How do resistant strains of tuberculosis develop and spread? One of the largest genomic studies of tuberculosis in Ukraine to date shows that a large number of drug-resistant pathogens belong to just a few, closely related groups of pathogens. The findings highlight the importance of continuous genomic surveillance of tuberculosis and other antibiotic-resistant pathogens. Prof. Dr Stefan Niemann from the Research Alliance Leibniz INFECTIONS was involved in the study.

An international research team led by Ukrainian researchers and scientists from the Research Center Borstel, Leibniz Lung Center (FZB) has uncovered important drivers of the drug-resistant tuberculosis (TB) epidemic in Ukraine. Analysing data from more than 4,000 patients from 18 Ukrainian regions, the researchers found that highly drug-resistant TB is strongly dominated by closely related strains of Mycobacterium tuberculosis Lineage 2, pointing to transmission as an important driver of the epidemic. At the same time, the study reveals an encouraging trend: resistance to fluoroquinolones, key drugs for treating multidrug-resistant TB, declined from around 41% in 2019–2020 to approximately 28% in 2023. Treatment success increased from around 60% to more than 73% over the study period. The findings have now been published in The Lancet Regional Health – Europe.

Genomics reveals transmission of drug-resistant TB

The researchers analysed whole-genome sequences of M. tuberculosis complex isolates from 4,162 patients and combined these data with detailed clinical, treatment and radiological information collected through the NIAID TB Portals Program. Lineage 2 (Beijing) strains, accounted for approximately 70% of all isolates and were particularly dominant among multidrug-resistant and more extensively drug-resistant strains. More than half of the drug-resistant isolates were part of genomic clusters, with several large clusters formed by Lineage 2 strains.

“This shows that drug resistance is not only emerging independently during treatment. Successful resistant strains are being transmitted between patients and contribute substantially to the drug-resistant TB epidemic in Ukraine,” says Professor Dr Dmytro Butov, first author of the study and scientist at FZB and Kharkiv National Medical University. These findings underline the importance of genomic surveillance to identify outbreaks and interrupt transmission chains at an early stage.

Encouraging trends despite war and disruption

Despite the high overall burden of drug resistance, the study also identified positive developments. Fluoroquinolone resistance declined significantly, while resistance to several newer and repurposed drugs remained comparatively uncommon, including bedaquiline (2.5%), clofazimine (2.3%), linezolid (0.9%) and delamanid (0.1%). The study covers December 2019 to November 2023, a period spanning the COVID-19 pandemic and Russia’s full-scale invasion of Ukraine in February 2022. Despite massive disruption of healthcare infrastructure and population displacement, treatment outcomes improved during this period. Importantly, the detection of multidrug resistant strains which also had a combined resistance to fluoroquinolones, bedaquiline and linezolid represents an important warning signal, as these drugs are key components of the shorter all-oral regimens increasingly used to treat drug-resistant TB.

Research maintained under wartime conditions

The study was made possible by a nationwide network of approximately 100 physicians, laboratory specialists and researchers working across 18 Ukrainian regions within the TB Portals Ukraine team. Even under wartime conditions, the network maintained clinical documentation, sample collection and research activities.

“The commitment of our Ukrainian colleagues under these extraordinary circumstances cannot be overstated,” says Professor Dr Stefan Niemann, Head of Molecular and Experimental Mycobacteriology at FZB and scientists of the Research Alliance Leibniz INFECTIONS.

The study highlights a fundamental advantage of genomic methods: a conventional resistance test primarily shows which drugs a bacterium is resistant to. Whole-genome sequencing can, in addition, provide information on the genetic relationship between different pathogens. This makes it possible to track resistant pathogen lineages and clusters across time and space. For public health research, this opens up the possibility of distinguishing between resistance that has arisen independently and the spread of pathogen populations that are already resistant. This is particularly relevant in the case of tuberculosis. The pathogen can persist in human populations over long periods, and resistant strains can develop independently of one another or spread further within populations. Population movements and changes to healthcare systems can further influence these dynamics.

“The study shows why sustained genomic surveillance is so important: we need to know which resistant strains are spreading in order to adapt diagnostics, treatment and public-health interventions,” emphasizes last author Dr Viola Dreyer from FZB, who played a leading role in the genomic analyses and preparation of the study.

The findings are also relevant beyond Ukraine. War-related population displacement and cross-border mobility make coordinated genomic surveillance and continuity of TB diagnosis and treatment increasingly important across Europe.

Source

Dmytro Butov et al.: Drug-resistance profiles, population structure, genomic clustering, and temporal trends in drug resistance among Mycobacterium tuberculosis complex isolates in Ukraine, 2019–2023: a multicentre cohort study. The Lancet Regional Health – Europe 70 (2026), 101865. https://doi.org/10.1016/j.lanepe.2026.101865