Molecular epidemiological monitoring of the tuberculosis pathogen in the Arkhangelsk region

А. А. Vyazovaya, P. Eliseev, A. Gerasimova, N. S. Solovieva, E. Nikishova, O. Narvskaya, I. Mokrousov, Andrey O. Mariandyshev
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Abstract

Introduction. Against the background of improvement of the main epidemiological indicators (morbidity and mortality) for tuberculosis in the Arkhangelsk region, the proportion of newly diagnosed tuberculosis patients with multidrug-resistant pathogen (MDR-TB) increased from 18.7% in 2002 to 33.8% in 2018. The purpose of this study was the genotypic characterization of Mycobacterium tuberculosis strains obtained from newly diagnosed tuberculosis patients in the Arkhangelsk region in 2018. Materials and methods. 89 M. tuberculosis strains isolated in 2018 from newly diagnosed tuberculosis patients were studied. Beijing genotype, its clusters B0/W148 and Central Asian/Russian were determined by PCR detection of the specific markers: IS6110 insertions in the dnaA-dnaN region, mutations in codons 48 of the mutT4 gene (CGG GGG) and 58 of the mutT2 gene (GGA CGA), IS6110 insertions in the Rv2664 region-Rv2665 and Rv1359-Rv1360, substitutions G A in the sigE gene. Non-Beijing strains were spoligotyped. Results. Drug resistance was detected in 41.6% (37/89), MDR — in 33.7% of strains. In 90% (27/30) of MDR strains, resistance to rifampicin and isoniazid was due to rpoB Ser531Leu and katG Ser315Thr mutations. Following M. tuberculosis genotypes were identified: Beijing (67.4%), T (14.6%), Ural (4.5%), Haarlem (4.5%), LAM (2.3%) and CAS1-Delhi (1.1%). Among the Beijing strains, clusters Central-Asian/Russian (60%; 36/60) and B0/W148 (30%; 18/60) prevailed. The majority of MDR strains belonged to the Beijing family (93.3%; 28/30), of which 64.3% (18/28) and 21.4% (6/28) belonged to clusters B0/W148 and Central-Asian/Russian, respectively. Conclusion. In heterogeneous population of the causative agent of tuberculosis in the Arkhangelsk region, the most common strains were those of the Beijing genotype; in 2018 its share increased to 67.4% (40.4% in 1998–1999). Among MDR strains, the proportion of Beijing reached 93.3%, of which more than half (64.3%) belonged to the epidemiologically and clinically significant in Russia cluster B0/W148.
对阿尔汉格尔斯克州结核病病原体的分子流行病学监测
导言在阿尔汉格尔斯克州结核病主要流行病学指标(发病率和死亡率)得到改善的背景下,新确诊的结核病患者中耐多药病原体(MDR-TB)患者的比例从2002年的18.7%增至2018年的33.8%。 本研究的目的是对2018年从阿尔汉格尔斯克州新诊断的肺结核患者中获得的结核分枝杆菌菌株进行基因型鉴定。 材料与方法。研究了2018年从新诊断的肺结核患者中分离出的89株结核分枝杆菌。通过 PCR 检测特定标记确定了北京基因型、B0/W148 群和中亚/俄罗斯群:IS6110在dnaA-dnaN区域的插入,mutT4基因第48密码子(CGG GGG)和mutT2基因第58密码子(GGA CGA)的突变,IS6110在Rv2664区域-Rv2665和Rv1359-Rv1360的插入,sigE基因的G A替换。对非北京菌株进行了分离分型。 结果41.6%(37/89)的菌株检测出耐药性,33.7%的菌株检测出 MDR。90%(27/30)的 MDR 菌株对利福平和异烟肼的耐药性是由于 rpoB Ser531Leu 和 katG Ser315Thr 突变造成的。确定的结核杆菌基因型如下北京(67.4%)、T(14.6%)、乌拉尔(4.5%)、哈勒姆(4.5%)、LAM(2.3%)和 CAS1-德里(1.1%)。在北京的菌株中,中亚/俄罗斯(60%;36/60)和 B0/W148(30%;18/60)群占多数。大多数 MDR 菌株属于北京家族(93.3%;28/30),其中 64.3%(18/28)和 21.4%(6/28)分别属于 B0/W148 和中亚/俄罗斯群。 结论在阿尔汉格尔斯克地区结核病病原体的异质性人群中,最常见的菌株是北京基因型的菌株;2018年,其比例增至67.4%(1998-1999年为40.4%)。在MDR菌株中,北京型所占比例达到93.3%,其中一半以上(64.3%)属于在俄罗斯具有流行病学和临床意义的B0/W148群。
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