Epidemiologic and Bacterial Factors Facilitating Long-Term Transmission of Multidrug-Resistant Tuberculosis in Shanghai, China

Xiaoyu Lu; Yuan Jiang; Rui Zhang; Yangyi Zhang; Jing Li; Lili Wang; Qi Ye; Renjie Hou; Yixiao Lu; Xi Zhu; Yating Ji; Mingyu Gan; Minjuan Li; Qingyun Liu; Xin Shen; Chongguang Yang

doi:10.1093/cid/ciaf313

Epidemiologic and Bacterial Factors Facilitating Long-Term Transmission of Multidrug-Resistant Tuberculosis in Shanghai, China

Clin Infect Dis. 2025 Jun 18:ciaf313. doi: 10.1093/cid/ciaf313. Online ahead of print.

Authors

Xiaoyu Lu¹, Yuan Jiang², Rui Zhang¹, Yangyi Zhang², Jing Li², Lili Wang², Qi Ye¹, Renjie Hou¹, Yixiao Lu¹, Xi Zhu¹, Yating Ji¹, Mingyu Gan³, Minjuan Li¹, Qingyun Liu^{3

4}, Xin Shen², Chongguang Yang^{1

5

6}

Affiliations

¹ School of Public Health (Shenzhen), Shen Key Laboratory of Pathogen and Biosafety, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Guangdong, P.R. China.
² Division of TB and HIV/AIDS Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, P.R. China.
³ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT, 06511, USA.
⁶ Guangdong Provincial Highly Pathogenic Microorganism Science Data Center, Guangzhou, P.R. China.

PMID: 40576551
DOI: 10.1093/cid/ciaf313

Abstract

Background: Long-term transmission of multidrug-resistant tuberculosis (MDR-TB) challenges TB control by generating new cases and enabling the emergence of extensively resistant strains. We investigated its epidemiologic and bacterial drivers in Shanghai, China.

Methods: We conducted a retrospective study of M. tuberculosis isolates and associated epidemiological data from individuals diagnosed with rifampicin-resistant TB in Shanghai over 14 years (2004-2018). Using whole-genome sequencing, Bayesian reconstruction of transmission trees, and multivariable regression analysis to identify epidemiological and bacterial factors associated with the transmission of MDR-TB.

Results: Between 2004 and 2018, 1,456 individuals in Shanghai were diagnosed with MDR or rifampicin-resistant TB, with whole-genome sequences available for 1,100 isolates. The overall genomic clustering rate was 55.3%, with large clusters (those containing ≥5 cases) accounting for 39.9% of the clustered strains. Risk factors for clustered MDR-TB transmission included local residency (aOR 2.28, 95% CI 1.67-3.11), diagnostic delays ≥2 months (aOR 1.75, 95% CI 1.24-2.47), specific M. tuberculosis sublineages (L2.3.3-L2.3.6), and the rpoB S450L mutation with compensatory mutations (aOR 2.14, 95% CI 1.64-2.78). Large MDR-TB clusters were significantly associated with long-term transmission (>5 years, p<0.001). Long-term transmission clusters correlated with same-street residence, local residency, and MDR-TB strains carrying katG315T, rpoB450L and compensatory mutations.

Conclusions: Despite ample healthcare resources, MDR-TB persists in urban areas due to both epidemiological and bacterial factors. The rpoB S450 mutation with compensatory mutations enhances transmission even in the absence of clear epidemiologic links. Effective control measures must address both epidemiological and bacterial factors.

Keywords: Compensatory mutations; Long-term transmission; Multidrug-resistant tuberculosis; Whole-genome sequencing.

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