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

Matúš Dohál; Věra Dvořáková; Miluše Šperková; Igor Porvazník; Andrea Maurizio Cabibbe; Alberto Trovato; Andrea Spitaleri; Erik Michael Rasmussen; Kristián Pršo; Mária Škereňová; Daniela Maria Cirillo; Ivan Solovič; Juraj Mokrý

doi:10.1016/j.jctube.2021.100292

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

J Clin Tuberc Other Mycobact Dis. 2021 Dec 20:26:100292. doi: 10.1016/j.jctube.2021.100292. eCollection 2022 Feb.

Affiliations

¹ Department of Pharmacology and Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University, Slovakia.
² National Reference Laboratory for Mycobacteria, National Institute of Public Health, Praha, Czech Republic.
³ National Institute of Tuberculosis, Lung Diseases and Thoracic Surgery, Vyšné Hágy, Slovakia, Faculty of Health, Catholic University, Ružomberok, Slovakia.
⁴ Faculty of Health, Catholic University, Ružomberok, Slovakia.
⁵ Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁶ International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.
⁷ Biomedical Center Martin, Department of Molecular Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovakia, Department of Clinical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovakia.

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.

Publication types

Review