Highlights

• Delivery of care for patients with diagnosed Chagas disease encompasses 2 modalities: the specific trypanocidal therapy with regulatory agencies–approved drugs; and the management of clinical manifestations of the disease.
• It is well recognized that the etiological treatment of Chagas disease is controversial, especially regarding its classes of recommendations and less robust levels of evidence, as well as the lack of reliable scientific evidence for efficacy and safety in the late chronic phase.
• Several limitations in the etiological treatment include low rates of parasitemia cure specifically in the late stage of the disease, lack of adequately reliable laboratory tests to follow-up parasite eradication and respective serology, Trypanosoma cruzi strains' resistance to benznidazole and nifurtimox, side effects not rare and not mild, and neglecting behavior related to the disease in endemic regions and recently affected nations.
• Currently, large randomized, adequately powered multicenter trials, with sufficient long-term follow-up and independent adjudication of clinically relevant outcomes have not been conducted to assess whether the parasiticide treatment effect yields favorable impact on the natural history of the disease. However, The BENEFIT study will provide definitive results.
• The best approach for the control and treatment of Chagas disease in Latin American countries would be a combined strategy of vector control associated with new drug treatment, which would provide highly cost-effective beneficial effects on both morbidity and mortality.