The objective: to study the epidemiology and incidence of XDR tuberculosis given the updated definition.

Subjects and Methods. The results of replies to the specialized inquiry by the Russian Ministry of Health about results of microbiological diagnostics and MTB drug susceptibility tests were studied. To assess the incidence of pre-extensive drug resistance, general population data were used, and for extensive drug resistance, data from 8 regions of Russia were used.

Results. The incidence of pre-extensive drug resistance was 39,1% [95% CI 38,4–39,8] among tuberculosis cases with rifampicin resistance including 26,8% in new cases [95% CI 25,8–27,9]; among all cases receiving treatment for whom DST results were available, it made 20,2%, including primary resistance in 9,7%. The incidence of XDR among cases with pre-extensive drug resistance was 3,0% [95% uncertainty interval 1,8–5,3] for all cases, including primary resistance in 1,6% [95% uncertainty interval 0,2–5,7].

Conclusion. Despite the low incidence of pre-extensive drug resistance, it is expected to increase primarily due to growing resistance to fluoroquinolones. Resistance to innovative drugs, in particular XDR, is not yet a serious problem.

The objective: to determine the indications and possibility of surgical treatment of giant malignant intrathoracic tumors.

Subjects and Methods. The authors presents their own experience of treatment of 19 patients with giant malignant intrathoracic tumors.

Results. Overall resectability was 79% (15/19 patients). 4 patients underwent combined surgery: in 2 patients, the tumor was removed with resection of a part of the upper lobe of the lung; 1 patient had this left lung resected (pneumoectomy); and 1 patient had type A thymoma, so resection and reconstruction of the pulmonary arterial trunk was performed. Radicality was assessed both during surgery (R2 – in 3 patients) and during morphological testing of surgical specimens (R1 – in 1 patient).

Among the operated giant neoplasms of the chest, which did not include lymphomas and extra-gonadal dysgerminogenic tumors, thymoma (7/19; 36.8%) and neoplasms of neurogenic origin (3/19; 31.6%) of varying degrees of differentiation were more often diagnosed.

The examination algorithm of these patients and decision-making on surgical tactics are presented. The article discusses access options and technical surgical methods for removing large tumor masses with a specific clinical examples.

The objective: to analyze the effectiveness of etiological verification of pulmonary mycobacteriosis when using various biological materials at different diagnostic stages.

Subjects and Methods. In Center for Diagnosis and Rehabilitation of Respiratory Diseases, CTRI, the results of stage-by-stage examinations of 142 patients (from 2018 to 2022) were analyzed. A retrospective, prospective, cohort, open study was conducted. Inclusion criteria: pulmonary mycobacteriosis etiologically verified by comprehensive microbiological examinations (molecular genetic and cultural tests) (with retrospective analysis after all stages of examination). Exclusion criteria: HIV infection. 115 women and 27 men were enrolled in the study, the age ranged from 21 to 86 years, the mean age was 57,9 years.

All patients referred to CTRI for examination due to newly detected changes in the lungs (bronchiectasis, focal changes, and cavities). For etiological verification of the diagnosis, microbiological sputum testing was performed (Stage 1 of the examination); when negative results were obtained, bronchoscopy was prescribed and bronchobiopsies were used for microbiological and molecular genetic diagnostics – Stage 2. In case of negative results of Stage 2, the patient was recommended to undergo a diagnostic resection of the lung – Stage 3 of the examination. At all stages, specimens were sent for comprehensive microbiological testing: fluorescent microscopy to detect acid-fact mycobacteria, real-time polymerase chain reaction (PCR-RV) to detect NTBM DNA. Identification of NTBMB was carried out by molecular genetic methods (PCR for the presence of MTB DNA/NTBM (SYNTOL, Russia), and on DNA strips (GenoType Mycobacterium CM\AS Hain Livescience, Germany)). Specimens were cultured on a liquid medium in the ВАСТЕС MGIT960 (BD, USA).

The diagnosis of mycobacteriosis was established in accordance with the diagnostic criteria proposed in the guidelines of the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) (2020): detection of NTBM in 2 sputum samples or in 1 sample of bronchobiopsy specimens or in 1 surgical specimens [15].

The studied data were entered to the Microsoft Office Excel sheet (Microsoft, USA) for statistical processing; the level of statistical significance of differences was taken as 0.05.

