278-287.257. Lee KH, Chang UI, Kim HW, et al. Acute respiratory failure associated with cryptococcal pneumonia and disseminated cryptococcosis in an AIDS patient. Korean J Intern Med. 2006; 21:39-42.258. Visnegarwala F, Graviss EA, Lacke CE, et al. Acute respiratory failure associated with cryptococcosis in patients with AIDS?: Analysis of predictive factors. Clin Infect Dis. 1998; 27:1231-1237.259. Meyohas MC, Roux P, Bollens D, et al. Pulmonary cryptococcosis: localized and disseminated infections in 27 patients with AIDS. Clin Infect Dis. 1995; 21:628-633.260. Parkes-Ratanshi R, Wakeham K, Levin J, et al. Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: A double-blind, randomised, placebo-controlled trial. Lancet Infect Dis. 2011; 11:933-941.261. McKinsey DS, Wheat LJ, Cloud GA, et al. Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis. 1999; 28:1049-1056.262. Powderly WG, Finkelstein DM, Feinberg J, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced Human Immunodeficiency Virus infection. N Engl J Med. 1995:700-705.263. Hole CR, Wormley FL. Vaccine and immunotherapeutic approaches for the prevention of cryptococcosis: Lessons learned from animal models. Front Microbiol. 2012; 3:1-7.264. Leopold Wager CM, Wormley FL. Is development of a vaccine against Cryptococcus neoformans feasible? PLOS Pathog. 2015; 11:e1004843.265. Datta K, Lees A, Pirofski LA. Therapeutic efficacy of a conjugate vaccine containing a peptide mimotope of cryptococcal capsular polysaccharide glucuronoxylomannan. Clin Vaccine Immunol. 2008; 15:1176-1187.266. Specht CA, Lee CK, Huang H, et al. Protection against experimental cryptococcosis following vaccination with glucan particles containing cryptococcus alkaline extracts. MBio. 2015; 6:1-11.267. Srichatrapimuk S, Sungkanuparph S. Integrated therapy for HIV and cryptococcosis. AIDS Res Ther. 2016; 13:1-15.268. Perfect JR, Bicanic T. Cryptococcosis diagnosis and treatment?: What do we know now. Fungal Genet Biol. 2015; 78:49-54.269. Wormley FL, Perfect JR, Steele C, Cox GM. Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain. Infect Immun. 2007; 75:1453-1462.270. Devi SJN, Schneerson R, Egan W, et al. Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: Synthesis, characterization, and immunogenicity. Infect Immun. 1991; 59:3700-3707.271. Fleuridor R, Lees A, Pirofski L. A cryptococcal capsular polysaccharide mimotope prolongs the survival of mice with Cryptococcus neoformans infection. J Immunol. 2001; 166:1087-1096.272. Duperval R, Hermans PE, Brewer NS, Roberts GD. Cryptococcosis, with emphasis on the significance of isolation of Cryptococcus neoformans from the respiratory tract. Chest. 1977; 72:13-19.273. Chechani V, Kamholz SL. Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS. CHEST J. 1990; 98:1061-1066.Table 1. Classification and distribution of Cryptococcus spp.*SpeciesVarietiesSerotypesSubgroup by MLSTMost common nichesDistribution(more prevalent regions)C. neoformansvar. grubiiAVNIPigeons, other birds, trees, soilGlobalvar. grubiiAVNIIUnknownGlobal (Australia, Africa, North America)var. grubiiAVNBTrees (mopane)Southern Africa (Botswana, South Africa)var. neoformansDVNIVPigeons, soil, other birdsGlobal (Europe)HybridsAD hybridVNIIIPigeons, soil, other birdsGlobal (Europe)C. gattii-B or CVGITrees (eucalypt)Global (Australia)-B or CVGIITrees (eucalypt)North America (Canada, United States), South America (Columbia)-B or CVGIIITrees (almond)South America-B or CVGIVTreesNorth America*Adapted from Mitchell et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Thomas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaneda", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wanke", "given" : "Bodo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lazera", "given" : "Marcia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cryptococcus: From Human Pathogen to Model Yeast", "editor" : [ { "dropping-particle" : "", "family" : "Heitman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwon-Chung", "given" : "Kyung J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casadevall", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "237-260", "publisher" : "ASM Press", "title" : "Enviromental niches for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹", "plainTextFormattedCitation" : "21", "previouslyFormattedCitation" : "²¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21 and Chang et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0031-1295720", "ISBN" : "0046-8177 (Print)\\r0046-8177 (Linking)", "ISSN" : "00099252", "PMID" : "22167400", "abstract" : "Cryptococcosis is a common opportunistic infection in acquired immunodeficiency syndrome (AIDS) patients, also occurring in other immunosuppressed patients and occasionally those with no apparent immunocompromise. The majority of cases are caused by the ubiquitous encapsulated yeast, Cryptococcus neoformans, whereas Cryptococcus GATTII accounts for a smaller proportion of cases, often in immunocompetent patients. Severe meningoencephalitis is the commonest presentation; however, pulmonary cryptococcosis in human immunodeficiency virus (HIV)-seropositive individuals is underdiagnosed and without appropriate treatment leads to severe disseminated disease. The natural history of pulmonary cryptococcal infection in other immunosuppressed patients is also of dissemination and progression in the majority of cases, whereas immunocompetent patients may present with more localized, self-limiting disease. The presentation is usually with nonspecific respiratory symptoms, although severe respiratory failure has been reported in both immunocompromised and immunocompetent patients. Radiological presentations are varied and nonspecific, influenced by the underlying immune status of the patient. Diagnosis is based on isolation of Cryptococcus from, or detection of cryptococcal antigen in, a pulmonary specimen, coupled with appropriate clinical, radiological, and histopathological findings. Antifungal treatment with amphotericin B +/- flucytosine is recommended for severe disease, whereas fluconazole is the treatment of choice for mild and localized infections", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "C. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "T. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "S. C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Sem Respir Crit Care Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "681-691", "title" : "Pulmonary cryptococcosis", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²²", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "²²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22Table 2. Clinical manifestations of pulmonary cryptococcosis.SymptomsCryptococcus neoformansCryptococcus gattii References ImmunocompromisedImmunocompetentAll subjectsAsymptomatic-24 - 54%34%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "9702216400", "ISSN" : "0149-2195", "PMID" : "20651643", "abstract" : "This article reports some details regarding the dengue epidemic in Puerto Rico in 1-15 July 2010. During the period, a total of 6321 suspected dengue cases were reported to the Puerto Rico Department of Health (PRDH) and Centre for Disease Control and Prevention (CDC). Of the suspected cases, 2831 (45%) have been laboratory-confirmed; the incidence of confirmed cases was 74.3 cases per 100 000 population, with 35% of patients hospitalized and five deaths reported, all adults. The incidence of confirmed cases was highest among children aged 10-14 years (165 cases per 100 000); 15-19 years (163), 5-9 years (91), infants (83), adults aged 20-24 years (77). 