Molecular Epidemiology of Tuberculosis in the Kaliningrad Region of Russia: 10 Years After

Вязовая, А. А.; Akhmedova, Gulnora; Соловьева, Н. С.; Gerasimova, Alena; Старкова, Д. А.; Turkin, Eugeni; Zhuravlev, Viacheslav; Нарвская, О. В.; Mokrousov, Igor

doi:10.15789/2220-7619-2017-4-367-374

Cited by 10 publications

(12 citation statements)

References 23 publications

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“…This region is located in the westernmost part of the Russian Federation and makes an exclave on the Baltic Sea inside the European Union separated from the mainland Russia by Lithuania and Poland. Virtually closed from foreign contact from the 1950s until 1991, Kaliningrad today is a busy Russian–European crossroad that has an impact on the epidemiological situation of communicable diseases not only in Russia but also in northern Europe [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis

Mokrousov

Vyazovaya

Akhmedova³

et al. 2020

Antibiotics

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Perchlozone ([PCZ] 4-thioureido-iminomethylpyridinium perchlorate) is a new thiosemicarbazone approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia and some other countries. The ethA and hadABC mutations may confer PCZ resistance. At the same time, ethA mutations are known to mediate resistance to ethionamide (ETH) and prothionamide (PTH). We aimed to study the genetic variation underlying Mycobacterium tuberculosis resistance to PCZ through whole genome sequencing (WGS) of consecutive isolates recovered during long-term treatment. This prospective study included patients admitted in 2018–2019 to the regional tuberculosis dispensary, Kaliningrad, Russia, whose treatment regimen included PCZ. Multiple M. tuberculosis isolates were recovered during PCZ treatment, and the bacterial DNA was subjected to WGS followed by bioinformatics analysis. We identified mutations in the genes putatively associated with PCZ resistance, ethA, and hadA. The most frequent one was a frameshift ethA 106 GA > G (seven of nine patients) and most of the other mutations were also likely present before PCZ treatment. In one patient, a frameshift mutation ethA 702 CT > C emerged after six months of PCZ treatment. A frequent presence of cross-resistance mutations to PCZ and ETH/PTH should be taken into consideration when PCZ is included in the treatment regimen of MDR-TB patients.

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Section: Methodsmentioning

confidence: 99%

Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis

Mokrousov

Vyazovaya

Akhmedova³

et al. 2020

Antibiotics

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“…Given the absence of the Beijing isolates from Estonia-born before 1941, it seems reasonable to conclude that its high prevalence in this country is a result of the Soviet period of its history . The prevalence of the Beijing genotype in Estonia (37%) is similar to the neighbouring Russian Pskov region, 44% but is higher than in Latvia, 25% (Pole et al, 2020 (Mäkinen et al, 2011), Belarus, reanalysed (Zalutskaya et al, 2013), Sweden (Jonsson et al, 2014), Pskov , Kaliningrad (Vyazovaya et al, 2017), Finland (Smit et al, 2013) and Karelia (Mokrousov et al, 2015). Free map: http://www.amaps.com/mapst oprin t/OUTLI NE%20MAP S/free_map_of_world.htm in Estonia than in Latvia (49% versus 11%).…”

Section: Estonian M Tuberculosis Population In the Regional Contextmentioning

confidence: 87%

Spatiotemporal dynamics of drug‐resistant Mycobacterium tuberculosis : Contrasting trends and implications for tuberculosis control in EU high‐priority country

Mokrousov

Vyazovaya

Levina

et al. 2020

Transbounding Emerging Dis

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Different and contrasting trends related to human migration and the implementation of health control programmes influence the spread of drug-resistant tuberculosis (TB). We analysed the Mycobacterium tuberculosis population structure in Estonia, a high-priority EU country for TB control, to detect the dynamic changes and underlying factors. The study collection included 278 M. tuberculosis isolates recovered in 1999 and 2014-2015. The isolates were subjected to drug susceptibility testing, genotyping and analysis of sublineage/cluster-specific markers and drug resistance mutations. The Beijing genotype was the most prevalent, and its rate increased from 28.6% in 1999 to 38.5% in 2015 (p = .09). The non-Beijing strains represented Euro-American lineage (Latin American Mediterranean [LAM], Ural, Haarlem, T, X genotypes) and Indo-Oceanic lineage (one EAI-IND isolate). The proportion of isolates resistant to two or more drugs increased from 22.4% to 29.1% (p = .1). The pre-XDR/ XDR isolates were identified only within the Beijing genotype. In contrast, the drug resistance rate decreased in the LAM genotype from 42.1% to 11.8% (p = .05). The Beijing B0/W148-cluster ('successful Russian strain') included only MDR, pre-XDR or XDR isolates. All B0/W148-cluster isolates were resistant to two or more drugs compared to 28% of the Beijing 94-32-cluster (p = .0002). The Beijing genotype was not identified in the isolates from patients born in Estonia before 1940 compared to its 35.2% rate among other patients. In summary, the circulation of the highly drugresistant isolates of the Beijing B0/W148 subtype, the increased prevalence of the Beijing genotype among HIV-coinfected patients and the increased number of patients with alcohol abuse (47.5%) present major challenges of the current TB control in Estonia. The Beijing genotype was likely brought to Estonia after 1945 due to the massive human influx from the Soviet Union. In contrast, the main genotypes of the Euro-American lineage were likely endemic in Estonia during all 20th century.

