ATOPICA monography
WAVD Clinical consensus guidelines for demodicosisRalf S. Mueller*, Wayne Rosenkrantz?, Emmanuel Bensignor?, Joanna Kara?-T?cza §, Tara Paterson ?, Michael A. Shipstone*** Centre for Clinical Veterinary Medicine, LMU Munich, Veterinaerstra?e 13, 80539 Munich, Germany? Animal Dermatology Clinic, 2965 Edinger Ave, Tustin, California 92780, USA ? Dermatology Referral Service, 75003 Paris, 35510 Rennes-Cesson and 44000 Nantes and 13008 Marseille, France§ Dermawet Dermatology Service for Dogs and Cats, Odyńca 37 lok.1/2, 02-606 Warszawa, Poland ? Small Animal Medicine & Surgery Department, School of Veterinary Medicine, St. George's University, PO Box #7, St. George’s, Grenada, W.I.** Dermatology for Animals, 263 Appleby Road, Stafford Heights, QLD 4053, AustraliaConflict of interestRalf Mueller has been a consultant, lecturer, or has received financial support for studies from Bayer Animal Health (manufacturer of Advocate?), Elanco Animal Health (manufacturer of Interceptor? and Lotilaner?), Merial (manufacturer of Ivomec? and NexgardTM), MSD (manufacturer of Bravecto?), Novartis (manufacturer of Interceptor?), and Zoetis (manufacturer of Mitaban?, Simparica? and Stronghold?/ Revolution?). Wayne Rosenkrantz has been a consultant, lecturer, or has received financial support for studies from Merial (manufacturer of Ivomec? and NexgardTM), Merck Animal Health (manufacturer of Bravecto?), Elanco Animal Health (manufacturer of Interceptor? and Lotilaner?), and Zoetis (manufacturer of Mitaban?, Simparica? and Stronghold?/ Revolution?).Emmanuel Bensignor has been a consultant, lecturer, or has received financial support for studies from Merial (manufacturer of Ivomec? and NexgardTM), Merck Animal Health (manufacturer of Bravecto?), Elanco Animal Health (manufacturer of Interceptor? and Lotilaner?), and Zoetis (manufacturer of Mitaban?, Simparica? and Stronghold?). Joanna Kara?-T?cza has lectured for Bayer Animal Health (manufacturer of Advocate?), MSD (manufacturer of Bravecto?), Zoetis (manufacturer of Mitaban?, Simparica? and Stronghold?/ Revolution?).Tara Paterson has received financial support for studies from Bayer Animal Health (manufacturer of Advocate?).Michael Shipstone has been a consultant, lecturer, or has received financial support for studies from Merck Animal Health (manufacturer of Bravecto?), Elanco Animal Health (manufacturer of Interceptor? and Lotilaner?), and Zoetis (manufacturer of Mitaban?, Simparica? and Stronghold?).ContributionsRalf Mueller wrote the introduction, the sections about the pathogenesis, general treatment considerations, lotilaner, miscellaneous drugs and treatment of feline demodicosis, collected the contributions of the other authors, and edited, formatted and finalised the manuscript. Emmanuel Bensignor wrote the sections on diagnosis and milbemycin oxime, Joanna Kara?-T?cza those on breeding considerations, fluralaner and sarolaner, Tata Paterson the sections about moxidectin and ivermectin, Michael Shipstone those about clinical signs and doramectin, and Wayne Rosenkrantz initiated these clinical consensus guidelines and contributed the sections on amitraz, afoxolaner and the future outlook. AcknowledgementsThe authors would like to thank the WAVD for supporting this initiative, the many colleagues that published studies evaluating demodicosis in various species and its treatments and thus indirectly contributed to this manuscript, and Dr. Sonya Bettenay for her input on the manuscript.IntroductionIn the last couple of decades, position papersPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Xb2xsZW5iZXJnPC9BdXRob3I+PFllYXI+MjAxNjwvWWVh
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ADDIN EN.CITE.DATA 2 have become very popular in human medicine. This trend has also reached the veterinary field, where such papers are published with increasing frequency.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NdWVsbGVyPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE.DATA 6,7 Additionally, papers written by experts in the field may contain recommendations not feasible or understandable for lay people and general practitioners. With the clinical consensus guidelines, the World Association of Veterinary Dermatology has made an effort to provide up-to-date and relevant information about certain topics in veterinary dermatology, written by international panels reflecting expert opinions from different regions of the world and publish them as open access providing worldwide distribution.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3JpZWxsbzwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+
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ADDIN EN.CITE.DATA 8,9 The process of development of these clinical consensus guidelines were developed is unique, as input from other specialists and practitioners with expertise and interest in the topics are sought in addition to the authors and reviewers. The drafts of these papers are presented at national and international meetings and made available for comments from members of various dermatology organizations prior to final publication of the manuscript. The authors are proud to be part of this laudable effort and sincerely hope that these clinical consensus guidelines for demodicosis will be of help to many veterinarians all over the world. PathogenesisDemodicosis is a common disease in canine practicePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaXNjaG88L0F1dGhvcj48WWVhcj4xOTg5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 12-18 that are transmitted during the first days of life from the dam to the puppies. ADDIN EN.CITE <EndNote><Cite><Author>Greve</Author><Year>1966</Year><RecNum>43</RecNum><DisplayText><style face="superscript">19</style></DisplayText><record><rec-number>43</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849819">43</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Greve, J. H.</author><author>Gaafar, S. M.</author></authors></contributors><titles><title>Natural transmission of Demodex canis in dogs</title><secondary-title>J Am Vet Med Assoc</secondary-title></titles><periodical><full-title>J Am Vet Med Assoc</full-title></periodical><pages>1043-5</pages><volume>148</volume><number>9</number><edition>1966/05/01</edition><keywords><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>*Dog Diseases</keyword><keyword>Dogs</keyword><keyword>Mite Infestations/*veterinary</keyword></keywords><dates><year>1966</year><pub-dates><date>May 1</date></pub-dates></dates><isbn>0003-1488 (Print)
0003-1488 (Linking)</isbn><accession-num>5949148</accession-num><urls><related-urls><url> In most species, demodicosis only occurs when patients are immunocompromised due to other diseases or undergoing immunosuppressive therapies. Demodicosis in immunosuppressed individuals has been reported in humans, dogs and cats amongst others.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZXJuc3RlaW48L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA 20-26 With the exception of Demodex (D.) gatoi in the cat, the dog is the only species where young and otherwise healthy animals develop demodicosis. This juvenile demodicosis has been presumed to be due to a cell-mediated deficiency. ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006591">376</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Miller, W. Jr.</author><author>Griffin, C.E.</author><author>Campbell, C.A. </author></authors></contributors><titles><title>Canine demodicosis</title><secondary-title>Muller and Kirk's Small Animal Dermatology</secondary-title></titles><edition>7th</edition><dates><year>2012</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B.Saunders</publisher><urls></urls></record></Cite></EndNote>27 ImmunologyEarly studies showed a normal humoral response, but decreased lymphocyte blastogenesis in young dogs with naturally occurring demodicosis.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IaXJzaDwvQXV0aG9yPjxZZWFyPjE5NzU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 28,29 Treatment of puppies with anti-lymphocyte serum led to generalized demodicosis in eight puppies while their untreated littermates remained healthy. ADDIN EN.CITE <EndNote><Cite><Author>Owen</Author><Year>1972</Year><RecNum>409</RecNum><DisplayText><style face="superscript">30</style></DisplayText><record><rec-number>409</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499416552">409</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Owen, L. N.</author></authors></contributors><titles><title>Demodectic mange in dogs immunosuppressed with antilymphocyte serum</title><secondary-title>Transplantation</secondary-title></titles><periodical><full-title>Transplantation</full-title></periodical><pages>616-7</pages><volume>13</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>*Antilymphocyte Serum</keyword><keyword>Dog Diseases/*immunology</keyword><keyword>Dogs</keyword><keyword>Humans</keyword><keyword>*Immunosuppression</keyword><keyword>Mite Infestations/immunology/*veterinary</keyword><keyword>Skin Transplantation</keyword></keywords><dates><year>1972</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0041-1337 (Print)
0041-1337 (Linking)</isbn><accession-num>4556075</accession-num><urls><related-urls><url> Subsequently, a T cell exhaustion characterized by low numbers of circulating CD4+ T cells, ADDIN EN.CITE <EndNote><Cite><Author>Ferrer</Author><Year>2014</Year><RecNum>367</RecNum><DisplayText><style face="superscript">31</style></DisplayText><record><rec-number>367</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1497953698">367</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ferrer, L.</author><author>Ravera, I.</author><author>Silbermayr, K.</author></authors></contributors><auth-address>Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA, 01536, USA.</auth-address><titles><title>Immunology and pathogenesis of canine demodicosis</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>427-e65</pages><volume>25</volume><number>5</number><keywords><keyword>Animals</keyword><keyword>Dog Diseases/etiology/immunology/*parasitology</keyword><keyword>Dogs/immunology/parasitology</keyword><keyword>Mite Infestations/etiology/immunology/*veterinary</keyword><keyword>Mites/immunology</keyword></keywords><dates><year>2014</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1365-3164 (Electronic)
0959-4493 (Linking)</isbn><accession-num>24910252</accession-num><urls><related-urls><url> together with increased serum concentrations of IL-5, ADDIN EN.CITE <EndNote><Cite><Author>Tani</Author><Year>2002</Year><RecNum>366</RecNum><DisplayText><style face="superscript">32</style></DisplayText><record><rec-number>366</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1497953486">366</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tani, K.</author><author>Morimoto, M.</author><author>Hayashi, T.</author><author>Inokuma, H.</author><author>Ohnishi, T.</author><author>Hayashiya, S.</author><author>Nomura, T.</author><author>Une, S.</author><author>Nakaichi, M.</author><author>Taura, Y.</author></authors></contributors><auth-address>Department of Veterinary Surgery, Faculty of Agriculture, Yamaguchi University, Japan.</auth-address><titles><title>Evaluation of cytokine messenger RNA expression in peripheral blood mononuclear cells from dogs with canine demodicosis</title><secondary-title>J Vet Med Sci</secondary-title></titles><periodical><full-title>J Vet Med Sci</full-title></periodical><pages>513-8</pages><volume>64</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Cytokines/*biosynthesis/blood/genetics</keyword><keyword>Dog Diseases/*blood/immunology/parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Leukocytes, Mononuclear/*metabolism</keyword><keyword>Male</keyword><keyword>Mite Infestations/blood/immunology/*veterinary</keyword><keyword>RNA, Messenger/*blood/genetics</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction/veterinary</keyword><keyword>Skin Diseases, Parasitic/blood/immunology/parasitology/*veterinary</keyword><keyword>Statistics, Nonparametric</keyword></keywords><dates><year>2002</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0916-7250 (Print)
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ADDIN EN.CITE.DATA 33,34 and TGF-beta ADDIN EN.CITE <EndNote><Cite><Author>Tani</Author><Year>2002</Year><RecNum>366</RecNum><DisplayText><style face="superscript">32</style></DisplayText><record><rec-number>366</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1497953486">366</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tani, K.</author><author>Morimoto, M.</author><author>Hayashi, T.</author><author>Inokuma, H.</author><author>Ohnishi, T.</author><author>Hayashiya, S.</author><author>Nomura, T.</author><author>Une, S.</author><author>Nakaichi, M.</author><author>Taura, Y.</author></authors></contributors><auth-address>Department of Veterinary Surgery, Faculty of Agriculture, Yamaguchi University, Japan.</auth-address><titles><title>Evaluation of cytokine messenger RNA expression in peripheral blood mononuclear cells from dogs with canine demodicosis</title><secondary-title>J Vet Med Sci</secondary-title></titles><periodical><full-title>J Vet Med Sci</full-title></periodical><pages>513-8</pages><volume>64</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Cytokines/*biosynthesis/blood/genetics</keyword><keyword>Dog Diseases/*blood/immunology/parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Leukocytes, Mononuclear/*metabolism</keyword><keyword>Male</keyword><keyword>Mite Infestations/blood/immunology/*veterinary</keyword><keyword>RNA, Messenger/*blood/genetics</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction/veterinary</keyword><keyword>Skin Diseases, Parasitic/blood/immunology/parasitology/*veterinary</keyword><keyword>Statistics, Nonparametric</keyword></keywords><dates><year>2002</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0916-7250 (Print)
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ADDIN EN.CITE.DATA 16,33-35 In contrast, the proinflammatory cytokine TNF-alpha was reduced in dogs with demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Kumari</Author><Year>2017</Year><RecNum>382</RecNum><DisplayText><style face="superscript">34</style></DisplayText><record><rec-number>382</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499329587">382</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kumari, P.</author><author>Nigam, R.</author><author>Singh, A.</author><author>Nakade, U. P.</author><author>Sharma, A.</author><author>Garg, S. K.</author><author>Singh, S. K.</author></authors></contributors><auth-address>College of Biotechnology, DUVASU,Mathura - 281 001, U.P.,India.
Department of Veterinary Medicine,College of Veterinary Science and Animal Husbandry, DUVASU,Mathura - 281 001, U.P.,India.
Department of Pharmacology and Toxicology,College of Veterinary Science and Animal Husbandry, DUVASU,Mathura - 281 001, U.P.,India.</auth-address><titles><title>Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis</title><secondary-title>Parasitology</secondary-title></titles><periodical><full-title>Parasitology</full-title></periodical><pages>1-5</pages><keywords><keyword>cholinesterase</keyword><keyword>generalized demodicosis</keyword><keyword>interleukin-10</keyword><keyword>localized demodicosis</keyword><keyword>pyoderma</keyword><keyword>tumour necrosis factor-alpha</keyword></keywords><dates><year>2017</year><pub-dates><date>Jun 06</date></pub-dates></dates><isbn>1469-8161 (Electronic)
0031-1820 (Linking)</isbn><accession-num>28583218</accession-num><urls><related-urls><url> The CD4/CD8 ratio was lower and the number of CD8 positive cells was reported to be increased in dogs with generalized demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Singh</Author><Year>2010</Year><RecNum>423</RecNum><DisplayText><style face="superscript">35</style></DisplayText><record><rec-number>423</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499427866">423</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Singh, S. K.</author><author>Dimri, U.</author><author>Sharma, M. C.</author><author>Sharma, B.</author><author>Saxena, M.</author></authors></contributors><auth-address>Division of Medicine, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, India. pshankervet@</auth-address><titles><title>Determination of CD4+ and CD8+ T cells in the peripheral blood of dogs with demodicosis</title><secondary-title>Parasitology</secondary-title></titles><periodical><full-title>Parasitology</full-title></periodical><pages>1921-4</pages><volume>137</volume><number>13</number><keywords><keyword>Acari/immunology/*pathogenicity</keyword><keyword>Animals</keyword><keyword>CD4-CD8 Ratio</keyword><keyword>CD4-Positive T-Lymphocytes/*immunology</keyword><keyword>CD8-Positive T-Lymphocytes/*immunology</keyword><keyword>Dog Diseases/*immunology/parasitology/pathology</keyword><keyword>Dogs</keyword><keyword>Flow Cytometry</keyword><keyword>Mite Infestations/immunology/parasitology/pathology/*veterinary</keyword><keyword>Skin/immunology/parasitology/pathology</keyword><keyword>Skin Diseases, Parasitic/immunology/pathology/*veterinary</keyword><keyword>T-Lymphocyte Subsets</keyword></keywords><dates><year>2010</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1469-8161 (Electronic)
0031-1820 (Linking)</isbn><accession-num>20619062</accession-num><urls><related-urls><url> Histologically, demodicosis is characterized by a mural folliculitis with infiltrating CD8+ cytotoxic T cells, which resolves quickly with resolution of the demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Caswell</Author><Year>1997</Year><RecNum>24</RecNum><DisplayText><style face="superscript">36</style></DisplayText><record><rec-number>24</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849818">24</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Caswell, J. L.</author><author>Yager, J. A.</author><author>Parker, W. M.</author><author>Moore, P. F.</author></authors></contributors><auth-address>Department of Pathobiology, Ontario Veterinary College, University of Guelph, Canada.</auth-address><titles><title>A prospective study of the immunophenotype and temporal changes in the histologic lesions of canine demodicosis</title><secondary-title>Vet Pathol</secondary-title></titles><periodical><full-title>Vet Pathol</full-title></periodical><pages>279-87</pages><volume>34</volume><number>4</number><edition>1997/07/01</edition><keywords><keyword>Animals</keyword><keyword>Antigens, Differentiation, T-Lymphocyte/analysis</keyword><keyword>Biopsy</keyword><keyword>Dog Diseases/immunology/parasitology/*pathology</keyword><keyword>Dogs</keyword><keyword>Immunohistochemistry</keyword><keyword>Immunophenotyping</keyword><keyword>Mite Infestations/immunology/parasitology/pathology/*veterinary</keyword><keyword>Skin/*immunology/parasitology/pathology</keyword><keyword>Skin Diseases, Parasitic/immunology/*veterinary</keyword><keyword>T-Lymphocyte Subsets/cytology/immunology</keyword><keyword>T-Lymphocytes/*cytology/immunology</keyword></keywords><dates><year>1997</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0300-9858 (Print)
0300-9858 (Linking)</isbn><accession-num>9240836</accession-num><urls><related-urls><url> MHC class II receptors are upregulated in the skin of dogs with demodicosis, particularly in keratinocytes. ADDIN EN.CITE <EndNote><Cite><Author>Huisinga</Author><Year>2007</Year><RecNum>420</RecNum><DisplayText><style face="superscript">37</style></DisplayText><record><rec-number>420</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499427451">420</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Huisinga, M.</author><author>Failing, K.</author><author>Reinacher, M.</author></authors></contributors><auth-address>Institut fur Veterinar-Pathologie, Justus-Liebig-Universitat Giessen, Frankfurter Strasse 96, 35392 Giessen, Germany. maike.huisinga@vetmed.uni-giessen.de</auth-address><titles><title>MHC class II expression by follicular keratinocytes in canine demodicosis--an immunohistochemical study</title><secondary-title>Vet Immunol Immunopathol</secondary-title></titles><periodical><full-title>Vet Immunol Immunopathol</full-title></periodical><pages>210-20</pages><volume>118</volume><number>3-4</number><keywords><keyword>Animals</keyword><keyword>Dog Diseases/immunology/*metabolism</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>*Gene Expression Regulation</keyword><keyword>Hair Follicle/cytology</keyword><keyword>Histocompatibility Antigens Class II/*metabolism</keyword><keyword>Immunohistochemistry/*veterinary</keyword><keyword>Keratinocytes/immunology/*metabolism</keyword><keyword>Male</keyword><keyword>Mite Infestations/*immunology</keyword><keyword>Plasma Cells/cytology/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug 15</date></pub-dates></dates><isbn>0165-2427 (Print)
0165-2427 (Linking)</isbn><accession-num>17604845</accession-num><urls><related-urls><url> An immunosuppression as the cause of the demodicosis is further supported by a severe combined immunodeficiency (SCID) mouse model. SCID mice, which have no B and T cells, received skin grafts from dogs which were later infected with D. canis collected from a dog with demodicosis. Within one to three months mites proliferated in the grafted canine skin, but not the surrounding murine skin. ADDIN EN.CITE <EndNote><Cite><Author>Caswell</Author><Year>1996</Year><RecNum>25</RecNum><DisplayText><style face="superscript">38</style></DisplayText><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849818">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Caswell, J. L.</author><author>Yager, J. A.</author><author>Barta, J. R.</author><author>Parker, W.</author></authors></contributors><auth-address>Department of pathobiology, Ontario Veterinary College, University of Guelph, Ontario, Canada.</auth-address><titles><title>Establishment of Demodex canis on canine skin engrafted onto scid-beige mice</title><secondary-title>J Parasitol</secondary-title></titles><periodical><full-title>J Parasitol</full-title></periodical><pages>911-5</pages><volume>82</volume><number>6</number><edition>1996/12/01</edition><keywords><keyword>Animals</keyword><keyword>*Disease Models, Animal</keyword><keyword>Dog Diseases/*parasitology</keyword><keyword>Dogs</keyword><keyword>Mice</keyword><keyword>*Mice, SCID</keyword><keyword>Mite Infestations/parasitology/*veterinary</keyword><keyword>Mites/*growth & development</keyword><keyword>Skin/*parasitology</keyword><keyword>Skin Transplantation/veterinary</keyword></keywords><dates><year>1996</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0022-3395 (Print)
0022-3395 (Linking)</isbn><accession-num>8973399</accession-num><urls><related-urls><url> In another immunodeficient double knock-out mouse model lacking CD28 (a co-stimulatory molecule involved in T cell activation) and STAT6 (essential for a pathway that plays a role in IL-4 signal transduction and Th2 differentiation), mice developed a severe dermatitis due to a proliferation of Demodex mites. ADDIN EN.CITE <EndNote><Cite><Author>Liu</Author><Year>2004</Year><RecNum>496</RecNum><DisplayText><style face="superscript">39</style></DisplayText><record><rec-number>496</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502590328">496</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu ,Q.</author><author>Arseculeratne, C. </author><author>Liu, Z. </author><author>Whitmire, J. </author><author>Grusby, M.J. </author><author>Finkelman, F.D. </author><author>Darling, T.N. </author><author>Cheever, A.W. </author><author>Swearengen, J. </author><author>Urban, J.F. </author><author>Gause, W.C.</author></authors></contributors><titles><title>Simultaneous deficiency in CD28 and STAT6 results in chronic ectoparasite-induced inflammatory skin disease</title><secondary-title>Infect Immunol</secondary-title></titles><periodical><full-title>Infect Immunol</full-title></periodical><pages>3706-3715</pages><volume>72</volume><number>7</number><dates><year>2004</year></dates><urls></urls></record></Cite></EndNote>39 Initially there was debate as to whether the secondary bacterial infection seen with generalised demodicosis was contributing to, or in some way causing those immunological changes.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXJ0YTwvQXV0aG9yPjxZZWFyPjE5ODM8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 42,43 and at least the decreased lymphoblastogenesis seems to be a consequence rather than a cause of the disease. ADDIN EN.CITE <EndNote><Cite><Author>Paulik</Author><Year>1996</Year><RecNum>416</RecNum><DisplayText><style face="superscript">43</style></DisplayText><record><rec-number>416</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499419489">416</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Paulik, S.</author><author>Mojzisova, J.</author><author>Bajova, V.</author><author>Baranova, D.</author><author>Paulikova, I.</author></authors></contributors><auth-address>University of Veterinary Medicine, Kosice, Slovak Republic.</auth-address><titles><title>Lymphocyte blastogenesis to concanavalin A in dogs with localized demodicosis according to duration of clinical disease</title><secondary-title>Vet Med (Praha)</secondary-title></titles><periodical><full-title>Vet Med (Praha)</full-title></periodical><pages>245-9</pages><volume>41</volume><number>8</number><keywords><keyword>Animals</keyword><keyword>Concanavalin A/*pharmacology</keyword><keyword>Dog Diseases/*immunology/pathology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Lymphocyte Activation/*drug effects</keyword><keyword>Male</keyword><keyword>Mite Infestations/immunology/pathology/*veterinary</keyword><keyword>Time Factors</keyword></keywords><dates><year>1996</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0375-8427 (Print)
0375-8427 (Linking)</isbn><accession-num>8856995</accession-num><urls><related-urls><url> Not surprisingly, demodicosis is accompanied by an increase in markers for oxidative stress. ADDIN EN.CITE <EndNote><Cite><Author>Dimri</Author><Year>2008</Year><RecNum>419</RecNum><DisplayText><style face="superscript">44</style></DisplayText><record><rec-number>419</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499427405">419</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dimri, U.</author><author>Ranjan, R.</author><author>Kumar, N.</author><author>Sharma, M. C.</author><author>Swarup, D.</author><author>Sharma, B.</author><author>Kataria, M.</author></authors></contributors><auth-address>Division of Medicine, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, UP, India. udimri@ivri.up.nic.in</auth-address><titles><title>Changes in oxidative stress indices, zinc and copper concentrations in blood in canine demodicosis</title><secondary-title>Vet Parasitol</secondary-title></titles><periodical><full-title>Vet Parasitol</full-title></periodical><pages>98-102</pages><volume>154</volume><number>1-2</number><keywords><keyword>Animals</keyword><keyword>Case-Control Studies</keyword><keyword>Copper/*blood</keyword><keyword>Dog Diseases/*blood</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Lipid Peroxides/blood</keyword><keyword>Male</keyword><keyword>Mite Infestations/blood/*veterinary</keyword><keyword>Oxidative Stress/*physiology</keyword><keyword>Zinc/*blood</keyword></keywords><dates><year>2008</year><pub-dates><date>Jun 14</date></pub-dates></dates><isbn>0304-4017 (Print)
0304-4017 (Linking)</isbn><accession-num>18440148</accession-num><urls><related-urls><url> the overwhelming majority of affected juvenile dogs do not suffer from a recurrence following successful therapy, ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>15030556</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>45 it seems likely that the presumed cell-mediated deficiency is a temporary problem. -1250953352165Consensus Statement 1: Generalised demodicosis is most likely a consequence of temporary immunodeficiency in young dogs and is often associated with an immunosuppressive condition or treatment in older dogs.00Consensus Statement 1: Generalised demodicosis is most likely a consequence of temporary immunodeficiency in young dogs and is often associated with an immunosuppressive condition or treatment in older dogs.The first clinical signs of juvenile demodicosis in dogs occur typically in the first 18 months of life. ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006591">376</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Miller, W. Jr.</author><author>Griffin, C.E.</author><author>Campbell, C.A. </author></authors></contributors><titles><title>Canine demodicosis</title><secondary-title>Muller and Kirk's Small Animal Dermatology</secondary-title></titles><edition>7th</edition><dates><year>2012</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B.Saunders</publisher><urls></urls></record></Cite></EndNote>27 Adult-onset demodicosis also exists and is comparable to the demodicosis seen in other species. In the dog, this was reported to be associated with diseases or drugs leading to a compromised immune system such as leishmaniasis, ADDIN EN.CITE <EndNote><Cite><Author>Mozos</Author><Year>1999</Year><RecNum>22</RecNum><DisplayText><style face="superscript">46</style></DisplayText><record><rec-number>22</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849818">22</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mozos, E.</author><author>Perez, J.</author><author>Day, M. J.</author><author>Lucena, R.</author><author>Ginel, P. J.</author></authors></contributors><auth-address>Facultad de Veterinaria, Universidad de Cordoba, Avenida Medina Azahara 9, Cordoba, 14005, Spain.</auth-address><titles><title>Leishmaniosis and generalized demodicosis in three dogs: a clinicopathological and immunohistochemical study</title><secondary-title>J Comp Pathol</secondary-title></titles><periodical><full-title>J Comp Pathol</full-title></periodical><pages>257-68</pages><volume>120</volume><number>3</number><edition>1999/04/24</edition><keywords><keyword>Alopecia/complications/pathology/veterinary</keyword><keyword>Animals</keyword><keyword>Antigens, CD3/analysis</keyword><keyword>Dog Diseases/*pathology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Immunohistochemistry</keyword><keyword>Leishmaniasis/complications/pathology/*veterinary</keyword><keyword>Male</keyword><keyword>Mite Infestations/complications/pathology/*veterinary</keyword><keyword>Pyoderma/complications/pathology/veterinary</keyword><keyword>T-Lymphocytes/pathology</keyword></keywords><dates><year>1999</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0021-9975 (Print)
0021-9975 (Linking)</isbn><accession-num>10213670</accession-num><urls><related-urls><url>(98)90273-0 [pii]
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ADDIN EN.CITE.DATA 22 babesiosis, ADDIN EN.CITE <EndNote><Cite><Author>Tarello</Author><Year>2007</Year><RecNum>422</RecNum><DisplayText><style face="superscript">48</style></DisplayText><record><rec-number>422</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499427670">422</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tarello, W.</author></authors></contributors><titles><title>Remission of cunical signs of adult-onset generalized demodicosis after treatment for concurrent babesiosis and/or granulocytic ehrlichiosis in dogs</title><secondary-title>Parasite</secondary-title></titles><periodical><full-title>Parasite</full-title></periodical><pages>339-41</pages><volume>14</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Anti-Bacterial Agents/*therapeutic use</keyword><keyword>Antiprotozoal Agents/*therapeutic use</keyword><keyword>Babesiosis/drug therapy/*veterinary</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Ehrlichiosis/drug therapy/veterinary</keyword><keyword>Female</keyword><keyword>Insecticides/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>Retrospective Studies</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2007</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1252-607X (Print)
1252-607X (Linking)</isbn><accession-num>18225424</accession-num><urls><related-urls><url> ehrlichiosis, ADDIN EN.CITE <EndNote><Cite><Author>Tarello</Author><Year>2007</Year><RecNum>422</RecNum><DisplayText><style face="superscript">48</style></DisplayText><record><rec-number>422</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499427670">422</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tarello, W.</author></authors></contributors><titles><title>Remission of cunical signs of adult-onset generalized demodicosis after treatment for concurrent babesiosis and/or granulocytic ehrlichiosis in dogs</title><secondary-title>Parasite</secondary-title></titles><periodical><full-title>Parasite</full-title></periodical><pages>339-41</pages><volume>14</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Anti-Bacterial Agents/*therapeutic use</keyword><keyword>Antiprotozoal Agents/*therapeutic use</keyword><keyword>Babesiosis/drug therapy/*veterinary</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Ehrlichiosis/drug therapy/veterinary</keyword><keyword>Female</keyword><keyword>Insecticides/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>Retrospective Studies</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2007</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1252-607X (Print)
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ADDIN EN.CITE.DATA 22 One report mentioned atopic dermatitis as a frequent concurrent disease, but many dogs received glucocorticoid therapy. ADDIN EN.CITE <EndNote><Cite><Author>Bowden</Author><Year>2017</Year><RecNum>522</RecNum><DisplayText><style face="superscript">49</style></DisplayText><record><rec-number>522</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1506431274">522</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bowden, D. G.</author><author>Outerbridge, C. A.</author><author>Kissel, M. B.</author><author>Baron, J. N.</author><author>White, S. D.</author></authors></contributors><auth-address>William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California Davis, 1 Garrod Drive, Davis, CA, 95616, USA.
