BACKGROUND: The war in Ukraine has led to significant migration to neighboring countries, raising public health concerns. Notable tuberculosis (TB) incidence rates in Ukraine emphasize the immediate requirement to prioritize approaches that interrupt the spread and prevent new infections. METHODS: We conducted a prospective genomic surveillance study to assess migration's impact on TB epidemiology in the Czech Republic and Slovakia. Mycobacterium tuberculosis isolates from Ukrainian war refugees and migrants, collected from September 2021 to December 2022 were analyzed alongside 1574 isolates obtained from Ukraine, the Czech Republic, and Slovakia. RESULTS: Our study revealed alarming results, with historically the highest number of Ukrainian tuberculosis patients detected in the host countries. The increasing number of cases of multidrug-resistant TB, significantly linked with Beijing lineage 2.2.1 (p < 0.0001), also presents substantial obstacles to control endeavors. The genomic analysis identified the three highly related genomic clusters, indicating the recent TB transmission among migrant populations. The largest clusters comprised war refugees diagnosed in the Czech Republic, TB patients from various regions of Ukraine, and incarcerated individuals diagnosed with pulmonary TB specialized facility in the Kharkiv region, Ukraine, pointing to a national transmission sequence that has persisted for over 14 years. CONCLUSIONS: The data showed that most infections were likely the result of reactivation of latent disease or exposure to TB before migration rather than recent transmission occurring within the host country. However, close monitoring, appropriate treatment, careful surveillance, and social support are crucial in mitigating future risks, though there is currently no evidence of local transmission in EU countries.
- MeSH
- dospělí MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- molekulární epidemiologie * MeSH
- multirezistentní tuberkulóza epidemiologie MeSH
- Mycobacterium tuberculosis * genetika izolace a purifikace MeSH
- osoby s přechodným pobytem a migranti * statistika a číselné údaje MeSH
- ozbrojené konflikty MeSH
- prospektivní studie MeSH
- tuberkulóza * epidemiologie přenos MeSH
- uprchlíci * statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
- Ukrajina MeSH
OBJECTIVES: Rapidly diagnosing drug-resistant TB is crucial for improving treatment and transmission control. WGS is becoming increasingly accessible and has added value to the diagnosis and treatment of TB. The aim of the study was to perform WGS to determine the rate of false-positive results of phenotypic drug susceptibility testing (pDST) and characterize the molecular mechanisms of resistance and transmission of mono- and polyresistant Mycobacterium (M.) tuberculosis. METHODS: WGS was performed on 53 monoresistant and 25 polyresistant M. tuberculosis isolates characterized by pDST. Sequencing data were bioinformatically processed to infer mutations encoding resistance and determine the origin of resistance and phylogenetic relationship between isolates studied. RESULTS: The data showed the variable sensitivity and specificity of WGS in comparison with pDST as the gold standard: isoniazid 92.7% and 92.3%; streptomycin 41.9% and 100.0%; pyrazinamide 15% and 94.8%; and ethambutol 75.0% and 98.6%, respectively. We found novel mutations encoding resistance to streptomycin (in gidB) and pyrazinamide (in kefB). Most isolates belonged to lineage 4 (80.1%) and the overall clustering rate was 11.5%. We observed lineage-specific gene variations encoding resistance to streptomycin and pyrazinamide. CONCLUSIONS: This study highlights the clinical potential of WGS in ruling out false-positive drug resistance following phenotypic or genetic drug testing, and recommend this technology together with the WHO catalogue in designing an optimal individualized treatment regimen and preventing the development of MDR TB. Our results suggest that resistance is primarily developed through spontaneous mutations or selective pressure.