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“…1), что сопоставимо с данными по Ка лининградской области (63,0%) [1]. Для сравнения: в среднем по СЗФО доля генотипа Beijing в разные периоды составляла около 50,0% [2,11,15].…”

Section: результаты и обсуждениеunclassified

“…В ряде регионов СЗФО доля штаммов M. tuber culosis генотипа Beijing у впервые выявленных больных ТБ составляла 45-63% [1,2,11,15]. По Вологодской области информация о распространенности генетических семейств возбудителя туберкулеза отсутствует, поскольку популяционные исследования M. tuberculosis на данной территории до настоящего времени не проводились.…”

Section: Introductionunclassified

Molecular and genetic analysis of <i>Mycobacterium tuberculosis</i> population in the Vologda Region with low tuberculosis incidence

Вязовая¹,

Лебедева²,

Ушакова³

et al. 2021

Russian Journal of Infection and Immunity

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The Vologda Region is characterized by a relatively calm epidemic situation for tuberculosis in Russia: the incidence rate in 2010—2018 is decreased from 45.2 to 15.8 per 100 thousand of the population (44.4 in Russia). However, the proportion of patients with multiple drug resistance (MDR) of the pathogen increased from 12.1% in 2016 to 23.7% in 2018. The aim of the study was to characterize the genetic structure of the M. tuberculosis population and identify the main genotypes associated with the primary multidrug resistance of the pathogen in the Vologda Region. A total of 82 strains of M. tuberculosis isolated in 2018 from newly diagnosed tuberculosis patients were studied. Drug susceptibility testing was performed using the standard method of absolute concentration and BACTEC MGIT 960 kit. M. tuberculosis strains were assigned to the Beijing genotype and its main subtypes based on the analysis of specific markers. The Beijing strains were subtyped by the MIRU-VNTR method (24 standard loci), calculating the Hunter-Gaston Discriminatory Index (HGDI). Other strains of the non-Beijing group were spoligotyped. The majority of the strains were of the Beijing genotype (62.2%; 51 of 82). The most numerous cluster was Central Asian/Russian (41.5%; 34 of 82 strains). The shares of the Central Asia Outbreak (CAO) subtype and cluster B0/W148 amounted to 8.5% and 7.3%, respectively. The non-Beijing strains belonged to the genetic families T (11%; 9 of 82), LAM (11%), Haarlem (6.1%), and Ural (4.9%). Among 82 M. tuberculosis isolates, 33 (40.2%) MDR strains were identified, counting 27 of the Beijing genotype, including those of the Central Asian/Russian — 18 (66.7%), B0/W148 and CAO — 4 each (14.8%) clusters. MIRU-VNTR typing of 51 Beijing strains revealed 22 profiles (HGDI = 0.852); the largest clusters were 94-32 (35.3%) and 95-32 (15.7%), which included strains Central Asian/Russian and CAO. Four strains of genotype B0/W148 belonged to cluster 100-32. The loci QUB26 (HGDI = 0.493) and MIRU26 (HGDI = 0.388) had the highest polymorphism. For the first time, a molecular genetic study carried out in the Vologda region revealed the heterogeneity of the M. tuberculosis population with strains of the Beijing genotype dominated. At the same time, the share of the associated with MDR, epidemiologically and clinically significant cluster Beijing B0/W148, well defined in Russia and abroad, was only 7.3%, which is significantly less than in other regions of the Northwestern Federal District of the Russian Federation (~19%). Concurrent, representatives of the Central Asian/Russian cluster of the Beijing genotype prevailed in the structure of genotypes and among MDR M. tuberculosis strains.

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Molecular Epidemiology of Tuberculosis in the Kaliningrad Region of Russia: 10 Years After

Cited by 10 publications

References 23 publications

Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis

Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis

Spatiotemporal dynamics of drug‐resistant Mycobacterium tuberculosis : Contrasting trends and implications for tuberculosis control in EU high‐priority country

Molecular and genetic analysis of <i>Mycobacterium tuberculosis</i> population in the Vologda Region with low tuberculosis incidence

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