Molecular epidemiological analysis of Mycobacterium tuberculosis isolates from rural population of nationwide tuberculosis prevalence survey in Mongolia

Authors

DOI:

https://doi.org/10.24079/CAJMS.2025.04.004

Keywords:

M. tuberculosis, Whole-genome sequencing, Beijing lineage, Drug resistance, Transmission

Abstract

Objective: Mongolia is among the 30 high-burden countries for TB and DR-TB. Whole-genome sequencing (WGS) offers precise insights into TB transmission, strain diversity, and antimicrobial resistance (AMR), which are vital for TB control strategies. This study aimed to investigate the molecular epidemiology, lineage distribution, transmission clustering, and drug resistance patterns of M.tuberculosis collected from rural areas of Mongolia using NGS.
Methods: A total of 50,194 individuals were screened in a national TB prevalence survey conducted according to WHO guidelines. From rural participants, 102 TB isolates were obtained; 100 with sufficient DNA quality were subjected to WGS. Bioinformatics analyses included lineage identification, AMR mutation profiling, and phylogenetic and clustering analyses. Results: Among the 100 isolates, lineage 2 (Beijing genotype) accounted for 72.0% and lineage 4 (Euro-American) for 28.0%. The Beijing type was dominant across all regions, especially the central region (84.6%) and showed high clustering (56.4%). A total of 13 clusters (≤12 SNVs) were identified; 86.6% were Beijing strains. MDR-TB comprised 10% of isolates, with 100% of MDR-TB strains belonging to the Beijing genotype. Resistance to isoniazid (23%) was common. Mutations associated with resistance were mainly found in katG, inhA, rpoB, pncA, rpsL, rrs, and embB genes. No resistance was observed to new drugs such as bedaquiline, linezolid, or clofazimine. Conclusions: In rural of Mongolia, M. tuberculosis Lineage 2 (modern Beijing genotype) is predominant, accounting for 72% of cases, with consistent distribution across geographic locations. Beijing strains demonstrated higher drug resistance compared to Euro-American types. Importantly, no resistance was detected to newly introduced TB drugs.

Downloads

Download data is not yet available.
Abstract
20
PDF
31

Author Biographies

Oyuntuya Tumenbayar, The Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

The National Center for Communicable Diseases, Ulaanbaatar, Mongolia

Tsetsegtuya Borolzoi, The Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

The National Center for Communicable Diseases, Ulaanbaatar, Mongolia

Satoshi Mitarai, The Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan

Basic Mycobacteriosis, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Sarantuya Jav, The Department of Molecular biology and Genetics, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

The Institute of Biomedical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

References

1. Global tuberculosis report 2023. Geneva: World Health Organization; 2023. Licence: CC BY-NC-SA 3.0 IGO. https://www.who.int/publications/i/item/9789240083851.

2. Global tuberculosis report 2022. Geneva: World Health organization; 2022. licence: cc bY-Nc-sa 3.0 iGo. https://www.who.int/publications/i/item/9789240061729. Geneva;2022.

3. Mongolia TB report 2022. National TB program: Mongolia;2022.

4. WHO operational handbook on tuberculosis. Module 3: diagnosis - rapid diagnostics for tuberculosis detection. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO. https://www.who.int/publications/i/item/9789240089501.

5. WHO rapid communication. Diagnosis of tuberculosis and detection of drug-resistance. 2024. Geneva, World Health Organization. 2024

6. WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO. https://www.who.int/publications/i/item/9789240107243

7. Zumla A, Nahid P, Cole ST. Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov. 2013;12(5):388-404. https://doi.org/10.1038/nrd4001

8. Murray CJL, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022;399(10325):629-655. https://doi.org/10.1016/S0140-6736(21)02724-0

9. Cole ST, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998;393(6685):537-544. https://doi.org/10.1038/31159

10. Yimer SA, Norheim G, Namouchi A, et al. Mycobacterium tuberculosis Lineage 7 Strains Are Associated with Prolonged Patient Delay in Seeking Treatment for Pulmonary Tuberculosis in Amhara Region, Ethiopia. J Clin Microbiol. 2015;53. https://doi.org/10.1128/jcm.03566-14

