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Monotherapy and combination chemotherapy for Chagas disease treatment: a systematic review of clinical efficacy and safety based on randomized controlled trials

Published online by Cambridge University Press:  12 August 2022

Silas Santana Nogueira ,
Eliziária Cardoso Santos ,
Roberta Oliveira Silva ,
Reggiani Vilela Gonçalves ,
Graziela Domingues Almeida Lima  and
Rômulo Dias Novaes Open the ORCID record for Rômulo Dias Novaes [Opens in a new window]
Silas Santana Nogueira
Affiliation:
Programa de Pós-Graduação em Biociências Aplicadas à Saúde, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, 37130-000, Minas Gerais, Brazil Instituto Federal do Sul de Minas Gerais, Pouso Alegre, Minas Gerais, Brazil
Eliziária Cardoso Santos
Affiliation:
Faculdade de Medicina, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, MG, Brazil
Roberta Oliveira Silva
Affiliation:
Programa de Pós-Graduação em Biociências Aplicadas à Saúde, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, 37130-000, Minas Gerais, Brazil
Reggiani Vilela Gonçalves
Affiliation:
Departamento de Biologia Animal, Universidade Federal de Viçosa, Viçosa, 36570-900, Minas Gerais, Brazil
Graziela Domingues Almeida Lima
Affiliation:
Programa de Pós-Graduação em Biociências Aplicadas à Saúde, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, 37130-000, Minas Gerais, Brazil
Rômulo Dias Novaes*
Affiliation:
Programa de Pós-Graduação em Biociências Aplicadas à Saúde, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, 37130-000, Minas Gerais, Brazil Departamento de Biologia Estrutural, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, 37130-000, Minas Gerais, Brazil
*
Author for correspondence: Rômulo Dias Novaes, E-mail: romuonovaes@yahoo.com.br
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Abstract

From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day−1, 200 mg day−1, 150 mg day−1 and 2.5 mg kg−1) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day−1 for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.

Keywords

Antiparasitic chemotherapyChagas diseaseparasitologyTrypanosoma cruzi
Type
Systematic Review
Information
Parasitology , Volume 149 , Issue 13 , November 2022 , pp. 1679 - 1694
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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