The aim of the study was to analyze epidemiological data on tuberculosis in the Kursk region, taking into account the changing socio-economic situation in the region, as well as to study the possibilities of using remaxol in the regimens of accompanying therapy for hepatotoxic reactions in patients with tuberculosis. During the analysis of the data array, it was noted that the dynamics of infectious processes were similar to the other regions of the Russian Federation: a decrease against the background of COVID-19 and a gradual increase in morbidity in the post-pandemic period. A third of the patients included in the study were diagnosed with comorbid forms of tuberculosis, characterized by greater severity of the disease and lower effectiveness of therapy: recovery (with deregistration) was recorded in half (49.8%) of patients with monoinfection, while in patients with a comorbid course of the disease, this figure was 35%. At the same time, clinical recovery was diagnosed in 38.2% of patients with monoinfection and in 47% of patients with comorbid tuberculosis (P<0.5). The inclusion of remaxol (intravenous drip, 400 ml/day, every other day — course No. 5, then 1 time per week No. 4) in the treatment regimens for hepatotoxic reactions during the main course of treatment in patients with tuberculosis, in both monoinfection and comorbid forms, contributed to a more rapid relief of deviations in clinical and laboratory parameters and an increase in the effectiveness of treatment: 84.2% in patients with tuberculosis and 85.7% with a comorbid form of tuberculosis versus 81.9% and 83.7% in patients in the comparison group (P≤0.05).

The aim of the study was to identify the dynamics on the incidence of major socially significant infectious diseases (SIDs) before, during, and after the COVID-19 pandemic in penitentiary populations. The effectiveness of accompanying therapy was assessed using the example of clinical observation of comorbid widespread destructive pulmonary tuberculosis.Material and methods. Statistical reporting data on the administrative unit of the Federal Penitentiary Service of one of the constituent entities of the Russian Federation was analyzed. Verification of diagnosis and treatment was carried out using generally accepted methods in accordance with regulatory documentation and standards of therapy. At the first stage, the dynamics of incidence for the periods 2000–2019 (before the COVID-19 pandemic) and 2020–2022 (against the background and after the COVID-19 pandemic) was analyzed . The second stage of the study was the analysis of data on tuberculosis (TB): features of the clinical course, etiotropic treatment, and the possibility of increasing efficiency through accompanying therapy.Results. At the first stage of epidemiological data analysis, it was revealed that in the pre-pandemic period, the incidence of SIDs in the Federal Penitentiary Facilities decreased. HIV infection was the exception, the incidence of which increased by 3.8 times during this period. The COVID-19 pandemic did not have a significant impact on the formation of the epidemiological situation. However a change in the structure of the pathology was noted: multidirectional dynamics were recorded in parasitic infections — a 1.8-fold increase (from 38.7 to 69.5 per 100 thousand people) in scabies and a 2.8-fold decrease (from 290.4 to 104.2 per 100 thousand) in head lice (P>0.05). Moreover, all cases were detected in pre-trial detention centers when detainees were admitted to them; these diseases were not recorded in correctional facilities. The same pattern of incidence was noted for the main sexually transmitted infections: against the background of a 4.5-fold increase in trichomoniasis (from 58.1 to 260.6 per 100 thousand) a 4.4-fold decrease in the incidence of syphilis (from 154.9 to 34 .7 per 100 thousand), (P>0.05) was recorded. At the same time, the incidence of TB and HIV infection has almost halved. A further decrease in the incidence of the main SIDs was recorded in the post-Covid period (2020–2022). The exceptions were gonorrhea (a 1.8-fold increase — from 18.2 to 32.7 per 100 thousand) and tuberculosis (a 1.5-fold increase — from 364.8 to 552.1 per 100 thousand), P>0.05. At the second stage, it was noted that TB/HIV comorbidity in combination with viral hepatitis remains a problem in correctional facilities. In this regard, accompaniment therapy becomes an important element of treatment — in the event of the adverse events development in response to the main (etiotropic) therapy, in particular. The presented clinical case describes the positive effect of including remaxol, a polyionic infusion hepatotropic drug, in the treatment regimen for comorbid common destructive TB/HIV and poor tolerability of anti-tuberculosis drugs, which helped reduce the severity of hepatotoxicity and made it possible not to introduce changes to the main treatment regimen.

