Efficacy and Safety of Pharmacological Treatments of Chagas Disease

Abstract

Background: Chagas disease is a neglected tropical disease that causes a high burden of disease in the Americas. Current trypanocidal treatments vary drastically in efficacy, depending on the stage of disease and the drugs administered. Conventional trypanocidals present a significant risk of adverse events. Concerns about efficacy in the indeterminate and chronic stage, and safety in all stages remain a barrier to treatment. The objective of this review was to provide an update on the efficacy and safety of trypanocidals used in the treatment of Chagas disease. Methods: Eligible studies were retrieved from electronic databases, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), LILACS (iAHx), PubMed, and SciELO from January 2015-December 2020. Language was restricted to English, Spanish, and Portuguese. Our review examined the efficacy and safety of the current trypanocidal drugs for Chagas disease compared to no treatment or placebo. Results: We included 13 studies (3 RCTs and 10 observational) involving 8022 participants. All 13 studies tested nitroderivative drugs, Benznidazole or Nifurtimox, two studies also tested azoles, Posaconazole or E1224 (Ravucanazole). Of the four trypanocidals, BNZ was shown to be the most efficacious in both types of studies. POS and E1224 both had an antiparasitic effect during the course of treatment, but the effect was not sustained and returned to near placebo levels. Of the two RCTs reporting patient- related outcomes neither found significant differences between groups in terms of development of ECG abnormalities or mortality. Among the observational studies, three found no significant differences in development of ECG abnormalities or mortality. Three studies found a significant difference in development of ECG abnormalities and two found a reduction in mortality in patients treated with trypanocidals. Conclusion: This review provides evidence that BNZ is still the most efficacious treatment despite its high frequency of AEs and treatment discontinuation due to them. Trypanocidal treatment may reduce the development of ECG abnormalities and reduce the risk of mortality, but confirmatory studies are required. As well, better markers for cure are needed to evaluate efficacy. Fully understanding the mechanisms of action of the conventional trypanocidals will also increase our knowledge on the efficacy/tolerance equilibrium.