The objective: to conduct comparative analysis of tuberculosis incidence of among ethnic groups living in the South Aral Sea region and to establish whether belonging to the Karakalpak ethnic group presents a risk factor of developing tuberculosis.

Subjects and Methods. Tuberculosis incidence over 5 years (2016-2020) among people of Uzbek and Karakalpak ethnicities living in the Republic of Karakalpakstan was compared and retrospectively analyzed.

Results. In 2016-2020, tuberculosis incidence among people of the Karakalpak ethnicity (whose ancestors were nomadic and seminomadic people) made 147,08 per 100,000 population on the average (2016 - 178,8; 2017 - 174,8; 2018 - 139,4; 2019 - 136,9; 2020 - 108,1 per 100,000 population), among people of the Uzbek ethnicity (whose ancestors lived sedentary lives), tuberculosis incidence made 85,3 per 100,000 population on the average (2016 - 92,4; 2017 - 89,5; 2018 - 139,4; 2019 - 136,9; 2020 - 60,9 per 100,000 population). A statistically significant difference was demonstrated in tuberculosis incidence among people of the Karakalpak and Uzbek ethnic groups.

The objective: to evaluate the effectiveness of screening for tuberculosis infection in risk groups among adults using the skin test with tuberculous recombinant allergen (TRA) - Diaskintest®.

Subjects and Methods. In 2019-2021, screening for tuberculosis infection in risk groups and in the population with an unknown risk was carried out covering 449,842 people. People aged 18 years and older were examined - patients of the Tuberculosis Control Center, polyclinics and hospitals of medical organizations of the Moscow Health Department. Questionable results were taken into account as positive results of the TRA test.

Results. The frequency of positive results of the TRA test in healthy population was as follows: in those contacting pregnant women and newborns - 2.0% (95% CI 1,54-2,10); in decreed groups (workers in food industry, water supply organizations, utilities) - 2,68% (95% CI 2,54-2,82). The situation was different in social risk groups (foreign citizens and stateless persons) - they responded positively to the TRA test in 21,05% (95% CI 20,08-22,06). Most of them arrived to Moscow from states with a high burden of tuberculosis. High-risk groups also include those abusing alcohol and substances; they had positive results in 10,58% (95% CI 8,41-13,24). Among the medical risk groups, the highest rates were observed in those followed up by tuberculosis control services after tuberculosis treatment completion - 39,96% (95% CI 38,31-41,64).

Conclusion. Screening in the groups facing the highest risk of developing tuberculosis had a positive effect and once again confirmed the need to screen both resident and migrating population. The immunological skin test with Diaskintest is a reliable tool for examining tuberculosis risk groups.

The objective: assessment of changes in the parameters of complete blood count, clinical urine tests, and blood chemistry during chemotherapy of patients with MDR/XDR pulmonary tuberculosis receiving the short-course regimen containing bedaquiline, pretomanid, and linezolid (B-Pa-L).

Subjects and Methods. 18 patients with MDR/pre-XDR/XDR pulmonary tuberculosis were enrolled into the study. They all received treatment at Central Tuberculosis Research Institute from 2015 to 2022.

Results. In the course of chemotherapy of these patients, changes in laboratory test results were noted at different times. Abnormal changes in complete blood count were detected in 10/18 (55,6%) patients during chemotherapy for the 1st time. Hemoglobin levels, erythrocyte and leukocyte counts decreased. Hematuria and bacteriuria were detected by clinical urine test. Proteinuria was observed in almost in half of the patients. Elevated serum potassium level was frequently noted. Blood chemistry demonstrated elevated levels of ALT and AST, which is typical of cytolytic effect on hepatocytes of drugs within chemotherapy. In most cases, all above abnormalities were degree 1 of toxicity and resolved within 2-4 weeks after they were detected. Abnormalities in grade 2-3 of toxicity were mainly observed in patients receiving linezolid at the dose of 1200 mg/day. In most cases, the above abnormalities were detected during the first 4 weeks of chemotherapy.

Tuberculosis incidence and HIV infection incidence in the regions of the Russian Federation are declining, but the proportion of HIV positive people among the entire cohort of tuberculosis patients is clearly growing.

The objective: to determine causes for increasing proportion of HIV infected people among tuberculosis patients and to provide additional recommendations for enhancement of tuberculosis detection in HIV infected patients. as well as prevention of its transmission.

Subjects and Methods. The cohort of new tuberculosis patients with concurrent HIV infection (TB/HIV coinfection) in the Russian Federation region with a high prevalence of HIV infection was studied based personal medical records of patients for the first 6 months of 2022 (682 cases totally).

