Globally, mutations in the katG gene account for the majority of isoniazid-resistant strains of Mycobacterium tuberculosis. Buyankhishig et al. analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA mutations (B. Buyankhishig, T. Oyuntuya, B. Tserelmaa, J. Sarantuya, et al., Int J Mycobacteriol 1:40–44, 2012, https://doi.org/10.1016/j.ijmyco.2012.01.007). The GenoType MTBDRplus assay was performed for isolates collected in the First National Tuberculosis Prevalence Survey and the Third Anti-Tuberculosis Drug Resistance Survey to investigate genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis in Mongolia. Of the 409 isoniazid-resistant isolates detected by the GenoType MTBDRplus assay, 127 (31.1%) were resistant to rifampin, 294 (71.9%) had inhA mutations without katG mutations, 113 (27.6%) had katG mutations without inhA mutations, and 2 (0.5%) had mutations in both the inhA and katG genes. Of the 115 strains with any katG mutation, 114 (99.1%) had mutations in codon 315 (S315T). Of the 296 strains with any inhA mutation, 290 (98.0%) had a C15T mutation. The proportions of isoniazid-resistant strains with katG mutations were 25.3% among new cases and 36.2% among retreatment cases (P = 0.03) and 17.0% among rifampin-susceptible strains and 52.8% among rifampin-resistant strains (P < 0.01). Rifampin resistance was significantly associated with the katG mutation (adjusted odds ratio, 5.36; 95% confidence interval [CI], 3.3 to 8.67, P < 0.001). Mutations in inhA predominated in isoniazid-resistant tuberculosis in Mongolia. However, the proportion of katG mutations in isolates from previously treated cases was higher than in those from new cases, and the proportion in cases with rifampin resistance was higher than in cases without rifampin resistance.

No abstract

Spatiotemporal analysis indicates likely cross-border spread of MDR-TB along the Trans-Siberian Railway line, with subsequent spatial expansion across Mongolia. The frequency of MDR-TB among young patients with pan-resistance to all first-line drugs suggests ongoing MDR-TB transmission within the community.

OBJECTIVES: To assess the performance of the GenoType MTBDRsl v1, a line-probe assay (LPA), to exclude baseline resistance to fluoroquinolones (FQs) and second-line injectables (SLIs) in the Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB 1 (STREAM 1) trial.METHODS: Direct sputum MTBDRsl results in the site laboratories were compared to indirect phenotypic drug susceptibility testing (pDST) results in the central laboratory, with DNA sequencing as a reference standard.RESULTS: Of 413 multidrug-resistant TB (MDR-TB) patients tested using MTBDRsl and pDST, 389 (94.2%) were FQ-susceptible and 7 (1.7%) FQ-resistant, while 17 (4.1%) had an inconclusive MTBDRsl result. For SLI, 372 (90.1%) were susceptible, 5 (1.2%) resistant and 36 (8.7%) inconclusive. There were 9 (2.3%) FQ discordant pDST/MTBDRsl results, of which 3 revealed a mutation and 5 (1.3%) SLI discordant pDST/MTBDRsl results, none of which were mutants on sequencing. Among the 17 FQ- and SLI MTBDRsl-inconclusive samples, sequencing showed 1 FQ- and zero SLI-resistant results, similar to frequencies among the conclusive MTBDRsl. The majority of inconclusive MTBDRsl results were associated with low bacillary load samples (acid-fast bacilli smear-negative or scantily positive) compared to conclusive results (P < 0.001).CONCLUSION: MTBDRsl can facilitate the rapid exclusion of FQ and SLI resistances for enrolment in clinical trials.

Всемирное распространение Mycobacterium tuberculosis и масштабы заболеваемости туберкулёзом обусловливают важность эпидемиологических исследований возбудителя: бактериологических, физиологических, генетических,-и, кроме того, особенностей пространственной структуры групп микроорганизмов, отличающихся по патогенетическому потенциалу и филогенетическим дистанциям. Данная работа посвящена изучению филогеографии эпидемически значимых генетических групп M. tuberculosis, циркулирующих в Монголии-регионе с высокой заболеваемостью туберкулёзом. По результатам исследования 309 штаммов возбудителя методами MIRU-VNTR типирования, LSP-типирования и субтипирования (сравнение результатов с референсными MIRU-VNTR профилями, выявление специфичных SNPs) в качестве доминирующего идентифицирован генотип Beijing (субтип CC4). Для данного генотипа характерна высокая частота кластеризации, что свидетельствует как о его эпидемической опасности, так и об относительно недавнем заносе «успешных» штаммов на территорию Монголии. Выявлена также достаточно однородная структура распределения генотипов и субтипов возбудителя в пределах изучаемого региона, которая отличается от структуры российской популяции M. tuberculosis своим субтипическим составом. Таким образом, в качестве возможного источника распространения штаммов субтипа CC4 генотипа Beijing на территорию Монголии предполагаются соседние Восточно-Азиатские регионы, наиболее вероятно-северные провинции Китая (Внутренняя Монголия) или ближайшие страны Юго-Восточной Азии.