MOLECULAR EPIDEMIOLOGY OF TUBERCULOSIS IN THE KALININGRAD REGION OF RUSSIA: 10 YEARS AFTER

Cover Page


Cite item

Full Text

Abstract

In the Kaliningrad region, the incidence of tuberculosis (TB) has declined significantly over the past decade (from 134/100 000 in 2006 to 50.6/100 000 in 2015), but still exceeds the average for the North-West Russia (40.7/100 000). In view of the increase in the proportion of primary multidrug resistance (MDR) of the causative agent from 23.9% in 2010 to 30.5% in 2015, the aim of this study was to analyze the current Mycobacterium tuberculosis population structure in the Kaliningrad region and to evaluate its spatial-temporal trends. The 73 M. tuberculosis isolates from patients with pulmonary TB newly diagnosed in 2015 were studied. Drug resistance (DR) was detected in 46 (63.0%) M. tuberculosis strains; of these, 32 (43.8%) were multidrug-resistant (MDR). The 46 (63.0%) of 73 M. tuberculosis strains were of the Beijing genotype with 19.2% (14 out of 73) share of the B0/W148 cluster. Spoligotyping of 27 non-Beijing M. tuberculosis strains made it possible to identify 15 spoligotypes of 5 genetic families — T, LAM, Ural, S, X. About half (16; 51.6%) of non-Beijing strains were represented by spoligotypes — SIT42, SIT53, SIT262, and SIT444. In a heterogeneous group T, mostly drugsusceptible strains of spoligotype SIT53 were prevailing. More than half (55.6%) of the LAM genotype strains exhibited DR. The Ural family was small (5.5%) and included strains of well-known in Russia M. tuberculosis spoligotypes SIT35 and SIT262, and one new, not found previously. MDR was statistically significantly associated with the Beijing genotype: 56.5% versus 25.9% in strains of other genotypes (in total) (P = 0.0134). Moreover, all 14 strains of epidemiologically and clinically significant B0/W148 cluster were MDR. The proportion of MDR strains of the Beijing genotype did not change significantly: in 2006 it was 61.3%, in 2015 — 56.5% (P = 0.6773). However, the spectrum of drug resistance to first-line anti-TB drugs expanded. If previously the majority (78.9%) of MDR strains additionally exhibited resistance to streptomycin only, in present study 72.0% of MDR strains were resistant to streptomycin, ethambutol, and pyrazinamide. The proportion of MDR strains of non-Beijing genotypes was 25.9%, a significantly higher than the similar indicators in 2006 — 2.2% (P = 0.0124). A relatively smaller proportion of strains of the Beijing genotype (50%) was found in TB patients from the shores of the Baltic Sea, a territory with a relatively more favorable socio-economic situation and a higher standard of living. Thus, the current epidemiological situation of TB in the Kaliningrad region is crucially determined by the growing circulation of MDR Beijing family strains, as well as a significant increase in the proportion of MDR strains of other genotypes.

 

About the authors

A. A. Vyazovaya

St. Petersburg Pasteur Institute, St. Petersburg

Author for correspondence.
Email: annavyazovaya@pasteurorg.ru
PhD (Biology), Senior Researcher, Laboratory of Molecular Epidemiology and Evolutionary Genetics Россия

G. M. Akhmedova

Tuberculosis Dispensary of the Kaliningrad region, Kaliningrad

Email: annavyazovaya@pasteurorg.ru
PhD (Medicine), Head of the Bacteriological Laboratory Россия

N. S. Solovieva

Research Institute of Phthisiopulmonology, St. Petersburg

Email: annavyazovaya@pasteurorg.ru
PhD (Medicine), Head of the Bacteriological Laboratory Россия

A. A. Gerasimova

St. Petersburg Pasteur Institute, St. Petersburg

Email: annavyazovaya@pasteurorg.ru
Junior Researcher, Laboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur Institute Россия

D. A. Starkova

St. Petersburg Pasteur Institute, St. Petersburg

Email: annavyazovaya@pasteurorg.ru
PhD (Biology), Researcher, Laboratory of Molecular Epidemiology and Evolutionary Genetics Россия

