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Therapeutic responses to different anti-Trypanosoma cruzi drugs in experimental infection by benznidazole-resistant parasite stock

Published online by Cambridge University Press:  21 July 2014

SÉRGIO CALDAS ,
IVO SANTANA CALDAS ,
ALZIRA BATISTA CECÍLIO ,
LÍVIA DE FIGUEIREDO DINIZ ,
ANDRÉ TALVANI ,
ISABELA RIBEIRO  and
MARIA TEREZINHA BAHIA
SÉRGIO CALDAS
Affiliation:
Laboratório de Doença de Chagas, Departamento de Ciências Biológicas and Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário, Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Gameleira, Belo Horizonte, Minas Gerais, Brazil
IVO SANTANA CALDAS
Affiliation:
Laboratório de Doença de Chagas, Departamento de Ciências Biológicas and Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário, Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil Departamento de Patologia e Parasitologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG, Brazil
ALZIRA BATISTA CECÍLIO
Affiliation:
Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Gameleira, Belo Horizonte, Minas Gerais, Brazil
LÍVIA DE FIGUEIREDO DINIZ
Affiliation:
Laboratório de Doença de Chagas, Departamento de Ciências Biológicas and Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário, Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil
ANDRÉ TALVANI
Affiliation:
Laboratório de Doença de Chagas, Departamento de Ciências Biológicas and Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário, Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil
ISABELA RIBEIRO
Affiliation:
Drugs for Neglected Disease initiative (DNDi), 1202 Geneva, Switzerland
MARIA TEREZINHA BAHIA*
Affiliation:
Laboratório de Doença de Chagas, Departamento de Ciências Biológicas and Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário, Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil
*
*Corresponding author: Laboratório de Doença de Chagas, sala 39, Instituto de Ciências Biológicas, ICEB II, Universidade Federal de Ouro Preto, Ouro Preto, MG, 35400-000, Brazil. E-mail: [email protected]
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Summary

This study describes the role of parasite clearance time induced by benznidazole, fexinidazole and posaconazole treatments upon mice infection with a benznidazole-resistant Trypanosoma cruzi strain in the pathological outcomes. Trypanosoma cruzi-infected mice were treated with different drugs and parasite clearance time was detected by blood and tissue qPCR, to determine the dynamic relationship between the efficacy of the treatments and the intensity of heart lesion/serum inflammatory mediators. Our results indicate that anti-T. cruzi treatments were able to reduce parasite replication and consequently induce immunomodulatory effects, where the degree of the immunopathology prevention was related to the time of parasite clearance induced by different treatments. Nevertheless, in benznidazole and posaconazole treatments, parasite rebounding was detected with parasitism reaching levels similar to infected and non-treated mice; the time for parasitic rebound being earlier among benznidazole-treated mice. In parallel, an increase of cardiac lesions and plasma chemokine levels was also detected and was more accentuated in benznidazole-treated animals. Interestingly, in the presence of parasitological cure (fexinidazole treatment), basal levels of these inflammatory mediators were evidenced as well as an absence of cardiac inflammation or fibrosis. Overall, our data indicate that all treatments have positive effects on the clinical evolution of T. cruzi infection, with success in preventing cardiac alterations being drug-dependent.

Keywords

Trypanosoma cruzireal-time PCRchemotherapyinflammationbenznidazoleposaconazolefexinidazole
Type
Research Article
Information
Parasitology , Volume 141 , Issue 12 , October 2014 , pp. 1628 - 1637
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Copyright
Copyright © Cambridge University Press 2014 

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