72 of the 78 municipalities of Puerto Rico were affected. PRDH and the CDC are working with municipal leadership to raise awareness about dengue prevention measures and eliminate mosquito production sites, and are providing continuing medical education on dengue clinical management and educational materials for patients.", "author" : [ { "dropping-particle" : "", "family" : "Feliciano", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deseda", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomashek", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munoz-Jordan", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunsperger", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Padro", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santiago", "given" : "L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soto", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perez", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriguez", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seda", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arguello", "given" : "D F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Margolis", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Morbidity and Mortality Weekly Report, CDC", "id" : "ITEM-1", "issue" : "28", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "865-893", "title" : "Emergence of <i>Cryptococcus gattii </i>-Pacific Northwest, 2004-2010", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.bjid.2012.07.004", "ISBN" : "1413-8670", "ISSN" : "1678-4391", "PMID" : "23154046", "abstract" : "OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients.\\n\\nMETHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied.\\n\\nRESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2\u00b111.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients.\\n\\nCONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.", "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Jin-Quan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Ke-Jing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Bing-Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Can-Mao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Light", "given" : "Richard W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "531-9", "publisher" : "Elsevier Editora Ltda", "title" : "Pulmonary cryptococcosis in non-AIDS patients.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wei-Chou Chang, Ching Tzao, Hsian-He Hsu, Shih-Chun Lee, Kun-Lun Huang, Ho-Jui Tung", "given" : "and Cheng-Yu Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chest", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "333-340", "title" : "Pulmonary cryptococcosis * Comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1007/s00408-011-9362-8", "ISSN" : "1432-1750", "PMID" : "22246551", "abstract" : "Pulmonary cryptococcosis typically occurs in immunocompromised patients, but it can also occur in immunocompetent patients. 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During the period, a total of 6321 suspected dengue cases were reported to the Puerto Rico Department of Health (PRDH) and Centre for Disease Control and Prevention (CDC). Of the suspected cases, 2831 (45%) have been laboratory-confirmed; the incidence of confirmed cases was 74.3 cases per 100 000 population, with 35% of patients hospitalized and five deaths reported, all adults. The incidence of confirmed cases was highest among children aged 10-14 years (165 cases per 100 000); 15-19 years (163), 5-9 years (91), infants (83), adults aged 20-24 years (77). 72 of the 78 municipalities of Puerto Rico were affected. PRDH and the CDC are working with municipal leadership to raise awareness about dengue prevention measures and eliminate mosquito production sites, and are providing continuing medical education on dengue clinical management and educational materials for patients.", "author" : [ { "dropping-particle" : "", "family" : "Feliciano", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deseda", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomashek", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munoz-Jordan", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunsperger", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Padro", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santiago", "given" : "L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soto", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perez", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriguez", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seda", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arguello", "given" : "D F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Margolis", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Morbidity and Mortality Weekly Report, CDC", "id" : "ITEM-1", "issue" : "28", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "865-893", "title" : "Emergence of <i>Cryptococcus gattii </i>-Pacific Northwest, 2004-2010", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/clinids/13.1.64", "ISSN" : "1058-4838", "author" : [ { "dropping-particle" : "", "family" : "Cameron", "given" : "M. 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A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Infectious Diseases", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "64-67", "title" : "Manifestations of pulmonary cryptococcusis in patients with acquired immunodeficiency syndrome", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Chechani", "given" : "Vijay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamholz", "given" : "Stephan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST Journal", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "1061-1066", "title" : "Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS", "type" : "article-journal", "volume" : "98" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1007/s00408-011-9362-8", "ISSN" : "1432-1750", "PMID" : "22246551", "abstract" : "Pulmonary cryptococcosis typically occurs in immunocompromised patients, but it can also occur in immunocompetent patients. 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Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. 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During the period, a total of 6321 suspected dengue cases were reported to the Puerto Rico Department of Health (PRDH) and Centre for Disease Control and Prevention (CDC). Of the suspected cases, 2831 (45%) have been laboratory-confirmed; the incidence of confirmed cases was 74.3 cases per 100 000 population, with 35% of patients hospitalized and five deaths reported, all adults. The incidence of confirmed cases was highest among children aged 10-14 years (165 cases per 100 000); 15-19 years (163), 5-9 years (91), infants (83), adults aged 20-24 years (77). 72 of the 78 municipalities of Puerto Rico were affected. 