The review is dedicated to the description of studies that characterized the current state of the problem of latent TB infection. Particular attention is paid to the description of features of the pathogen in a latent («dormant») state and response of host organism to «dormant» mycobacteria (dormant loci, the reaction of macrophages and others).

In the article, we presented description of laboratory facilities, performing microbiological tests for tuberculosis (TB) diagnosis in 12 Siberian and 9 Far Eastern Federal Districts. We conducted effectiveness evaluation of TB detection by light microscopy with the Ziehl-Neelsen coloring in primary health care clinics. The dynamic of effectiveness of TB detection by different microbiological methods in the period from 2010 to 2014 in the TB bacteriological laboratories was presented. In the paper, we focused on the relevant points in the work of TB laboratories that require further improvement and optimization.

This study presents genotyping and drug resistance mutations data of M. tuberculosis isolated from tuberculosis patients from 2012 to 2016 in Ural Research Institute of Phthisiopulmonology, Ekaterinburg. We performance capabilities of Amplitub-Beijing (Sintol, Russia), GenoType® MTBDR (Hain Lifescience, Germany) and TB-TEST (Biochip-IMB, Russia) test-systems for differentiation and diagnostic of epidemiology significant variants of M. tuberculosis (Beijing MDR) in clinical samples.

We carried out a retrospective study of 150 MTB isolates to detect drug resistance genetic determinants by “TB–TEST” system and estimate their correlation with the results of the microbiological drug susceptibility testing in BACTEC MGIT 960 and Sensititre MycoTB Plate.
It was found that the substitution S531L in rpoB gene detected in MDR, XDR and monoresistant MTB isolates most frequently among all the spectrum of mutations leading to MTB resistance to high concentration of rifampicin. On the contrary, MTB with the D516Y, H526L and H526N substitutions in rpoB gene were intermediately or low-resistant and were detected as susceptible to rifampicin by standard microbiological methods. The substitution S315T in katG leading to MTB resistance to high concentration of isoniazid was detected in MDR, XDR and monoresistant MTB isolates most frequently.
In most cases high and moderate level of resistance of MTB to fluoroquinolones connected with mutations in gyrA or both in gyrA and gyrB genes and intermediate and low resistance connected with mutations only in gyrB. Detection of mutations in eis gene (low resistance to KAN) increases a correlation with phenotypic DST in Bactec MGIT 960 up to 93.2%. In Moscow region as well as in other regions of the Russian Federation Beijing genotype of MTB prevailed and were detected in 78.0% of cases. 20.0% of Beijing strains had BO/W148 genotype associated with high level of resistance of MTB to antituberculosis drugs.

To estimate the potential impact of mutations leading to the RIFresistance on the «fitness» of M. tuberculosis (MTB) we analyzed using TB-BIOCHIP («BIOCHIP IMB» Russia) the spectrum of single nucleotide polymorphisms (SNP) in rpoB gene in 309 MDR-MTB strains obtained from new-detected and 324 MDR-MTB strains obtained from previously treated TB-patients. It was found that in the group of MBT strains isolated from previously treated TB-patients was detected more mutant variants in comparison with MTB strains obtained from newdetected patients. Also MBT strains isolated from previously treated TB-patients had compensatory mechanisms aimed at severization of drug resistance due to additional mutations in the analyzed rpoB region. The strains with SNP 531 Ser → Leu prevailed in both groups (87,4% and 71,3%, respectively), that is clearly pointed to maintenance of «fitness» of strains with this SNP.

We investigated 99 M. tuberculosis clinical isolates obtained from TB patients. Bactec MGIT 960 (Bactec960) and Sensititre MycoTB testsystem performed DST for antituberculosis drugs. All the investigated M. tuberculosis clinical isolates were XDR in Bactec960. The DST results performed by Sensititre MycoTB and Bactec960 showed a high rate of coincidence. On the other hand, the great number of investigated MTB isolates were detected as intermediately susceptible by Sensititre MycoTB test-system. It concerned to such useful drugs for combined chemotherapy as etambutol, maxifloxacin, ethionamide, kanamycin, ofloxacin, paraaminosalicylic acid, amikacin.
Information about intermediate susceptibility had a great practice value and gave a certain reserve for chemotherapy of such challenging category as XDR-TB patiens.

