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The advent of the COVID-19, specialists are increasingly encountering previously unknown pathological conditions in their practice. For some time, we have believed that COVID-19 in children is most often mild and asymptomatic. However, with the passage of time and the accumulation of the experience, it became obvious that the new infectious disease it will be quite severe in children. Differential diagnosis of multiple organ disorders in children during the COVID-19 pandemic should be primary carried out with the Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C), as well as Long-COVID-19. According to published data, the manifestations of these conditions are due to frequent lesions of the gastrointestinal tract (60–100 %), cardiovascular (80 %), nervous (29–58 %) and respiratory (21–65 %) systems. At present, there is no exact idea of these pathological conditions, the criteria for their diagnosis and the tactics of managing children, not only at the stage of diagnosis, but also at the stage of observation. The authors present a diagnostically complex clinical case describing the development of multiple organ damage in a 7-year-old child after contact with a mother who was sick with COVID-19. The data on the course features, the results of the examination and the difficulties of differential diagnosis of this case with other diseases with a similar clinic are summarized.

The epidemic situation is monitored by numerous rates that may not reflect it objectively which will subsequently lead to higher incidence rates and severe forms of tuberculosis in both adults and children in the regions with the most unfavorable situation.The objective: to evaluate epidemiological rates for tuberculosis in the Northwestern Federal District to identify the most significant, and assess the epidemic situation in the region using these most significant rates.Subjects and Methods. We analyzed the main epidemiological rates of pediatric tuberculosis according to federal statistics (Forms 8 and 33) in 11 districts of the Northwestern District in 2019-2021. Annual figures were obtained from open demographic data of the state statistics (https://www.fedstat.ru). Statistical analysis was pe`rformed using the free software R (v.3.5.1) and the commercial Statistical Package for the Social Sciences (SPSS Statistics for Windows, Version 24.0, IBM Corp., 2016). Hierarchical cluster analysis and k-means clustering were used with the selection of the lowest and highest values of rates. A formula is proposed for calculating the coefficient of full coverage with preventive screening (COP) for tuberculosis of the population which allows adjusting the analyzed epidemic rates taking into account the maximum coverage of the population with preventive screening and determining the accuracy of previous analysis.Results. According to the data obtained, in 2017 and 2018, Vologda Oblast and Nenets Autonomous Okrug were epidemically favorable regions, while in 2020 and 2021 Kaliningrad, Leningrad and Novgorod Oblasts were regarded as favorable regions that were steadily improving their performance. Regions with unfavorable tuberculosis situation include Pskov Oblast, St. Petersburg and the Komi Republic. At the same time, the first two regions occupy this position stably from 2017 to 2021. The use of the coefficient of low coverage with screening for tuberculosis made it possible to determine that Murmansk Oblast, St. Petersburg, Leningrad and Pskov Oblasts in 2020 and 2021 are prognostically unfavorable regions despite a decline in official tuberculosis rates. The data obtained correlate with a high percentage of positive tests with the tuberculosis recombinant tuberculosis allergen (TRA) in children in the regions mentioned above.Conclusions. The analysis of the data clearly demonstrates the possibility of determining the epidemically most favorable or unfavorable regions using four rates: coverage with preventive screening, incidence in the adult population, incidence in children aged 0 to 17 years, and tuberculosis mortality. Cluster analysis using these rates, calculation of rates using the developed coefficient of low coverage with screening for tuberculosis, and analysis of positive results of TRA test in children allows identifying the most epidemically unfavorable regions, despite the decrease in some rates that can be regarded as favorable.