11. Reed M, Pichler V, McIntosh F, et al. Major Mycobacterium tuberculosis Lineages Associate with Patient Country of Origin. J Clin Microbiol. 2009;47:1119-1128. https://doi.org/10.1128/jcm.02142-08

12. Shabbeer A, Cowan LS, Ozcaglar C, et al. TB-Lineage: An online tool for classification and analysis of strains of Mycobacterium tuberculosis complex. Infect Genet Evol. 2012;12(4):789-797. https://doi.org/10.1016/j.meegid.2012.02.010

13. Aminian M, Shabbeer A, Bennett KP. A conformal Bayesian network for classification of Mycobacterium tuberculosis complex lineages. BMC Bioinformatics. 2010;11(3):S4. https://doi.org/10.1186/1471-2105-11-S3-S4

14. Ezewudo M, Borens A, Chiner-Oms Á, et al. Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase. Sci Rep. 2018;8(1):15382. https://doi.org/10.1038/s41598-018-33731-1

15. Casali N, Nikolayevskyy V, Balabanova Y, et al. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat Genet. 2014;46(3):279-286. https://doi.org/10.1038/ng.2878

16. Walker TM, Kohl TA, Omar SV, et al. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. The Lancet Infec Dis. 2015;15(10):1193-1202. https://doi.org/10.1016/s1473-3099(15)00062-6

17. Lee RS, Behr MA. The implications of whole-genome sequencing in the control of tuberculosis. Ther Adv Infec Dis. 2015;3(2):47-62. https://doi.org/10.1177/2049936115624630

18. Koleske BN, Jacobs WR, Jr, Bishai WR. The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions. J Clin Invest. 2023;133(19). https://doi.org/10.1172/jci173156

19. Pankhurst LJ, del Ojo Elias C, Votintseva AA, et al. Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study. The Lancet Resp Med. 2016;4(1):49-58. https://doi.org/10.1016/s2213-2600(15)00466-x

20. The use of next-generation sequencing for the surveillance of drug-resistant tuberculosis: an implementation manual. Geneva: World Health Organization; 2023. Licence: CC BY-NC-SA 3.0 IGO. https://www.who.int/publications/i/item/9789240078079

21. The use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex: technical guide. Geneva: World Health Organization; 2018 (WHO/CDS/TB/2018.19). Licence: CC BY-NCSA 3.0 IGO. https://www.who.int/publications/i/item/WHO-CDS-TB-2018.19

22. National tuberculosis prevalence surveys 2007-2016. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO. https://www.who.int/publications/i/item/9789240022430

23. Richard Lumb, Armand Van Deun, IvanBastian, et al. The handbook: Laboratory Diagnosis of Tuberculosis by Sputum Microscopy. 2013. https://www.stoptb.org/sites/default/files/imported/document/TB_MICROSCOPY_HANDBOOK_FINAL.pdf.

24. Standard Operating Procedures for Solid Culture Examination. National TB Reference Laboratory. NCCD. 2022;SOP-NTRL-008-02

25. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO. https://www.who.int/publications/i/item/9789240028173

26. Kirillova NV, Fedosova EA, Naranbat N, et al. Structure of the M. tuberculosis population in Mongolia according to the results of genotyping of large-sequence polymorphisms. Molecular Genetics, Microbiology and Virology. 2011;26:141-145. https://doi.org/10.3103/S0891416811040033

27. Park YK, Bai GH, Kim SJ. Restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolated from countries in the western pacific region. J Clin Microbiol. 2000;38(1):191-197. https://doi.org/10.1128/jcm.38.1.191-197.2000

28. S. N. Zhdanova OT, M. V. Badleeva, and O. B. Ogarkov. “Molecular epidemiology of tuberculosis in Mongolia: sources and pathways of MDR Mycobacterium tuberculosis strains,” Инфекция и иммунитет. 2018;8(4):707–707. https://doi.org/10.15789/2220-7619-MEO-1368

