Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Dec 20:26:100292.
doi: 10.1016/j.jctube.2021.100292. eCollection 2022 Feb.

Anti-tuberculosis drug resistance in Slovakia, 2018-2019: The first whole-genome epidemiological study

Matúš Dohál  1 , Věra Dvořáková  2 , Miluše Šperková  2 , Igor Porvazník  3   4 , Andrea Maurizio Cabibbe  5 , Alberto Trovato  5 , Andrea Spitaleri  5 , Erik Michael Rasmussen  6 , Kristián Pršo  1 , Mária Škereňová  7 , Daniela Maria Cirillo  5 , Ivan Solovič  3 , Juraj Mokrý  1
Affiliations
Review

Anti-tuberculosis drug resistance in Slovakia, 2018-2019: The first whole-genome epidemiological study

Matúš Dohál et al. J Clin Tuberc Other Mycobact Dis. .

Abstract

Objective: The resistance of Mycobacterium (M.) tuberculosis to antituberculosis drugs poses a major threat to global public health. Whole genome sequencing (WGS) is an increasingly preferred method in the diagnostics and monitoring of the transmission dynamics of resistant forms of tuberculosis (TB). The aim of the study was to, for the first time, use the sequencing-based analysis to study the transmission and resistance patterns of a systematic and recent collection of extensively drug resistant (XDR) and multidrug resistant tuberculosis (MDR-TB) isolates and to expand our knowledge about drug resistant (DR) TB epidemiological dynamics in Slovakia.

Design: A total of 495 patients with pulmonary TB, who were referred to National Reference Laboratory for Mycobacteriology (Vyšné Hágy, Slovakia) in the years 2018-2019, were studied. Out of the total of 495 patients, 4 XDR-TB (0.8%) and 8 (1.6%) MDR-TB isolates were identified by conventional drug susceptibility testing on Löwenstein-Jensen solid medium and subjected to whole genome sequencing. Sequencing data were evaluated for molecular-epidemiological analysis and identification of resistance patterns.

Results: Phylogenetic and cluster analysis showed extensive recent transmission events and the predominance of Euro-American lineage 4.7 in Slovakia. However, phylogenetic analysis revealed the circulation of several lineages that originally occurred in Eastern European countries. Resistance patterns for first- and second-line antituberculosis drugs characterized by whole genome sequencing were in high concordance with the results of phenotypic drug susceptibility testing.

Conclusion: Forty percent of at least MDR-TB isolates were not genetically linked, indicating that appropriate measures should be taken to monitor and prevent the spread of drug-resistant tuberculosis within the country as well as in other regions.

Keywords: Extensively drug resistant; Multi drug resistant; Slovakia; Tuberculosis; Whole genome sequencing.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Classification of XDR-TB and MDR-TB isolates in the respective lineage.
Fig. 2
Fig. 2
Minimum spanning tree based on SNP differences between the strains, including the XDR-TB and MDR-TB strains collected in Slovakia during 2018 and 2019. Maximum distance set to 5 SNPs for linked transmission. Distant matrix generated from MTBseq (version 1.0.2) and a minimum spanning tree was constructed using GrapeTree software.
See this image and copyright information in PMC

References

    1. Analýza situácie TBC na Slovensku – NÚTPCHaHCH Vyšné Hágy n.d. https://www.hagy.sk/narodny-register-tbc/analyza-situacie-tbc-na-slovensku/ (accessed September 8, 2021).
    1. Cirillo D.M., Miotto P., Tortoli E. Evolution of Phenotypic and Molecular Drug Susceptibility Testing. Adv Exp Med Biol. 2017;1019:221–246. doi: 10.1007/978-3-319-64371-7_12. - DOI - PubMed
    1. Dohál M., Porvazník I., Pršo K., Rasmussen E.M., Solovič I., Mokrý J. Whole-genome sequencing and Mycobacterium tuberculosis: Challenges in sample preparation and sequencing data analysis. Tuberculosis. 2020;123:101946. doi: 10.1016/j.tube.2020.101946. - DOI - PubMed
    1. Nikolayevskyy V., Niemann S., Anthony R., van Soolingen D., Tagliani E., Ködmön C., et al. Role and value of whole genome sequencing in studying tuberculosis transmission. Clin Microbiol Infect. 2019;25(11):1377–1382. - PubMed
    1. Jagielski T., van Ingen J., Rastogi N., Dziadek J., Mazur P.K., Bielecki J. Current methods in the molecular typing of mycobacterium tuberculosis and other Mycobacteria. Biomed Res Int. 2014;2014:1–21. doi: 10.1155/2014/645802. - DOI - PMC - PubMed