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California Davis, 1 Garrod Drive, Davis, CA, 95616, USA.</auth-address><titles><title>Canine demodicosis: a retrospective study of a veterinary hospital population in California, USA (2000-2016)</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><dates><year>2017</year><pub-dates><date>Sep 03</date></pub-dates></dates><isbn>1365-3164 (Electronic)
0959-4493 (Linking)</isbn><accession-num>28868794</accession-num><urls><related-urls><url> In cats, demodicosis has been reported in association with feline immunodeficiency virus,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGFsbWVyczwvQXV0aG9yPjxZZWFyPjE5ODk8L1llYXI+
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ADDIN EN.CITE.DATA 52 and diabetes mellitus. ADDIN EN.CITE <EndNote><Cite><Author>White</Author><Year>1987</Year><RecNum>495</RecNum><DisplayText><style face="superscript">53</style></DisplayText><record><rec-number>495</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502589240">495</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>White, S. D.</author><author>Carpenter, J. L.</author><author>Moore, F. M.</author><author>Ogilvie, G.</author></authors></contributors><auth-address>Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536.</auth-address><titles><title>Generalized demodicosis associated with diabetes mellitus in two cats</title><secondary-title>J Am Vet Med Assoc</secondary-title></titles><periodical><full-title>J Am Vet Med Assoc</full-title></periodical><pages>448-50</pages><volume>191</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>*Cat Diseases</keyword><keyword>Cats</keyword><keyword>Diabetes Complications</keyword><keyword>Diabetes Mellitus/*veterinary</keyword><keyword>Male</keyword><keyword>Mite Infestations/complications/*veterinary</keyword><keyword>Mites</keyword></keywords><dates><year>1987</year><pub-dates><date>Aug 15</date></pub-dates></dates><isbn>0003-1488 (Print)
0003-1488 (Linking)</isbn><accession-num>3654322</accession-num><urls><related-urls><url> The localised form has been described in lesions of feline squmous cell carcinoma in situ. ADDIN EN.CITE <EndNote><Cite><Author>Bensignor</Author><Year>2000</Year><RecNum>500</RecNum><DisplayText><style face="superscript">54,55</style></DisplayText><record><rec-number>500</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503305353">500</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bensignor, E.</author><author>Carlotti, D.N.</author></authors></contributors><titles><title>Epidermoid carcinoma in situ associated with localised demodicosis in a cat</title><secondary-title>Pratique medicale et chirugicale de l'animal de compagnie</secondary-title></titles><periodical><full-title>Pratique medicale et chirugicale de l'animal de compagnie</full-title></periodical><pages>559-562</pages><volume>35</volume><number>6</number><dates><year>2000</year></dates><urls></urls></record></Cite><Cite><Author>Guaguere</Author><Year>1999</Year><RecNum>501</RecNum><record><rec-number>501</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503305479">501</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Guaguere, E.</author><author>Olivry, T.</author><author>Delverdier-Poujade, A.</author><author>Et al.</author><author>VETERINARY DERMATOLOGY Volume: 10 Issue: 1 Pages: 61-67 Published: MAR 1999 </author></authors></contributors><titles><title>Demodex cati infestation in association with feline cutaneous squamous cell carcinoma in situ: a report of five cases</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>61-67</pages><volume>10</volume><number>1</number><dates><year>1999</year></dates><urls></urls></record></Cite></EndNote>54,55 In humans, demodicosis is described as a primary immunosuppressive disorder based on a hereditary T cell defect ADDIN EN.CITE <EndNote><Cite><Author>Mumcuoglu</Author><Year>2005</Year><RecNum>365</RecNum><DisplayText><style face="superscript">56</style></DisplayText><record><rec-number>365</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1497953331">365</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mumcuoglu, K. Y.</author><author>Akilov, O. E.</author></authors></contributors><auth-address>Department of Parasitology, Hebrew University-Hadassah Medical School, Jerusalem, Israel. kostam@cc.huji.ac.il</auth-address><titles><title>The role of HLA A2 and Cw2 in the pathogenesis of human demodicosis</title><secondary-title>Dermatology</secondary-title></titles><periodical><full-title>Dermatology</full-title></periodical><pages>109-14</pages><volume>210</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Animals</keyword><keyword>Antigens, CD/*immunology</keyword><keyword>Female</keyword><keyword>HLA-A2 Antigen/*immunology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Mites</keyword><keyword>Phenotype</keyword><keyword>Skin Diseases, Parasitic/*immunology/parasitology</keyword></keywords><dates><year>2005</year></dates><isbn>1018-8665 (Print)
1018-8665 (Linking)</isbn><accession-num>15724092</accession-num><urls><related-urls><url> or as a consequence of immunosuppression. ADDIN EN.CITE <EndNote><Cite><Author>Ivy</Author><Year>1995</Year><RecNum>491</RecNum><DisplayText><style face="superscript">25</style></DisplayText><record><rec-number>491</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502587846">491</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ivy, S. P.</author><author>Mackall, C. L.</author><author>Gore, L.</author><author>Gress, R. E.</author><author>Hartley, A. H.</author></authors></contributors><auth-address>Department of Pediatrics, Children's National Medical Center, Washington, DC 20010, USA.</auth-address><titles><title>Demodicidosis in childhood acute lymphoblastic leukemia; an opportunistic infection occurring with immunosuppression</title><secondary-title>J Pediatr</secondary-title></titles><periodical><full-title>J Pediatr</full-title></periodical><pages>751-4</pages><volume>127</volume><number>5</number><keywords><keyword>Antineoplastic Combined Chemotherapy Protocols/therapeutic use</keyword><keyword>Child</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>*Immunosuppression</keyword><keyword>Insecticides/administration & dosage</keyword><keyword>Male</keyword><keyword>Mite Infestations/*diagnosis/drug therapy/etiology</keyword><keyword>Ointments</keyword><keyword>Opportunistic Infections/*diagnosis/drug therapy/etiology</keyword><keyword>Permethrin</keyword><keyword>Precursor Cell Lymphoblastic Leukemia-Lymphoma/*complications/drug therapy</keyword><keyword>Pyrethrins/administration & dosage</keyword><keyword>Remission Induction</keyword><keyword>Skin/pathology</keyword></keywords><dates><year>1995</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0022-3476 (Print)
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ADDIN EN.CITE.DATA 49,57 A further multi-centered and well-powered study in the United States identified the American Staffordshire terrier, Staffordshire bull terrier and Chinese shar-pei as predisposed breeds. ADDIN EN.CITE <EndNote><Cite><Author>Plant</Author><Year>2011</Year><RecNum>326</RecNum><DisplayText><style face="superscript">57</style></DisplayText><record><rec-number>326</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307613285">326</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plant, J. D.</author><author>Lund, E. M.</author><author>Yang, M.</author></authors></contributors><auth-address>Animal Dermatology Consulting, Lake Oswego, OR, USA. jon.plant@</auth-address><titles><title>A case-control study of the risk factors for canine juvenile-onset generalized demodicosis in the USA</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>95-9</pages><volume>22</volume><number>1</number><edition>2010/08/17</edition><keywords><keyword>Animals</keyword><keyword>Case-Control Studies</keyword><keyword>Dog Diseases/epidemiology/*etiology/genetics</keyword><keyword>Dogs</keyword><keyword>Genetic Predisposition to Disease</keyword><keyword>Odds Ratio</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Factors</keyword><keyword>Skin Diseases/epidemiology/etiology/genetics/*veterinary</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1365-3164 (Electronic)
0959-4493 (Linking)</isbn><accession-num>20707860</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>57 Those breed predilections and the frequent occurrence of juvenile demodicosis in certain lines, sibling puppies and related dogs make a hereditary basis very likely. In addition, there is anecdotal evidence that preventing affected dogs from breeding decreases the frequency of the disease. ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006591">376</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Miller, W. Jr.</author><author>Griffin, C.E.</author><author>Campbell, C.A. </author></authors></contributors><titles><title>Canine demodicosis</title><secondary-title>Muller and Kirk's Small Animal Dermatology</secondary-title></titles><edition>7th</edition><dates><year>2012</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B.Saunders</publisher><urls></urls></record></Cite></EndNote>27 However, to the authors' knowledge only one study has been published evaluating the genetic basis in more detail. In this study using microsatellite markers, a significant association was found between generalised demodicosis and the DLA haplotypes FH2002, FH2975 and FH2054 in Argentinian mastiffs and Boxers. ADDIN EN.CITE <EndNote><Cite><Author>It</Author><Year>2010</Year><RecNum>2</RecNum><DisplayText><style face="superscript">58</style></DisplayText><record><rec-number>2</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849817">2</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>It, V.</author><author>Barrientos, L.</author><author>Lopez Gappa, J.</author><author>Posik, D.</author><author>Diaz, S.</author><author>Golijow, C.</author><author>Giovambattista, G.</author></authors></contributors><auth-address>Instituto de Genetica Veterinaria (IGEVET), CCT La Plata-CONICET, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina.</auth-address><titles><title>Association of canine juvenile generalized demodicosis with the dog leukocyte antigen system</title><secondary-title>Tissue Antigens</secondary-title></titles><periodical><full-title>Tissue Antigens</full-title></periodical><pages>67-70</pages><volume>76</volume><number>1</number><edition>2010/03/25</edition><dates><year>2010</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1399-0039 (Electronic)
0001-2815 (Linking)</isbn><accession-num>20331837</accession-num><urls><related-urls><url> [pii]
10.1111/j.1399-0039.2010.01463.x</electronic-resource-num><language>eng</language></record></Cite></EndNote>58Demodicosis in juvenile dogs shows a wide variety of clinical signs, from mild, localised alopecia to severe generalised forms with prominent systemic signs. These variations may be seen within the same litter of puppies. In addition, patients respond differently to the various therapeutic approaches. Thus, it is likely that several genes are involved in the pathogenesis and more and larger studies are needed to elucidate the genetic background of the disease. Further support for a multi-gene involvement is the above mentioned immunodeficient double knock-out mouse strain lacking CD28 and STAT6. ADDIN EN.CITE <EndNote><Cite><Author>Liu</Author><Year>2004</Year><RecNum>496</RecNum><DisplayText><style face="superscript">39</style></DisplayText><record><rec-number>496</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502590328">496</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu ,Q.</author><author>Arseculeratne, C. </author><author>Liu, Z. </author><author>Whitmire, J. </author><author>Grusby, M.J. </author><author>Finkelman, F.D. </author><author>Darling, T.N. </author><author>Cheever, A.W. </author><author>Swearengen, J. </author><author>Urban, J.F. </author><author>Gause, W.C.</author></authors></contributors><titles><title>Simultaneous deficiency in CD28 and STAT6 results in chronic ectoparasite-induced inflammatory skin disease</title><secondary-title>Infect Immunol</secondary-title></titles><periodical><full-title>Infect Immunol</full-title></periodical><pages>3706-3715</pages><volume>72</volume><number>7</number><dates><year>2004</year></dates><urls></urls></record></Cite></EndNote>39 In contrast to the double knock-out mice, single knock-out siblings kept in close contact and lacking either CD28 or STAT6 did not show any clinical signs. ADDIN EN.CITE <EndNote><Cite><Author>Liu</Author><Year>2004</Year><RecNum>496</RecNum><DisplayText><style face="superscript">39</style></DisplayText><record><rec-number>496</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502590328">496</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu ,Q.</author><author>Arseculeratne, C. </author><author>Liu, Z. </author><author>Whitmire, J. </author><author>Grusby, M.J. </author><author>Finkelman, F.D. </author><author>Darling, T.N. </author><author>Cheever, A.W. </author><author>Swearengen, J. </author><author>Urban, J.F. </author><author>Gause, W.C.</author></authors></contributors><titles><title>Simultaneous deficiency in CD28 and STAT6 results in chronic ectoparasite-induced inflammatory skin disease</title><secondary-title>Infect Immunol</secondary-title></titles><periodical><full-title>Infect Immunol</full-title></periodical><pages>3706-3715</pages><volume>72</volume><number>7</number><dates><year>2004</year></dates><urls></urls></record></Cite></EndNote>390264795Consensus Statement 2: In young dogs, demodicosis has a genetic basis and most likely multiple genes are involved.00Consensus Statement 2: In young dogs, demodicosis has a genetic basis and most likely multiple genes are involved.Demodex species in the dog and catSeveral mite species have been reported in dogs and cats. In the dog, initially three different species were reported. D. canis is the most common demodectic mite of dogs. A longer-bodied mite was also reportedPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IaWxsaWVyPC9BdXRob3I+PFllYXI+MjAwMjwvWWVhcj48
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ADDIN EN.CITE.DATA 59-62 and named D. injai ("inja" being the Zulu name for "dog"). ADDIN EN.CITE <EndNote><Cite><Author>Hillier</Author><Year>2002</Year><RecNum>18</RecNum><DisplayText><style face="superscript">59</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849817">18</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hillier, A.</author><author>Desch, C. E.</author></authors></contributors><auth-address>Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus 43210, USA.</auth-address><titles><title>Large-bodied Demodex mite infestation in 4 dogs</title><secondary-title>J Am Vet Med Assoc</secondary-title></titles><periodical><full-title>J Am Vet Med Assoc</full-title></periodical><pages>623-7, 613</pages><volume>220</volume><number>5</number><edition>2002/11/07</edition><keywords><keyword>Animals</keyword><keyword>Dog Diseases/diagnosis/drug therapy/*parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Insecticides/therapeutic use</keyword><keyword>Male</keyword><keyword>Skin/parasitology</keyword><keyword>Trombiculiasis/diagnosis/drug therapy/parasitology/*veterinary</keyword><keyword>Trombiculidae/*anatomy & histology/growth & development</keyword></keywords><dates><year>2002</year><pub-dates><date>Mar 1</date></pub-dates></dates><isbn>0003-1488 (Print)
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ADDIN EN.CITE.DATA 67,68 revealed only one ADDIN EN.CITE <EndNote><Cite><Author>de Rojas</Author><Year>2012</Year><RecNum>397</RecNum><DisplayText><style face="superscript">67</style></DisplayText><record><rec-number>397</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499329839">397</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>de Rojas, M.</author><author>Riazzo, C.</author><author>Callejon, R.</author><author>Guevara, D.</author><author>Cutillas, C.</author></authors></contributors><auth-address>Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Sevilla, Prof. Garcia Gonzalez s/n., 41012 Sevilla, Spain. derojas@us.es</auth-address><titles><title>Molecular study on three morphotypes of Demodex mites (Acarina: Demodicidae) from dogs</title><secondary-title>Parasitol Res</secondary-title></titles><periodical><full-title>Parasitol Res</full-title></periodical><pages>2165-72</pages><volume>111</volume><number>5</number><keywords><keyword>Acari/anatomy & histology/*classification/*genetics</keyword><keyword>Animals</keyword><keyword>Biometry/methods</keyword><keyword>China</keyword><keyword>Cluster Analysis</keyword><keyword>Dog Diseases/*parasitology</keyword><keyword>Dogs</keyword><keyword>Ectoparasitic Infestations/parasitology/veterinary</keyword><keyword>Electron Transport Complex IV/genetics</keyword><keyword>Entomology/methods</keyword><keyword>*Genetic Variation</keyword><keyword>Humans</keyword><keyword>Molecular Sequence Data</keyword><keyword>Phylogeny</keyword><keyword>Sequence Analysis, DNA</keyword><keyword>Spain</keyword></keywords><dates><year>2012</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1432-1955 (Electronic)
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ADDIN EN.CITE.DATA 68 In one report it was suggested that D. cornei?are dead or near dead?D. canis mites further supporting that only two species of mites exist. ADDIN EN.CITE <EndNote><Cite><Author>Fiorucci</Author><Year>2015</Year><RecNum>523</RecNum><DisplayText><style face="superscript">69</style></DisplayText><record><rec-number>523</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1506433404">523</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fiorucci, G.</author><author>Fogel, F.</author><author>Paradis, M. </author></authors></contributors><titles><title>Demodex cornei: podrían ser ácaros Demodex canis transformados, moribundos o muertos</title><secondary-title>Revista Veterinaria Argentina</secondary-title></titles><periodical><full-title>Revista Veterinaria Argentina</full-title></periodical><pages>1-14</pages><volume>XXXII</volume><number>322</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>69There are 3 different species of Demodex mites in the cat: D. cati, ADDIN EN.CITE <EndNote><Cite><Author>Desch</Author><Year>1979</Year><RecNum>129</RecNum><DisplayText><style face="superscript">70</style></DisplayText><record><rec-number>129</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849875">129</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Desch, C.</author><author>Nutting, W. B.</author></authors></contributors><titles><title>Demodex cati Hirst 1919: a redescription</title><secondary-title>Cornell Vet</secondary-title></titles><periodical><full-title>Cornell Vet</full-title></periodical><pages>280-5</pages><volume>69</volume><number>3</number><edition>1979/07/01</edition><keywords><keyword>Animals</keyword><keyword>Cats/*parasitology</keyword><keyword>Ear, External/parasitology</keyword><keyword>Female</keyword><keyword>Male</keyword><keyword>Mites/anatomy & histology/*classification</keyword></keywords><dates><year>1979</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0010-8901 (Print)
0010-8901 (Linking)</isbn><accession-num>477325</accession-num><urls><related-urls><url> D. gatoi HYPERLINK \l "_ENREF_71" \o "Desch, 1999 #121" ADDIN EN.CITE <EndNote><Cite><Author>Desch</Author><Year>1999</Year><RecNum>121</RecNum><DisplayText><style face="superscript">71</style></DisplayText><record><rec-number>121</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849875">121</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Desch, C. E., Jr.</author><author>Stewart, T. B.</author></authors></contributors><auth-address>Department of Veterinary Microbiology & Parasitology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, 70803-8416, USA.</auth-address><titles><title>Demodex gatoi: new species of hair follicle mite (Acari: Demodecidae) from the domestic cat (Carnivora: Felidae)</title><secondary-title>J Med Entomol</secondary-title></titles><periodical><full-title>J Med Entomol</full-title></periodical><pages>167-70</pages><volume>36</volume><number>2</number><edition>1999/03/20</edition><keywords><keyword>Animals</keyword><keyword>Cats</keyword><keyword>Feline Acquired Immunodeficiency Syndrome/*parasitology</keyword><keyword>Female</keyword><keyword>Male</keyword><keyword>Mite Infestations/parasitology/*veterinary</keyword><keyword>Mites/anatomy & histology/*classification</keyword></keywords><dates><year>1999</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0022-2585 (Print)
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ADDIN EN.CITE.DATA 21,72 The unnamed species had a longer gnathosoma and a shorter opisthotoma than D. cati. The length:width ratio of the opisthosoma was approximately 2:1 whereas in D. cati it is approximately 5:1. ADDIN EN.CITE <EndNote><Cite><Author>Lowenstein</Author><Year>2005</Year><RecNum>114</RecNum><DisplayText><style face="superscript">21</style></DisplayText><record><rec-number>114</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849875">114</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lowenstein, C.</author><author>Beck, W.</author><author>Bessmann, K.</author><author>Mueller, R. S.</author></authors></contributors><auth-address>Tierarztliche Klinik fur Kleintiere, Bereich Dermatologie, 65719 Hofheim, Germany.</auth-address><titles><title>Feline demodicosis caused by concurrent infestation with Demodex cati and an unnamed species of mite</title><secondary-title>Vet Rec</secondary-title></titles><periodical><full-title>Vet Rec</full-title></periodical><pages>290-2</pages><volume>157</volume><number>10</number><edition>2005/09/15</edition><keywords><keyword>Animals</keyword><keyword>Cat Diseases/*diagnosis/parasitology</keyword><keyword>Cats</keyword><keyword>Diagnosis, Differential</keyword><keyword>Male</keyword><keyword>Mite Infestations/diagnosis/*veterinary</keyword><keyword>Mites/*classification</keyword><keyword>Skin Diseases, Parasitic/diagnosis/*veterinary</keyword></keywords><dates><year>2005</year><pub-dates><date>Sep 3</date></pub-dates></dates><isbn>0042-4900 (Print)
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ADDIN EN.CITE.DATA 73,74 It was considered a very regional disease, predominantly diagnosed in the Southeastern United States. ADDIN EN.CITE <EndNote><Cite><Author>Morris</Author><Year>2000</Year><RecNum>502</RecNum><DisplayText><style face="superscript">74</style></DisplayText><record><rec-number>502</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503307724">502</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Morris, D.O.</author><author>Beale, K.O.</author></authors><secondary-authors><author>Bonagura, J.D.</author></secondary-authors></contributors><titles><title>Feline demodicosis</title><secondary-title>Kirk's Current Veterinary Therapy XIII</secondary-title></titles><pages>580-582</pages><volume>XIII</volume><dates><year>2000</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B. Saunders</publisher><urls></urls></record></Cite></EndNote>74 -76200755650Consensus Statement 3: In dogs, two Demodex species occur, the shorter D. canis and the longer D. injai. In cats, the shorter D. gatoi has a more regional occurence and different clinical signs than the classical D. cati.00Consensus Statement 3: In dogs, two Demodex species occur, the shorter D. canis and the longer D. injai. In cats, the shorter D. gatoi has a more regional occurence and different clinical signs than the classical D. cati.However, more recently there have been reports from other areas of the world.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaWxsZXk8L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 73,75,76 Clinical signs in dogsThe signs develop after clinically relevant mite proliferations have occurred and the clinical signs can depend on the degree of the mites’ proliferation and vary greatly. Initially there may be a non-inflammatory hypotrichosis/alopecia and/or an inflammatory dermatitis with mild erythema, comedone formation, scaling and associated hypotrichosis/ alopecia. The lesions may be focal or multifocal to coalescing involving large areas of the body. Dilation and hyperpigmentation of follicular ostea may be present and if seen, is a clinical clue for the disease (Figure). In more inflammatory presentations, follicular-oriented papules may develop (Figure). Pruritus is generally not thought to be characteristic of milder presentations, however it is more common if the short-bodied morphological variant of D. canisPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYXJpZG9taWNoZWxha2lzPC9BdXRob3I+PFllYXI+MTk5
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ADDIN EN.CITE.DATA 63,64 is present and/or if secondary bacterial infection develops. Follicular casts (scale adherent to the hair shafts) may be present. With more severe or advanced disease, secondary bacterial infection may lead to follicular pustules, furunculosis with scale, crust, exudation and ulceration with draining tracts. Severe, generalised pustular demodicosis may be painful and associated with hyperpigmentation, lymphadenopathy, lethargy and fever. In those severely affected dogs, septicaemia due to the invariably present secondary bacterial infection is possible. Pedal demodicosis commonly causes quite marked hyperpigmentation (of both follicles and surrounding skin) and may present with significant interdigital inflammation, oedema and pain.D. injai has been reported in several dog breeds but seems over-represented in terrier breeds and their crosses. ADDIN EN.CITE <EndNote><Cite><Author>Robson</Author><Year>2003</Year><RecNum>290</RecNum><DisplayText><style face="superscript">62</style></DisplayText><record><rec-number>290</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1305026598">290</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Robson, D.C.</author><author>Burton, G.G.</author><author>Bassett, R.</author><author>Mueller, R.S.</author></authors></contributors><titles><title>Eight cases of demodicosis caused by a long-bodied Demodex species (1997-2002)</title><secondary-title>Aust Vet Pract</secondary-title></titles><periodical><full-title>Aust Vet Pract</full-title></periodical><pages>64-72</pages><volume>33</volume><number>2</number><dates><year>2003</year></dates><urls></urls></record></Cite></EndNote>62 Whilst it may cause erythema, comedone formation, hyperpigmentation and alopecia, similar to D. canis, the most striking and consistent clinical feature is marked greasiness of the dorsal trunk.Clinical Signs in catsD. cati can cause localised or generalised disease and lesions include erythema, hypotrichosis/alopecia, scale and crusting (Figure). Pruritus is variable but may be intense in some individuals. Generalised disease is commonly associated with an underlying disease such as feline immunodeficiency virus,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGFsbWVyczwvQXV0aG9yPjxZZWFyPjE5ODk8L1llYXI+
