Transmission dynamics and attributable burden of tuberculosis among young and middle-aged adults in urban Shanghai: a genomic epidemiology study.

BACKGROUND

China remains a high tuberculosis (TB) burden country, and large urban centers such as Shanghai continue to face persistent transmission challenges driven by high population mobility. Whole-genome sequencing (WGS) provides high-resolution discrimination between recent transmission and reactivation; however, evidence at the district level remains limited. This study aimed to integrate WGS with epidemiological data to characterize local TB transmission dynamics in Xuhui District, Shanghai, and to identify demographic risk factors for recent transmission.

METHODS

A retrospective study was conducted among culture-positive pulmonary TB cases diagnosed between August 2021 and February 2025. WGS was performed for all available Mycobacterium tuberculosis isolates, and genomic clusters were defined using a threshold of ≤12 single-nucleotide polymorphisms. Epidemiological links were assessed through routine field investigations. Multivariable Firth penalized logistic regression and population attributable fraction (PAF) analyses were used to identify demographic predictors of recent transmission.

RESULTS

Among 170 genotyped patients, the Beijing lineage predominated (90.0%, 153/170). Fluoroquinolone resistance mutations were detected in 12.4% of strains. Demographic disparities in sex and age were observed between local and migrant residents (both p < 0.05). Six genomic clusters involving 17 patients (10.0%) were identified, and 50% of clusters contained at least one student case. Field investigations revealed close spatial proximity among clustered cases, including one pair residing within 50 meters. Multivariate analysis identified younger age as an independent correlate of genomic clustering. Compared with patients aged ≥45 years, the adjusted odds ratios for clustering were 42.75 (95% CI: 5.79-315.50) for those aged 15-24 years and 18.06 (95% CI: 3.76-86.73) for those aged 25-44 years (both p < 0.001). Notably, the joint PAF for individuals aged 15-44 years was 88.69%, with the 25-44-year age group accounting for the largest share of clustered cases (52.9%).

CONCLUSION

Recent TB transmission in Xuhui District was predominantly driven by younger and middle-aged populations. Although students represent a high-risk subgroup, the broader working-age population contributed most to the overall transmission burden. These findings highlight the importance of integrating school-based interventions with community-level strategies targeting the active workforce in order to effectively interrupt transmission.