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ABSTRACT
China, with the third largest share of global tuberculosis cases, faces a substantial challenge in its healthcare system as a result of the high burden of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). This study employs a genomic epidemiological approach to assess recent tuberculosis transmissions between individuals, identifying potential risk factors and discerning the role of transmitted resistant isolates in the emergence of drug-resistant tuberculosis in China. We conducted a population-based retrospective study on 5052 Mycobacterium tuberculosis (MTB) isolates from 70 surveillance sites using whole genome sequencing (WGS). Minimum spanning tree analysis identified resistance mutations, while epidemiological data analysis pinpointed transmission risk factors. Of the 5052 isolates, 23% (1160) formed 452 genomic clusters, with 85.6% (387) of the transmissions occurring within the same counties. Individuals with younger age, larger family size, new cases, smear positive, and MDR/RR were at higher odds for recent transmission, while higher education (university and above) and occupation as a non-physical workers emerged as protective factors. At least 61.4% (251/409) of MDR/RR-TB were likely a result of recent transmission of MDR/RR isolates, with previous treatment (crude OR = 2.77), smear-positive (cOR = 2.07) and larger family population (cOR = 1.13) established as risk factors. Our findings highlight that local transmission remains the predominant form of TB transmission in China. Correspondingly, drug-resistant tuberculosis is primarily driven by the transmission of resistant tuberculosis isolates. Targeted interventions for high-risk populations to interrupt transmission within the country will likely provide an opportunity to reduce the prevalence of both tuberculosis and drug-resistant tuberculosis.
Acknowledgments
We thank members of the Working Group on National Tuberculosis Drug Resistance Surveillance. We also thank the tireless contributions of staff in the Ministry of Health, provincial health bureaus, provincial CDCs, and local CDCs in undertaking the tuberculosis drug-resistant prevalence surveys. We thank Dr. Courtney M Yuen from Harvard Medical School for her valuable comments on this manuscript. We thank Mr. Jasper Luong for his help in language modification. All M. tuberculosis genomes (n = 5052) data is deposited in China National Microbiology Data Center (NMDC) with accession numbers NMDC10018526.
Author contributions
Y Zhao, DL, LZ, and QW contributed to the study design, DL, WH, PH, HZ, XH, SW, BZ, XO, YS, ZS, LMei and LL collected the data and did the laboratory testing, LM, SW and YZ help do bioinformatics analysis, HF, YL and DL did the data analysis and prepared the report for publication.
Disclosure statement
No potential conflict of interest was reported by the author(s).