The objective of the study: to assess tuberculosis treatment outcomes in children of 0-14 years old following up changes over the time Subjects and Methods: A retrospective cohort analysis of tuberculosis outcomes in 15,794 children of 0-14 years old was performed, those children were registered for treatment from 2011 to 2018.

Results. The percentage of children switched to MDR regimens increased from 1.3% to 12.0%. The rate of successful treatment of new TB cases in children varied from 93.2% to 96.6% in different years. In children registered for treatment in 2016-2018, 95.7% of new cases with negative or undocumented sputum smear microscopy, 87.8% with positive sputum smear microscopy, and only 83.3% of children with TB relapse were successfully treated. From 2015 to 2018, the percentage of children with treatment failures increased from 0.6% to 1.5%.

Conclusion. Compared to other countries, Russia has a high rate of successful treatment in children with tuberculosis which may be due to their active detection. Nevertheless, there are certain defects in drug susceptibility testing of index cases. Treatment outcomes for children registered in 2020 are expected to be less favorable because of later detection due to the COVID-19 pandemic. The spread of HIV infection among children as well poses a threat of increased mortality in children ill with tuberculosis. To reduce the level of unfavorable outcomes, it is necessary to consider the treatment of children at the age of 0-14 years old ill with tuberculosis in federal centers.

The objective: to evaluate the ability of the combination of theophylline and budesonide to suppress proinflammatory cytokine production byblood cells in patients with chronic obstructive pulmonary disease (COPD).

Subjects and Methods. Peripheral blood mononuclear cells (PBMCs) or whole blood cells of COPD patients (n = 27) were incubated with budesonide (10 nM), theophylline (1 μM), or the combination thereof and stimulated with phytohemagglutinin (PHA) or phorbol myristate acetate (PMA) and ionomycin. The enzyme immunoassay was used to evaluate the secretion of thymic stromal lymphopoietin (TSLP), macrophage migration inhibitory factor (MIF), interleukin 17A (IL-17A), IL-33, and other mediators of PBMC cells, and induced PHA. The flow cytometry was used to analyze intracellular production of proinflammatory cytokines stimulated by PMA/ionomycin in T-helpers (CD4⁺) and cytotoxic T-lymphocytes (CD8⁺).

Results. Theophylline reduced the secretion of IL-4 and IL-17A by PBMC cells. The combination of budesonide with theophylline inhibited the synthesis of IL-4, IL-5, IL-8, IL-13, IL-17A, IL-33, TSLP, MIF by PBMC cells as well as the production of IL-4, IL-8, tumor necrosis factor-α, and interferon-γ by cytotoxic T-lymphocytes and T-helpers. The combination of theophylline and budesonide had a more pronounced inhibitory effect on the production of IL-4 and IL-8 by PBMC cells as well as the synthesis of IL-4 by CD4⁺ T-cells and IL8 by CD8⁺ T-lymphocytes versus the effect of monotherapy with budesonide.

Extrapulmonary tuberculosis is widespread in the territory of the Kyrgyz Republic (KR). General practitioners fail to diagnose in time a significant number of cases of extrapulmonary tuberculosis. In the Kyrgyz Republic, in 2019 the incidence of extrapulmonary tuberculosis made 19.5 per 100,000 population, tuberculous exudative pleurisy (50.6%) and bone and joint tuberculosis (18.1%) prevailed in the structure.

The objective: to identify clinical factors with the highest sensitivity and specificity associated with an unfavorable outcome in the patient with tuberculosis and HIV infection.

Subjects. 363 patients with TB/HIV co-infection. Group 1 – 59 (16.3%) patients with the unfavorable outcome, Group 2 – 304 (83.7%) patients with a favorable outcome.

Methods: analysis of paired contingency tables by Pearson criterion, quantitative signs by Mann – Whitney test, simple and multiple logistic regression.

Results. The following factors promoting unfavorable outcomes in the patient with TB/HIV co-infection with the highest sensitivity and specificity were identified: hemoglobin level (sensitivity – 78.0%; specificity – 73.7%), gastrointestinal candidiasis (72.9% and 84.5%), loose stool (40.7% and 97.4%), no lymphadenopathy (89.8% and 57.2%), and headache (49.2% and 88.5%). The combination of these clinical manifestations provides sensitivity of 78.0% and specificity of 94.4%.

