Wang Feifei, Shao Lingyun, Fan Xiaoping, Shen Yaojie, Diao Ni, Jin Jialin, Sun Feng, Wu Jing, Chen Jiazhen, Weng Xinhua, Cheng Xunjia, Zhang Ying, Zhang Wenhong
Key Laboratory of Medical Molecular Virology, Huashan Hospital, Fudan University, Shanghai, China Department of Medical Microbiology and Parasitology, Shanghai Medical College, Fudan University, Shanghai, China.
Key Laboratory of Medical Molecular Virology, Huashan Hospital, Fudan University, Shanghai, China.
Antimicrob Agents Chemother. 2015 Feb;59(2):818-25. doi: 10.1128/AAC.03504-14. Epub 2014 Nov 17.
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.
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了日益严重的威胁。本研究旨在确定在中国结核病高度流行地区人群中XDR-TB的进化模式和传播动态。我们分析了2003年至2009年在中国重庆收集的95株XDR-TB分离株。通过PCR扩增覆盖定义XDR-TB的7种药物的8个耐药基因，随后进行DNA测序。使用可变数目串联重复序列16位点（VNTR-16）基因分型和基因型耐药谱来确定XDR-TB菌株的进化或传播模式。我们的结果表明，北京基因型在XDR-TB菌株中占主导地位（85/95 [89.5%]），并且基于VNTR-16基因分型和耐药突变谱，多达40.0%（38/95）的分离株被分为6个簇。每个簇中的所有分离株在耐药基因rpoB、katG、inhA启动子、embB、rpsL和gidB中都有多达6个相同的耐药突变。在9例从耐多药（MDR）到XDR-TB的连续分离株病例中，4例代表获得性耐药，4例由传播引起，1例归因于外源性重叠感染。中国的XDR-TB流行主要由高度的克隆传播引起，但也可能发生从MDR到XDR的进化，甚至是新的XDR菌株的重叠感染。
