The objective: to determine the most significant parameters in the diagnosis of tuberculosis in children with chronic non-specific lung diseases in order to form groups facing a high risk of developing tuberculosis.

Subject and Methods: 236 children were enrolled in the study, who were divided into three groups: TB+CNSLD group – 65 children with primary tuberculosis and concomitant chronic non-specific respiratory disease, TB group - 93 children with active respiratory tuberculosis and a group of 78 children and adolescents with chronic non-specific respiratory diseases without tuberculosis but infected with MTB.

Results. Chronic non-specific lung diseases increase the risk of earlier development of tuberculosis in children. For the first time, effectiveness of IGRA tests and TRA tests for detecting tuberculosis in children infected with tuberculous mycobacteria with both allergic and infectious-inflammatory non-specific lung diseases has been proven.

The objective: to optimize diagnostics of cardiovascular disorders in respiratory tuberculosis patients during anti-tuberculosis therapy.

Subjects and Methods. A total of 93 patients with pulmonary tuberculosis without concomitant cardiovascular diseases (CVD) were examined. Daily electrocardiogram monitoring was performed for at least 24 hours using 3 leads. The parameters of the myocardial repolarization were analyzed. The results of the study were processed using MS EXCEL 2016 for Windows and STATISTICA 10 by nonparametric methods.

Results. Various signs of electrophysiological remodeling (ER) combining with each other were identified. Most often, these changes were expressed in hyperadaptation of QT to heart rate and decrease in dQT and Tp-e values. Increased QTcFmin, dQT, Tp-e were rare. Elevated values of the iCEB index were more often detected in patients with a higher average daily QT duration. No statistically significant differences in ER indices were found between the groups of patients with limited and widespread tuberculosis. Patients with respiratory tuberculosis should have their QT dynamics analyzed and signs of ER should not be limited to QT interval testing alone. QT changes do not depend on the degree of pulmonary tuberculosis dissemination.

The objective: to assess the impact of the COVID-19 pandemic on epidemiological situation, regularity of preventive screening, and structure of clinical forms of new pediatric tuberculosis cases in Smolensk Oblast in 2015-2019 and during the pandemic in 2020-2022.

Subjects and Methods. We studied the incidence, coverage with preventive screening, exposure to tuberculosis infection, age and clinical structure of tuberculosis (TB), presence of lung tissue decay, positive results of sputum tests, and drug resistance covering two periods of 2015-2019 and 2020-2022 in children and adolescents in Smolensk Oblast.

Results. During the pandemic, tuberculosis incidence in children and adolescents tended to increase and exceeded the Russian average rate, while the coverage with preventive screening decreased. A higher number of children and adolescents infected with tuberculosis after exposure to two and more TB cases and exposure to fatal and drug resistant cases was established. Local forms of respiratory tuberculosis predominated the in structure of clinical forms; however, during the COVID-19 pandemic, the proportion of the disease with pulmonary tissue destruction and positive results of sputum tests increased sharply among both children and adolescents indicating the late detection.

Conclusion. In the event of any pandemic, preventive screening for tuberculosis should be maintained as much as possible and measures should be in place to avoid exposure of children to infectious tuberculosis cases.

The objective: to demonstrate differential diagnosis techniques of pulmonary tuberculosis with lung malformation (sequestration) in adult patients.

Subjects and Methods. In 2021-2023, 5 patients with pulmonary sequestration underwent surgery in Surgery Department of National Medical Research Center of Phthisiopulmonology and Infectious Diseases. All patients were followed up by TB service, and 3 patients were already receiving anti-tuberculosis therapy at the time of surgery.

Results. Chest computed tomography was the main tool to visualize lesions and establish preliminary diagnosis. All patients received lower lobectomy. Intralobar sequestration was confirmed in 3 patients, while extralobar sequestration within the chest was confirmed in 2 patients. According to results of surgical specimen tests, pulmonary tuberculosis was ruled out in 4 patients, and 1 patient was diagnosed with concurrent pulmonary sequestration and tuberculosis. This article presents 3 clinical cases of patients with pulmonary sequestration, including 1 case with co-morbid tuberculosis.

The objective: to estimate the proportion of those lost to follow-up at individual stages of the cascade medical care for tuberculosis infection, to identify factors influencing these losses.

Subjects and Methods. A total of 810 homeless individuals were included in the prospective cohort study from January 1, 2019 to December 31, 2022. When active tuberculosis (TB) was ruled out and indications for preventive anti-tuberculosis therapy (PTBT) were established, the optimal regimen for the patient was suggested. After completion of preventive anti-tuberculosis therapy, follow-up of patients continued for at least 12 months. By the end of follow-up, patients underwent control chest X-ray to detect tuberculosis manifestations.