The objective: to compare treatment efficacy of pulmonary tuberculosis patients with multiple (MDR) and extensive drug resistance (XDR) using a standard chemotherapy regimen and the regimen containing bedaquiline.Subjects and Methods. A retrospective study was conducted to analyze treatment outcomes in 219 patients with pulmonary tuberculosis and MDR/XDR of Mycobacterium tuberculosis (MTB) aged 18-75 years old who were treated in in-patient and out-patient facilities of St. Petersburg from 2016 to 2019. Treatment outcomes were analyzed by subgroups formed taking into account resistance patterns and addition of bedaquiline to the treatment regimens: Ia – n = 94 (MDR TB; Bq-) and IIa ‒ n = 80 (XDR TB; Bq-); Ib ‒ n = 22 (MDR TB; Bq+) and IIb ‒ n = 23 (XDR TB; Bq+). Clinical and laboratory parameters of patients, the severity of comorbidity were assessed before the start of treatment, after 3, 6, 12-14 and 18-24 months of therapy, as well as after therapy completion and during the follow-up period. Statistical analysis was carried out using Statistica 10.0 and methods of parametric and nonparametric statistics and the SPSS 16.0 software, where p ≤ 0.05 was considered significant.Results. XDR TB patients in Subgroup IIb were significantly more likely to have a high level of comorbidity according to Charlson index (from 5 to 6 points) – in 34.7% of cases versus 5.0% in Subgroup IIa. At all stages of treatment in MDR TB patients with Bq+ (Ib), sputum conversion was recorded significantly more often versus patients of Subgroup Ia with Bq- when examined at all stages, with maximum effectiveness achieved by 18-24 months of treatment (90.9%). Treatment efficacy of XDR TB patients (IIb, Bq+) was also significantly higher versus treatment regimen containing no bedaquiline (60.8% (IIb, Bq+) versus 25.0% (IIa, Bq-), χ2 = 4.61, p < 0.05).Conclusions. Achieved high efficacy of therapy in Subgroups Ib and IIb containing Bq provided a positive impact on treatment default rates, that were recorded in a low percentage of cases in those subgroups. An ineffective course of treatment in MDR TB patients treated with regimens containing no Bq was observed in 42.5% in Subgroup Ia, while this rate made only 0.09% in Subgroup Ib. Treatment effectiveness was the highest in XDR TB patients of Subgroup IIb when Bq was added to the treatment regimen.

2020 began with the most significant pandemic COVID-19 in the history of this century. The epidemiology indicators are growing every day. The spread of COVID-19 may affect an increase in the incidence of tuberculosis, despite a decrease in the incidence rate that is associated with objective difficulties in detecting tuberculosis against the background of COVID-19 and severe complications after the new coronavirus infection. Tuberculosis is one of the infectious diseases, and the problem of its spread continues to be relevant throughout the World. The effect of the SARS-CoV-2 virus can cause certain difficulties in the diagnosis and treatment of tuberculosis infection. The possibility of concomitant these infectious diseases can affect the clinical course of tuberculosis, an influence on mortality of the disease, but at the same time, there is a decrease in the number of cases that is not objective. The authors analyzed the currently published data on detecting tuberculosis in the conditions of the COVID-19 problem and presented difficulties in the diagnosis of COVID-19 and TB concomitant diseases with a description in the clinical case.

The objective of the study: to run a multicenter non-interventional observational study to assess treatment outcomes in tuberculosis patients receiving combination drugs with fixed doses, and to evaluate tolerability and safety of these drugs.Subjects and methods. 13 TB units participated in this study which lasted from 2016 to 2018. The primary population (PP) included of 489 patients, after applying the exclusion criteria – the subpopulation (subPP) included 267 patients with newly detected pulmonary tuberculosis and relapses who received treatment as per chemotherapy regimen I or III. Descriptive statistics methods were used for statistical data processing.Results. Of all PP, 267 (54.6%) completed the main course of chemotherapy. (subPP). Out of 489 patients, treatment was discontinued in 118 (24.1%) of them. Primary drug resistance was detected in 30 (6.1%) patients out of 489 patients, secondary drug resistance – in 74 (15.1%) of 489. In subPP, by the end of the intensive phase the sputum conversion was achieved in 78 (96.3%) of 81 patients. Clinical and X-ray changes had been observed in this subgroup for 106.2 to 63.3 days (median 90). The duration of the intensive phase in the subPP made 107.9 ± 50.5 days. In safety assessment, 191 adverse events (AE) were registered in 149 (30.5%) of 489 patients. By severity, most AEs were minor (164 out of 191), moderate AEs were less frequent (20 out of 191), and there were 7 cases of serious AEs. 61 AEs in 57 (38.2%) out of 149 patients were confidently associated with in-take of the studied drugs. The structure of those AEs, transient transaminase level elevation prevailed (45 (73.8%) of 61 AEs, but there was a single case (1.6%) drug-induced hepatitis). Among the serious AEs, two cases were safely resolved by the end of the protocol, two of them were fatal in TB/HIV co-infection, and three cases were diagnosed with cancer.

The article presents a review of 60 publications from international and Russian databases (PubMed, Web of Science, and Elsevier) from 1960 to 2018 with the keywords "sarcoidosis," "autoimmune reactions," "antibodies," and "HLA-genotype" characterizing sarcoidosis as an autoimmune disease. The information is divided into sections: the role of triggers, clinical manifestations and combination with autoimmune diseases, immunogenetic predisposition, features of cellular immune response, humoral immune response, and immunosuppressive therapy.