Introduction. Currently, immunological research is one of the priorities in the field of tuberculosis, since the effectiveness of treatment and, consequently, the outcome of the disease in most cases are determined by the immune and genetic characteristics of the macroorganism. Aim. To study the dynamics of cytokines (IL-6, IL-8, IL-4, IL-10, TNF-α, IFN-γ) in patients with pulmonary disseminated tuberculosis (DST) and fibrous-cavernous tuberculosis (FCT) after 2 months of specific chemotherapy. Materials and methods. The study group consisted of 100 patients with pulmonary tuberculosis (DST – 48 people, FCT – 52 people) aged 40 to 69 years who received specific chemotherapy in the intensive phase. The concentration of cytokines (IL-6, IL-8, IL-4, IL-10, TNF-α, IFN-γ) was determined at baseline and after 2 months of chemotherapy, as well as the cytokine balance (IL-6 + IL-8/IL-4 + IL-10) at baseline and after 2 weeks of chemotherapy. Results. After 2 months of chemotherapy, patients with DST showed a significant decrease in the level of IFN-γ, TNF-α, IL-6, IL-10, and the level of IL-8 tended to increase, however, this dynamic was not statistically significant; in patients with FCT, there was a significant decrease in the level of IFN-γ, IL-8, IL-6, as well as IL-4 – from 5.6 to 5.11 pg/ml, TNF-α – from 3.6 to 3.1 pg/ml, however, this trend was not statistically significant. The cytokine balance values tended to decrease: in patients with DST – from 7.7 to 7.48, and in patients with FCT – from 7.69 to 4.97. Conclusion. The cytokine system plays an important role in the regulation of inflammatory processes in patients with DST and FCT of lungs.

The interrelation between the TNFα gene polymorphism and the effectiveness of the intensive phase of chemotherapy in patients with pulmonary tuberculosis, as well as the formation of diameter of the sizes of destruction cavities was studied. It was revealed that the most adverse course of the disease and a high frequency of formation of destruction cavities are associated with the GG genotype of the TNFα gene.

The aim of the study was to investigate the effect on the psycho-emotional state and adherence to treatment in patients with pulmonary tuberculosis of remaxol inclusion in the accompanying therapy regimens.Material and methods. The data from 326 patients (252 men and 74 women) with various forms of pulmonary tuberculosis treated at the Regional Clinical Tuberculosis Dispensary were analyzed; the average age of patients was 41.3±1.6 years. A low level of adherence to treatment, as well as clinical and laboratory signs of grade I hepatotoxicity were revealed in patients receiving a course of etiotropic therapy in the main group (N=72). In this regard, in addition to the psychological support for the main course of treatment, accompanying therapy was prescribed: remaxol 400 ml intravenous drip every other day (course No. 5), after-wards — 1 time a week (course No. 4). Patients in the comparison group (N=254) received standard treatment. In addition to the standard examination, the cytokine profile (the level of IL-1β, 4, 6), TNF-α and IFN-γ) was determined in dynamics according to the indications in patients. The level of adherence to the treatment was also determined in dynamics through testing according to the original methodology.Results. The study revealed that the inclusion of remaxol in the treatment regimens facilitated more pronounced positive dynamics in clinical and laboratory data compared with the standard regimen: a decrease in signs of hepatotoxicosis and a tendency towards improvement in cytokine profile parameters. This contributed to maintaining the etiotropic therapy regimen and improving the well-being of patients, which, in turn, increased the level of adherence and therefore the effectiveness of treatment in patients.Conclusions. The combination of positive effects of remaxol use in patients with pulmonary tuberculosis contributes to an increase in their psycho-emotional state and thereby increases adherence to treatment and its effectiveness.