Results. Of the 810 people included in the study, 207 (25.6%) received preventive treatment of tuberculosis. Of them, 77/207 (37.2%) did not start a course of preventive treatment (loss to follow-up). The age of 28-37 years, alcohol addiction, and positive HIV status were associated with the biggest loss at this stage. Of the 130 people who started preventive treatment, 42 (32.3%) did not complete the full course of treatment. However, the chances of incomplete treatment on regimens of three months or longer were 5.4 (CI: 2.2-15.4) times higher versus a one-month regimen. The biggest loss of 64/88 (72.7%) cases was recorded during the follow-up period (after completion of preventive treatment). No tuberculosis cases were detected among those who received the full course of preventive treatment. While among those who refused or interrupted preventive therapy, 3 cases of tuberculosis were diagnosed. 

The objective: to determine the types and prevalence of Mycobacterium tuberculosis DNA mutations associated with resistance to rifampicin, isoniazid, ethambutol, fluoroquinolones and injectable drugs in MDR TB patients in Arkhangelsk Oblast.

Subjects and Methods. In Arkhangelsk Oblast, all patients underwent examination by molecular genetic testing and phenotypic methods for drug susceptibility. In 2010-2017 in Arkhangelsk Oblast, 1064 new MDR TB cases were registered. A total of 1340 cases of MDR TB were registered during this period, including 276 cases with recurrent MDR. Mutations associated with resistance to rifampicin (rpoB gene) and isoniazid (inhA, katG genes) were identified by Genоtype MTBDRplus (Hain Lifescince); mutations associated with resistance to fluoroquinolones (gyrA gene), injectable drugs (rrs gene) and ethambutol (emB gene) were identified using GenoType MTBDRsl (Hain Lifescince) in accordance with the manufacturer's recommendations.

Results. In 2010–2017 among 1064 new MDR TB cases, Mycobacterium tuberculosis mutations associated with simultaneous resistance to rifampicin and isoniazid were detected in 922/1064 (87%) cases; mutations associated with monoresistance to isoniazid were found in 2/1064 people. 1196/1340 (89%) MDR TB cases underwent examination with GenoTуре MTBDRsl. The predominant mutation in the rpoB gene was the S531L mutation (86.6%), the second and third most frequent mutations were D516V (5.3%) and L511P (2.6%), respectively. Mutations in codon 526 were less frequent than the others. In all MDR TB cases, mutations in the katG gene were detected, which were combined with mutations in the inhA gene in 85 (9.2%) cases. Only two cases had isolated mutations in the inhA gene. The predominant mutation among M. tuberculosis isolates associated with resistance to isoniazid was S315T1 (98.8%) in the katG gene, and C15T in the inhA gene. According to the results of our study, mutations in the gyrA gene were present in 13.6% (163/1196; 95% CI 11.7–15.7%) of cases, in the embB gene – in 49.7% (594/1196; 95% CI 46.8–52.5%), in the rrs gene – in 7.1% (85/1196; CI 95% 5.7–8.7%). Among all studied isolates with resistance to fluoroquinolones, the most common mutation in the gyrA gene was D94G (79/163; 48.5%), including cases without wild-type dropout. The A90V mutation was present in 19% of cases. The S91P mutation was detected in 11.7% of isolates. The D94N and D94A mutations occurred in 9.2% and 7.4% of cases, respectively. In 3 cases, two mutations were present simultaneously. All isolates in our study had mutations in the rrs gene associated with high levels of resistance to injectable drugs (A1401G and G1484T). In the rrs gene, the rrs A1401G mutation was most common (81/85; 95.3%), including cases of simultaneous detection of “mutant samples” and “wild type” samples. In 4.7% of cases, the G1484T mutation was detected. In Arkhangelsk Oblast, 81.5% (95% CI 78.1% to 84.5%) of mutations in the embB gene were M306V mutations and 18.5% (95% CI 15.5% to 21.9%) were M306I mutations.

The objective: to evaluate diagnostic efficacy of adenosine deaminase and other biochemical markers (total protein, glucose, and lactate dehydrogenase) in pleural fluid in pleurisy of various etiologies.

Subjects and Methods. The following parameters in pleural fluid and clinical data of 89 patients with pleural effusion of various etiologies were retrospectively analyzed: tuberculous (TBP), metastatic (MP) and other (OP) pleurisy. In the pleural fluid, the activity of ADA, lactate dehydrogenase (LDG), levels of total protein (TP), and glucose (Glu) were assessed.

