In vivo susceptibility to benznidazole of Trypanosoma cruzi strains from the western Brazilian Amazon

摘要

Objective: To assess the susceptibility of Trypanosoma cruzi strains from Amazon to benznidazole. Methods: We studied 23 strains of T. cruzi obtained from humans in the acute phase of Chagas disease, triatomines and marsupials in the state of Amazonas and from chronic patients and triatomines in the state of Paraná, Brazil. The strains were classified as TcI (6), TcII (4) and TcIV (13). For each strain, 20 Swiss mice were inoculated: 10 were treated orally with benznidazole 100 mg/kg/day (TBZ group) for 20 consecutive days and 10 comprised the untreated control group (NT). Fresh blood examination, haemoculture (HC), PCR, and ELISA were used to monitor the cure. Results: The overall cure rate was 60.5% (109/180 mice) and varied widely among strains. The strains were classified as resistant, partially resistant or susceptible to benznidazole, irrespective of discrete typing units (DTUs), geographical origin or host. However, the TcI strains from Amazonas were significantly (P = 0.028) more sensitive to benznidazole than the TcI strains from Paraná. The number of parasitological, molecular and serological parameters that were significantly reduced by benznidazole treatment also varied among the DTUs; the TBZ group of mice inoculated with TcIV strains showed more reductions (8/9) than those with TcI and TcII strains. Conclusions: Benznidazole resistance was observed among natural populations of the parasite in the Amazon, even in those never exposed to the drug.