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ADDIN EN.CITE.DATA 52 or diabetes mellitus. ADDIN EN.CITE <EndNote><Cite><Author>White</Author><Year>1987</Year><RecNum>495</RecNum><DisplayText><style face="superscript">53</style></DisplayText><record><rec-number>495</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502589240">495</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>White, S. D.</author><author>Carpenter, J. L.</author><author>Moore, F. M.</author><author>Ogilvie, G.</author></authors></contributors><auth-address>Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536.</auth-address><titles><title>Generalized demodicosis associated with diabetes mellitus in two cats</title><secondary-title>J Am Vet Med Assoc</secondary-title></titles><periodical><full-title>J Am Vet Med Assoc</full-title></periodical><pages>448-50</pages><volume>191</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>*Cat Diseases</keyword><keyword>Cats</keyword><keyword>Diabetes Complications</keyword><keyword>Diabetes Mellitus/*veterinary</keyword><keyword>Male</keyword><keyword>Mite Infestations/complications/*veterinary</keyword><keyword>Mites</keyword></keywords><dates><year>1987</year><pub-dates><date>Aug 15</date></pub-dates></dates><isbn>0003-1488 (Print)
0003-1488 (Linking)</isbn><accession-num>3654322</accession-num><urls><related-urls><url>. In some cats, no other disease may be identified. Demodex mites have also been reported to proliferate within the scaly alopecic lesions of bowenoid in situ carcinoma (BISC). ADDIN EN.CITE <EndNote><Cite><Author>Bensignor</Author><Year>2000</Year><RecNum>500</RecNum><DisplayText><style face="superscript">54,55</style></DisplayText><record><rec-number>500</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503305353">500</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bensignor, E.</author><author>Carlotti, D.N.</author></authors></contributors><titles><title>Epidermoid carcinoma in situ associated with localised demodicosis in a cat</title><secondary-title>Pratique medicale et chirugicale de l'animal de compagnie</secondary-title></titles><periodical><full-title>Pratique medicale et chirugicale de l'animal de compagnie</full-title></periodical><pages>559-562</pages><volume>35</volume><number>6</number><dates><year>2000</year></dates><urls></urls></record></Cite><Cite><Author>Guaguere</Author><Year>1999</Year><RecNum>501</RecNum><record><rec-number>501</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503305479">501</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Guaguere, E.</author><author>Olivry, T.</author><author>Delverdier-Poujade, A.</author><author>Et al.</author><author>VETERINARY DERMATOLOGY Volume: 10 Issue: 1 Pages: 61-67 Published: MAR 1999 </author></authors></contributors><titles><title>Demodex cati infestation in association with feline cutaneous squamous cell carcinoma in situ: a report of five cases</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>61-67</pages><volume>10</volume><number>1</number><dates><year>1999</year></dates><urls></urls></record></Cite></EndNote>54,55 D. gatoi is a contagious mite that inhabits the stratum corneum (like Sarcoptes) and the most common clinical feature is pruritus ranging from mild to very intense. Skin lesions aside from traumatic alopecia and scale are secondary hyperpigmentation, superficial erosion and ulceration. The changes are predominantly truncal with the ventral abdomen having been reported as a site of predilection.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3JyaXM8L0F1dGhvcj48WWVhcj4yMDAwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 73,74-76835339725Consensus Statement 4: Demodicosis in dogs is characterised by follicular papules and pustules that in more severely affected dogs may develop into alopecia and crusting with secondary bacterial infections and systemic signs. D. injae occurs more often in terrier breeds and additionally causes excessive greasiness. In cats, D. cati shows similar clinical signs, while in contrast infestations with the contagious D. gatoi often lead to trunkal pruritus.00Consensus Statement 4: Demodicosis in dogs is characterised by follicular papules and pustules that in more severely affected dogs may develop into alopecia and crusting with secondary bacterial infections and systemic signs. D. injae occurs more often in terrier breeds and additionally causes excessive greasiness. In cats, D. cati shows similar clinical signs, while in contrast infestations with the contagious D. gatoi often lead to trunkal pruritus.DiagnosisDeep skin scrapingsAt this time, deep skin scrapings are the diagnostic tool of choice in most patients with suspected demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2017</Year><RecNum>506</RecNum><DisplayText><style face="superscript">77</style></DisplayText><record><rec-number>506</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503308903">506</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Mueller, R. S.</author><author>Bettenay, S.V.</author></authors><secondary-authors><author>Ettinger, S.J.</author><author>Feldman, E.C.</author><author>Cote, E.</author></secondary-authors></contributors><titles><title>Scraping, fine-needle aspiration and biopsy of skin and subcutaneous tissues</title><secondary-title>Textbook of Veterinary Internal Medicine</secondary-title></titles><pages>342-345</pages><volume>1</volume><edition>8th Edition</edition><dates><year>2017</year></dates><pub-location>St. Louis</pub-location><publisher>Elsevier</publisher><urls></urls></record></Cite></EndNote>77 Samples may be collected with curettes, spatulae, sharp or dull scalpel blades. Placing a drop of mineral oil on the sampling instrument or directly on the skin is helpful for better adherence of the sampled debris to the instrument. Multiple scrapings of approximately 1 cm2 of affected skin should be performed in the direction of the hair growth and importantly the skin should be squeezed constantly or intermittently during scraping to extrude the mites from the depth of the follicles to the surface. Squeezing the skin has been shown to increase the number of mites found. ADDIN EN.CITE <EndNote><Cite><Author>Beco</Author><Year>2007</Year><RecNum>271</RecNum><DisplayText><style face="superscript">78</style></DisplayText><record><rec-number>271</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291626395">271</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Beco, L.</author><author>Fontaine, F.</author><author>Bergvall, K.</author><author>Favrot, C.</author></authors></contributors><titles><title>Comparison of skin scrapes and hair plucks for detecting Demodex mites in canine demodicosis, a multicentre, prospective study</title><secondary-title>Annual Conference of the European Society of Veterinary Dermatology/European College of Veterinary Dermatology</secondary-title></titles><pages>381</pages><volume>18</volume><dates><year>2007</year></dates><pub-location>Mainz</pub-location><publisher>Veterinary Dermatology</publisher><urls></urls></record></Cite></EndNote>78 Primary lesions such as follicular papules and pustules should be selected in order to obtain the best yield. Ulcerated areas are not suited as it is less likely to find parasites in such areas. The skin is scraped until capillary bleeding occurs indicating sufficient depth of the scraping. If necessary in a long- or medium-haired dog, gently clipping the area (in the direction of hair growth) to be scraped will minimize the loss of the scraped material into the surrounding hair. Debris is then transferred to a slide, mixed with mineral or paraffin oil and examined with a cover slip under the microscope at low magnification (x40 or x100). Magnification occurs with both the ocular lens (typically x10) and the objective lenses (x4 or x10). Recognition of mites is easier with a lowered microscope condensor and decreased light to increase the contrast in the microscope field (Figure). As Demodex mites are part of the normal microfauna, one mite identified on several deep skin scrapings could be a normal but uncommon finding. However, more than one mite is strongly suggestive of clinical demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2012</Year><RecNum>318</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307269305">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Bensignor, E.</author><author>Ferrer, L.</author><author>Holm, B. R.</author><author>Lemarie, S.</author><author>Paradis, M.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>86-96</pages><volume>23</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>3 Different life stages (eggs, larvae, nymphs and adults) and their numbers should be recorded and compared from the same sites at each visit to objectively measure the treatment success. TrichogramsTrichograms have been reported as an alternative to deep skin scrapings ADDIN EN.CITE <EndNote><Cite><Author>Beco</Author><Year>2007</Year><RecNum>271</RecNum><DisplayText><style face="superscript">78,79</style></DisplayText><record><rec-number>271</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291626395">271</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Beco, L.</author><author>Fontaine, F.</author><author>Bergvall, K.</author><author>Favrot, C.</author></authors></contributors><titles><title>Comparison of skin scrapes and hair plucks for detecting Demodex mites in canine demodicosis, a multicentre, prospective study</title><secondary-title>Annual Conference of the European Society of Veterinary Dermatology/European College of Veterinary Dermatology</secondary-title></titles><pages>381</pages><volume>18</volume><dates><year>2007</year></dates><pub-location>Mainz</pub-location><publisher>Veterinary Dermatology</publisher><urls></urls></record></Cite><Cite><Author>Bensignor</Author><Year>2003</Year><RecNum>272</RecNum><record><rec-number>272</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291626587">272</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bensignor, E.</author></authors></contributors><titles><title>Comparaison de trois techniques diagnostiques de demodecie a Demodex canis chez le chien</title><secondary-title>Pratique Medicale and Chirurgicale de l'Animal de Compagnie</secondary-title></titles><periodical><full-title>Pratique Medicale and Chirurgicale de l'Animal de Compagnie</full-title></periodical><pages>167</pages><volume>38</volume><dates><year>2003</year></dates><urls></urls></record></Cite></EndNote>78,79 and are particularly useful in areas that are difficult to scrape, such as periocular and interdigital areas. An area of 1cm2 should be plucked with a forceps in the direction of the hair growth and placed in a drop of mineral or paraffin oil on a slide. The use of a coverslip allows more thorough and rapid inspection of the specimen (Figure). To increase the chance of a positive trichogram, a large number of hairs (50-100) should be plucked. When performed properly, trichograms have a high diagnostic yield. However, negative trichograms should be followed by deep skin scrapings before ruling out demodicosis. Positive trichograms in healthy dogs are rare. ADDIN EN.CITE <EndNote><Cite><Author>Fondati</Author><Year>2010</Year><RecNum>3</RecNum><DisplayText><style face="superscript">80</style></DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849817">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fondati, A.</author><author>De Lucia, M.</author><author>Furiani, N.</author><author>Monaco, M.</author><author>Ordeix, L.</author><author>Scarampella, F.</author></authors></contributors><auth-address>Centro Veterinario Prati, 1/A, viale delle Milizie, 00192 Rome, Italy.</auth-address><titles><title>Prevalence of Demodex canis-positive healthy dogs at trichoscopic examination</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>146-51</pages><volume>21</volume><number>2</number><edition>2009/08/27</edition><keywords><keyword>Animals</keyword><keyword>Dog Diseases/diagnosis/*epidemiology/parasitology</keyword><keyword>Dogs</keyword><keyword>Mite Infestations/parasitology/*veterinary</keyword><keyword>Mites/*classification/physiology</keyword><keyword>Skin/parasitology</keyword></keywords><dates><year>2010</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1365-3164 (Electronic)
0959-4493 (Linking)</isbn><accession-num>19706007</accession-num><urls><related-urls><url> [pii]
10.1111/j.1365-3164.2009.00769.x</electronic-resource-num><language>eng</language></record></Cite></EndNote>80 Tape strips (“scotch tests”)Tape strips have also been reported as an excellent diagnostic method for canine demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Pereira</Author><Year>2012</Year><RecNum>363</RecNum><DisplayText><style face="superscript">81</style></DisplayText><record><rec-number>363</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1497950081">363</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pereira, A. V.</author><author>Pereira, S. A.</author><author>Gremiao, I. D.</author><author>Campos, M. P.</author><author>Ferreira, A. M.</author></authors></contributors><auth-address>Laboratory of Clinical Research on Dermatozoonosis in Domestic Animals, Evandro Chagas Clinical Research Institute/Oswaldo Cruz Foundation (Fiocruz), Av Brasil, 4365 - Manguinhos, 21045-900, Rio de Janeiro, Brazil. alessandravieiravet@</auth-address><titles><title>Comparison of acetate tape impression with squeezing versus skin scraping for the diagnosis of canine demodicosis</title><secondary-title>Aust Vet J</secondary-title></titles><periodical><full-title>Aust Vet J</full-title></periodical><pages>448-50</pages><volume>90</volume><number>11</number><keywords><keyword>Acaricides/*pharmacology</keyword><keyword>Acetates/*pharmacology</keyword><keyword>Animals</keyword><keyword>Dog Diseases/*diagnosis/parasitology/pathology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Male</keyword><keyword>Mite Infestations/diagnosis/pathology/*veterinary</keyword><keyword>Mites</keyword><keyword>Skin/*parasitology/pathology</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2012</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1751-0813 (Electronic)
0005-0423 (Linking)</isbn><accession-num>23106326</accession-num><urls><related-urls><url> While squeezing the skin, the acetate tape is pressed onto the skin with the sticky surface down. This technique was initially reported to be more sensitive than deep skin scrapings. ADDIN EN.CITE <EndNote><Cite><Author>Pereira</Author><Year>2012</Year><RecNum>363</RecNum><DisplayText><style face="superscript">81</style></DisplayText><record><rec-number>363</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1497950081">363</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pereira, A. V.</author><author>Pereira, S. A.</author><author>Gremiao, I. D.</author><author>Campos, M. P.</author><author>Ferreira, A. M.</author></authors></contributors><auth-address>Laboratory of Clinical Research on Dermatozoonosis in Domestic Animals, Evandro Chagas Clinical Research Institute/Oswaldo Cruz Foundation (Fiocruz), Av Brasil, 4365 - Manguinhos, 21045-900, Rio de Janeiro, Brazil. alessandravieiravet@</auth-address><titles><title>Comparison of acetate tape impression with squeezing versus skin scraping for the diagnosis of canine demodicosis</title><secondary-title>Aust Vet J</secondary-title></titles><periodical><full-title>Aust Vet J</full-title></periodical><pages>448-50</pages><volume>90</volume><number>11</number><keywords><keyword>Acaricides/*pharmacology</keyword><keyword>Acetates/*pharmacology</keyword><keyword>Animals</keyword><keyword>Dog Diseases/*diagnosis/parasitology/pathology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Male</keyword><keyword>Mite Infestations/diagnosis/pathology/*veterinary</keyword><keyword>Mites</keyword><keyword>Skin/*parasitology/pathology</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2012</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1751-0813 (Electronic)
0005-0423 (Linking)</isbn><accession-num>23106326</accession-num><urls><related-urls><url> However, follow-up studies have shown contradicting results. ADDIN EN.CITE <EndNote><Cite><Author>Vogelnest</Author><Year>2016</Year><RecNum>508</RecNum><DisplayText><style face="superscript">82,83</style></DisplayText><record><rec-number>508</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503310316">508</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vogelnest, L.</author><author>Garibotto, V.</author></authors></contributors><titles><title>Evaluation of the squeeze tape impression for the diagnosis of canine demodicosis</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>38</pages><volume>27</volume><number>Supplement 1</number><dates><year>2016</year></dates><urls></urls></record></Cite><Cite><Author>Lousada</Author><Year>2016</Year><RecNum>510</RecNum><record><rec-number>510</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503310914">510</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lousada, R.</author><author>Fonseca, I.</author><author>Nunes. T.</author><author>Matias, D.</author><author>Schmidt, V.M.</author><author>Lourenco, A.M.</author></authors></contributors><titles><title>New atraumatic techniqur for Demodex canis diagnosis</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>114</pages><volume>27</volume><number>Supplement 1</number><dates><year>2016</year></dates><urls></urls></record></Cite></EndNote>82,83Skin biopsiesIn some rare cases, skin scrapings, trichograms and tape preparations may be negative and skin biopsies may be needed to detect the Demodex mites in the hair follicles or in foreign body granulomas observed as a consequence of furunculosis. This may be more likely in certain body locations such as the paws and certain breeds such as the Shar Pei. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2012</Year><RecNum>318</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307269305">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Bensignor, E.</author><author>Ferrer, L.</author><author>Holm, B. R.</author><author>Lemarie, S.</author><author>Paradis, M.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>86-96</pages><volume>23</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>3Other methods of mite detectionDirect examination of the exudate from pustules or draining tracts may reveal mites in some patients. Specimens can be collected by squeezing the exudate onto a glass slide, and visualized by adding mineral oil and a coverslip. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2012</Year><RecNum>318</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307269305">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Bensignor, E.</author><author>Ferrer, L.</author><author>Holm, B. R.</author><author>Lemarie, S.</author><author>Paradis, M.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>86-96</pages><volume>23</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>3 In one study, exudate was collected from dogs showing exudative lesions with the blunt side of a second scalpel blade after gently removing the crusts and squeezing the lesion. ADDIN EN.CITE <EndNote><Cite><Author>Saridomichelakis</Author><Year>2007</Year><RecNum>418</RecNum><DisplayText><style face="superscript">84</style></DisplayText><record><rec-number>418</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499427375">418</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Saridomichelakis, M. N.</author><author>Koutinas, A. F.</author><author>Farmaki, R.</author><author>Leontides, L. S.</author><author>Kasabalis, D.</author></authors></contributors><auth-address>Companion Animal Clinic, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. msarido@vet.uth.gr</auth-address><titles><title>Relative sensitivity of hair pluckings and exudate microscopy for the diagnosis of canine demodicosis</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>138-41</pages><volume>18</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Biopsy/*veterinary</keyword><keyword>Dog Diseases/*diagnosis/parasitology/pathology</keyword><keyword>Dogs</keyword><keyword>Exudates and Transudates/parasitology</keyword><keyword>Female</keyword><keyword>Hair/parasitology</keyword><keyword>Male</keyword><keyword>Mite Infestations/diagnosis/*veterinary</keyword><keyword>*Mites</keyword><keyword>Predictive Value of Tests</keyword><keyword>Sensitivity and Specificity</keyword><keyword>Skin/parasitology</keyword></keywords><dates><year>2007</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>17355431</accession-num><urls><related-urls><url> In this particular study, the exudate sampling was compared to deep skin scrapings and trichograms and was positive in all dogs sampled. However, this technique is only possible in dogs with more severe forms of demodicosis. Cytological specimens stained with Diff Quik may also reveal Demodex mites (more easily recognised with the condensor lowered for searching). Although this is not a very sensitive method for the diagnosis, it is not uncommon to find mites on the evaluation of cytology samples of dogs with exudative forms of demodicosis. -127000354330Consensus Statement 5: Deep skin scrapings (currently the diagnostic method of choice), trichograms, tape strips and examinations of exudate may be useful in identifying Demodex mites. More than one mite on any given test is an indication of clinically relevant demodicosis.00Consensus Statement 5: Deep skin scrapings (currently the diagnostic method of choice), trichograms, tape strips and examinations of exudate may be useful in identifying Demodex mites. More than one mite on any given test is an indication of clinically relevant demodicosis.Diagnosing bacterial infections Frequently, generalized demodicosis is associated with secondary bacterial infections. Particularly in severe cases involving furunculosis, a bacterial septicemia is possible. When clinical signs of possible bacterial infection such as pustules or draining tracts are present, an impression smear should be obtained, stained and evaluated for an increased number and/or intracellular location of bacterial organisms. Most commonly, Staphylococcus pseudintermedius will be present, ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>15030556</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>45 but in some patients, particularly those with furunculosis, Gram-negative rods such as Escherichia coli or Pseudomonas aeruginosa may dominate. For these cases a culture and sensitivity testing is indicated. Breeding considerationsCanine generalized demodicosis is a relatively frequent and often very severe parasitic skin disease. As many as 0.58 % of the dogs in the USA suffer from the generalized form of the disease. ADDIN EN.CITE <EndNote><Cite><Author>Plant</Author><Year>2011</Year><RecNum>326</RecNum><DisplayText><style face="superscript">57</style></DisplayText><record><rec-number>326</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307613285">326</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plant, J. D.</author><author>Lund, E. M.</author><author>Yang, M.</author></authors></contributors><auth-address>Animal Dermatology Consulting, Lake Oswego, OR, USA. jon.plant@</auth-address><titles><title>A case-control study of the risk factors for canine juvenile-onset generalized demodicosis in the USA</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>95-9</pages><volume>22</volume><number>1</number><edition>2010/08/17</edition><keywords><keyword>Animals</keyword><keyword>Case-Control Studies</keyword><keyword>Dog Diseases/epidemiology/*etiology/genetics</keyword><keyword>Dogs</keyword><keyword>Genetic Predisposition to Disease</keyword><keyword>Odds Ratio</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Factors</keyword><keyword>Skin Diseases/epidemiology/etiology/genetics/*veterinary</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1365-3164 (Electronic)
0959-4493 (Linking)</isbn><accession-num>20707860</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>57 Multiple risk factors are involved in the development of canine demodicosis and one of the most important recognised risk factors is breed predisposition. Juvenile demodicosis is more common in purebred dogs of particular breeds. Selective breeding in order to obtain a certain set of desired characteristics in a particular breed can lead to a reduction of genetic variation within a breed. This may facilitate the clinical expression of recessive genes and in turn can result in a greater susceptibility to certain diseases. Knowledge about breed predispositions for certain diseases such as demodicosis is useful not only while creating a list of differential diagnoses and when advising clients which breed to purchase, but also when advising breeders. Implementing appropriate prophylactic strategies can markedly reduce the prevalence of generalized juvenile demodicosis in the dog. ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006591">376</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Miller, W. Jr.</author><author>Griffin, C.E.</author><author>Campbell, C.A. </author></authors></contributors><titles><title>Canine demodicosis</title><secondary-title>Muller and Kirk's Small Animal Dermatology</secondary-title></titles><edition>7th</edition><dates><year>2012</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B.Saunders</publisher><urls></urls></record></Cite></EndNote>27 Excluding bitches from breeding that have given birth to puppies with demodicosis will lead to a prominent decrease of puppies affected with demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006591">376</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Miller, W. Jr.</author><author>Griffin, C.E.</author><author>Campbell, C.A. </author></authors></contributors><titles><title>Canine demodicosis</title><secondary-title>Muller and Kirk's Small Animal Dermatology</secondary-title></titles><edition>7th</edition><dates><year>2012</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B.Saunders</publisher><urls></urls></record></Cite></EndNote>27 As early as 1981, the American Academy of Veterinary Dermatology adopted a resolution recommending ‘neutering all dogs who have had generalized demodicosis so that the incidence of the disease is decreased and not perpetuated’. ADDIN EN.CITE <EndNote><Cite><Author>Dermatology</Author><Year>1983</Year><RecNum>354</RecNum><DisplayText><style face="superscript">85</style></DisplayText><record><rec-number>354</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="0">354</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>American Academy of Veterinary Dermatology</author></authors></contributors><titles><title>Dermatologists recommend neutering of canine patients with demodicosis</title><secondary-title>Journal of the American Veterinary Medical Association</secondary-title></titles><periodical><full-title>Journal of the American Veterinary Medical Association</full-title></periodical><pages>1048</pages><volume>182</volume><number>10</number><dates><year>1983</year></dates><urls></urls></record></Cite></EndNote>85 Today, it is consensus among veterinary dermatologists worldwide that affected dogs or there parents should not be used for breeding. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2012</Year><RecNum>318</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307269305">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Bensignor, E.</author><author>Ferrer, L.</author><author>Holm, B. R.</author><author>Lemarie, S.</author><author>Paradis, M.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>86-96</pages><volume>23</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>3 28575350520Consensus Statement 6: Dogs with generalised demodicosis should not be bred.00Consensus Statement 6: Dogs with generalised demodicosis should not be bred.TreatmentGeneral considerationsDemodicosis varies from mild localised to severe generalised disease. Mild localised disease will spontaneously resolve in most cases. How many dogs with more severe disease would also spontaneously resolve without treatment is unclear. Although a study has attempted to evaluate the proportion of dogs with the generalised form of the disease that undergo spontaneous remission, ADDIN EN.CITE <EndNote><Cite><Author>Bruzinska-Schmidhalter</Author><Year>2011</Year><RecNum>327</RecNum><DisplayText><style face="superscript">86</style></DisplayText><record><rec-number>327</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307613591">327</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Bruzinska-Schmidhalter, R.</author><author>Nett-Mettler, C.S.</author></authors><secondary-authors><author>Foster, A. P.</author></secondary-authors></contributors><titles><title>Spontaneous remission in canine generalized demodicosis - predisposing factors</title><secondary-title>North American Veterinary Dermatology Forum</secondary-title></titles><pages>301</pages><volume>22</volume><dates><year>2011</year></dates><pub-location>Galveston</pub-location><publisher>Veterinary Dermatology</publisher><urls></urls></record></Cite></EndNote>86 such studies are difficult to conduct and robust data is lacking to answer this question. In addition, in most countries it is considered unethical to withhold treatment of dogs with severe demodicosis and owners of such dogs usually will not consent to observation instead of interventional (and typically efficacious) acaricidal therapy. Nevertheless, there is some evidence that spontaneous remission can occur in a subset of dogs with generalised disease.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcnV6aW5za2EtU2NobWlkaGFsdGVyPC9BdXRob3I+PFll
