BACKGROUND: Chagas disease, caused by Trypanosoma cruzi, is endemic to the Americas but has spread worldwide due to migration. Benznidazole is effective, but long-term follow-up efficacy studies with benznidazole are few and they include only small numbers of patients. METHODS: We analyzed data from a retrospective cohort of Chagas disease patients treated with benznidazole at a large tertiary center in Argentina (1980–2019). Treatment response was assessed through clinical, parasitological, and serological follow-up. Parasitemia was evaluated by direct visualization or qPCR. RESULTS:A total of 567 benznidazole-treated patients were identified; 411 were children (median age: 46 months (IQR: 9.5 - 124 months) and 53 adults (median: 26 years, IQR 20 - 34 years) ). At diagnosis, 11/411 (2.68%) of children and 1/53 (1.9%) of adults were symptomatic, all of whom improved after treatment. Baseline parasitemia was detected in 289/445 (64.94%) of patients, and 279/289 (96.54%) had parasitological follow-up for at least three years. Benznidazole dosing was 6.6 mg/kg/day for children and 5.6 mg/kg/day for adults, with median treatment durations of 8 weeks and 31 days, respectively. All patients cleared parasitemia at the end of treatment. Median serological follow-up was 4.8 years for children (IQR: 22.4–111.5 months) and 2.8 years for adults (IQR: 10.3–67.9 months). At one-year follow-up, 38.8% of patients showed >20% reduction in T. cruzi antibody titers, and 29.8% achieved seronegativity, with younger patients converting faster (p < 0.01). CONCLUSIONS: In this Argentinian cohort, Benznidazole was highly effective, leading to sustained parasitemia clearance and declining antibody titers, supporting early treatment initiation.

AIM: Chagas disease (ChD) is a neglected disease affecting approximately 7 million individuals in Latin America. Benznidazole (BZ) is the most commonly used treatment. Therefore, understanding the adverse effects of BZ is crucial for devising targeted monitoring and interventions to enhance patient management. METHODS: A retrospective cohort study of patients with ChD treated with BZ to identify and characterize BZ adverse drug reactions (ADRs). RESULTS: 518 patients were enrolled: 449 children (median age: 4yrs, range 1mo-17.75yrs) and 69 adults (median age: 25yrs, range 18-59). A 75% of pediatric patients received a median dose of BZ of 6.6 mg/kg/day (IQR25–75 = 5.7-7.3) for at least 60 days. Adult patients received a median BZ dose of 5.6 mg/kg/day (IQR25–75 = 5.2-6.1) for a median duration of 31 days (IQR25–75 = 30-60). Overall, 152/518 (29.34%) patients developed BZ-related ADRs, with an incidence of 116/449 (25.83%) in children and 36/69 (52.17%) in adults (OR = 0.32, CI95 = 0.19 to 0.54, p < 0.001). The study identified 240 ADRs, primarily mild to moderate, but severe ADRs occurred in 1.11% of children and 1.45% of adults. The skin was the most affected system in both groups. A 10.23% of patients abandoned treatment (53/518). Adults discontinued treatment more frequently than children (OR = 3.36 CI95 = 1.7 to 6.4, p < 0.001). CONCLUSION: Our study supports the safety of BZ for ChD in children and adults. Avoiding BZ treatment due to safety concerns does not seem to be supported by the evidence.