Association of tuberculosis infection with the development of active tuberculosis and comorbidities in rural China: a 10-year follow-up results of a population-based, multicentre, prospective study.

Background: In China, there is limited research on the role of recent and long-term infection of in relation to the incidence of pulmonary tuberculosis (PTB), as well as the impact of tuberculosis infection (TBI) on other diseases. A population-based, multicenter prospective study (LATENTTB-NSTM) was implemented since 2013 to assess the prevalence of TBI and to track the development of active disease in rural China. This cohort study provides an opportunity to address these gaps in knowledge.

Methods: In October 2023, all 21,832 participants from rural China who initially participated in the baseline survey of the LATENTTB-NSTM study were invited to take part in the 10-year follow-up survey. The data on the incident PTB and other health concerns including type 2 diabetes mellitus (T2DM), cancers, cardiovascular and cerebrovascular diseases were acquired from medical record or self-reported. The proportion of baseline TBI and newly acquired infection to the incident PTB and the association of baseline TBI status with the incidence of other diseases were analyzed.

Findings: Overall, 21,211 study participants with a sum of 170,152 person-years were included in final analysis. During the 10-year period, a total of 181 incident PTB patients were identified, including 134 patients developed from TBI defined at baseline and 47 patients developed from newly acquired infection during follow-up. The proportion of newly acquired infection during follow-up was statistically pronounced in incident PTB cases diagnosed in the latter 5 years as compared to in the first 5 years of the follow-up period (38·30% (18/47) vs. 21·64% (29/134), p = 0·031). The proportion of baseline TBI was statistically higher in incident PTB cases aged ≥60 years than in those aged <60 years (85·19% (69/81) vs. 65·00% (65/100), p = 0·002). In addition, baseline TBI status was found to be significantly associated with increased risk of incident T2DM, cancers and chronic bronchitis with adjusted hazard ratio of 1·22 (95% confidence interval (CI): 1·04-1·42), 1·81 (95% CI: 1·20-2·72), and 2·94 (95% CI: 1·06-8·15), respectively. The risk of incident T2DM slightly increased along with the increasing intensity of the immune response in TBI testing at baseline.

Interpretation: As compared to recent infection, TBI remains the dominating contributor of incident PTB in rural China. Alongside efforts to systematically manage infectious cases and close contacts, preventive treatment targeting individuals under high risk of developing active diseases from TBI is crucial for achieving rapid declining of PTB incidence. Moreover, the possible influence of TBI on the other health conditions further underscores the importance of TBI management from a new perspective.

Funding: The CAMS Innovation Fund for Medical Sciences and the National Natural Science Foundation of China.