Loyola University Chicago



MICRO CASE-BASED SMALL GROUP DISCUSSION

SESSION 28

HIV

TUESDAY, APRIL 17, 2001

10:30AM – 12:30PM

READING ASSIGNMENT:

SHERRIS MEDICAL MICROBIOLOGY, CHAP. 50, PP. 619-622;

CHAP. 52, PP. 655-658;

CHAP. 41, PP. 547-555.

Case 1

History. A 47 year-old woman presented with chief complaint of fever to 103 ºF, non-productive cough and dyspnea which has progressed over one week. She was tested HIV-positive 5 years ago at which time her CD4 lymphocyte count was 583. Zidovudine was started, but she stopped taking it after one month and did not return to her doctor for follow-up. She has anorexia and lost 70 pounds over the last 3 months.

She used heroin and cocaine intravenously for a six month period 6 years ago. She does not smoke or drink, has no past STD's and is not sexually active. She has no known drug allergies (NKDA).

Physical Examination. She was pale, diaphoretic and in acute respiratory distress. T 37.4º C, P 96/'min, R 30/min, BP 110/70. Oral thrush was present. Examination of the lungs disclosed poor inspiratory effort and bibasilar crackles 2/3 of the way up the posterior lung field. She had a tachycardia but no murmurs. Her abdomen was nontender, and there was no enlargement of the liver or spleen. Pelvic exam was normal except for vaginal candidiasis. Neurologic examination was normal.

Laboratory Evaluations:

Hgb 10.8 g/dl

WBC 7,500/mm3

Segs 43

Lymphs 41

Monos 9

Eos 6

Basos 1

Platelets 248k/mm3

ABG 7.48(pH)/32(pCO2)/51(pO2)/23(HCO3)

CD4 %=11.#=235/mm3

HIV RNA level 234,000 copies/ml

Induced sputum Direct fluorescence positive for Pneumocystis carinii

1. What is Pneumocystis?

Pneumocystis carinii is an organism of uncertain taxonomic position with ribosomal RNA sequences of fungi but DNA content, absent fungal protein elongation factor EF-3, and antimicrobial susceptibility characteristics all suggestive of protozoa. Its life cycle resembles sporozoa (protozoa). Similar (?identical) organisms are found in lungs of lower animals. It is a cause of serious pulmonary infections almost exclusively in immunocompromised humans.

2. How is Pneumocystis carinii acquired? Was this patient recently infected?

Study of epidemics suggest that person to person spread by airborne droplets occurs. Most cases in the US including those in AIDS patients are thought to represent reactivation of

latent infection. Nursery outbreaks in post-WWII Europe and more recently in Southeast Asia as well as reports of increased numbers of secondary cases on oncology wards in the US suggest person to person spread still occurs.

3. What is the mechanism by which Pneumocystis carinii causes pneumonia?

Pneumonia occurs in persons with suppressed T lymphocyte function as might be seen with starvation, corticosteroid administration or in HIV infection when CD4 T-lymphocyte count has dropped below 200/mM3. Virulence factors have not been identified. Pneumonia is characterized by alveoli filled with desquamated alveolar cells, monocytes, organisms and fluid producing a distinctive foamy appearance.

Type II pneumocytes are present. Round cells may be increased in the widened septa. Healing is generally complete but some fibrosis and even residual thin-walled cavities may be left.

4. How is infection with Pneumocystis carinii diagnosed?

Organisms can be identified morphologically in tissue biopsy or in pulmonary secretions. Induced sputum, bronchoalveolar lavage (obtained with bronchoscope) have reasonable yield. Organisms can be stained with Geimsa (trophozoite) or Gomori methenamine silver (cyst). A fluorescent tagged anti-pneumocystis monoclonal antibody direct fluorescence test is very useful.

The patient is started on intravenous trimethoprim/sulfamethoxazole (20 mg/kg/D trimethoprim: 100 mg/kg/D sulfamethoxazole) plus prednisone 40 mg twice daily. Two days later she is improved: respiratory rate is down to 18/min, O2 saturation is 98% with FiO2 of 21%. Trimethoprim sulfamethoxazole therapy is changed to oral. On day 5, she develops fever, a morbilliform rash and elevations of AST, ALT and alkaline phosphatase.