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ADDIN EN.CITE.DATA 86,87In juvenile dogs, treatment of the demodicosis and possibly the secondary bacterial infection, if present, is typically sufficient without the need for further diagnostic work-up. In contrast, for those cats and dogs with adult-onset disease, the possibility of an underlying, immunosuppressive disease should be investigated. In one dog with adult-onset demodicosis, treatment of the primary disease resulted in resolution of the demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Hillier</Author><Year>2002</Year><RecNum>18</RecNum><DisplayText><style face="superscript">59</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849817">18</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hillier, A.</author><author>Desch, C. E.</author></authors></contributors><auth-address>Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus 43210, USA.</auth-address><titles><title>Large-bodied Demodex mite infestation in 4 dogs</title><secondary-title>J Am Vet Med Assoc</secondary-title></titles><periodical><full-title>J Am Vet Med Assoc</full-title></periodical><pages>623-7, 613</pages><volume>220</volume><number>5</number><edition>2002/11/07</edition><keywords><keyword>Animals</keyword><keyword>Dog Diseases/diagnosis/drug therapy/*parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Insecticides/therapeutic use</keyword><keyword>Male</keyword><keyword>Skin/parasitology</keyword><keyword>Trombiculiasis/diagnosis/drug therapy/parasitology/*veterinary</keyword><keyword>Trombiculidae/*anatomy & histology/growth & development</keyword></keywords><dates><year>2002</year><pub-dates><date>Mar 1</date></pub-dates></dates><isbn>0003-1488 (Print)
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ADDIN EN.CITE.DATA 22Regardless of the specific miticidal therapy, treatment success is monitored both clinically and by repeated skin scrapings. Generally, it is recommended to examine dogs and cats with demodicosis monthly. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2012</Year><RecNum>318</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307269305">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Bensignor, E.</author><author>Ferrer, L.</author><author>Holm, B. R.</author><author>Lemarie, S.</author><author>Paradis, M.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>86-96</pages><volume>23</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>3 At each recheck, skin scrapings are taken from the same sites as in previous visits. In addition to clinical improvement, the numbers of mites and immature stages should decrease with each visit. If clinical improvement does not occur and mite numbers fail to improve, a change in therapy should be considered. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
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ADDIN EN.CITE.DATA 3,45 In dogs that responded very slowly to therapy, treatment may be extended even further. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2012</Year><RecNum>318</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307269305">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Bensignor, E.</author><author>Ferrer, L.</author><author>Holm, B. R.</author><author>Lemarie, S.</author><author>Paradis, M.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>86-96</pages><volume>23</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>3 In a systematic review of 124 dogs reported to have failed the initial therapy, two thirds responded to a change of therapy. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>15030556</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>45 Similarly, of 40 dogs with recurring demodicosis within 12 months after initially responding to therapy, more than two thirds went into remission after another treatment course with the same or an alternative medication. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>15030556</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>45 A follow-up of at least 12 months after treatment cessation has been recommended before calling a dog cured, although in some studies the disease recurred after more than 12 months of remission in a few dogs. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>15030556</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>450265430Consensus Statement 7: Treatment for generalised demodicosis should be monitored clinically and microscopically every month until the second negative skin scraping.00Consensus Statement 7: Treatment for generalised demodicosis should be monitored clinically and microscopically every month until the second negative skin scraping.In most dogs with demodicosis, a secondary bacterial infection will develop with time. In the past, systemic antibiotic therapy was recommended for all dogs in which a secondary bacterial infection could be demonstrated clinically and cytologically. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2012</Year><RecNum>318</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307269305">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Bensignor, E.</author><author>Ferrer, L.</author><author>Holm, B. R.</author><author>Lemarie, S.</author><author>Paradis, M.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>86-96</pages><volume>23</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>3 However, in a randomised controlled trial evaluating 58 dogs with generalised demodicosis half of the dogs were treated with systemic antibiotics in addition to miticidal therapy with daily ivermectin and topical weekly benzoyl peroxide shampoo, the other half received only shampoo and ivermectin.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LdXpuZXRzb3ZhPC9BdXRob3I+PFllYXI+MjAxMjwvWWVh
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ADDIN EN.CITE.DATA 88 In dogs with severe disease, previous antibiotic treatment or dogs with bacterial infections caused by rods, a bacterial culture and sensitivity should be recommended as a basis for the selection of appropriate antibiotic therapy. As the prevalence of skin infections with multiresistant bacteria is increasing, antibiotic stewardship with a judicial use of systemic antibiotics is recommended,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3JyaXM8L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 9 and topical antibacterial therapy alone should be considered for the majority of dogs with demodicosis.-1270523240Consensus Statement 8: In dogs with demodicosis systemic antibiotics will typically not be needed and topical antibacterial therapy combined with good miticidal agents will be sufficient unless severe bacterial infection is present.00Consensus Statement 8: In dogs with demodicosis systemic antibiotics will typically not be needed and topical antibacterial therapy combined with good miticidal agents will be sufficient unless severe bacterial infection is present.AmitrazAmitraz as a leave-on rinse has been the approved mainstay treatment for canine generalized demodicosis in many countries for decades. It is a diamide, N’-(2,4-dimethylphenyl)-N-[(2,4-dimethylphenyl) imino]1-8 methyl]-N-methylmethanidamide. ADDIN EN.CITE <EndNote><Cite><Author>Folz</Author><Year>1978</Year><RecNum>442</RecNum><DisplayText><style face="superscript">89</style></DisplayText><record><rec-number>442</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502508545">442</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Folz, S.D.</author><author>Geng, S.</author><author>Nowakowski, L.H.</author><author>Conklin, J.R.R.D.</author></authors></contributors><titles><title>Evaluation of a new treatment for canine scabies and. demodicosis</title><secondary-title>Journal of Veterinary Pharmacology and Therapeutics</secondary-title></titles><periodical><full-title>Journal of Veterinary Pharmacology and Therapeutics</full-title></periodical><pages>199-204</pages><volume>1</volume><dates><year>1978</year></dates><urls></urls></record></Cite></EndNote>89 Amitraz is a monoamine oxidase inhibitor, an alpha 2-adrenergic agonist and inhibits prostaglandin synthesis. ADDIN EN.CITE <EndNote><Cite><Author>Folz</Author><Year>1978</Year><RecNum>442</RecNum><DisplayText><style face="superscript">89</style></DisplayText><record><rec-number>442</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502508545">442</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Folz, S.D.</author><author>Geng, S.</author><author>Nowakowski, L.H.</author><author>Conklin, J.R.R.D.</author></authors></contributors><titles><title>Evaluation of a new treatment for canine scabies and. demodicosis</title><secondary-title>Journal of Veterinary Pharmacology and Therapeutics</secondary-title></titles><periodical><full-title>Journal of Veterinary Pharmacology and Therapeutics</full-title></periodical><pages>199-204</pages><volume>1</volume><dates><year>1978</year></dates><urls></urls></record></Cite></EndNote>89 In addition to the rinse, amitraz is also available in a 9% tick preventive collar, reported as a sole therapy ADDIN EN.CITE <EndNote><Cite><Author>Franc</Author><Year>1986</Year><RecNum>441</RecNum><DisplayText><style face="superscript">90</style></DisplayText><record><rec-number>441</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502508545">441</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Franc, M.</author><author>Soubeyroux, H.</author></authors></contributors><titles><title>Le traitement de la démodécie du chien par un collier a 9% d’amitraz</title><secondary-title>Revue de Médecine Vétérinaire</secondary-title></titles><periodical><full-title>Revue de Médecine Vétérinaire</full-title></periodical><pages>583-586</pages><volume>137</volume><dates><year>1986</year></dates><urls></urls></record></Cite></EndNote>90 and as a spot-on product in combination with other ectoparasiticides. ADDIN EN.CITE <EndNote><Cite><Author>Hnilica</Author><Year>2003</Year><RecNum>440</RecNum><DisplayText><style face="superscript">91</style></DisplayText><record><rec-number>440</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502508545">440</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hnilica, K.</author><author>Little, S.E.</author><author>Medleau, L.M.</author><author>Lower, K. </author></authors></contributors><titles><title>Evaluation of the use of Preventic (9% amitraz) collars as an adjunct treatment for generalized canine demodicosis</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>224</pages><volume>14</volume><dates><year>2003</year></dates><urls></urls></record></Cite></EndNote>91 However, amitraz tick collar efficacy for canine demodicosis is controversial. Pilot studies of the spot-on products (in combination with metaflumizone HYPERLINK \l "_ENREF_92" \o "Fourie, 2007 #292" PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3VyaWU8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 92-94 and with fipronil HYPERLINK \l "_ENREF_95" \o "Fourie, 2013 #393" ADDIN EN.CITE <EndNote><Cite><Author>Fourie</Author><Year>2013</Year><RecNum>393</RecNum><DisplayText><style face="superscript">95</style></DisplayText><record><rec-number>393</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499329765">393</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fourie, J.</author><author>Dumont, P.</author><author>Halos, L.</author><author>Beugnet, F.</author><author>Pollmeier, M.</author></authors></contributors><auth-address>Clinvet International (Pty) Ltd, PO Box 11186, 9321 Universitas, South Africa.</auth-address><titles><title>Efficacy of a topical application of Certifect(R) (fipronil 6.26% w/v, amitraz 7.48% w/v, (S)-methoprene 5.63% w/v) for the treatment of canine generalized demodicosis</title><secondary-title>Parasite</secondary-title></titles><periodical><full-title>Parasite</full-title></periodical><pages>46</pages><volume>20</volume><keywords><keyword>Administration, Topical</keyword><keyword>Animals</keyword><keyword>Antiparasitic Agents/*therapeutic use</keyword><keyword>Dog Diseases/*drug therapy/parasitology</keyword><keyword>Dogs</keyword><keyword>Drug Combinations</keyword><keyword>Female</keyword><keyword>Insecticides/*therapeutic use</keyword><keyword>Male</keyword><keyword>Methoprene/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/parasitology/*veterinary</keyword><keyword>Mites/drug effects/growth & development</keyword><keyword>Pyrazoles/administration & dosage</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2013</year></dates><isbn>1776-1042 (Electronic)
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Pn==
ADDIN EN.CITE.DATA 96,97 The manufacturer has discontinued the production of the amitraz-metaflumizone product but it may still be available in some parts of the world. The amitraz rinse has been shown to be an effective treatment option in many studies.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb2x6PC9BdXRob3I+PFllYXI+MTk4NDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 3,45 Amitraz rinses require adequate skin contact for optimal efficacy. Therefore it is recommended to clip the hair coat in medium- and long-haired dogs. ADDIN EN.CITE <EndNote><Cite><Author>Kwochka</Author><Year>1993</Year><RecNum>378</RecNum><DisplayText><style face="superscript">112</style></DisplayText><record><rec-number>378</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499007437">378</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Kwochka, K.</author></authors><secondary-authors><author> Griffin, C.</author><author>Macdonald, J,</author><author>Kwochka, K.W,</author></secondary-authors></contributors><titles><title>Demodicosis</title><secondary-title>Current Veterinary Dermatology</secondary-title></titles><pages>72</pages><dates><year>1993</year></dates><pub-location>St Louis</pub-location><publisher>Mosby Year Book</publisher><urls></urls></record></Cite></EndNote>112 The hair should be kept short throughout the treatment period. The rinse should be applied with a sponge and the skin soaked thoroughly and allowed to dry without rinsing. Dogs should not get wet between rinses, to avoid washing off the amitraz. Gentle removal of crusts and surface debris with a shampoo is recommended before application of the amitraz rinse. ADDIN EN.CITE <EndNote><Cite><Author>Kwochka</Author><Year>1993</Year><RecNum>378</RecNum><DisplayText><style face="superscript">112</style></DisplayText><record><rec-number>378</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499007437">378</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Kwochka, K.</author></authors><secondary-authors><author> Griffin, C.</author><author>Macdonald, J,</author><author>Kwochka, K.W,</author></secondary-authors></contributors><titles><title>Demodicosis</title><secondary-title>Current Veterinary Dermatology</secondary-title></titles><pages>72</pages><dates><year>1993</year></dates><pub-location>St Louis</pub-location><publisher>Mosby Year Book</publisher><urls></urls></record></Cite></EndNote>112 Dogs should be lightly towel-dried after shampooing and water rinsing prior to the application of the amitraz rinse. Rinses should be performed in a well-ventilated area and protective clothing should be worn by the handler, as adverse effects such as respiratory problems have been observed in humans.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaWxsZXI8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 27,45 Care should be taken to avoid inappropriate ingestion or excessive exposure. In addition to respiratory adverse effects, many other side effects have been reported in humans associated with amitraz poisoning. A systematic review in humans analyzed 32 studies describing 310 cases of amitraz poisoning. ADDIN EN.CITE <EndNote><Cite><Author>Dhooria</Author><Year>2016</Year><RecNum>437</RecNum><DisplayText><style face="superscript">113</style></DisplayText><record><rec-number>437</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501665261">437</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dhooria, S.</author><author>Agarwal, R.</author></authors></contributors><titles><title>Amitraz, an underrecognized poison: A systematic review</title><secondary-title>Indian Journal of Medical Research</secondary-title></titles><periodical><full-title>Indian Journal of Medical Research</full-title></periodical><pages>348-358</pages><volume>144</volume><dates><year>2016</year></dates><urls></urls></record></Cite></EndNote>113 The most commonly reported clinical features of amitraz poisoning were altered sensorium, miosis, hyperglycemia, bradycardia, vomiting, respiratory failure, hypotension and hypothermia. ADDIN EN.CITE <EndNote><Cite><Author>Dhooria</Author><Year>2016</Year><RecNum>437</RecNum><DisplayText><style face="superscript">113</style></DisplayText><record><rec-number>437</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501665261">437</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dhooria, S.</author><author>Agarwal, R.</author></authors></contributors><titles><title>Amitraz, an underrecognized poison: A systematic review</title><secondary-title>Indian Journal of Medical Research</secondary-title></titles><periodical><full-title>Indian Journal of Medical Research</full-title></periodical><pages>348-358</pages><volume>144</volume><dates><year>2016</year></dates><urls></urls></record></Cite></EndNote>113 Diabetic (humans) should avoid all contact with amitraz. Reported adverse effects of amitraz in dogs included depression, sleepiness, ataxia, pruritus, urticaria, oedema, skin irritations, polyphagia, polydipsia, hypotension, bradycardia, hyperglycaemia, vomiting and diarrhoea.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NdWVsbGVyPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48
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ADDIN EN.CITE.DATA 27,45 Severe reactions or intoxications in dogs can be treated with yohimbine, atipamezole, and other appropriate supportive measures. Smaller breed dogs, in particular toy-breed dogs, such as Pomeranians and Chihuahuas, are at increased risk for toxicity and deaths have been reported. ADDIN EN.CITE <EndNote><Cite><Author>Craig</Author><Year>2003</Year><RecNum>377</RecNum><DisplayText><style face="superscript">114</style></DisplayText><record><rec-number>377</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006758">377</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Craig, M.</author></authors></contributors><titles><title>Demodicosis.</title><secondary-title>British Small Animal Vet Ass </secondary-title></titles><periodical><full-title>British Small Animal Vet Ass</full-title></periodical><pages>153-158</pages><dates><year>2003</year></dates><urls></urls></record></Cite></EndNote>114 Chihuahuas are specifically excluded on the label. Amitraz should be used with caution in very young, geriatric and/or debilitated animals. Since amitraz is an α 2-adrenergic agonist, sedating agents that are also α-adrenergic agonists (e.g. benzodiazepines, xylazine) should be avoided due to possible synergistic toxicity. ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006591">376</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Miller, W. Jr.</author><author>Griffin, C.E.</author><author>Campbell, C.A. </author></authors></contributors><titles><title>Canine demodicosis</title><secondary-title>Muller and Kirk's Small Animal Dermatology</secondary-title></titles><edition>7th</edition><dates><year>2012</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B.Saunders</publisher><urls></urls></record></Cite></EndNote>27 The recommended concentration varies from 0.025 to 0.06% once weekly to every two weeks. Clinical efficacy increases with increasing concentration and shorter treatment intervals.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdWduZXQ8L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 103,104 Intensive protocols with daily rinsing of alternating body halves at a concentration of 0.125% ADDIN EN.CITE <EndNote><Cite><Author>Medleau</Author><Year>1995</Year><RecNum>203</RecNum><DisplayText><style face="superscript">106</style></DisplayText><record><rec-number>203</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291216183">203</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Medleau, L.</author><author>Willemse, T.</author></authors></contributors><auth-address>Department of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.</auth-address><titles><title>Efficacy of daily amitraz therapy for refractory, generalized demodicosis in dogs: two independent studies</title><secondary-title>J Am Anim Hosp Assoc</secondary-title></titles><periodical><full-title>J Am Anim Hosp Assoc</full-title></periodical><pages>246-9</pages><volume>31</volume><number>3</number><edition>1995/05/01</edition><keywords><keyword>Administration, Topical</keyword><keyword>Animals</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Drug Administration Schedule/veterinary</keyword><keyword>Female</keyword><keyword>Insecticides/administration & dosage/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/complications/drug therapy/*veterinary</keyword><keyword>Prospective Studies</keyword><keyword>Recurrence</keyword><keyword>Skin/parasitology</keyword><keyword>Toluidines/administration & dosage/*therapeutic use</keyword></keywords><dates><year>1995</year><pub-dates><date>May-Jun</date></pub-dates></dates><isbn>0587-2871 (Print)
