Introduction: The tuberculin skin test has significant limitations for use in individuals vaccinated with BCG. The presence in the genome of Mycobacterium tuberculosis of the RDI region, which is absent in the genome of Mycobacterium bovis BCG and most non-tuberculous mycobacteria, made it possible to develop new skin tests, which include a skin test with a recombinant tuberculosis allergen [RTA (Diaskintest®, JSC Generium, Russia)]. Diaskintest has shown high diagnostic performance in clinical trials and in conditions of high prevalence of tuberculosis infection. In 2021, the Russia was excluded from the WHO list of high TB burden countries, which makes relevant an assessment of the specificity of the RTA test under conditions of low epidemiologic risk for tuberculosis to confirm the high specificity of the test.Study objective: To assess the specificity of Diaskintest in the regions of the Russian Federation with low epidemiologic risk for tuberculosis.Methods: A multicenter, open-label, prospective study was conducted, which included 150 healthy volunteers aged 18–30 years old, vaccinated with BCG, who were not at risk of tuberculosis, from regions with low epidemiologic risk (Oryol region, Ryazan region, and Arkhangelsk region). During the study, 4 visits were scheduled for each participant: [Visit 0 (screening), Visit 1, Visit 2 (in 72 h) and Visit 3 (in 28 days)]. All participants, who excluded active and latent tuberculosis infection, underwent a test with RTA. To assess the safety of RTA tests, all systemic and local adverse events that occurred during 28 days were recorded. The trial was filed in the NIH clinical trials database ClinicalTrials.gov (NCT05203068).Results: In individuals with a negative T-SPOT.TB test, the specificity of the RTA test was 97% (95% CI: 92–99%) with a cut-off of >0 mm. The study findings confirm data 2009: 100.00 (95% CI: 94–100). When evaluating the safety of the RTA test during 28 days of follow-up, the participants did not report local and systemic adverse reactions that had a causal relationship with the RTA test.Conclusion: Diaskintest is highly specific and safe, therefore it is a valuable tool as a screening test for early detection of tuberculosis.

Treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is a current problem worldwide. Currently, special attention is paid to the possibility of using new high-cost chemotherapy regimens in the treatment of MDR/XDR-TB. Numerous studies have shown that, from a clinical point of view, the effectiveness of MDR/XDR-TB therapy increases with the inclusion of bedaquiline, delamanid, linezolid, fluoroquinolones (moxifloxacin, levofloxacin), and pretomanid. At the same time, there is an assumption that the use of new and repurposed anti-tuberculosis drugs (ATDs) may be associated with an increase in overall costs. This paper demonstrates the potential of pharmacoepidemiology and pharmacoeconomics to evaluate the widespread introduction of new anti-tuberculosis drugs (ATDs), taking into account all the typical features of MDR/XDR-TB therapy. The authors analyzed studies of pharmacoeconomic feasibility of using expensive drugs in treatment regimens of pulmonary tuberculosis patients with MDR/XDR pathogen. It was shown that the use of chemotherapy regimens containing new high-cost and highly effective drugs (moxifloxacin, linizolid, and bedaquiline) in rational combinations with other drugs of the basic and reserve series, selected concerning drug resistance of the pathogen, is associated with a significant economic effect. From the applicability of pharmacoeconomic analysis point of view, the introduction of short-term MDR-TB treatment regimens is also a promising direction in phthisiology. The key link to achieve effective MDR/XDR-TB treatment is the use of new drugs. Considering the specificity of pharmacoeconomic analysis in phthisiology and results of existing clinical and economic studies, the authors have formed recommendations aimed at a more complete realization of pharmacoeconomic analysis potential in MDR- and XDR-TB treatment.

