Discrepancy in the transmissibility of multidrug-resistant mycobacterium tuberculosis in urban and rural areas in China

ABSTRACT

The fitness of multidrug-resistant tuberculosis (MDR-TB) is thought to be an important determinant of a strain’s ability to be transmitted. Studies in the laboratory have demonstrated that MDR-TB strains have reduced fitness but the relative transmissibility of MDR-TB versus drug-susceptible (DS) TB strains in human populations remains unresolved. We used data on genomic clustering from our previous molecular epidemiological study in Songjiang (2011-2020) and Wusheng (2009-2020), China, to compare the relative transmissibility of MDR-TB versus DS-TB. Genomic clusters were defined with a threshold distance of 12-single-nucleotide-polymorphisms and the risk for MDR-TB clustering was analyzed by logistic regression. In total, 2212 culture-positive pulmonary TB patients were enrolled in Songjiang and 1289 in Wusheng. The clustering rates of MDR-TB and DS-TB strains were 19.4% (20/103) and 26.3% (509/1936), respectively in Songjiang, and 43.9% (29/66) and 26.0% (293/1128) in Wusheng. The risk of MDR-TB clustering was 2.34 (95% CI 1.38-3.94) times higher than DS-TB clustering in Wusheng and 0.64 (95% CI 0.38-1.06) times lower in Songjiang. Neither lineage 2, compensatory mutations nor rpoB S450L were significantly associated with MDR-TB transmission, and katG S315 T increased MDR-TB transmission only in Wusheng (OR 5.28, 95% CI 1.42-19.21). MDR-TB was not more transmissible than DS-TB in either Songjiang or Wusheng. It appears that the different transmissibility of MDR-TB in Songjiang and Wusheng is likely due to differences in the quality of the local TB control programmes. Suggesting that the most effective way to control MDR-TB is by improving local TB control programmes.

KEYWORDS:

• Multidrug-resistant tuberculosis
• transmissibility
• whole-genome sequencing
• urban and rural China
• TB control programmes

Acknowledgments

We thank the tuberculosis public health teams in the Songjiang District Centre for Disease Control and Prevention and the Wusheng County Centre for Disease Control and Prevention. We also thank Prof. Sebastien Gagneux for his valuable comments on this manuscript.

Authors’ contributions

M.L., Q.J., L.X., C.Y., X.S., C.C., and Q.G. conceived, designed and managed the study. L.L., M.G., Y.J., S.Z., Y.Q., J.H., and X.G. contributed the demographic, clinical and microbiological data. M.L., Q.J., and Y.C. did the data analyses. M.L., Q.J., C.Y., Y.C., H.T., and Q.G. drafted and revised the manuscript. All authors contributed to and gave input to the final article.

Data availability

The datasets used and analyzed during the current study are not accessible online, but may be made available upon written request to the corresponding author. Sequencing data were deposited in the Genome Sequence Archive (https://bigd.big.ac.cn/gsa) under BioProject PRJCA008815 and PRJCA010372.

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 (2017ZX10201302-006), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), and Shanghai Municipal Project for Academic Leaders in Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.