Terapêutica da fase crônica da infecção experimental pelo Trypanosoma cruzi com o Benzonidazol e o Nifurtimox

Abstract

Fifty-eight mice, chronically infected with different T. cruzi strains (Types II and III) were submitted to chemotherapy either with Nifurtimox (Bay 2502) or Benznidazole (Ro 7-1051). Twenty one mice were not treated and were used as infected controls. The duration of infection was from 90 to 400 days. Inocula varied from 1 x 10(4) to 5 x 10(4) blood forms. Treatment lasted for 90 days, doses being 200mg/kg/day during 4 days, followed by 50mg/kg/day for Nifurtimox and 100mg/kg/day for Benznidazole. Parasitological tests (xenodiagnosis, inoculations into baby mice and hemoculture) showed 85.3% negativation for Type II strains and 43% for Type III in animals treated with Benznidazole. As for Nifurtimox, there were 71.4% of parasitological negativation for the animals infected with Type II strains and 66% for those infected with Type III. IFA tests remained positive in 90% of treated and cured animals. Disappearance or marked regression of myocardial and skeletal muscle lesions was seen in the treated and parasitologically negative animals. The conclusion is that the treatment in the chronic phase of T. cruzi infection can result in parasitological cure in a high percentage of cases with regression of histopathological lesions, although with persistence of positivity of the IFA tests.

Chemotherapy with Benznidazole and Itraconazole for Mice Infected with Different Trypanosoma cruzi Clonal Genotypes

“…Discrepant data were also observed for BUG2148 cl1 and MN cl2 of genotype 39 and MVB cl8 and IVV cl4 of genotype 32. Similar results were previously described by Andrade et al (2), who demonstrated that T. cruzi I strains that were highly resistant to BZ and NFX during AP were partially susceptible to both drugs during CP.…”

“…Interestingly, during CP a different association between the zymodeme and the drug resistance pattern was found. Even strains highly resistant to BZ during AP, like T. cruzi I strains, were shown to be partially susceptible during CP, while no such differences were observed for T. cruzi II strains (2). Although the studies cited above have made significant contributions, they did not rely on a rigorous population genetics framework.…”

“…One factor that may contribute to these differences during treatment for Chagas' disease could be the type of strain predominant in each geographic area. A well-known feature involved in resistance to chemotherapy is the high degree of biological and genetic diversity of T. cruzi strains (1,2,4,31,33). The clonal evolution model postulated for T. cruzi (36) predicts a correlation between the phylogenetic divergence of T. cruzi clonal genotypes and their biological properties including their drug sensitivities.…”

2 nd Brazilian Consensus on Chagas Disease, 2015

“…This would lead to a reduction in the complications of the disease, especially those related to heart disease. Classical experimental studies in mice have already documented total or partial regression of early myocardial injuries and the prevention of cardiopathy with antiparasitic treatment (299) (300) . However, regression of inflammatory and fibrotic lesions, observed in experimental studies, has not been verified in the clinical context (20) .…”

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

“…However, treatment during the chronic phase promotes recovery in only 37% of cases, with few protective effects during the clinical course of the disease (6,7). However, some authors reported BNZ treatment as beneficial because the parasite is the major factor responsible for tissue lesions and the clinical course (8)(9)(10). Therefore, the usefulness of BNZ during the chronic phase is still undergoing investigation.…”