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The objective: to assess effectiveness of mass screening for tuberculosis infection in children and adolescents in Moscow, determine infection rate and incidence in different age groups.

Subjects and Methods. Screening was performed in 2023. Two different screening methods were used in different ages: all children aged 0 to 7 years were given Mantoux test with 2 TU PPD-L, and if the reaction increased versus the previous year, a test with tuberculous recombinant allergen (Diaskintest or TRA) was performed additionally. Children and adolescents aged 8-17 years were given the TRA test only. Mantoux test was used in 729,972 children from 0 to 7 years old. Positive responses were observed in 488,706 (66.9%) of them, which was due to the high rate of post-vaccination allergies at that age. When tuberculosis infection was suspected, the TRA test was performed in 21,552 people. (4.4% of all tuberculin-positive individuals). At the same time, positive reactions were noted in 201 people (0.9%). Among them, tuberculosis was detected in 7.5% (15 patients), post-tuberculosis changes (the calcification phase of the disease) were detected in 8.5% (17 people), while the proportion of positive reactions to the TRA test increased. Children of 8-17 years old were screened with the TRA test only. 1,170,461 people were examined, positive reactions were noted in 0.2%. The detection rate of tuberculosis among them was 1.6% (30 people), and the rate of the calcification phase of the disease indicating spontaneous recovery was 3.7%. The proportion of positive reactions is growing as the age of children increases, which corresponds to the higher incidence of pulmonary tuberculosis at these ages. The analysis of the incidence of various forms of tuberculosis in Moscow revealed the following. At the age of up to 7 years, tuberculosis of the lymphatic system predominates and this is the period with the highest incidence of this form. Then in the period before puberty, the lowest incidence is observed. After that, pulmonary forms of tuberculosis begin to predominate, and in adolescence, the incidence rises to maximum rates. BCG vaccination in the neonatal period resulted in the near disappearance of tuberculosis mortality, and such forms as miliary tuberculosis and meningitis. However, BCG vaccination and revaccination could not prevent pulmonary forms of tuberculosis in adolescence. The article presents age-specific mortality rates in Moscow in the pre-antibacterial era, when BCG vaccination was not available and the predominant forms of tuberculosis at different ages were the cause of death.

Results: Obviously, a one-stage screening (TRA test) performed in children of 8-17 years old, is more convenient for both medical workers and patients, and it is more cost effective. However, it is currently impossible to switch to this test when examining children under 7 years, since children receive BCG revaccination if the response to Mantoux test is negative.

The objective: to develop a new method to detect early subclinical signs of LTBI progression to the active disease.

Subjects and Methods. Children under 18 years of age were enrolled in the study, of them 8 children suffered from pulmonary tuberculosis (TB Group) and 91 had LTBI (LTBI Group). Detection of subclinical signs of tuberculosis infection activity in LTBI Group included testing the concentration of antigen-specific induction of IFN-γ at the level more than 14 pg/ml, IL-6 more than 8 pg/ml and positive values of threshold cycles (Ct) of mRNA samples based on the results of real-time PCR of genes: PDCD1, PDL2, BATF2 and GBP5.

Results. The developed method for detection of subclinical signs of tuberculosis infection activity in children and adolescents with LTBI consists of two components (immunological testing of concentration of IFN-γ and IL-6; and molecular genetic testing of mRNA expression of the PDL2, BATF2 and GBP5 genes). Simultaneous registration of IFN-γ and IL-6 levels and mRNA expression of the PDL2, BATF2 and GBP5 genes above reference values indicates a high risk of developing active tuberculosis. It was observed in 29/91 (31.9%) patients with LTBI, in whom chest CT revealed calcifications in the upper lymph nodes or pulmonary lesions within 1 year.

The objective: to study the factors influencing the risk and timing of a lethal outcome in tuberculosis patients with confirmed resistance to rifampicin in general population (Federal Register of Tuberculosis Cases of the Russian Federation (FRTBC)).

Subjects and Methods. 15,604 tuberculosis patients with confirmed resistance to at least rifampicin and registered for treatment in 2021 were enrolled in a retrospective cohort study of lethal outcome predictors in general population (Federal Register of Tuberculosis Cases of the Russian Federation (FRTBC)).

Results. The leading lethal risk factors were as follows: positive HIV status (aOR=2.82; 95% CI 2.60-3.06), history of treatment interruption (aOR=1.90; 95% CI 1.67-2.15), and patient age (aOR=1.03; 95% CI 1.02-1.03). The lower risk of mortality was noted in female patients (aOR=0.76; 95% CI 0.69-0.83), patients susceptible to fluoroquinolones (aOR=0.77; 95% CI 0.71-0.85), and patients with tuberculosis relapse (aOR=0.85; 95% CI 0.75-0.97). The time to death was shorter in new tuberculosis patients, patients with no confirmed resistance to fluoroquinolone, and HIV positive patients not receiving antiretroviral therapy (ART).

