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In 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).

Tuberculosis is one of the main problems of medicine in Kazakhstan. Kazakhstan is on the list of 30 countries with high rates of multidrug resistant tuberculosis in the world. Aim of this study is to conduct genotyping by MIRU-VNTR method to get preliminary data on M. tuberculosis genotypes distributed among the clinical isolates in Kazakhstan. 271 M. tuberculosis clinical isolates were gathered from new cases of tuberculosis from different regions of Kazakhstan in this study. Genotyping was done using 15 MIRU-VNTR (12 MIRU+3 ETR) loci. Obtained digital profiles of the clinical isolates were analyzed using the database on miru-vntrplus.org. Phylogenetic tree was built by UPGMA method. 97 genotypes were identified, 70 (25.8%) of them were unique and were determined in one isolate in the sample collection. The rest 201 (74.2%) isolates were grouped into 27 clusters, that contained from 2 to 102 isolates. According to genotyping results M. tuberculosis Beijing family strains were found in 65.3% cases. 121 out of 177 Beijing isolates (68.4%) were drug-resistant. Prevalence of MDR-TB was detected among drug-resistant Beijing (58.7% - 71/121) and LAM family (50% - 10/20) isolates.

Republic of Kazakhstan is among the 27 high multidrug-resistant tuberculosis (MDR-TB) burden countries in the world. Here, we analyzed the population structure and phylogeography of Mycobacterium tuberculosis in Kazakhstan and impact of the identified genotypes on spread of drug resistant strains. A total of 159 M. tuberculosis isolates from different regions of Kazakhstan were typed using 24-MIRU-VNTR and spoligotyping, and the profiles were compared to the MIRU-VNTRplus and SITVIT_WEB databases. Eight isolates with double VNTR alleles were excluded from further analysis that was performed on 151 isolates. They were assigned to 10 families, Beijing (n = 109) being the largest and dominated by a single clonal cluster 94-32 and derived profiles (n = 101). The other families were represented mainly by LAM (n = 17), Ural (n = 8), NEW-1 (n = 3) and a new cluster named KAZ-1 (n = 8). Beijing, LAM and Ural isolates were detected in all parts of the country while Iran-specific family NEW-1 was found only in southern Kazakhstan (P = 0.001). A reduced scheme of 10 most polymorphic VNTR loci provided a discrimination similar to that achieved by 15-MIRU scheme and may be recommended for rapid preliminary screening of the clinical isolates in Kazakhstan. Multi-drug resistance was significantly more prevalent among Beijing (64/109) and LAM (7/17) strains compared to strains of other families (1/25; P = 0.0006 and 0.01, respectively). High prevalence of the genetically closely related MDR strains of the Beijing genotype found in different regions of Kazakhstan highlights their crucial impact on the current TB epidemic in this country., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Setting: Pyrazinamide (PZA), an important first-line drug for anti-tuberculosis treatment, demonstrates potent activity against semi-dormant bacilli in acidic environments. However, the diagnosis of PZA resistance is often impeded by technical difficulties., Objective: To characterise mutations in the pncA and rpsA genes among PZA-resistant and PZA-susceptible clinical Mycobacterium tuberculosis isolates circulating in Kazakhstan. The potential use of genotyping to identify PZA resistance was also investigated., Design: PZA drug susceptibility testing and pncA and rpsA gene sequencing were performed on 77 clinical M. tuberculosis isolates; mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing was performed on 74 clinical M. tuberculosis isolates., Results: Of the 77 clinical M. tuberculosis isolates, 41 (53.2%) were phenotypically resistant to PZA, whereas 36 (46.7%) were susceptible; 48 (62.3%) of these isolates were also multidrug-resistant (MDR). Furthermore, 38 (49.3%) clinical isolates showed mutations in the pncA gene and its flanking region; the majority of these isolates (n = 36, 94.7%) were also MDR. Gene sequencing showed that only synonymous substitutions affecting rpsA occurred. MIRU-VNTR typing revealed that 78.4% of isolates were of the Beijing genotype., Conclusions: Sequencing revealed that mutations in pncA, but not in rpsA, occurred in PZA-resistant M. tuberculosis isolates circulating in the territory of Kazakhstan.

Kazakhstan is one of the 14 countries with a high rate of morbidity due to multidrug-resistant tuberculosis (MDR TB) in WHO European region. The aim of our study was to characterize mutations associated with drug resistance to rifampicin and isoniazid in Mycobacterium tuberculosis isolates from Kazakhstan. M. tuberculosis strains were isolated from TB patients in different regions of Kazakhstan. A drug susceptibility test was performed on Lowenstein-Jensen medium using the absolute concentration method. Sequencing analysis was performed of the rpoB rifampicin resistance-determining region and the katG gene, the oxyR-ahpC intergenic region, and the inhA promoter region in 259 MDR M. tuberculosis isolates, in 51 isoniazid-resistant isolates, and in 13 rifampicin-resistant isolates. The mutational analysis revealed that the most frequent mutations associated with rifampicin and isoniazid resistance in M. tuberculosis are the substitutions at codons 531 (82.7%) and 315 (98.4%) in the rpoB and katG genes, respectively. In addition, we have found mutations with lower frequency at codon 526 (8.4%), 533 (1.5%), and 516 (1.1%) in the rpoB gene. In 6.2% of the isolates, no mutations were found in the rpoB gene. The findings of this study provide useful data for a better understanding of the mutation spectrum of isoniazid and rifampicin resistance among strains isolated from patients in Kazakhstan. Our results are also useful for the development of diagnostic tests of MDR M. tuberculosis.