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ADDIN EN.CITE.DATA 103 Treatment of pedal demodicosis with amitraz rinses may be especially problematic in wet environments because it is difficult to maintain sufficient amitraz on the pedal skin in these circumstances. Daily treatment of the paws ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006591">376</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Miller, W. Jr.</author><author>Griffin, C.E.</author><author>Campbell, C.A. </author></authors></contributors><titles><title>Canine demodicosis</title><secondary-title>Muller and Kirk's Small Animal Dermatology</secondary-title></titles><edition>7th</edition><dates><year>2012</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B.Saunders</publisher><urls></urls></record></Cite></EndNote>27 or using other treatment modalities may be needed. As many as 20% of dogs with generalised demodicosis do not attain negative scraping results or experience a recurrence when treatment with amitraz is discontinued. ADDIN EN.CITE <EndNote><Cite><Author>Kwochka</Author><Year>1985</Year><RecNum>207</RecNum><DisplayText><style face="superscript">104</style></DisplayText><record><rec-number>207</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291216525">207</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kwochka, K. W.</author><author>Kunkle, G. A.</author><author>Foil, C.S.</author></authors></contributors><titles><title>The efficacy of amitraz for generalized demodicosis in dogs: A study of two concentrations and frequencies of application</title><secondary-title>The Compendium on Continuing Education</secondary-title></titles><periodical><full-title>The COmpendium on Continuing Education</full-title></periodical><pages>8-17</pages><volume>7</volume><dates><year>1985</year></dates><urls></urls></record></Cite></EndNote>104 The success rate of amitraz rinses was reported to be lower in dogs with adult-onset demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>15030556</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>45Combining amitraz with other miticidal therapies has been previously reported but is currently rarely used because of the high efficacy of other therapies. There is a report of potentiated neurotoxicity in a dog treated with ivermectin and amitraz. ADDIN EN.CITE <EndNote><Cite><Author>Kwochka</Author><Year>1993</Year><RecNum>378</RecNum><DisplayText><style face="superscript">112</style></DisplayText><record><rec-number>378</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499007437">378</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Kwochka, K.</author></authors><secondary-authors><author> Griffin, C.</author><author>Macdonald, J,</author><author>Kwochka, K.W,</author></secondary-authors></contributors><titles><title>Demodicosis</title><secondary-title>Current Veterinary Dermatology</secondary-title></titles><pages>72</pages><dates><year>1993</year></dates><pub-location>St Louis</pub-location><publisher>Mosby Year Book</publisher><urls></urls></record></Cite></EndNote>112-1270265430Consensus Statement 9: Weekly amitraz rinses at 0.025-0.05% are effective for canine demodicosis, long-haired animals should be clipped.00Consensus Statement 9: Weekly amitraz rinses at 0.025-0.05% are effective for canine demodicosis, long-haired animals should be clipped.IvermectinIvermectin is derived from the fermentation of molecularly synthesized Streptomyces avermitilis. ADDIN EN.CITE <EndNote><Cite><Author>Campbell</Author><Year>1983</Year><RecNum>371</RecNum><DisplayText><style face="superscript">115</style></DisplayText><record><rec-number>371</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498025476">371</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Campbell, W.C.</author><author>Fisher, M.H.</author><author>Stapley, E.O.</author><author>Albers-Sch?nberg, G.</author><author>Jacob, T.A. </author></authors></contributors><titles><title>Ivermectin: A Potent New Antiparasitic Agent</title><secondary-title>Science</secondary-title></titles><periodical><full-title>Science</full-title></periodical><pages>823-828</pages><volume>221</volume><dates><year>1983</year></dates><urls></urls></record></Cite></EndNote>115 Since its introduction as a broad-spectrum parasiticide in 1981, it has become widely used in veterinary medicine. For almost two decades, ivermectin was the most commonly used macrocyclic lactone in the treatment of canine demodicosis. However, it is only approved in dogs for the prevention of the heartworm Dirofilaria immitis - all other applications are considered extra-label. ADDIN EN.CITE <EndNote><Cite><Author>Plumb</Author><Year>2015</Year><RecNum>511</RecNum><DisplayText><style face="superscript">116</style></DisplayText><record><rec-number>511</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503311395">511</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Plumb, D.</author></authors></contributors><titles><title>Plumb’s Veterinary Drug Handbook</title></titles><edition>8th Edition</edition><dates><year>2015</year></dates><pub-location>Stockholm, Wisconsin</pub-location><publisher>Wiley Blackwell</publisher><urls></urls></record></Cite></EndNote>116Preliminary studies using ivermectin for the treatment of demodicosis evaluated various dosages and routes of administration. Initial results indicated that daily oral administration of ivermectin was the most efficacious protocol whilst weekly subcutaneous administration at 0.4 mg/kg ADDIN EN.CITE <EndNote><Cite><Author>Scott</Author><Year>1985</Year><RecNum>211</RecNum><DisplayText><style face="superscript">108</style></DisplayText><record><rec-number>211</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291304602">211</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Scott, D. W.</author><author>Walton, D.K.</author></authors></contributors><titles><title>Experiences with the use of amitraz and ivermectin for the treatment of generalized demodicosis in dogs</title><secondary-title>Journal of the American Animal Hospital Association</secondary-title></titles><periodical><full-title>Journal of the American Animal Hospital Association</full-title></periodical><pages>535-541</pages><volume>21</volume><dates><year>1985</year></dates><urls></urls></record></Cite></EndNote>108 or use of a 0.5% ivermectin topical pour-on three times weekly ADDIN EN.CITE <EndNote><Cite><Author>Paradis</Author><Year>1998</Year><RecNum>372</RecNum><DisplayText><style face="superscript">117</style></DisplayText><record><rec-number>372</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498025634">372</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Paradis, M.</author><author>Page, N.</author></authors></contributors><titles><title>Topical (pour-on) ivermectin in the treatment of chronic generalized demodicosis in dogs</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>55-59</pages><volume>9</volume><dates><year>1998</year></dates><urls></urls></record></Cite></EndNote>117 yielded poor results. Several studies have examined the use of oral ivermectin at varying dosages with contrasting results. Oral administration at 350 μg/kg ADDIN EN.CITE <EndNote><Cite><Author>Fondati</Author><Year>1996</Year><RecNum>172</RecNum><DisplayText><style face="superscript">118</style></DisplayText><record><rec-number>172</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214848">172</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fondati, A.</author></authors></contributors><titles><title>Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>99-104</pages><volume>7</volume><dates><year>1996</year></dates><urls></urls></record></Cite></EndNote>118 and 400 μg/kg ADDIN EN.CITE <EndNote><Cite><Author>Medleau</Author><Year>1996</Year><RecNum>213</RecNum><DisplayText><style face="superscript">119</style></DisplayText><record><rec-number>213</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291306707">213</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Medleau, L.</author><author>Ristic, Z.</author><author>McElveen, D. R.</author></authors></contributors><titles><title>Daily ivermectin for the treatment of generalized demodicosis in dogs</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>209-212</pages><volume>7</volume><dates><year>1996</year></dates><urls></urls></record></Cite></EndNote>119 daily demonstrated poor efficacy with only 30% and 48% rates of cure, respectively. However small sample size and concurrent administration of other drugs may have negatively impacted the results of these trials. 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ADDIN EN.CITE.DATA 121-123 The currently recommended protocols generally employ 300-600 μg/kg orally once daily until four to eight weeks beyond parasitological cure. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2012</Year><RecNum>318</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1307269305">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Bensignor, E.</author><author>Ferrer, L.</author><author>Holm, B. R.</author><author>Lemarie, S.</author><author>Paradis, M.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>86-96</pages><volume>23</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>3 Despite its frequent successful use in the treatment of demodicosis, it is unlikely that ivermectin will ever become labeled for this purpose due to its potential toxicity. Dogs treated with ivermectin should be closely monitored for potential neurotoxicity, especially ivermectin-sensitive breeds such as collie breeds, Australian shepherds, Shetland and Old English sheepdogs or dogs treated with high doses of ivermectin. Clinical signs of toxicosis may include mydriasis, lethargy, vomiting, ataxia, tremors and temporary blindness which may rapidly progress to seizures, stupor, coma, respiratory failure and death.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NdWVsbGVyPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48
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ADDIN EN.CITE.DATA 45,124,125 Mydriasis is typically the first clinical sign of ivermectin toxicity and the last to resolve. There is no specific antidote for ivermectin toxicosis. Depending on their severity, the clinical signs typically resolve within days to weeks following cessation of the drug along with supportive care. In the case of an acute oral overdose, repeated doses of activated charcoal may be administered in an effort to disrupt enterohepatic recirculation. ADDIN EN.CITE <EndNote><Cite><Author>Plumb</Author><Year>2015</Year><RecNum>511</RecNum><DisplayText><style face="superscript">116</style></DisplayText><record><rec-number>511</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503311395">511</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Plumb, D.</author></authors></contributors><titles><title>Plumb’s Veterinary Drug Handbook</title></titles><edition>8th Edition</edition><dates><year>2015</year></dates><pub-location>Stockholm, Wisconsin</pub-location><publisher>Wiley Blackwell</publisher><urls></urls></record></Cite></EndNote>116 Intravenous lipid emulsion therapy has been shown to be effective in the treatment of adverse reactions to all lipophilic drugs including ivermectin. ADDIN EN.CITE <EndNote><Cite><Author>Clarke</Author><Year>2011</Year><RecNum>373</RecNum><DisplayText><style face="superscript">126</style></DisplayText><record><rec-number>373</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498026170">373</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Clarke, D.L.</author><author>Lee, J.A.</author><author>Murphy, L.A.</author><author>Reineke, E.L.</author></authors></contributors><titles><title>Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie</title><secondary-title>Journal of the American Veterinary Medical Association</secondary-title></titles><periodical><full-title>Journal of the American Veterinary Medical Association</full-title></periodical><pages>1328-1333</pages><volume>239</volume><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>126 Its effect is thought to be due to the lipid sink mechanism whereby the drug is drawn out of the tissues and sequestered into a lipid phase within the intravascular space thereby decreasing CNS tissue concentrations. ADDIN EN.CITE <EndNote><Cite><Author>Clarke</Author><Year>2011</Year><RecNum>373</RecNum><DisplayText><style face="superscript">126</style></DisplayText><record><rec-number>373</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498026170">373</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Clarke, D.L.</author><author>Lee, J.A.</author><author>Murphy, L.A.</author><author>Reineke, E.L.</author></authors></contributors><titles><title>Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie</title><secondary-title>Journal of the American Veterinary Medical Association</secondary-title></titles><periodical><full-title>Journal of the American Veterinary Medical Association</full-title></periodical><pages>1328-1333</pages><volume>239</volume><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>126 Physostigmine, a parasympathomimetic alkaloid and reversible cholinesterase inhibitor, has been shown to cause short-term improvement in neurologic signs but is not recommended for prolonged use due to its significant cholinergic effects and only temporary action. ADDIN EN.CITE <EndNote><Cite><Author>Merola</Author><Year>2012</Year><RecNum>368</RecNum><DisplayText><style face="superscript">125</style></DisplayText><record><rec-number>368</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498024625">368</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Merola, V.M.</author><author>Eubig, P.A. </author></authors></contributors><titles><title>Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-Glycoprotein in dogs and cats</title><secondary-title>Veterinary Clinics of North America Small Animal Practice</secondary-title></titles><periodical><full-title>Veterinary Clinics of North America Small Animal Practice</full-title></periodical><pages>313-vii</pages><volume>42</volume><number>2</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>125 Flumazenil, a GABA-antagonist, has been shown to reverse the effects of ivermectin in experimental models in rodents.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZXJvbGE8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 125,127 However, its clinical efficacy in dogs has yet to be demonstrated. Ivermectin toxicity can occur as a result of acute overdose, elevated serum concentration following long-term administration or associated with genetic susceptibility which is seen most commonly in herding breeds such as collie breeds, Australian shepherds, Shetland and Old English sheepdogs and their crosses but has also been recognised to occur in other breeds.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXJiZXQ8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 124,128-130 Not uncommonly, this results in a severe and sometimes fatal idiosyncratic neurotoxicosis. Ivermectin-sensitivity occurs in individuals that carry a frame shift deletion mutation of the ABCB1 gene (formerly multi-drug resistance gene, mdr1), which is responsible for producing P-glycoprotein (P-gp) – an ATP-dependent transmembrane transporter protein which plays an important role in the blood-brain barrier.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWFsZXk8L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 129 The deletion mutation causes P-gp synthesis to terminate prematurely resulting in severely truncated, non-functional P-gp molecules. Consequently, transport of certain drugs out of the central nervous system (CNS) is impaired leading to accumulation of drug within the CNS to toxic levels.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWFsZXk8L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 129 Ivermectin is among the substrates for P-gp and therefore, individuals that are homozygous for this autosomal recessive gene demonstrate the ivermectin-sensitivity phenotype. Dogs can be tested for the ABCB1-1Δ genotype prior to beginning ivermectin therapy through a number of laboratories. ADDIN EN.CITE <EndNote><Cite><Author>Mealey</Author><Year>2008</Year><RecNum>279</RecNum><DisplayText><style face="superscript">125,130</style></DisplayText><record><rec-number>279</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1305024868">279</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mealey, K.L.</author><author>Meurs, K.M.</author></authors></contributors><titles><title>Breed distribution of the ABCB1-1Δ (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping</title><secondary-title>J Am Vet Med Assoc</secondary-title></titles><periodical><full-title>J Am Vet Med Assoc</full-title></periodical><pages>921-924</pages><volume>233</volume><dates><year>2008</year></dates><urls></urls></record></Cite><Cite><Author>Merola</Author><Year>2012</Year><RecNum>368</RecNum><record><rec-number>368</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498024625">368</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Merola, V.M.</author><author>Eubig, P.A. </author></authors></contributors><titles><title>Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-Glycoprotein in dogs and cats</title><secondary-title>Veterinary Clinics of North America Small Animal Practice</secondary-title></titles><periodical><full-title>Veterinary Clinics of North America Small Animal Practice</full-title></periodical><pages>313-vii</pages><volume>42</volume><number>2</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>125,130 However, dogs without this defect may also show signs of toxicity.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CaXNzb25uZXR0ZTwvQXV0aG9yPjxZZWFyPjIwMDk8L1ll
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ADDIN EN.CITE.DATA 131 In ivermectin-sensitive individuals, toxicity may be apparent four to twelve hours after oral administration. ADDIN EN.CITE <EndNote><Cite><Author>Merola</Author><Year>2012</Year><RecNum>368</RecNum><DisplayText><style face="superscript">125</style></DisplayText><record><rec-number>368</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498024625">368</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Merola, V.M.</author><author>Eubig, P.A. </author></authors></contributors><titles><title>Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-Glycoprotein in dogs and cats</title><secondary-title>Veterinary Clinics of North America Small Animal Practice</secondary-title></titles><periodical><full-title>Veterinary Clinics of North America Small Animal Practice</full-title></periodical><pages>313-vii</pages><volume>42</volume><number>2</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>125 Slow titration up to the therapeutic dose over several days is recommended when instituting ivermectin therapy in all breeds of dogs to enable close monitoring for adverse reactions and early identification of ivermectin-sensitive individuals. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>1999</Year><RecNum>171</RecNum><DisplayText><style face="superscript">124</style></DisplayText><record><rec-number>171</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">171</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author><author>Bettenay, S. V.</author></authors></contributors><auth-address>Animal Skin and Allergy Clinic, Mount Waverley, Victoria, Australia.</auth-address><titles><title>A proposed new therapeutic protocol for the treatment of canine mange with ivermectin</title><secondary-title>J Am Anim Hosp Assoc</secondary-title></titles><periodical><full-title>J Am Anim Hosp Assoc</full-title></periodical><pages>77-80</pages><volume>35</volume><number>1</number><edition>1999/02/06</edition><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Dog Diseases/*drug therapy/parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Insecticides/administration & dosage/adverse effects/*therapeutic use</keyword><keyword>Ivermectin/administration & dosage/adverse effects/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword></keywords><dates><year>1999</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0587-2871 (Print)
0587-2871 (Linking)</isbn><accession-num>9934933</accession-num><urls><related-urls><url> A starting dose of 0.05 mg/kg on Day 1 is recommended, then 0.1 mg/kg on Day 2 followed by incremental doses of 0.1 mg/kg/day until the final dose is achieved. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>1999</Year><RecNum>171</RecNum><DisplayText><style face="superscript">124</style></DisplayText><record><rec-number>171</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">171</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author><author>Bettenay, S. V.</author></authors></contributors><auth-address>Animal Skin and Allergy Clinic, Mount Waverley, Victoria, Australia.</auth-address><titles><title>A proposed new therapeutic protocol for the treatment of canine mange with ivermectin</title><secondary-title>J Am Anim Hosp Assoc</secondary-title></titles><periodical><full-title>J Am Anim Hosp Assoc</full-title></periodical><pages>77-80</pages><volume>35</volume><number>1</number><edition>1999/02/06</edition><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Dog Diseases/*drug therapy/parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Insecticides/administration & dosage/adverse effects/*therapeutic use</keyword><keyword>Ivermectin/administration & dosage/adverse effects/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword></keywords><dates><year>1999</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0587-2871 (Print)
0587-2871 (Linking)</isbn><accession-num>9934933</accession-num><urls><related-urls><url> Treatment should cease and an alternate therapy be considered if neurologic signs develop during this titration period. Owing to ivermectin’s long half-life (80 +/- 30 hours), ADDIN EN.CITE <EndNote><Cite><Author>Clarke</Author><Year>2011</Year><RecNum>373</RecNum><DisplayText><style face="superscript">126</style></DisplayText><record><rec-number>373</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498026170">373</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Clarke, D.L.</author><author>Lee, J.A.</author><author>Murphy, L.A.</author><author>Reineke, E.L.</author></authors></contributors><titles><title>Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie</title><secondary-title>Journal of the American Veterinary Medical Association</secondary-title></titles><periodical><full-title>Journal of the American Veterinary Medical Association</full-title></periodical><pages>1328-1333</pages><volume>239</volume><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>126 serum concentrations rise over weeks until after perhaps 6 weeks a steady-state is reached. Subchronic ivermectin toxicity has also been reported following long-term therapy as serum drug concentrations accumulate to toxic levels.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWRsZWF1PC9BdXRob3I+PFllYXI+MTk5NjwvWWVhcj48
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ADDIN EN.CITE.DATA 45,119 In a study of 28 dogs that developed subchronic toxicity while being treated for demodicosis with ivermectin or other macrocyclic lactones, only one dog was heterozygous and all others were homozygous for the normal ABCB1 gene.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CaXNzb25uZXR0ZTwvQXV0aG9yPjxZZWFyPjIwMDk8L1ll
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ADDIN EN.CITE.DATA 131 Interestingly, 10 dogs in this study were concurrently receiving one or more drugs that are also substrates of P-gp such as ketoconazole, cyclosporine or glucocorticoids. The concurrent use of ivermectin with other P-gp substrates should be avoided whenever possible. In addition, use of spinosad-containing products should be avoided as mild to moderate ivermectin toxicosis has been reported when these drugs are used concurrently.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdW5uPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 132 Spinosad has been shown to be a potent inhibitor of canine P-gp which accounts for its impact on ivermectin pharmacokinetics.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdW5uPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdW5uPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj
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ZE5vdGU+
ADDIN EN.CITE.DATA 132,133 Under the Animal Medicinal Drug Use Clarification Act (AMDUCA), off-label therapies should only be used in instances where a drug licensed for the purpose of treating demodicosis has either failed or is contra-indicated.Milbemycin oximeMilbemycin oxime is the fermentation product of Streptomyces hygroscopus aureolacrimosus. It is approved in many countries as an endoparasiticide. In some countries, oral milbemyin oxime is licensed for the treatment of canine demodicosis at a dose of 0.5-2 mg/kg daily. In studies from the USA and Australia, a clearly higher success rate was seen with the higher dose of 1-2 mg/kg compared to 0.5-1mg/kg.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYXJmaWVsZDwvQXV0aG9yPjxZZWFyPjE5OTI8L1llYXI+
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ADDIN EN.CITE.DATA 23,134,135 However, these studies were conducted in referral practices with potentially more chronic and severely affected patients. In contrast, a Swedish study showed a good response with the low dose protocol, ADDIN EN.CITE <EndNote><Cite><Author>Holm</Author><Year>2003</Year><RecNum>249</RecNum><DisplayText><style face="superscript">136</style></DisplayText><record><rec-number>249</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291374895">249</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Holm, B. R.</author></authors></contributors><auth-address>Department of Dermatology, Bla Stjarnan Small Animal Hospital, Gjutjarnsgatan 4, SE-417 07 Gothenburg, Sweden. birgit.holm@blastjarnan.se</auth-address><titles><title>Efficacy of milbemycin oxime in the treatment of canine generalized demodicosis: a retrospective study of 99 dogs (1995-2000)</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>189-95</pages><volume>14</volume><number>4</number><edition>2003/08/05</edition><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Anthelmintics/administration & dosage/*therapeutic use</keyword><keyword>Anti-Bacterial Agents/administration & dosage/*therapeutic use</keyword><keyword>Dog Diseases/*drug therapy/epidemiology/pathology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>*Macrolides</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>Mites</keyword><keyword>Skin/parasitology</keyword><keyword>Sweden/epidemiology</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>12895223</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>136 possibly because most dogs in that study were diagnosed early in the disease and had not previously been treated with other miticides. Alternatively, a different genetic background of the dogs or different sensitivity of the mites to milbemycin oxime may have influenced the results. The success rate of milbemycin oxime was shown to be much lower in dogs with adult-onset demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Garfield</Author><Year>1992</Year><RecNum>163</RecNum><DisplayText><style face="superscript">23,135</style></DisplayText><record><rec-number>163</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291213287">163</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Garfield, R.A.</author><author>Lloyd, R.</author></authors></contributors><titles><title>The use of oral milbemycin oxime (Interceptor) in the treatment of chronic generalized canine demodicosis</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>231-235</pages><volume>3</volume><dates><year>1992</year></dates><urls></urls></record></Cite><Cite><Author>Mueller</Author><Year>1995</Year><RecNum>248</RecNum><record><rec-number>248</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291374055">248</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author><author>Bettenay, S.V.</author></authors></contributors><titles><title>Milbemycin oxime in the treatment of canine demodicosis</title><secondary-title>Australian Veterinary Practitioner</secondary-title></titles><periodical><full-title>Australian Veterinary Practitioner</full-title></periodical><pages>122-126</pages><volume>25</volume><dates><year>1995</year></dates><urls></urls></record></Cite></EndNote>23,135 There seems to be a high safety margin with milbemycin oxime. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>15030556</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>45 It has been administered to Collies at a dose of 2.5 mg/kg daily for 10 days with no adverse effects observed. ADDIN EN.CITE <EndNote><Cite><Author>Sasaki</Author><Year>1990</Year><RecNum>267</RecNum><DisplayText><style face="superscript">137</style></DisplayText><record><rec-number>267</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291376196">267</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sasaki, Y.</author><author>Kitagawa, H.</author><author>Murase, S.</author></authors></contributors><titles><title>Susceptibility of rough-coated collies to milbemycin oxime</title><secondary-title>Japanese Journal of Veterinary Science</secondary-title></titles><periodical><full-title>Japanese Journal of Veterinary Science</full-title></periodical><pages>1269-1271</pages><volume>52</volume><dates><year>1990</year></dates><urls></urls></record></Cite></EndNote>137 However, dogs homozygous for the ABCB1-1Δ (MDR-1) mutation developed ataxia with milbemycin oxime at a dose of only 1.5 mg/kg daily, although they tolerated the drug at 0.6 mg/kg/day.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXJiZXQ8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 128 In herding breeds, it is thus prudent to evaluate the ABCB1-1Δ (MDR-1) genotype and to use lower doses or increase the dose gradually in dogs homozygous for the ABCB1-1Δ (MDR-1) mutation similar to what is recommended for oral ivermectin. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>1999</Year><RecNum>171</RecNum><DisplayText><style face="superscript">124</style></DisplayText><record><rec-number>171</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">171</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author><author>Bettenay, S. V.</author></authors></contributors><auth-address>Animal Skin and Allergy Clinic, Mount Waverley, Victoria, Australia.</auth-address><titles><title>A proposed new therapeutic protocol for the treatment of canine mange with ivermectin</title><secondary-title>J Am Anim Hosp Assoc</secondary-title></titles><periodical><full-title>J Am Anim Hosp Assoc</full-title></periodical><pages>77-80</pages><volume>35</volume><number>1</number><edition>1999/02/06</edition><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Dog Diseases/*drug therapy/parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Insecticides/administration & dosage/adverse effects/*therapeutic use</keyword><keyword>Ivermectin/administration & dosage/adverse effects/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword></keywords><dates><year>1999</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0587-2871 (Print)
