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

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-α 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.

Benznidazole alters the pattern of Cyclophosphamide-induced reactivation in experimental Trypanosoma cruzi-dependent lineage infection.

The factors involved in the reactivation of chronic Chagas disease infection are not clear enough and may be related to host immune unbalance and/or parasite genetic diversity. To evaluate the role of the Trypanosoma cruzi genetic background in the Chagas disease reactivation, we inoculated Cyclophosphamide-immunosupressed (CyI) Swiss mice with clonal stocks from T. cruzi I (Cuica cl1, P209 cl1, Gamba cl1, SP104 cl1), T. cruzi II (IVV cl4, MVB cl8) and T. cruzi (Bug2148 cl1, MN cl2) lineages. We used the parasitemia as the parameter for Chagas disease reactivation and observed that CyI animals infected with T. cruzi stocks showed no reactivation and those infected with T. cruzi II stocks showed only 5% of reactivation. In contrast, immunosuppressed mice infected with stocks from T. cruzi I lineage showed 77.5 and 51.25% reactivation of the infection when Cyclophosphamide treatment was performed 60 and 180 days after inoculation, respectively. Next, we evaluated the efficacy of the Benznidazole (Bz) pre-treatment in reducing or preventing the recurrence of the infection in these CyI animals. In general, the percentage of the parasite recurrence was not altered among the CyI mice that received the Bz pre-treatment during the acute phase of the infection. Interestingly, when pre-Bz treatment was performed during the chronic phase, we observed two different patterns of response: (i) an increased protection among the animals inoculated with the SP104 cl1 (genotype 19) and Cuica cl1 (genotype 20) stocks; (ii) an increased percentage of parasitemia reactivation among mice inoculated with Gamba cl1 (genotype 19) and P209 cl1 (genotype 20) T. cruzi stocks. Our results corroborate our hypothesis by showing that the T. cruzi genetic background in combination with specific Bz treatment has an important role in the Chagas disease reactivation in immunosuppressed animals.