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Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.", "author" : [ { "dropping-particle" : "", "family" : "Pappas", "given" : "P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cloud", "given" : "G a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankey", "given" : "G a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lancaster", "given" : "D J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauffman", "given" : "C a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haas", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saccente", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holloway", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warren", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "W E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "690-699", "title" : "Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{6,179,180,182,273}", "plainTextFormattedCitation" : "6,179,180,182,273", "previouslyFormattedCitation" : "^{6,178,181,182,273}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6,179,180,182,273Dyspnea33-50%22-48%51%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "9702216400", "ISSN" : "0149-2195", "PMID" : "20651643", "abstract" : "This article reports some details regarding the dengue epidemic in Puerto Rico in 1-15 July 2010. During the period, a total of 6321 suspected dengue cases were reported to the Puerto Rico Department of Health (PRDH) and Centre for Disease Control and Prevention (CDC). Of the suspected cases, 2831 (45%) have been laboratory-confirmed; the incidence of confirmed cases was 74.3 cases per 100 000 population, with 35% of patients hospitalized and five deaths reported, all adults. The incidence of confirmed cases was highest among children aged 10-14 years (165 cases per 100 000); 15-19 years (163), 5-9 years (91), infants (83), adults aged 20-24 years (77). 72 of the 78 municipalities of Puerto Rico were affected. PRDH and the CDC are working with municipal leadership to raise awareness about dengue prevention measures and eliminate mosquito production sites, and are providing continuing medical education on dengue clinical management and educational materials for patients.", "author" : [ { "dropping-particle" : "", "family" : "Feliciano", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deseda", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomashek", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munoz-Jordan", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunsperger", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Padro", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santiago", "given" : "L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soto", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perez", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriguez", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seda", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrera", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arguello", "given" : "D F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Margolis", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Morbidity and Mortality Weekly Report, CDC", "id" : "ITEM-1", "issue" : "28", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "865-893", "title" : "Emergence of <i>Cryptococcus gattii </i>-Pacific Northwest, 2004-2010", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/clinids/13.1.64", "ISSN" : "1058-4838", "author" : [ { "dropping-particle" : "", "family" : "Cameron", "given" : "M. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartlett", "given" : "J. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gallis", "given" : "H. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waskin", "given" : "H. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Infectious Diseases", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "64-67", "title" : "Manifestations of pulmonary cryptococcusis in patients with acquired immunodeficiency syndrome", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Chechani", "given" : "Vijay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamholz", "given" : "Stephan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CHEST Journal", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "1061-1066", "title" : "Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS", "type" : "article-journal", "volume" : "98" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jiac.2014.08.025", "ISBN" : "1341-321x", "ISSN" : "14377780", "PMID" : "25444673", "abstract" : "OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.\nMETHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.\nRESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.\nCONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable.", "author" : [ { "dropping-particle" : "", "family" : "Kohno", "given" : "Shigeru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izumikawa", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Taiga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "Katsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "Kotaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "Yoshitsugu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "Shigefumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasuoka", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "Takayoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Mariko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uetani", "given" : "Masataka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashizawa", "given" : "Kazuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "23-30", "publisher" : "Elsevier Ltd", "title" : "Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1007/s00408-011-9362-8", "ISSN" : "1432-1750", "PMID" : "22246551", "abstract" : "Pulmonary cryptococcosis typically occurs in immunocompromised patients, but it can also occur in immunocompetent patients. 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Our objective was to describe the clinical manifestations, diagnosis, and management of primary pulmonary cryptococcosis in immunocompetent patients.", "author" : [ { "dropping-particle" : "", "family" : "Ye", "given" : "Feng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Jia-xing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeng", "given" : "Qing-si", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Guo-qin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Shu-qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhong", "given" : "Nan-shan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lung", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "339-46", "title" : "Retrospective analysis of 76 immunocompetent patients with primary pulmonary cryptococcosis.", "type" : "article-journal", "volume" : "190" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1086/322597", "ISBN" : "1058-4838 (Print)\\n1058-4838", "ISSN" : "1058-4838", "PMID" : "11477526", "abstract" : "We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.", "author" : [ { "dropping-particle" : "", "family" : "Pappas", "given" : "P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cloud", "given" : "G a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankey", "given" : "G a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lancaster", "given" : "D J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauffman", "given" : "C a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haas", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saccente", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holloway", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warren", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "W E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "690-699", "title" : "Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1128/AAC.01299-15.Address", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "Kyle D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Achan", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hullsiek", "given" : "Kathy Huppler", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mcdonald", "given" : "Tami R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okagaki", "given" : "Laura H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alhadab", "given" : "Ali A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akampurira", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhein", "given" : "Joshua R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meya", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boulware", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Antimicrobial Agents and Chemotherapy", "id" : "ITEM-6", "issue" : "12", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "7197-7204", "title" : "Increased antifungal drug resistance in clinical isolates of <i> Cryptococcus neoformans</i> in Uganda", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "^{6,179,180,182,183,273}", "plainTextFormattedCitation" : "6,179,180,182,183,273", "previouslyFormattedCitation" : "^{6,178,179,181,182,273}" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6,179,180,182,183,273Table 3. Differential diagnosis of pulmonary cryptococcosis.