Tuberculosis is a granulomatous disease caused by Mycobacterium tuberculosis, being characterized by the development of caseous granulomas in various organs, mainly in lungs. M. tuberculosis is known to be a trigger for autoimmune inflammation, due to the possible mimicry of bacterial proteins as autoantigens. Recently, a significance of mesenchymal vimentin as an autoantigen in mycobacterial infections has been actively discussed. The aim of the present study was to determine autoantibodies for various vimentin modifications in the patients with tuberculosis.The study was performed in 2014-2017 and included 28 patients with pulmonary tuberculosis (group I), 30 patients with nonspecific lung diseases (group II): 15 with granulomatous polyangiitis, and 15 with different alveolites. Control group consisted of healthy subjects (n = 40). Concentration of antibodies to mutated citrullinated vimentin (anti-MCV) was measured using ELISA (ORGENTEC, Germany). The patients with elevated anti-MCV levels were tested for antibodies to cyclic citrullinated peptide (anti-CCP) using ELISA technique (EUROIMMUN, Germany). Statistical analysis was carried out using GraphPad Prism 6 (GraphPad Software, USA), Statistica 10 (Statsoft, USA) using nonparametric analysis of samples with Mann-Whitney and Chi-square criteria, and Spearman method for correlation analysis. The differences were considered statistically significant at p < 0.05.The anti-MCV concentrations were significantly higher in patients with tuberculosis (group I, 60.7% of cases, 17/28) than in group II, and control group (23.6 and 25.0% of cases, respectively). No statistically significant differences were revealed between the results of anti-MVC and anti-CCP levels in comparison group with the control group (p = 0.18).High levels of anti-MCV antibodies in the patients with pulmonary tuberculosis reflect an opportunity of developing autoimmune process in the disease pathogenesis. Measurement of plasma anti-MCV antibody concentrations may be important for correction of the therapy, especially upon administration of immunosuppressive and hormonal corticosteroid drugs. It has been shown that anti-CCP are not characteristic to the lung diseases.

Early diagnosis of tuberculosis remains essential for the prevention of the disease and control of its incidence. The diagnosis of latent tuberculosis infection (LTBI) has significantly improved over the last years due to the use of new immunological tests, including the Diaskintest.The aim of the study was to assess the potential of immunological assays for diagnosis of latent tuberculosis infection and determination of risk groups for tuberculosis among personnel of different institutions.Materials and methods: in 2015–2018, a prospective group-control study was conducted that included employees of various medical centres (n = 154) and healthy individuals (n = 30). There were no significant age differences between the subjects. All the subjects included in the study shared their medical history, underwent general examination, X-ray examination, and were tested with Diaskintest. Multispiral computed tomography (MSCT) of the chest was performed for every subject with a positive Diaskintest result.Results: the comparison of the number of persons with LTBI in general care hospitals, personnel of a manufacturing firm, and among healthy individuals showed that the risk of being infected with Mycobacterium tuberculosis is very similar in all the groups (from 6.8 to 10.0 %). The highest risk of developing LTBI was found in people who worked in an infectious area for more than 5 years (48.4 %). The analysis of the level of immune complexes (ICs) demonstrated that individuals with LTBI did not have isotypes of IgG3 and IgE immune complexes, which are found in patients with tuberculosis. The identification of particular isotypes indicates a borderline state between LTBI and tuberculosis and requires therapeutic intervention.Conclusions: the use of the Diaskintest makes it possible to distinguish groups of employees of various institutions who are at a higher risk of developing tuberculosis. At the same time, determination of the ICs helps to reveal the borderline condition which requires medical intervention.