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ADDIN EN.CITE.DATA 138-140 and 500 ?g/kg administered every 72 hours showed similar results. ADDIN EN.CITE <EndNote><Cite><Author>Delayte</Author><Year>2006</Year><RecNum>277</RecNum><DisplayText><style face="superscript">121</style></DisplayText><record><rec-number>277</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1305024868">277</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Delayte, E.H.</author><author>Otsuka, M.</author><author>Larsson, C.E.</author><author>Castro, R.C.C.</author></authors></contributors><titles><title>Efficacy of systemic macrocyclic lactones (ivermectin and moxidectin) for the treatment of generalized canine demodicosis</title><secondary-title>Arq. Bras. Med. Vet. Zootec.</secondary-title></titles><periodical><full-title>Arq. Bras. Med. Vet. Zootec.</full-title></periodical><pages>31-38</pages><volume>58</volume><dates><year>2006</year></dates><urls></urls></record></Cite></EndNote>121 When oral administration (500 ?g/kg) was compared to the subcutaneous route (500-1,000 ?g/kg), each administered every 72 hours, rates of cure were 75% and 86%, respectively. Adverse effects were reported in 10 to 37% of dogs in these studies,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZW5zaWdub3I8L0F1dGhvcj48WWVhcj4xOTk4PC9ZZWFy
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ADDIN EN.CITE.DATA 121,138-140 but were mostly mild and included emesis, salivation, anorexia, lethargy, dyspnoea, and facial oedema. Since these occurred more frequently with subcutaneous administration, ADDIN EN.CITE <EndNote><Cite><Author>Wagner</Author><Year>2000</Year><RecNum>20</RecNum><DisplayText><style face="superscript">140</style></DisplayText><record><rec-number>20</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849817">20</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wagner, R.</author><author>Wendlberger, U.</author></authors></contributors><auth-address>Dermatology Service, 1. Medical Clinic, Veterinary University, Veterinarplatz 1, A-1210, Vienna, Austria. regina.wagner@vu-wien.ac.at</auth-address><titles><title>Field efficacy of moxidectin in dogs and rabbits naturally infested with Sarcoptes spp., Demodex spp. and Psoroptes spp. mites</title><secondary-title>Vet Parasitol</secondary-title></titles><periodical><full-title>Vet Parasitol</full-title></periodical><pages>149-58</pages><volume>93</volume><number>2</number><edition>2000/10/18</edition><keywords><keyword>Animals</keyword><keyword>Anti-Bacterial Agents/therapeutic use</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Insecticides/*therapeutic use</keyword><keyword>Macrolides</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>Mites</keyword><keyword>*Rabbits</keyword><keyword>Scabies/drug therapy</keyword></keywords><dates><year>2000</year><pub-dates><date>Nov 10</date></pub-dates></dates><isbn>0304-4017 (Print)
0304-4017 (Linking)</isbn><accession-num>11035233</accession-num><urls><related-urls><url>(00)00357-5 [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>140 the oral route is preferable. The efficacy of moxidectin appears to be similar to that of ivermectin, and although neurologic signs such as mydriasis, tremor, ataxia and seizures have been reported with overdoses, ADDIN EN.CITE <EndNote><Cite><Author>Merola</Author><Year>2012</Year><RecNum>368</RecNum><DisplayText><style face="superscript">125</style></DisplayText><record><rec-number>368</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498024625">368</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Merola, V.M.</author><author>Eubig, P.A. </author></authors></contributors><titles><title>Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-Glycoprotein in dogs and cats</title><secondary-title>Veterinary Clinics of North America Small Animal Practice</secondary-title></titles><periodical><full-title>Veterinary Clinics of North America Small Animal Practice</full-title></periodical><pages>313-vii</pages><volume>42</volume><number>2</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>125 moxidectin seems to be better tolerated by ivermectin-sensitive individuals than is ivermectin. ADDIN EN.CITE <EndNote><Cite><Author>Burrows</Author><Year>1997</Year><RecNum>245</RecNum><DisplayText><style face="superscript">139</style></DisplayText><record><rec-number>245</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291367002">245</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Burrows, A.</author></authors></contributors><titles><title>Evaluation of the clinical efficacy of two different doses of moxidectin in the treatment of generalized demodicosis in the dog</title><secondary-title>Annual Meeting of the Australian College of Veterinary Scientists</secondary-title></titles><dates><year>1997</year></dates><pub-location>Sydney</pub-location><urls></urls></record></Cite></EndNote>139 Nevertheless, a gradual dose increase over several days similar to what is recommended for ivermectin HYPERLINK \l "_ENREF_124" \o "Mueller, 1999 #171" ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>1999</Year><RecNum>171</RecNum><DisplayText><style face="superscript">124</style></DisplayText><record><rec-number>171</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">171</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author><author>Bettenay, S. V.</author></authors></contributors><auth-address>Animal Skin and Allergy Clinic, Mount Waverley, Victoria, Australia.</auth-address><titles><title>A proposed new therapeutic protocol for the treatment of canine mange with ivermectin</title><secondary-title>J Am Anim Hosp Assoc</secondary-title></titles><periodical><full-title>J Am Anim Hosp Assoc</full-title></periodical><pages>77-80</pages><volume>35</volume><number>1</number><edition>1999/02/06</edition><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Dog Diseases/*drug therapy/parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Insecticides/administration & dosage/adverse effects/*therapeutic use</keyword><keyword>Ivermectin/administration & dosage/adverse effects/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword></keywords><dates><year>1999</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0587-2871 (Print)
0587-2871 (Linking)</isbn><accession-num>9934933</accession-num><urls><related-urls><url> seems prudent to identify the few dogs intolerant to the drug, before adverse effects become severe and potentially fatal. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
0959-4493 (Linking)</isbn><accession-num>15030556</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>45Topical application appears to be better tolerated than either of the aforementioned routes. A 2.5% preparation of moxidectin combined with 10% imidacloprid was well-tolerated even in ivermectin-sensitive breeds that were given three monthly applications of up to five times the recommended dose. ADDIN EN.CITE <EndNote><Cite><Author>Paul</Author><Year>2004</Year><RecNum>369</RecNum><DisplayText><style face="superscript">141</style></DisplayText><record><rec-number>369</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1498024920">369</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Paul, A.J.</author><author>Hutchens, D.E.</author><author>Firkins, L.D.</author><author>Borgstrom, M. </author></authors></contributors><titles><title>Dermal safety study with imidacloprid/moxidectin topical solution in the ivermectin-sensitive Collie</title><secondary-title>Veterinary Parasitology </secondary-title></titles><periodical><full-title>Veterinary Parasitology</full-title></periodical><pages>285-291</pages><volume>121</volume><number>3-4</number><dates><year>2004</year></dates><urls></urls></record></Cite></EndNote>141 When applied every two weeks, efficacy was greater in dogs with juvenile-onset versus adult-onset disease - similar to studies using other treatment protocols.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NdWVsbGVyPC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48
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ADDIN EN.CITE.DATA 144 Since this spot-on is commonly prescribed to young dogs as a monthly agent for the treatment and prevention of other parasitic diseases, its influence on the progression of localised demodicosis to the more generalised form should be evaluated. However, the high rate of spontaneous resolution of localized disease complicates interpretation of such studies. ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499006591">376</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Miller, W. Jr.</author><author>Griffin, C.E.</author><author>Campbell, C.A. </author></authors></contributors><titles><title>Canine demodicosis</title><secondary-title>Muller and Kirk's Small Animal Dermatology</secondary-title></titles><edition>7th</edition><dates><year>2012</year></dates><pub-location>Philadelphia</pub-location><publisher>W.B.Saunders</publisher><urls></urls></record></Cite></EndNote>27DoramectinDoramectin is a longer-acting macrocyclic lactone that has been reported as a successful treatment for canine demodicosis.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Kb2huc3RvbmU8L0F1dGhvcj48WWVhcj4yMDAyPC9ZZWFy
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ADDIN EN.CITE.DATA 145-147 In the first study, twenty-three dogs were injected once weekly with 600 μg/kg subcutaneously for 5–23 weeks. ADDIN EN.CITE <EndNote><Cite><Author>Johnstone</Author><Year>2002</Year><RecNum>270</RecNum><DisplayText><style face="superscript">145</style></DisplayText><record><rec-number>270</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291377579">270</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Johnstone, I.P.</author></authors></contributors><titles><title>Doramectin as a treatment for canine and feline demodicosis</title><secondary-title>Australian Veterinary Practitioner</secondary-title></titles><periodical><full-title>Australian Veterinary Practitioner</full-title></periodical><pages>98-103</pages><volume>32</volume><dates><year>2002</year></dates><urls></urls></record></Cite></EndNote>145 Ten of the dogs were cured, seven relapsed after 1–24 months (two of which responded to repeat doramectin treatment) and six were lost to follow-up. None of the animals in this study were reported to show any adverse effects with therapy. In a second study, doramectin was given orally to 29 dogs with generalised demodicosis with good efficacy. ADDIN EN.CITE <EndNote><Cite><Author>Murayama</Author><Year>2010</Year><RecNum>269</RecNum><DisplayText><style face="superscript">146</style></DisplayText><record><rec-number>269</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291377522">269</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Murayama, N.</author><author>Shibata, K.</author><author>Nagata, M.</author></authors></contributors><auth-address>Animal Dermatology Center, Animal Specialist Center, Jindaijihigashi Chofu, Tokyo, Japan. murayama@asc.jp</auth-address><titles><title>Efficacy of weekly oral doramectin treatment in canine demodicosis</title><secondary-title>Vet Rec</secondary-title></titles><periodical><full-title>Vet Rec</full-title></periodical><pages>63-4</pages><volume>167</volume><number>2</number><edition>2010/07/14</edition><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Antiparasitic Agents/*administration & dosage</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Drug Administration Schedule/veterinary</keyword><keyword>Female</keyword><keyword>Ivermectin/administration & dosage/*analogs & derivatives</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2010</year><pub-dates><date>Jul 10</date></pub-dates></dates><isbn>0042-4900 (Print)
0042-4900 (Linking)</isbn><accession-num>20622206</accession-num><urls><related-urls><url> [pii]
10.1136/vr.b4885</electronic-resource-num><language>eng</language></record></Cite></EndNote>146 Ataxia as an adverse effect of doramectin therapy for demodicosis was seen in one Golden retriever. ADDIN EN.CITE <EndNote><Cite><Author>Murayama</Author><Year>2010</Year><RecNum>269</RecNum><DisplayText><style face="superscript">146</style></DisplayText><record><rec-number>269</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291377522">269</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Murayama, N.</author><author>Shibata, K.</author><author>Nagata, M.</author></authors></contributors><auth-address>Animal Dermatology Center, Animal Specialist Center, Jindaijihigashi Chofu, Tokyo, Japan. murayama@asc.jp</auth-address><titles><title>Efficacy of weekly oral doramectin treatment in canine demodicosis</title><secondary-title>Vet Rec</secondary-title></titles><periodical><full-title>Vet Rec</full-title></periodical><pages>63-4</pages><volume>167</volume><number>2</number><edition>2010/07/14</edition><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Antiparasitic Agents/*administration & dosage</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Drug Administration Schedule/veterinary</keyword><keyword>Female</keyword><keyword>Ivermectin/administration & dosage/*analogs & derivatives</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2010</year><pub-dates><date>Jul 10</date></pub-dates></dates><isbn>0042-4900 (Print)
0042-4900 (Linking)</isbn><accession-num>20622206</accession-num><urls><related-urls><url> [pii]
10.1136/vr.b4885</electronic-resource-num><language>eng</language></record></Cite></EndNote>146 The most recent study involved 400 client-owned dogs treated with weekly subcutaneous doramectin injections (0.6 mg/kg), 232 of which successfully completed the protocol. Two-hundred and twenty of these dogs (94.8%) achieved clinical remission with two consecutive negative skin scrapes collected two weeks apart. The time taken to achieve this remission ranged from 4 to 20 weeks (mean duration 7.1 weeks). Three dogs (1.3%) relapsed within a month of treatment cessation but all were successfully treated with a second round of injections. Ten (4.3%) were failures, with no detectable difference in mite numbers seen on follow-up skin scrapings (mean treatment duration 6.4 weeks). The treatment was well tolerated and only two adverse reactions were seen, one was a local irritation reaction at the injection site and the other ataxia, both developed under and resolved upon cessation of therapy. There were seventeen adult animals (greater than 4 years), 47% had an underlying concurrent disease diagnosed. The efficacy was lower in this group and only 66.7% achieved remission in 6 to 8 weeks (mean duration 7.1 weeks). Overall this appears to be a well-tolerated and useful therapy for the treatment of canine generalised demodicosis. -49530325755Consensus Statement 10: Oral ivermectin at 0.03-0.06 mg/kg daily, moxidectin at 0.03-0.05 mg/kg daily, milbemcyin oxime at 1.0-2.0 mg/kg daily and doramectin injected subcutaneously every week at 0.06 mg/kg are effective therapies for canine demodicosis, but an initial gradual dose increase is recommended for systemic moxidectin and ivermectin to identify dogs sensitive to toxicoses induced by those macrocyclic lactones. Topical moxidectin/imidacloprid should be considered for mild-moderate cases of canine demodicosis.00Consensus Statement 10: Oral ivermectin at 0.03-0.06 mg/kg daily, moxidectin at 0.03-0.05 mg/kg daily, milbemcyin oxime at 1.0-2.0 mg/kg daily and doramectin injected subcutaneously every week at 0.06 mg/kg are effective therapies for canine demodicosis, but an initial gradual dose increase is recommended for systemic moxidectin and ivermectin to identify dogs sensitive to toxicoses induced by those macrocyclic lactones. Topical moxidectin/imidacloprid should be considered for mild-moderate cases of canine demodicosis.IsoxazolinesRecently, a new group of parasiticides also effective against canine demodicosis has been introduced to veterinary medicine.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XZWJlcjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 148 These ectoparasiticides are isoxazolines and include fluralaner, sarolaner, afoxolaner and lotilaner. These molecules have been shown to target a binding site that inhibits insect and acarine ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYWhtPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 149 Prolonged isoxazoline-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines. The selective toxicity of isoxazolines between insects, acarines and mammals may be inferred by the differential sensitivity of the insects' and acarines' GABA receptors versus mammalian GABA receptors.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYXNzZWw8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaWxwPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 152 Absorption is increased when fluralaner is given with food,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWx0aGVyPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 153 it is predominately excreted unchanged in the faeces by hepatic elimination.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaWxwPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 154 Following intravenous administration fluralaner exhibits a relatively high apparent volume of distribution, a low plasma clearance, a long terminal half-life of 12-15 days, and a long mean residence time of 15-20 days thereby demonstrating a long persistence of fluralaner in both dogs and cats.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaWxwPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaWxwPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 155 Fluralaner every three months was compared to a spot-on containing imidacloprid/moxidectin administered once monthly.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3VyaWU8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 156 A reduction of 99.8% and 98% in mite numbers was achieved after 28 days respectively. Scrapings were negative in all dogs treated with fluralaner after 56 days.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3VyaWU8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 156 However, the dogs used in this study were probably not comparable to privately owned dogs in Europe or North America. In a larger clinical study, 163 dogs of various breeds with generalised demodicosis (63% with juvenile- and 37% with adult- onset of the disease) were treated with fluralaner once at a single dose of 25 mg/kg. ADDIN EN.CITE <EndNote><Cite><Author>Karas-Tecza</Author><Year>2015</Year><RecNum>380</RecNum><DisplayText><style face="superscript">157</style></DisplayText><record><rec-number>380</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499008894">380</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Karas-Tecza, J.</author><author>Dawidowicz, J.</author></authors></contributors><titles><title>Efficacy of fluralaner for the treatment of canine demodicosis</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>307</pages><volume>26</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>157 The majority of dogs (87%, all of the dogs with juvenile onset and most with adult-onset demodicosis) had negative skin scrapings after one month and all dogs were negative on scraping after two months. Adverse effects were not seen. ADDIN EN.CITE <EndNote><Cite><Author>Karas-Tecza</Author><Year>2015</Year><RecNum>380</RecNum><DisplayText><style face="superscript">157</style></DisplayText><record><rec-number>380</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499008894">380</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Karas-Tecza, J.</author><author>Dawidowicz, J.</author></authors></contributors><titles><title>Efficacy of fluralaner for the treatment of canine demodicosis</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>307</pages><volume>26</volume><number>5</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>157 A recent study that included 67 dogs also demonstrated that fluralaner when given at the recommended dose for flea and tick prevention is also effective for the treatment of canine generalized demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Duangkaew</Author><Year>2017</Year><RecNum>525</RecNum><DisplayText><style face="superscript">158</style></DisplayText><record><rec-number>525</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1508158434">525</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Duangkaew, L.</author><author>Larsuprom, L.</author><author>Anakkul, P.</author><author>Chen, C.</author><author>Lekcharoensuk, C.</author></authors></contributors><titles><title>Ef?cacy of oral ?uralaner for the treatment of generalized demodicosis in dogs from Bangkok, Thailand</title><secondary-title>North American Veterinary Dermatology Forum</secondary-title></titles><pages>432</pages><volume>28</volume><dates><year>2017</year></dates><pub-location>Orlando</pub-location><publisher>Veterinary Dermatology</publisher><urls></urls></record></Cite></EndNote>158 In 46 individuals with adult-onset demodicosis 63%, 85% and 100% cure rates were observed after 2, 3 and 4 months, respectively. In 21 dogs diagnosed with juvenile-onset demodicosis in this same study, 81% and 100% cure rates were observed after 2 and 3 months, respectively.Adverse reactions in fluralaner-treated dogs in studies evaluating flea and tick control were uncommon to rare. During a 12-week period only four of 223 fluralaner-treated dogs (2.0%) had an adverse event, this was in all cases transient gastrointestinal-related signs including vomiting and anorexia.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb2hkaWNoPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 154 Of 224 dogs participating in a 182-day field study, 7.1%, 6.7%, and 4.9% showed emesis, decreased appetite and diarrhoea respectively. Lethargy, polydipsia and flatulence were seen in 5.4%, 1.8% and 1.3% of the dogs. ADDIN EN.CITE <EndNote><Cite><Author>Administration</Author><Year>2014</Year><RecNum>454</RecNum><DisplayText><style face="superscript">160</style></DisplayText><record><rec-number>454</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502514919">454</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>Food and Drug Administration</author></authors><secondary-authors><author>Federal Drug Administration</author></secondary-authors></contributors><titles><title>New Animal Drug Application 141-426 Bravecto Fluralaner</title></titles><dates><year>2014</year></dates><urls><related-urls><url> can be used without additional risk for collies and other sensitive herding breeds that have the MDR1 mutation.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWx0aGVyPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 154 No adverse events were observed subsequent to fluralaner treatment of ABCB1-1Δ (-/-) Collies at three times the highest expected clinical dose. Thus, fluralaner seems to be an effective, safe and convenient treatment option for all breeds of dogs with generalized demodicosis.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3VyaWU8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 156,157AfoxolanerAfoxolaner [1-Naphthalenecarboxamide, 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]- 4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}] is one of the members of the isoxazoline family. In a variety of studies, afoxolaner was demonstrated to be a highly effective and safe form of flea and tick control.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LdW5rbGU8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 161-164Afoxolaner is a palatable beef-flavoured product that can be given with or without food. After oral administration to dogs, it is rapidly absorbed into the systemic circulation, where the drug becomes active. Afoxolaner is highly protein bound (>99%), the unbound fraction distributes moderately into tissues.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZXRlbmRyZTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+
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ADDIN EN.CITE.DATA 165 It is slowly eliminated from the body via biliary excretion of free afoxolaner and via hepatic metabolism and subsequent biliary and renal clearance of afoxolaner metabolites. This slow clearance gives afoxolaner a long half-life in dogs and sustained ectoparasitic activity. In an oral bioavailability study, afloxolaner was rapidly absorbed (Tmax = 2-4 hours), achieved a maximum plasma concentration (Cmax) of 1655 +/- 332 ng/ml, demonstrated a bioavailability of 73.9% and exhibited a terminal plasma half-life (T1/2) of 15 days.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZXRlbmRyZTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+
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ADDIN EN.CITE.DATA 165 Company-generated study data showed no differences in pharmacokinetics in fed or fasted dogs supporting that it can be given without food. Adverse reactions in flea and tick studies are rare. In a 90-day US field study vomiting was seen in 17 of 415 dogs (4.1%), 13 (3.1%) showed dry flaky skin, diarrhoea without blood was seen in 13 (3.1%) and lethargy in 7 (1.7%). ADDIN EN.CITE <EndNote><Cite><Author>Administration</Author><Year>2013</Year><RecNum>453</RecNum><DisplayText><style face="superscript">166</style></DisplayText><record><rec-number>453</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502514524">453</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>Food and Drug Administration</author></authors><secondary-authors><author>Federal Drug Administration</author></secondary-authors></contributors><titles><title>New Animal Drug Application 141-406 Nexgard Afoxolaner</title></titles><dates><year>2013</year></dates><urls><related-urls><url> Only five dogs showed anorexia during the study, and two of those dogs experienced anorexia with the first dose but not subsequent doses. Three dogs in this field study had a history of seizures. One dog experienced a seizure on the same day after receiving first and second dosing and a third seizure one week after the third dosing but completed the study. One other dog with a history of seizures had one seizure 19 days after the third dose. The third dog with a history of seizures, had no seizures during the study trial. ADDIN EN.CITE <EndNote><Cite><Author>Administration</Author><Year>2013</Year><RecNum>453</RecNum><DisplayText><style face="superscript">166</style></DisplayText><record><rec-number>453</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502514524">453</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>Food and Drug Administration</author></authors><secondary-authors><author>Federal Drug Administration</author></secondary-authors></contributors><titles><title>New Animal Drug Application 141-406 Nexgard Afoxolaner</title></titles><dates><year>2013</year></dates><urls><related-urls><url> The safety profile of afoxolaner was further evaluated in two studies in 8-week-old Beagle dogs. ADDIN EN.CITE <EndNote><Cite><Author>Drag</Author><Year>2014</Year><RecNum>471</RecNum><DisplayText><style face="superscript">163</style></DisplayText><record><rec-number>471</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502517443">471</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Drag, M.</author><author>Saik, J.</author><author>Harriman, J.</author><author>Larsen, D.</author></authors></contributors><auth-address>Merial Limited, 3239 Satellite Boulevard, Duluth, GA 30096-4640, USA. Electronic address: Marlene.Drag@.
