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.

ОЧАГ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ КАК РИСК РАЗВИТИЯ У ДЕТЕЙ ТУБЕРКУЛЕЗА С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ

Current trials are underway to design chemotherapy regimens that include bedaquiline to treat children with rifampicin and isoniazid resistant mycobacterium tuberculosis. This clinical observation is interesting from the viewpoint of experience of the potential effective and safe use of the new anti-tuberculosis drug bedaquiline (Sirturo) in children under 12 years of age, as the publications of clinical trials of the drug use in children is limited. The female patient was diagnosed with primary tuberculosis complex complicated by infusional pleurisy based on the epidemiological anamnesis (family contact with tuberculosis patients), immunodiagnostic tests – a positive ATR-test result (Diaskin-test), pathological changes in the lung tissue and intrathoracic lymph nodes found on the chest CT scans. The diagnosis was confirmed by detection of MBT in pleural effusion by PCR and liquid culture method (BACTEC MGIT-960), which are resistant to isoniazid and rifampicin (multidrug resistance, MDR). The girl was enrolled in a clinical trial and treated according to chemotherapy regimen IV including a new anti-tuberculosis drug, which she received for 6 months. There was a positive clinical and X-ray dynamics of the tuberculosis process with minimal residual changes throughout the entire course of chemotherapy followed by confirmed clinical cure of TB (after 24-month follow-up). Based on the example of this clinical observation, it can be concluded that bedaquiline is safe and showed good clinical efficacy in the chemotherapy regimen to treat MDR MBT in children under 12 years of age.

Background. Long-term immunosuppressive therapy in children (including genetically engineered biologic drugs, GEBD) is associated with a high risk of local tuberculosis (TB) development. Objective. The aim of the study was to examine efficacy of tuberculosis services in children with high risk of developing tuberculosis associated with immunosuppressive therapy.Methods. The study included children at the age from 0 to 17 years on immunosuppressive therapy due to autoimmune disease and who were referred to phthisiatrician consultation. The incidence of TB was estimated one year after in groups receiving preventive TB services (isoniazid and pyrazinamide for 3–6 months) due to the high risk of TB development (contact with TB patients and/or controversial or positive test results with tubercular recombinant allergen) or not receiving such therapy (no indications for preventive treatment, parents’ refusal). The source of any data was medical documentation.Results. Preventive tuberculosis service was performed in 167 (60%) out of 279 children included in the study, 112 children did not receive such treatment (5 cases — parents’ refusal, 107 cases — lack of indications for preventive treatment). TB was detected in 1 (0.6%) child after one year in the preventive treatment group, and in 14 (12.5%) children (p < 0.001) in the group without preventive treatment. Thoracic lymph nodes tuberculosis was diagnosed in 4 (27%) patients among all who has developed TB, tuberculous primary complex — in 3 (20%) patients, focal tuberculosis in 7 (46%) patients, disseminated tuberculosis in 1 (7%) patient.Conclusion. Preventive tuberculosis service reduces the risk of tuberculosis in children on administration of immunosuppressive drugs, including GEBD.

Introduction. The treatment of children with multidrug-resistant and extensively drug-resistant tuberculosis (MDR / XDR-TB) is a difficult task due to many factors: the duration of treatment, the lack of drugs with children’s dosages, age restrictions (according to the drug instructions).Purpose of the study. To assess the efficacy and safety of regimen with the inclusion of bedaquiline in children and adolescent with respiratory tuberculosis with drug-resistant tuberculosis.Materials and methods. The study is prospective, cohort, non-comparative from the period 2017–2019. We included 24 patients aged 5 to 17 years with MDR-TB (established or suspected) began regimen containing bedaquiline for 24 weeks. The duration of observation of patients included in the study was 24 months.Results. We can state a sufficient level of safety of using the latter for 24 weeks: adverse events presumably associated directly with the intake of bedaquiline were noted in only 1 patient out of 24 (4.2%; 95% CI 0.7-20.3). The efficacy of a regimen containing bedaquiline in combination with other anti-tuberculosis reserve drugs is beyond doubt: positive clinical and radiological dynamics and cessation of bacterial excretion by the end of the 24-week course of treatment were noted in all patients included in the study. In the course of 2-year follow-up, no exacerbation of the tuberculous process was observed in any case. All patients achieved clinical cure of tuberculosis.Conclusion. Regimen containing bedaquiline for children aged 5–17 years with multidrug-resistant tuberculosis is effective and safe.

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.