Results. The cohort of patients with TB/HIV co-infection belonged to socially vulnerable population. Among them, the parenteral route of HIV infection transmission still prevails, while in the whole country, among new HIV patients, the sexual (heterosexual) route of transmission already prevails. The majority of patients with TB/HIV co-infection, who had been infected with HIV for more than 5 years by the time tuberculosis was detected, were not registered with the Center for AIDS Prevention and Control and accordingly received no antiretroviral therapy. In most cases, HIV-infected patients sought medical care in general medical services when they developed symptoms of tuberculosis, however they referred for help when the disease was advanced. When assessing effectiveness of tuberculosis treatment, the specific parameters of tuberculosis course in HIV-infected patients with compromised immunity have not been taken into account.

The objective: to evaluate the modulating effect of the Notch signaling pathway on differentiation of Th1 and Th2 lymphocytes in vitro in patients with infiltrative pulmonary tuberculosis.

Subjects and Methods. 14 new patients with infiltrative pulmonary tuberculosis were enrolled in the study. Mononuclear leukocytes were isolated from blood by gradient centrifugation. Only Mycobacterium tuberculosis antigens in the form of the CFP10-ESAT6 protein or together with Y-secretase inhibitor DAPT (5 μМ/l or 10 μМ/l) were added to the incubation medium. Cells were cultured for 72 h in a complete nutrient medium with 5% CO₂ at 37°C. Counts of Th1 and Th2 lymphocytes were determined by flow cytometry by evaluating the expression of CD4 receptor and intracellular transcription factors T-bet and GATA-3.

Results. Cell stimulation with the CFP10-ESAT6 protein was accompanied by increasing number of Th1 and Th2 lymphocytes only in patients with pulmonary tuberculosis resistant to isoniazid + rifampicin. Adding DAPT at the concentration of 10 μМ/L to the incubation medium in these patients led to the growing number of Th1 lymphocytes and decrease in Th2 lymphocytes. In pulmonary tuberculosis patients who were susceptible to isoniazid + rifampicin, only decrease in the number of Th2-lymphocytes was regeistered. In all groups of subjects, suppression of the Notch signaling pathway led increase in the Th1/Th2 index versus Th1/Th2 stimulated with CFP10-ESAT6 antigens.

The objective: to perform intraspecific differentiation of M. abscessus strains isolated from patients with pulmonary lesions using molecular genetic tests.

Results. Intraspecific differentiation of 164 cultures of M. abscessus from 114 patients without cystic fibrosis showed that the subspecies M. abscessus subsp. dominated in the analysis set (90 of 114 patients; 78,95%), followed by M. abscessus subsp. massiliense (24/114; 21,05%). In 54 examined cystic fibrosis patients excreting non-tuberculous mycobacteria, M. abscessus was most often detected (41 patients out of 54; 75,93%). Intraspecific identification of the obtained M. abscessus isolates demonstrated the prevalence of the subspecies M. abscessus subsp. abscessus (29/41; 70,73%) over M. abscessus subsp. massiliense (11/41; 26,83%). In one case, a rare M. abscessus subsp. bolletii (1/41; 2,44%) was detected.

The objective: to evalute effectiveness in clinical trials of the new kit of reagents of AmpliTest® MBT-Resist-I based on real-time PCR (RT-PCR) versus similar kits of reagent registered in Russia, to identify genetic markers of M. tuberculosis complex (MTB) resistance to rifampicin (RIF) and isoniazid (INH) in human biological samples and MTB cultures.

Subjects and Methods. 200 DNA samples were studied, they had been obtained from biological specimens (sputum (N=100), bronchoalveolar lavage (N=50), biopsy (surgical material; N=50)) of pulmonary tuberculosis patients and containing MTB DNA at a concentration of at least 1 x 103 GE/ml, and from 100 DNA samples of MTB cultures. Efficiency of detecting mutations associated with MTB resistance to RIF and INH using the new kit of reagent of AmpliTest® MBT-Resist-I was evaluated in comparison with HP Amplitube-MDR-RV (OOO Sintol, Russia). In the case of discordant results, the target MTB DNA loci were sequenced by Sanger.

Results. We observed complete agreement of the results and consequently high efficiency rates (positive and negative concordance of results - 100%, respectively) of the new kit of reagents of AmpliTest® MBT-Resist-I in comparison with the kit of reagent of Amplitube-MDR-RV in detection of mutations associated with MTB resistance to both RIF and INH, both for human samples and for MTB cultures. In two DNA samples of MTB cultures, an additional mutation (I572L) in the rpoB gene was detected using the new kit of reagents which was not detected by the comparison kit and was confirmed by Sanger sequencing.