Merial Limited, 3239 Satellite Boulevard, Duluth, GA 30096-4640, USA.</auth-address><titles><title>Safety evaluation of orally administered afoxolaner in 8-week-old dogs</title><secondary-title>Vet Parasitol</secondary-title></titles><periodical><full-title>Vet Parasitol</full-title></periodical><pages>198-203</pages><volume>201</volume><number>3-4</number><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Antiparasitic Agents/administration & dosage/pharmacokinetics/*pharmacology</keyword><keyword>Body Weight/drug effects</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Isoxazoles/administration & dosage/*pharmacokinetics/*pharmacology</keyword><keyword>Male</keyword><keyword>Naphthalenes/administration & dosage/*pharmacokinetics/*pharmacology</keyword><keyword>Random Allocation</keyword><keyword>Safety</keyword><keyword>Afoxolaner</keyword><keyword>Oral treatment</keyword></keywords><dates><year>2014</year><pub-dates><date>Apr 02</date></pub-dates></dates><isbn>1873-2550 (Electronic)
0304-4017 (Linking)</isbn><accession-num>24629431</accession-num><urls><related-urls><url> In the first study, 32 Beagle dogs were randomly assigned to receive 1x, 3x or 5x the maximum exposure dose (6.3mg/kg). Treatments were administered at three one-month dose intervals (Days 0, 28 and 56) followed by three fortnightly dose intervals (Days 84, 98 and 112). Physical examinations, and blood collections for clinical pathology analysis and afoxolaner plasma concentrations, were performed throughout the study. No afoxolaner related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically or statistically significant health abnormalities related to the administration of afoxolaner were observed. Vomiting and diarrhoea were observed sporadically across all groups including the controls. ADDIN EN.CITE <EndNote><Cite><Author>Drag</Author><Year>2014</Year><RecNum>471</RecNum><DisplayText><style face="superscript">163</style></DisplayText><record><rec-number>471</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502517443">471</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Drag, M.</author><author>Saik, J.</author><author>Harriman, J.</author><author>Larsen, D.</author></authors></contributors><auth-address>Merial Limited, 3239 Satellite Boulevard, Duluth, GA 30096-4640, USA. Electronic address: Marlene.Drag@.
Merial Limited, 3239 Satellite Boulevard, Duluth, GA 30096-4640, USA.</auth-address><titles><title>Safety evaluation of orally administered afoxolaner in 8-week-old dogs</title><secondary-title>Vet Parasitol</secondary-title></titles><periodical><full-title>Vet Parasitol</full-title></periodical><pages>198-203</pages><volume>201</volume><number>3-4</number><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Antiparasitic Agents/administration & dosage/pharmacokinetics/*pharmacology</keyword><keyword>Body Weight/drug effects</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Isoxazoles/administration & dosage/*pharmacokinetics/*pharmacology</keyword><keyword>Male</keyword><keyword>Naphthalenes/administration & dosage/*pharmacokinetics/*pharmacology</keyword><keyword>Random Allocation</keyword><keyword>Safety</keyword><keyword>Afoxolaner</keyword><keyword>Oral treatment</keyword></keywords><dates><year>2014</year><pub-dates><date>Apr 02</date></pub-dates></dates><isbn>1873-2550 (Electronic)
0304-4017 (Linking)</isbn><accession-num>24629431</accession-num><urls><related-urls><url> In the second study, afoxolaner was combined with milbemycin and the same protocol was repeated as performed in the first study. No treatment-related changes were observed in any of the examinations described above. Vomiting and diarrhoea were observed sporadically across all groups including the control group. ADDIN EN.CITE <EndNote><Cite><Author>Drag</Author><Year>2016</Year><RecNum>473</RecNum><DisplayText><style face="superscript">167</style></DisplayText><record><rec-number>473</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502518120">473</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Drag, M.</author><author>Saik, J.</author><author>Harriman, J.</author><author>Letendre, L.</author><author>Yoon, S.</author><author>Larsen, D.</author></authors></contributors><auth-address>Merial Inc., Duluth, GA, USA.
Formerly Merial Inc., Duluth, GA, USA.</auth-address><titles><title>Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight-week-old dogs</title><secondary-title>J Vet Pharmacol Ther</secondary-title></titles><periodical><full-title>J Vet Pharmacol Ther</full-title></periodical><dates><year>2016</year><pub-dates><date>Nov 27</date></pub-dates></dates><isbn>1365-2885 (Electronic)
0140-7783 (Linking)</isbn><accession-num>27891622</accession-num><urls><related-urls><url> In the USA, afoxolaner is approved to be given to 8-week-old puppies. The safety of afoxolaner in breeding, pregnant and lactating dogs has not been evaluated. Afoxolaner has been shown to be highly effective for treatment of demodicosis in case reports ADDIN EN.CITE <EndNote><Cite><Author>Chavez</Author><Year>2016</Year><RecNum>487</RecNum><DisplayText><style face="superscript">168,169</style></DisplayText><record><rec-number>487</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502586686">487</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chavez, F. </author></authors></contributors><titles><title>Case report of afoxolaner treatment for canine demodicosis in four dogs naturally infected with Demodex canis</title><secondary-title>Intern J Appl Res Vet Med</secondary-title></titles><periodical><full-title>Intern J Appl Res Vet Med</full-title></periodical><pages>123-127</pages><volume>14</volume><dates><year>2016</year></dates><urls></urls></record></Cite><Cite><Author>Mueller</Author><Year>2017</Year><RecNum>512</RecNum><record><rec-number>512</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503311920">512</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Update on the diagnosis and treatment of canine demodicosis</title><secondary-title>Advances in Veterinary Dermatology</secondary-title></titles><periodical><full-title>Advances in Veterinary Dermatology</full-title></periodical><pages>206-209</pages><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>168,169 and one controlled study.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZXVnbmV0PC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48
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ADDIN EN.CITE.DATA 170 The controlled published report looked at eight dogs diagnosed with generalized demodicosis and compared the efficacy with a topical combination of imidacloprid/moxidectin. Afoxolaner was administered at the recommended dose (at least 2.5 mg/kg) on Days 0, 14, 28 and 56 and the topical combination of imidacloprid/moxidectin was given at the same intervals at the recommended concentration. Clinical examinations and deep skin scrapings were performed every month to evaluate the effect on mite numbers and the resolution of clinical signs. The percentage reductions of mite counts were 99.2%, 99.9% and 100% on Days 28, 56 and 84, respectively, in the afoxolaner-treated group, compared to 89.8%, 85.2% and 86.6% on Days 28, 56 and 84 in the imidacloprid/moxidectin-group. Mite reductions were significantly higher on Days 28, 56 and 84 in the afoxolaner-treated group compared to the imidacloprid/moxidectin treated group.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZXVnbmV0PC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48
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ADDIN EN.CITE.DATA 170 In a large series of clinical case evaluations at a referral dermatology practice 102 cases of generalized demodicosis were treated with excellent results. Of the 102 cases, 68 were dogs with adult onset demodicosis. The product was administered at 2.5 mg/kg per os, initially used every two weeks in the first ten dogs. With the high degree of efficacy seen in those dogs, the dosage was reduced to monthly in the remaining cases. Ninety percent of the cases were negative after two months of treatment, the remaining dogs after three months. The only dog needing every two week administration was a dog on immunosuppressive therapy for pemphigus foliaceus, that became mite positive when the interval was increased to four weeks, but remained mite negative when afoxolaner was administered every two weeks. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2017</Year><RecNum>512</RecNum><DisplayText><style face="superscript">169</style></DisplayText><record><rec-number>512</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503311920">512</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author><author>Shipstone, M.A.</author></authors></contributors><titles><title>Update on the diagnosis and treatment of canine demodicosis</title><secondary-title>Advances in Veterinary Dermatology</secondary-title></titles><periodical><full-title>Advances in Veterinary Dermatology</full-title></periodical><pages>206-209</pages><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>169 SarolanerSarolaner (1-(5'-((5S)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3'-H-spiro(azetidine-3,1'-(2) benzofuran)-1-yl)-2-(methylsulfonyl) ethanone) was discovered through a targeted synthesis and screening program and was selected for development on the basis of structural uniqueness, potency, mammalian safety, and pharmacokinetic suitability. ADDIN EN.CITE <EndNote><Cite><Author>Breitschwerdt</Author><Year>2016</Year><RecNum>458</RecNum><DisplayText><style face="superscript">171</style></DisplayText><record><rec-number>458</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502515591">458</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Breitschwerdt, E.</author><author>Little, S.</author><author>Rugg, D.</author></authors></contributors><titles><title>Sarolaner-a novel isoxazoline-addresses the need for enhanced flea and tick control</title><secondary-title>Vet Parasitol</secondary-title></titles><periodical><full-title>Vet Parasitol</full-title></periodical><pages>1-2</pages><volume>222</volume><keywords><keyword>Animals</keyword><keyword>Ectoparasitic Infestations/prevention & control/therapy/*veterinary</keyword><keyword>*Isoxazoles/administration & dosage</keyword><keyword>*Siphonaptera</keyword><keyword>Tick Control/*standards</keyword><keyword>*Ticks</keyword></keywords><dates><year>2016</year><pub-dates><date>May 30</date></pub-dates></dates><isbn>1873-2550 (Electronic)
0304-4017 (Linking)</isbn><accession-num>26992661</accession-num><urls><related-urls><url> This isoxazoline can be safely used for puppies from 8 weeks of age.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NY1RpZXI8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxS
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Pn==
ADDIN EN.CITE.DATA 172 Sarolaner chewable tablets are generally well tolerated with rare treatment-related adverse reactions. The majority of observed adverse events are typical of those commonly seen in the general dog population. In a 90-day study, vomiting was observed in ten of 315 dogs (3.5%), and lethargy in eight dogs (2.5%).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGVybmk8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 173 Sarolaner is currently authorised as chewable tablet with indications for the treatment of fleas, ticks and ear mites in dogs. In a recent study, 16 dogs with generalised demodicosis were treated either with monthly oral sarolaner or with a weekly spot-on containing imidacloprid and moxidectin.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaXg8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 174 The sarolaner-treated dogs and the dogs treated with the spot-on had a reduction of over 99% and 96% in mite numbers after one month and negative scrapings after one month and after 11 weeks respectively.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaXg8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 174 In addition, the Demodex-infested dogs showed a marked improvement in their clinical signs. There were no treatment-related adverse events observed. The excellent response of the dogs in this study receiving the weekly spot-on containing imidacloprid and moxidectin after one month suggests that these dogs may not be comparable to the dogs presented with generalised demodicosis in Europe or North America that were treated with this spot-on.0340360Consensus Statement 11: Although not many published studies have evaluated the efficacy of isoxazolines for canine demodicosis in pet dogs, preliminary data is very encouraging and makes this drug class a promising treatment option for dogs with demodicosis.00Consensus Statement 11: Although not many published studies have evaluated the efficacy of isoxazolines for canine demodicosis in pet dogs, preliminary data is very encouraging and makes this drug class a promising treatment option for dogs with demodicosis.Other drugsVarious other drugs have been used to treat generalized demodicosis. As described above, an immune aberration seems to contribute to the development of generalized demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Scott</Author><Year>1976</Year><RecNum>429</RecNum><DisplayText><style face="superscript">175</style></DisplayText><record><rec-number>429</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501606273">429</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Scott, D.W.</author><author>Schultz, R.D.</author><author>Baker, E.B.</author></authors></contributors><titles><title>Further studies on the therapeutic and immunologic aspects of generalized demodectic mange in the dog</title><secondary-title>Journal of the American Animal Hospital Association</secondary-title></titles><periodical><full-title>Journal of the American Animal Hospital Association</full-title></periodical><pages>203-213</pages><volume>12</volume><dates><year>1976</year></dates><urls></urls></record></Cite></EndNote>175 Thus it seems logical, that immunomodulatory agents may be beneficial for dogs with demodicosis and a number of those agents were evaluated in several studies. A mycobacterial cell wall component, muramyl dipeptide, was injected subcutaneously at 0.2 mg/kg weekly in dogs with generalized demodicosis either as monotherapy or in combination with amitraz at two different concentrations (0.025 and 0.05% twice weekly) and compared to therapy with amitraz alone at 0.025% twice weekly. ADDIN EN.CITE <EndNote><Cite><Author>Kraiss</Author><Year>1983</Year><RecNum>430</RecNum><DisplayText><style face="superscript">176</style></DisplayText><record><rec-number>430</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501606412">430</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kraiss, A.</author><author>Gothe, R.</author></authors></contributors><titles><title>Demodikosetherapie mit Muramyl dipeptide und Amitraz</title><secondary-title>Kleintierpraxis</secondary-title></titles><periodical><full-title>Kleintierpraxis</full-title></periodical><pages>9-30</pages><volume>28</volume><dates><year>1983</year></dates><urls></urls></record></Cite></EndNote>176 Remission was achieved in all dogs. The study numbers were very small (two dogs per treatment group) and there was no follow-up period, thus it is difficult to ascertain if the muramyl dipeptide was of any benefit. Muramyl dipeptide was also shown in a separate study to increase the lymphocyte response to mitogens in 8 dogs with demodicosis, without reaching the comparative values of healthy dogs. ADDIN EN.CITE <EndNote><Cite><Author>Kraiss</Author><Year>1987</Year><RecNum>412</RecNum><DisplayText><style face="superscript">29</style></DisplayText><record><rec-number>412</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499417101">412</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kraiss, A.</author></authors></contributors><titles><title>[Proliferating ability of the lymphocytes of demodectic dogs during immune cell-stimulating therapy]</title><secondary-title>Tierarztl Prax</secondary-title></titles><periodical><full-title>Tierarztl Prax</full-title></periodical><pages>63-6</pages><volume>15</volume><number>1</number><keywords><keyword>Acetylmuramyl-Alanyl-Isoglutamine/*therapeutic use</keyword><keyword>Adjuvants, Immunologic/therapeutic use</keyword><keyword>Animals</keyword><keyword>Biological Products/*therapeutic use</keyword><keyword>Dog Diseases/*immunology/therapy</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>*Lymphocyte Activation</keyword><keyword>Male</keyword><keyword>Mite Infestations/immunology/therapy/*veterinary</keyword><keyword>Mites</keyword></keywords><dates><year>1987</year></dates><orig-pub>Zur Proliferationsfahigkeit von Lymphozyten demodikosekranker Hunde bei immunzellstimulierender Therapie.</orig-pub><isbn>0303-6286 (Print)
0303-6286 (Linking)</isbn><accession-num>3590169</accession-num><urls><related-urls><url> Adverse effects were not mentioned.Levamisole at a dose from 3 to 10 mg/kg given at different intervals was used in two studies, ADDIN EN.CITE <EndNote><Cite><Author>Scott</Author><Year>1976</Year><RecNum>429</RecNum><DisplayText><style face="superscript">175,177</style></DisplayText><record><rec-number>429</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501606273">429</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Scott, D.W.</author><author>Schultz, R.D.</author><author>Baker, E.B.</author></authors></contributors><titles><title>Further studies on the therapeutic and immunologic aspects of generalized demodectic mange in the dog</title><secondary-title>Journal of the American Animal Hospital Association</secondary-title></titles><periodical><full-title>Journal of the American Animal Hospital Association</full-title></periodical><pages>203-213</pages><volume>12</volume><dates><year>1976</year></dates><urls></urls></record></Cite><Cite><Author>Mojzisova</Author><Year>1987</Year><RecNum>431</RecNum><record><rec-number>431</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501606687">431</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mojzisova, J.</author><author>Paulik, S.</author><author>Bajova, V. </author><author>et al. .</author></authors></contributors><titles><title>The immunomodulatory effect of levamisole with the use of amitraz in dogs with uncomplicated generalized demodicosis</title><secondary-title>Vet Medical-Czech</secondary-title></titles><periodical><full-title>Vet Medical-Czech</full-title></periodical><pages>307-311</pages><volume>42</volume><dates><year>1987</year></dates><urls></urls></record></Cite></EndNote>175,177 which showed a positive effect on lymphocyte proliferation assays, but did not improve efficacy based on clinical or parasitologic resolution of demodicosis. In another study, 16 dogs with generalized demodicosis were treated either with amitraz rinses at 0.0375% every five days alone or in combination with 2ml of inactivated Parapox virus suis subcutaneously on day 0, 2 and 9.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZWttZXpjaTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+
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ADDIN EN.CITE.DATA 178 The dogs receiving combination therapy achieved remission within 85 days compared to 104 days in the control group (p<0.05), although a power analysis was not presented. To the authors’ knowledge, this is the first randomised trial showing a beneficial effect of an immunostimulant as treatment for canine demodicosis.Thirty-six dogs with generalized demodicosis were treated with 1000 mg of vitamin E daily, weekly amitraz rinses at 0.05% or a combination of both therapies. ADDIN EN.CITE <EndNote><Cite><Author>Figueiredo</Author><Year>1993</Year><RecNum>432</RecNum><DisplayText><style face="superscript">179</style></DisplayText><record><rec-number>432</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501610573">432</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Figueiredo, C.</author><author>Viana, J.A.</author><author>Curi, P.R.</author></authors><secondary-authors><author>hrke, P.J.</author><author>Mason, I.S.</author><author>White, S.D.</author></secondary-authors></contributors><titles><title>Clinical evaluation of the effect of vitamin E in the treatment of generalized canine demodicosis</title><secondary-title>Advances in Veterinary Dermatology</secondary-title></titles><periodical><full-title>Advances in Veterinary Dermatology</full-title></periodical><pages>247-261</pages><dates><year>1993</year></dates><pub-location>Oxford</pub-location><publisher>Pergamon Press</publisher><urls></urls></record></Cite></EndNote>179 All dogs went into remission, the dogs on combination therapy had the shortest time until remission (7.1 weeks vs. 7.3 weeks with amitraz only and 8.5 weeks with vitamin E only) but a statistical evaluation was not performed. Compared to a control group, affected dogs had lower serum vitamin E concentrations. However, it was not known if inadequate dietary intake of vitamin E at the beginning of the study or the disease caused this difference. When the mean serum vitamin E concentration was compared among dogs with pyoderma, generalized demodicosis and normal dogs, no significant differences were found between groups. ADDIN EN.CITE <EndNote><Cite><Author>Gilbert</Author><Year>1992</Year><RecNum>433</RecNum><DisplayText><style face="superscript">180</style></DisplayText><record><rec-number>433</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501610683">433</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gilbert, P.A.</author><author>Griffin, C.E.</author><author>Rosenkrantz, W.S.</author></authors></contributors><titles><title>Serum vitamin E levels in dogs with pyoderma and generalized demodicosis</title><secondary-title>Journal of the American Animal Hospital Association</secondary-title></titles><periodical><full-title>Journal of the American Animal Hospital Association</full-title></periodical><pages>407-410</pages><volume>28</volume><dates><year>1992</year></dates><urls></urls></record></Cite></EndNote>180Lufenuron is a chitin synthesis inhibitor. As chitin is found in the shells and exoskeletons of all life stages of Demodex spp. ADDIN EN.CITE <EndNote><Cite><Author>Stromberg</Author><Year>1972</Year><RecNum>434</RecNum><DisplayText><style face="superscript">181</style></DisplayText><record><rec-number>434</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501610801">434</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stromberg, B.E.</author><author>Nutting, W.B.</author></authors></contributors><titles><title>Adaptive features of the exoskeleton and ‘pigment’ deposits in Demodex spp. (Demodicidae)</title><secondary-title>Acarologia</secondary-title></titles><periodical><full-title>Acarologia</full-title></periodical><pages>605-611</pages><volume>XIV</volume><dates><year>1972</year></dates><urls></urls></record></Cite></EndNote>181 it was proposed that this compound might interrupt the life cycle of the Demodex mite. However, lufenuron at mean doses of up to 15.8 mg/kg three times weekly for 2–3 months did not lead to improvement of canine demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Schwassmann</Author><Year>1997</Year><RecNum>480</RecNum><DisplayText><style face="superscript">182</style></DisplayText><record><rec-number>480</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502585705">480</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schwassmann, M.</author><author>Kunkle, G.A.</author><author>Hepler, D.I. </author><author>Lewis, D.T.</author></authors></contributors><titles><title>Use of lufenuron for treatment of generalized demodicosis in dogs</title><secondary-title>Veterinary Dermatology</secondary-title></titles><periodical><full-title>Veterinary Dermatology</full-title></periodical><pages>11-18</pages><volume>8</volume><dates><year>1997</year></dates><urls></urls></record></Cite></EndNote>182 Three dogs with generalized demodicosis were sprayed weekly with a deltamethrin spray at 0.005%. After 3 weekly applications there was no difference in clinical signs or numbers of mites on skin scrapings. ADDIN EN.CITE <EndNote><Cite><Author>Kamboj</Author><Year>1993</Year><RecNum>448</RecNum><DisplayText><style face="superscript">110</style></DisplayText><record><rec-number>448</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502509577">448</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kamboj, D.S.</author><author>Singh, K.B.</author><author>Avtar, S.</author><author>et al. </author></authors></contributors><titles><title>Studies on the therapeutic efficacy of amitraz, deltamethrin and ivermectin on canine demodicosis</title><secondary-title>Indian Veterinary Journal </secondary-title></titles><periodical><full-title>Indian Veterinary Journal</full-title></periodical><pages>70</pages><dates><year>1993</year></dates><urls></urls></record></Cite></EndNote>110 Deltamethrin at 12.5% was used in another report and compared with an indigenous preparation containing extracts of Mallotus phillipensis, Oleum pinus, Oleum terebinth and Sulphur sublimatum. Topicals were applied twice daily until skin scrapings were negative, which took 7 days in the group treated with the indigenous preparation and 11 days for deltamethrin. ADDIN EN.CITE <EndNote><Cite><Author>Das</Author><Year>1998</Year><RecNum>478</RecNum><DisplayText><style face="superscript">183</style></DisplayText><record><rec-number>478</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502585172">478</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Das, S.S.</author></authors></contributors><titles><title>Efficacy of ‘Maggacite’, an indigenous preparation against demodecosis in dogs and its comparison with deltamethrin</title><secondary-title>Indian Veterinary Journal</secondary-title></titles><periodical><full-title>Indian Veterinary Journal</full-title></periodical><pages>157-158</pages><volume>75</volume><dates><year>1998</year></dates><urls></urls></record></Cite></EndNote>183 Dogs had to be restrained for 1 h after the topical application to prevent excessive licking. Skin scrapings were still negative in all dogs one month after cessation of therapy.Homeopathic preparations containing Sulphur 200, Heparsulphuris 200 or Psorinum 200 were given orally at 5 drops daily for 5 weeks to three groups of six puppies experimentally infected with Demodex canis. ADDIN EN.CITE <EndNote><Cite><Author>Nayak</Author><Year>1998</Year><RecNum>477</RecNum><DisplayText><style face="superscript">184</style></DisplayText><record><rec-number>477</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502585052">477</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nayak, D.C.</author><author>Tripathy, S.B.</author><author>Dey, P.C. </author><author>et al. .</author></authors></contributors><titles><title>Therapeutic efficacy of some homeopathic preparations against experimentally produced demodicosis in canines</title><secondary-title>Indian Veterinary Journal</secondary-title></titles><periodical><full-title>Indian Veterinary Journal</full-title></periodical><pages>342-344</pages><volume>75</volume><dates><year>1998</year></dates><urls></urls></record></Cite></EndNote>184 The post-treatment mean demodicosis indices were lower in the groups treated with Sulphur 200 and Psorinum 200 compared with the group treated with Heparsulphuris 200 and a control group, but neither complete clinical nor microscopic resolution could be achieved. A herbal preparation containing extracts of Cedrus deodara, Azadirecta indica and Embelia ribes was sprayed on lesions of 14 dogs with apparent generalized demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Das</Author><Year>1993</Year><RecNum>435</RecNum><DisplayText><style face="superscript">185</style></DisplayText><record><rec-number>435</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501611212">435</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Das, S.S. </author></authors></contributors><titles><title>Efficacy of Pestoban aerosol spray in treatment of canine demodecosis</title><secondary-title>Journal of Veterinary Parasitology</secondary-title></titles><periodical><full-title>Journal of Veterinary Parasitology</full-title></periodical><pages>67-69</pages><volume>7</volume><dates><year>1993</year></dates><urls></urls></record></Cite></EndNote>185 Dogs were reevaluated after 24 h and if skin scrapings were still positive for D. canis, dogs were retreated once. Subsequent weekly skin scrapings for 6 weeks were negative in all dogs.Closantel ({N 9–5-chloro-4-(4-chlorophenyl cyanomethyl)-2-methylphenyl}-2-hydroxyl 3,5 diiodobenzamide) is an anthelminthic of the salicylanilide family and was used to treat nine dogs with generalized demodicosis at a dose of 5 mg/kg subcutaneously for the first injection and 2.5 mg/kg for subsequent weekly injections. ADDIN EN.CITE <EndNote><Cite><Author>Losson</Author><Year>1980</Year><RecNum>436</RecNum><DisplayText><style face="superscript">186</style></DisplayText><record><rec-number>436</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1501611315">436</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Losson, B.</author><author>Benakhla, A.</author></authors></contributors><titles><title> Efficacite du closantel dans le traitement de la gale demodectique du chien</title><secondary-title>Annales de Médecine Vétérinaire</secondary-title></titles><periodical><full-title>Annales de Médecine Vétérinaire</full-title></periodical><pages>521-526</pages><volume>124</volume><dates><year>1980</year></dates><urls></urls></record></Cite></EndNote>186 All dogs improved, but only six dogs went into microscopic remission after six injections. A follow-up period was not specified.Overall, for almost all of those drugs there is insufficient evidence to be recommended as treatment of canine generalised demodicosis, either due to low numbers of patients in the studies, unclear methods, insufficient efficacy, or prominent adverse effects. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2004</Year><RecNum>169</RecNum><DisplayText><style face="superscript">45</style></DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1291214723">169</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mueller, R. S.</author></authors></contributors><auth-address>Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. rmueller@colostate.edu</auth-address><titles><title>Treatment protocols for demodicosis: an evidence-based review</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>75-89</pages><volume>15</volume><number>2</number><edition>2004/03/20</edition><keywords><keyword>Administration, Cutaneous</keyword><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Baths</keyword><keyword>Cat Diseases/*drug therapy</keyword><keyword>Cats</keyword><keyword>Dog Diseases/*drug therapy</keyword><keyword>Dogs</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Insecticides/*administration & dosage</keyword><keyword>Ivermectin/administration & dosage</keyword><keyword>Macrolides/administration & dosage</keyword><keyword>Mite Infestations/drug therapy/*veterinary</keyword><keyword>*Mites</keyword><keyword>Toluidines/administration & dosage</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-4493 (Print)