A formula is proposed for calculating the probability of an unfavorable outcome in the patient TB/HIV co-infection.

The objective of the study: to evaluate the efficacy and safety of short course chemotherapy regimens for multiple/extensive drug resistant tuberculosis of the respiratory system (MDR/XDR) in older children and adolescents.

Subjects and Methods. A cohort prospective controlled study (2017 to 2019) included 23 patients from 13 to 17 years old with various clinical forms of respiratory tuberculosis with multiple/extensive drug resistance.

Results. In 22 out of 23 cases, the following chemotherapy regimen was used: 6 months - the intensive phase / 6 months - the continuation phase, in one patient – 3 months of the intensive phase / 9 months of the continuation phase. In 15 out of 23 cases, the chemotherapy regimens in the intensive phase, taking into account the MBT drug sensitivity test, consisted of 5 drugs, in 8 cases – of 4 drugs. During the continuation phase, all patients received 3 drugs. Of the 23 patients, 8 patients used bedaquiline in short course chemotherapy regimens: 2 – 1 course, 6 – 2 courses.

Conclusion. The possibility of reducing the main course of chemotherapy for MDR/XDR TB in children and adolescents to 12 months instead of 18-24 months has been proved.

The objective of the study: to evaluate the impact of HIV infection on the nature and results of surgical interventions in respiratory tuberculosis (RTB) patients with the relevance of their immune status.

Subjects and Methods. An ambispective observational study with continuous sampling included 565 patients above 18 years old who underwent surgical interventions. The study participants were divided into RTB+HIV Group (90 patients) with HIV-associated respiratory tuberculosis and RTB Group which included 475 HIV negative patients with respiratory tuberculosis. In RTB+HIV Group, patients were divided into three subgroups: with CD4-lymphocyte count below 200 cl/μL (n = 41), 200-499 cl/μL (n = 26), and 500 or more cl/μL (n = 23).

Results. Compared to RTB Group, RTB+HIV Group was found to have less frequent resection surgery (24%; p < 0.0001; OR = 3.0) with acomparable frequency of collapsed surgery (4%; p > 0.05) and much more frequent thoracic diagnostic surgery (11%; p < 0.0001; OR = 10.6) and extrathoracic surgery (50%; p < 0.0001; OR = 6.8). In RTB+HIV Group, patients with CD4-lymphocyte count below 200 cells/μL (46%; p < 0.05) who had no resection surgery predominated, and the rate of collapsed surgery was 2.4% (p < 0.0001). There were no statistically significant differences in the incidence of postoperative complications for each individual type of surgery when stratifying participants by CD4-lymphocyte count in the intergroup comparison, as well as in RTB+HIV Group.

The objective of the study: to study the possibilities of skin tests with tuberculosis recombinant allergen (TRA) in the diagnosis of tuberculosis in HIV-positive patients in the region with a high prevalence of tuberculosis.

Subjects and Methods. Medical files of 85 patients were retrospectively analyzed, all the patients suffered from TB/HIV coinfection and underwent the skin test with TRA.

Results. The skin test with TRA was found to be significantly valuable for the diagnosis of tuberculosis in patients with TB/HIV coinfection. The correlation between the intensity of response to the TRA test and CD4⁺ count was detected (p = 0.011). The lowest values were observed for CD4⁺ counts below 100 cells/μL. The direct correlation between the intensity of response to TRA and the stage of HIV infection was proved. No effect of the form of tuberculosis, the phase of the tuberculosis disease, or drug sensitivity on the intensity of response to TRA was found. Among tuberculosis patients with bacterial excretion (n = 48), 68.8% of patients responded positively to the TRA test, and in those with no bacterial excretion, the positive reaction was observed in 81.1%.

The objective: to run the comparative study of frequencies of variants of polymorphic loci of NAT2 gene in the development of multiple drug resistant tuberculosis (MDR TB) and drug sensitive tuberculosis (DS TB) in patients with HIV infection.

