Citywide transmission of MDR-TB under China’s rapid urbanization: a retrospective population-based genomic spatial epidemiological study

BACKGROUND: Population movement could extend multidrug-resistant tuberculosis (MDR-TB) transmission and complicate its global prevalence. We sought to identify the high-risk populations and geographic sites of MDR-TB transmission in Shenzhen, the most common destination for internal migrants in China. METHODS: We performed a population-based, retrospective study of patients who were diagnosed with MDR-TB in Shenzhen during 2013-2017. By defining genomic clusters with a threshold of 12 SNP distance based on whole-genome sequencing their clinical strains, the clustering rate was calculated to evaluate the level of recent transmission. Risk factors for MDR-TB transmission were identified by multivariable logistic regression. To further delineate the epidemiological links, we invited the genomic-clustered patients to an in-depth social network investigation. RESULTS: In total, 105 (25.2%) of the 417 enrolled MDR-TB patients were grouped into 40 genome clusters, suggesting recent transmission of MDR strains. The adjusted risk for students to have a clustered strain was 4.05 (95% confidential intervals [CI], 1.06-17.0) times greater than other patients. The majority (70%, 28/40) of the genomic clusters involved patients who lived in different districts, with residences separated by an average of 8.76 kilometers. Other than household members, confirmed epidemiological links were also identified among classmates and workplace colleagues. CONCLUSIONS: These findings demonstrate that local transmission of MDR-TB is a serious problem in Shenzhen city. While most transmission occurred between people who lived distant from each other, there was clear evidence that transmission occurred in schools and workplaces, which should be included as targeted sites for active case finding.