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

CALDAS, SÉRGIO ; CALDAS, IVO SANTANA ; CECÍLIO, ALZIRA BATISTA ; DINIZ, LÍVIA DE FIGUEIREDO ; TALVANI, ANDRÉ ; RIBEIRO, ISABELA ; BAHIA, MARIA TEREZINHA

In: Parasitology, 2014, vol. 141, no. 12, p. 1628-1637

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    Titre
    • Therapeutic responses to different anti-Trypanosoma cruzi drugs in experimental infection by benznidazole-resistant parasite stock
    Auteur
    • CALDAS, SÉRGIO. 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
    • CALDAS, IVO SANTANA. 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
    • CECÍLIO, ALZIRA BATISTA. Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Gameleira, Belo Horizonte, Minas Gerais, Brazil
    • DINIZ, LÍVIA DE FIGUEIREDO. 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
    • TALVANI, ANDRÉ. 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
    • RIBEIRO, ISABELA. Drugs for Neglected Disease initiative (DNDi), 1202 Geneva, Switzerland
    • BAHIA, MARIA TEREZINHA. 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
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Parasitology, 2014, vol. 141, no. 12, p. 1628-1637. Cambridge University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:297569
    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