Conclusion. To reduce the risk of a lethal outcome in addition to early detection of tuberculosis, it is advisable to administer antiretroviral therapy in HIV positive patients in a timely manner, as well as to monitor the adequacy of anti-tuberculosis therapy prescribed and the patient's adherence to treatment.

The objective: to study the role of CaD proteins, αV integrin and TIMP-1 in the development of pulmonary tuberculosis.

Subjects and Methods. 27 specimens of pulmonary tuberculomas were used for this study. The specimens were divided into 3 goups in accordance with the degree of inflammatory and reparative changes occurring in the tuberculoma tissue. The targeting proteins were visualized by immunohistochemical methods. For quantification, the relative area of expression of signaling molecules was counted. The obtained data were statistically processed based on nonparametric criteria.

Results. Data analysis showed an increased level of CaD expression during wall epithelialisation compared to the group with no connective tissue repair, which was associated with the involvement of CaD in the concomitant repair and fibrosis formation. Statistically significant differences in the expression levels of αV integrin between Groups 2 and 3 were found in the case of granuloma inflammation. The decrease in the protein levels from Group 2 to Group 3 may be due to activation of the anti-inflammatory mediator TGFβ1 and induction of M2 macrophages. The results of testing TIMP-1 expression level demonstrated its involvement both in granuloma fibrosis and formation of connective tissue complex in the inflammation site. The obtained data indicate that the studied proteins can be considered as informative biomarkers in molecular diagnostics and assessment of prognosis of pulmonary tuberculosis development.

The objective: to evaluate the hepatoprotective and neuroprotective activity of the nootropic drug of deanol aceglumate (nooclerin) in rats during the administration of a hepatotoxic combination of anti-tuberculosis drugs.

Subjects and Methods. Young non-linear female rats divided in 3 groups were used in this study. For 14 days, daily, rats from experimental Groups 1 and 2 received a regimen containing 5 anti-tuberculosis drugs: Mxf+ Lzd+ Cs+ Pto+ Z. Additionally, rats of Group 2 were injected with nooclerin before the administration of anti-tuberculosis drugs. Rats from Control Group received only starch suspension. Doses of anti-tuberculosis drugs and nooclerin corresponded to recommended doses for humans. The manifestation of neurotoxicity was assessed by changes in behavioral reactions according to Open Field Test, hepatotoxicity was assessed according to biochemical and morphological criteria.

Results. The hepatoprotective effect of nooclerin was confirmed by statistically significant decrease in the transaminases and bilirubin activity, which elevation was caused by anti-tuberculosis drugs, and a significant (4-fold) decrease in the severity of pathological changes in the liver tissue. Studies of behavioral reactions showed that nooclerin slightly improved the exploratory activity of rats, which was slightly reduced under the influence of anti-tuberculosis drugs.

The objective: to assess elution characteristics of certain antiviral drugs immersed in bone cement samples and placed in a liquid medium to determine the fundamental possibility of using such systems.

Subjects and Methods. For the in vitro study, dispersed ART formulation mixed with bone cement were used. To study kinetics of drug elution, a spectrophotometry was used.

Results. It was found out that raltegravir, emtricitabine and lamivudine possessed satisfactory thermostability and elution parameters thus allowing their use in a mixture with bone cement. The results demonstrated the fundamental possibility of developing systems with controlled release of these drugs immersed in bone cement and placed into a liquid medium.

The objective: to evaluate the effectiveness of short-curse chemotherapy regimens for treatment of MDR/pre-XDR tuberculosis in combination with surgery in older children and adolescents.

Subjects and Methods. 51 patients with MDR/pre-XDR respiratory tuberculosis aged 13-17 years were enrolled in a prospective open study (2017-2021). The statistical correlation between certain factors and prescription of continuous or short-course chemotherapy to a patient after surgery was calculated using the Pearson χ² test.

Results. Of the 51 patients, short-course chemotherapy regimen (12 months) was administered to 37 (72.5%) patients, while continuous treatment regimen (13 months or more) was used in 14 (27.5%) patients. It was found that surgical treatment was taken into account as a risk factor when prescribing continuous chemotherapy (χ² = 5.307; p = 0.022). In 40 operated patients, continuous chemotherapy was statistically significantly more often prescribed when following factors were observed: surgery after 10 months and more after the start of treatment (χ² = 21.567; p < 0.001), two-stage surgery (χ² = 8.254; p = 0.005), and tuberculosis progression after surgery (χ² = 3.910; p = 0.049). TB relapses after a year of follow-up in the patients treated with continuous chemotherapy regimens made 11%, while in case of short-course treatment, they were 9%. The results of our study indicate the possibility of using short-course chemotherapy regimens in combination with surgical treatment.

