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Molecular-Genetic Monitoring of the Mycobacterium tuberculosis Population in Murmansk Oblast

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Abstract

In Murmansk oblast, the first molecular-genetic studies of circulating strains of Mycobacterium tuberculosis were carried out during the years of an increase in the incidence of tuberculosis (TB) (2003–2006). The study’s aim was to carry out a genotypic characterization of the M. tuberculosis population in Murmansk oblast and analysis of changes in its structure over 15 years. Sixty-seven M. tuberculosis strains from patients with TB newly diagnosed in 2017 were studied. The strains were assigned to the Beijing genotype and its major clusters based on analysis of specific markers. The Beijing strains were typed by 24 MIRU–VNTR loci. All non-Beijing strains were subjected to spoligotyping. Genotypes of M. tuberculosis were identified: Beijing (52.2%), Ural (19.4%), T (9.0%), LAM (7.5%), Haarlem (3.0%), and X (1.5%). Among Beijing strains, the Central Asian/Russian cluster with heterogeneous MIRU–VNTR profiles was predominant—34.3% (23/67). Multiple drug resistance (MDR)—resistance to rifampicin and isoniazid caused by mutations rpoB Ser-531Leu (TCG → TTG) and katG Ser315Thr (AGC → ACC)—was detected in 26.9% of the strains; the largest proportion of MDR strains were found in the Beijing B0/W148 cluster (85.7%), represented mainly by the MIRU–VNTR profile 100-32. High levels of clustering of Beijing Central Asian/Russian (CR = 0.68) and B0/W148 (CR = 0.71) strains reflect their current dissemination. In 2003–2017, a steady dominance of the Beijing genotype with a tendency to an increase from 44.0 to 52.2% was observed. The proportion of MDR strains in the cluster B0/W148 Beijing increased by 3.5 times, which indicates the selection and accumulation of this epidemiologically and clinically unfavorable variant of the tuberculosis pathogen in Murmansk oblast.

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Notes

  1. Decree of the Ministry of Health of Russia no. 951, December 29, 2014.

  2. Decree of the Ministry of Health of Russia no. 951, December 29, 2014.

REFERENCES

  1. Gagneux, S., Ecology and evolution of Mycobacterium tuberculosis, Nat. Rev. Microbiol., 2018, vol. 16, no. 4, pp. 202–213. https://doi.org/10.1038/nrmicro.2018.8

    Article  CAS  PubMed  Google Scholar 

  2. Narvskaya, O., Mokrousov, I., Otten, T., and Vishnevsky, B., Molecular markers: Application for studies of Mycobacterium tuberculosis population in Russia, in Trends in DNA Fingerprinting Research, Read, M.M., Ed., New York: Nova Science Publ., 2005, pp. 111–125. https://doi.org/10.13140/RG.2.1.1389.3526.

  3. Mokrousov, I., Insights into the origin, emergence, and current spread of a successful Russian clone of Mycobacterium tuberculosis, Clin. Microbiol. Rev., 2013, vol. 26, no. 2, pp. 342–360. https://doi.org/10.1128/CMR.00087-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Merker, M., Blin, C., Mona, S., Duforet-Frebourg, N., Lecher, S., Willery, E., Blum, M.G., Rüsch-Gerdes, S., Mokrousov, I., Aleksic, E., Allix-Béguec, C., Antierens, A., Augustynowicz-Kopeć, E., Ballif, M., Barletta, F., Beck, H.P., and Barry, C.E. III, Bonnet, M., Borroni, E., Campos-Herrero, I., Cirillo, D., Cox, H., Crowe, S., Crudu, V., Diel, R., Drobniewski, F., Fauville-Dufaux, M., Gagneux, S., Ghebremichael, S., Hanekom, M., Hoffner, S., Jiao, W.W., Kalon, S., Kohl, T.A., Kontsevaya, I., Lillebæk, T., Maeda, S., Nikolayevskyy, V., Rasmussen, M., Rastogi, N., Samper, S., Sanchez-Padilla, E., Savic, B., Shamputa, I.C., Shen, A., Sng, L.h., Stakenas, P., Toit, K., Varaine, F., Vukovic, D., Wahl, C., Warren, R., Supply, P., Niemann, S., and Wirth, T., Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage, Nat. Genet., 2015, vol. 7, no. 3, pp. 242–249. https://doi.org/10.1038/ng.3195

    Article  CAS  Google Scholar 

  5. Vyazovaya, A., Mokrousov, I., Solovieva, N., Mushkin, A., Manicheva, O., Vishnevsky, B., Zhuravlev, V., and Narvskaya, O., Tuberculous spondylitis in Russia and prominent role of multidrug-resistant clone Mycobacterium tuberculosis Beijing B0/W148, Antimicrob. Agents Chemother., 2015, vol. 59, no. 4, pp. 2349–2357. https://doi.org/10.1128/AAC.04221-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhdanova, S.N., Ogarkov, O.B., Sin’kov, V.V., Khromova, P.A., Orlova, E.A., Koshcheev, M.E., and Savilov, E.D., Epidemiological study of main clones distribution genotype Beijing of Mycobacterium tuberculosis within Irkutsk region, J. Microbiol., Epidemiol. Immunobiol., 2017, no. 6, pp. 88–94. https://elibrary.ru/item.asp? id=37136208.

