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.

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.

The fight against tuberculosis (TB) continues throughout the world. The causative agents of TB are slow-growing bacteria Mycobacterium tuberculosis complex (MTB), which must be quickly and effectively identified in order to promptly prescribe therapy to the patient. For this purpose, fast and highly sensitive molecular genetic methods are used based on nucleic acid amplification, in particular polymerase chain reaction (PCR). Currently, more rapid methods are used, such as isothermal loop amplification (LAMP). “AmpliTest MTB-LAMP” kit for the detection of MTB DNA in human biological material samples and bacterial cultures has been developed at the Centre for Strategic Planning of FMBA of Russia. Objective. To evaluate effectiveness of new “AmpliTest MTB-LAMP” kit based on isothermal amplification during analysis of biological samples and bacterial cultures in comparison with reference kit during pre-registration clinical trials. The reference kit was identical in intended purpose and registered In Russian Federation as in vitro diagnostic medical device (IVD). Material and methods. 471 samples of biological material obtained from patients with pulmonary and extrapulmonary tuberculosis localization (sputum (n=110), bronchoalveolar lavage (n=110), urine (n=106), biopsy (surgical material (n=145)) and 100 samples of bacterial cultures were tested. Samples, except for bacterial cultures, were treated with NALC-NaOH [1], and obtained sediment was divided into five equal volumes. Four volumes of the sediment were analyzed using new kit four forms, and a fifth part of the sediment was analyzed using reference “AmpliTest MTB” kit (Centre for Strategic Planning of FMBA of Russia). Amplification was performed using Rotor-Gene 6000, CFX96, DTprime, QuantStudio 5, by hand and special software for automatically results interpretation. Effectiveness indicators (positive and negative agreement of results) of the “AmpliTest MTB-LAMP” kit were calculated using formulas with 95% confidence interval. Results. The results of sample analysis obtained by new kit and reference kit have completely coincided. There weren’t discordants. Therefore, the effectiveness indicators (positive (PAR) and negative (NAR) agreement of results) of “AmpliTest MTB-LAMP” kit were 100% for all samples. Conclusion. The results obtained indicate the high efficiency of new «AmpliTest MTB-LAMP» kit. It can be used for rapid detection of MTB DNA in order to timely prescribe to a patient antituberculosis regimen and to select samples of MTB DNA which will be appropriate for analysis using kits of AmpliTest brand to identify mutations, associated with MTB resistance to rifampicin and isoniazid.

Aim. Quantitative assessment of TREC and KREC in infants and preschool children infected with tuberculosis infection (TI). Material and methods. A prospective cross-sectional study was conducted in 2022. The observation group consisted of 87 children of early childhood age in contact with TB patients, of whom 27 were diagnosed with TB, 34 were tested positive to TB based on skin tests without signs of a local specific process (TI), 26 were children without signs of tuberculosis infection according to the results of skin tests and local process (conditionally healthy children).Results. The following factors significant in the assessment of tuberculosis infection were determined: anti-tuberculosis therapy (F = 42.001; p = 0.000001); positive or negative response to the tuberculosis recombinant allergen (RTA) during an intradermal test (F = 39.394; p = 0.000001); high TREC levels in the blood (F = 12.707; p = 0.000001); the presence of a tuberculin response (F = 10.625; p = 0.000006); and KREC levels (F = 3.182; p = 0.039). Conclusions. According to the obtained results, TREC levels can be considered as a personalized risk predictor of tuberculosis infection in infants and preschool children.

Despite the steady decline in the main epidemiologically significant indicators of tuberculosis in Russia, the problem remains of choosing an affordable and informative diagnostic test for the timely detection of latent tuberculosis infection (LTI).The aim of this study was to evaluate the compatibility of various methods of immunological diagnosis in adult patients with LTI with a high (LTI-HR) and low (LTI-LR) risk of developing tuberculosis, as well as in patients with established tuberculosis of the respiratory system.Methods. A cross-sectional open single-center study was conducted, which included 100 adult patients. The first group included 50 conditionally healthy individuals with LTI-LR. The second group of patients consisted of 25 people with LTI-HR. The third group of patients included 25 patients with tuberculosis of the respiratory system (TRS). All participants were examined once using six immunological diagnostic tests: Mantoux test with 2 units PPD-L, Diaskintest, T-SPOT®.TB, QuantiFERON®-TB Gold Plus, Standard E TB-Feron IGRA and IGRA-TB. The end point of the study was the overall percentage consistency of the results, that is, the ability of the tests to correctly predict the condition assumed by the combination of clinical signs.Results. The proportion of “correct results” (positive in the TRS and LTI-HR group and negative in the LTI-LR group) was 83% for the IGRA-TB test, 80% for the Diaskintest, 80% for the QuantiFERON®-TB Gold Plus test, 78% for the Standard E TB-Feron IGRA test, 67% for the T-SPOT®.TB test (p > 0.05). Only the Mantoux test with 2 units PPD-L showed significantly lower “accuracy” in our study (53%; p < 0.05).Conclusion. The new Russian test IGRA-TB is not inferior to its foreign counterparts and can be recommended in practical healthcare as a diagnosis of latent tuberculosis infection in adults. It seems fundamentally important to continue studying the informative value of tests in adult patients in real clinical practice without applying strict selection criteria. The immunological features of the patients, which determine the different sensitivity of the tests, need to be further studied.

The problem of multidrug resistant pathogens has significantly limited the capabilities of tuberculosis chemotherapy, reinstating the need for pathogenetic treatment methods in phthisiology. The practitioner is faced with a difficult choice between the expediency and even necessity of prescribing drugs for pathogenetic therapy and the risk of prescribing drugs whose effectiveness and safety have not been proven. The aim of the work was to familiarize doctors with the principles of prescribing pathogenetic therapy included in the current version of the clinical recommendations “Tuberculosis in adults”. Conclusion. Today, the phthisiological service has drugs of various pharmacological groups in its toolkit that can influence the pathogenesis of tuberculosis and have a high level of evidence from pre-clinical and clinical studies. The new data should be reflected in future versions of the clinical guidelines.