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Allopurinol is the main drug for long-term management of the disease, and clinical relapses of <jats:italic>L. infantum<\/jats:italic> infection treated with this drug are described. Resistance to allopurinol has been demonstrated in-vitro, but there is only little knowledge on in vivo resistance in dogs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Findings<\/jats:title>\n                <jats:p>A two-year-old female spayed Akita Inu that was adopted from a breeding facility near Nice in France was initially diagnosed with primary immune-mediated hemolytic anemia. Immunosuppressive treatment was initiated, and the dog was referred for a second opinion to the Clinique Veterinaire Alliance in France. PCR testing for <jats:italic>L. infantum<\/jats:italic> was performed out of EDTA blood and IFA as well as ELISA testing out of serum. Resistance to allopurinol was associated with chromosome and gene copy number (CN) variations including a decrease in the S-adenosylmethionine synthetase (<jats:italic>METK<\/jats:italic>) gene CN.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The dog showed pale mucous membranes, fever (39.1 \u00b0C), and a relapse of the anemia. The diagnosis of leishmaniasis was based on the cytological finding of <jats:italic>Leishmania<\/jats:italic> amastigotes (bone marrow, spleen, liver), positive PCR testing, and positive IFAT serology. The dog was treated with allopurinol over a period of 1316 days and additionally received two cycles of Glucantime\u00ae (meglumine antimoniate), before samples were submitted to the LABOKLIN laboratory to test for resistance against allopurinol. The laboratory work-up revealed mild thrombocytopenia, mild hyperproteinemia with hyperglobulinemia, a marked elevation of the c-reactive protein, and decreased iron concentration. Serum protein electrophoresis showed a polyclonal peak in the gamma globulins. Serology was positive in both  ELISA (21.5 LE) and IFAT (1:1024). Quantitative PCR testing of blood was positive with low numbers of Leishmania (10\/ml blood) at the timepoint of suspicion for resistance. The urinary protein-to-creatinine ratio was markedly elevated (2.5) and xanthine crystalluria was detected. A CN level of below 3 is considered suspicious for resistance, as revealed in the described Akita Inu dog.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Relapse of <jats:italic>L. infantum<\/jats:italic> infection after applying allopurinol for 1316 days due to resistance was suspected clinically. Positive PCR testing, consistent hematological and biochemistry abnormalities, and reduction in the <jats:italic>METK<\/jats:italic> gene CN backed up the clinical suspicion of resistance. Dogs infected with allopurinol resistant strains of <jats:italic>L. infantum<\/jats:italic> may represent a great risk for infection of na\u00efve dogs, cats, and humans.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s13071-024-06583-0","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T12:53:41Z","timestamp":1734353621000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Evidence for in vivo resistance against allopurinol in a dog infected with Leishmania infantum by reduction in copy numbers of the S-adenosylmethionine synthetase (METK) gene"],"prefix":"10.1186","volume":"17","author":[{"given":"Ingo","family":"Sch\u00e4fer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Faucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaarit","family":"Nachum-Biala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00eds","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Carrasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten J.","family":"Naucke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad","family":"Baneth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"6583_CR1","first-page":"1","volume":"949","author":"World Health Organization","year":"2010","unstructured":"World Health Organization. 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Testing for resistance was indicated by the treating veterinarian M.F.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"506"}}