Cross-sectional Whole-genome Sequencing and Epidemiological Study of Multidrug-resistant Mycobacterium tuberculosis in China.
Cross-sectional Whole-genome Sequencing and Epidemiological Study of Multidrug-resistant Mycobacterium tuberculosis in China.
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中国耐多药结核杆菌横断面全基因组测序及流行病学研究
DOI：
10.1093/cid/ciy883
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发表时间：
2019-07-18
期刊：
影响因子：
--
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Huang H;Ding N;Yang T;Li C;Jia X;Wang G;Zhong J;Zhang J;Jiang G;Wang S;Zong Z;Jing W;Zhao Y;Xu S;Chen F
摘要背景在全球耐多药结核病负担第二高的国家中国，耐多药结核病的增加严重阻碍了结核病的预防和控制。全国首个耐药结核病监测项目为全面调查中国耐多药结核病的流行病学/耐药特征、潜在耐药突变和有效人群变化提供了机会。方法对调查期间收集的4600份具有代表性的结核分枝杆菌阳性痰标本(31个省70个县)的357株耐多药菌株进行测序。使用18种抗结核药物进行了药敏试验，代表了迄今为止最全面的耐药情况。我们使用3种统计方法和1种机器学习方法来识别耐药基因/单核苷酸多态(SNPs)。我们使用贝叶斯天际线分析来调查有效种群数量的变化。结果中国7个行政区的流行/耐药特征表现出不同的多药耐药谱、共耐药模式、首选联合用药和推荐用药方案。这些因素不仅反映了中国耐多药结核病严重的多药耐药和药物滥用现象，而且对制定合理的耐多药方案具有重要意义。进一步的研究发现了86个耐药基因/基因间隔区/SNPs(58个新的)，为耐多药结核病的诊断和治疗提供了潜在的靶点。此外，中国耐多药结核病的有效人口在1993-2000年期间呈现出强劲的增长，反映了中国国内的社会经济转型。这种扩张现象在2000年后受到了抑制，这可能是由于诊断/治疗技术的进步和政府的支持。结论本研究结果为提高中国对耐多药结核病的认识提供了重要参考，对实现耐多药结核病防治的精准医学目标具有重要意义。
Abstract Background The increase in multidrug-resistant tuberculosis (MDR-TB) severely hampers tuberculosis prevention and control in China, a country with the second highest MDR-TB burden globally. 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. Methods 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. Results 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 1993–2000, 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. Conclusions 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.
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10.7
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通讯作者：
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