Chagas disease and all-cause mortality in a community-based cohort in Colombia

Background Chagas disease (CD) is a leading cause of cardiomyopathy in Latin America, yet prospective community-based data on its association with all-cause mortality remain scarce. Prior evidence is dominated by referral-based cohorts subject to selection bias, and most studies originate from Brazil, limiting generalizability to other endemic settings. We investigated the association between serologically confirmed CD and all-cause mortality, and assessed potential effect modification by age, in a large community-based cohort from northeastern Colombia. Methods We analysed data from the ANTORCHA prospective cohort, which enrolled adults from Chagas-endemic municipalities in Colombia, between 2015 and 2025. CD status was defined by two concordant serological assays. The primary outcome was all-cause mortality, ascertained through periodic follow-up contacts and vital statistics registries. Cox proportional hazards models were fitted using a hierarchical adjustment strategy across four nested models. Effect modification by age group (<60 vs. ≥60 years) was evaluated using multiplicative interaction terms and likelihood ratio tests. Multiple imputation by chained equations, inverse probability of treatment weighting, and exclusion of early follow-up were performed as sensitivity analyses. Results Among 1,509 participants (314 Chagas-positive; median age 50.5 years; 41.8% male), 81 deaths occurred over a median follow-up of 5.6 years. After full multivariate adjustment, CD was not associated with mortality overall (HR 1.02, 95% CI 0.61–1.72). However, significant age effect modification was identified (interaction p=0.007). Among participants aged <60 years, CD was independently associated with a nearly five-fold increase in mortality (HR 4.96, 95% CI 1.80–13.71), whereas no association was observed among those aged ≥60 years (HR 0.73, 95% CI 0.43–1.22). Results were consistent across all sensitivity analyses. Conclusions In this community-based endemic cohort, CD conferred a substantial excess mortality risk selectively among younger and middle-aged adults, while the overall association was null. These findings underscore the importance of age-stratified risk assessment and support intensified cardiovascular surveillance in younger Chagas-positive individuals.