E. N. Turkin

Tuberculosis Dispensary of the Kaliningrad region, Kaliningrad

Email: annavyazovaya@pasteurorg.ru
Head Physician Россия

V. Yu. Zhuravlev

Research Institute of Phthisiopulmonology, St. Petersburg

Email: annavyazovaya@pasteurorg.ru
PhD (Medicine), Head of Department of the Laboratory Diagnostics Россия

O. V. Narvskaya

St. Petersburg Pasteur Institute, St. Petersburg;
Research Institute of Phthisiopulmonology, St. Petersburg

Email: annavyazovaya@pasteurorg.ru
PhD, MD (Medicine), Professor, Leading Researcher, Laboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation; Scientific Advisor, Department of Laboratory Diagnostics, Research Institute of Phthisiopulmonology Россия

I. V. Mokrousov

St. Petersburg Pasteur Institute, St. Petersburg

Email: annavyazovaya@pasteurorg.ru
PhD, MD (Biology), Head of the Laboratory of Molecular Epidemiology and Evolutionary Genetics Россия

References

  1. Вязовая А.А., Ветров В.В., Лялина Л.В., Мокроусов И.В., Соловьева Н.С., Журавлев В.Ю., Вишневский Б.И., Нарвская О.В. Характеристика штаммов Mycobacterium tuberculosis (по материалам 15-летнего наблюдения в Ленинградской области) // Инфекция и иммунитет. 2017. Т. 7, № 1. С. 34–40. [Vyazovaya A.A., Vetrov V.V., Lyalina L.V., Mokrousov I.V., Solovieva N.S., Zhuravlev V.Y., Vishnevskiy B.I., Narvskaya O.V. Characterization of Mycobacterium tuberculosis strains (a 15-year survey in Leningrad region, Russia). Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2017, vol. 7, no. 1, pp. 34–40. doi: 10.15789/2220-7619-2017-1-34-40 (In Russ.)]
  2. Вязовая А.А., Мокроусов И.В., Журавлев В.Ю., Соловьева Н.С., Оттен Т.Ф., Маничева О.А., Вишневский Б.И., Нарвская О.В. Молекулярная характеристика мультирезистентных штаммов Mycobacterium tuberculosis, выделенных на Северо-Западе России // Молекулярная генетика, микробиология и вирусология. 2016. № 1. С. 30–33. [Vyazovaya A.A., Mokrousov I.V., Zhuravlev V.Yu., Solovieva N.S., Otten T.F., Manicheva O.A., Vishnevsky B.I., Narvskaya O.V. Molecular characteristics of multidrug-resistant Mycobacterium tuberculosis strains in Northwest Russia. Molekulyarnaya gene-tika, mikrobiologiya i virusologiya = Mol. Genet. Microbiol. Virol., 2016, no. 1, pp. 30–33. (In Russ.)]
  3. Вязовая А.А., Соловьева Н.С., Сунчалина Т.В., Мокроусов И.В., Журавлев В.Ю., Нарвская О.В. Характеристика популяции Mycobacterium tuberculosis в Республике Карелия // Туберкулез и болезни легких. 2016. № 8. С. 48–53. [Vyazovaya A.A., Solovieva N.S., Sunchalina T.V., Mokrousov I.V., Zhuravlev V.Y., Narvskaya O.V. Characteristics of Myco-bacterium tuberculosis population in Republic of Karelia. Tuberkulez i bolezni legkih = Tuberculosis and Lung Diseases, 2016, no. 8, pp. 48–53. doi: 10.21292/2075-1230-2016-94-8-48-53 (In Russ.)]
  4. Нарвская О.В., Мокроусов И.В., Оттен Т.Ф., Вишневский Б.И. Генетическое маркирование полирезистентных штаммов Mycobacterium tuberculosis, выделенных на Северо-Западе России // Проблемы туберкулеза. 1999. № 3. С. 39–41. [Narvskaia O.V., Mokrousov I.V., Otten T.F., Vishnevskiĭ B.I. Genetic marking of polyresistant mycobacterium tuberculosis strains isolated in the north-west of Russia. Problemy tuberkuleza = Problems of Tuberculosis, 1999, no. 3, pp. 39–41 (In Russ.)]
