Veterinarian Laboklin GmbH & Co. KG Bad Kissingen, Bayern, Germany
Abstract: Background Rising numbers of autochthonous infections with Leishmania infantum are described in the U.S. Allopurinol is the main drug for long-term management. Hypothesis/Objectives Resistance to allopurinol was associated with reduction in S-adenosylmethionine synthetase (METK) gene copy numbers (CNs) in-vitro, but knowledge regarding clinical significance is limited. Animals/Methods Samples of 3 dogs diagnosed with leishmaniasis were submitted due to clinical suspicion of allopurinol resistance. All dogs were tested for METK gene CNs by PCR. Results The dogs originated from Israel, Southern France, and Germany (imported from Spain 2 years before). The dogs were treated with allopurinol for 7 (one additional three-week-course of miltefosine and one-month course of domperidone), 3.5 (two additional cycles of meglumine antimonate), and 2 years (two additional 4-week-courses of miltefosine). Steroids were applied in 2 dogs shortly before relapsing. Relapses were suspected by reoccurrence of clinical signs and/or results of laboratory workups (mild/moderate anemia (n=3), mild thrombocytopenia (n=2), hyperproteinemia with hyperglobulinemia (n=3), mild azotemia (n=1), and marked elevation of the c-reactive protein (n=2)) and were confirmed by positive PCR. Testing for resistance revealed decreased METK gene CNs < 3 in all dogs. Conclusions and clinical importance Relapse of L. infantum infection after treatment with allopurinol for a minimum of 2 years due to resistance was suspected clinically, backed by the reduction in the METK gene CNs and laboratory workup results. Recognizing drug resistance in relapses is crucial for further management. Allopurinol resistant L. infantum strains represent a great risk for infection of naïve dogs, cats, and humans.
