Genomic characterization of MDR/XDR-TB in Kazakhstan by a combination of high-throughput methods predominantly shows the ongoing transmission of L2/Beijing 94-32 central Asian/Russian clusters.

BACKGROUND: Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community benefit. METHODS: A convenience sample of 700 MTC DNA cultures extracts from 630 tuberculosis patients recruited from 12 out of 14 regions in Kazakhstan, between 2010 and 2015, was independently studied by high-throughput hybridization-based methods, TB-SPRINT (59-Plex, n = 700), TB-SNPID (50-Plex, n = 543). DNA from 391 clinical isolates was successfully typed by two methods. To resolve the population structure of drug-resistant clades in more detail two complementary assays were run on the L2 isolates: an IS6110-NTF insertion site typing assay and a SigE SNP polymorphism assay. RESULTS: Strains belonged to L2/Beijing and L4/Euro-American sublineages; L2/Beijing prevalence totaled almost 80%. 50% of all samples were resistant to RIF and to INH., Subtyping showed that: (1) all L2/Beijing were "modern" Beijing and (2) most of these belonged to the previously described 94-32 sublineage (Central Asian/Russian), (3) at least two populations of the Central Asian/Russian sublineages are circulating in Kazakhstan, with different evolutionary dynamics. CONCLUSIONS: For the first time, the global genetic diversity and population structure of M. tuberculosis genotypes circulating in Kazakhstan was obtained and compared to previous local studies. Results suggest a region-specific spread of a very limited number of L2/Beijing clonal complexes in Kazakhstan many strongly associated with an MDR phenotype.

[Development of technology and study of the immunobiological properties of a sour milk beverage based on camel milk].

The article presents data on the technology of production of a fermented milk product based on camel milk and the evaluation of its immunotropic properties in еthe experiment on 60 male mice F1 (CBAxC57Bl/6) with an initial body weight 17.8±0.1 g. To simulate immune suppression, mice were injected cyclophosphamide intraperitoneally (125 mg/kg b.w.). The fermented milk product was daily administered orally in a volume of 0.5 ml/mouse for 30 days (n=30). The animals of the control group (n=30) received a similar amount of distilled water. The study of the immunotropic activity of a fermented milk drink on the model of immune deficiency showed that a 30-day administration to mice caused an increase in the number of antibody-plaque-forming cells (IgM-AFC) by 1.3 times in spleen of mice (32.4×103 vs 24.7×103 per organ in the control group). The analyzed drink strengthened the effector phase of the response of the cellular response to erythrocytes of the sheep. Thus, in mice treated with distilled water (control group), the reaction index was 7.80%, while in mice of the main group it increased by 70% and amounted to 13.26%. The use of a fermented dairy product in immune-deficient mice resulted in a significant (by 63%) increase of antioxidant activity of blood plasma. At the same time, the imbalance in the functioning of antiradical protection enzymes (catalase and superoxide dismutase) reduced sharply, indicating an increase in the adaptive capacity of the organism, disturbed by the introduction of an immune suppressive compound. The obtained data indicate a pronounced immune modulating and antioxidant effects of the fermented dairy product based on camel milk, which can be used in the prevention and in complex therapy of secondary immune deficiencies and inflammatory diseases.

Molecular epidemiology of Mycobacterium tuberculosis strains circulating in the penitentiary system of Kazakhstan.

A total of 60 Mycobacterium tuberculosis isolates collected from patients in prisons in Kazakhstan and 125 from the civilian sector were examined using mycobacterial interspersed repetitive units-variable number of tandem repeat analysis in 2012. The proportion of tuberculosis strains with unique genotypes isolated from the civilian patients was 50.4%, while that in the prison patients was 31.7%. This difference was statistically significant (χ(2) 4.42, P 0.035), and may reflect a low genetic diversity of M. tuberculosis strains isolated from prison patients. The frequencies of mutations in the rpoB531 and katG315 genes of the M. tuberculosis strains isolated from the civilians and in the penitentiary system were not significantly different (rpoB531: 82.4% vs. 88.3%, and katG315: 98.4% vs. 100%, respectively).

HLA-class II alleles in patients with drug-resistant pulmonary tuberculosis in Kazakhstan.

The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Some studies have reported that HLA class II genes play a strong role in severe cases of pulmonary tuberculosis (PTB) in several populations. Thus the aim of the study was to compare the HLA-class II alleles of patients with drug resistant tuberculosis with those of healthy controls from the same ethnic group in Kazakhstan. The aim of the present study was to evaluate the correlation of HLA-class II alleles by patients with drug resistant tuberculosis and the healthy controls of the same ethnic group in Kazakhstan. The HLA-class II alleles of 76 patients with tuberculosis (TB) and 157 healthy volunteers were investigated using sequence-based typing (SBT)-method. HLA-DQA1*03:02 HLA-DRB1*08:01 and DRB1*08:03 occurred more frequently (P = 0.05) in patients with drug resistant tuberculosis than in controls. We observed a possible association between certain HLA alleles and TB that are specific for the Kazakh population. Further studies are needed to confirm our findings using a larger number of patients with drug resistant tuberculosis.

