Genetic variation of Mycobacterium tuberculosis circulating in Kharkiv Oblast, Ukraine

Maya A Dymova,Valeriy S Krutko,Oleksander O Liashenko,Eugeny A Khrapov,Maxim L Filipenko,Petro I Poteiko

doi:10.1186/1471-2334-11-77

Maya A Dymova, Valeriy S Krutko + Show 4 more

Open Access

https://doi.org/10.1186/1471-2334-11-77

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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.

Highlights

A persistent increase of tuberculosis cases has recently been noted in the Ukraine
Isolates of M. tuberculosis belonging to the Beijing strain family are associated with drug resistance in Iran, Afghanistan, and Russia [6,7,8]
The reported incidence of drug-resistant isolates of M. tuberculosis is growing steadily; 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

Summary

Introduction

The reported incidence of drug-resistant isolates of M. tuberculosis is growing steadily; 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. Tuberculosis remains to this day the most widespread infectious disease in many parts of the world and has high mortality rate. Among the estimated 9 million new cases that are annually recorded, antibiotic drug resistance of Mycobacterium tuberculosis has become an increasing problem. A detailed study of regional population structures of M. tuberculosis and identification of the specific genotypes associated with drug resistance can facilitate both a more effective drug therapy regime and give information at the molecularepidemiological level

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