Tuberculosis is a chronic infectious disease, usually localized in the respiratory system and representing one of the most important global social and biomedical health problems associated with the spread of therapy-resistant forms (multidrug-resistant and extensively drug-resistant tuberculosis). One of the most promising targets for the development of antimycobacterial drugs is the enzyme DprE1, which is involved in the synthesis of the cell wall of mycobacteria. In the series of DprE1 inhibitor drugs, the most advanced drug is PBTZ169 (INN maсozinone). Clinical trials (CT) of the efficacy and safety of macozinone are conducted by the pharmaceutical company LLC NEARMEDIC PLUS in the Russian Federation, and in other countries (Sponsors: Innovative Medicines for Tuberculosis Foundation, cole polytechnique fdrale de Lausanne and Bill and Melinda Gates Foundation). The publication describes results of completed I, IIa and Ib phases CT, conducted in the Russian Federation. Aim. The goal of phase I CT was to assess the safety, tolerability and pharmacokinetics (PK) of PBTZ169, 40 mg capsule, after single and multiple administration under fasting conditions in increasing doses in healthy volunteers. The goal of phase IIa CT was to study the efficacy (in terms of early bactericidal activity EBA), safety and PK of the drug PBTZ169, 80 mg capsules, in various doses, when used as monotherapy in patients with newly diagnosed respiratory tuberculosis with bacterial excretion and retained sensitivity to isoniazid and rifampicin. The purpose of phase Ib CT was to evaluate the safety, tolerability, PK of PBTZ169, 80 mg capsule, after single, double and multiple administration under fasting conditions in increasing doses, as well as the effect of food on its bioavailability in healthy volunteers. Materials and methods. The data of 100 healthy volunteers and 15 patients with newly diagnosed pulmonary tuberculosis, who received the study medication PBTZ169, capsules 40 mg and 80 mg, in the dose range 40 mg 1280 mg of PBTZ169, obtained during phase I, IIa and Ib CTs were analyzed. During I phases CTs, safety, tolerability, and PK of the drug after a single and multiple administration under fasting condition and after meals at rising doses were evaluated. The safety assessment included evaluation of AE/SAE, vital signs, ECG results, and laboratory tests results in the safety population. In the course of phase IIa CT, in addition to safety, tolerance, and PK evaluation, the efficacy of the drug (in terms of EBA) using sputum culture on agar with CFU/ml counting (main method) and quantitative PCR method (auxiliary method) was evaluated. Results. During all CTs, a high safety and tolerability profile was shown, the main PK parameters of the drug and the efficacy were described. PBTZ169 demonstrated linear PK in the dosage range up to 640 mg after single and multiple administration, a statistically significant of EBA of the drug after monotherapy at the dose of 640 mg/day was demonstrate, and it was concluded that the preferred regimen of the drug PBTZ169 intake is administration after meals. Good tolerability and a favorable safety profile of the drug in the studied doses range were demonstrate during all the CTs. Conclusion. One of the most promising and currently studied drugs-inhibitors of DprE1, a new target for the cell wall of mycobacteria, is PBTZ169 or macozinone, which is being develop by the Russian pharmaceutical company NEARMEDIC PLUS ltd.

Scientists around the Globe are making deliberate attempts to develop the new methods for predicting and diagnosing tuberculosis, but these measures are not enough to end its epidemic. The purpose of the study was to evaluate the excisional rings of the T-cell receptor (TREC) and K-deletion element of B-cells (KREC) in infants and preschool children at high risk of tuberculosis as a promising prognostic marker for tuberculosis infection activity. A cross-sectional study was conducted in Jan. - Sept. 2022. The observation group consisted of 87 children aged 1 to 7 [6 (5‒7)] y/o, of which 13 (14.9%) aged 1 to 3 y/o and 74 aged 4 to 7 y/o; 53 (60.9%) boys/34 (39.1%) girls. The three groups were formed: G1 (n=27) with an established diagnosis of tuberculosis (TB), G2 (n=34) with TB infection diagnosis made based on the results of tuberculin diagnosis and without signs of a local specific process, and [control] G3 (n=26) without signs of TB infection according to the results of specific skin tests and without signs of TB, i.e., conditionally healthy. All children, in addition to methods to confirm or exclude TB and methods of specific immunodiagnostics, have undergone a molecular genetic study: DNA extraction from a dry blood spot and quantitative determination of TREC and KREC by real-time PCR in values of TREC and KREC copies per 105 cells. In order to build the reference values of TREC and KREC quantitative indicators in dry blood spots, the results obtained in G3 were analyzed as well. Results: the reference values of TREC and KREC were established for children of early and preschool ages when extracting DNA from a dry blood spot. When assessing tuberculosis infection in children of early and preschool ages, statistically significant criteria were determined, such as: anti-tuberculosis therapy (F=42.001; p<0.001), positive or negative reaction to the recombinant tuberculosis allergen during an intradermal test (F=39.394; p<0.001), high blood TREC level (F=12.707; p<0.001), tuberculin reaction (F=10.625; p<0.001), and KREC level (F=3.182; p=0.039). Conclusion: high level of TREC can be considered as a marker for the activity or a personalized predictor for the risk of progression of TB infection in children of early and preschool ages with high risk of TB.