The objective: to study the effectiveness and safety of new chemotherapy regimens at the end of the intensive phase in the patients suffering from multiple drug resistant tuberculosis (MDR TB), concurrent HIV infection (HIV), and chronic hepatitis C (HCV).

Subjects and Methods. The effectiveness and safety of MDR TB treatment regimens containing bedaquiline, linezolid, delamanid, and clofazimine in various combinations were studied in 68 patients with the triple infectious disease MDR TB/HIV/HCV. The control group included 64 patients receiving treatment with the regimens free of these drugs.

Results. Bacteriological effectiveness was achieved in all patients. In the group of new drugs, the timing was shorter: culture conversion after taking 30 doses was registered in 70.6% versus 43.8% of patients in the control group. Positive radiographic changes such as decreased focal infiltrative shadows, were noted in 41.1% versus 25% of patients, cavity healing was observed in 18.1% versus 5.1% of patients, respectively. The incidence of adverse reactions (ARs) was higher in the control group (90.6% vs. 52.9%). In both groups, the most common adverse event outcome was discontinuation of one anti-tuberculosis drug (69% vs. 42%).

Conclusion. Chemotherapy regimens containing new anti-tuberculosis drugs are more effective and have a more favorable safety profile.

The objective: to identify differences in the composition of microbial markers detected by mass spectrometry of microbial markers in specimens of bronchial washings from patients with different clinical and radiological forms of tuberculosis.

Subjects and Methods. Specific features of microbiota of the lower respiratory tract in patients with various forms of pulmonary tuberculosis receiving anti-tuberculosis therapy were studied.

Results. Using mass spectrometry of microbial markers we studied bronchial washings obtained from the lung lobe with pathological changes and from another lung without pathology, which were selected according to computed tomography data. A high degree of inverse correlation was revealed between the number of markers of two groups of microorganisms: Group 1 (Clostridium ramosum + Corynebacterium spp. + Streptomyces spp.) and Group 2 (Eubacterium spp. + Eggerthella lenta + Lactobacillus spp. + Propionibacterium freudenreichii + Actinomyces viscosu + Prevotella spp. + Rhodococcus spp.). It was found that when Group 2 microorganisms predominated, bronchial washings in 58.8% were obtained from fibrotic cavernous tuberculosis lesions. When Group 1 microorganisms predominated, bronchial washings were obtained from sites of resolving infiltrative tuberculosis (13.3%) or sites without pathological changes (46.6%).

The objective: to identify specific features of the COVID-19 course in HIV positive patients and risk factors for unfavourable outcomes in such patients.

Subjects and Methods. Patients with COVID-19 regardless of their HIV status admitted to hospital were enrolled in a retrospective observational study.

Results. HIV positive patients experienced a more severe course of COVID-19 including more extensive lung tissue damage and severe respiratory failure. Shortness of breath was more common of patients with HIV infection. Laboratory tests revealed adecreased antiviral immune response, signs of anemia and liver damage, and a tendency to develop blood clots. When developing a prognostic logistic regression model in patients with COVID-19 and HIV infection, it was revealed that the risk of an unfavorable outcome was associated with such factors as a decrease in the relative number of lymphocytes and level of total protein in peripheral blood at the moment of admission to hospital.

Conclusions. Given the elevated risk of a severe course and unfavorable outcome of COVID-19 in case of concurrent HIV infection, it is necessary to monitor symptoms of respiratory failure in these patients, and if they appear, make a decision about hospitalization at an earlier stage of the disease.

The article describes a unique clinical case of 18-year comprehensive treatment of the patient with disseminated fibrous cavernous pulmonary tuberculosis with extensive drug resistance, continuous bacterial excretion and severe concomitant pathology resulting in successful cure of tuberculosis. It demonstrates the complexity of the decision-making on patient management tactics as well as a rare example of exceptional patient adherence to treatment.

Cough ensures cleansing of the upper respiratory tract from foreign particles, mucus, and microorganisms, so a health care professional specializing in any field needs to know the physiology of this unconditional reflex for a better understanding of its nature. 43 publications are presented in the review. It analyzes types, frequency, prevalence of chronic cough, afferent and efferent links of the cough reflex, central regulation, and involvement of inflammatory mediators.

The review analyzes of 56 publications that address the problem of comorbid diabetes mellitus, thyroid dysfunction and tuberculosis. It presents data on the incidence and prevalence of these nosologies and their combinations.