Background: Relapses of canine leishmaniasis during allopurinol treatment are a common complication. S-adenosylmethionine synthetase (METK) gene copy numbers (CN) < 3.0 have been demonstrated in allopurinol resistant Leishmania infantum strains in vitro. The clinical impact in vivo remains unclear. Hypothesis/
Objectives: Treatment failure in dogs with leishmaniasis receiving allopurinol leads to recurrent active leishmaniasis but occurs also in recently diagnosed cases that never received allopurinol. Animals: 14 dogs with active Leishmania infantum infection defined by a positive PCR were divided into two cohorts. Cohort one (CI): nine dogs (64%) under allopurinol treatment with signs of disease relapse; cohort two (CII): five dogs (36%) recently diagnosed with active leishmaniasis and treatment-naïve.
Methods: METK gene CN were quantified by droplet digital PCR. Complete blood counts and biochemical profiles were performed if suitable samples were available.
Results: METK gene CN ranged from 0.7 to 3.4 (CN < 3.0: n = 13, 93%; CN = 3.4: n = 1, 7%; CI: CN = 1.2 - 3.4; CII: CN < 2.0 each). Clinicopathological abnormalities consistent with active leishmaniasis were observed in all dogs. Conclusions and Clinical Importance: Allopurinol is used for long-term management of canine leishmaniasis and identification of resistance is crucial. Resistant Leishmania infantum strains in dogs with active leishmaniasis prior to treatment make their transmission by sand flies very likely. Resistance in dogs represents a risk for humans (One-Health-Aspect) and for other animal reservoirs (All-Species-Approach). The threshold of METK gene CN < 3.0 in vivo seems questionable in individual cases.