Introduction. In the context of a decrease in the intensity of the epidemic situation of tuberculosis In Russia, the search for new ways to increase the effectiveness of preventive measures to combat tuberculosis among the adult population remains relevant. Aim. To study the prevalence of latent tuberculosis infection in adult tuberculosis risk groups, and to conduct a comparative assessment of the effectiveness of detecting active tuberculosis by immunodiagnostics and fluorography among adults at risk of tuberculosis. Mat erials and methods. In a retrospective study, the results of a survey of people at risk of developing tuberculosis over the age of 18 with a positive test result from ATR-test were analyzed. At the first stage, the prevalence of latent tuberculosis infection was studied. At the second stage, a comparative analysis of the detectability of active tuberculosis during immunodiagnostics and during preventive fluorographic studies was carried out. Results. It was found that among adults at risk of tuberculosis, the prevalence of latent tuberculosis infection in the medical risk group was 2.7 times higher, and in the social risk group it was 8.7 times higher than the average in the population. The detection rate of active tuberculosis according to the results of immunodiagnostics was the highest in the social risk group – 3.8 cases per 1,000 examined. In terms of the effectiveness of tuberculosis detection in adults at risk of tuberculosis, immunodiagnostics is comparable to fluorographic studies (0.19 and 0.17 per 1,000 at-risk subjects, respectively). Conclusions. Conducting annual immunodiagnostics among adults at risk of tuberculosis allows timely detection of latent tuberculosis infection, and also increases the effectiveness of early detection of active tuberculosis, which helps reduce the reservoir of tuberculosis infection.

The OBJECTIVE was to reduce the risk of complications and mortality after pleuropneumonectomy in patients with pulmonary tuberculosis complicated by pleural empyema.METODS AND MATERIALS. The immediate and long-term results of surgical treatment were analyzed in 910 patients who underwent pneumonectomy between 1984 and 2021. Among these, 342 patients (37.6 %) underwent pleuropneu- monectomy (Group I), while 568 patients (62.4 %) underwent pneumonectomy (Group II). Group I was further divided into two subgroups. Subgroup Ia consisted of 278 patients (main group) who received stump-free suturing of the main bronchus according to D. B. Giller’s method, long-term drainage management of the pleural cavity using an original technique, and the proposed staged surgical tactics. Subgroup Ib comprised 64 patients who were treated using traditional methods for the main bronchus and puncture management of the pleural cavity.RESULTS. Postoperative complications were more frequent after pleuropneumonectomy (PPE); however, the mortality rate in Subgroup Ia and Group II did not significantly differ. In contrast, the hospital mortality rate in Subgroup Ib, which utilized traditional approaches for the treatment of the main bronchus and puncture management of the pleural cavity, was 2.3 times higher than the mortality rate after pneumonectomy (PE). The incidence of complications, mortality, recurrence of tuberculosis, and empyema differed significantly between Subgroups Ia and Ib, with the best outcomes observed in Subgroup Ia. These results are attributed to the applied method of treating the main bronchus, pleural cavity management, and differentiated surgical tactics.

With the annual increase in the prevalence of multidrug-resistant (MDR) pathogen, the effectiveness of etiotropic chemotherapy of tuberculosis is decreasing; the demand for surgical treatment, the use of which remains limited in the world and in the Russian Federation, is increasing.The aim of the study is to evaluate the effectiveness of the strategy of treatment of first detected destructive pulmonary tuberculosis based on early and wide application of surgical treatment, including minimally invasive techniques.Materials and methods. A retrospective cohort multicenter study included patients of tuberculosis institutions in 51 regions of the Russian Federation, analyzed the performance of phthisiosurgical departments for the period 2007–2016. The long-term results of treatment were evaluated in 1090 patients operated for MDR/XDR tuberculosis (Group 1) and in 888 patients who refused surgery (Group 2).Results. In Penza region, 92.8% of patients were abacilliated one year after application of the developed strategy, lethality decreased 3 times compared to the results of treatment in the previous 2 years; in 3 years clinical cure was registered in 94% of operated patients. During 4 years of active surgery in Chuvashia the contingent of patients with fibrotic cavernous tuberculosis was reduced 2.3 times, in Tambov region “bacillary core” in the region was reduced 3.6 times. Effective course of treatment was noted in 92,6% of patients of group 1 (operated) and only in 17,1% of patients of group 2 (refused surgery), р < 0,001. Clinical cure in 3 years was achieved in 85.7% of group 1 patients and only 5.2% of group 2 patients (р < 0,001).Conclusion. Wide application of surgical treatment and collapse therapy is a prerequisite for achieving the target indicators of treatment efficiency in tuberculosis patients.

The success of antibacterial therapy has overshadowed non-drug pathogenetic methods of tuberculosis treatment. However, the growth of drug resistance requires not only the search for new reserve drugs for the treatment of the disease but also the active study and conscious use of longknown non-drug methods.The aim of the work was to familiarize doctors with the main directions of non-drug pathogenic treatment and to create motivation for a more detailed study of individual directions and their implementation in clinical practice.Conclusion. The use of most non-drug treatment methods is justified from the point of view of modern understanding of the pathogenesis of the disease. Evidence criteria have to be developed for a more complete study of their effectiveness and subsequent inclusion in clinical guidelines.