Detection of tuberculosis (TB) infection and prophylactic anti-tuberculosis treatment in order to prevent cases of the disease is a current priority in phthisiatry. The effective screening of the TB infection requires the availability of effective tests with high sensitivity and specificity. The purpose of the study was to assess the concordance of a negative result of a recombinant tuberculosis allergen (RTA) test and the absence of specific changes on multi-slice computed tomography (MSCT) of the chest organs in children aged 3 to 14 years old who are not at risk for the TB development in territories with a low incidence of TB. Materials and methods of the study: a multicenter cohort retrospective study of children 3 to 14 years old who do not belong to risk groups for the TB development, without clinical symptoms of any disease and with a negative RTA test result. An analysis of the data of the objective examination of the child, of the general blood test study, of the results of previous immunodiagnostics, and of the results of MSCT of the chest organs (the presence of changes of any nature in the lungs and intrathoracic lymph nodes) was performed. Results: 43 children were included in the study, 65% (28) males. The average age of children was 7.0 [6.0; 11.0] years. Two age groups of children were studied - 3 to 7 and 8 to 14 years old. In the group of children aged 3 to 7 years old, only 68% had information about a previous tuberculinogram, on the basis of which it was possible to judge the presence of a possible active TB infection. In 14 children of this age group, pronounced reactions to tuberculin were noted, which was an indication for the Mantoux test with 2 tuberculin units (2TU) for an in-depth examination and consultation with a phthisiatrician (increase in tuberculin sensitivity). The concordance of the negative result of the RTA test and the negative result of the Mantoux test with 2TU was 50% - the value is random, while in all children according to MSCT of the chest organs, there were no specific changes. The concordance of a negative result of the RTA test and the absence of specific changes on MSCT of the chest organs was 100%. Conclusion: in children who do not belong to the risk group for the TB development, a negative result of the RTA test was accompanied by the absence of changes in the MSCT of the chest organs (100% concordance). The tuberculin diagnostics using the Mantoux test with 2TU has significant limitations for detection of the TB infection in children under 7 years of age. For children aged 3 to 7 years old who have been diagnosed with mycobacterium TB infection and do not need to be re-introduced with BCG vaccine, it is reasonable to screen for TB using the RTA test.

Aim: Because of the COVID-19 pandemic, many support programs for tuberculosis (TB) patients have been discontinued and TB mass screening activities decreased worldwide, resulting in a decrease in new case detection and an increase in TB deaths (WHO, WHO global lists of high burden countries for TB, multidrug/rifampicin-resistant TB (MDR/RR-TB) and TB/HIV, 2021–2025, 2021). The study aimed to assess changes in epidemiological indicators of tuberculosis in the Russian Federation and to simulate these indicators in the post-COVID-19 period. Materials and Methods: The main epidemiological indicators of tuberculosis were analyzed with the use of government statistical data for the period from 2009 to 2021. Further mathematical modeling of epidemiological indicators for the coming years was carried out, taking into account the TB screening by chest X-ray. Statistical analysis was carried out using the software environment R (v.3.5.1) for statistical computing and the commercial software Statistical Package for the Social Sciences (SPSS Statistics for Windows, version 24.0, IBM Corp., 2016). Time series forecasting was performed using the programming language for statistical calculations R, version 4.1.2 and the bsts package, version 0.9.8. Study Results: The study has found that the mean regression coefficient of a single predictor differs in the model for TB incidence and mortality (0.0098 and 0.0002, respectively). Forecast of overall incidence, the incidence of children and the forecast for mortality using the basic scenario (screening 75–78%) for the period from 2022 to 2026 was characterized by a mean decrease rate of 23.1%, 15.6% and 6.0% per year, respectively. A conservative scenario (screening 47–63%) of overall incidence indicates that the incidence of children and the forecast for mortality will continue to decrease with a mean decrease rate of 23.2%, 15.6% and 6.0% per year, respectively. Comparable data were obtained from the forecast of overall incidence, the incidence of children and the forecast for mortality using the optimistic scenario (screening 82–89%) with a mean decrease rate of 22.9%, 15.4% and 6.0% per year, respectively. Conclusions: It has been proven that the significance of screening with chest X-ray as a predictor of mortality is minimal. However, TB screening at least 60% of the population (chest X-ray in adults and immunological tests in children) have provided relationship between the TB screening rate and TB mortality rate (TB mortality rate increases with an increase in the population coverage and, conversely, decreases with a decrease in the population coverage).