Tuberculosis (TB) is one of the most common infections worldwide. Eradication of an intracellular pathogen M. tuberculosis requires to induce a Th1 response by activating IFNγ-producing tissue macrophages. Along with Th1 cells, various subsets of Th17 and follicular T-helper cells (Tfh) able to secrete a broad range of cytokines, including IFNγ, can also be involved in eliminating bacterial pathogens. It justified analyzing in this study changes in percentage of various peripheral blood Th subsets, including Th1, Th2, Th17 and Tfh cells, in TB patients. For this, major CD3+CD4+ T cell subsets were assessed by using multicolor flow cytometry in TB patients (n = 40) and healthy volunteers (n = 30). It was found that in TB patients vs. control group percentage of peripheral blood CD45RA–CCR7+ central memory (CM) Th was decreased also affecting frequency of some functional T cell subsets, e.g. either lowering Th2 cells (9.11% (6.95; 13.77) vs. 7.21% (5.64; 9.84), p = 0.012) or elevating CCR6+ Th17 subsets (35.92% (27.72; 41.06) vs. 40.39% (35.41; 47.79; p = 0.016), respectively, but not influencing Th1 and Tfh subsets frequencies. Moreover, percentage of total CCR6+ CM Th cells in TB patients vs. control was decreased in CCR4–CXCR3+ Th17.1 cell subset (42.87% (33.64; 49.45) vs. 52.26% (46.45; 56.95), p < 0.001), whereas standard CCR4+CXCR3– Th17 and CCR6+ DP Th17 subsets were elevated (p = 0.005 and p = 0.002, respectively). In addition, altered Tfh subset composition associated with the increased (p = 0.021) percentage of CXCR3–CCR6– Tfh2 cells, but decreased CXCR3+CCR6– Tfh1 cells (p = 0.036) was observed. Finally, frequency of peripheral blood Th subsets noted above was also analyzed within effector memory (CD45RA–CCR7–) cells. It was found that in TB patients vs. volunteers frequency of Th17.1 cells was also significantly lower (p = 0.006) in CCR6+ EM Th (54.43% (41.19; 91.92) vs. 61.76% (54.01; 65.63), whereas percentage of double-positive Th17 was significantly increased (20.83% (15.12; 30.87) and 12.93 % (9.80; 19.01), respectively, p < 0.001). Thus, it suggests that during M. tuberculosis infection percentage of IFNγ-producing Th17 and Tfh cells was reduced compared to control group also affecting both central memory Th cells patrolling peripheral lymphoid organs as well as effector memory Th cells able to exit to site of infection.

The etiology of sarcoidosis is not completely understood. A hypothesis exists about the relationship between sarcoidosis and a complex of pathological autoimmune reactions that occur under the influence of triggering factors. In this study, specific immune complexes in the blood plasma of patients have been determined, which can indirectly reveal the causes of the disease.The study included 33 patients with lung sarcoidosis (I group), compared to 24 healthy donors who served as a control group (II group). The patients underwent standard examination. Their blood plasma was investigated by the dynamic light scattering method with addition of tuberculosis antigens (ESAT-6/SFP-10) and “lung healthy tissue extract”. Statistical analysis was performed using the Statistica 7.0 program. Test results were considered significant at p < 0.05.Аccording to the data obtained, addition of ESAT-6/SFP-10 to patient’s blood plasma almost did not lead to the formation of immune complexes in most samples. Meanwhile, development of such complexes after addition of “lung tissue extract” was revealed in all the patients. The immune complexes were not detected in any donor from control group after stimulation with both kinds of antigens (p < 0.01).The data on distinct formation of immune complexes with the addition of “lung healthy tissue extract” in patients with lung sarcoidosis may be considered an indirect evidence for occurrence of autoimmune reaction under the influence of some pathogenic factors. Absence of de novo immune complex formation after addition of tuberculosis antigens (ESAT-6/SFP-10) makes it unlikely any direct effects of tuberculosis bacteria upon development of sarcoidosis.

The introduction of a new generation of immunological tests based on in vitro or in vivo reactions using specific ЕSAT-6 and CFP-10 peptides allowed changing the understanding of the diagnosis of latent tuberculosis infection, as well as improving the diagnosis of tuberculosis in pediatric and adult practice. The article presents the analysis of the Russian studies conducted over the past ten years aimed to investigate the informativeness of a skin test with tuberculosis recombinant allergen. High diagnostic significance of the skin test, comparable to the internationally recognized IGRA-tests has been proved. Today, the test with TRA in the form of locally manufactured Diaskintest has been introduced inRussianot only to the practice of TB units, but also in the practice of pediatricians, pulmonologists and infectious disease specialists.

