title: Therapeutic responses to different anti-Trypanosoma cruzidrugs in experimental infection by benznidazole-resistant parasite stock.
abstract: This study describes the role of parasite clearance time induced by benznidazole, fexinidazole and posaconazole treatments upon mice infection with a benznidazole-resistantTrypanosoma cruzistrain 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. cruzitreatments 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 ofT. cruziinfection, with success in preventing cardiac alterations being drug-dependent.
authors.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.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Caldas
authors.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.
authors.forename: Ivo Santana
authors.initials: IS
authors.lastname: Caldas
authors.affiliation: Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Gameleira, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Alzira Batista
authors.initials: AB
authors.lastname: Cecílio
authors.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.
authors.forename: Lívia DE Figueiredo
authors.initials: LF
authors.lastname: Diniz
authors.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.
authors.forename: André
authors.initials: A
authors.lastname: Talvani
authors.affiliation: Drugs for Neglected Disease initiative (DNDi), 1202 Geneva, Switzerland.
authors.forename: Isabela
authors.initials: I
authors.lastname: Ribeiro
authors.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.
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: Bahia
keywords: Trypanosoma cruzi; benznidazole; chemotherapy; fexinidazole; inflammation; posaconazole; real-time PCR