  7. Mokrousov, I., Chernyaeva, E., Vyazovaya, A., Skiba, Y., Solovieva, N., Valcheva, V., et al., Rapid assay for detection of the epidemiologically important central Asian/Russian strain of the Mycobacterium tuberculosis Beijing genotype, J. Clin. Microbiol., 2018, vol. 56, no. 2, article no. e01551-17. https://doi.org/10.1128/JCM.01551-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pasechnik, O., Vyazovaya, A., Vitriv, S., Tatarintseva, M., Blokh, A., Stasenko, V., and Mokrousov, I., Major genotype families and epidemic clones of Mycobacterium tuberculosis in Omsk region, Western Siberia, Russia, marked by a high burden of tuberculosis-HIV coinfection, Tuberculosis (Edinburgh), 2018, vol. 108, pp. 163–168. https://doi.org/10.1016/j.tube.2017.12.003.

  9. Khromova, P.A., Kornilov, M.S., Zhdanova, S.N., Yakovlev, A.A., and Ogarkov, O.B., The detection of epidemic subtypes of Beijing genotype of Mycobacterium tuberculosis circulated in the Primorskii Krai, Acta Biomed. Sci., 2018, vol. 3, no. 5, pp. 154–158. https://doi.org/10.29413/ABS.2018-3.5.23

    Article  Google Scholar 

  10. Umpeleva, T., Belousova, K., Golubeva, L., Boteva, T., Morozova, I., Vyazovaya, A., et al., Molecular characteristics of Mycobacterium tuberculosis in the “closed” Russian town with limited population migration, Infect., Genet. Evol., 2020, vol. 79, p. 104174. https://doi.org/10.1016/j.meegid.2020.104174

    Article  CAS  Google Scholar 

  11. Mokrousov, I., Vyazovaya, A., Solovieva, N., Sunchalina, T., Markelov, Y., Chernyaeva, E., et al., Trends in molecular epidemiology of drug-resistant tuberculosis in Republic of Karelia, Russian Federation, BMC Microbiol., 2015, vol. 15, p. 279. https://doi.org/10.1186/s12866-015-0613-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Umpeleva, T.V., Vyazovaya, A.A., Eremeeva, N.I., Kravchenko, M.A., Narvskaya, O.V., and Skornyakov, S.N., Specific genetic features of tuberculous mycobacteria in Ural federal district of Russia, Tuberc. Lung Dis., 2016, vol. 94, no. 8, pp. 60–65. https://doi.org/10.21292/2075-1230-2016-94-8-60-65

    Article  Google Scholar 

  13. Vyazovaya, A.A., Akhmedova, G.M., Solovieva, N.S., Gerasimova, A.A., Starkova, D.A., Turkin, E.N., et al., Molecular epidemiology of tuberculosis in the Kaliningrad region of Russia: 10 years after, Russ. J. Infect. Immun., 2017, vol. 7, no. 4, pp. 367–374. https://doi.org/10.15789/2220-7619-2017-4-367-374

    Article  Google Scholar 

  14. Salina, T.Yu. and Morozova, T.I., Clinical and epidemiological value of various genotypes of M. tuberculosis and changes in their transmission in Saratov region during 4-year period, Tuberc. Lung Dis., 2018, vol. 96, no. 4, pp. 32–37. https://doi.org/10.21292/2075-1230-2018-96-4-32-37

    Article  Google Scholar 

  15. Mäkinen, J., Marjamäki, M., Haanperä-Heikkinen, M., Marttila, H., Endourova, L.B., Presnova, S.E., et al., Extremely high prevalence of multidrug resistant tuberculosis in Murmansk, Russia: A population-based study, Eur. J. Clin. Microbiol. Infect. Dis., 2011, vol. 30, no. 9, pp. 1119–1126. https://doi.org/10.1007/s10096-011-1200-7

    Article  CAS  PubMed  Google Scholar 

  16. Baranov, A., Mariandyshev, A., Mannsåker, T., Dahle, U., and Bjune, G., Molecular epidemiology and drug resistance of widespread genotypes of Mycobacterium tuberculosis in northwestern Russia, Int. J. Tuberc. Lung Dis., 2009, vol. 13, no. 10, pp. 1288–1293.

    CAS  PubMed  Google Scholar 

  17. Resursy i deyatel’nost’ protivotuberkuleznykh organizatsii Rossiiskoi Federatsii v 2017–2018 gg. (Resources and Activities of Anti-Tuberculosis Organizations of the Russian Federation in 2017–2018 Years), Moscow, 2019. https://mednet.ru/images/materials/CMT/tb-res_2017-2018.pdf.

