Severe Clinical Outcomes of Tuberculosis in Kharkiv Region, Ukraine, Are Associated with Beijing Strains of Mycobacterium tuberculosis

Konstantynovska, Olha; Rekrotchuk, Mariia; Hrek, Ivan; Rohozhyn, Anton; Rudova, Nataliia; Poteiko, Petro; Gerilovych, Anton; Bortz, Eric; Solodiankin, Oleksii

doi:10.3390/pathogens8020075

Cited by 6 publications

(7 citation statements)

References 24 publications

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“…Further, we show that MDR/XDR TB patients in southern Ukraine are infected mainly with 3 distinct MTBC Beijing outbreak clades. However, inhabitants of southeastern Ukraine were indeed at higher risk for primary MDR TB (36,37). This finding might be linked to the circulation of the Beijing outbreak strains we describe but we cannot extrapolate our results to the whole country which was shown to have an asymmetric distribution of MDR TB (37).…”

Section: Discussionmentioning

confidence: 62%

Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Beijing Clades, Ukraine, 2015

Merker¹,

Nikolaevskaya²,

Kohl³

et al. 2020

Emerg. Infect. Dis.

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E ach year, approximately half a million new cases of multidrug-resistant (MDR) tuberculosis (TB) challenge global health (1,2). MDR TB is caused by Mycobacterium tuberculosis complex (MTBC) strains, resistant to at least isoniazid and rifampin (3). In Europe, Ukraine is a hotspot of drug-resistant TB, with 6,564 laboratory-confirmed MDR and rifampin-resistant cases (2) and the third highest burden of extensively drug-resistant (XDR) TB (1,097 laboratory confirmed cases) globally in 2017 (2). XDR TB is a complicated form of MDR TB with additional resistances to >1 second-line injectable antimicrobial drug and a fluoroquinolone (1). Treatment of XDR TB can take up to 2 years (4), and treatment of a single XDR TB case has been reported to exceed €100,000 (5,6), even though treatment success rates remain ≈30% in the European region of the World Health Organization (40 countries reported) (7). Improvement of MDR/XDR TB prevention, diagnosis, and treatment is one of the core activities prioritized by WHO and the European Respiratory Society to eliminate TB (6). In addition to shortcomings in TB diagnosis and treatment, bacterial genetic factors might play a role in the epidemiologic success of certain MDR strains, especially of lineage 2 (Beijing) in Eurasia (8-11). Beijing MDR outbreak strains were shown to acquire fitness-enhancing mutations (i.e., mutations that increase in vitro growth rates) that may result in higher virulence and increased transmissibility, thus fostering the MDR TB epidemic in Eastern Europe (8-10). In line with this assumption, recent computational models predict that in many high TB incidence countries, person-to-person transmission but not treatment-related acquisition accounts for almost all (95.9%) incident MDR TB cases (12). Whole-genome sequencing (WGS) coupled with a molecular drug resistance prediction has provided insight into MTBC transmission networks and the transmissibility of MDR/XDR MTBC strains (8-10,13-15). We applied a WGS-based molecular epidemiologic approach to identify molecular resistance patterns, dominant strain types, and Multidrug-and Extensively Drug-Resistant Mycobacterium tuberculosis Beijing Clades,

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Section: Discussionmentioning

confidence: 62%

Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Beijing Clades, Ukraine, 2015

Merker¹,

Nikolaevskaya²,

Kohl³

et al. 2020

Emerg. Infect. Dis.

