4.4 Article

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

期刊

PARASITOLOGY
卷 141, 期 12, 页码 1628-1637

出版社

CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0031182014000882

关键词

Trypanosoma cruzi; real-time PCR; chemotherapy; inflammation; benznidazole; posaconazole; fexinidazole

资金

  1. DNDi
  2. Fundacao de Amparo a Pesquisa do Estado de Minas Gerais
  3. Universidade Federal de Ouro Preto
  4. FAPEMIG
  5. CNPq
  6. Department for International Development (DFID), UK
  7. Medecins sans Frontieres/Doctors without Borders (MSF), International
  8. Spanish Agency for International Development Cooperation (AECID), Spain
  9. Swiss Agency for Development and Cooperation (SDC), Switzerland

向作者/读者索取更多资源

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.

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