Results. It was found that slow-growing NTBM were identified as etiologically significant in 93.0%, of which 78.1% was M. avium, fast-growing NTBM were represented only by M. abscessus, 7% of observations. During X-ray examination, the bronchiectatic form – 52.1% (74/142) was detected more often compared to the abdominal – 30.9% (44/142) and focal forms – 16.9% (24/142) (p<0.001). When verifying mycobacteriosis in patients with a negative sputum test – Stage 2 of the examination – the effectiveness was 91.0% (80/88). Regardless of the radiological form of the disease and dissemination of the disease, bronchoscopy revealed pathology of the tracheobronchial tree in 85.2% of cases, mainly in the form of bronchitis with purulent secretions.

The objective: to evaluate the toxicity of combinations of delamanid and drugs for treatment of drug resistant tuberculosis with different safety profiles in an experiment.

Results. During 14 days of the study, the animals of both experimental groups satisfactorily tolerated the administration of drug combinations, no animals died, and no negative impact on body weight changes was observed (physiological weight gain). In rats from Group OG-1, the change in the skin color (orange tint) was noted.

This change in the tissue color is an adverse reaction, but according to the literature [4], it is reversible. The prolongation of QT interval on ECG in rats treated with the combination of drugs with cardiotoxic potential (Dlm, Bdq, Cfz, Pto) was insignificant, and with the combination of Dlm, Lzd, Cs, Pto did not differ from the baseline level. The neurotoxicity of the combination of Dlm, Lzd, Cs, Pto combination manifested through a decrease in motor and exploratory activity. A decrease in exploratory activity in rats treated with Dlm, Bdq, Cfz, Pto was observed against the background of the preservation of their motor activity. There were no significant changes in laboratory and morphometric parameters in both experimental groups compared to the control group.

The objective: analysis of clinical cases of tuberculous spondylitis in HIV-infected patients with the detection of HIV RNA in the focus of vertebral bodies destruction.

Subjects and Methods. Medical records of 2 HIV-infected patients who underwent surgery for verified tuberculous spondylitis were analyzed. Parts of the vertebral bodies collected during surgery were examined (PCR, microbiological and histological tests), those were parts with destruction and fragments of healthy iliac bone necessary to fill the implant during corporodesis.

Results. RNA HIV was detected in the foci of bone destructionas as well as M. tuberculosis DNA. The viral load in the fragments of healthy iliac bone and peripheral blood of these patients was undetectable.

The objective: to assess the incidence of tuberculous peritonitis, to identify its gender and age characteristics, to describe typical comorbidities preceding the development of peritoneal tuberculosis.

Subjects and Methods. The following documents were statistically analyzed: Forms no. 003/u Medical Record of an In-patient Patient for new tuberculous peritonitis patients for 2013–2020, who were treated at Clinic 2 of Moscow Municipal Scientific Practical Center of Tuberculosis Control, Moscow Health Department, and Rosstat Forms No. 8 on Active Tuberculosis Cases for the same period, as well as information from registers of the city tuberculosis monitoring system that has been operating in Moscow since 1996.

Results. According to different definitions, the expected incidence of tuberculous peritonitis in the coming years will make from 0.03 to 0.1 per 100,000 population per year in Moscow and 0.1–0.2 per 100,000 in Russia. In Moscow, the main cohort of tuberculous peritonitis patients includes young women after pregnancy and childbirth, who came from other regions of the Russian Federation or neighboring countries. Men develop tuberculous peritonitis 1.6 times less frequently versus women. The most common factors influencing the development of peritoneal tuberculosis in men are drug-induced immunosuppression, dialysis, and diabetes mellitus. HIV infection, unlike other forms of extrapulmonary tuberculosis, is not a major risk factor faced by individuals with tuberculous peritonitis.

The objective: substantiation of the possibility of surgical treatment of various lung diseases in HIV-infected patients.

Subjects and Methods. Comorbidities, medical history, bad habits, ongoing antiretroviral therapy (ARVT), viral load and CD4+count before and after lung surgery were assessed. Blood loss during the operation, intra- and postoperative complications was analyzed. Causes of postoperative lethality were analyzed.

Results. According to results of the study, planned surgical treatment for chronic abscess, tuberculosis, cancer, mycotic pulmonary lesions and cicatricial stenosis of the trachea in HIV-infected patients is justified, and should be performed based on indications common for these diseases. This is confirmed by the level of postoperative complications in HIV-negative patients. The vast majority of complications were temporary, not severe, and were resolved by conservative treatment. Achievment of the best results is facilitated by ongoing ART.

The objective: study of the burden and effectiveness of treatment of multiple drug resistant pulmonary tuberculosis (MDR TB) with different chemotherapy regimens in the Republic of Tajikistan.

Subjects and Methods. To achieve this objective, the prevalence of drug resistant tuberculosis in 2009–2020 was studied by analyzing statistical documents on drug resistant tuberculosis, official reporting data from the Center for Medical Statistics and Republican TB Control Center by the Ministry of Health and Population Social Welfare of the Republic of Tajikistan.

