Multidrug-Resistant Tuberculosis in Central and Eastern Europe: Implementation and Maturity of Whole-Genome Sequencing for Surveillance.

BACKGROUND/OBJECTIVES: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health challenge in the WHO European Region, which reports the highest global proportion of rifampicin-resistant and MDR-TB cases. Whole-genome sequencing (WGS) has emerged as a key tool for improving drug-resistance detection and supporting molecular surveillance. However, the level of genomic implementation across Central and Eastern Europe (CEE) remains insufficiently characterized. This scoping review aimed to evaluate the use of WGS for MDR-TB in CEE countries and to classify implementation maturity using a predefined framework (L0-L4).

METHODS: A structured search of PubMed/MEDLINE and Web of Science identified original studies published in English between 2015 and 2026 reporting genomic applications in MDR-TB across 13 predefined CEE countries. Data were extracted on sequencing approaches, resistance prediction, transmission analysis, monitoring of new or repurposed drugs, bioinformatic pipelines, and programmatic integration. Countries were categorized according to a five-level maturity model based on documented capacity, scope of application, and integration into national tuberculosis programs (NTPs).

RESULTS: Twenty-eight studies were included. WGS was used in 23/28 studies (82.1%), predominantly for genomic resistance prediction (25/28). Transmission analysis was reported in 19/28 studies, with heterogeneous single nucleotide polymorphism (SNP) thresholds and clustering methodologies. Monitoring of resistance to new or repurposed drugs was described in 8/28 studies. No country achieved Level L4 (formally integrated genomic surveillance). Four countries were classified as L3 and nine as L2, while no L0 or L1 settings were identified.

CONCLUSIONS: Countries in Central and Eastern Europe demonstrate increasing operational use of WGS for MDR-TB, primarily driven by clinical resistance prediction. However, the lack of formal integration into national surveillance systems highlights a persistent gap between technological adoption and structured public health implementation. Strengthening programmatic integration and methodological standardization is essential for advancing genomic surveillance of MDR-TB in the region.