The article presents the results oftuberculosis epidemic situation analysis in 15 Russian regions supervised by the Institute in 2014-2015. Tuberculosis incidence decreased in 11 regions out of 15 in 2014-2015. 4 regions demonstrated minor increase. Tuberculosis incidence among children in the age from 0-17 years old went down in 10 regions and increased in 5. Tuberculosis mortality decreased butin 3 regions itis higher than the average Russian rate (9.2 per 100,000 pop.). Treatment efficiency among new tuberculosis cases registered for treatment in 2014 with positive sputum microscopy varied from 69.8% in Orel Region down to 32.6% in Ulyanovsk Region, treatment efficiency as persputum conversion by culture – from 70.6% in Orel Region down to 34.2% in Ulyanovsk Region, treatment efficiency as per cavity healing – from 72.3% in Orel Region down to 40.2% in Ulyanovsk Region. The main reasons of low chemotherapy effectiveness are defaults from treatment, multiple drug resistance and insufficient surgical activities. In order to enhance the treatment efficiency, rapid drug susceptibility testing techniques are to be introduced everywhere with susceptibility testing to all anti-tuberculosis drugs and adequate chemotherapy regimens are to be applied consisting only of those drugs to which tuberculous mycobacteria are susceptible, surgical treatment is to be used more often.

Goal of the study: to compare efficiency of anti-tuberculosis chemotherapy prescribed basing on drug susceptibility testing results obtained by GeneXpertMTB/RIF with relevant correction as per data of culture on liquid media and basing on drug susceptibility testing through culture on liquid media only.

Materials and methods. 185 pulmonary tuberculosis patients in the age from 18 to 60 years were included into the study and divided into three groups: Groups 1 and 2 included those susceptible and resistant to rifampicin respectively which was detected by GeneXpert MTB/RIF. Group 3 was formed retrospectively out of patients suffering from multiple drug resistance in whom no test systems had been used.

Results. If chemotherapy regimen was appropriately chosen basing on rifampicin susceptibility data obtained only through GeneXpert MTB/RIF, the time of sputum conversion confidently did not differ for those suffering from multiple drug resistance and those without it.

Prescription of chemotherapy regimen basing on GeneXpert MTB/RIF results with consequent correction as per culture results obtained by Bactec MGIT 960 confidently enhances treatment outcomes in multiple drug resistant tuberculosis patients both regarding sputum conversion rate and cavity healing compared to the group where treatment regimen was corrected basing on results of culture on liquid media. Using GeneXpert MTB/RIF significantly reduces the number of chemotherapy regimens corrections or transfers to the other regimen. Under-detection of rifampicin resistance when using GeneXpert MTB/RIF compared to Bactec MGIT 960 was fixed on the level of 1.5% (95% CI 0.42-5.44%).

Goal of the study: to develop individual approaches to the choice of chemotherapy regimens for respiratory tuberculosis in children exposed to multiple drug resistant tuberculous infection.

Materials and methods. Totally 39 children (3-12 years old) with tuberculosis of chest lymph nodes or pulmonary tuberculosis. Patients were divided into 3 groups: Group 1 (9 persons) with minimal changes – 3 drugs (ZPASPtо), Group 2 (15 persons) with limited lesions – 4 drugs (ZPtоPASE), Group 3 (15 persons) with disseminated lesions – 5 drugs (ZPASPtоAmFq). Duration of chemotherapy: Group 1 – 9.4 ± 0.7 months; Group 2 – 9.0 ± 1.1 months (administration of 4 drugs during the whole treatment course) and 10.5 ± 0.9 months, (transfer after the intensive phase (3.1 ± 0.7 months) to 3 drugs), Group 3 – 13.4 ± 0.7 months. (Transfer after the intensive phase (4.0 ± 0.4 months) to 4 drugs).

Results. Chemotherapy course was assessed assuccessful in all groups. Individual approaches to the choice of chemotherapy regimens oftuberculosis in children exposed to multiple drug resistant tuberculous infection should consider not only the data on drug susceptibility of the infection source but also the dissemination of tuberculous lesions in the child.