It were investigated the drug sensitivity (DS) of Mycobacterium tuberculosis (Mtb) and the bacterial burden of respiratory (RS) and surgery (OS) samples derived from previously treated patients (clinics of SPb Institute for Phthisiopulmonology, 2010-2014): I group – patients without surgery treatment (153 strains), II – operated patients, mainly with chronic and hyperchronic disease (546 strains), III – reference group, non-operated patients with MTB DS (79 strains). It was found that the growth properties of MTB with MDR and XDR have no differences with the growth properties of MTB with drug sensitivity. The known regularity was confirmed that in the cases of MDR the frequency of MTB burden in RS is much higher than in OS – 63.7% vs 41,9%. In OS high and medium degree of MTB burden in the cases of XDR was observed much more frequently than in MDR cases – totally 71.7% vs 53.7%. Persons with the high degree of MTB burden in RS had dominated in the group of operated patients. This confirms that the high viability of MTB is retained both in MDR cases as in XDR cases.

The algorithm of laboratory diagnosis of pulmonary aspergillosis in patients with various forms of pulmonary tuberculosis is described. The diagnostic criteria of results of mycological (microscopy and cultural studies) and immunological laboratory investigations are represented.

The present study reviewed the role of one of the mechanisms of regulation of tuberculous inflammation, namely, a signal transmitted through the receptor (IFNAR1) for type I interferons in the course of experimental tuberculosis in mice. On the basis of studying of the characteristics of the course of TB in wild-type mice of 129S2 line and Ifnar1-/- mice on the same genetic basis we have shown that the signal transmitted through the IFNAR1-receptor worsens the course of experimental tuberculosis; It don’t prevent the proliferation of Mycobacterium tuberculosis in the lungs; It has no impact on the formation of an immune response to the BCG vaccine; It enhances the influx of neutrophils into the lungs with the redistribution of mycobacteria in these cellular elements; It serves to the accelerated development of the pathology and death of infected mice.

Our data demonstrate that drug resistance to subtoxic concentrations of rifampicin can form in monocyte-macrophagic and epithelial cell lines. The index of cytotoxicity IC50 (50% cell survival) increased 1.5–2.5 times during the first 3 months of drug administration. Rifampicin resistant cells were characterized by high functional activity of Pgp, one of the major MDR proteins mediating resistance to multiple structurally diverse drugs. In drug resistant macrophages, phagocytic activity increased. Thus, the index of phagocytosis of M. bovis-GFP increased 1.5 times after 3 month of drug administration. The phenomenon of resistance of monocytic and epithelial cell lines to rifampicin depended on the time of exposure to the drug and was reversible.

We analized the results of application of skin test with Diaskintest® and T-SPOT®.TB laboratory test in 75 HIV-patients with lung TB. It was found, that percentage of positive results consisted of 60.0% (95%CI 48.7–70.4%) using T-SPOT®.TB test and 22.7% (95%CI 14.6–33.4%) using skin test. Moderate correlation relationship of results of both tests and number of CD4+ Т-cells was shown. The percentage of positive results using T-SPOT®.TB in patients with number of CD4+ Т-cells from 50 cells/μl and more was significantly higher than those one in patients with number of CD4+ Т-cells lower than 50 cells/μl (81.1% against 9.1%, according to χ2, p < 0,01). The results of both tests coincided in 48.0% of cases and were discordant in 52.0%, coherence of the tests was low (κ = 0.17; р < 0.05). The given results allow us to conclude that using T-SPOT®.TB test was highly effective in HIV-patients with lung TB. The limitation for the test application was severe immunosuppression with number of CD4+ Т-cells lower than 50 cells/μl.

We analyzed the antibiotic-induced complications in a period of 2013–2015. We investigated 46 autopsies and material of biopsy (17 cases) to carry out a comprehensive pathological study of antibiotic-induced complications of large bowel. Investigation of autopsy material showed the annual growth of antibioticassociated colitis, which played a role in tanatogenesis (1.0%, 4.8% and 6.2%). We stated a tendency to the growth of bacterial and mycotic superinfection, which caused not only enteropathy, but also the development of generalized forms (generalized anaerobic infection in 0%, 0.25%, and 1.1% of cases and generalized mycosises in 1.2%, 2.5%, and 3.9% of cases respectively). In all the cases, we revealed pseudomembranous colitis of type 3 according to the classification of A. Price and D. Devis, 1977. A great role in pathology development play such factors as lack of information about the high risk of uncontrolled receiving of antibacterial agents among people and doctors’ underestimation of the danger of incorrect antibiotic therapy for the health and life of patients.