First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal.
First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal.
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DOI：
10.1371/journal.pone.0052297
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gagneux S
中科院分区：
文献类型：
--
作者：
Malla B;Stucki D;Borrell S;Feldmann J;Maharjan B;Shrestha B;Fenner L;Gagneux S
结核病是尼泊尔的一个主要公共卫生问题。结核分枝杆菌的菌株变异可能影响结核感染和疾病的结局。迄今为止，M.尼泊尔的结核病情况尚不清楚。我们分析了261 M。从2009年8月至2010年8月在尼泊尔招募的肺结核患者中回收的结核分离株。M.通过单核苷酸多态性（SNP）分型和spoligotyping确定结核病谱系。通过对相关靶基因的热点区域进行测序来确定耐药性。总体而言，164名（62.8%）结核病患者是新的，97名（37.2%）以前接受过治疗。50株（19.2%）分离株中检测到任何耐药，16株（6.1%）为多重耐药。最常见的M结核分枝杆菌谱系是谱系3（CAS/Delhi），106个分离株（40.6%），其次是谱系2（东亚谱系，包括北京基因型），84个分离株（32.2%），谱系4（欧美谱系），41个分离株（15.7%），和谱系1（印度洋谱系），30个分离株（11.5%）。基于spoligotyping，我们发现了45个不同的spoligotyping模式，以前描述。北京菌株83株（31.8%）和CAS菌株52株（19.9%）为优势菌株。共有36株（13.8%）分离株不能分配到任何已知的spoligotyping模式。谱系2与女性性别（校正比值比[aOR] 2.58，95%置信区间[95% CI] 1.42-4.67，p = 0.002）和任何耐药性（aOR 2.79; 95% CI 1.43-5.45; p = 0.002）相关。 我们没有发现谱系2与年龄或卡介苗接种状态相关的证据。我们发现M.结核病在尼泊尔的所有四个主要血统的代表。第三系和第二系占据主导地位。谱系2与临床特征相关。本研究填补了M.亚洲地区的结核病遗传多样性。
Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42–4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43–5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian region.
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作者：
Comas I;Homolka S;Niemann S;Gagneux S
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Gagneux S