High proportion of tuberculosis transmission among social contacts in rural China: a 12-year prospective population-based genomic epidemiological study

ABSTRACT

Tuberculosis (TB) is more prevalent in rural than urban areas in China, and delineating TB transmission patterns in rural populations could improve TB control. We conducted a prospective population-based study of culture-positive pulmonary TB patients diagnosed between July 1, 2009 and December 31, 2020 in two rural counties in China. Genomic clusters were defined with a threshold distance of 12-single-nucleotide-polymorphisms, based on whole-genome sequencing. Risk factors for clustering were identified by logistic regression. Transmission links were sought through epidemiological investigation of genomic-clustered patients. Of 1517 and 751 culture-positive pulmonary TB patients in Wusheng and Wuchang counties, respectively, 1289 and 699 strains were sequenced. Overall, 624 (31.4%, 624/1988) patients were grouped into 225 genomic clusters. Epidemiological links were confirmed in 41.8% (196/469) of clustered isolates, including family (32.7%, 64/196) and social contacts (67.3%, 132/196). Social contacts were generally with relatives, within the community or in shared aggregated settings outside the community, but the proportion of clustered contacts in each category differed between the two sites. The time interval between diagnosis of student cases and contacts was significantly shorter than family and social contacts, probably due to enhanced student contact screening. Transmission of multidrug-resistant (MDR) strains was likely responsible for 81.4% (83/102) of MDR-TB cases, with minimal acquisition of additional resistance mutations. A large proportion of TB transmission in rural China occurred among social contacts, suggesting that active screening and aggressive contact tracing could benefit TB control, but contact screening should be tailored to local patterns of social interactions.

KEYWORDS:

• Tuberculosis
• transmission
• social contacts
• whole-genome sequencing
• rural China

Acknowledgments

We thank the tuberculosis public health teams in the Wusheng County Centre for Disease Control and Prevention and the Wuchang City Centre for Tuberculosis Control and Prevention.

Authors’ contributions

M.L., Q.J., C.Y., L.X., F.L., C.C., and Q.G. conceived, designed and managed the study. S.Z. (Sheng Zhong), X.S., Y.P., S.Z. (Shu Zhang), M.G., and Y.Q. contributed the demographic, clinical and microbiological data. M.L., M.G., Y.P., S.Z. (Sheng Zhong), X.S., and P.M. contributed to the epidemiological investigations. M.L., Q.M., Q.J., and P.M. did the data analyses. M.L., Q.J., C.Y., H.T., and Q.G. drafted and revised the manuscript. All coauthors reviewed and approved the final manuscript before submission.

Data availability

Sequencing data were deposited in the Genome Sequence Archive (https://bigd.big.ac.cn/gsa) under BioProject PRJCA008815 and PRJCA008816. De-identified participant data from the study will be made available with publication to medical researchers on a not for profit basis by email request to the corresponding author for the purposes of propensity matching or meta-analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

The study was approved by the institutional review board of Biomedical Sciences, Fudan University and all enrolled patients provided written informed consent.

Additional information

Funding

This study was made possible by the generous support of the National Science and Technology Major Project of China [grant no 2017ZX10201302-006], Natural Science Foundation of China [grant no 81661128043] and Shanghai Municipal Science and Technology Major Project [grant no 2018ZX10715-012]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.