Key impact of Beijing strains including new resistant clusters on spread of multidrug-resistant tuberculosis in northern Russia.

Northern Russia is characterized by socio-environmental conditions contributing to the spread of tuberculosis (TB) and a high ~30% rate of primary multidrug-resistant (MDR) TB. We applied high-resolution molecular methods to study thepopulation in the Arkhangelsk region of Northern Russia. All availableisolates recovered from newly diagnosed patients from January to December 2018 (= 88) were genotyped using 24-loci MIRU-VNTR, spoligotyping, and, partly, by whole-genome sequencing (WGS). The population structure revealed a predominance of the Beijing genotype and Euro-American lineage, with significant drug resistance burden associated with Beijing and its B0/W148 strain. Beijing strains showed a significantly higher association with MDR and pre-extensively drug-resistant (pre-XDR) TB compared to non-Beijing strains (= 0.0013). All Beijing B0/W148 isolates were MDR, whereas the majority (71.4%) of Beijing Central Asian/Russian subtype strains were drug-sensitive. WGS analysis of newly discovered Beijing clusters 3828-32 and 10167-32 in this area indicated a historical transmission over several decades, reflecting long-term endemic circulation. The presence of compensatory mutations inamong MDR strains suggests enhanced fitness facilitating their ongoing transmission. An intriguing cluster of recent transmission of a non-Beijing strain (spoligotype SIT53, L4.8 sublineage) was identified through combined epidemiological and genomic investigation. To conclude, the prevalence of Beijing strains rose from 39.3% in 1998 to 67.0% (< 0.001), and Russian epidemic MDR strain B0/W148 increased its rate from 11.2% in 1998 to 20.5% (= 0.097). This highlights the key role of MDR Beijing strains, including new resistant clusters, in disseminating MDR-TB in the region and the importance of continuous surveillance using high-resolution genotyping.IMPORTANCEThe Arkhangelsk region is the largest province of northern European Russia. One-third of newly diagnosed tuberculosis patients are infected with multidrug-resistant (MDR)strains. We assessed the molecular population structure ofin the Arkhangelsk region in the COVID-19 pre-pandemic year 2018. We identified important MDR clusters and elucidated tuberculosis transmission patterns. An intriguing cluster of recent transmission was identified through the combined use of epidemiological investigation and whole-genome sequencing. The prevalence of Beijing genotype strains increased from 39.3% in 1998 to 67.0%, and the Russian epidemic MDR strain B0/W148 doubled from 11.2% in 1998 to 20.5%. Furthermore, we described new MDR clusters emerging within the Beijing genotype. This highlights the key impact of the MDR Beijing strains and the importance of continuous surveillance using high-resolution genotyping. This study of the pre-pandemic strain collection provides an indispensable intermediate time point between earlier studies carried out 25 years ago and ongoing surveillance.