Risk and determinants of tuberculosis recurrence: a 12-year population-based cohort study

Tuberculosis recurrence remains a challenge to elimination efforts in high-burden settings. We aimed to estimate the incidence and timing of tuberculosis recurrence and to identify its risk factors to inform post-treatment care.

We conducted a population-based cohort study of tuberculosis survivors successfully treated for a first tuberculosis episode from 2013 through 2024 in São Paulo state, Brazil. Data were obtained from the state tuberculosis surveillance system (TBweb), and deaths were identified through linkage with the national mortality database. We applied competing risks survival analysis to estimate incidence and assess risk factors for recurrence. Covariates included demographic, clinical, behavioral, and social vulnerability indicators, measured at treatment initiation for the first tuberculosis episode. Risk factor models were stratified by age (<15 vs. ≥15 years).

Among 154,579 individuals who completed treatment for a first episode of tuberculosis, we identified 9,464 first recurrences over a median follow-up of 5.4 years (IQR 2.5-8.2). The overall recurrence incidence was 1,127.2 per 100,000 person-years. Rates were highest between 3-12 months after treatment completion, yet recurrence incidence remained over 1,000 per 100,000 person-years in the 2-5 years after treatment completion. In adults, hospitalization (adjusted subdistribution hazard ratio [aSHR] 2.53, 95%CI 2.36-2.71), and incarceration during the initial episode (aSHR 2.30, 2.13-2.48), together with pulmonary tuberculosis as initial diagnosis (aSHR 2.10, 1.87-2.35) were the strongest independent risk factors for recurrence. In children, HIV (aSHR 6.38, 2.64-15.40) was the strongest predictor.

The high and persistent risk of tuberculosis recurrence reinforces the importance of post-treatment care with risk-based follow-up strategies.