Transborder molecular analysis of MDR tuberculosis dynamics in Mongolia and Eastern Siberia, Russia

Mongolia and Eastern Siberia, Russia are border regions in Asia with high incidence of tuberculosis (TB). In this study, we aimed to investigate MDR - TB transborder transmission with a focus on endemic and epidemic Mycobacterium tuberculosis clones and drug resistance patterns. M. tuberculosis strains (291 from Mongolia and 754 from Russia) were collected within cross-sectional population-based surveys in 2010-2016. DNA was genotyped in 24 MIRU-VNTR loci and by PCR testing of the key SNP markers to discriminate within Beijing genotype. In total, 1045 isolates were divided into 435 MIRU-types that were assigned to Lineage 2 (Beijing isolates) and Lineage 4 (Ural, Haarlem, Latin-American-Mediterranean [LAM], S, and unclassified isolates). Beijing genotype was dominant in both countries, but most of Russian and all Mongolian Beijing strains belonged to different subtypes of the modern Beijing sublineage with only negligible overlap between the two countries. In particular, the Beijing types #342-32, #3819-32, #1773-32 (Asian African 2 group) were found only in Mongolia. LAM was the most common non-Beijing genotype (11.0% in Mongolia and 14.7% in Russia) and its isolates mostly belonged to LAM-RUS branch. MDR rate was higher in Russia compared to Mongolia among newly diagnosed patients: 29.4% versus 4.2% (p < 0.001) but similar and high in the retreatment subgroups (65.8% and 67.4%, respectively). In Russian collection, a higher MDR rate was observed in (i) Beijing compared to non-Beijing (47.5% versus 38.8%, p = 0.03), (ii) Beijing B0/W148 subtype compared to Beijing Central Asian/Russian subtype (64.5% versus 39.3%, p <0.001). In Mongolia, MDR rate was similar in Beijing (29.7%) and non-Beijing (27.5%) genotypes. In conclusion, population structures of the Beijing genotype in Mongolia and Russian borderline regions differ significantly including specific patterns of drug resistance. In contrast, largely overlapping LAM subtypes may correlate with historical endemic circulation of the LAM-RUS branch in Northern Eurasia.