5. To what can we attribute the rash? Are the rash, fever and abnormalities in liver function related?

Rash, fever and hepatitis are characteristic of reaction to trimethoprim/sulfamethoxazole.

6. What alternative therapies are available?

Alternative treatments include pentamidine, trimetrexate, a dihydrofolate reductase inhibitor, atovaquone, a hydroxynapthoquinone, or the combination of primaquine and clindamycin can all be used. Seriously ill patients as indicated by a large a-A gradient benefit from systemic corticosteroids. In patients with moderate to severe pneumonia, pentamidine should probably be the first alternative.

7. What is the likelihood of an adverse reaction to trimethoprim sulfamethoxazole in a patient

with AIDS?

Over 50%.

8. Can relapses of pneumonia due to Pneumocystis carinii be prevented? How?

Yes, prophylactic low dose T/S or dapsone or aerosolized pentamidine will reduce the frequency or prevent recurrences.

Case 2

A 29 year-old woman with AIDS was admitted with fever, profuse watery diarrhea and right upper quadrant abdominal pain for 23 days. outpatient stool evaluation disclosed Cryptosporidium parvum but no WBC's. Paromomycin and anti-diarrheal agents failed to stop the diarrhea. She had no tenesmus and denied blood in the stools. She felt warm but did not take her temperature.

Her past history includes HIV infection diagnosed 3 years ago. Oral candidiasis was diagnosed last year. She is single and lives with her mother and 9 year old daughter. She is actively using heroin and cocaine.

Physical Examination. She appeared weak and emaciated but in no acute distress.

T 37.10C, P 120/min, R 24/min, BP 90/50 supine.

Head, eyes, ears, nose and mouth were normal. There was no cervical adenopathy. Lungs were clear to percussion and auscultation. There were increased bowel sounds and mild diffuse abdominal tenderness most prominent in the right upper quadrant. The rectum was unremarkable and stool guaiac was negative. Extremities and neurological examinations were normal.

Laboratory Evaluations:

Hgb 12.0

WBC 2,900

Segs 66

Lymphs 15

Monos 18

Platelets 203k/mm3

Na 133 meq/L

K 3.3 meq/L

Cl 107 meq/L

CO2 14 meq/L

Creatinine 2.3 mg/dl

X-rays of chest and abdomen normal

In the hospital hyperalimentation was started. Octreotide plus azithromycin were started without effect.

Colonoscopy and EGD showed cryptosporidia on the colonic mucosa and in the area of the ampulla.. AFB blood cultures grew Mycobacterium avium complex and she was started on clarithromycin and ethambutol.

1. What is Cryptosporidia? Describe its life cycle.

Cryptosporidia are sporozoan protozoan parasites that infect the intestinal tract of a wide range of mammals including humans. Life Cycle. The fully mature, infective oocysts are excreted in the stool of the parasitized animal. Following ingestion by another animal,

sporozoites are released from the oocyst and attach to the microvilli of the small bowel epithelial cells where they are transformed into trophozoites. They divide asexually by multiple fission (schizogony) to form schizonts containing eight daughter cells known as type 1 merozoites. Upon release from the schizont, each daughter cell attaches

itself to another epithelial cell, where it repeats the schizogony cycle, producing another generation of type I merozoites. Eventually, schizonts containing four type 2 merozoites are seen. Incapable of continued asexual reproduction, these develop into male (microgamete) and female (macrogamete) sexual forms. Following fertilization, the resulting zygote develops into an oocyst that is shed into the lumen of the bowel. The majority possess a thick protective cell wall that ensures their intact passage in the feces and survival in the external environment. Approximately 20% fail to develop the thick wall. The cell

membrane ruptures releasing infective sporozoites into the intestinal lumen and initiating a new "autoinfective" cycle within the original host. In the normal host, acquired immunity dampens both the cyclic production of type 1 merozoites and the formation of thin walled oocysts, halting further parasite multiplication and terminating the acute infection. In the immunocompromised (AIDS) both processes continue resulting in chronic infection.

2. How is cryptosporidia acquired?

Domestic animals are the major reservoir in this country. Transmission occurs by person to person, animal to person, and from the environment, particularly water. The principle route of transmission is by direct fecal-oral spread. Waterborne outbreaks, including one in Milwaukee affecting 403,000 persons, have occurred.