Results. ADA activity was statistically significantly higher in patients with tuberculous pleurisy versus patients with metastatic pleurisy and pleurisy of some other etiology. High enzyme activity was due to a statistically significant increase in activity of the ADA-2 isoenzyme. The LDG/ADA and LDG/ADA-2 ratios, the Glu level in patients with tuberculous plerisy were statistically significantly lower, and, on the contrary, the ADA/TP and ADA-2/TP, ADA/Glu and ADA-2/Glu ratios were higher than in patients from the other two groups. High diagnostic efficacy of ADA, ADA-2, LDG/ADA and LDG/ADA-2 was revealed: sensitivity of the tests made 91, 82, 100%, specificity made 87, 81, 83 and 92%, respectively.

Conclusions. For differential diagnosis of tuberculous pleurisy, the LDG/ADA ratio can be used along with ADA which is the effective biomarker. The ratios of ADA/TP and ADA-2/TP, ADA/Glu and ADA-2/Glu activity are of little information value for the differential diagnosis of tuberculous pleurisy.

The objective: to study factors that reduce the diagnostic efficiency of rapid testing for tuberculosis based on the detection of antibodies to PstS1 and PstS3 antigens of M. tuberculosis and highly purified lipoglycan of the M. tuberculosis cell wall.

Subjects and Methods. Clinical and laboratory data of 290 tuberculosis patients were analyzed. Logistic regression analysis and ROC analysis were used to identify factors associated with a negative result of rapid tuberculosis testing.

Results. 45/290 (16%) patients had a positive result of the rapid test for PstS1, PstS3 antigens and 154/290 (53%) patients responded positively to lipoglycan antigen. The number of people who tested positive was 164/290 (57%). However, in HIV negative patients these values were higher and amounted to 41/196 (21%), 137/196 (70%) and 144/196 (73%), respectively. The following factors were found to be positively associated with a negative result of rapid testing: positive HIV status (OR=7.803; 95% CI 3.845-15.834; p<0.001) and male gender (OR=2.040; 95% CI 1.117-3.725; p =0.020). The combination of these two factors had a more significant predictive value (AUC 0.787; p<0.0001) of a negative rapid test result. In case of HIV infection, the lipoglycan antigen showed a greater degree of immunogenicity versus the PstS1, PstS3 antigens (18% positive results for lipoglycan versus 4% positive results for the PstS1, PstS3 antigens), OR = 4.968; 95% CI 1.603-15.392; p=0.003).

The objective: to study the effectiveness of sanatorium treatment of children with latent tuberculosis infection and metatuberculous changes exposed to tuberculosis infection, to improve selection of children to undergo preventive anti-tuberculosis treatment in a sanatorium.

Subjects and Methods. In 2018-2023, 2007 children aged 1-15 years were treated in TB Sanatorium. Two groups of children were compared to assess the effectiveness of preventive treatment of tuberculosis: 156 children who received treatment in the sanatorium, and 54 children who received outpatient treatment with no observation. The treatment lasted 3 or 6 months, and the following regimens were used: isoniazid+rifampicin/etambutol/pyrazinamide, and pyrazinamide+etambutol/prothionamide in case of exposure to MDR-TB.

Results. Children were selected for preventive anti-tuberculosis treatment in a sanatorium based on epidemic and social risk factors, degree of intensity of the response to TRA. As a result of the sanatorium treatment, the number of children with positive and hyperergic reactions to the TRA test decreased, while during outpatient treatment, the number of children with positive results increased. After one year, 41.1% of children who received preventive anti-tuberculosis treatment in the sanatorium were taken off the follow-up register, and no child became ill with tuberculosis. Among children who received preventive anti-tuberculosis treatment in outpatient settings, only 16.7% were taken off the follow-up register; 1 (1.9%) child became ill with tuberculosis. 

The objective: to analyze cases of tuberculosis with a different range of mutations in the M. tuberculosis genes associated with resistance to isoniazid and rifampicin, to determine prevalence of such mutations, clinical significance and molecular genetic characteristics of pathogens. The cases detected in Saratov Oblast were included in the analysis.

Subjects and Methods. A total of 437 sputum samples obtained from HIV-negative tuberculosis patients in 2006-2020 living in

Saratov Oblast were examined by biological microarray method. The range of mutations was studied in katG, inhA, ahpC genes associated with drug resistance to isoniazid and in rpoB gene associated with drug resistance to rifampicin.