  5. Шульженко С., Семенчук Н.О. Социально-экономическое развитие административно-территориальных образований как ключевой фактор прогресса эксклавного региона РФ // Молодой ученый. 2015. № 10.2. С. 20–26. [Shulzhenko S., Semenchuk N.O. Socio-economic development of administrative-territorial entities as a key factor in the progress of the exclave region of the Russian Federation. Molodoi uchenyi = Young scientist, 2015, no. 10.2, pp. 20–26 (In Russ.)]
  6. Brudey K., Gordon M., Moström P., Svensson L., Jonsson B., Sola C., Ridell M., Rastogi N. Molecular epidemiology of Myco-bacterium tuberculosis in Western Sweden. J. Clin. Microbiol., 2004, vol. 42, no. 7, pp. 3046–3051.
  7. Dymova M.A., Liashenko O.O., Poteiko P.I., Krutko V.S., Khrapov E.A., Filipenko M.L. Genetic variation of Mycobacterium tuberculosis circulating in Kharkiv Oblast, Ukraine. BMC Infect. Dis., 2011, vol. 11:77.
  8. Gibson A., Huard R., Gey van Pittius N., Lazzarini L., Driscoll J., Kurepina N., Zozio T., Sola C., Spindola S., Kritski A., Fitzgerald D., Kremer K., Mardassi H., Chitale P., Brinkworth J., Garcia de Viedma D., Gicquel B., Pape J., Van Soolingen D., Kreiswirth B., Warren R., Van Helden P., Rastogi N., Suffys P., Lapa e Silva J., Ho J. Application of sensitive and specific molecular methods to uncover global dissemination of the major RDRio Sublineage of the Latin American-Mediterranean Mycobacterium tuberculosis spoligotype family. J. Clin. Microbiol., 2008, vol. 46, no. 4, pp. 1259–1267.
  9. Jagielski T., Augustynowicz-Kopeć E., Zozio T., Rastogi N., Zwolska Z. Spoligotype-Based Comparative Population structure analysis of multidrug-resistant and isoniazid-monoresistant Mycobacterium tuberculosis complex clinical isolates in Poland. J. Clin. Microbiol., 2010, vol. 48, no. 11, pp. 3899–3909.
  10. Kamerbeek J., Schouls L., Kolk A., Van Agterveld M., Van Soolingen D., Kuijper S., Bunschoten A., Molhuizen H., Shaw R., Goyal M., Van Embden J. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J. Clin. Microbiol., 1997, vol. 35, no. 4, pp. 907–914.
  11. Kozińska M., Zientek J., Augustynowicz-Kopeć E., Zwolska Z., Kozielski J. Transmission of tuberculosis among people living in the border areas of Poland, the Czech Republic, and Slovakia. Pol. Arch. Med. Wewn., 2016, vol. 126, pp. 32–40.
  12. Krüüner A., Hoffner S.E., Sillastu H., Danilovits M., Levina K, Svenson S.B., Ghebremichael S., Koivula T., Källenius G. Spread of drug-resistant pulmonary tuberculosis in Estonia. J. Clin. Microbiol., 2001, vol. 39, pp. 3339–3345.
  13. Marttila H.J., Soini H., Eerola E., Vyshnevskaya E., Vyshnevskiy B.I., Otten T.F., Vasilyef A.V., Viljanen M.K. A Ser315Thr substitution in KatG is predominant in genetically heterogeneous multidrug-resistant Mycobacterium tuberculosis isolates originating from the St. Petersburg area in Russia. Antimicrob. Agents Chemother., 1998, vol. 42, no. 9, pp. 2443–2445.
  14. 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.
  15. Mokrousov I. Mycobacterium tuberculosis phylogeography in the context of human migration and pathogen’s pathobiology: insights from Beijing and Ural families. Tuberculosis, 2015, vol. 95, suppl. 1, pp. 167–76.
  16. Mokrousov I., Narvskaya O., Vyazovaya A., Otten T., Jiao W., Gomes L., Suffys P., Shen A.D., Vishnevsky B. 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.
  17. Mokrousov I., Otten T., Zozio T., Turkin E., Nazemtseva V., Sheremet A., Vishnevsky B., Narvskaya O., Rastogi N. At Baltic crossroads: a molecular snapshot of Mycobacterium tuberculosis population diversity in Kaliningrad, Russia. FEMS Immunol. Med. Microbiol., 2009, vol. 55, no. 1, pp. 13–22.