*ConditionSimilarity with pulmonary cryptococcosisDifferentiating testBacterial, mycobacterial, viral, or other pulmonary fungal infectionsBacteria: Fusobacterium, Pseudomonas, StreptococcusAtypical pathogen and Mycobacteria:Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophilaMycobacterium tuberculosis, M. kansasiiVirus: cytomegalovirusOther pulmonary fungal infections:Aspergillus, Pneumocystis, Histoplasma, CoccidioidesThe same signs and symptomsThe same radiological appearancesBAL/ Sputum microscopy and culture: positive for specific organismSerum/BAL CrAG testDetection of mycobacteria using GenXpert TB or Ziehl-Neelsen stain to show acid-fast bacilli: to differentiate mycobacteriaImmunofluorescence, Gomori methenamine, or Wright-Giemsa staining of sputum/bronchoalveolar lavageHIV and CD4 countPrimary lung cancer or metastatic neoplasm The same radiological appearancesCould be asymptomatic at allCT or MRI of the lung or other organ shows presence of primary or metastatic tumour(s)Tissue biopsy: malignant cells *Adapted from Limper et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1513/pats.200906-049AL", "ISSN" : "1943-5665", "PMID" : "20463243", "abstract" : "Fungal lung infections are being diagnosed with increasing frequency. This is related to the increased numbers of immune-compromised and other susceptible patient groups. This article will focus on the evolving epidemiology of fungal lung infections and clinical manifestations that should prompt the clinician to consider the possibility of fungal lung infection. In addition, current approaches for the diagnosis of these infection are also reviewed. Heightened awareness of fungal lung infection, and appropriate use of the available diagnostic modalities, will permit appropriate treatment of these important clinical infections in immune-compromised individuals.", "author" : [ { "dropping-particle" : "", "family" : "Limper", "given" : "Andrew H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the American Thoracic Society", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "163-168", "title" : "The changing spectrum of fungal infections in pulmonary and critical care practice: clinical approach to diagnosis.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁵", "plainTextFormattedCitation" : "15", "previouslyFormattedCitation" : "¹⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }15 ; Li et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/myc.12645", "ISSN" : "09337407", "PMID" : "28857298", "abstract" : "Diabetes mellitus II (DM II) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. This retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in Chinese DM II patients. This study included 30 cases of cryptococcosis with DM II occurring from 1993 to 2015 in mainland China. The hospital-based prevalence of cryptococcosis in DM II was 0.21%. The mean age of the patients was 56.1 years (95% confidence interval: 51.5, 60.6), and 93% of the patients were older than 40 years. Sixty-two per cent of the patients experienced untreated or poorly controlled blood glucose before infection. Multilocus sequence typing analysis categorised all cultured strains as Cryptococcus neoformans and sequence type 5. Sixty-nine per cent of pulmonary cryptococcosis patients experienced misdiagnoses and treatment delays. Sixty per cent of cryptococcal meningitis patients received substandard antifungal therapy. The overall death rate was 33%. Considering the large population size of DM II patients in China, improved attention should be paid to the high prevalence of cryptococcosis as revealed by us. We also emphasised the importance of blood glucose control for infection prevention, especially among the elderly.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "Yingfang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Wenjie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiang", "given" : "Weiwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hagen", "given" : "Ferry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Xiaoguang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lei", "given" : "Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Danqi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jianping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boekhout", "given" : "Teun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Mycoses", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "706-713", "title" : "Cryptococcosis in patients with diabetes mellitus II in mainland China: 1993-2015", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁶³", "plainTextFormattedCitation" : "163", "previouslyFormattedCitation" : "¹⁶³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }163 ; Riha, Pataka.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Riha", "given" : "Renata L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pataka", "given" : "Athanasia D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Medical Journals", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "BMJ Best Practice: Cryptococcosis", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁸⁷", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "¹⁸⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187 ; Guimares et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00408-013-9506-0", "ISBN" : "0341-2040", "ISSN" : "03412040", "PMID" : "24043490", "abstract" : "OBJECTIVE: The purpose of this study was to evaluate the clinical and radiological features of patients with fungal infection mimicking thoracic malignancy and to establish a diagnostic approach for both clinicians and radiologists to avoid misdiagnosis. METHODS: In this retrospective study, we reviewed clinical and computed tomography (CT) findings from 27 patients who presented with suspicion of thoracic malignancy who were ultimately diagnosed with fungal disease. RESULTS: Patients' median age was 55.7 (range 31-78) years. The most common clinical findings were cough (48.1 %), expectoration (33.3 %), chest pain (25.9 %), weakness (25.9 %), weight loss (18.5 %), and hemoptysis, dyspnea, and fever (7.4 % each). The median lesion size was 35.5 (range 10-85) mm. CT findings included a solid nodule (51.9 %), solid mass (37 %), or both (11.1 %). Nodule and mass margins were lobulated in 9 (33.3 %) patients, ill-defined in 5 (18.5 %), spiculated in 4 (14.8 %), and smooth in 4 (14.8 %) patients. Additional findings included consolidation in 4 (14.8 %) patients, cavitation in 3 (11.1 %), pleural effusion in 2 (7.4 %), and lymphadenopathy in 11 (40.7 %) patients. In all patients, specific diagnoses were made and confirmed by histopathology; final diagnoses were histoplasmosis (25.9 %), coccidiomycosis (22.2 %), cryptococcosis (22.2 %), aspergillosis (14.8 %), North American blastomycosis (7.4 %), mucormycosis (3.75 %), and paracoccidioidomycosis (3.75 %). CONCLUSIONS: Fungal infection can present with clinical and radiological features that are indistinguishable from thoracic malignancy, such as lung nodules or masses. Because the management and outcomes of fungal infection and malignancy are entirely distinct, the establishment of a specific diagnosis is critical to provide appropriate therapy.", "author" : [ { "dropping-particle" : "", "family" : "Guimaraes", "given" : "Marcos Duarte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchiori", "given" : "Edson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza Portes Meirelles", "given" : "Gustavo", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hochhegger", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santana", "given" : "Pablo Rydz Pinheiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gross", "given" : "Jefferson Luiz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bitencourt", "given" : "Almir Galvao Vieira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boonsirikamchai", "given" : "Piyaporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godoy", "given" : "Myrna Corbos Barco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lung", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "655-662", "title" : "Fungal infection mimicking pulmonary malignancy: Clinical and radiological characteristics", "type" : "article-journal", "volume" : "191" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "¹⁹⁰", "plainTextFormattedCitation" : "190", "previouslyFormattedCitation" : "¹⁹⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }190 ; Guarner, Brandt.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/CMR.00053-10", "ISBN" : "1098-6618 (Electronic)\\r0893-8512 (Linking)", "ISSN" : "08938512", "PMID" : "21482725", "abstract" : "Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.", "author" : [ { "dropping-particle" : "", "family" : "Guarner", "given" : "Jeannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandt", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "247-280", "title" : "Histopathologic diagnosis of fungal infections in the 21st century", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁰⁴", "plainTextFormattedCitation" : "204", "previouslyFormattedCitation" : "²⁰⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }204 ; Thibodeau, Viera.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1726-426X", "abstract" : "Atypical organisms such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila are implicated in up to 40 percent of cases of community-acquired pneumonia. Antibiotic treatment is empiric and includes coverage for both typical and atypical organisms. Doxycycline, a fluoroquinolone with enhanced activity against Streptococcus pneumoniae, or a macrolide is appropriate for outpatient treatment of immunocompetent adult patients. Hospitalised adults should be treated with cefotaxime or ceftriaxone plus a macrolide, or with a fluoroquinolone alone. The same agents can be used in adult patients in intensive care units, although fluoroquinolone monotherapy is not recommended; ampicillin-sulbactam or piperacillin-tazobactam can be used instead of cefotaxime or ceftriaxone. Outpatient treatment of children two months to five years of age consists of high-dose amoxicillin given for seven to 10 days. A single dose of ceftriaxone can be used in infants when the first dose of antibiotic is likely to be delayed or not absorbed. Older children can be treated with a macrolide. Hospitalised children should be treated with a macrolide plus a beta-lactam inhibitor. In a bioterrorist attack, pulmonary illness may result from the organisms that cause anthrax, plague, or tularaemia. Sudden acute respiratory syndrome begins with a flu-like illness, followed two to seven days later by cough, dyspnoea and, in some instances, acute respiratory distress. Copyright\u00a9 2004 American Academy of Family Physicians.", "author" : [ { "dropping-particle" : "", "family" : "Thibodeau", "given" : "Kristopher P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viera", "given" : "Anthony J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Academy of Family Physicians", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "14-19", "title" : "Atypical pathogens and challenges in community-acquired pneumonia", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁰⁵", "plainTextFormattedCitation" : "205", "previouslyFormattedCitation" : "²⁰⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }205 ; and Shibuya et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S1201-9712(01)90030-X", "ISSN" : "12019712", "PMID" : "11468102", "abstract" : "OBJECTIVE: To gain insight into the histopathologic characteristics of fungal infection in acquired immunodeficiency syndrome (AIDS). METHODS: A review was conducted of the histopathology for 162 patients with evident fungal infection. RESULTS: The microscopic appearance of esophageal candidiasis that was common in patients with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida infection. Eighteen patients had generalized cryptococcosis, representing the commonest generalized fungal disease. The essential histologic features of the disease consisted of yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from the manifestations of both Candida and Aspergillus infections. The two histologic patterns recognized in the pulmonary cryptococcal lesions could be graded with respect to the degree and type of inflammatory reaction. The milder one consisted of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which might be simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in all 18 patients.", "author" : [ { "dropping-particle" : "", "family" : "Shibuya", "given" : "Kazutoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coulson", "given" : "Walter F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wollman", "given" : "Jerome S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wakayama", "given" : "Megumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ando", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oharaseki", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takahashi", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naoe", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of infectious diseases", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "78-85", "title" : "Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁰⁶", "plainTextFormattedCitation" : "206", "previouslyFormattedCitation" : "²⁰⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }206Table 4. Review of PCR methods for Cryptococcus spp. NoPCR methodSamplesDNA extractionPrimer/target geneAccuracy & LoDReference1Singleplex PCR (Cryptococcus neoformans var. grubii, C. neoformans var. neoformans, C. gattii and hybrids)References strain-STR1F and STR1RSensitivity: 99.2%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/JCM.00064-13", "ISBN" : "0095-1137", "ISSN" : "00951137", "PMID" : "23536400", "abstract" : "A singleplex PCR assay using a single primer pair targeting the putative sugar transporter gene was developed here to distinguish Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, and Cryptococcus gattii according to the distinct size of the amplicon. The interspecies and intravarietal hybrids were also characterized on the basis of distinct combined profiles of amplicons. This PCR assay is a rapid, simple, and reliable approach suitable for laboratory diagnoses and large-scale epidemiologic studies.", "author" : [ { "dropping-particle" : "", "family" : "Feng", "given" : "Xiaobo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fu", "given" : "Xiaohua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ling", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Lei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wanqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yao", "given" : "Zhirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1920-1923", "title" : "Development of a singleplex PCR assay for rapid identification and differentiation of <i>Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. neoformans, Cryptococcus gattii</i>, and hybrids.", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁵", "plainTextFormattedCitation" : "235", "previouslyFormattedCitation" : "²³⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2352PCR and restriction digest (C. neoformans and C. gattii)Clinical isolates collectionThermal shock methodITS4-ITS5 continue with restriction digest with NS7-ITS2 and NS7-ITS4-ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/jclinpath-2014-202790", "author" : [ { "dropping-particle" : "", "family" : "Ogundeji", "given" : "Adepemi O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albertyn", "given" : "Jacobus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pohl", "given" : "Carolina H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sebolai", "given" : "Olihile M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Pathol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-6", "title" : "Method for identification of <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> useful in resource-limited settings", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴⁰", "plainTextFormattedCitation" : "240", "previouslyFormattedCitation" : "²⁴⁰" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2403Nested PCR (C. neoformans) Sputum, BAL, biopsy, bronchial aspirates from PC patientsglass bead technique and heat treatmentURA5 gene10 pg;1x103 CFUADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0095-1137", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyazaki", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maesaki", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitsutake", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakeya", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanagihara", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hossain", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tashiro", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohno", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "2826-2828", "title" : "Detection of <i>Cryptococcus neoformans</i> gene in patients with pulmonary crptococcosis", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴¹", "plainTextFormattedCitation" : "241", "previouslyFormattedCitation" : "²⁴¹" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2414Multiplex PCR (serotype and mating type of C. neoformans)Pigeon droppingsglass bead techniqueSTE20 gene-ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1590/S0036-46652007000400002", "ISBN" : "0036-4665 (Print)\\r0036-4665 (Linking)", "ISSN" : "00364665", "PMID" : "17823747", "abstract" : "Cryptococcus neoformans is an encapsulated yeast, etiological agent of cryptococcosis. The species is commonly associated with pigeon droppings and plant materials. The aim of the present work was to verify the presence of the yeast in pigeon droppings, and to identify the isolates obtained in serotypes and mating types (MAT). Ten samples of pigeon droppings were collected in the rural area of the city of Alfenas, Brazil. Samples were inoculated in agar Niger medium for fungal isolation and 22 isolates with characteristics of C. neoformans were obtained. The serotypes and MAT were determined by multiplex PCR using specific primers. Serotypes were also determined by using the Kit Crypto Check. Among the 22 samples evaluated, eight were identified as C. neoformans by classic identification tests. These samples were characterized as serotype A by the Kit Crypto check and as serotype A MAT alpha by the multiplex PCR. The present study reinforces the evidence that pigeon droppings are a reservoir for C. neoformans and confirms the prevalence of C. neoformans var. grubii (A alpha) among environmental isolates. It also demonstrates that multiplex PCR is an acceptable alternative for serotype analysis because it reduces the costs for each reaction and analyses serotype and MAT simultaneously.", "author" : [ { "dropping-particle" : "", "family" : "Carvalho", "given" : "Vivian Goncalves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Terceti", "given" : "Mateus Souza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dias", "given" : "Amanda Latercia Tranches", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paula", "given" : "Claudete Rodrigues", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyon", "given" : "Juliana Pereira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siqueira", "given" : "Antonio Martins", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franco", "given" : "Marilia Caixeta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Revista do Instituto de Medicina Tropical de Sao Paulo", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "207-210", "title" : "Serotype and mating type characterization of <i>Cryptococcus neoformans</i> by multiplex PCR", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴²", "plainTextFormattedCitation" : "242", "previouslyFormattedCitation" : "²⁴²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2425Nested and real time PCRBrain from infected miceQIAamp tissue kitrRNA (18S rDNA)1 to 10 CFUADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/CDLI.9.2.461", "ISBN" : "1071-412X (Print)\\r1071-412X (Linking)", "ISSN" : "1071-412X", "PMID" : "11874894", "abstract" : "Two PCR protocols targeting the 18S rRNA gene of Cryptococcus neoformans were established, compared, and evaluated in murine cryptococcal meningitis. One protocol was designed as a nested PCR to be performed in conventional block thermal cyclers. The other protocol was designed as a quantitative single-round PCR adapted to LightCycler technology. One hundred brain homogenates and dilutions originating from 20 ICR mice treated with different azoles were examined. A fungal burden of 3 x 10(1) to 2.9 x 10(4) CFU per mg of brain tissue was determined by quantitative culture. Specific PCR products were amplified by the conventional and the LightCycler methods in 86 and 87 samples, respectively, with products identified by DNA sequencing and real-time fluorescence detection. An analytical sensitivity of 1 CFU of C. neoformans per mg of brain tissue and less than 10 CFU per volume used for extraction was observed for both PCR protocols, while homogenates of 70 organs from mice infected with other fungi were PCR negative. Specificity testing was performed with genomic DNA from 31 hymenomycetous fungal species and from the ustilaginomycetous yeast Malassezia furfur, which are phylogenetically related to C. neoformans. Twenty-four strains, including species of human skin flora like M. furfur and Trichosporon spp., were PCR negative. Amplification was observed with Cryptococcus amylolentus, Filobasidiella depauperata, Cryptococcus laurentii, and five species unrelated to clinical specimens. LightCycler PCR products from F. depauperata and Trichosporon faecale could be clearly discriminated by melting curve analysis. The sensitive and specific nested PCR assay as well as the rapid and quantitative LightCycler PCR assay might be useful for the diagnosis and monitoring of human cryptococcal infections.", "author" : [ { "dropping-particle" : "", "family" : "Bialek", "given" : "Ralf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bekure-Nemariam", "given" : "Kubrom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Najvar", "given" : "Laura K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alberdi", "given" : "Maria B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graybill", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reischl", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and diagnostic laboratory immunology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "461-9", "title" : "Detection of <i>Cryptococcus neoformans</i> DNA in tissue samples by nested and real-time PCR assays.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴³", "plainTextFormattedCitation" : "243", "previouslyFormattedCitation" : "²⁴³" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2436Multiplex PCR (C. gattii, C. neoformans var neoformans and var. grubii)Clinical isolates recovered by cultureCTAB technique CNa-70S and CNa- 70A for C. neoformans, CNb-49S and CNb-49A for C. gattii1.25 ng, 100% agreement with serotypingADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/13693780701824429", "ISBN" : "1369-3786 (Print)\\r1369-3786 (Linking)", "ISSN" : "13693786", "PMID" : "18415847", "abstract" : "Members of the Cryptococcus species complex are encapsulated basidiomycetous yeasts, which can affect the central nervous system (CNS) and if untreated may cause meningitis. Cryptococcus neoformans is an opportunistic pathogen causing infections mainly in immunocompromised individuals. Cryptococcus gattii is a primary pathogen responsible for a high incidence of cryptococcomas in the lung and brain and shows a delayed response to antifungal therapy. The differentiation between the two species is primarily based on their growth on and color change of canavanine - glycine-bromothymol blue agar (CGB). Since this test is not always reliable, a multiplex PCR to identify both Cryptococcus species using more than 130 samples was standardized and the results obtained compared to those with the CGB test, using the Crypto Check serotyping kit as the standard. The multiplex PCR was shown to be more specific than the CGB test, in that results obtained with it were in agreement with those from serotyping all the samples, while the data from the CGB test disagreed with 6 out of 131 samples.", "author" : [ { "dropping-particle" : "", "family" : "Leal", "given" : "Ana Lusia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faganello", "given" : "Josiane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassanesi", "given" : "Maria Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vainstein", "given" : "Marilene H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical mycology : official publication of the International Society for Human and Animal Mycology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "377-383", "title" : "<i>Cryptococcus</i> species identification by multiplex PCR.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁷", "plainTextFormattedCitation" : "237", "previouslyFormattedCitation" : "²³⁷" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2377Multiplex RT PCR (C. neoformans)Clinical samples (BAL, sputum, blood)-OLI CRYPTO 1 2OLI CRYPTO 22 fg, sensitivity: 90.7%, specificity: 100%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1128/JCM.02895-13", "ISBN" : "0095-1137", "ISSN" : "1098660X", "PMID" : "24478409", "abstract" : "A molecular diagnostic technique based on real-time PCR was developed for the simultaneous detection of three of the most frequent causative agents of fungal opportunistic pneumonia in AIDS patients: Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii. This technique was tested in cultured strains and in clinical samples from HIV-positive patients. The methodology used involved species-specific molecular beacon probes targeted to the internal transcribed spacer regions of the rDNA. An internal control was also included in each assay. The multiplex real-time PCR assay was tested in 24 clinical strains and 43 clinical samples from AIDS patients with proven fungal infection. The technique developed showed high reproducibility (r(2) of >0.98) and specificity (100%). For H. capsulatum and Cryptococcus spp., the detection limits of the method were 20 and 2 fg of genomic DNA/20 \u03bcl reaction mixture, respectively, while for P. jirovecii the detection limit was 2.92 log10 copies/20 \u03bcl reaction mixture. The sensitivity in vitro was 100% for clinical strains and 90.7% for clinical samples. The assay was positive for 92.5% of the patients. For one of the patients with proven histoplasmosis, P. jirovecii was also detected in a bronchoalveolar lavage sample. No PCR inhibition was detected. This multiplex real-time PCR technique is fast, sensitive, and specific and may have clinical applications.", "author" : [ { "dropping-particle" : "", "family" : "Gago", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esteban", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valero", "given" : "Clara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaragoza", "given" : "Oscar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "La Bellacasa", "given" : "Jorge Puig", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buitrago", "given" : "Maria Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Microbiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1168-1176", "title" : "A multiplex real-time PCR assay for identification of <i>Pneumocystis jirovecii</i>, <i>Histoplasma capsulatum</i>,and <i>Cryptococcus neoformans</i>/<i>Cryptococcus gattii</i> in samples from AIDS patients with opportunistic pneumonia", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁴", "plainTextFormattedCitation" : "234", "previouslyFormattedCitation" : "²³⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2348Nested PCR (C. neoformans)Cerebrospinal fluidchloroform techniqueFirst run:ITS-1and CN-4 Second run: CN-5 and CN-610 cellsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0095-1137", "PMID" : "9774618", "abstract" : "We report the development of a nested-PCR-based assay for the detection of Cryptococcus neoformans in cerebrospinal fluid. The specificity and sensitivity of the test were assessed. The technique was then applied to 40 cerebrospinal fluid samples. We obtained positive reactions for all 21 clinical samples from patients who had been previously diagnosed as having cryptococcal meningitis by conventional techniques and negative reactions for all 19 negative controls. Nested PCR is here compared with other diagnostic methods currently used in patients' follow-up exams during anticryptococcal therapy.", "author" : [ { "dropping-particle" : "", "family" : "Rappelli", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Are", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Casu", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fiori", "given" : "P L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappuccinelli", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aceti", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical microbiology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "3438-40", "title" : "Development of a nested PCR for detection of <i>Cryptococcus neoformans</i> cerebrospinal fluid.