Abstract: Chagas disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi. Current treatment options are limited to nifurtimox and benznidazole, which have long regimens, frequent adverse effects, and reduced efficacy, particularly in the chronic phase, when most patients are diagnosed. This review aims to analyze preclinical studies on combination therapy for experimental Chagas disease, evaluating their potential to improve treatment efficacy, safety, and duration. A systematic review was conducted following PRISMA guidelines, analyzing preclinical studies that assessed combination therapies against T. cruzi. Key factors considered included study design, drug combinations, efficacy outcomes, and translational potential. Over the past decade, combination therapy has been extensively investigated in experimental models of T. cruzi infection. Achieving a successful translation of findings from preclinical studies to clinical settings requires careful consideration of various factors, including study design, outcome measures, and the use of standard treatment. Combination therapy represents a promising strategy to optimize Chagas disease treatment. However, further research is needed to bridge the gap between preclinical findings and clinical application. This review provides a comprehensive synthesis of experimental data related to Chagas disease, highlighting key trends, limitations, and future research directions.
Pagotti et al. (Mon,) studied this question.