Molecular epidemiology and prevalence of mutations conferring rifampicin and isoniazid resistance in Mycobacterium tuberculosis strains from the southern Ukraine

Molecular epidemiology and prevalence of mutations conferring rifampicin and isoniazid resistance in Mycobacterium tuberculosis strains from the southern Ukraine
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DOI:
10.1111/j.1469-0691.2006.01583.x
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发表时间:
2007-02-01
影响因子:
14.2
通讯作者:
Drobniewski, F. A.
Drobniewski, F. A.
中科院分区:
医学1区
文献类型:
--
作者:
Nikolayevskyy, V. V.;Brown, T. J.;Drobniewski, F. A.

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了解结核病的分子流行病学和与耐药性相关的基因突变可能有助于制定适当的干预措施,以改善结核病控制。2003-2004年,在乌克兰敖德萨和尼古拉耶夫地区,采用结构式问卷调查收集了589例经放射学确诊的结核病患者的基本流行病学数据。使用非商业反向杂交试验和DNA测序检测与利福平和异烟肼耐药相关的突变。采用多位点可变数目串联重复序列(VNTR)分型和spoligotyping进行基因分型。在225株来自个体连续患者的结核分枝杆菌分离株中,分别检测到32.9%和44.0%的利福平和异烟肼耐药突变。rpoB和katG基因的密码子531和密码子315的突变分别在耐药分离株中占主导地位。与非囚犯相比,前监狱囚犯的多药耐药率显著较高(54.8% vs. 27.3%; RR 2.01; 95%CI 1.35-2.97),共享VNTR标签223325173533424的北京菌株的突变患病率高于其他北京菌株(71.4% vs. 45.7%; RR 1.74; 95% CI 1.17-2.57),表明该人群可能是乌克兰南部MDR TB快速传播的原因。
Understanding the molecular epidemiology of tuberculosis (TB) and mutations in genes associated with drug resistance may contribute to the development of appropriate interventions to improve tuberculosis control. A structured questionnaire was used to collect basic epidemiological data from 589 patients with radiologically confirmed TB in the Odessa and Nikolaev regions of the Ukraine in 2003-2004. A non-commercial reverse hybridisation assay and DNA sequencing were used to detect mutations associated with rifampicin and isoniazid resistance. Genotyping was performed using multilocus variable number tandem repeat (VNTR) typing and spoligotyping. Mutations conferring rifampicin and isoniazid resistance were detected in 32.9% and 44.0%, respectively, of 225 Mycobacterium tuberculosis isolates from individual consecutive patients. Mutations in codon 531 and codon 315 of the rpoB and katG genes, respectively, were predominant among drug-resistant isolates. Multidrug (MDR) resistance rates were significantly higher among former prison inmates compared with non-prisoners (54.8% vs. 27.3%; RR 2.01; 95% CI 1.35-2.97) and the prevalence of mutations was higher in Beijing strains sharing the VNTR signature 223325173533424 than in other Beijing strains (71.4% vs. 45.7%; RR 1.74; 95% CI 1.17-2.57), suggesting that this group may be responsible for rapid transmission of MDR TB in the southern Ukraine.