Goal of the study: to investigate the changes in ventilation and gas exchange function of the lungs before and after 1-1.5 months after installation of endobronchial valve (EV) aimed at cavity healing in pulmonary destructive tuberculosis patients.

Materials and methods. 74 HIV negative patients in the age from 18 to 61 years old suffering from destructive pulmonary tuberculosis were examined. The changes in the pulmonary ventilation capacity (VC, FEV1 , FEV1 /VC%, PEF, MEF25,75) and blood gases (РаО2 , РаСО2, SaО2 %) before and in 4-6 weeks after EV installation have been studied.

Results. After 1-1.5 months after EV installation no significant changes in the pulmonary ventilation function were found in 62.2% of patients, 43.2% of patients demonstrated no significant changes in gas exchange function and there were certain changes in the remaining patients. Reduction of pulmonary ventilation capacity due to large bronchi obstruction, restrictive changes and pulmonary gas exchange were manifested through reduction of FEV1 in 18.9% (95% CI 11.6-29.3%) of patients, PEF – in 20.3% (95% CI 12.7-30.8%), VC – in 22.9% (95% CI 14.9%-33.8%) and PaO2 – in 32.4% (95% CI 22.9-43.7%) of patients.

Reduction of carbonic acid content in blood was observed in 27.0% (95% CI 18.3-38.1%) of patients. The improvement of gas exchange and ventilation function was the following: VC in 14.9% of patients (95% CI 8.5-24.7%), РаО2 – in 24.3% (95% CI 16.0-35.2%) and SаO2 – in 20.3% (95% CI 12.7-30.8%) of patients. Patients remained stable due to moderate intensity of changes.

Frequency of negative and positive functional changes after installation of endobronchial valve for valve bronchial blocking (VBB) varies to some extent depending on the place of EV installation, volume of VBB and dissemination of tuberculous lesions.

Lower installation of VBB versus upper one: VC increases more rarely (in 8.3 and 21.6% of patients, p < 0.05 respectively), FEV1 decreases more often (in 41.7 and 13.5% of patients p < 0.05 respectively), VC, PEF, РаО2 and SаO2 go down more often (p < 0.05).

If tuberculous lesions are limited the cases when pulmonary ventilation capacity decreases after EV installation occur more often compared to disseminated tuberculous lesions and the cases when pulmonary ventilation capacity improves were observed only in case of the disseminated disease.

Goal of the study: to investigate the frequency of mycobacteriosis in the practice of pulmonologists and phthisiologists.

Materials and methods. The analysis included medical files of 156 patients with various non-specific respiratory diseases and tuberculosis who were examined in 2011-2014 and non-tuberculous mycobacteria were found in their sputum.

Results of the study. pulmonary mycobacteriosis was diagnosed in 93 (59.6%) patients out of 156 who corresponded the criteria of American Thoracic Society and etiotropic treatment was prescribed. While detection of non-tuberculous mycobacteria in the other patients was considered as innidiation of respiratory tract by those mycobacteria in case of chronic non-specific pulmonary disease and/or tuberculosis. Mycobacterioses were treated with the relevance to drug susceptibility of the causative agent and there were numerous obstacles due to high frequency of adverse reactions.

The study investigated the dynamic changes in the content of pentraxin-3 and C-Reactive Protein in blood serum of children and adolescents suffering from respiratory tuberculosis with destruction and minor tuberculous changes in chest lymph nodes and lungs (minor forms). Level of PTX3 in tuberculosis patients with destructive lesions confidently reduced by the 6th month of treatment (end of the intensive phase of treatment): from 3 285.2 ± 387.1 down to 1 280.0 ± 65.4 pg/ml In the group ofthose with minor forms oftuberculosis the content of PTX3 confidently increased after 6 months of treatment (completion of the main course of chemotherapy): from 2 990.0 ± 330.3 down 5 329.7 ± 421.3 pg/ml. Such changes of PTX3 in this group were observed for the first time and it had not been described before. It is possible that the increase of PTX3 level after completion of chemotherapy course is temporary and it is related to activation of the lung tissue healing. Content of C-Reactive Protein before treatment start was typically higher in those with destructive lesions and it confidently reduced in 6 months of chemotherapy in the patients from this group (from 15.7 ± 2.9 down to 5.95 ± 1.2 mg/l) and remained unchanged in the patients with minor forms of tuberculosis (4.5 ± 1.1; 2.9 ± 0.1 mg/l).

117,662 children and adolescents were examined with the skin test of Diaskintest when registered for dispensary follow-up for the first time in tuberculosis control units in Orenburg Region from 2010 to 2015. Positive and questionable results of Diaskintest were in 96.4% (86.8 and 10.6%) of children with active tuberculosis. 435 patients with latent tuberculous infection, 6 patients with questionable active disease and 3 with active tuberculosis were missed basing on the results of tuberculin diagnostics only and detected with Diaskintest. No case of active tuberculosis has been registered forthe last 5 years among patients with negative reaction to Diaskintest in Group VI ofthe dispensary follow-up. When using traditional methods including tuberculin diagnostics 90% of children registered for dispensary follow-up were groundlessly treated with preventive chemotherapy.

Cells of the host containing special proteins-transporters, so-called proteins of multiple drug resistance (MDR proteins) can contribute to the drug resistance formation.

Goal of the study: to define specific expression of gene and distribution of main MDR proteins (MDR1/Pgp, MRP1, lRP, BCRP) in the pulmonary cells in case of active tuberculosis.

Materials and methods. Expression of MDR protein genes was evaluated by RT-PCR for mRNA isolated from the surgical specimen of fibrous cavernous tuberculosis patients. Localization of MDR proteins was performed by immunohistochemical staining and confocal laser microscopy.

Main results. Intensity of MDR protein genes expression varies in different zones of tuberculous lesions: MDR1 and BCRP are characterized by the highest level and MRP1 gene is characterized by the minimum level. The level of lRP gene expression depends on the inflammation zone and it is maximum in perifocal zone where protein is detected in the cells of alveolar epithelium and macrophages. High expression of MDR protein genes in various parts of tuberculous lesions witnesses about the potential involvement of these proteins in the development of drug resistance to anti-tuberculosis drugs.

Goal of the study: to investigate structural and functional specific features of macrophages and cytokine profiles of bronchoalveolar lavage in new and relapsing respiratory sarcoidosis (RS).

Materials and methods. The study included comparative light optical and electronic microscopic examinations of macrophages, macrophage formula and cytokine profile of bronchoalveolar lavage in 120 patients suffering from different forms of RS. It was found that in case of new RS mostly macrophages of M1 phenotype were detected in the lavage. They had high level of IL-8, IL-2, IL-1β production and ultrastructural signs of hypersecretion which was especially typical of platycytes. High level of IL-4, IL-5 content is typical of relapsing sarcoidosis: additionally to macrophages of M1 phenotype, there are macrophages of M2 phenotype with ultrastructural signs of phagocytic function which can be used for diagnostics of this form of RS.

73 pulmonary tuberculosis patients with concurrent diabetes were examined, ofthem 28 patients suffered from diabetes oftype 1 (D1) and 45 patients had diabetes of type 2 (D2). The following was tested in the blood serum: triglycerides (TG), general cholesterol (GC), high density lipoproteins cholesterol (HDLC) and low density lipoproteins cholesterol (LDLC). Very low density lipoproteins cholesterol (VLDLC) was estimated as perthe following formula: VLDLC = C – (C-HDLC + C-LDLC). Atherogenicity coefficient and atherogenic plasma index were estimated. It was found that pulmonary tuberculosis patients with concurrent diabetes manifested atherogenic changes in respect of lipid exchange: minor changes in D1 and greater changes in D2. Intensity ofsystem inflammatory response syndrome (SIRS) and nutritive status ofthe host provided significant impact on the state of lipid exchange in those suffering from the concurrent conditions. SIRS was related to reduction of cholesterol transporting function of HDLC which reduced anti-atherogenic blood potential. Besides development of SIRS results in the reduction of nutritive status, and the increase of catabolic process in lipid metabolism becomes the part of the above. Intensification of lipolysis is accompanied by the increase of VLDL which together with reduction of HDL defines atherogenic changes in lipid exchange in those suffering from the concurrent conditions. As nutritional insufficiency increases, synthesis of cholesterol becomes lower than the consumption and the level of its circulation (and within atherogenic lipids) goes down which provided anti-atherogenic effect, more intensive in D1. SIRS provides dominating influence on the state of lipid exchange in those suffering from the concurrent conditions.

Goal of the study: to study the specific in vitro action of PBTZ169, hydrochloride, in respect of clinical strains of M. tuberculosis with extensive drug resistance (XDR).

Materials and methods. Strains of M. tuberculosis isolated from 20 XDR tuberculosis patients (10 strains from HIV positive patients and 10 strains from HIV negative patients) were used in the study, their susceptibility to 10 anti-tuberculosis first and second lines drugs plus linezolid was tested by Bactec MGIT 960. Bacteriostatic and bactericidal action of PBTZ169, hydrochloride, was defined as per the growth speed of M. tuberculosis strains in Bactec MGIT 960 compared to the growth of strains on the medium free from drugs and the medium containing control drugs (INH 0.1 мcg/ml, RIF 1 мcg/ml, AMK 1 мcg/ml and LFX 1.5 мcg/ml).

Results. The used clinical strains of Mycobacterium tuberculosis were resistant to 7-10 anti-tuberculosis drugs, of them 3 were resistant to linezolid. When testing bacteriostatic action it was found that PBTZ169, hydrochloride, in the concentration of 0.037 mcg/ml fully suppressed growth of all 10 strains isolated from HIV negative patients and of the majority of strains isolated from HIV positive tuberculosis patients (7 out of 10). In the same concentration PBTZ169HCl demonstrated bactericidal action in respect of all strains isolated from HIV negative tuberculosis patients and 4 out of 10 strains isolated from HIV positive tuberculosis patients. Forthe remaining 6 out of 10 strains from HIV positive tuberculosis patients minimum bactericide concentration made 0.111 mcg/ml.

Goal of the study: to define the design of primers and probes specific to DNA of non-tuberculous mycobacteria and evaluate their diagnostic value in case of simultaneous detection of non-tuberculous mycobacteria and M. tuberculosis complex by real time PCR.

Materials and methods. Primer 3, Primer BLAST, Ugene Uni Pro were used to design primers and probes. Preliminary assessment of specificity and sensitivity of detection of non-tuberculous mycobacteria DNA was performed on cultures belonging to 18 types of non-tuberculous mycobacteria, 16 strains of M. tuberculosis complex and 14 types of microorganisms being none Mycobacterum. Analytic sensitivity was tested on 284 cultures of non-tuberculous mycobacteria and diagnostic sensitivity was tested on 124 sputum samples. The kit ofM-Sorb-Tub-Avtomat (ZAO Sintol) was used for DNA isolation. Cultures were subcultured on the liquid medium of Middlebrook 7H9 in Bactec MGIT 960. Cultures were identified with the use of standard microbiological techniques. Analysis of DNA isolated from cultures was performed by the reagent kit of GenoTypeCM/AS (Hain Lifescience, Germany).

Results. 100% specificity and sensitivity of PCR was demonstrated in mycobacterial cultures and 100% specificity and 69-70% sensitivity was demonstrated in diagnostic material analysis.

Cavernous form of tuberculosis being important in its clinical aspects is presented with the reference to pathogenesis, morphogenesis, structure of cavitary wall as acute pneumoniogenic cavity, bronchogenic cavity, cavity from the focus with pre-existing capsule, without expressed fibrosis, with perifocal changes and without them, with semination foci and without them.

The statement of the long-lasting impropriety of official statistic rates received through current clinical classification of tuberculosis (ICD-10) explains the increase oftuberculosis prevalence and raises the need to review the classification oftuberculosis and points atthe urgency oftuberculosis control actions adequate for current unfavorable epidemic situation.