Abstract
Settings: The study was carried out in 4 administrative territories of the North-western federal region of Russia Federation. Namely, in Arkhangelsk oblast, Murmansk oblast, Republic of Karelia, and Republic of Komi.
Study design: An epidemiological cross-sectional study. 176 M. tuberculosis strains were isolated from tuberculosis patients diagnosed with new cases of pulmonary tuberculosis in the North-western federal region of Russia during 2004, 2005 and 2006. The isolates were tested for drug susceptibility with BACTEC 460 and typed with Restriction Fragment Length Polymorphism (RFLP) method and spoligotyping.
Objectives: Superior objectives:
1. To describe the level of drug resistance and the genetic diversity of Mycobacterium tuberculosis (M. tuberculosis) in the North-western federal region of Russia in new spear-positive civilian patients.
2. To disclose risk factors which are associated with drug resistant strains of M. tuberculosis circulating in the North-western federal region of Russia.
Specific objectives:
1. To describe the drug resistance patterns of M. tuberculosis isolates to the first-line and some of the second-line drugs in new smear-positive cases in the North-western federal region of Russia to outline the magnitude of the problem in these communities.
2. To describe the genetic diversity of the M. tuberculosis population isolated from patients residing in the study area by use of RFLP and spoligotyping.
3. To reveal social, demographical and medical characteristics of the study population that are significantly associated with possession of drug resistant tuberculosis among the current collection of M. tuberculosis strains from the North-western federal region of Russia.
Results: Rates of drug resistance for the first-line anti-tuberculosis drugs in M. tuberculosis isolates were quite high – drug resistance to isoniazid and rifampicin, the most effective anti-tuberculosis drugs, was detected in 44.9% and 31.3% of cases, respectively. Drug resistance for the second-line anti-tuberculosis drugs was lower, with the highest rates of resistance found to ethionamid– 32.9% of cases, capreomycin – in 17.0% of all isolates and kanamycin – 14.2%.
By use of spoligotyping we could reveal that there are three main lineages of M. tuberculosis which are prevalent in the study area. The Beijing lineage was identified in 46.8% of isolates. 25.1% of all the strains belonged to the T lineage, and 12.2% - to the Haarlem lineage.
By assimilating spoligotyping with RFLP data, we found 5 clades of M. tuberculosis isolates, with the biggest clade (about half of all cases) characterized by similar RFLP patterns. This clade mainly contained isolates belonging to the Beijing lineage.
On the other hand, the Beijing lineage, despite the fact of having similar RFLP pattern in most isolates, had one subgroup with heterogeneous RFLP patterns.
The Beijing lineage was found to be significantly associated with multi-drug resistance (MDR), drug resistance to all first-line anti-tuberculosis drugs and drug resistance to ethionamid, in comparison with the other two prevalent lineages of M. tuberculosis – T and Haarlem.
Conclusions: M. tuberculosis strains circulating in the North-western federal region of Russia possess high rates of drug resistance to the first-line anti-tuberculosis drugs, which have increased in comparison with the collection of strains isolated in Arkhangelsk oblast 6 years ago (1). The core of the current M. tuberculosis population was constituted by the Beijing lineage, to which about half of M. tuberculosis strains were assigned.
The Beijing family had significantly higher percentage of MDR, drug resistance to all first-line drugs, and drug resistance to ethionamid, than the other two most prevalent families – T and Haarlem. This could be one of the factors favoring the abundance of this particular lineage.
Many RFLP clusters comprised of isolates from different lineages were shared by strains from different territories in the North-western federal region of Russia. This suggested that in order to handle the tuberculosis epidemic in the North-western federal region of Russia, one may need to strengthen anti-tuberculosis programs in all regions.