Differential effects of PM2.5 constituents on tuberculosis infection and disease progression in 40,379 student close contacts

RATIONALE: Outdoor PM2.5 has been increasingly implicated in tuberculosis, yet evidence has largely focused on total PM2.5 mass and has usually considered Mycobacterium tuberculosis (M. tuberculosis) infection and active tuberculosis separately. Whether specific PM2.5 chemical constituents differ in their associations with infection and subsequent progression to active disease remains unclear. OBJECTIVES: To assess the associations of PM2.5 and five major constituents with M. tuberculosis infection and subsequent progression to active tuberculosis within the same high-risk population. METHODS: We conducted two complementary analyses among student close contacts of tuberculosis patients from 458 schools in 12 cities in eastern China during 2020-2024. Daily residential outdoor exposures were assigned from daily modeled estimates of PM2.5 and five major constituents (sulfate, nitrate, ammonium, organic matter, and black carbon) on an approximately 10-km grid, which were interpolated to geocoded addresses. We first assessed associations between exposure averaged over the five years preceding contact screening and M. tuberculosis infection identified by the ESAT6-CFP10 skin test during the contact investigation. We then followed infected students identified at the contact screening to examine associations between time-varying annual exposure and progression to active tuberculosis. RESULTS: Among 40,379 students, 1,269 had M. tuberculosis infection, and 70 infected students progressed to active tuberculosis during follow-up. Each 1-µg/m3 increase in PM2.5 was associated with higher infection risk (OR: 1.043; 95% CI: 1.018, 1.068) and progression risk (HR: 1.094; 95% CI: 1.010, 1.185). All five constituents were positively associated with infection (ORs: 1.156-5.390). Sulfate, nitrate, and ammonium were also positively associated with progression to active tuberculosis (HRs: 1.462-2.680). The findings remained generally consistent in sensitivity analyses. CONCLUSIONS: In this large multi-city close-contact study, PM2.5 was associated with both M. tuberculosis infection and subsequent progression to active tuberculosis. Three secondary inorganic aerosol (SIA) constituents, namely sulfate, nitrate, and ammonium, showed the most consistent association patterns across the two outcomes. These findings reinforce the importance of overall PM2.5 control and support further evaluation of coordinated reductions in SIA precursor emissions.