Tuberculosis molecular surveillance status report, focussing on rifampicin and multi-drug resistance in the EU/EEA

Between 2020 and 2023, the European Centre for Disease Prevention and Control (ECDC) analysed whole genome sequencing (WGS) profiles of rifampicin resistant (RR)- and multi-drug resistant (MDR) Mycobacterium tuberculosis strains isolated in the European Union (EU) and European Economic Area (EEA). The results obtained were added to and compared with tuberculosis (TB) WGS data collected during the period 2017−2019 as a part of an EU/EEA pilot project on TB molecular surveillance.

Analysis of 2 490 RR/MDR TB isolates with complete WGS data showed:

• a sub-optimal typing coverage at EU/EEA level. Only nine countries contributed, with 514 strain sequences during the period 2020−2022;
• wide variation in the sequencing coverage. The highest sequencing coverage was achieved in 2018(71.0%), while the lowest coverage was observed in 2020 (18.8%);
• a relatively stable clustering proportion. The lowest clustering percentage was observed in 2018 (53.9%)and the highest in 2020 and 2021 (64.1%);
• the identification of 67 cross-border molecular clusters, comprising 632 RR/MDR TB strains in total. Only 18clusters included 10 or more strains, involving two to nine countries in each cluster;
• limitations due to the incompleteness of data for some non-mandatory variables (e.g. country ofbirth/nationality). As a consequence, in-depth analyses of cluster dynamics and possible transmission routes within the clusters was not possible;
• successful lineage assignment in 87.5% of the strains. The most prevalent lineages were Beijing (N=749,30.1%), Mainly T (N=534, 21.4%) and Haarlem (N=303, 12.2%). Due to the low number of countries submitting WGS data during the period 2020−2022, Beijing lineage became a dominant strain, however this should be interpreted with caution.

The COVID-19 pandemic had a significant impact on TB laboratory services in the EU/EEA [1]. In acknowledgement of this fact, and so as to continue supporting EU/EEA countries in consolidating TB WGS-based surveillance activities, ECDC offered sequencing support to countries wishing to have their RR/MDR TB strains sequenced. Six countries showed interest and benefited from this support. A further three countries with in-country WGS capacity also submitted WGS data during the period 2020−2022.

In conclusion, despite the support and IT infrastructure available at ECDC, efforts are still needed to consolidate the WGS-based surveillance of TB in the EU/EEA in order to achieve the 2017−2019 level as a minimum. A higher coverage of WGS will contribute to a better understanding of rifampicin resistant (RR)- and multi-drug resistant (MDR) TB strain diversity, early detection and tracing of trans-national outbreaks and the mapping of transmission routes across Europe, as well as changes in the resistance pattern and mechanism.