Abstract
Chagas disease remains a neglected tropical disease, causing significant burden in the Americas and countries that receive immigrants from endemic nations. Current pharmaceutical treatments are suboptimal, not only varying drastically in efficacy, depending on the stage of disease, but also presenting significant risk of adverse events. The objective of this review is to provide a timely update on the efficacy and safety of current trypanocidals. Eligible studies published from January 2015 to December 2020 were retrieved by one reviewer from six electronic databases. Ana-lysis was done with review management software and risk of bias was assessed using tools appropriate for the type of study (i.e., experimental or observational). Thirteen studies (10 observational and three RCTs) were included in the analysis. All 13 studies tested Benznidazole (BNZ) or Nifurtimox (NFX), and two studies also tested Posaconazole (POS) or E1224 (Ravucanazole). BNZ was found to be the most efficacious trypanocidal drug compared to Nifurtimox, POS, and E1224; it also resulted in the highest percentage of adverse effects (AEs) and treatment discontinuation due to its toxicity. Adults experienced higher frequency of neurological AEs while taking BNZ or NFX compared to children. Children had a higher frequency of general AEs compared to adults while taking BNZ. Overall, BNZ is still the most efficacious, but development of new, less toxic drugs is paramount for the quality of life of patients. Studies testing combination therapies and shorter regimens are needed, as is the devising of better clinical parameters and laboratory biomarkers to evaluate treatment efficacy. Considering the variability in methodology and reporting of the studies included in the present analysis, we offer some recommendations for the improvement and replicability of clinical studies investigating pharmacological treatment of Chagas disease. These include full disclosure of methodology, standardization of outcome measures, and always collecting and reporting data on both the efficacy of trypanocidals and on safety outcomes.
Highlights
Introduction published maps and institutional affilChagas disease, scientifically known as American Trypanosomiasis, is caused by Trypanosoma cruzi, a hemoflagellate protozoan parasite transmitted most commonly to humans by triatomine hematophagous vectors
This review provides an update on the pharmaceutical treatment of Chagas disease
Our findings confirm that BNZ is still the most efficacious trypanocidal drug compared to other drugs (NFX, POS, and E1224) as well as to no treatment, or placebo
Summary
Introduction published maps and institutional affilChagas disease, scientifically known as American Trypanosomiasis, is caused by Trypanosoma cruzi, a hemoflagellate protozoan parasite transmitted most commonly to humans by triatomine hematophagous vectors. Despite great progress in its control, Chagas disease remains a significant public health problem in 21 countries in the Americas, where approximately 65–120 million people live at risk of infection, of which 6-12 million people are infected [1,2,3,4,5,6,7,8,9]. The current pharmaceuticals approved for the treatment of acute infection, are Benznidazole (BNZ) and Nifurtimox (NFX). Both trypanocidals were developed in the 1960–. These treatments are not accessible for many infected individuals, especially those already living in poverty [11].
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