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The first nationwide drug-resistant tuberculosis surveillance program provides an opportunity to comprehensively investigate the epidemiological\/drug-resistance characteristics, potential drug-resistance mutations, and effective population changes of Chinese MDR-TB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We sequenced 357 MDR strains from 4600 representative tuberculosis-positive sputum samples collected during the survey (70 counties in 31 provinces). Drug-susceptibility testing was performed using 18 anti-tuberculosis drugs, representing the most comprehensive drug-resistance profile to date. We used 3 statistical and 1 machine-learning methods to identify drug-resistance genes\/single-nucleotide polymorphisms (SNPs). We used Bayesian skyline analysis to investigate changes in effective population size.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Epidemiological\/drug-resistance characteristics showed different MDR profiles, co-resistance patterns, preferred drug combination\/use, and recommended regimens among 7 Chinese administrative regions. These factors not only reflected the serious multidrug co-resistance and drug misuse but they were also potentially significant in facilitating the development of appropriate regimens for MDR-TB treatment in China. Further investigation identified 86 drug-resistance genes\/intergenic regions\/SNPs (58 new), providing potential targets for MDR-TB diagnosis and treatment. In addition, the effective population of Chinese MDR-TB displayed a strong expansion during 1993\u20132000, reflecting socioeconomic transition within the country. The phenomenon of expansion was restrained after 2000, likely attributable to the advances in diagnosis\/treatment technologies and government support.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide an important reference and improved understanding of MDR-TB in China, which are potentially significant in achieving the goal of precision medicine with respect to MDR-TB prevention and treatment.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciy883","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T19:29:48Z","timestamp":1539113388000},"page":"405-413","source":"Crossref","is-referenced-by-count":56,"title":["Cross-sectional Whole-genome Sequencing and Epidemiological Study of Multidrug-resistant Mycobacterium tuberculosis in China"],"prefix":"10.1093","volume":"69","author":[{"given":"Hairong","family":"Huang","sequence":"first","affiliation":[{"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Ding","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics"},{"name":"University of Chinese Academy of Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuidan","family":"Li","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics"},{"name":"University of Chinese Academy of Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmiao","family":"Jia","sequence":"additional","affiliation":[{"name":"Central Research Laboratory, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guirong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhong","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanglu","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojing","family":"Zong","sequence":"additional","affiliation":[{"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jing","sequence":"additional","affiliation":[{"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences"},{"name":"Chinese Academy of Sciences Key Laboratory of Genomic and Precision Medicine, Beijing Institute of 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"key":"2019071803460934700_CIT0001","unstructured":"World Health Organization. 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Rapid communication: key changes to treatment of multidrug- and rifampicin-resistant tuberculosis (MDR\/RR-TB). Available at: http:\/\/www.who.int\/tb\/publications\/2018\/rapid_communications_MDR\/en\/. Accessed 02 October 2018."},{"key":"2019071803460934700_CIT0031","unstructured":"Word Health Organization. Frequently asked questions on bedaquiline. Available at: http:\/\/www.who.int\/tb\/challenges\/mdr\/bedaquilinefaqs\/en\/. Accessed 02 October 2018."},{"key":"2019071803460934700_CIT0032","unstructured":"National Statistics Bureau of the People\u2019s Republic of China. The China statistical yearbook. Available at: http:\/\/www.stats.gov.cn\/tjsj\/ndsj\/. 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