Trypanocidal Treatment for Chronic Chagas Disease: Past, Present, and Future

This article reviews the trypanocidal therapy for chronic Chagas disease, emphasizing its indications, efficacy, limitations, and future perspectives. The etiological treatment is based on the use of benznidazole and nifurtimox, both of which were developed over five decades ago. These drugs are most effective in the acute phase, but are also recommended for children, adolescents, and adults aged <50 years without severe organ damage, and women of childbearing age to prevent congenital transmission. Adherence to treatment is limited by adverse drug reactions, which affect approximately half of the patients, leading to treatment discontinuation in approximately 30% of cases. The cure criteria included parasitological, serological, and clinical responses that required long-term follow-up. Clinical trials and systematic reviews have shown heterogeneous results that are influenced by age, clinical stage, and geographical region. Recent public policies supported by non-governmental organizations and academic networks have expanded access to diagnosis and treatment, although structural and informational barriers persist. New therapeutic strategies include shortened benznidazole regimens, drug repositioning, and combination therapies aimed at reducing adverse drug reactions and improving efficacy. Novel molecules with distinct mechanisms and vaccines with therapeutic and preventive potentials are under investigation. Despite these advances, the challenge remains in translating these innovations into concrete benefits for affected populations, particularly in the most vulnerable regions.