Cardiomyopathy prognosis after benznidazole treatment in chronic canine Chagas' disease.

Abstract

Objectives: To evaluate the effects of benznidazole on Chagas’ disease cardiac prognosis using an experimental dog model of infection. Methods: A total of 28 dogs were divided into three groups: 10 were infected with Trypanosoma cruzi and treated benznidazole during the chronic phase, 10 were infected but untreated, and 8 were non-infected/ healthy. The trypanocidal efficacy was measured by parasite kDNA detection in blood and cardiac tissue samples. The effects of benznidazole in ameliorating the cardiac systolic function were evaluated by echodopplercardiogram. Results: The benznidazole initially induced a potent suppression of parasitaemia in treated animals. However, 12 months post-treatment, the parasite kDNA detections were similar between infected groups. In the baseline echocardiographic parameters there was no variation among all animals. Similarly, 1 month post-treatment there was no significant difference among healthy and infected animals with regard to systolic function. At 12 months post-treatment, an increase in cardiac chamber size related to cardiomegaly was detected among treated and untreated animals, but not in the healthy controls. Interestingly, in spite of both groups of infected animals developing a decrease in their systolic cardiac function, this decline was slightly less in the treated animals. We also evaluated levels of tumour necrosis factor-a and interleukin-10 in peripheral blood mononuclear cell culture supernatant. Cytokine profiles were similar between infected animal groups and correlated with alterations in cardiac function. Conclusions: The temporary suppression of the T. cruzi infection induced by benznidazole treatment was efficient in reducing systolic cardiac function alterations, but not in preventing the development of cardiomyopathy.