Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley, Minas Gerais, Brazil, with Chagas disease.

Jaquelline Carla Valamiel De Oliveira-Silva,Marta De Lana,Cláudia Martins Carneiro,Girley Francisco Machado-De-Assis,Nívia Carolina Noguieira Paiva,Olindo Assis Martins-Filho,Márcio Sobreira Silva Araújo,Maykon Tavares Oliveira,Helen Rodrigues Martins

doi:10.1590/0074-02760140260

Abstract

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.

Highlights

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is an important tropical disease that affects 10 million people worldwide
As no in vivo data exist regarding the experimental susceptibility or resistance to chemotherapeutic agents of the T. cruzi strains in these municipalities and that these characteristics may range even within the same T. cruzi discrete taxonomic units (DTUs) or genetic group or clones originating from the same T. cruzi strain (Camandaroba et al 2003), the goal of the present work was to evaluate the experimental efficacy of BZ in the acute and chronic phases of infection in mice infected with the T. cruzi II strains that are predominant in this region (Oliveira-Silva 2013)
A significant reduction was observed in the mean day of MPP (DMPP) of animals of the the acute phase (TAP) group compared to animals of the NT group

Summary

Introduction

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is an important tropical disease that affects 10 million people worldwide. Several studies have experimentally demonstrated a significant link between the genetic diversity of T. cruzi strains and their biological properties (Andrade & Magalhães 1977, de Lana et al 1998, Revollo et al 1998, Toledo et al 2002), including susceptibility to chemotherapeutic agents (Andrade et al 1985, 1989, Filardi & Brener 1987, Toledo et al 2003) in human and experimental conditions (Andrade et al 1992). The drug susceptibility of T. cruzi strains isolated from patients with different clinical forms of the disease has been evaluated (Andrade et al 1985, 1992, Filardi & Brener 1987, Toledo et al 1997, Oliveira-Silva 2013)

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Conclusion