Abstract:

Objective: To explore the association between the magnitude of tuberculin skin test (TST) reactions and the risk of active pulmonary tuberculosis (PTB) among senior high school students, so as to provide scientific evidence for optimizing school-based PTB screening strategies. Methods: A prospective cohort study was conducted. From September to December 2022, stratified random cluster sampling was adopted to recruit 27339 Grade 1 and Grade 2 senior high school students from 15 administrative districts of Chongqing to establish the study cohort. All participants were followed up for 2 years to monitor incident active PTB. Cox proportional hazards regression models were used to analyze the association and dose-response relationship between TST reaction intensity and PTB risk. Results: Among the 27339 participants, 15641 (57.21%) had negative TST results, 3352 (12.26%) mild positive reactions, 4455 (16.30%) moderate positive reactions, and 3891 (14.23%) strong positive reactions. The total person-years of observation were 54663. A total of 35 new active PTB cases were identified, with an overall incidence density of 64.03/100000 person-years and a 2-year cumulative incidence of 128.02/100000. Both incidence density and 2-year cumulative incidence rose markedly as TST reaction intensity increased. Significant differences were observed in the distribution of TST reaction grades across subgroups stratified by gender, school type and regional epidemic level (χ²=32.928, 146.846, 318.985, all P<0.001). Among the 3891 students with strong TST positivity, males accounted for 49.78% (1937 students) and females 50.22% (1954 students); 55.69% (2167 students) attended public schools and 44.31% (1724 students) private schools; 48.34% (1881 students) resided in high-burden areas and 51.66% (2010 students) in medium-burden areas. In terms of disease onset timing, the peak incidence in the strong-positive and moderate-positive groups occurred within the first year of follow-up (179.90/100000 (7/3891) and 112.23/100000 (5/4455), respectively), while the peak for the negative and mild-positive groups appeared in the second year (70.33/100000 (11/15641) and 149.16/100000 (5/3352), respectively). Multivariate Cox regression revealed that students with strong TST positivity had a 2.470 (95%CI: 1.065-5.736)-fold higher risk of developing PTB compared with TST-negative students. Each 1 mm increase in the mean induration diameter corresponded to a 5.1% elevation in disease risk (HR=1.051, 95%CI: 1.018-1.086). Stratified analysis demonstrated that the strongest association between strong TST positivity and PTB risk was found in the medium epidemic burden subgroup (HR=4.983, 95%CI: 1.115-22.266). Conclusion: Strong TST positivity is an independent risk factor for active PTB among senior high school students, with a clear dose-response relationship and distinct temporal distribution of disease onset. Tiered and categorized management strategies are recommended for students with varying TST reaction intensities.

Key words: Skin tests, Students, Tuberculosis, pulmonary, Incidence, Factor analysis, statistical