Results. DNA of M. tuberculosis was isolated from 70.9% of samples, of which 53.8% had mutations. Single-nucleotide substitutions in one of katG, inhA, ahpC, rpoB genes were found in 36.1%, double mutations were found in 10.9%, and multiple mutations (substitutions of three or more nucleotides) were found in 6.8%. The largest number of double and multiple mutations was registered in rpoB gene - 8.9% and 10.2%, respectively. The largest number of combined mutations in different genes was observed in the combination katG+rpoB – 23.4% and katG+inhA+rpoB – 19.2% 17 (5.48%) samples with simultaneous multiple and combined mutations in different genes katG, inhA, ahpC were identified. Of these, 14 (82.3%) people had multiple mutations in katG, inhA, ahpC genes combined with multiple mutations in rpoB gene, of which 57.2% had severe forms of tuberculosis with destruction and positive results of sputum tests. Thus in Saratov Oblast among patients with pulmonary tuberculosis, a group was identified in which M. tuberculosis had multiple mutations in katG, inhA, ahpC genes in combination with multiple mutations in rpoB gene.

The objective: to determine the place of surgery in the diagnosis of genitourinary tuberculosis (GUTB).

Subjects and Methods. We retrospectively analyzed the surgical protocols and medical records of 174 patients who underwent surgery in Extrapulmonary Department of Clinic no. 2, Moscow Research and Clinical Center for Tuberculosis Control of the Moscow Government Department of Health from 2018 to 2021. Of them 112 patients were suspected of having genitourinary tuberculosis.

Results. It was found that after diagnostic and treatment surgery, genitourinary tuberculosis was confirmed in 47/112 (42.0%) people. The test with tuberculous recombinant allergen (TRA) demonstrated low sensitivity for genitourinary tuberculosis. Only

5/36 (13.9%) patients with isolated genitourinary tuberculosis responded positively to this test. The result of urine PCR test for M. tuberculosis was negative in all 47 patients. Signs such as HIV infection, persistent and intermittent erythrocyturia, statistically significantly correlated with the diagnosis of genitourinary tuberculosis (p <0.05).

Conclusions. Genitourinary tuberculosis remains a difficult form of extrapulmonary tuberculosis to diagnose. Treatment and diagnostic surgery with pathomorphological verification of suspected genitourinary tuberculosis are often the only diagnostic method.

The objective: to study toxicity modifying effects of Coenzyme Q10 in toxic reactions caused by a combination of antituberculosis drugs in the rat experiment.

Subjects and Methods. 30 non-linear female rats weighing 230-250 g, divided into 3 groups were used in the experiment. Control Group (CG) received 1% starch gel. Experimental Group 1 (EG1) received a combination of 5 antituberculosis drugs: Mxf + Bdq + Lzd + Cs + Z, Experimental Group 2 (EG2) received the same antituberculosis drugs, and additionally Coenzyme Q10 as the drug product of Qudesan, 30 min before the combination of antituberculosis drugs. Doses of antituberculosis drugs and Coenzyme Q10 were equivalent to human therapeutic doses used in the clinic. The manifestation of toxic reactions in rats was evaluated by body weight changes, clinical and biochemical blood parameters, changes in ECG and behavioral reactions in the open field test, and morphological changes in organs and tissues.

Results. Coenzyme Q10 showed the ability to modify cardio-, hepato-, hematoto- and nephrotoxicity induced by antituberculosis drugs at functional and morphologic levels. It was impossible to assess the neuroprotective effect of Coenzyme Q10 in the dose used due to weakly expressed changes in behavioral reactions in rats after the combination of antituberculosis drugs compared to Control Group.

The article presents problems that arise during differential diagnosis of recurrent tuberculosis of intrathoracic lymph nodes in the elderly, it describes bronchial tuberculous lesions and treatment opportunities.

The article describes a clinical case of generalized tuberculosis with lung and skin lesion in an immunocompetent patient. It was diagnosed based on detection of M. tuberculosis in sputum and wound discharge by microscopy, molecular genetic tests and culture. Genes typical of rifampicin resistance were also found in M. tuberculosis DNA.  The following anti-tuberculosis drugs had been used for treatment which was success: Bedaquiline 400 mg, Cycloserine 750 mg, Linezolid 600 mg, Clofazimine 100 mg, and Levofloxacin 1000 mg. In the 9th month of treatment, the patient demonstrated a favorable treatment outcome: conversion was confirmed by sputum and would discharge microscopy. The wounds on the skin of the body and extremities healed.

This review presents publications on the immunopathogenesis of nontuberculous mycobacteria (NTMB). The publications were selected according to the PRISMA design from international and Russian databases (PubMed, elibrary) using the keywords “non-tuberculous mycobacteriosis”, “immunology”, “genetics”, “diagnostics” in accordance with the MeSH classifier. A total of 50 literature sources were found and analyzed. We identidied main directions in the study of mycobacterial infection pathogenesis, risk factors among immunocompetent individuals, and genetic features of predisposition to mycobacteriosis.