Chagas-specific death and competing risk of mortality in Chile: A nationwide retrospective cohort study, 2007-2021

Abstract Background Chagas disease (CD) in Chile has shifted towards a post-vector-control, ageing-cohort scenario in which chronic sequelae increasingly shape outcomes. We quantified Chagas-specific mortality and associated factors using competing-risks methods. Methods We conducted a nationwide retrospective cohort study of confirmed CD cases notified in Chile during 2007–2021, linked to mortality and hospital discharge records. Chagas-specific death was the primary outcome, with other-cause death as a competing event. We estimated cumulative incidence functions (CIFs), applied Gray’s test, and fitted Fine–Gray models for subdistribution hazard ratios (sHRs). Complementary cause-specific Cox models included hospitalisation as time-fixed and time-varying markers of clinical severity. Models accounted for the national cohort structure and competing mortality. Results Among 17,508 individuals, 261 (1.49%) died from CD and 1,021 (5.83%) from other causes. Ten-year CIF was higher in men (2.66%) and increased with age, reaching 4.80% at 65–74 years and 8.89% at ≥75 years. CIF was highest for chronic digestive disease (B57.3, 6.49%) and elevated for chronic cardiac disease (B57.2, 2.93%) compared with Z22.8 (1.47%; Gray p<0.005). In adjusted Fine–Gray models, mortality was associated with each 10-year age increase (sHR 2.31), male sex (sHR 1.47), B57.2 (sHR 1.92), and B57.3 (sHR 3.36). Cause-specific Cox models showed a graded association between recurrent hospitalisations and Chagas-specific death (≥3 admissions: HR 83.94), consistent with advanced clinical deterioration. Conclusions Although Chagas-specific death was uncommon, it was concentrated among identifiable high-risk groups. Risk-stratified chronic care and structured follow-up should prioritise patients with organ involvement or recurrent hospitalisation.