Laboratory of Molecular Epidemiology and Evolutionary Genetics, St Petersburg Pasteur Institute, St Petersburg, Russia.
North Estonian Medical Centre Foundation, Tallinn, Estonia.
J Antimicrob Chemother. 2018 Feb 1;73(2):325-331. doi: 10.1093/jac/dkx372.
We assessed the genetic structure of the Mycobacterium tuberculosis population in Estonia with a special focus on major epidemic/endemic clones and drug resistance determinants. We investigated the hypothesis of the decisive impact of massive human influx on the locally circulating genotypes. Estonia received a mass immigration from Russia during 1945-90 followed by enhanced interaction with the EU since 1991.
The study sample included M. tuberculosis isolates from patients newly diagnosed with TB in 2014 in North Estonia (including the capital Tallinn). The isolates were subjected to first- and second-line drug susceptibility testing, detection of mutations in rpoB, katG, inhA, rrs, embB and gyrA and lineage/clone-specific genotyping.
Of the M. tuberculosis isolates, 39.8% were assigned to the Beijing genotype; 56.8% of them were MDR. In contrast, all three major non-Beijing genotypes (LAM, Haarlem and Ural) were mainly drug susceptible. MDR was more prevalent among Beijing B0/W148-cluster isolates (81.8%) compared with other Beijing isolates (20.0%; P = 0.0007). The pre-XDR phenotype was found in eight isolates, of which six belonged to Beijing B0/W148. All rifampicin-resistant and ofloxacin-resistant and 97% of isoniazid-resistant isolates harboured resistance mutations in rpoB, gyrA and katG. The rpoB S531L, katG S315T and embB M306V mutations were the most prevalent.
The major pool of the Beijing isolates was brought to Estonia before 1990. However, an active circulation of the most hazardous MDR-associated Beijing B0/W148-cluster started only in the last 20 years and its significantly increased circulation presents the major threat to TB control in Estonia. The overwhelming prevalence of the rpoB531 and katG315 mutations in the MDR-associated Beijing isolates requires attention.
我们评估了爱沙尼亚结核分枝杆菌群体的遗传结构，特别关注主要的流行/地方性克隆和耐药决定因素。我们研究了一个假设，即大规模人口流入对当地流行基因型具有决定性影响。1945 年至 1990 年间，爱沙尼亚接收了大量来自俄罗斯的移民，随后自 1991 年以来与欧盟的互动更加频繁。
研究样本包括 2014 年在爱沙尼亚北部（包括首都塔林）新诊断为结核病的患者的结核分枝杆菌分离株。对分离株进行一线和二线药物敏感性试验、rpoB、katG、inhA、rrs、embB 和 gyrA 突变检测以及谱系/克隆特异性基因分型。
39.8%的结核分枝杆菌分离株被归为北京基因型；其中 56.8%为耐多药。相比之下，所有三种主要的非北京基因型（LAM、 Haarlem 和 Ural）均主要为药物敏感型。北京 B0/W148 聚类分离株的耐多药（81.8%）比其他北京分离株（20.0%）更为普遍（P=0.0007）。发现了 8 株前耐多药广泛型（XDR）表型，其中 6 株属于北京 B0/W148。所有利福平耐药和氧氟沙星耐药以及 97%的异烟肼耐药分离株均在 rpoB、gyrA 和 katG 中存在耐药突变。rpoB S531L、katG S315T 和 embB M306V 突变最为常见。
大多数北京分离株在 1990 年之前被带到爱沙尼亚。然而，自 20 年前开始，最危险的与耐多药相关的北京 B0/W148 聚类的分离株开始活跃传播，其传播显著增加对爱沙尼亚的结核病控制构成了重大威胁。在与耐多药相关的北京分离株中，rpoB531 和 katG315 突变的压倒性流行值得关注。
