Long-Term Parasitological Clearance and Cardiac Progression in Trypanosoma cruzi TcI: A Phase-Stratified Cohort from Colombia

infection are heterogeneous, and the determinants of post-treatment parasitological dynamics and cardiac progression remain incompletely characterized, particularly in TcI-predominant regions. This study assessed, in both the acute phase and the indeterminate chronic form, the association between TcI infection and molecular clearance kinetics, cardiac progression, and the prognostic value of early molecular response. An ambispective cohort in Colombia included patients with acute or indeterminate chronic infection followed between 2000 and 2023. Sustained clearance was defined as two consecutive negative quantitative polymerase chain reaction results obtained at separate visits. Time-to-event analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models. TcI infection was consistently associated with delayed molecular clearance in both clinical presentations. Although long-term clearance was achieved in most patients, TcI infection was independently associated with a higher risk of cardiac progression. In contrast, quantitative polymerase chain reaction negativity at 12 months was associated with reduced subsequent progression risk, indicating that sustained molecular response is a clinically meaningful prognostic marker. Collectively, these findings support the incorporation of early molecular monitoring into risk-stratified follow-up strategies in TcI-predominant settings and reinforce the need for phase-specific clinical management approaches.