  18. Mokrousov I., Vyazovaya A., Otten T., Zhuravlev V., Pavlova E., Tarashkevich L., Krishevich V., Vishnevsky B., Narvskaya O. Mycobacterium tuberculosis population in northwestern Russia: an update from Russian-EU/Latvian border region. PLoS One, 2012, vol. 7, no. 7:e41318. doi: 10.1371/journal.pone.0041318
  19. Mokrousov I., Vyazovaya A., Zhuravlev V., Otten T., Millet J., Jiao W.W., Shen A.D., Rastogi N., Vishnevsky B., Narvskaya O. 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.
  20. Narvskaya O., Mokrousov I., Otten T., Vishnevsky B. Molecular markers: application for studies of Mycobacterium tuberculosis population in Russia. Trends in DNA Fingerprinting Research. Ed. Read M.M. New York: Nova Science Publishers 2005, pp. 111–125.
  21. Narvskaya O., Otten T., Limeschenko E., Sapozhnikova N., Graschenkova O., Steklova L., Nikonova A., Filipenko M., Mokrousov I., Vyshnevskiy B. Nosocomial outbreak of multidrug-resistant tuberculosis caused by a strain of Mycobacterium tuberculosis W-Beijing family in St. Petersburg, Russia. Eur. J. Clin. Microbiol. Infect. Dis., 2002, vol. 21, pp. 596–602.
  22. Nikolayevskyy V.V., Brown T.J., Bazhora Y.I., Asmolov A.A., Balabanova Y.M., Drobniewski F.A. Molecular epidemiology and prevalence of mutations conferring rifampicin and isoniazid resistance in Mycobacterium tuberculosis strains from the southern Ukraine. Clin. Microbiol. Infect., 2007, vol. 13, no. 2, pp. 129–138.
  23. Portaels F., Rigouts L., Bastian I. Addressing multidrug-resistant tuberculosis in penitentiary hospitals and in the general population of the former Soviet Union. Int. J. Tuberc. Lung Dis., 1999, vol. 3, pp. 582–588.
  24. Smit P.W., Haanperä M., Rantala P., Couvin D., Lyytikäinen O., Rastogi N., Ruutu P., Soini H. Molecular epidemiology of tuberculosis in Finland, 2008–2011. PLoS One, 2013, vol. 8, no. 12:e85027. doi: 10.1371/journal.pone.0085027
  25. Toit K., Altraja A., Acosta C.D., Viiklepp P., Kremer K., Kummik T., Danilovitš M., Van den Bergh R., Harries A.D., Supply P. A four-year nationwide molecular epidemiological study in Estonia: risk factors for tuberculosis transmission. Public Health Action, 2014, vol. 21, no. 4, suppl. 2, pp. 34–40.
  26. Tracevska T., Jansone I., Baumanis V., Marga O., Lillebaek T. Prevalence of Beijing genotype in Latvian multidrug-resistant Mycobacterium tuberculosis isolates. Int. J. Tuberc. Lung Dis., 2003, vol. 7, pp. 1097–1103.
  27. Van Embden J., Cave M., Crawford J., Dale J., Eisenach K., Gicquel B., Hermans P., Martin C., McAdam R., Shinnick T., Small P. Strain identification on Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized metho dology. J. Clin. Microbiol., 1993, no. 31, pp. 406–409.
  28. Zalutskaya A., Wijkander M., Jureen P., Skrahina A., Hoffner S. Multidrug-resistant Myobacterium tuberculosis caused by the Beijing genotype and a specific T1 genotype clone (SIT No. 266) is widely transmitted in Minsk. Int. J. Mycobacteriol., 2013, vol. 2, no. 4, pp. 194–198.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2017 Vyazovaya A.A., Akhmedova G.M., Solovieva N.S., Gerasimova A.A., Starkova D.A., Turkin E.N., Zhuravlev V.Y., Narvskaya O.V., Mokrousov I.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies