Gizzarelli, Manuela (2014) Valutazione dell'attività anti-Leishmania del Domperidone in cani naive esposti a infezione naturale. [Tesi di dottorato]

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Canine leishmaniasis (CanL), is a zoonotic systemic infectious disease caused by protozoan Leishmania infantum, an obligatory intracellular parasite of macrophages, transmitted by the bite of phlebotomine sandflies. The aim of this study, is to evaluate the use of domperidone, a dopamine D2 receptor antagonist, in naïve dogs naturally exposed to canine leishmaniosis. Materials and Methods. The study was performed in an open-air kennel sited in Sant’Anastasia, a rural municipality of the Naples province (Southern Italy) where both human visceral leishmaniasis and CanL are highly endemic. 25 naïve beagle dogs,of 5-7 months old, were housed in kennel and regularly treated with domperidone, during two consecutive seasons of transmission of CanL. During the study, dogs neither received mechanical nor chemical protection against sand fly bites, nor anti-Leishmania drugs if they showed clinical manifestation of Leishmania infection during the study. The following time points have been considered in this analysis: M5,M9 ad M17. At each M point the following biological samples were obtained from dogs: peripheral blood for IFAT serology, full blood count, total proteins, albumin/globulin ratio, and urea and creatinine values; bone marrow (BM) aspirate for Leishmania DNA detection by nested polymerase chain reaction (n-PCR); popliteal limph node (LN) aspirate for parasite culture. Before samplings, a complete clinical assessment was performed by accurate inspection of dogs for the presence of any clinical signs attributable to Leishmania infection. By the comparative analysis of clinical, serological and parasitological findings, the dogs were assigned to one of the following stages of CanL: negative, subpatent infection, asymptomatic active infection and symptomatic active infection. Results were compared with similar data, obtained from a group of dogs, housed in the same kennel in the same period, but that didn’t receive any treatment. Results. At M5 all dogs of first group (treated with domperidone) were still negative to the infection. A M9, 60% of dogs was negative, 25% showed subpatent infection, 5% had asymptomatic active infection and 10% symptomatic active infection. At M17, 55% of dogs was negative, 10% had subpatent infection, 5% asymptomatic active infection and 30% symptomatic active infection. In control group (no treatment), at M5 all dogs were negative. At M9, 90,5% of dogs was negative, 6% had subpatent infection, 4% asymptomatic active infection. At M17, 79 % of dogs was negative, 7,5% showed subpatent infection, 7,5% asymptomatic active infection and 7,5% symptomatic active infection. Conclusions. The present study, is part of a longer study, so data should not be considered conclusive. Despite this, it is clear that the treatment with domperidone, was not effective in preventing the infection. Should be carried out further studies to test the drug in groups of dogs that live in highly endemic areas and exposed to highly stressful conditions, like those due to life in kennel.

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