Intravenous immunoglobulin increases survival time in the acute phase of experimental Chagas disease.

Chagas disease induced by Trypanosoma cruzi (Tc) infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are insufficient and largely inadequate. Intravenous immunoglobulin (IVIg) is a therapeutic preparation containing normal polyspecific IgG obtained from plasma pools of several thousand healthy donors and is used in several autoimmune, inflammatory and infectious diseases. In the study of heart from mice chronically infected with Tc, we observed that IVIg restores type 1 atrioventricular block or bradycardia. In the present study, we investigated the effects of IVIg in acute Tc infection. Intravenous immunoglobulin administration after the first week of infection was associated with an increase in survival time. Taken together, results observed in the chronic and in the acute phase associate IVIg treatment with a favourable outcome in T. cruzi infection.

Benznidazole therapy in Trypanosoma cruzi-infected mice blocks thymic involution and apoptosis of CD4+CD8+ double-positive thymocytes.

Several alterations involving peripheral lymphoid organs have been extensively described after experimental Trypanosoma cruzi infection. Thymic involution occurs as well in infected mice, with both structural and functional alterations in the organ. Despite these abnormalities, specific immune response proceeds to control parasitemia and the participation of T lymphocytes is essential. However, there are relatively few studies on the impact of benznidazole (N-benzyl-2-nitroimidazole acetamide) upon this response. In this present work, we decided to evaluate the impact of benznidazole treatment upon the thymus involution following acute T. cruzi infection in mice. We have provided evidence that benznidazole treatment controls the severe abnormalities seen in the thymus due to T. cruzi infection. The thymocyte loss related to the depletion of double-positive CD4(+)CD8(+) thymocytes was clearly prevented, corroborating the idea that the mechanism responsible for the prevention of thymus involution is related to the decrease of apoptosis rate in this subset after benznidazole treatment. Furthermore, we demonstrated the prevention of enhanced extracellular matrix deposition in the thymus. In conclusion, the preservation of thymus homeostasis, even though partial, was accomplished after benznidazole treatment. Our data are consistent with the notion that different outcomes of T. cruzi infection may be linked to differences in the parasite load concomitant to fine tuning of the host immune response.

Enzymatic markers of heart lesion in mice infected with Trypanosoma cruzi and submitted to benznidazole chemotherapy.

Creatine kinase (CK total and CK-MB) were studied as markers of lesion progression induced by Trypanosoma cruzi infection. After 3 weeks mice infected with 10(4) parasites showed an increase in both enzyme levels and in their frequency distribution. A trend to increase was already detected in the 2nd week. A short duration per os treatment with benznidazole (Bz) prevented the occurrence of tissue lesions, since no changes were observed in enzymes. However, in the 4th week, about 40% of Bz-treated mice showed an increase in CK-MB, as did those that survived until the 8th week. Long-term treatment with Bz in drinking water of mice infected with 10(2) parasites showed, after 32 weeks, a partial reversion of the occurrence of high CK-MB levels from 85.7% to 50%. We found a positive correlation between inflammatory infiltrates and CK-MB levels, indicating that this marker could be useful to monitor the occurrence of experimental chagasic myocarditis.