Different infective forms trigger distinct lesions in the colon during experimental Chagas disease.

With the control of vectorial transmission of Chagas disease caused by metacyclic trypomastigotes (MT) in endemic countries, other pathways of infection have become important. The infection caused by blood trypomastigotes (BT) is relevant in places where the blood transfusion and organ transplantation are poorly controlled. This study aimed to evaluate immunopathogenic parameters in the colon during the acute and chronic phases of experimental infection in Swiss mice infected with BT or MT forms of VL-10 strain of Trypanosoma cruzi. We have found that animals infected with MT forms presented lower survival rate, and higher tissue parasitism in the acute phase of the disease, which may be associated with the exacerbated activation of the immune system with the production of pro-inflammatory cytokines even in the chronic phase of infection. Taken together, these results can also be associated to the maintenance of the inflammatory process in chronic phase and an earlier denervation of myenteric plexus in colon. These findings emphasized the importance of the inoculum source and the strain, once different forms of different strains seem to promote distinct diseases.

Benznidazole Treatment: Time- and Dose-Dependence Varies with the Trypanosoma cruzi Strain.

As the development of new drugs for Chagas disease is not a priority due to its neglected disease status, an option for increasing treatment adherence is to explore alternative treatment regimens, which may decrease the incidence of side effects. Therefore, we evaluated the efficacy of different therapeutic schemes with benznidazole (BNZ) on the acute and chronic phases of the disease, using mice infected with strains that have different BNZ susceptibilities. Our results show that the groups of animals infected by VL-10 strain, when treated in the chronic phase with a lower dose of BNZ for a longer period of time (40 mg/kg/day for 40 days) presented better treatment efficacy than with the standard protocol (100 mg/kg/day for 20 days) although the best result in the treatment of the animals infected by the VL-10 strain was with100 mg/kg/day for 40 days. In the acute infection by the Y and VL-10 strains of T. cruzi, the treatment with a standard dose, but with a longer time of treatment (100 mg/kg/day for 40 days) presented the best results. Given these data, our results indicate that for BNZ, the theory of dose and time proportionality does not apply to the phases of infection.