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ADDIN EN.CITE.DATA 187-190 rotenone, ADDIN EN.CITE <EndNote><Cite><Author>Gabbert</Author><Year>1976</Year><RecNum>519</RecNum><DisplayText><style face="superscript">187,191</style></DisplayText><record><rec-number>519</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503316874">519</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gabbert, N.</author><author>Feldman, B.F.</author></authors></contributors><titles><title>Feline Demodex</title><secondary-title>Feline Practice</secondary-title></titles><periodical><full-title>Feline Practice</full-title></periodical><pages>32-33</pages><number>11</number><dates><year>1976</year></dates><urls></urls></record></Cite><Cite><Author>Chesney</Author><Year>1988</Year><RecNum>125</RecNum><record><rec-number>125</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1285849875">125</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chesney, C. J.</author></authors></contributors><titles><title>An unusual species of demodex mite in a cat</title><secondary-title>Vet Rec</secondary-title></titles><periodical><full-title>Vet Rec</full-title></periodical><pages>671-3</pages><volume>123</volume><number>26-27</number><edition>1988/12/24</edition><keywords><keyword>Animals</keyword><keyword>Cat Diseases/*parasitology</keyword><keyword>Cats</keyword><keyword>Female</keyword><keyword>Male</keyword><keyword>Mite Infestations/parasitology/*veterinary</keyword><keyword>Mites/*anatomy & histology</keyword></keywords><dates><year>1988</year><pub-dates><date>Dec 24-31</date></pub-dates></dates><isbn>0042-4900 (Print)
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ADDIN EN.CITE.DATA 24 and a moxidectin/imidacloprid spot-on. ADDIN EN.CITE <EndNote><Cite><Author>Short</Author><Year>2016</Year><RecNum>504</RecNum><DisplayText><style face="superscript">197</style></DisplayText><record><rec-number>504</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503308136">504</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Short, J.</author><author>Gram, D.</author></authors></contributors><auth-address>From Animal Allergy and Dermatology, Chesapeake, VA.</auth-address><titles><title>Successful Treatment of Demodex gatoi with 10% Imidacloprid/1% Moxidectin</title><secondary-title>J Am Anim Hosp Assoc</secondary-title></titles><periodical><full-title>J Am Anim Hosp Assoc</full-title></periodical><pages>68-72</pages><volume>52</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Cat Diseases/drug therapy/*parasitology</keyword><keyword>Cats</keyword><keyword>Drug Combinations</keyword><keyword>Female</keyword><keyword>Imidazoles/administration & dosage/*therapeutic use</keyword><keyword>Insecticides/administration & dosage/*therapeutic use</keyword><keyword>Macrolides/administration & dosage/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/parasitology/*veterinary</keyword><keyword>Mites/*classification</keyword><keyword>Nitro Compounds/administration & dosage/*therapeutic use</keyword></keywords><dates><year>2016</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0587-2871 (Print)
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ADDIN EN.CITE.DATA 73,196 to 0.025% ADDIN EN.CITE <EndNote><Cite><Author>Carlotti</Author><Year>1986</Year><RecNum>516</RecNum><DisplayText><style face="superscript">194</style></DisplayText><record><rec-number>516</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503316114">516</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Carlotti, D.N.</author><author>Lemaire, C.</author><author>Lavayssiere, J.</author><author>Magnol, J.-P.</author></authors></contributors><titles><title>La demodecie feline. A propos de trois cas</title><secondary-title>Pratique medicale et chirugicale de l'animal de compagnie</secondary-title></titles><periodical><full-title>Pratique medicale et chirugicale de l'animal de compagnie</full-title></periodical><pages>203-208</pages><volume>21</volume><number>3</number><dates><year>1986</year></dates><urls></urls></record></Cite></EndNote>194 up to 0.1% ADDIN EN.CITE <EndNote><Cite><Author>Guaguere</Author><Year>1993</Year><RecNum>517</RecNum><DisplayText><style face="superscript">195</style></DisplayText><record><rec-number>517</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503316585">517</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Guaguere, E.</author></authors></contributors><titles><title>Demodecie feline: etude retrospective de 9 cas</title><secondary-title>Pratique medicale et chirugicale de l'animal de compagnie</secondary-title></titles><periodical><full-title>Pratique medicale et chirugicale de l'animal de compagnie</full-title></periodical><pages>31-36</pages><volume>28</volume><dates><year>1993</year></dates><urls></urls></record></Cite></EndNote>195 weekly and 12/14 cats responded to treatment. However, both treatments are not always tolerated well by the affected cats. In a more recent case series, 8 of 13 cats in one household showed pruritic skin disease and skin scrapings were positive for D. gatoi in two of those cats. Weekly administration of a spot-on containing moxidectin/imidacloprid for 10 weeks was tolerated well and pruritus resolved in all cats following treatment. ADDIN EN.CITE <EndNote><Cite><Author>Short</Author><Year>2016</Year><RecNum>504</RecNum><DisplayText><style face="superscript">197</style></DisplayText><record><rec-number>504</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1503308136">504</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Short, J.</author><author>Gram, D.</author></authors></contributors><auth-address>From Animal Allergy and Dermatology, Chesapeake, VA.</auth-address><titles><title>Successful Treatment of Demodex gatoi with 10% Imidacloprid/1% Moxidectin</title><secondary-title>J Am Anim Hosp Assoc</secondary-title></titles><periodical><full-title>J Am Anim Hosp Assoc</full-title></periodical><pages>68-72</pages><volume>52</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Cat Diseases/drug therapy/*parasitology</keyword><keyword>Cats</keyword><keyword>Drug Combinations</keyword><keyword>Female</keyword><keyword>Imidazoles/administration & dosage/*therapeutic use</keyword><keyword>Insecticides/administration & dosage/*therapeutic use</keyword><keyword>Macrolides/administration & dosage/*therapeutic use</keyword><keyword>Male</keyword><keyword>Mite Infestations/drug therapy/parasitology/*veterinary</keyword><keyword>Mites/*classification</keyword><keyword>Nitro Compounds/administration & dosage/*therapeutic use</keyword></keywords><dates><year>2016</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0587-2871 (Print)
0587-2871 (Linking)</isbn><accession-num>26606209</accession-num><urls><related-urls><url> Thus, at least for D. gatoi, this spot-on may be a more convenient efficacious therapy. -45085289560Consensus Statement 12: Demodicosis in cats may be treated with weekly lime sulphur dips at a concentration of 2% or amitraz baths at a concentration of 0.0125%. An easier alternative may be weekly administration of a spot-on containing moxidectin/imidacloprid.00Consensus Statement 12: Demodicosis in cats may be treated with weekly lime sulphur dips at a concentration of 2% or amitraz baths at a concentration of 0.0125%. An easier alternative may be weekly administration of a spot-on containing moxidectin/imidacloprid.Prognosis and future outlookWith the advent and widespread use of isoxazoline therapy for flea and tick control, the future incidence of canine demodicosis could be impacted. How prominent this effect will be, remains to be seen in the coming years. Fifteen breeding bitches with a history of producing consistent litters of puppies which developed generalised demodicosis were followed and showed marked reduction in the number of puppies breaking with generalized demodicosis. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2016</Year><RecNum>376</RecNum><DisplayText><style face="superscript">198</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1523791338">376</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Shipstone, M.</author></authors></contributors><titles><title>Update on the diagnosis and treatment of canine demodicosis</title><secondary-title>8th World Congress of Veterinary Dermatology</secondary-title></titles><pages>206-209</pages><dates><year>2016</year></dates><pub-location>Bordeaux</pub-location><publisher>World Association of Veterinary Dermatology</publisher><urls></urls></record></Cite></EndNote>198 In this trial, all bitches were treated with 25 mg/kg fluralaner 10 days prior to the scheduled mating and 3 months later with a second dose. All 15 bitches included in the study gave birth to litters of healthy puppies and 14 of those 15 litters did not develop demodicosis in the first 12 months, two puppies of one litter developed localised demodicosis only. ADDIN EN.CITE <EndNote><Cite><Author>Mueller</Author><Year>2016</Year><RecNum>376</RecNum><DisplayText><style face="superscript">198</style></DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="z0vzav5dc2d9epez09650p5n5s2pvzrrr52v" timestamp="1523791338">376</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Mueller, R.S.</author><author>Shipstone, M.</author></authors></contributors><titles><title>Update on the diagnosis and treatment of canine demodicosis</title><secondary-title>8th World Congress of Veterinary Dermatology</secondary-title></titles><pages>206-209</pages><dates><year>2016</year></dates><pub-location>Bordeaux</pub-location><publisher>World Association of Veterinary Dermatology</publisher><urls></urls></record></Cite></EndNote>198 The obtained result indicates a high efficiency of fluralaner not only as a treatment but also as a preventive strategy in cases of breed predisposed, generalized, juvenile onset canine demodicosis. Although these results are impressive, isoxazoline therapy should not replace the need for withholding affected and carrier dogs from breeding programs. There is also concern about the possible impact of isoxazoline therapy on normal canine cutaneous Demodex populations. Demodex mites are considered part of the microbiota of most mammals, including dogs. Under normal circumstances, they appear to live as commensals, feeding on their host’s sebum and are only opportunistically pathogenic. Similar to bacterial flora found on the skin, follicular mites have been shown to contain immune-reactive lipase, ADDIN EN.CITE <EndNote><Cite><Author>Jimenez-Acosta</Author><Year>1989</Year><RecNum>481</RecNum><DisplayText><style face="superscript">199</style></DisplayText><record><rec-number>481</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502585790">481</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jimenez-Acosta, F.</author><author>Planas, L.</author><author>Penneys, N.</author></authors></contributors><titles><title>Demodex mites contain immunoreactive lipase</title><secondary-title>Arch Dermatol</secondary-title></titles><periodical><full-title>Arch Dermatol</full-title></periodical><pages>1436-7</pages><volume>125</volume><number>10</number><keywords><keyword>Animals</keyword><keyword>Humans</keyword><keyword>Lipase/*analysis</keyword><keyword>*Mite Infestations/parasitology</keyword><keyword>Mites/*enzymology</keyword><keyword>*Skin Diseases, Parasitic/parasitology</keyword></keywords><dates><year>1989</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0003-987X (Print)
0003-987X (Linking)</isbn><accession-num>2802655</accession-num><urls><related-urls><url> which can produce free fatty acids from sebum triglycerides. Therefore, the mites could play a role in the defense of the skin against pathogenic bacteria, particularly against Staphylococcus aureus and Streptococcus pyogenes. ADDIN EN.CITE <EndNote><Cite><Author>Namazi</Author><Year>2007</Year><RecNum>482</RecNum><DisplayText><style face="superscript">200</style></DisplayText><record><rec-number>482</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502585882">482</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Namazi, M. R.</author></authors></contributors><titles><title>A possible role for human follicle mites in skin's defense against bacteria</title><secondary-title>Indian J Dermatol Venereol Leprol</secondary-title></titles><periodical><full-title>Indian J Dermatol Venereol Leprol</full-title></periodical><pages>270</pages><volume>73</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Bacterial Infections/*physiopathology</keyword><keyword>Hair Follicle/*parasitology</keyword><keyword>Humans</keyword><keyword>Immunity/physiology</keyword><keyword>Mites/*physiology</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>0973-3922 (Electronic)
0378-6323 (Linking)</isbn><accession-num>17675744</accession-num><urls><related-urls><url> The investigation of the normal cutaneous Demodex populations has been, until recently, elusive due to the low number of individual mites present on healthy dogs. The development of PCR techniques targeting Demodex-DNA in skin samples has allowed advancement of the study of Demodex populations. ADDIN EN.CITE <EndNote><Cite><Author>Ravera</Author><Year>2011</Year><RecNum>483</RecNum><DisplayText><style face="superscript">201</style></DisplayText><record><rec-number>483</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502586052">483</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ravera, I.</author><author>Altet, L.</author><author>Francino, O.</author><author>Bardagi, M.</author><author>Sanchez, A.</author><author>Ferrer, L.</author></authors></contributors><auth-address>Departament de Medicina i Cirurgia Animals, Universitat Autonoma de Barcelona, 08193, Bellaterra, Barcelona, Spain.</auth-address><titles><title>Development of a real-time PCR to detect Demodex canis DNA in different tissue samples</title><secondary-title>Parasitol Res</secondary-title></titles><periodical><full-title>Parasitol Res</full-title></periodical><pages>305-8</pages><volume>108</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Biopsy</keyword><keyword>DNA, Protozoan/*analysis/genetics</keyword><keyword>Dog Diseases/diagnosis/*parasitology</keyword><keyword>Dogs</keyword><keyword>Hair/*parasitology</keyword><keyword>Mite Infestations/diagnosis/*veterinary</keyword><keyword>Mites/*genetics</keyword><keyword>Predictive Value of Tests</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction/*veterinary</keyword><keyword>Skin/*parasitology</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1432-1955 (Electronic)
0932-0113 (Linking)</isbn><accession-num>20865428</accession-num><urls><related-urls><url> A previous study using a real-time PCR (RT-PCR) for D. canis detected Demodex-DNA in approximately 18% of healthy dogs after sampling hairs from two to five body sites. ADDIN EN.CITE <EndNote><Cite><Author>Ravera</Author><Year>2013</Year><RecNum>425</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>425</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499428606">425</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ravera, I.</author><author>Altet, L.</author><author>Francino, O.</author><author>Sanchez, A.</author><author>Roldan, W.</author><author>Villanueva, S.</author><author>Bardagi, M.</author><author>Ferrer, L.</author></authors></contributors><auth-address>Department of Animal Medicine and Surgery Servei Veterinari de Genetica Molecular, Veterinary School, Universitat Autonoma de Barcelona, 08193 Barcelona, Spain.</auth-address><titles><title>Small Demodex populations colonize most parts of the skin of healthy dogs</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>168-72 e37</pages><volume>24</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Dog Diseases/*parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Immunocompromised Host</keyword><keyword>Male</keyword><keyword>Mite Infestations/parasitology/*veterinary</keyword><keyword>Mites/*classification</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1365-3164 (Electronic)
0959-4493 (Linking)</isbn><accession-num>23331694</accession-num><urls><related-urls><url> Direct proportionality between the number of positive dogs and the number of sampled sites and hairs was demonstrated clearly, as positive results increased to 100% when the number of sampled sites increased to 20. ADDIN EN.CITE <EndNote><Cite><Author>Ravera</Author><Year>2013</Year><RecNum>425</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>425</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499428606">425</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ravera, I.</author><author>Altet, L.</author><author>Francino, O.</author><author>Sanchez, A.</author><author>Roldan, W.</author><author>Villanueva, S.</author><author>Bardagi, M.</author><author>Ferrer, L.</author></authors></contributors><auth-address>Department of Animal Medicine and Surgery Servei Veterinari de Genetica Molecular, Veterinary School, Universitat Autonoma de Barcelona, 08193 Barcelona, Spain.</auth-address><titles><title>Small Demodex populations colonize most parts of the skin of healthy dogs</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><pages>168-72 e37</pages><volume>24</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Dog Diseases/*parasitology</keyword><keyword>Dogs</keyword><keyword>Female</keyword><keyword>Immunocompromised Host</keyword><keyword>Male</keyword><keyword>Mite Infestations/parasitology/*veterinary</keyword><keyword>Mites/*classification</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1365-3164 (Electronic)
0959-4493 (Linking)</isbn><accession-num>23331694</accession-num><urls><related-urls><url> A recent study investigated if healthy dogs treated with the isoxazolines afoxolaner and fluralaner at the labelled dose for flea and tick prevention would maintain a normal population of Demodex mites as part of their cutaneous microbiota. The study demonstrated that after 30 and 90 days of treatment, healthy dogs still had Demodex mites similar to the population of healthy dogs not receiving these treatments. ADDIN EN.CITE <EndNote><Cite><Author>Zewe</Author><Year>2017</Year><RecNum>381</RecNum><DisplayText><style face="superscript">202</style></DisplayText><record><rec-number>381</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1499329585">381</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zewe, C. M.</author><author>Altet, L.</author><author>Lam, A. T. H.</author><author>Ferrer, L.</author></authors></contributors><auth-address>Cummings Veterinary Medical Center, Tufts University, 200 Westboro Road, North Grafton, MA, 01536, USA.
Vetgenomics, Parc de Recerca de la Universitat Autonoma de Barcelona, Edifici Eureka, Bellaterra, 08193, Spain.</auth-address><titles><title>Afoxolaner and fluralaner treatment do not impact on cutaneous Demodex populations of healthy dogs</title><secondary-title>Vet Dermatol</secondary-title></titles><periodical><full-title>Vet Dermatol</full-title></periodical><dates><year>2017</year><pub-dates><date>May 23</date></pub-dates></dates><isbn>1365-3164 (Electronic)
0959-4493 (Linking)</isbn><accession-num>28544307</accession-num><urls><related-urls><url> However, PCR will also detect antigen from dead mites, the duration of the study was only three months and to the authors' knowledge the maximum time to eliminate dead mites from the follicle is not known although the interfollicular epidermal turnover is faster than three months. This data may thus suggest that dogs on isoxazoline treatment may maintain Demodex populations as part of their cutaneous microbiota, despite the apparent ability of these medications to resolve clinical demodicosis. To date, no studies have been performed to detect Demodex DNA post-treatment in dogs with demodicosis. Isoxazolines may not affect Demodex mites in normal dogs to the same degree or may have no effect at all on normal mite populations in unaffected dogs. More studies of longer duration are needed to characterise the response of the Demodex populations in dogs with clinical disease to isoxazolines and in comparison to other treatments for demodicosis. Currently the isoxazoline derivatives have shown impressive results in controlling demodicosis and are likely to be the mainstay therapy for many years to come. The development of resistance is less likely to occur due to their selective inhibition of insect and acarid GABACls and GluCls. This novel binding site is key to the innovative activity profile, which bypasses the critical cross-resistance observed in other non-competitive antagonists ADDIN EN.CITE <EndNote><Cite><Author>Zhao</Author><Year>2014</Year><RecNum>486</RecNum><DisplayText><style face="superscript">203</style></DisplayText><record><rec-number>486</rec-number><foreign-keys><key app="EN" db-id="2995se2vmeve0mefdz35xescaevvdrtf2ff5" timestamp="1502586404">486</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhao, C.</author><author>Casida, J. E.</author></authors></contributors><auth-address>Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy, and Management, University of California , Berkeley, California 94720-3112, United States.</auth-address><titles><title>Insect gamma-aminobutyric acid receptors and isoxazoline insecticides: toxicological profiles relative to the binding sites of [(3)H]fluralaner, [(3)H]-4'-ethynyl-4-n-propylbicycloorthobenzoate, and [(3)H]avermectin</title><secondary-title>J Agric Food Chem</secondary-title></titles><periodical><full-title>J Agric Food Chem</full-title></periodical><pages>1019-24</pages><volume>62</volume><number>5</number><keywords><keyword>Androstenols/chemistry/toxicity</keyword><keyword>Animals</keyword><keyword>Binding Sites</keyword><keyword>Bridged Bicyclo Compounds, Heterocyclic/chemistry/*toxicity</keyword><keyword>GABA Antagonists/chemistry/metabolism/*toxicity</keyword><keyword>Houseflies/*drug effects/genetics/metabolism</keyword><keyword>Insect Proteins/*antagonists & inhibitors/metabolism</keyword><keyword>Insecticides/chemistry/*toxicity</keyword><keyword>Receptors, GABA/metabolism</keyword></keywords><dates><year>2014</year><pub-dates><date>Feb 05</date></pub-dates></dates><isbn>1520-5118 (Electronic)
0021-8561 (Linking)</isbn><accession-num>24404981</accession-num><urls><related-urls><url> and will likely slow development of resistance to this class of molecules. A combination product combining afoxolaner and milbemycin oxime has been released in Europe for flea, tick, nematode infestation and heartworm prevention.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaXg8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 174 No studies are reported to date regarding demodicosis treatment with this product. However, the combined molecules of afoxolaner and milbemycin oxime could have additive effects, as both have efficacy for Demodex mites as sole molecules. In view of these developments, further derivatives and combinations are likely to be approved and more treatment options will be likely be available in the future.References ADDIN EN.REFLIST 1.Wollenberg A, Oranje A, Deleuran M, et al. ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol 2016; 30: 729-747.2.Jutel M, Agache I, Bonini S, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol 2015; 136: 556-568.3.Mueller RS, Bensignor E, Ferrer L, et al. Treatment of Demodicosis in Dogs: 2011 Clinical Practice Guidelines. Veterinary Dermatology 2012; 23: 86-96.4.Olivry T, DeBoer DJ, Favrot C, et al. 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