Population structure of drug-resistant Mycobacterium tuberculosis in Central Asia

Abstract

BackgroundDrug-resistant tuberculosis (TB) is a major public health concern threathing the success of TB control efforts, and this is particularily problematic in Central Asia. Here, we present the first analysis of the population structure of Mycobacterium tuberculosis complex isolates in the Central Asian republics Uzbekistan, Tajikistan, and Kyrgyzstan.MethodsThe study set consisted of 607 isolates with 235 from Uzbekistan, 206 from Tajikistan, and 166 from Kyrgyzstan. 24-loci MIRU-VNTR (Mycobacterial Interspersed Repetitive Units - Variable Number of Tandem Repeats) typing and spoligotyping were combined for genotyping. In addition, phenotypic drug suceptibility was performed.ResultsThe population structure mainly comprises strains of the Beijing lineage (411/607). 349 of the 411 Beijing isolates formed clusters, compared to only 33 of the 196 isolates from other clades. Beijing 94–32 (n = 145) and 100–32 (n = 70) formed the largest clusters. Beijing isolates were more frequently multidrug-resistant, pre-extensively resistant (pre-XDR)- or XDR-TB than other genotypes.ConclusionsBeijing clusters 94–32 and 100–32 are the dominant MTB genotypes in Central Asia. The relative size of 100–32 compared to previous studies in Kazakhstan and its unequal geographic distribution support the hypothesis of its more recent emergence in Central Asia. The data also demonstrate that clonal spread of resistant TB strains, particularly of the Beijing lineage, is a root of the so far uncontroled MDR-TB epidemic in Central Asia.

Genotyping, Assessment of Virulence and Antibacterial Resistance of the Rostov Strain of Mycobacterium tuberculosis Attributed to the Central Asia Outbreak Clade

“…It largely correlates with the 94-32 cluster and M2 subtype according to multilocus variable-number tandem-repeat analysis (MLVA) and mycobacterial interspersed repetitive unit (MIRU) typing, respectively [19,20]. The members of the population are characterized by a high level of drug resistance and comprise about one-fourth of the pathogen population in Uzbekistan, Tajikistan, Kyrgyzstan, and Kazakhstan [21][22][23]. Additionally, these strains distributed in Russia and other former Soviet Republics [7].…”

Genetic profiling of Mycobacterium tuberculosis revealed “modern” Beijing strains linked to MDR-TB from Southwestern Colombia

“…Additionally, an important trend between female and MDR-TB in patients from South America and other geographical areas has been reported [41][42][43][44]. The link we found between female and MDR "modern" Beijing strains is intriguing since Mtb has affected mostly men specially in low and middle-income countries [45] and there is also evidence of some Beijing strains affecting more frequently men than women (2:1 ratio approximately) [4,46,47].…”

Transmission of pre-XDR and XDR-TB in the Mumbai Metropolitan Region, India

“…Previously, we determined dominant MDR clones in Eastern European settings, and could show that the spread of a few dominant MDR MTBC strains with compensatory mutations e.g. in rpoC can significantly affect the MDR-TB epidemic in specific regions 8,9,23,24 . However, pre-XDR and XDR-TB cases have until now been found at a comparably lower frequency and FQ resistance has not been present in more than 30% of the isolates 8,9,23,24 .…”

“…in rpoC can significantly affect the MDR-TB epidemic in specific regions 8,9,29,30 . However, pre-XDR and XDR-TB cases have until now been found at a comparably lower frequency and FQ resistance has not been present in more than 30% of the isolates 8,9,29,30 . Thus, our data extend these findings to pre-XDR/XDR-TB and demonstrate that pre-XDR/XDR-TB can be propelled by a few lineages that have obviously acquired compensatory mutations, transmit efficiently and reach high prevalence in the population.…”