[Informative value of polymerase chain reaction in the diagnosis of a tuberculous process]. / Informativnost' polimeraznoi tsepnoi reaktsii v diagnostike tuberkuleznogo protsessa.

The informative value of the polymerase chain reaction (PCR) in the diagnosis of a tuberculous process in patients with pulmonary and extrapulmonary tuberculosis was studied. Sputum, urine, pleural and spinal fluids, and other specimens from 111 patients and 14 healthy individuals were tested. An analysis of sputum from 58 persons clinically diagnosed as having tuberculosis showed the following comparative sensitivity of the used methods: 82.8%, PCR; 65.5%, bacterioscopy; and 67.2%, inoculation. The detection rate of specific DNA from different samples was the following: 82.8% from the sputum, 66.6% from urine, and 54.5% from pleural fluid. The informative value of PCR in 14 patients with osteoarticular tuberculosis and in 39 with urinary tuberculosis was 42.8 and 40.6%, respectively. Thus, the application of PCR to a comprehensive examination of patients with tuberculosis of different sites is justifiable.

[Interaction of types of drug resistance and immunity in patients with pulmonary tuberculosis]. / Vzaimovliianie tipov lekarstvennoï rezistentnosti i immuniteta u bol'nykh tuberkulezom legkikh.

The authors carried out a comparative clinical and immunological study of different types of drug-resistance (mono-, poly-, MDR of primary and secondary genesis) and immunity in 54 patients with a specific process in the lung. The level of suppression, immunodeficiency, and the incidence of adverse effects were found to be on the increase in the group with the preserved sensitivity to the that with mono-, poly-, and MDR. Impaired immune homeostasis was more pronounced in patients with secondary MDR versus those with primary MDR.

[HIV infection and tuberculosis in the Republic of Kazakhstan]. / VICh-infektsiia i tuberkulez v respublike Kazakhstan.

The incidence of HIV infection is now recorded in all 14 regions of the Republic of Kazakhstan and in the cities of Astana and Almaty. A total of 1010 HIV-infected persons were recorded as of January 1, 2000. There were 29 patients with AIDS. Tuberculosis was detected in 93 of the HIV-infected patients recorded as of January 1, 2000, which amounts to 12.5% of the examinees. It was found in 39 of the HIV-infected prisoners, which accounts for 41.9% of the total number of patients having a contaminant infection and for 19.4% of those convicted. However, it should be believed that these data do not reflect the true state of affairs, which involves some difficulties associated with the diagnosis of tuberculosis in patients HIV infection both in its early and late stages.

[Effectiveness of hyperbaric oxygenation in the treatment of postresection bronchial fistulas]. / Znachenie giperbaricheskoi oksigenatsii v lechenii postrezek- tzionnykh bronkhial'nykh svishchei.

The article discusses the results of treatment of 84 patients with postresection tuberculous pyothorax and bronchial fistulas with hyperbaric oxygenation session (HBO) included in the complex of therapeutic measures. As a result, the bronchial fistulas closed in 30 (35.7%) patients, the diameter of the fistulas reduced markedly in 20 (24.3%) patients, the bronchial fistulas failed to close in 40% of cases. As the result of HBO therapy the count of red cells and lymphocytes increased, leukocytosis and eosinophilia reduced, the ESR diminished. The content of ALT transaminase, sugar, total protein and bilirubin decreased. The migration index for all immune antigens in the reaction of leukocyte migration inhibition and in the nitro blue tetrazolium test increased. HBO promoted the efficacy of radical operations by 29.4% as compared to that in the control group of the similar patients.

[The use of hyperbaric oxygenation in the combined treatment of postresection tuberculous pleural empyema with bronchial fistulae]. / Primenenie giperbaricheskoi oksigenatsii v kompleksnom lechenii postrezektsionnykh tuberkuleznykh émpiem plevry s bronkhial'nymi svishchami.

The results of treating 67 patients with postresection tuberculous empyema of the pleura and bronchial fistulas are presented. The complex treatment included courses of hyperbaric oxygenation. The treatment procedure is described. Closure of the bronchial fistula and decrease in the fistula diameter were observed in 23 (33.8 per cent) and 16 (24.5 per cent) patients, respectively. No closure of the bronchial fistula in 41.7 per cent of the patients was recorded. Increased erythropoiesis, decreased leukocytosis and higher leukocyte counts, retarded ESR, lower contents of transaminases, increased inhibition of leukocyte migration, lower levels of immunoglobulin E and fewer numbers of immune complexes circulating in blood were revealed.

[Immunologic indices of tuberculosis in pregnant women]. / Nekotorye immunologicheskie pokazateli pri tuberkuleze u beremennykh.

The results of immunological examination of 40 pregnant women recovered from tuberculosis and 7 healthy pregnant women are presented. The highest titers of antituberculous antibodies, the highest levels of leukocyte migration inhibition in response to tuberculin and the highest percentage of formazan-positive neutrophils were characteristic of the women recovered from tuberculosis. There was an increase in the indices by the pregnancy terms from the 36th to the 40th weeks. Simultaneous detection of the high indices of the immunological tests was prognostically unfavourable which could be used as a basis for arrangements on preventing tuberculosis aggravation during pregnancy.