The diagnostic of tuberculosis infection, including the use of immunological methods, evolved significant changes. The introduction of new diagnostic tests allowed to improve the diagnosis of latent tuberculosis infection (LTI). However, the positive results of immunological tests in both tuberculosis patients and in those with LTI do not allow to divide these conditions, which requires the development and implementation of new diagnostic approaches.Materials and methods. A prospective study with a survey of two groups of patients was conducted: group I (n=50) - patients with verified pulmonary tuberculosis, MBT (+); group II (n =15) – subjects with LTI and control group – healthy subjects (n=14). The examination complex included clinical, radiological, bacteriological, immunological (Mantoux test with 2 TU, T-SPOT.TB, QFT and Diaskintest) methods. Immune complexes were determined in all patients and healthy individuals by the method of dynamic light scattering after the in vitro addition of specific antigens - peptides ESAT-6 and SFP-10.Results. The obtained data demonstrate the low informativeness of the clinical method in the diagnostic of pulmonary tuberculosis. In the presence of characteristic X-ray changes, bacteriological verification of tuberculosis was obtained only in 46% of cases. The use of various immunological tests allows to obtain positive test results in 84-90% of cases simultaneously with the 100% of the positive results in subjects with LTI. Determination of specific immune complexes by the method of dynamic light scattering allows to determine the activity of tuberculosis infection in 100 % of cases and to identify a high-risk group for the development of active tuberculosis in people with latent tuberculosis infection.Conclusions: the obtained data can be applied not only in the diagnosis of active tuberculosis in the absence of diagnosis verification, but also allow to identify a high-risk group for the development of the disease in people with latent tuberculosis infection.

Cutaneous tuberculosis is a clinically and morphologically heterogeneous group of skin diseases directly or indirectly caused by mycobacteria of the tuberculosis complex, occupying the 5th place among all localizations of extra-pulmonary tuberculosis. Manifestations of cutaneous tuberculosis are extremely diverse and depend on the immune status and ways of penetration of mycobacteria into the skin. Skin involvement can occur as a result of exogenous inoculation, contiguous spread from an adjacent focus, or hematogenous spread from other foci. Family cases of disseminated cutaneous tuberculosis are described. A combination of several clinical forms of cutaneous tuberculosis — scrofuloderma, tuberculosis cutis lichenoides (moniliformis scrophulosorum) and lupus — are observed in a 5 year old child with a family history of tuberculosis. The issues of pathogenesis and advanced methods of diagnosis of cutaneous tuberculosis are also discussed.

Objective: to study inflammatory response in patients with drug-resistant Mycobacterium tuberculosis. Materials and methods. 56 patients were examined. The first group consisted of (n=38) patients with extensively drug-resistant pathogen (23 men and 15 women) from 17,0 to 63,0 years old, the second group (n=18) – patients with multi-drug resistant pathogen (12 men and 6 women) from 16,0 to 69,0 years old. Reference group – 30 practically healthy donors. Were examined: level of ceruloplasmin, haptoglobin, α1acid glycoprotein, activity of α1-proteasome inhibitor, α2macroglobulin, activity of adenosine deaminase and elastase. Statistical data processing was performed using Statistica 7.0. Results. In both groups average level of haptoglobin exceeded the upper limit of normal range 2,5 times; grade depended on clinical form of tuberculosis. Level of α1-acid glycoprotein in both groups was increased on average 1,5 times (p

So far, there is no clear understanding for the reasons causing tuberculosis generalization in children. Development of generalized infection could be also determined by some features of immune response which may depend on genetic markers. The aim of our work was to study the features of HLA-DRB1 and HLADQB1 allele distribution in children with generalized tuberculosis (gTBC). Materials and methods: we have observed 40 children at the age of 1 to 15 years suffering from gTBC. After performing a standard phthysiatric examination, including molecular-genetic diagnostics of surgical material, multispiral CT, immunological testing, as well as HLA-DRB1 and DQB1 alleles. We have studied distribution of the HLA-DRB1 and DQB1 alleles comparing it with a group of healthy donors (n = 100).The results did not show significant differences in HLA-DQB1 allele distribution between the gTBC patients and comparison group. Meanwhile, when comparing genotypes for HLA-DRB1 loci, we have revealed a significantly lower prevalence of the *01 allele of HLA-DRB1 (12.5% versus 31.0%; χ2 = 4.08; р < 0.05), which could be considered a predisposing factor, as well as a higher incidence of *14 allele (7.5% against 1.0%; χ2 = 3.67, р < 0.05) of HLA-DRB1 gene, thus suggesting its protective role.Conclusions: we did not find any significant differences for HLA-DQB1 distribution between pediatric patients with generalized tuberculosis and healthy donors, whereas * 01 allele of HLA-DRB1 may predispose for gTBC, and the *14 allele could be protective in evolving generalized tuberculosis in children.