Conclusion. Inhalers vary significantly by the patients' ability to use them correctly. Asthma patients master the correct inhalation technique better versus COPD patients. Liquid inhalers were more difficult to be used correctly, and the best results were observed with multi-dose powder inhalers. The patient's training by a healthcare professional is critical to assure the correct use of inhalers.

The objective: immunohistochemical and electron microscopic imaging of the SARS-CoV-2 coronavirus in lung, lymph nodes and kidney tissues of patients who died of COVID-19.

Subjects and Methods. For immunohistochemical tests, specimens of sections of formalin-fixed and paraffin-embedded tissues of the lungs, lymph nodes and kidneys of patients who died from COVID-19 were used. Quantitative assessment of the SARS-CoV-2 viral load level was carried by the original RT qPCR and calculated by the formula: SARS-CoV-2 copy number/ABL1 х 100 copies, expressed as the ratio of the true number of SARS-CoV-2 cDNA copies per 100 copies cDNA of the ABL1 gene. For morphological tests, samples of native lung, lymph node and kidney tissues were taken.

Results. Immunohistochemical and electron microscopic tests revealed particles of the SARS-CoV-2 coronavirus in the cytoplasm of endothelial cells of air-blood barrier of the lungs, the vascular glomerulus of the kidneys, in the cytoplasm of macrophages of the lymph node, and also in cytoplasm of lymphocytes in the lumen of lung capillaries.

The objective: to increase the effectiveness of comprehensive treatment of patients with advanced fibrous cavernous pulmonary tuberculosis using the new method of extrapleural upper-posterior thoracoplasty with a mesh implant.

Subjects and Methods. It was an open, prospective, randomized, controlled study of treatment outcomes of 233 patients with fibrous cavernous pulmonary tuberculosis who had contraindications to resection surgery. Patients were divided into three groups depending on the type of thoracoplasty: thoracoplasty with a mesh implant was performed in 70 patients, thoracoplasty according to Bjork - in 60 people, and traditional upper-posterior thoracoplasty - in 103 patients.

Results. In operated patients, additional support with a mesh implant during the formation of a new pleural dome reduced pathological flotation of chest organs, which prevented decreased respiratory function, the right heart overload, and protected from the development of bronchopulmonary complications in the early postoperative period. The chances of cavity healing and sputum conversion by the discharge from hospital increased by 3,3 times (OR=3,3; 95% CI 1,6-6,7), a year later by 3,0 times (OR=3,0; 95% CI 1,48-7,5); in the long-term assessment it increased chances of survival by 4,8 times (OR=4,8; 95% CI 1,4-16,4) versus the Bjork operation and traditional upper-posterior thoracoplasty.

The objective: to evaluate immediate and postponed efficacy of MDR TB patients' treatment with short-course chemotherapy regimens.

Subjects and Methods. Efficacy and safety of treatment with short-course chemotherapy were evaluated in 42 MDR TB patients.

Results. 36 (85,7%) patients completed treatment successfully, 1 (2,4%) patient died of non-tuberculosis, and 5 (11,9%) patients defaulted from treatment. There were no such outcomes as treatment failure and died of TB. Over the 4-year follow-up period after successful treatment completion, tuberculosis relapse was detected in 1 (1,8%) patient. No adverse events that required chemotherapy discontinuation were reported, amendment of chemotherapy regimen was required in 7 (16,7%) patients.

The article describes a clinical case of chemotherapy for drug susceptible rapidly progressive pulmonary tuberculosis in a patient with systemic lupus erythematosus taking glucocorticosteroids on regular basis. Due to adverse events that occurred when using the regimen of first line drugs, the patient discontinued taking first line drugs and was immediately switched to second line drugs. A timely decision to completely cancel the chemotherapy regimen with first line drugs that caused AE, the immediate start of the individual regimen (Bq, Lzd, Lfx, and Tzd) made it possible to cure pulmonary and bronchial tuberculosis in this patient. At the same time, data were obtained on the effective and safe use of tuberculosis treatment regimen (Bq, Lzd, Lfx, and Tzd) while taking GCS for SLE.

We analyzed 57 publications devoted to study of genetic mechanisms of formation of drug resistance of Mycobacterium tuberculosis to bedaquiline, delamanid, pretomanid, linezolid, and clofazimine. Identification of genetic factors of MTB drug resistance make the basis to search for new targets in development of anti-tuberculosis drugs and methods for drug susceptibility testing.