Air Pollution, Health Coverage, and Global Tuberculosis Trajectories: A Longitudinal Country-Level Analysis with Projections to 2050

Background Tuberculosis burden is declining, but progress remains far below End TB targets. We aimed to identify country-level structural, epidemiological, health-system, and environmental characteristics associated with the burden of tuberculosis among people without HIV—the GBD-classified outcome that excludes HIV-related tuberculosis—and to project disability-adjusted life years (DALYs) to 2050. Methods We linked GBD 2023 estimates with World Bank and World Health Organization indicators for 204 countries in 2000-2023. To evaluate potentially modifiable factors, a within-between model separated characteristics of countries with sustained high burden from changes within the same country. Five-year lagged and annualized-change models assessed temporal patterns, including a sensitivity model additionally adjusting for annualized change in GDP per capita and urbanization. Age-specific country trajectories were partially pooled toward regional trends and projected to 2050 using 2,000 simulations. Results DALYs decreased from 80.1 million in 2000 to 43.6 million in 2023, and the population-adjusted rate fell from 1,306.6 to 542.9 per 100,000. DALY rates were higher with TB/HIV fraction (+52%), undernutrition (+38%), and vulnerable employment (+88%), and lower with universal health coverage (-58%) and treatment coverage (-32%). Improving treatment success and rising PM2.5 tracked faster and slower national declines, respectively, and were the only two of eight temporal predictors to survive false-discovery-rate correction (both adjusted P=0.025); both associations persisted after additional adjustment for annualized change in GDP per capita and urbanization (adjusted P≤0.03). Median DALYs were projected at 38.2 million in 2030, 32.9 million in 2040, and 29.4 million in 2050. Conclusions Current trajectories would leave a large tuberculosis burden through 2050. These ecological findings support prioritizing modifiable structural conditions, including air pollution, alongside treatment performance, and warrant further longitudinal and quasi-experimental investigation to establish causality.