Contribuição para o manejo terapêutico de intervenção na Leishmaniose Canina: definição de um modelo de resposta preditiva ao tratamento e efeito clínico da suplementação com adjuvantes nutricionais

Abstract

Canine leishmaniasis (CanL) is a zoonotic disease caused by the intracellular protozoan Leishmania infantum in Brazil. The dog (Canis familiaris) is considered the main domestic reservoir of the parasite, in addition to being a species susceptible to the development of serious and fatal forms of the disease. The course of CanL is characterized by changes in immune and oxidative metabolism, and an effective response to treatment will depend on several factors such as the sensitivity of the protozoan to the antiparasitic drug, the inherent pathogenicity of the strain of L. infantum involved and the quality of the immune response developed by the canine host. Aiming to contribute to the knowledge about inherent aspects to the response of the canine hos, this is study proposed: 1) to identify possible predictive biomarkers of an effective therapeutic response in dogs with CanL; and 2) to evaluate whether the association of nutritional adjuvants with antioxidant properties and anti-Leishmania drugs would be able to promote improvement of clinical and laboratory parameters, alter some of the biomarkers of oxidative stress in dogs with CanL, and thus the outcome of the treatment. Dogs with confirmed infection were divided into two groups: treatment responders (who showed a reduction in the L. infantum parasitic load by qPCR; n = 12) and non-responders (who did not show a reduction in the parasite load; n = 14). The dogs were monitored by clinical, hematological and serum biochemical evaluation at 30 days, two, three, six and twelve months after treatment. A mathematical model has been developed to estimate the success of anti-Leishmania treatment. Erythrocytes and serum phosphorus were identified as early predictive markers of therapeutic response in CanL. Data obtained in this study indicate that dogs that responded to treatment showed an early difference in their profile of laboratory parameters when compared to dogs that did not respond to treatment. For the second objective, dogs with confirmed infection at different clinical stages were randomly grouped, according to the therapeutic criterion into two other groups: G1 (dogs that used nutritional adjuvants before and during anti-Leishmania chemotherapy; n = 6) and G2 (dogs that used only previous anti-Leishmania drugs; n = 12) for comparative evaluation. Nutritional adjuvants included commercial nutraceuticals based on fish oil (rich in DHA and EPA fatty acids - omega 3) and complex B vitamins. The data showed that dogs that received supplements exhibited indicators of inflammation control, with a reduction in: total globulins, specific anti-Leishmania immunoglobulins, total proteins and C reactive protein, in addition to an increase in serum albumin. Nutritional adjuvants positively influenced the response of dogs to treatment for CanL. Thus, our data encourage the use of nutrional adjuvants in clinical routine as well as the development of further studies on the use 11 of antioxidants in the form of nutraceuticals and oral vitamins as a co-therapeutic strategy in the treatment of the disease.