3. How does cryptosporidia cause disease?

Organisms apear as spherical structures arranged in rows along the microvilli of epithelial cells. They are covered by a double membrane derived from reflection, fusion and attenuation of the microvilli and are thus considered intracellular. There may be villous atrophy and blunting, crypt hyperplasia and lengthening, and infiltration of the lamina propria with inflammatory cells. Mechanism of diarrhea is not known. Studies in AIDS patients have shown secretory mechanisms unaffected by fasting and malabsorptive mechanisms with positive D-xylose and decreased absorption of vitamin B12 as well as

steatorrhea.

4. How is it treated?

There is no palliative or curative treatment for cryptosporidiosis. The disease is self-limited in the immunocompetent. Currently paromomycin (a luminal antimicrobic) or azithromycin to treat infection or octreotide (a somatostatin analogue) to control the diarrhea are used in persons with AIDS. Bovine transfer factor and hyperimmune bovine colostrum have been experimentally shown to ameliorate the symptoms. Recent publications have documented clinical resolution of cryptosporidiosis in patients who responded to highly active antiretroviral therapy.

5. What is Mycobacterium avium complex (MAC)?

Mycobacterium avium complex is a group of related acid-fast organisms that grow only slightly faster than M. tuberculosis and can be divided into a number of serotypes. Some cause disease in birds; others cause disease in mammals but not birds. They are found in soil and water and in infected animals.

6. Describe the pathogenesis of infection with MAC in persons infected with HIV.

Asymptomatic colonization after ingestion or inhalation precedes infection. Symptomatic localized infection can occur either in the lung or the G1 tract. The GI tract is probably the most common portal of entry. Focal pneumonias are uncommon in AIDS and dissemination usually ensues. Localized GI infection can occur from esophagus to rectum but the duodenum is most common. Dissemination usually involves many organs-- most commonly the blood, bone marrow, liver, spleen. and lymph nodes; but the organism has been recovered from the eye, brain, meninges, CSF. skin, tongue. heart, lung, stomach,

thyroid, breast, parathyroid, adrenals, kidney, pancreas, prostate, testis and urine. Microscopically, tissues are filled with large numbers of distended histiocytes that on Ziehl-Neelson staining are packed with acid-fast bacilli. The histologic picture in disseminated MAC disease is similar to that seen in lepromatous leprosy and reflects an inability of the host to mount an efftective cell-mediated immune response which would be manifest as a granulomatous reaction. Phagocytosis by macrophages in patients with AIDS appears to be intact but intracellular killing does not occur.

7. What are the clinical manifestations of infection with MAC in persons with AIDS?

Fever and weight loss are characteristic with chronic diarrhea, abdominal pain and signs of

extrahepatic biliary obstruction occurring less commonly. Severe anemia is common. Rarely reported are localized pneumonia, endobronchial lesions, arthritis, skin lesions and endophthalmitis.

8. How is infection with MAC diagnosed? What specimens are useful for culture?

Diagnosis is established by recovery of the organism from a normally sterile site but blood, bone marrow, lymph node, and liver are most common. Blood cultures are set up in specialized liquid medium with radiometric detection systems developed specifically for mycobacteria. DNA probes are used to rapidly identify any growth of acid- fast- positive organisms. Tissue samples show infiltration with swollen macrophages containing large numbers of mycobacteria on acid-fast staining.

9. Is infection with MAC treatable? What medications are used in its treatment? For prevention?

Yes, initial antimicrobial treatment should be with clarithromycin (high dose) or azithromycin plus ethambutol. Additional drugs may be used but recent results of clinical trials have shown that addition of clofazimine to a two drug regimen containing one of the macrolides plus ethambutol provided no benefit.

Besides clofazimine, amikacin , rifampin, rifabutin ciprofloxacin can all be used. AT LEAST TWO DRUGS SHOULD BE USED TO PREVENT EMERGENCE OF RESISTANT MUTANTS. Clinical response may require 2 - 8 weeks and therapy should be continued for life. PREVENTIVE THERAPY in patients at high risk (T-cell counts ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download