  18. Van Embden, J., Cave, M., Crawford, J., Dale, J., Eisenach, K., Gicquel, B., et al., Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology, J. Clin. Microbiol., 1993, vol. 31, no. 2, pp. 406–409. https://doi.org/10.1128/JCM.31.2.406-409.1993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mokrousov, I., Vyazovaya, A., Zhuravlev, V., Otten, T., Millet, J., Jiao, W.W., et al., Real-time PCR assay for rapid detection of epidemiologically and clinically significant Mycobacterium tuberculosis Beijing genotype isolates, J. Clin. Microbiol., 2014, vol. 52, no. 5, pp. 1691–1693. https://doi.org/10.1128/JCM.03193-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mokrousov, I., Narvskaya, O., Vyazovaya, A., Otten, T., Jiao, W., Gomes, L., et al., Russian “successful” clone B0/W148 of Mycobacterium tuberculosis Beijing genotype: a multiplex PCR assay for rapid detection and global screening, J. Clin. Microbiol., 2012, vol. 50, no. 11, pp. 3757–3759. https://doi.org/10.1128/JCM.02001-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shitikov, E., Vyazovaya, A., Malakhova, M., Guliaev, A., Bespyatykh, J., et al., Simple assay for detection of the central Asia outbreak clade of the Mycobacterium tuberculosis Beijing genotype, J. Clin. Microbiol., 2019, vol. 57, no. 7, article no. e00215-19. https://doi.org/10.1128/JCM.00215-19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Supply, P., Allix, C., Lesjean, S., Cardoso-Oelemann, M., Rüsch-Gerdes, S., Willery, E., et al., Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis, J. Clin. Microbiol., 2006, vol. 44, no. 12, pp. 4498–4510. https://doi.org/10.1128/JCM.01392-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hunter, P.R. and Gaston, M.A., Numerical index of the discriminatory ability of typing systems: An application of Simpson’s index of diversity, J. Clin. Microbiol., 1988, vol. 26, no. 11, pp. 2465–2466. https://doi.org/10.1128/JCM.26.11.2465-2466.1988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kamerbeek, J., Schouls, L., Kolk, A., Van Agterveld, M., Van Soolingen, D., Kuijper, S., et al., Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology, J. Clin. Microbiol., 1997, vol. 35, no. 4, pp. 907–914. https://doi.org/10.1128/JCM.35.4.907-914.1997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Vyazovaya, A., Proshina, E., Gerasimova, A., Avadenii, I., Solovieva, N., Zhuravlev, V., et al., Increased transmissibility of Russian successful strain Beijing B0/W148 of Mycobacterium tuberculosis: Indirect clues from history and demographics, Tuberculosis (Edinburgh), 2020, vol. 122, p. 101937. https://doi.org/10.1016/j.tube.2020.101937.

  26. Iwamoto, T., Grandjean, L., Arikawa, K., Nakanishi, N., Caviedes, L., and Coronel, J., et al., Genetic diversity and transmission characteristics of Beijing family strains of Mycobacterium tuberculosis in Peru, PLoS One, 2012, vol. 7, no. 11, article no. e49651. https://doi.org/10.1371/journal.pone.0049651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mokrousov, I., Vyazovaya, A., Otten, T., Zhuravlev, V., Pavlova, E., Tarashkevich, L., et al., Mycobacterium tuberculosis population in northwestern Russia: An update from Russian-EU/Latvian border region, PLoS One, 2012, vol. 7, no. 7, article no. e41318. https://doi.org/10.1371/journal.pone.0041318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Balabanova, Y., Nikolayevskyy, V., Ignatyeva, O., Kontsevaya, I., Rutterford, C.M., Shakhmistova, A., et al., Survival of civilian and prisoner drug-sensitive, multi- and extensive drug-resistant tuberculosis cohorts prospectively followed in Russia, PLoS One, 2011, vol. 6, no. 6, article no. e20531. https://doi.org/10.1371/journal.pone.0020531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. St. Petersburg Pasteur Institute, 197101, St. Petersburg, Russia

    A. A. Vyazovaya, A. A. Gerasimova, I. V. Mokrousov & O. V. Narvskaya

  2. Murmansk Regional TB Dispensary, 183034, Murmansk, Russia

    N. Yu. Gavrilova, A. O. Bychkova & E. V. Anikieva

  3. St. Petersburg Research Institute of Phthisiopulmonology, 194064, St. Petersburg, Russia

    I. Avadenii, N. S. Solovieva, V. Yu. Zhuravlev & O. V. Narvskaya

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  1. A. A. Vyazovaya
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  2. N. Yu. Gavrilova
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  3. A. A. Gerasimova
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  4. A. O. Bychkova
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  6. E. V. Anikieva
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  7. N. S. Solovieva
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  8. V. Yu. Zhuravlev
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  9. I. V. Mokrousov
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  10. O. V. Narvskaya
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Correspondence to A. A. Vyazovaya.

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Conflict of interest. The authors declare that they have no conflict of interest.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants involved in the study.

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Translated by A. Kazantseva

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Vyazovaya, A.A., Gavrilova, N.Y., Gerasimova, A.A. et al. Molecular-Genetic Monitoring of the Mycobacterium tuberculosis Population in Murmansk Oblast. Mol. Genet. Microbiol. Virol. 37, 71–77 (2022). https://doi.org/10.3103/S0891416822020070

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