Evolution and Transmission Patterns of Extensively Drug-Resistant Tuberculosis in China
Evolution and Transmission Patterns of Extensively Drug-Resistant Tuberculosis in China
复制标题
中国广泛耐药结核病的演变和传播模式
DOI：
10.1128/aac.03504-14
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发表时间：
2015-02-01
影响因子：
4.9
通讯作者：
Zhang, Wenhong
中科院分区：
文献类型：
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作者：
Wang, Feifei;Shao, Lingyun;Zhang, Wenhong
摘要广泛耐药结核病（XDR-TB）的出现和传播对全球结核病控制构成日益严重的威胁。本研究旨在确定广泛耐药结核病在中国结核病高度流行地区人群中的演变模式和传播动力学。我们分析了2003年至2009年在中国重庆收集的95株广泛耐药结核分离株。通过PCR扩增了8个耐药基因，涵盖了定义广泛耐药结核的7种药物，然后进行DNA测序。可变数目串联重复16位点（VNTR-16）基因分型和基因型耐药谱用于确定广泛耐药结核菌株的进化或传播模式。结果表明，北京基因型占绝对优势（85/95 [89.5%]），40.0%（38/95）的XDR-TB菌株根据VNTR-16基因分型和耐药突变谱可分为6个簇。每个簇的所有分离株在耐药基因rpoB、katG、inhA启动子、embB、rpsL和gidB中携带多达6个相同的耐药突变。在9例多重耐药（MDR）XDR-TB连续分离株中，4例为获得性耐药，4例为传播性耐药，1例为外源性重叠感染。中国的XDR-TB流行主要是由高度的克隆传播引起的，但也可能发生从MDR到XDR的进化，甚至与新的XDR菌株的重叠感染。
ABSTRACT The emergence and transmission of extensively drug-resistant tuberculosis (XDR-TB) pose an increasing threat to global TB control. This study aimed to identify the patterns of evolution and transmission dynamics of XDR-TB in populations in a region of China where TB is highly endemic. We analyzed a total of 95 XDR-TB isolates collected from 2003 to 2009 in Chongqing, China. Eight drug resistance genes covering 7 drugs that define XDR-TB were amplified by PCR followed by DNA sequencing. Variable-number tandem repeat 16-locus (VNTR-16) genotyping and genotypic drug resistance profiles were used to determine the evolution or transmission patterns of XDR-TB strains. Our results indicated that the Beijing genotype was predominant (85/95 [89.5%]) in XDR-TB strains, and as many as 40.0% (38/95) of the isolates were distributed into 6 clusters based on VNTR-16 genotyping and drug resistance mutation profiles. All isolates of each cluster harbored as many as six identical resistance mutations in the drug resistance genes rpoB, katG, inhA promoter, embB, rpsL, and gidB. Among the nine cases with continuous isolates from multidrug-resistant (MDR) to XDR-TB, 4 cases represented acquired drug resistance, 4 cases were caused by transmission, and 1 case was due to exogenous superinfection. The XDR-TB epidemic in China is mainly caused by a high degree of clonal transmission, but evolution from MDR to XDR and even superinfection with a new XDR strain can also occur.