29. Gurjav U, Erkhembayar B, Burneebaatar B, et al. Transmission of multi-drug resistant tuberculosis in Mongolia is driven by Beijing strains of Mycobacterium tuberculosis resistant to all first-line drugs. Tuberculosis. 2016;101:49-53. https://doi.org/10.1016/j.tube.2016.07.010

30. B. Buyankhishig, Oyuntuya T, B. Tserelmaa, al e. A study of 46 MDR-TB strains using MIRU VNTR-24. Mongolian Journal of Infectious Disease Research. 2009.

31. Yu Q, Su Y, Lu B, et al. Genetic Diversity of Mycobacterium tuberculosis Isolates from Inner Mongolia, China. PLOS ONE. 2013;8(5):e57660. https://doi.org/10.1371/journal.pone.0057660

32. Mokrousov I, Vyazovaya A, Solovieva N, et al. Trends in molecular epidemiology of drug-resistant tuberculosis in Republic of Karelia, Russian Federation. BMC Microbiology. 2015;15(1):279. https://doi.org/10.1186/s12866-015-0613-3

33. Balabanova Y, Nikolayevskyy V, Ignatyeva O, et al. Beijing clades of Mycobacterium tuberculosis are associated with differential survival in HIV-negative Russian patients. Infect Gen Evo. 2015;36:517-523. https://doi.org/10.1016/j.meegid.2015.08.028

34. Merker M, Blin C, Mona S, et al. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet. 2015;47(3):242-249. https://doi.org/10.1038/ng.3195

35. Mokrousov I, Vyazovaya A, Pasechnik O, et al. Early ancient sublineages of Mycobacterium tuberculosis Beijing genotype: unexpected clues from phylogenomics of the pathogen and human history. Clin Mic Infect. 2019;25(8):1039.e1031-1039.e1036. https://doi.org/10.1016/j.cmi.2018.11.024

36. B. Buyankhishig NN, S. Mitarai, and H. L. Rieder. “Nationwide survey of anti-tuberculosis drug resistance in Mongolia,” Inter J of Tuber and Lung Dis. 2011;15( 9):1201–1205. https://doi.org/10.5588/ijtld.10.0594

37. Yang C, Shen X, Peng Y, et al. Transmission of Mycobacterium tuberculosis in China: A Population-Based Molecular Epidemiologic Study. Clin Inf Dis. 2015;61(2):219-227. https://doi.org/10.1093/cid/civ255

38. Hoffner S, Sahebi L, Ansarin K, et al. Mycobacterium tuberculosis of the Beijing Genotype in Iran and the World Health Organization Eastern Mediterranean Region: A Meta-Analysis. Micro Drug Res. 2017;24(6):693-698. https://doi.org/10.1089/mdr.2017.0160

39. Mokrousov I, Narvskaya O, Vyazovaya A, et al. Mycobacterium tuberculosis Beijing Genotype in Russia: in Search of Informative Variable-Number Tandem-Repeat Loci. J Clin Microb. 2008;46(11):3576-3584. https://doi.org/10.1128/JCM.00414-08

40. European Concerted Action on New Generation Genetic Markers and Techniques for the Epidemiology and Control of Tuberculosis. Beijing/W genotype Mycobacterium tuberculosis and drug resistance. Emerg Infec Dis. 2006;12(5):736-743. https://doi.org/10.3201/eid1205.050400

Downloads

Published

2025-12-26

How to Cite

Tumenbayar, O., Boldoo, T., Murase, Y., Borolzoi, T., Dambaa, N., Sovd, T., … Jav, S. (2025). Molecular epidemiological analysis of Mycobacterium tuberculosis isolates from rural population of nationwide tuberculosis prevalence survey in Mongolia. Central Asian Journal of Medical Sciences, 11(4), 187–201. https://doi.org/10.24079/CAJMS.2025.04.004

Issue

Section

Articles