Development of new methods of immune diagnostics of tuberculous infection and their introduction into tuberculosis control practice have changed approaches to diagnostics of tuberculosis in Russia. Along with world recognized IGRA-tests the test with tuberculous recombinant allergen (TRA) developed by Russian researchers is also widely used. High diagnostic value of each of the methods is proved by multiple national and international trials however there is no research comparing results of these methods in the diagnostics of tuberculous infection in children, including those with concurrent conditions. During the study data of testing in 654 children in the age from 0 to 14 years old with positive sensitivity to tuberculin as per Mantoux test with 2 TU were analyzed. All patients had modern immunological tests done: TRA and IGRA-tests (QuantifeRON® Gold ELISA (QFT) and T-SPOT.TB). The study confirmed the low value of Mantoux test with 2 TU as a method of early tuberculosis detection in children; it detected underdiagnosis (10-50%) and overdiagnosis (78%) of latent tuberculous infection in the children with different sensitivity level as per data of Mantoux test with 2 TU. Comparing the results of TRA and IGRA tests it is possible to state that they are compatible for 76-81% of cases. The group of children was detected who had allergic and endocrine disorders (obesity), for whom IGRA tests were recommended to exclude chances of false-positive results of TRA tests.

Concomitant infection is known to decrease non-specific immunity levels, thus negatively affecting clinical outcomes in tuberculosis patients. Development of specific immune response against most common pediatric infections, e.g., pneumococcal infection, is possible both in children with latent tuberculosis and in respiratory tuberculosis. The study contains data concerning results of immunization with Pneumo23 vaccine against pneumococcal infection in 35 children (3 to 14 years old) with different manifestations of MBT infection observed at the St. Petersburg Research Institute of Phthisiopulmonology. The vaccination efficiency was evaluated by incidence of acute respiratory infectionsm acute otitis media, and community pneumonias within one year before and after vaccination performed. Clinical safety of the vaccination was determined as the number of general and local reactions registered following vaccination.Incidence of post-vaccinal reactions did not differ significantly between the clinical groups and did not exceed the values reported by the vaccine manufacturer. Post-vaccinal period was event-free in 94.3% of vaccinated children, without any negative effects upon the underlying tuberculosis process. In Group 2, all the children were complication-free over the post-vaccinal period. Both groups exhibited a statistically significant increase of IGg levels by the post-vaccination day 14…45. The PPV23 vaccination was not followed by postvaccinal complications, or worsening of tuberculosis infection. Hence, anti-pneumococcal vaccination is effective for prevention of acute respiratory infections, both in MBT-infected children and in patients with local tuberculosis affection.

Co-infection of tuberculosis and HIV-infection continues to be the current crucial issue not only due to the persistent growth of HIV-infection but also due difficulties in diagnostics of tuberculosis. Often X-ray changes in the lungs are atypical, clinical signs are manifested only in case of the severe and disseminated disease. At present the IGRA-tests are widely used worldwide while in Russia TRA tests are used. The trial provided the data on the use and comparative efficiency of the above immunological tests against Mantoux test with 2 TU when examining 239 persons from 2014 to 2015. The comparativeness of diagnostic sensitivity of all immunological tests had been proved. The specificity of IGRA-tests and TRA tests is twice higher compared to Mantoux test with 2 TU. Also it was proved that when diagnosing tuberculosis in HIV patients the skin tests (Mantoux test with 2 TU and TRA test) had low diagnostic informativeness compared to IGRA tests, among which ELISPOT was the most sensitive.

The article describes the study of comparative efficiency of fenazid (isonicotinoilhydrazine-О,N’) ferrous dihydrate sulphate (II) and isoniazid in drug susceptible pulmonary tuberculosis patients.The high treatment efficiency namely significant improvement and improvement was observed in the patients of Group 1 – 84.1% which could be compared to the standard treatment regimen (85-7%) in Group 2. The total number of adverse reactions in the main group was confidently lower – 18.6% against 33.9%, p < 0.05. Hepatotoxic reactions with 2-3 fold increase of alaninetransferase level was registered significantly less (9.3%) in Group 1 compared to the Group treated with isoniazid.

Goal of the study: to detect specific immune response in children with latent tuberculous infection and define factors to forecast the development of the active disease in this group.Materials and methods. The changes in clinical, X-ray and immunological data were analyzed in 127 children when latent tuberculous infection was diagnosed and after 12 months of follow-up. The number of immunological tests was done for evaluation of humoral and cellular immunity in those suffering from latent tuberculous infection and active disease.Results. The obtained results showed high negative prognostic relevance of exposure to tuberculosis, concurrent disease, refusal to have preventive treatment and low efficiency of short-course preventive treatment, specific features of humoral and cellular immunity were defined which could be used as additional forecasting criteria for active tuberculosis development in children with latent tuberculous infection.