Aim of the study was to investigate susceptibility to pulmonary tuberculosis in men and women depending on polymorphism of genes of xenobiotic biotransformation enzymes NAT2 (590G> A (rs1799930)), CYP2E1 (9896C> G (rs2070676)), ABCB1 (3435T> C (rs1045642)), GSTM1 (E/D) and GSTT1 (E/D). Material and methods. The study included 335 patients with pulmonary tuberculosis aged 18 to 65 years (212 patients with newly diagnosed pulmonary tuberculosis and 123 people with chronic pulmonary tuberculosis receiving intensive phase of chemotherapy). Statistical data processing was carried out on a personal computer using IBM SPSS Statistics 26 and MS Excel 2013 software packages. The control group consisted of relatively healthy individuals without chronic diseases. Genotyping of polymorphisms NAT2 (590G>A (rs1799930)), CYP2E1 (9896C>G (rs2070676)), ABCB1 (3435T>C (rs1045642)) and extended deletions GSTM1 (E/D), GSTT1 (E/D) was performed using real time PCR. Results. It has been established that the genotype EЕ of GSTT1 gene identified in 89.1 % men was statistically significantly associated with increased susceptibility to pulmonary tuberculosis, while the genotype DD of the GSTT1 gene (10.9 % cases) was associated with reduced susceptibility. A similar trend is observed in women: the greatest susceptibility to pulmonary tuberculosis is characteristic for the genotype ЕЕ GSTT1 gene (87.2 %), the least (12.8 %) – for the DD genotype. Conclusions. It is advisable to introduce genotyping of genes of xenobiotic biotransformation enzymes into the practice of a phthisiologist in order to develop measures to improve the effectiveness of prevention and treatment of patients with pulmonary tuberculosis.

The study used predicting the effectiveness of treatment of patients with pulmonary tuberculosis using neural network technologies. The most optimal neural network model was obtained, which allows predicting the effectiveness of treatment with a forecast accuracy of at least 78.4%. As a result of constructing a neural network model, the most significant «input» parameters of the neural network were identified: the presence of hepatotoxic reactions, the level of IL-1ß, IL-6, IL-4, IL-10, IFN-γ, C-reactive protein before the start of the intensive phase of chemotherapy, the presence of antibiotic resistance, the presence of mycobacterium tuberculosis before the appointment of a specific chemotherapy by seeding, the volume of lung tissue damage, the chemotherapy regimen, the clinical form of pulmonary tuberculosis, as well as the genotype of ЕЕ gene GSTT1.

Currently, a decrease is seen in the effectiveness of treatment in patients with tuberculosis due to the appearance of adverse reactions to anti-tuberculosis drugs. Hepatotoxic reactions play an especially important role in anti-tuberculosis therapy, and phthisiologists often have to deal with the cancellation of a number of anti-tuberculosis drugs. The aim of the study was to investigate the relationship of polymorphic gene variants of xenobiotic biotransformation metabolizing enzymes (NAT2 (590G>A (rs1799930), CYP2E1 (9896C>G (rs2070676), ABCB1 (3435T>C (rs1045642), GSTM1 (E/D), GSTT1 (E/D) with the risk of hepatotoxic reactions in patients with pulmonary tuberculosis. Material and methods. The logistic regression analysis method was used to predict the probability of hepatoxic reactions during specific anti-tuberculosis therapy. Results: 1 statistically significant model was obtained, which reflects the association with hepatotoxic reactions to anti-tuberculosis drugs of the TS genotypes or the TS gene (T allele) ABSV1 (rs1045642). Conclusion. Pharmacogenetic testing used in the study allows us to identify risk groups of patients with pulmonary tuberculosis according to the likelihood of hepatotoxic reactions, which may provide an individualized approach to the treatment of these patients in the future.