Results. The analysis of official statistics indicates a stable trend towards a decrease in tuberculosis incidence from 2014 to 2019, annually on average up to 1% – from 60,8 to 56,5 per 100,000 population. During the pandemic in 2019–2020, this trend increased, according to statistics the incidence made 39.7 per 100,000 population. From 2014 to 2019, tuberculosis mortality also declined steadily from 3,9 to 2,2 per 100,000 population. During the pandemic in 2019–2020, a rapid decline was noted – from 2,2 to 1,4, while in 2020–2022, it decreased from 1,4 to 1,0 per 100,000 population. From 2013 to 2020 treatment success reached 90%. The detection of drug resistant tuberculosis is close to 900 cases per year, and more than 90% of them were covered with treatment. In 2018–2020, successful treatment of drug resistant tuberculosis increased from 72,5% to 80,6% due to the introduction of new and repurposed anti-tuberculosis drugs.

The objective: to evaluate the efficacy and safety of bedaquiline in new chemotherapy regimens in HIV-positive tuberculosis patients.

Subjects and Methods. Treatment results of 60 patients with TB/HIV co-infection using treatment regimens containing bedaquiline were analyzed.

Results. Patients with TB/HIV co-infection demonstrated poor adherence to treatment, so 46/60 (76.6%) patients did not complete the intensive phase of chemotherapy. The use of bedaquiline did not cause a critical prolongation of the QT according to ECG results, manifestations of arrhythmia, and it was well combined with ART. Sputum conversion (by culture) was registered in the following cases: by the end of the 2nd month of chemotherapy in 36/60 (60.0%) patients, by the end of the 6th month of chemotherapy – in 11/14 (78.6%) patients.

The objective: to assess risk factors for tuberculosis relapse during the COVID-19 pandemic.

Results. During the retrospective study, medical documents of patients treated for tuberculosis in 2020-2022 were analyzed. 140 patients above 18 years old with confirmed tuberculosis were included: newly diagnosed tuberculosis – 50 patients, early relapses – 50 patients, and late relapses – 40 patients. At the first stage, significant factors for relapse development were identified (ANOVA): diabetes (F=19402,8; p=0,000000), substances abuse (F=547,6; p=0,000000), alcohol abuse (F=149,7; p=0,000000), MDR MTB (F=107,8; p=0,000000), HIV infection (F=72,4; p=0,000000), imprisonment (F=49,5; p=0,000000), chronic respiratory diseases (F=47,1; p=0,000000), smoking (F=29,0; p=0,000000), and social status (F=28,9; p= 0,000000). At the second stage (cluster analysis), factors implementing the risks of development of early or late relapses were identified.

As well as before the COVID-19 pandemic, social, medical and biological risk factors play a significant role in the development of tuberculosis relapses; history of COVID-19 was not one of the risk factors; and stratification of the risk factors made it possible to identify factors that contribute to development of both early and late relapses and to determine preventive measures.

The objective: to study the changes in the lung microbiota in inbred C57BL/6 mice after aerogenic infection with M. tuberculosis in an experimental tuberculosis model.

Subjects and Methods. This study was carried out on 20 female mice of inbred line C57BL/6 weighing 20-22 grams which were infected in a Glas-Col aerosol chamber (USA) with the culture of M. tuberculosis of virulent strain H37Rv at the dose of 400 CFU/lung. Morphological and microbiological assessment of the lungs state was performed before (day 0) (n=5) and 7 (n=5), 30 (n=5) and 60 (n=5) days after the infection. The results obtained were subjected to statistical processing using ANOVA test and Student t-test.

Results. 7, 30, and 60 days after aerosol infection with M. tuberculosis against the background of successive morphological and microbiological changes typical of the experimental tuberculosis model, we established an imbalance of bacterial population in the lung microbiota. Before infection with M. tuberculosis, a scanty biotope was recorded with a predominance of lactobacilli –Lactobacillus murinus, Lactobacillus apodeme. 7, 30 and 60 days after infection with M. tuberculosis, consistent changes were recorded, such as increase in the number and diversity of the bacterial population. The most indicative markers of the recorded imbalance were: Streptococcus thoraltensis, Streptococcus acidominiminus, Arthrobacter crystallopoietes, Staphylococcus hominis, Micrococcus luteus.

Conclusion. Tuberculosis infection is a significant factor affecting the state of the lung microbiota. With increased duration of the infection with M. tuberculosis, imbalance of the bacterial flora is formed in the lungs of C57BL/6 mice, accompanied by characteristic tissue inflammation and growing mycobacterial load.