Молекулярная эпидемиология туберкулеза c множественной лекарственной устойчивостью в Монголии и Восточной Сибири: два независимых процесса распространения доминирующих штаммов

Mongolia and Russia are among the countries with the high tuberculosis (TB) burden. The prevalence of tuberculosis, including multidrug-resistant tuberculosis (MDR), in Eastern Siberia bordering Mongolia is significantly higher than that in the European part of Russia. In addition, unlike Mongolia, Eastern Siberia is characterized by a high prevalence of HIV infection. The cross-border spread of socially significant infections in these countries seems to be possible due to their wide-ranging cooperation and cultural exchange. Whereas the HIV infection has no epidemiological significance for Mongolia at the moment, tuberculosis on both sides of the border has a similar prevalence. The aim was evaluation of the cross-border distribution of MDR M. tuberculosis in Mongolia and Eastern Siberia by molecular genetic data. Materials and methods : A total of 1045 strains of M. tuberculosis from Mongolia (291) and three regions of Eastern Siberia (754) were studied using the MIRU-VNTR - 24 loci genotyping. The CC2/W148 subtype was identified by the specific deletion in the kdpD gene, the CC1 subtype was identified by the SNP in pks17 gene at the position 1887060. Phylogenetic analysis of MIRU-VNTR patterns was carried out by the UPGMA tree and maximum likelihood tree. Results. The Beijing genotype was present in 75.3% (219/291) of Mongolian collection and 69.0% (520/754) of East Siberian samples. The common minor are the genotypes LAM (11.0% and 15.1%), T (10.3% and 4.5%), Haarlem (1.4% and 2.4%) in Mongolia and Eastern Siberia respectively. The genotypes S (1.3%) and Ural (5.0%) were found in the Russian samples. The main epidemic Beijing subtypes in each country belonged to different clonal complexes (CC): Mongolian Beijing strains in the majority had profiles of 342-32, 3819-32, 1773-32 MLVA types and belonged to the CC4 subtype; Russian Beijing strains mainly belonged to the CC1 (43.7% - 227/520) and CC2/W148 (34.8% - 181/520) subtypes. The level and distribution patterns of drug resistance differed significantly in Mongolia and Eastern Siberia.  Modeling of Beijing strains expansion indicates the extremely insignificant contribution of the cross-border transmission phenomenon of M. tuberculosis between Mongolia and Russia. The phylogenetic reconstruction of Beijing CC4 subtype evolution in Mongolia suggests that its distribution is primarily associated with China and other countries of the West Pacific region. Three main phylogenetic branches of CC4 subtype are found, which probably spread throughout Mongolia in the 11-12th centuries. The spread of the epidemic Beijing CC4 subtype probably occurred in two stages: early period is the emergence of ancestral CC4 variants in Mongolia or their introduction from China (they are homologous to the strains preserved in the Chinese population); later period is dissemination due to the active exchange of M. tuberculosis with countries of Southeast Asia, but not Russia.  Conclusion. Using genotyping of MIRU-VNTR 24 and classification according to specific single nucleotide polymorphisms of Beijing subtypes, separate patterns of the epidemic variants spread in Mongolia and Russia were described. It has been demonstrated that the occurrence and spread of MDR-TB in Mongolia is exclusively iatrogenic in nature, while the epidemic subtypes of the Beijing genotype (subtypes CC1 and CC2 / W148) make a significant contribution to the spread of MDR-TB in Eastern Siberia.