The aim of the work was to study the effectiveness of remaxol inclusion in treatment regimens designed for patients with comorbid tuberculosis and hepatotoxic response to etiotropic therapy.Materials and Methods. Case histories of 25 patients (21 men and 4 women) with a confirmed diagnosis of tuberculosis infection and hepatotoxic reactions to etiotropic treatment were analyzed. Of these, 9 patients had a comorbid (TB/HIV) pathology and 16 patients had TB/HIV with concomitant diseases. To stop the signs of hepatotoxicity, all patients were prescribed with remaxol: 400 ml intravenously on alternate days (course No. 5), then 1 time per week (course No. 4). In addition to the standard clinical and laboratory examination, all patients underwent follow-up (before and after the course of remaxol) examination of the levels of aspartate aminotransferase and total bilirubin in the blood, as well as the levels of interleukin production (1β, 4, 6 and 10) and tumor necrosis factors (TNF-α and TNF-γ). Standard regimens were used when conducting anti-tuberculosis chemotherapy.Results. It was noted that the presence of a comorbidity aggravates the course of tuberculosis and reduces the effectiveness of etiotropic therapy due to the development of hepatotoxicity. The inclusion of remaxol contributed to a decrease in the severity of hepatotoxic reactions and made it possible to avoid the correction of the main treatment course. The revealed positive dynamic in cytokine profile indicators can be regarded as a mediated immunological effect of the drug and requires further research.

The aim of the study . To analyze formation features of the epidemic situation for tuberculosis (TB) in the context of the COVID-19 pandemic in order to predict the further actions of medical organizations. Materials and methods . The data for the region for the last 5 years (2017–2021) were analyzed, including 1,762 newly diagnosed cases of patients with TB and comorbidities (according to the data of the Regional Public Health Organization «Regional Clinical Anti-Tuberculosis Dispensary»). All cases were verified using standard diagnostic methods, including molecular genetic methods, to determine the resistance of pathogens to antibacterial drugs. Results . It was revealed that the epidemiological situation in the region was multidirectional: thus, during the COVID-19 epidemic, the most pronounced incidence decrease was observed among cases of chronic course hepatitis (by 16.4 times), while among patients with tuberculosis the incidence decreased by 2.75 times, and among patients with acute hepatitis — only by 1.5 times (P<0.05). Among the cases of comorbid infection, the most severe course was observed in patients with combined (TB + HIV) infection: there was both a more severe general condition, and the development of adverse (undesirable) reactions to anti-TB drugs, which required an extension of maintenance therapy. Conclusions . The results of the study showed that against the background of the COVID-19 pandemic in the region, there was no tendency towards a worsening of the epidemic situation, primarily for the more socially significant infection — tuberculosis. At the same time, there was an increase in the number of cases of comorbid pathology, including HIV + TB. In the treatment of patients with comorbid forms of infection, it is necessary to take into account the possibility of developing hepatotoxic reactions and, as a result, the appointment of accompanying drugs with hepatoprotective and detoxification effects in therapy.

The aim of the study was to evaluate the effectiveness of psychological (adherence to treatment) and accompanying drug therapy depending on the form of pulmonary tuberculosis. The results of complex therapy of 326 patients with various forms of pulmonary tuberculosis are considered. All patients received etiotropic treatment, taking into account the sensitivity of the pathogen to anti-tuberculosis drugs, as well as support therapy, including psychological support and, if indicated, hepatoprotective therapy with Remaxol. When analyzing the dependence of the psychoemotional state of patients on the form of the tuberculous process in the lungs, it was noted that high adherence to therapy was observed in one third of patients in all groups (DTL — 26.1%, ITL — 28.6%, FCTL — 32.8% and ATL — 31.8%, respectively, P >0.05). The results obtained may be associated with a high level of resistance of mycobacterium tuberculosis excreted from pa tients: out of 232 patients with low adherence to treatment (NUP and UUP), 97 (36.2%) showed drug resistance of the pathogen to two or more etiotropic drugs, which, in turn, caused prescription of reserve drugs. Thus, the determination of the level of adherence to treatment is justified and is aimed at correcting the psychological support of patients with pulmonary tuberculosis, which makes it possible to increase the effectiveness of therapy in these patients. The appointment of the latter in a number of patients led to the development of hepatotoxic reactions, which served as the basis for the inclusion in the therapy regimens of the accompaniment of Remaxol (intravenous drip of 400 ml, course No. 5–7). Pronounced hepatoprotective (improved transaminase parameters) and insignificant immunoprotective (positive dynamics of the cytokine profile) effects were noted during treatment. The noted changes in the immunogram can be associated with the proven antioxidant and membrane stabilizing effect of succinic acid, which is part of Remaxol. These changes require further research.

