Genetic variation of Mycobacterium tuberculosis circulating in Kharkiv Oblast, Ukraine

Abstract

BackgroundA persistent increase of tuberculosis cases has recently been noted in the Ukraine. The reported incidence of drug-resistant isolates of M. tuberculosis is growing steadily; however, data on the genetic variation of isolates of M. tuberculosis circulating in northern Ukraine and on the spectrum and frequency of occurrence of mutations determining resistance to the principal anti-tuberculosis drugs isoniazid and rifampicin have not yet been reported.MethodsIsolates of M. tuberculosis from 98 tuberculosis patients living in Kharkiv Oblast (Ukraine) were analyzed using VNTR- and RFLP-IS6110-typing methods. Mutations associated with resistance to rifampicin and isoniazid were detected by RFLP-PCR methods, and also confirmed by sequencing.ResultsWe identified 75 different genetic profiles. Thirty four (34%) isolates belonged to the Beijing genotype and 23 (23%) isolates belonged to the LAM family. A cluster of isolates belonging to the LAM family had significant genetic heterogeneity, indicating that this family had an ancient distribution and circulation in this geographical region. Moreover, we found a significant percentage of the isolates (36%) belonged to as yet unidentified families of M. tuberculosis or had individual non-clustering genotypes. Mutations conferring rifampicin and isoniazid resistance were detected in 49% and 54% isolates, respectively. Mutations in codon 531 of the rpoB gene and codon 315 of the katG gene were predominant among drug-resistant isolates. An association was found for belonging to the LAM strain family and having multiple drug resistance (R = 0.27, p = 0.0059) and also for the presence of a mutation in codon 531 of the rpoB gene and belonging to the Beijing strain family (R = 0.2, p = 0.04).ConclusionsTransmission of drug-resistant isolates seems to contribute to the spread of resistant TB in this oblast. The Beijing genotype and LAM genotype should be seen as a major cause of drug resistant TB in this region.

Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolates from China

“…Studies in Russia (54) and Ukraine (55) found that rpoB531 was highly prevalent in strains of the Beijing genotype. In contrast, we found no significant association between the genotype and any resistance-conferring mutation, including rpoB531.…”

Molecular Epidemiology of Tuberculosis in the Kaliningrad Region of Russia: 10 Years After

“…В Республике Карелия на протяжении по-следнего десятилетия доля штаммов данного генотипа оставалась практически неизмен-ной (около 55%) [3]. В целом штаммы генотипа Beijing преобладают в структуре российской популяции M. tuberculosis (в среднем около 50%) и в странах постсоветского пространства: Бе-ларусь -36,2%, Украина -31,6%, Эстония -39,2% [7,15,20,25,28]. Напротив, в других странах Европы распространенность штаммов Beijing относительно невелика: Финляндия -5,2%, Швеция -5,8%, Польша -6,5%, причем их источники иные и более разнообразные, включая, в частности, штаммы, занесенные из Восточной Азии [6,11,24].…”

“…Так, если в Карелии и Ле-нинградской области их доля составляла 10,3% (что сопоставимо с Финляндией -7,3%), то в Псковской области превышала 20%, что близ-ко к показателю в Эстонии (17,8%) [1,3,18,24,25]. В Беларуси и Украине штаммы семейства LAM занимают второе место по распростра-ненности (около 23%) после Beijing и в структу-ре МЛУ штаммов (39,5 и 22,9% соответственно) [7,22,28].…”

“…При этом все 14 штаммов Таблица 2. Генотипы и лекарственная устойчивость штаммов M. tuberculosis [7,12,22,26,28], тогда как в Польше -лишь 8,7% [9]. Следует отметить, что за прошедшее деся-тилетие в Калининградской области доля МЛУ штаммов генотипа Beijing существенно не из-менилась: в 2006 г.…”

IS6110 the Double-Edged Passenger

“…The study showed that MDR-TB strains were actively transmitted in the northern Russia (Mäkinen et al, 2011). In Ukraine, where increase of TB cases is maintained, the number of drug-resistant isolates was reported to be growing steadily, and transmission of drug-resistant isolates seems to contribute to the spread of resistant TB (Dymova et al, 2011). The MDR-TB genotyping databases allow the comparison of M. tuberculosis strains to improve the application of appropriate public health actions at a national level and, ideally, it should be extended across country borders (Bifani et al, 2001;Gavin et al, 2011;Ritacco et al, 2011).…”