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“…On the other hand, the L2 Beijing genotype was more frequently found among foreign-born patients (P<0.05). Overall, the high prevalence of the Beijing isolates in Poland evidenced in this study, coupled with a high proportion of the Beijing genotype among foreign-born TB patients may reflect an ongoing circulation of this genotype imported to Poland mainly from FSU countries ( Niemann et al., 2010 ; Konstantynovska et al., 2019 ). Of note, one patient born in Poland was infected with type MLVA 1071-32, which has been recently described as an emerging resistant Beijing variant that is circulating in Siberia.…”

Section: Discussionmentioning

confidence: 73%

Phylogenetic relationships of Mycobacterium tuberculosis isolates in Poland: The emergence of Beijing genotype among multidrug-resistant cases

Bakuła

Marczak

Bluszcz

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionThe epidemiological situation of tuberculosis (TB) in Poland urges for its continuous and scrupulous monitoring. The objective of this study was to explore the genetic diversity of multidrug-resistant (MDR) and drug-susceptible (DS) Mycobacterium tuberculosis isolates from Poland with a combination of spoligotyping and high-resolution mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis. The results were placed in the Northern and Eastern Europe context.MethodsThe study included 89 (39 MDR and 50 DS) M. tuberculosis isolates collected from as many patients between 2018 and 2021 in Poland. The analysis was done using spoligotyping, and MIRU-VNTR typing at 24 standard loci. The data were compared to those available on Poland and neighbors and global M. tuberculosis datasets.ResultsThe main identified families were Beijing (28.1%) and Haarlem (16.8%) while 34.8% of isolates were in the heterogeneous L4-unclassified group. Although the Beijing family was the most prevalent (61.5%) among MDR-TB cases, it accounted for only 2% of DS isolates. Among foreign-born patients, a higher ratio of MDR isolates were observed when compared with those who Poland-born (64.3% vs. 40%). Furthermore, all patients from the Former Soviet Union (FSU) countries were infected with MDR-TB.DiscussionWhereas DS M. tuberculosis population in Poland is dominated by L4 isolates, MDR isolates are mostly of the Beijing genotype. The rise in the prevalence of the Beijing isolates in Poland, coupled with high proportion of the Beijing genotype among foreign-born TB patients may reflect an ongoing transmission of this family, imported to Poland mainly from FSU countries.

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“…Ukraine has a recent history of outbreaks of infections such as polio and measles, 19 , 20 , drug-resistant tuberculosis 21 , 22 , and numerous veterinary pathogens 23 , which are sustainably controlled in other countries. Furthermore, despite a high HIV and hepatitis C virus prevalence, infectious disease genomic epidemiology is currently not integrated into public health decision making in Ukraine 24 , 25 .…”

Section: Introductionmentioning

confidence: 99%

Tracking SARS-COV-2 variants using Nanopore sequencing in Ukraine in 2021

Yakovleva

Kovalenko

Redlinger

et al. 2022

Sci Rep

Self Cite

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The use of real-time genomic epidemiology has enabled the tracking of the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), informing evidence-based public health decision making. Ukraine has experienced four waves of the Coronavirus Disease 2019 (COVID-19) between spring 2020 and spring 2022. However, insufficient capacity for local genetic sequencing limited the potential application of SARS-CoV-2 genomic surveillance for public health response in the country. Herein, we report local sequencing of 103 SARS-CoV-2 genomes from patient samples collected in Kyiv in July-December 2021 using Oxford Nanopore technology. Together with other published Ukrainian SARS-CoV-2 genomes, our data suggest that the third wave of the epidemic in Ukraine (June-December 2021) was dominated by the Delta Variant of Concern (VOC). Our phylogeographic analysis revealed that in summer 2021 Delta VOC was introduced into Ukraine from multiple locations worldwide, with most introductions coming from Central and Eastern European countries. The wide geographic range of Delta introductions coincides with increased volume of travel to Ukraine particularly from locations outside of Europe in summer 2021. This study highlights the need to urgently integrate affordable and easily scaled pathogen sequencing technologies in locations with less developed genomic infrastructure, in order to support local public health decision making.

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Severe Clinical Outcomes of Tuberculosis in Kharkiv Region, Ukraine, Are Associated with Beijing Strains of Mycobacterium tuberculosis

Cited by 6 publications

References 24 publications

Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Beijing Clades, Ukraine, 2015

Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Beijing Clades, Ukraine, 2015

Phylogenetic relationships of Mycobacterium tuberculosis isolates in Poland: The emergence of Beijing genotype among multidrug-resistant cases

Tracking SARS-COV-2 variants using Nanopore sequencing in Ukraine in 2021

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