The objective: to study the degree of specific sensitization according to the results of intradermal immunodiagnostic tests in children with different manifestations of tuberculosis infection under the current epidemic situation.Subjects and Methods. The degree of tuberculin sensitization was studied in 299 children from different age groups (0-14 years old) who were registered for dispensary follow-up in 2018-2019.Based on the results of a tuberculosis recombinant allergen test (TRA), the degree of specific sensitization was studied in children with tuberculin tests conversion (n = 102) and infected with Mycobacterium tuberculosis (MTB) for 2 years or more (n = 165) exposed to tuberculous infection in their families and from healthy environment, and 145 patients under 14 years old with local respiratory tuberculosis.Results. Moderate sensitization to tuberculin predominated in children with converted tuberculin test exposed to tuberculous infection in their families and those from healthy environments. According to the results of TRA test, a high degree of sensitization was observed 4.7 times more frequently in children with tuberculin test conversion exposed to tuberculosis in their families. In children from healthy environments, negative responses to TRA test were registered 2.4 times more frequently. In 73% of children infected with MTB, results of annual Mantoux tests didn’t differ much. Hyperergic reactions to TRA test in infected children exposed to tuberculous infection were 10 times more frequent than in those from healthy environments. A direct correlation was found between the high degree of sensitization to active M. tuberculosis and exposure to a tuberculosis case with a positive result of sputum test (χ² < 0.001, p < 0.05). In the case of converted tuberculin test and infection with M. tuberculosis for 2 years or more, pronounced and hyperergic reactions to TRA test were registered with equal frequency and did not depend on the timing and duration of infection. A high risk factor and predictor of the disease development is high sensitization of the host to active M. tuberculosis which is found in patients with tuberculosis using TRA test six times more frequently versus Mantoux test (OR 5.951, 95% CI 3.548 and 9.981). The demonstrated results are important for the identification of children facing a high risk to develop active tuberculosis and preventive treatment prescription.

Introduction. The priority of anti-tuberculosis work in the Saratov Region is the early detection of the disease and the prevention of new cases of pathology. The presence of medical and social risk factors for developing tuberculosis significantly increases the risk of developing local forms of tuberculosis, especially if patients have latent tuberculosis infection (LTBI).Aim. To assess the prevalence of LTBI in the adult population with an increased risk of developing tuberculosis in the adult population.Materials and methods. The design of the study is a retrospective non-comparative. The data of patients from high-risk groups for the development of the disease for the period of 2015–2019, examined using a skin test with a recombinant tuberculosis allergen (Diaskintest, Generium JSC, Russia) in the Saratov Region, were analyzed.Results. 153,120 people from medical outpatient risk groups and 3,099 people from social risk groups were examined. Among adults with medical risk factors for developing tuberculosis, the largest number of positive and doubtful results of Diaskintest were recorded in patients with chronic bronchopulmonary pathology – 15.88%; among the group of those surveyed with social risk factors for developing tuberculosis – in persons released from penitentiary institutions (25.88%).Conclusions. The decrease in incidence rates in the Saratov Region confirms the correctness of the chosen tactics regarding the use of the Diaskintest test to identify individuals with LTBI among the adult population and the implementation of measures to reduce the reservoir of tuberculosis infection. Given the effectiveness of the measures taken, it is advisable to work with risk groups for Diaskintest and further examination in a general medical network. To do this, it is necessary to make additions to the current Order of the Ministry of Health of the Russian Federation dated March 21, 2017 No. 124n “On approval of the procedure and terms for conducting preventive medical examinations of citizens in order to detect tuberculosis” regarding the use of recombinant tuberculosis allergen samples in the adult population.