The aim of this study was to evaluate effectiveness of remaxol inclusion in the supporting therapy regimen in patients with the fibrous-cavernous form of drug-resistant tuberculosis. Treatment of 173 patients with fibrous-cavernous pulmonary tuberculosis was analyzed. Standard clinical laboratory methods and x-ray diagnostic were conducted in all patients as well as the spectrum of pathogen sensitivity to anti-tuberculosis drugs was defined. Changes in immune status and state of liver detoxification function were evaluated in dynamics (before and after hepatoprotective therapy course) taking in consideration level of cytokines (interleukins 1,4,6 and 10, tumor necrosis factor, interferon-gamma) and liver enzymes (AST, ALT). Two groups of patients were formed using randomization: group 1 (main) with 111 patients who received etiotropic therapy and complex of treatment and rehabilitation activities, and group 2 (comparisons) with 62 patients who, in addition to the main complex of therapy, received remaxol: intravenously, 400 ml once a day, a course of 12 droppers. In this research it was revealed that remaxol inclusion in the supporting treatment regimen showed hepatoprotective (improved transaminase) and minor immunoprotective (positive cytokine profile) effects. The obtained laboratory results correlate with clinical data: prevalence of high (53.8%) and absence of low treatment efficacy cases and a higher degree of patients adherence to treatment.

The aim of the study was to analyze the features of the organization of therapy for patients with HIV-associated tuberculosis (TB/HIV) and the effectiveness of pharmacotherapeutic approaches under the conditions of penitentiary institutions. Materials and methods: the data on the incidence and effectiveness of specialized medical care for TB/HIV patients were analyzed for a ten-year period in the population of penitentiary institutions of the Federal Penitentiary Service of one of the subjects of the Central Federal District of the Russian Federation. Therapy and examination of patients with TB/HIV was carried out in accordance with regulatory documents and using generally accepted diagnostic methods. The patients consulted the staff of the departments of the FSBEI HE KSMU to verify the diagnosis and correct treatment regimens. Results: the analysis showed that, despite the stabilization of the TB epidemic situation, the epidemiological indicators for comorbid TB/HIV are increasing in the penitentiary health sector, which is due to an increase in the number of HIV-infected patients. In order to intensify the treatment of patients with TB/HIV in the population of the penitentiary system, it is necessary to give priority to social and sanitary prevention, primarily in risk groups — HIV-infected and individuals with residual lung changes. The inclusion of Remaxol in the therapy regimens for TB/HIV patients promotes rapid relief of hepatotoxic reactions and, as a consequence, increases the effectiveness of the primary therapy, which is illustrated by clinical observation.

One of the fundamental features of tuberculosis pathomorphism in modern conditions is secondary immune deficiency, which manifests itself at the initial stage of the infection process and aggravates as the disease progresses. This review presents analysis results of cumulative clinical and laboratory data, confirming high efficiency of cycloferon as a support drug in the treatment of newly diagnosed tuberculosis forms and in patients with advanced forms, which allows recommending its inclusion in the treatment regimens of these disease forms. The effectiveness of the drug in treatment of comorbid tuberculosis and features of its non-specific prophylaxis require further research.

