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