Domperidone Against Leishmaniasis: Preliminary Results from First Therapeutic Trial
*Pablo Gomez Ochoa, Manuel Gascon Perez, Juan Antonio Castillo Hernandez, Javier Lucientes Curdi, Juan Jose Zarate Ramos, Jose Ignacio Arbea Sarasa
Canine leishmaniasis is a zoonotic disease widespread in Spain, as in the other Mediterranean basin countries. During the illness the decrease of the cell-mediated immunity (Th1) and the raising of antibodies (Th2) is the key, that leads the dog to visceral forms. Domperidone is a gastric pro-kinetic drug that induces an enhancement in prolactin seric level, as a secondary reaction. This hormone from pituitary gland, also generated by lymphocytes, as a pro-inflammatory cytokine, is able to stimulate cellular immunity (Th1) increasing the INF-gamma, IL2, IL12, TNF-alfa production. The research's main objective, was to evaluate the efficacy of immunostimulation induced by domperidone in fifty-seven leishmaniasic dogs.
To accomplish the assay, fifty-seven naturally infected dogs, from SMIPA of "Facultad de Veterinaria de Zaragoza", were included. A complete physical examination, blood and general biochemistry profile, in addition to a serologic test, using DAT, (Direct Agglutination Test, 1/800 cut-off titre), were also made all along the process. The therapeutic protocol was fixed for each dog, on 1 mg per kg every 12 hours, during 1 month. Serial controls were established at 15th, 30th, 90th, 180th and 365th days, since treatment starting date. In order to analyze the results two groups of dogs were made. (Group "A") 40 dogs with 1/800-1/1600 DAT titre, 32 of them were asymptomatic and the other 8 dogs had mild lymph node enlargement. (Group "B") 17 dogs with more than 1/1600 DAT titre, all of them polysymptomatic.
During scheduled controls, none of the dogs from group A revealed any symptom and a raising in antibody titre wasn't noticed either. As a matter of fact antibody titre decreased on some 75% of the dogs from this group, and it was absolutely negative on 30% of them. About "B" group, in which 17 dogs were initially included, one of them, with severe renal failure, was euthanized at day 15th, by owner's decision. An increase in antibody titre, was detected in two dogs, after performing the last control. In remaining nine dogs, titre kept equal along the 365 days of test lasting. As a summary of data above, we can say that 12.5% of the whole number of dogs worsened, meanwhile a considerable decrease of antibody titre, were noticed in a 31.25%, being completely DAT negative 18.75% of the dogs that reduced its initial amount. After one year of testing, 87.5% of the dogs didn't show any worsening at all, and a clear improving on symptom disappearing could be observed on about 81.25% of them.
Stimulation of cellular response may be the key for many diseases, such as leishmaniasis. Hyperprolactinemia induced by domperidone should be considered in the therapeutic management of canine leishmaniasis. Advantages of this protocol in comparison with traditional ones with anfotericin or antimonials are very clear. Domperidone is a cheap drug, which oral administration to dogs is easy to accomplish by dog's owners, it has not presented any renal injury or other adverse reactions. Immunostimulation in leishmaniasic dogs had been probed before, but this is the first assay with domperidone, so, lack of references involves, that other dosage, time administration and possible associations with other drugs, might be taken into account.