Vanessa Mohr (Borstel / DE), Lena Bös (Berlin / DE), Sönke Andres (Borstel / DE), Thomas Kohl (Borstel / DE), Martin Kuhns (Borstel / DE), Walter Haas (Berlin / DE), Inna Friesen (Borstel / DE), Stefan Kröger (Berlin / DE), Stefan Niemann (Borstel / DE)
Introduction
Emerging multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) create significant challenges for TB control, particularly in Eastern European countries such as the Ukraine. International spread of highly resistant Mycobacterium tuberculosis complex (Mtbc) strains potentially impacts the MDR TB epidemiology in low incidence countries in Europe.
Materials & Method
Since 2020, WGS of Mtbc strains was carried out as part of the integrated molecular surveillance of TB (IMS-TB) by the Robert Koch Institute (RKI) and the National Reference Center (NRC) for Mycobacteria. Including retrospective data (years 1993 – 2019), whole genome sequencing (WGS) data of more than 11,000 Mtbc strains from Germany, containing more than 5,000 datasets from 2020 to 2023, are available at the NRC. Genome sequencing data were used for phylogenetic strain classifications, genomic resistance predictions based on the extended WHO catalogue (2021) and allele-based core genome cluster analysis using a threshold of 12 Alleles.
Results
Among the dataset, 67 rifampicin resistant (RR) lineage 2 (Beijing) Mtbc strains were identified between 2000 and 2023 (analyses for 2023 ongoing) based on their particular mutation profile (e.g. embB Y334H mutation) that also show a close genomic relationship with a pairwise distance of 16. Since the beginning of the war in Ukraine, 13 isolates were detected in 2022 and 9 in 2023. Out of all isolates, 35 were RR/MDR, 28 pre-XDR (MDR plus fluoroquinolone resistance), and four XDR. Cluster analysis with a threshold of 5 alleles revealed substructures with 7 clusters ranging in size from 2 to 22 isolates. Similarity analysis linked all isolates to a previously described MDR strain detected in Ukraine. Of the 22 isolates from 2022 and 2023, 16 cases were born in Ukraine, while 6 were born in other countries outside of Germany.
Summary
Our data suggest that the emergence of the described highly resistant MDR Mtbc isolates in Germany is linked to migration from Ukraine. Prospective surveillance is crucial to monitor potential long-term impacts on the MDR TB epidemiology in Germany.