Genetic Diversity of Mycobacterium tuberculosis in Peru and Exploration of Phylogenetic Associations with Drug Resistance
Genetic Diversity of Mycobacterium tuberculosis in Peru and Exploration of Phylogenetic Associations with Drug Resistance
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DOI：
10.1371/journal.pone.0065873
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发表时间：
2013-06-24
期刊：
影响因子：
3.7
通讯作者：
Moore, David A. J.
中科院分区：
文献类型：
--
作者：
Sheen, Patricia;Couvin, David;Moore, David A. J.
背景：关于秘鲁结核分枝杆菌菌株多样性的现有数据有限，尽管在这种情况下，尽管DOTS控制规划显然运作良好，但耐多药结核病已成为一个主要问题，这可能会带来有趣的经验教训。方法：对秘鲁利马市1999年至2005年从553名社区患者和241名医院HIV合并感染肺结核患者中收集的794株结核分枝杆菌进行孢子分型。系统发育和流行病学分析允许鉴定聚类并探索与耐药性相关的spoligotype。结果：患者平均年龄31.9岁，男性占63%，HIV阳性占30.4%。利福平单药耐药、异烟肼单药耐药和多药耐药（MDR）分别占4.7%、8.7%和17.3%。在794例患者的794株中，有149种不同的spoligotypes。其中有27株（3.4%）具有新颖独特的孤儿孢子亚型。498株（62.7%）聚集在9个最常见的spoligotypes中：16.4%的SIT 50 （H3枝）、12.3%的SIT 53 （T1枝）、8.3%的SIT 33 （LAM3枝）、7.4%的SIT 42 （LAM9枝）、5.5%的SIT1 （Beijing）、3.9%的SIT 47 （H1）、3.0%的SIT 222（分支未知）、3.0%的SIT1355 （LAM）和2.8%的SIT 92 （X3）。在艾滋病毒阴性的社区结核病患者中，未发现耐药性与特定孢子亚型之间存在关联；相比之下，hiv相关的耐多药结核病与SIT42和SIT53菌株相关，但与异烟肼或利福平单药耐药无关。结论：两种spoligotypes与MDR相关，特别是在HIV患者中。在控制了SIT42和SIT53状态后，耐多药hiv相关性显著降低；残留混淆可以解释剩余的明显关联。这些数据提示在HIV患者中出现了长期的、克隆的、以医院为基础的耐多药疾病暴发，但不支持菌株特异性倾向于获得耐药突变的假设。
Background: There is limited available data on the strain diversity of M tuberculosis in Peru, though there may be interesting lessons to learn from a setting where multidrug resistant TB has emerged as a major problem despite an apparently well-functioning DOTS control programme.Methods: Spoligotyping was undertaken on 794 strains of M tuberculosis collected between 1999 and 2005 from 553 community-based patients and 241 hospital-based HIV co-infected patients with pulmonary tuberculosis in Lima, Peru. Phylogenetic and epidemiologic analyses permitted identification of clusters and exploration of spoligotype associations with drug resistance.Results: Mean patient age was 31.9 years, 63% were male and 30.4% were known to be HIV+. Rifampicin mono-resistance, isoniazid mono-resistance and multidrug resistance (MDR) were identified in 4.7%, 8.7% and 17.3% of strains respectively. Of 794 strains from 794 patients there were 149 different spoligotypes. Of these there were 27 strains (3.4%) with novel, unique orphan spoligotypes. 498 strains (62.7%) were clustered in the nine most common spoligotypes: 16.4% SIT 50 (clade H3), 12.3% SIT 53 (clade T1), 8.3% SIT 33 (LAM3), 7.4% SIT 42 (LAM9), 5.5% SIT 1 (Beijing), 3.9% SIT 47 (H1), 3.0% SIT 222 (clade unknown), 3.0% SIT1355 (LAM), and 2.8% SIT 92 (X3). Amongst HIV-negative community-based TB patients no associations were seen between drug resistance and specific spoligotypes; in contrast HIV-associated MDRTB, but not isoniazid or rifampicin mono-resistance, was associated with SIT42 and SIT53 strains.Conclusion: Two spoligotypes were associated with MDR particularly amongst patients with HIV. The MDR-HIV association was significantly reduced after controlling for SIT42 and SIT53 status; residual confounding may explain the remaining apparent association. These data are suggestive of a prolonged, clonal, hospital-based outbreak of MDR disease amongst HIV patients but do not support a hypothesis of strain-specific propensity for the acquisition of resistance-conferring mutations.