Problem of differential diagnostics of granulematous diseases remains actual till nowadays. Despite the use of modern radiological, microbiological, immunological and routine morphological methods they don’t allow always to formulate correct diagnosis. Use of immunechistochemistry frequently reveals the pathogen, this is very important to elaborate the tactic of patients treatment. In the paper are clinically characterized 17 cases in which clinical and laboratory data allowed to exclude tuberculosis and sarcoidosis. Are presented morphological data concerning mycoplasmosis (4) and chlamydiosis (4). As an example are given the details related to the first in the literature observation of respiratory granulematous chlamydiosis.

Treatment of multiple drug resistant tuberculosis presents a serious challenge. Use of perchlozon (thioureidoiminomethylpyridini um) in the combination with the other five anti-tuberculosis drugs during 6 months of treatment allowed achieving cessation of bacillary excretion and X-ray improvement in all patients from the main group. Monitoring and evaluation of adverse events have not detected any confident difference in the number of adverse events apart from endocrine and allergic ones while taking perchlozon in the combination with other drugs. All adverse events were minor and moderate as regards severity degree and were managed by symptomatic treatment and did not cause cancellation of the drug. The obtained results will promote achieving the high tuberculosis treatment effciency by the end of the main chemotherapy course and this will require further investigation.

Combination of TB and HIV-infection is still the most nowadays important problem, and it connects not only with steady growth of HIV infection, but with difficulties in TB diagnosis. X-ray lung studies often have unusual nature, clinical symptomatology appears when process are hard and spread. At the same time in global practice IGRAtests applying, to which they belong to SPOT.TB test and QuantiFERON®-TB Gold test, they pay great attention to it, particularly among patients with HIV- infection. In study there were data when 41 patients with lung TB were examined, 56 HIV-positive patients with lung TB and 58 healthy donors. When active TB IGRA-test and test with Diaskin test show comparable same results. Against the backdrop of HIV skin tests (Mantoux test with 2 TE and tests with Diaskin test) it was demonstrated direct dependence of level immunosuppression in contrast to IGRA – tests, that allows to carry out these researches in conditions when standard skin tests do not work.

The articles presents materials of the three defended and approved doctor’s dissertations, devoted to individual approaches to children ill with tuberculosis and having the risks of developing tuberculosis depending on social conditions, state of the host, cellular and molecular-genetic levels. The options of working with children and adolescents being within the studied categories, basing on the innovative computer technology have been o|ered. The examples are given how the innovative approaches have been introduced into the practical works of pediatricians and TB pediatricians.

According to the WHO data, tuberculosis still represents a serious public health problem worldwide. Deterioration of socio-economic conditions in the population complicates epidemic situation for tuberculosis inRussia, thus leading to increase in acute progressive and complicated forms of tuberculosis in children and, consequently, to worsening structure of its clinical forms. Objectives: to determine associations between certain HLA-DRB1 alleles and risk of tuberculosis development in children. We examined 188 children aged from 3 to 14 years with various manifestations of tuberculous infection. Along with thorough examination of the patients, including multi-spiral CT scans of chest, we undertook genotyping of HLA-DRB1 alleles. Activity of tuberculous infection was determined by a set of immunological tests, i.e., tuberculin skin test, DIASKINTEST® (recombinant allergen of tuberculosis DIASKINTEST®). X ray diagnostics was performed with multi-spiral «Aquilion-32» computed tomograph (Toshiba), according to standard procedures. Molecular genetic typing of HLA-DRB1 alleles was performed by polymerase chain reaction (PCR-SSP), using standard commercial kits PROTRANS Ceclerplate System Protrans HLA-DRB1*. The children were divided into two groups: I group, 90 healthy children, II group, 98 children with tuberculosis. A comparisons group consisted of healthy donors (n = 346). Statistical processing of genetic material included evauation and analysis of the following parameters: frequency distribution of the antigen (F), χ2 criterion for significance (chi-square), the relative risk ratio (RR), etiologic fraction (EF), preventive fraction (PF). Children of the II group had significantly higher *04 allele HLADRB1*, as compared with control group (36.7% vs. 21.1%, χ2 = 10.08; р < 0.01). This finding may suppose a predisposal of these allele carriers to development of tuberculosis. At the same time, the rates of *07 (14.3% vs. 27.5%, χ2 = 7.15, р < 0.01) and *15 (18.4% vs. 28.3%, χ2 = 3.92; р < 0.01) HLA-DRB1* alleles were significantly lower, thus suggesting a protective effect of this allele. *04 allele seems to be a predisposing factor, whereas *07 and *15 alleles are protective for development of tuberculosis in children.