Subjects and Methods. 70 patients with TB/HIV co-infection at the age from 24 to 58 years old were examined when admitted to hospital.

54 (77.1%) patients were new cases, the remaining 16 cases underwent repeated treatment. MDR TB was diagnosed in 47 patients: 33 patients had primary MDR, and 14 patients suffered from acquired MDR. Drug susceptible tuberculosis was diagnosed in 23 patients. Allele-specific PCR was used for genotyping of patients by rs1208, rs1799930, and rs1799929 polymorphic loci of N-acetyltransferase-2 (NAT2) gene.

Results. A high probability of carriage of wild genotype of NAT2^{Arg197Arg(G590G)} and allele NAT2^Arg197(590G) was revealed in MDR TB(n = 70, OR = 3.63, p = 0.02 and OR = 2.24, p = 0.05, respectively) and it was found low in DS TB (n = 70, OR = 0.28, p = 0.02 and OR = 0.45, p = 0.05, respectively). Among patients with acquired MDR TB (n = 14), carriers of the wild genotype of NAT2^{Arg197Arg(G590G)} prevailed (n = 11; 79%), of them 10 were chronic cases and 1 had a relapse. Among patients with DS TB (n = 23), the carriage of the wild genotype of NAT2^{Arg197Arg G590G} was found in 35% of patients (n = 8), of them 7 were new cases and 1 patient suffered from chronic tuberculosis.

Carriage of a combination of three studied wild genotypes of NAT2^{Lys268Lys(A803A)}×NAT2^{Arg197Arg(G590G)}×NAT2^{Leu161Leu(C481C)} was more often recorded in secondary MDR TB. In secondary MDR TB, the risk of carriage of wild genotypes of NAT2 gene versus primary MDR TB turned out to be high among all cases of diagnosed MDR TB (n = 43, OR = 6.67 [1.28-34.86], p = 0.0277 ) and in the entire sample (n = 65, OR = 11.91 [2.32-61.11], p = 0.0039).

Conclusion. The results of genotyping in patients with TB/HIV co-infection and secondary MDR TB are associated with the carriage of acombination of wild genotypes of gene NAT2^{Lys268Lys(A803A)}×NAT2^{Arg197Arg(G590G)}×NAT2^{Leu161Leu(C481C)}.

The objective of the study: to obtain a live attenuated strain and investigate its properties by multiple cultures of the virulent strain of Mycobacterium tuberculosis H37Rv.

Subjects and Methods. The original virulent strain H37Rv was subcultured 70 times in 7H9 liquid medium. Genetic properties of the new strain, degree of avirulence, and vaccine properties were studied.

Results. Mycobacteria of the new strain MtbBN lost their virulence to inbred mice. Eight mutations were identified by whole genome sequencing: single nucleotide insertions and deletions (in/del) distinguishing the MtbBN and H37Rv strains. The MtbBN strain demonstrated vaccine potential at the BCG level. Additionally, in some genetic models, the attenuated strain was highly effective in protecting inbred mice when infected with Mtb H37Rv as opposed to BCG.

The article presents a clinical case of pulmonary tuberculosis with destruction and bacterial excretion in the patient with systemic sarcoidosis and cerebral lesions. Tuberculosis was characterized by the infiltrate and cavity in S₁₊₂ of the left lung, tuberculous mycobacteria were detected by microscopy, GeneXpertMBT/Rif, and culture. Systemic sarcoidosis with brain involvement was diagnosed based on intrathoracic lymphadenopathy in 2015, development of dissemination in the lungs and neurological symptoms by 2018, deterioration of changes by 2019, rapid partial resolution of foci in the lungs, and moderate regression of neurological disorders during the treatment with prednisolone. A full course of anti-tuberculosis chemotherapy (316 doses) resulted in persistent sputum conversion, resolution of the infiltrate and cavity healing. Prednisolone was administered simultaneously for 318 days with increased doses (45-35 mg) for the first 2 months, then titrated down to 15 mg and remained so until the end of the treatment with gradual reduction and discontinuation. Changes in the lungs and improvement of clinical and radiological manifestations of neurosarcoidosis were documented.