- Publikační typ
- časopisecké články MeSH
Celosvětově bylo v roce 2021 hlášeno 6,4 milionu případů TBC, podle odhadů SZO však onemocnělo 10,6 milionu lidí (134/100 000). Na TBC zemřelo 1,6 milionu lidí (20/100 000). Horší přístup k diagnóze a léčbě TBC jako důsledek pandemie covid-19 se promítl do nárůstu počtu úmrtí na TBC na úroveň roku 2017. V Evropě TBC postihuje v první řadě zranitelné populace, například migranty, bezdomovce, vězně, HIV pozitivní apod. Na Ukrajině SZO odhaduje incidenci TBC na 71/100 000. Přibližně každá třetí TBC je tam multirezistentní a každý pátý nemocný je současně nakažen HIV. Česká republika se řadí ke státům s nejnižším výskytem TBC na světě. V roce 2021 bylo do Registru TBC hlášeno 357 případů (3,4/100 000). Údaje za rok 2022 ještě nejsou dostupné, je však pravděpodobné, že celkový počet TBC v České republice meziročně vzroste, a to v důsledku nárůstu hlášených TBC u Ukrajinců v souvislosti s válkou na Ukrajině. Příznivé je, že počty TBC u ukrajinských uprchlíků jsou výrazně nižší, než činily odhady na začátku války.
The emergence and spread of resistant tuberculosis (TB) pose a threat to public health, so it is necessary to diagnose the drug-resistant forms in a clinically short time frame and closely monitor their transmission. In this study, we carried out a first whole genome sequencing (WGS)-based analysis of multidrug resistant (MDR) M. tuberculosis strains to explore the phylogenetic lineages diversity, drug resistance mechanisms, and ongoing transmission chains within the country. In total, 65 isolates phenotypically resistant to at least rifampicin and isoniazid collected in the Czech Republic in 2005-2020 were enrolled for further analysis. The agreement of the results obtained by WGS with phenotypic drug susceptibility testing (pDST) in the determination of resistance to isoniazid, rifampicin, pyrazinamide, streptomycin, second-line injectables and fluoroquinolones was more than 80%. Phylogenetic analysis of WGS data revealed that the majority of MDR M. tuberculosis isolates were the Beijing lineage 2.2.1 (n = 46/65; 70.8%), while the remaining strains belonged to Euro-American lineage. Cluster analysis with a predefined cut-off distance of less than 12 single nucleotide polymorphisms between isolates showed 19 isolates in 6 clusters (clustering rate 29.2%), located mainly in the region of the capital city of Prague. This study highlights the utility of WGS as a high-resolution approach in the diagnosis, characterization of resistance patterns, and molecular-epidemiological analysis of resistant TB in the country.
- MeSH
- antituberkulotika farmakologie terapeutické užití MeSH
- fylogeneze MeSH
- genotyp MeSH
- isoniazid MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- mnohočetná bakteriální léková rezistence genetika MeSH
- multirezistentní tuberkulóza * diagnóza farmakoterapie epidemiologie MeSH
- mutace MeSH
- Mycobacterium tuberculosis * MeSH
- rifampin MeSH
- sekvenování celého genomu metody MeSH
- tuberkulóza * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
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.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- diagnostické zobrazování MeSH
- dospělí MeSH
- extenzivně rezistentní tuberkulóza * diagnostické zobrazování diagnóza epidemiologie terapie MeSH
- lidé MeSH
- mladý dospělý MeSH
- počítačová rentgenová tomografie MeSH
- příčina smrti MeSH
- rentgendiagnostika MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- antituberkulotika * MeSH
- ethambutol aplikace a dávkování terapeutické užití MeSH
- isoniazid aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- multirezistentní tuberkulóza MeSH
- pyrazinamid aplikace a dávkování terapeutické užití MeSH
- rifampin aplikace a dávkování terapeutické užití MeSH
- streptomycin aplikace a dávkování terapeutické užití MeSH
- tuberkulóza * farmakoterapie terapie MeSH
- Check Tag
- lidé MeSH
- MeSH
- analgetika MeSH
- antikoagulancia MeSH
- antikonvulziva MeSH
- antituberkulotika MeSH
- cykloserin MeSH
- ethambutol aplikace a dávkování terapeutické užití MeSH
- inhibitory protonové pumpy MeSH
- isoniazid aplikace a dávkování terapeutické užití MeSH
- kanamycin MeSH
- kapreomycin MeSH
- lidé MeSH
- pyrazinamid MeSH
- rifampin aplikace a dávkování terapeutické užití MeSH
- streptomycin aplikace a dávkování terapeutické užití MeSH
- tuberkulóza * farmakoterapie MeSH
- Check Tag
- lidé MeSH
