Results on the implementation of a domperidone-based treatment program for the prevention of canine leishmaniosis in a dog kennel

RESULTS ON THE IMPLEMENTATION OF A DOMPERIDONE-BASED Gómez-Ochoa P, Llinás J, Sabaté D, Homedes J. and Ferrer, L It is widely recognised that in canine leishmaniosis the dog’s immune system plays a pivotal role both in the establishment and in the progress of infection. Indeed, protective immunity to the disease is associated with the production of an effective cell-mediated immune response through the release of specific cytokines that induce macrophage anti- Leishmania activity (Solano-Gallego L et al. 2009). Prolactin is a neuroendocrine hormone that plays a stimulatory role of the immune system as a proinflammatory cytokine, specifically inducing the cell-mediated immune response (Freeman M et al. 2000). Its protective role against Leishmania infection has been previously demonstrated in hyperprolactinemic lactating animals (Gómez-Ochoa P Domperidone is a gastrokinetic and antiemetic drug known to increase blood levels of prolactin through the blockade of dopamine D2 receptors in the pituitary gland (Browers JR et al. 1980). Repeated administration of domperidone to dogs has been claimed to activate their cell-mediated immune response through the increase blood levels of prolactin (Gómez-Ochoa P et al. 2009). This confers to this molecule a potential use for prevention of canine leishmaniosis in endemic areas. The aim of the present controlled, randomized clinical trial was to evaluate the effectiveness of a Domperidone-based treatment program for the prevention of canine A total of 240 clinically healthy dogs, sero-negative to Leishmania (Direct Agglutination Test, DAT<1/400), of different age, breed and sex, were included in the study. All dogs were housed in open-air premises in a dog kennel of an animal protection society located in Valladolid (Spain), with a previously known seroprevalence around 8%. The study was performed with the authorization of the All the animals were included simultaneously in the study and randomly assigned either to a Treated or to a Non-Treated group with 120 dogs each. The treatment program implemented to the animals in the Treated group was based on the results of previous studies dealing with prolactin levels and duration of domperidone effects on cellular immunity after its administration to healthy dogs (unpublished data). It consisted on two treatments with domperidone (0.5mg/kg/day for 30 consecutive days), one at the beginning of the estimated vector’s activity period (May-June) and another one at the end of this period (September-October). The 120 animals in the Non-Treated group did not receive any product. No insect repellents were applied at all to any animal in both During the study, the animals underwent periodic blinded clinical examinations and two blood samplings determination of anti-Leishmania antibody titters: before the initiation of the first treatment and 3 months after the end of the second treatment (December- January). When, at a given examination, an animal was showing some clinical sign compatible with the disease, it underwent complementary serological analyses for anti- Leishmania antibody titters’ determination. In case of positive results (DAT ≥ 1/400) the animal was withdrawn from the study and treated according to the decision of the kennel’s veterinary staff. All the animals in the Treated group remain healthy and seronegative to Leishmania right up to the end of the 9-month follow-up period. In contrast, seven dogs out of 120 (5.83%) in the Non-Treated group developed clinical signs compatible with canine leishmaniosis (peripheral lymphadenopathy and alopecia) and anti-Leishmania antibody titters >1/400 during the last month of the study (Figure 1), thus indicating active infection and disease progression. Differences between groups were statistically significant (p<0.001). In all seropositive dogs the presence of the parasite was confirmed by means of direct visualization in lymph node or bone marrow fine needle aspirate. No side effects were observed during the administration of the drug in the The results of this study demonstrate that the implementation of a domperidone-based treatment program strategically established according to the parasite’s transmission season is highly efficacious in the prevention of canine leishmaniosis in seronegative communities of dogs living in an endemic region. Browers JR, Assies J and Wiersinga W.M et al.; Plasma prolactin levels after acute ans subchronic oral administration of Domperidone and Metoclopramide. Clinical Freeman ME, Kanyicska B, Lerant A et al.; Prolactin: Structure, Function and Regulation of Secretion. Phisiological Reviews 2000, Vol. 80. Nº.4: 1523-1631. Gómez-Ochoa P, Castillo JA, Gascón FM et al.; Use of Domperidone in the treatment of canine visceral leishmaniasis: A clinical trial., Vet J. 2009, Feb; 179(2):259-263. Gómez-Ochoa P, Gascón FM, Lucientes J et al.; Lactating females Syrian hamster (Mesocricetus auratus) show protection against experimental Leishmania infantum infection. Vet. Parasitol. 2003, 116:61-64. Solano-Gallego L, Koutinas A, Miró G et al.; Directions for the diagnosis ans clinical classification of leishmaniosis in dog. Vet. Parasitol. 2009, Oct 28; 165(1-2-):1-18. Figure 1. Anti-Leishmania antibody titters’ distribution in both groups, up to the end of the study (Direct Agglutination Test, DAT, cut-off titter <1/400).

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