Genomic and Spatial Analysis on the Recent Transmission of Mycobacterium tuberculosis in Eastern China: A 10-Year Retrospective Population-Based Study

Xiwen Yin,1,&ast; Qiang Zhang,1,&ast; Yuting Wang,1 Bilin Tao,1 Xiaolong Zhang,2 Jinyan Shi,3 Xiaowei Deng,1 Jianming Wang1,4,5 1Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing, 211166, People’s Republic of China; 2Department of Tuberculosis Control, Center for Disease Control and Prevention, Suzhou, 215000, People’s Republic of China; 3Department of Clinical Laboratory, The Fourth People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China; 4Department of Tuberculosis, The Third People’s Hospital of Changzhou, Changzhou, 215000, People’s Republic of China; 5National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianming Wang, Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing, 211166, People’s Republic of China, Tel +86-25-86868414, Email [email protected]: Understanding the mode of Mycobacterium tuberculosis (M. tuberculosis) transmission is crucial for disease prevention and control. Compared to traditional genotyping methods, whole genome sequencing (WGS) provides higher resolution and comprehensive genetic information, enabling the tracing of infection sources and determining of transmission routes to resolve extensive tuberculosis (TB) outbreaks. We conducted a ten-year study on the transmission of M. tuberculosis in a population in eastern China.Patients and Methods: We selected Lianyungang, an eastern city in China, as the study site. Patients diagnosed with active pulmonary TB from 2011 to 2020 were enrolled as the study subjects. We isolated and sequenced 2252 M. tuberculosis. Strains with pairwise genetic distances of less than 12 single nucleotide polymorphisms were defined as genomic clusters and which were considered recent transmissions. Kernel density estimation and K-function analysis were applied to explore the spatial distribution of recently transmitted strains.Results: After excluding non-tuberculous mycobacteria and duplicated samples, 2114 strains were included in the final analysis. These strains comprised lineage 2 (1593, 75.35%) and 4 (521, 24.65%). There were 672 clustered strains, with a recent transmission rate of 31.79%. The logistic regression model showed that the risk of recent transmission was high in students [adjusted odds ratio (aOR): 2.68, 95% confidence interval (CI): 1.63– 4.49, P< 0.001] and people infected with L2.2.1 strains (aOR: 1.59, 95% CI: 1.20– 2.12). Higher spatial aggregation of TB transmission has been concentrated in Haizhou, Donghai, and Guanyun for the past 10 years. Three outbreaks affecting 46 patients were spatially spaced, with 11 to 23 persons each. Different groups exhibited varying geographic distances between the initial and later cases.Conclusion: There are areas with a high risk of transmission for M. tuberculosis in the research site, and the risk varies among different populations. Accurate prevention strategies targeted at specific regions and key populations can help curb the prevalence of TB.Keywords: tuberculosis, transmission, cluster, whole genome sequencing, spatial analysis