气候变化领域集成服务门户(CCPortal): The Evolution and Transmission Dynamics of Multidrug-Resistant Tuberculosis in an Isolated High-Plateau Population of Tibet, China

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DOI	10.1128/spectrum.03991-22
	The Evolution and Transmission Dynamics of Multidrug-Resistant Tuberculosis in an Isolated High-Plateau Population of Tibet, China
	Jiang, Qi; Liu, Hai-Can; Liu, Qing-Yun; Phelan, Jody E.; Tao, Feng-Xi; Zhao, Xiu-Qin; Wang, Jian; Glynn, Judith R.; Takiff, Howard E.; Clark, Taane G.; Wan, Kang-Lin; Gao, Qian
发表日期	2023
ISSN	2165-0497
卷号	11 期号:2
英文摘要	On the Tibetan Plateau, most tuberculosis is caused by indigenous Mycobacterium tuberculosis strains with a monophyletic structure and high-level drug resistance. This study investigated the emergence, evolution, and transmission dynamics of multidrug-resistant tuberculosis (MDR-TB) in Tibet. The whole-genome sequences of 576 clinical strains from Tibet were analyzed with the TB-profiler tool to identify drug-resistance mutations. The evolution of the drug resistance was then inferred based on maximum-likelihood phylogeny and dated trees that traced the serial acquisition of mutations conferring resistance to different drugs. Among the 576 clinical M. tuberculosis strains, 346 (60.1%) carried at least 1 resistance-conferring mutation and 231 (40.1%) were MDR-TB. Using a pairwise distance of 50 single nucleotide polymorphisms (SNPs), most strains (89.9%, 518/576) were phylogenetically separated into 50 long-term transmission clusters. Eleven large drug-resistant clusters contained 76.1% (176/231) of the local multidrug-resistant strains. A total of 85.2% of the isoniazid-resistant strains were highly transmitted with an average of 6.6 cases per cluster, of which most shared the mutation KatG Ser315Thr. A lower proportion (71.6%) of multidrug-resistant strains were transmitted, with an average cluster size of 2.9 cases. The isoniazid-resistant clusters appear to have undergone substantial bacterial population growth in the 1970s to 1990s and then subsequently accumulated multiple rifampicin-resistance mutations and caused the current local MDR-TB burden. These findings highlight the importance of detecting and curing isoniazid-resistant strains to prevent the emergence of endemic MDR-TB.IMPORTANCE Emerging isoniazid resistance in the 1970s allowed M. tuberculosis strains to spread and form into large multidrug-resistant tuberculosis clusters in the isolated plateau of Tibet, China. The epidemic was driven by the high risk of transmission as well as the potential of acquiring further drug resistance from isoniazid-resistant strains. Eleven large drug-resistant clusters consisted of the majority of local multidrug-resistant cases. Among the clusters, isoniazid resistance overwhelmingly evolved before all the other resistance types. A large bacterial population growth of isoniazid-resistant clusters occurred between 1970s and 1990s, which subsequently accumulated rifampicin-resistance-conferring mutations in parallel and accounted for the local multidrug-resistant tuberculosis burden. The results of our study indicate that it may be possible to restrict MDR-TB evolution and dissemination by prioritizing screening for isoniazid (INH)-resistant TB strains before they become MDR-TB and by adopting measures that can limit their transmission. Emerging isoniazid resistance in the 1970s allowed M. tuberculosis strains to spread and form into large multidrug-resistant tuberculosis clusters in the isolated plateau of Tibet, China. The epidemic was driven by the high risk of transmission as well as the potential of acquiring further drug resistance from isoniazid-resistant strains.
关键词	tuberculosis multidrug-resistant tuberculosis (MDR-TB)whole-genome sequencing (WGS)drug resistance evolution
英文关键词	MYCOBACTERIUM-TUBERCULOSIS; EMERGENCE; HISTORY; SPREAD
WOS研究方向	Microbiology
WOS记录号	WOS:000948435500001
来源期刊	MICROBIOLOGY SPECTRUM
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/283000
作者单位	Wuhan University; Chinese Center for Disease Control & Prevention; National Institute for Communicable Disease Control & Prevention, Chinese Center for Disease Control & Prevention; Harvard University; Harvard T.H. Chan School of Public Health; University of London; London School of Hygiene & Tropical Medicine; University of London; London School of Hygiene & Tropical Medicine; Venezuelan Institute Science Research; The Third People's Hospital of Shenzhen
推荐引用方式 GB/T 7714	Jiang, Qi,Liu, Hai-Can,Liu, Qing-Yun,et al. The Evolution and Transmission Dynamics of Multidrug-Resistant Tuberculosis in an Isolated High-Plateau Population of Tibet, China[J],2023,11(2).
APA	Jiang, Qi.,Liu, Hai-Can.,Liu, Qing-Yun.,Phelan, Jody E..,Tao, Feng-Xi.,...&Gao, Qian.(2023).The Evolution and Transmission Dynamics of Multidrug-Resistant Tuberculosis in an Isolated High-Plateau Population of Tibet, China.MICROBIOLOGY SPECTRUM,11(2).
MLA	Jiang, Qi,et al."The Evolution and Transmission Dynamics of Multidrug-Resistant Tuberculosis in an Isolated High-Plateau Population of Tibet, China".MICROBIOLOGY SPECTRUM 11.2(2023).