Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation.
Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation.
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中国上海多重耐药结核分枝杆菌的传播：利用全基因组测序和流行病学调查的回顾性观察研究。
DOI：
10.1016/s1473-3099(16)30418-2
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Gao Q
中科院分区：
文献类型：
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作者：
Yang C;Luo T;Shen X;Wu J;Gan M;Xu P;Wu Z;Lin S;Tian J;Liu Q;Yuan Z;Mei J;DeRiemer K;Gao Q
耐多药结核病（MDR-TB）是全球消除结核病的重大威胁。了解传播模式对于控制它至关重要。我们采用基因组流行病学方法评估耐多药结核病的近期传播情况和潜在的传播风险因素。在一项基于人群的回顾性研究中，我们对2009-2012年中国上海所有耐多药结核病患者的分离株进行了可变串联重复序列（VNTR）基因分型，随后进行了全基因组测序（WGS）。我们测量了基因组聚集患者内部和之间的菌株多样性。结合基因组和流行病学数据构建传播网络。7982例结核病患者中有367例（5%）患有MDR结核病，其中324例（88%）具有可用于基因组分析的分离株。324株MDR菌株中有103株（32%）位于38个基因组簇中，这些基因组簇之间存在12个或更少的单核苷酸多态性（SNP），表明MDR菌株最近传播。延迟诊断或年龄超过45岁的患者最近传播的风险很高。235例（73%）耐多药结核病患者可能传播了耐多药菌株。传播网络分析显示，38个簇中的33个（87%）通过传播过程中突变的出现或固定积累了额外的耐药突变。103株MDR聚集株中有68株（66%）存在利福平耐药补偿突变。最近MDR菌株的传播，随着耐药性的增加，有助于推动中国上海的MDR-TB流行。WGS提供了宿主内和宿主之间耐药突变异质性的衡量标准，并增强了我们确定耐多药结核病传播模式的能力。国家科技重大专项、国家自然科学基金、美国国立卫生研究院。
Multidrug-resistant tuberculosis (MDR-TB) is a significant threat to tuberculosis elimination worldwide. Understanding the transmission pattern is crucial for its control. We used a genomic epidemiological approach to assess the recent transmission of MDR-TB and potential risk factors for transmission. In a population-based retrospective study, we performed variable-number-of-tandem-repeat (VNTR) genotyping, followed by whole-genome sequencing (WGS) of isolates from all MDR-TB patients in Shanghai, China, 2009-2012. We measured strain diversity within and between genomically clustered patients. Genomic and epidemiologic data were combined to construct transmission networks. 367 (5%) of 7982 patients with tuberculosis had MDR tuberculosis and 324 (88%) of these had isolates available for genomic analysis. 103 (32%) of the 324 MDR strains were in 38 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating recent transmission of MDR strains. Patients who had delayed diagnosis or were older than 45 years had high risk of recent transmission. 235 (73%) patients with MDR tuberculosis probably had transmission of MDR strains. Transmission network analysis showed that 33 (87%) of the 38 clusters accumulated additional drug-resistance mutations through emergence or fixation of mutations during transmission. 68 (66%) of 103 clustered MDR strains had compensatory mutations of rifampicin resistance. Recent transmission of MDR strains, with increasing drug-resistance, helps drive the MDR-TB epidemic in Shanghai, China. WGS provides a measure of the heterogeneity of drug-resistant mutations within and between hosts and enhances our ability to determine the transmission patterns of MDR-TB. National Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health.