A Whole-Genome Sequencing-Based Study to Delineate the Risk and Characteristics of Tuberculosis Transmission in an Insular Population Over 10 Years in Shanghai

BACKGROUND: Tuberculosis (TB) has remained a tough problem in China. This study aims to identify the risk of tuberculosis transmission and to assess its characteristics. METHODS: We performed a molecular epidemiological study for patients with culture-positive Mycobacterium tuberculosis (M. tuberculosis) in Shanghai, from 2009 to 2018. Demographic information was obtained from the Tuberculosis Information Management System. Whole-genome sequencing (WGS) was conducted with a threshold of 12 single-nucleotide polymorphisms (SNPs) to distinguish the genomic cluster. To analyze the characteristics of TB transmission, the contact investigation for clustered cases was performed. RESULTS: In total, 94 (27.25%) of the 345 enrolled patients were grouped into 42 genomic clusters, indicating local transmission of M. tuberculosis strains. Compared to a health system delay <14 days, patients with a health system delay ≥14 days [adjusted odds ratios (AOR) = 2.57, 95% confidence interval (CI): 1.34–4.95] were more likely to be clustered. Patients under 65 years old (AOR = 3.11, 95% CI: 1.76–5.49), residents (AOR = 2.43, 95% CI: 1.18–4.99), and Beijing genotype strains (AOR = 3.35, 95% CI: 1.32–8.53) were associated with increased risk of clustering. Interestingly, patients with resistance to isoniazid (AOR = 2.36, 95% CI: 1.15–4.88) had a higher risk of transmission. Sixteen confirmed/probable epidemiological links were identified. Local transmission of imported cases and household transmission were prominent. CONCLUSION: Health system delay is a crucial factor for TB transmission. Patients with resistance to isoniazid should be priority targets for contact investigation to reduce transmission.