A single-centre, open-label, controlled, randomized clinical trial to assess the preventive efficacy of a domperidone-based treatment programme against clinical canine leishmaniasis in a high prevalence area.
The innate immune response acting immediately after initial infection with Leishmania parasites is known to play a relevant role in prevention against clinical progression of the disease. Domperidone is a dopamine D2 receptor antagonist that has shown to enhance the innate cell-mediated immune response. The aim of this study was to assess the preventive efficacy of a domperidone-based treatment programme against clinical canine leishmaniasis (CanL) in a high prevalence area. The study was performed with 90 healthy, seronegative dogs of different sex, age, weight and breed from a single veterinary clinic located in Valencia (Spain). Dogs were randomly allocated into two groups. Dogs in one group (domperidone-treated group; n=44) were administered an oral suspension of domperidone at 0.5 mg/kg bw/day during 30 consecutive days, every 4 months. Dogs in the other group (negative control group; n=46) were left untreated. A 21-month follow-up period was implemented covering two seasonal phases of the sand fly vector. During this period all animals underwent periodic clinical examinations and blood samplings for anti-Leishmania serological testing. Dogs seropositive for Leishmania (IFAT antibody titre≥1:80) plus at least one clinical sign consistent with CanL (indicative of active infection and incipient disease progression) were categorized as a 'prevention failure'. These dogs were withdrawn from the study after confirming the infection by direct observation of the parasite in smears of lymph nodes and/or bone marrow aspirates. The cumulative percentage of 'prevention failure' after 12 months was significantly lower in the domperidone-treated group than in the negative control group (7% versus 35%, p=0.003). Differences between groups persisted after 21 months (11% versus 48%, p<0.001). The prevention rate provided by domperidone was 80% during the first 12 months and 77% throughout the complete 21-month follow-up period, with odds ratios of 7.3 (p=0.001) and 7.15 (p<0.001), respectively, this indicating that the risk for domperidone-treated dogs to develop the clinical disease is quite 7 times lower than for dogs left untreated. The results of this study demonstrate that the implementation of a strategic domperidone-based treatment programme consisting in quarterly repeated 30-day treatments with domperidone effectively reduces the risk to develop clinical CanL in areas with high prevalence of the disease.
Department of Research and Development, ESTEVE veterinaria, Lab. Dr. ESTEVE, S.A. Avda. Mare de Déu de Montserrat 221, CP 08041 Barcelona, Spain. Electronic address: dsabate@esteve.es.
David
D
Sabaté
Hospital Veterinario Valencia Sur, Av. Picassent 28, CP 46460 Silla, Valencia, Spain.
Jorge
J
Llinás
Department of Research and Development, ESTEVE veterinaria, Lab. Dr. ESTEVE, S.A. Avda. Mare de Déu de Montserrat 221, CP 08041 Barcelona, Spain.
Josep
J
Homedes
Department of Clinical Research, Lab. Dr. ESTEVE, S.A. Avda. Mare de Déu de Montserrat 221, CP 08041 Barcelona, Spain.
Mariano
M
Sust
Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, United States.
Lluís
L
Ferrer
D000284:Administration, Oral; D000818:Animals; D004283:Dog Diseases / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control*; D004285:Dogs; D004294:Domperidone / Q000494:pharmacology / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D007113:Immunity, Innate / Q000187:drug effects; D007891:Leishmania / Q000502:physiology; D007898:Leishmaniasis, Visceral / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control / Q000662:veterinary*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D015995:Prevalence; D013030:Spain / Q000453:epidemiology
D065127:Dopamine D2 Receptor Antagonists; D004294:Domperidone
Canine leishmaniasis; Domperidone; Efficacy clinical trial; Prevention