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴⁴", "plainTextFormattedCitation" : "244", "previouslyFormattedCitation" : "²⁴⁴" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2449Comparison primer sets (C. gattii and C. neoformans)Cerebrospinal fluidQIAamp DNA mini kitCN4–CN5(coding rDNA) & the multiplex CNa70S–CNa70A/CNb49S–CNb-49A Sensitivity: 94.8% Specificity: 98.5%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bjid.2014.09.004", "ISSN" : "16784391", "PMID" : "25523072", "abstract" : "Aim: This study evaluated the use of polymerase chain reaction for cryptococcal meningitis diagnosis in clinical samples. Materials and methods: The sensitivity and specificity of the methodology were evaluated using eight Cryptococcus neoformans/C. gattii species complex reference strains and 165 cerebrospinal fluid samples from patients with neurological diseases divided into two groups: 96 patients with cryptococcal meningitis and AIDS; and 69 patients with other neurological opportunistic diseases (CRL/AIDS). Two primer sets were tested (CN4-CN5 and the multiplex CNa70S-CNa70A/CNb49S-CNb-49A that amplify a specific product for C. neoformans and another for C. gattii). Results: CN4-CN5 primer set was positive in all Cryptococcus standard strains and in 94.8% in DNA samples from cryptococcal meningitis and AIDS group. With the multiplex, no 448-bp product of C. gattii was observed in the clinical samples of either group. The 695. bp products of C. neoformans were observed only in 64.6% of the cryptococcal meningitis and AIDS group. This primer set was negative for two standard strains. The specificity based on the negative samples from the CTL/AIDS group was 98.5% in both primer sets. Conclusions: These data suggest that the CN4/CN5 primer set was highly sensitive for the identification of C. neoformans/C. gattii species complex in cerebrospinal fluid samples from patients with clinical suspicion of cryptococcal meningitis.", "author" : [ { "dropping-particle" : "", "family" : "Martins", "given" : "Marilena dos Anjos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brighente", "given" : "Kate Bastos Santos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matos", "given" : "Terezinha Aparecida", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vidal", "given" : "Jose Ernesto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hipolito", "given" : "Daise Damaris Carnietto", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira-Chioccola", "given" : "Vera Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brazilian Journal of Infectious Diseases", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "62-67", "publisher" : "Elsevier Editora Ltda", "title" : "Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: Comparison of primer sets for <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> species complex", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²³⁶", "plainTextFormattedCitation" : "236", "previouslyFormattedCitation" : "²³⁶" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }236PCR, polymerase chain reaction; RT, real-time; BAL, bronchoalveolar lavage; DNA, deoxyribonucleic acid; LoD, limit of detection; PC, pulmonary cryptococcosis; CFU, colony forming unit; CTAB, cetyl trimethylammonium bromide.Table 5. Summary of antifungal therapy for pulmonary cryptococcosis.*HIV and immunocompromised patientsAsymptomatic, Mild disease, and/or positive cultureFluconazole 400-800 mg/d or itraconazole 400 mg/d for 6-12 months, followed by maintenanceMaintenance discontinued after HAART therapy if disease free and CD4 count > 200 cells/?L for MaintenanceFluconazole (200 mg/d)-64135000ImmunocompetentColonisedNo specific antifungal therapy-6413545402500Symptomatic, mild-moderate diseaseFluconazole (400-800 mg/d initially), for 6-12 months or itraconazole (400mg/d for 6 months)Suggested extended duration if the response is not complete *Adapted from Perfect et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/649858", "ISBN" : "1537-6591 (Electronic)\\r1058-4838 (Linking)", "ISSN" : "1537-6591", "PMID" : "20047480", "abstract" : "Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.", "author" : [ { "dropping-particle" : "", "family" : "Perfect", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dromer", "given" : "Francoise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graybill", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamill", "given" : "Richard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lortholary", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "Minh-Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pappas", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powderly", "given" : "William G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Nina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sobel", "given" : "Jack D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorrell", "given" : "Tania C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "291-322", "title" : "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²¹²", "plainTextFormattedCitation" : "212", "previouslyFormattedCitation" : "²¹²" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }212 and Limper et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1164/rccm.2008-740ST", "ISBN" : "1535-4970 (Electronic)\\r1073-449X (Linking)", "ISSN" : "1073449X", "PMID" : "21193785", "abstract" : "With increasing numbers of immune-compromised patients with malignancy, hematologic disease, and HIV, as well as those receiving immunosupressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, the incidence of fungal infections has dramatically increased over recent years. Definitive diagnosis of pulmonary fungal infections has also been substantially assisted by the development of newer diagnostic methods and techniques, including the use of antigen detection, polymerase chain reaction, serologies, computed tomography and positron emission tomography scans, bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. At the same time, the introduction of new treatment modalities has significantly broadened options available to physicians who treat these conditions. While traditionally antifungal therapy was limited to the use of amphotericin B, flucytosine, and a handful of clinically available azole agents, current pharmacologic treatment options include potent new azole compounds with extended antifungal activity, lipid forms of amphotericin B, and newer antifungal drugs, including the echinocandins. In view of the changing treatment of pulmonary fungal infections, the American Thoracic Society convened a working group of experts in fungal infections to develop a concise clinical statement of current therapeutic options for those fungal infections of particular relevance to pulmonary and critical care practice. This document focuses on three primary areas of concern: the endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections of special concern for immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections.", "author" : [ { "dropping-particle" : "", "family" : "Limper", "given" : "Andrew H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knox", "given" : "Kenneth S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarosi", "given" : "George A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ampel", "given" : "Neil M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "John E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Catanzaro", "given" : "Antonino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "Scott F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dismukes", "given" : "William E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hage", "given" : "Chadi A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marr", "given" : "Kieren A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mody", "given" : "Christopher H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perfect", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "David A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Respiratory and Critical Care Medicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "96-128", "title" : "An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients", "type" : "article-journal", "volume" : "183" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "²⁴⁵", "plainTextFormattedCitation" : "245", "previouslyFormattedCitation" : "²⁴⁵" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }245 ................
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