To solve the problems of tuberculosis (TB) in penitentiary institutions, it is advisable to conduct a retrospective analysis, to find the most successful ways to prevent the spread of the infection in this system.Objective: to study the historical aspects of tuberculosis control in the penitentiary system of the Russian Federation.Methods. Information analysis methods were used. Data from 61 sources were studied.Results. The most significant attention was given to tuberculosis control in the penitentiary units at the beginning of the XXI century, which resulted in the significant improvement of the situation. In recent years, less attention has been paid to this problem, which is capable of stagnating positive changes. It is proposed, along with the continued implementation of proven measures, to intensify research activities, the interaction between civil and penitentiary health care and social communication.

The aim of this research was to study the effectiveness of cycloferon inclusion in the complex of treatment and rehabilitation measures for patients with fibrous-cavernous pulmonary tuberculosis. In this regard, an analysis of 158 patients with fibrous-cavernous pulmonary tuberculosis was performed. The patients were divided into 2 groups: the main group (54 patients), in addition to etiotropic therapy, received a complex of therapeutic and rehabilitation measures, including preparation of cycloferon administered according to a modified procedure at a dose of 0.25 g 2 times per week until the end of the intensive phase of the main treatment. The comparison group consisted of 104 patients who received etiotropic therapy and a complex of therapeutic and rehabilitation measures: vitamin therapy, physiotherapy, and psychological support. The effectiveness of etiotropic therapy was evaluated after the end of the intensive phase of the main course of treatment which lasted no more than 3 months, and 5 months in the presence of drug-resistant forms and other aggravating factors. It was revealed that the effectiveness of treatment in patients with fibrous-cavernous pulmonary tuberculosis is determined not only by the etiology of the disease course, the duration of the main course of treatment, and the presence of a pathogen resistant to anti-tuberculosis drugs, but also by a number of factors that influence patient adherence to treatment in a complex way. Unfavorable outcomes of treatment of this form of the disease were observed in patients with chronic course of the disease (F6=0.89), caused by a multidrug-resistant agent (F8=0.65), and among those released from prison (F2=0.34). However, even short-term use of accompanying therapy with cycloferon allows increasing the effectiveness of treatment, improving the course of the process, including stopping the release of mycobacteria in 94.1% of patients with concomitant diseases. It is possible that the described effect of cycloferon as an accompanying therapy is based not only on its direct effect on patient's immunodeficiency, but also its indirect effect on the increase in adherence to treatment due to cessation of violations of the treatment regimen and other purely psychological factors that require further study.

Исследована безопасность и эффективность применения препарата циклоферон при иммуномодулирующей терапии сопровождения у пациентов с запущенными формами туберкулёза лёгких. Наблюдали 176 пациентов с фиброзно-кавернозным туберкулёзом лёгких. Больные первой группы (n = 56), кроме этиотропной терапии и комплекса лечебно-реабилитационных мероприятий (КЛРМ), получали препарат циклоферон, второй группы (n = 60) – препарат «Омега-3», третьей группы (n = 30) – этиотропную терапию, а также КЛРМ без применения циклоферона и ОМ-3, а четвертой группы (n = 30) – только этиотропную терапию. Приверженность лечению больных туберкулёзом определяли (количественно) по авторской методике. Использование циклоферона позволило добиться прекращения и сократить сроки бактериовыделения возбудителя (в том числе МЛУ-МБТ) у (94,1 ± 3,3) % больных. Возможно, выраженный эффект паллиативной терапии циклофероном обусловлен как его прямым иммунопротективным действием, так и опосредованным – за счёт улучшения общего состояния пациента и повышения его приверженности к лечению.

Авторским коллективом из 14 компетентных специалистов ведущих учреждений системы противотуберкулезной службы здравоохранения и АН РФ опубликована объемная и своевременная статья с рекомендациями по дальнейшему усовершенствованию этиологической диагностики туберкулеза, в основном по разработке новых учетных форм для бактериологических лабораторий [2].