Abstract
BACKGROUND: Targeted strategies for marginalized populations, including high-altitude communities, are crucial for TB elimination. This study assessed TB infection (TBI) prevalence across altitudinal gradients and evaluated altitude-dependent risk factors in Tibet, China. METHODS: A cross-sectional survey by multistage stratified random cluster sampling was conducted using ESAT6-CFP10 skin test (C-TST), symptom screening, chest X-rays, and bacteriological tests. The influencing factors of C-TST positivity were analyzed via generalized linear mixed models (GLMMs) and Boruta algorithm feature ranking. The TBI prevalence was estimated using WHO-recommended methods. Causal mediation analysis was performed to explore mediating variables contributing to association between altitude and TBI prevalence. RESULTS: The estimated TBI prevalence in Tibet was 20.7% (95% CI 14.3%-33.0%). Residential altitude was the strongest predictor of C-TST positivity (aOR=0.53, p<0.001). The interaction analyses revealed significant modification effects of both smoking status (interaction p=0.0065) and BCG vaccination (interaction p=0.028) on the altitude-C-TST positivity association. Mediation analysis indicated that the observed inverse relationship between study site altitude and crude TBI prevalence was mediated by per capita land space (IE= -6.29e-05, p=0.04). The prevalence of TBI in very high-altitude (VHA) areas was 12.8%, approximately one-third of that in high-altitude (HA) areas (35.0%). Stratified analyses revealed distinct risk profiles - occupational exposures predominated in HA regions, whereas physiological factors (age, BMI, smoking) drove positivity in VHA areas. CONCLUSION: Our results suggest that TB infection is significantly associated with altitude, necessitating accelerated research into plateau-specific disease mechanisms and the development of targeted public health strategies tailored to local socio-medical conditions. This integrated biological and socio-economic approach is essential to overcome the compounded vulnerabilities of high-altitude populations and ensure that China equitably achieves its goal of eliminating TB.