adolescents. Fluorography is the basic method used as usual to detect tuberculosis in adolescents. The use of diaskintest in the diagnosis of tuberculosis infection in adolescents has reinforced its high informative value. The test was positive in 96.7% of the patients with tuberculosis and could reveal dormant tuberculosis infection in 29.2% of the cases. In the patterns of its clinical forms, there is a preponderance of secondary tuberculosis (infiltrative forms, including those with bacterial excretion); most (64.3%) cases show multidrug resistance (MDR) in Mycobacterium tuberculosis (MBT). Accelerated methods for determining MBT resistance in a number of patients can reveal MDR in MBT in early periods, which allows antituberculosis therapy to be timely corrected. Multidrug-resistant pulmonary tuberculosis is characterized by severe clinical symptoms and multisegmental destruction in the lung.

The paper analyzes changes in the pattern of clinical forms of registered tuberculosis cases, in the proportion of detected complications and phases of the specific process in children in 2007 to 2012. The findings were compared with registered morbidity rates and changes in the set of performed examinations [introduction of diaskintest (DST) and computed tomography (CT)] in 5 areas of the North-Western Region of the Russian Federation. There was a rise in the notified number of children with tuberculosis in some areas and a decline in the others, which is due to different frequencies to use DST and CT in the diagnostic complex. The wide introduction of CT may be a cause of more frequent detection of the specific process in the phase of involution and calcification because standard radiographic techniques used in the early stages of the specific process fail to diagnose these changes. The findings suggest the untimely detection of the disease and necessitate an improvement in the screening of children for the early manifestations of tuberculosis infection.

Diagnosing tuberculosis in children is very difficult. There are no clear diagnostic criteria for intrathoracic lymph node (ITLN) tuberculosis, the most common form of tuberculosis in children (78%). Current immunological methods used in combination with computed tomography make it possible to characterize a child’s status more clearly and to establish a correct diagnosis. The positive results of immunological tests in the presence of Mycobacterium tuberculosis infection require a set of radiological examination. ITLN tuberculosis is characterized by the fact that one group or more contains single or multiple ITLNs that measure more than 5 cm and differ in structure and density in the presence of positive immunological tests (Diaskintest and QuantiFERON test).

Two-hundred-eleven patients 3 to 14 years old (mean age 8.60±0.22 years) were observed and clinically evaluated at the Department of Pediatric Phthisiopulmonology, St.Petersburg Institute of Phthisiopulmonology during 2011-2013. The diagnostic protocol included: clinical data, X-rays diagnostics and immunologic assessment. All the patients were examined by DIASKINTEST® (DST) and QuantiferonTB Gold (QFT-G). They were divided into 2 groups, as based on laboratory data, as follows: group I (n= 63), patients with negative DST and QFT-G results; group II (n = 148), with positive results of specific tests. The study was aimed for intergroup comparisons of immune response markers. Positive results of DST and QFT-G suggested clinical activity of tuberculosis infection and are associated with high scores of tuberculin skin test (TST); increased cytokine levels (TNFα, IL-2, IFNγ), higher percentage of CD3+, CD4+ и CD95+ cells, elevated levels of specific IgG antibodies (anda TB ELISA); high titers of complement fixation test for mycobacteria, and activation of neutrophils. Positive results of DST and QFT-G in the patients are more often associated with active infection.

Present study has revealed low diagnostic value of Mantoux test with 2 TE in detection of tuberculosis in MBT-infected children, thus requiring implementation of novel methods. Detectable activity of tuberculosis infection among observed children with low tuberculin sensitivity was found in 23.8% of cases, as revealed by Diaskin test, as compared to 42.7% cases in a group with moderate sensitivity to tuberculin. As shown by radiological data it was accompanied by enlargement of intrathoracic lymphatic nodes in 14.3% and 53.0% cases, respectively. The data obtained with Diaskin probe were confirmed by a reference QuantiFERON testing in 95% cases. Parameters of diagnostic value for Diaskin test are two-fold higher than for Mantoux test with 2 TE. Positivity for Diaskin test reflects activity of tuberculosis infection which is accompanied by clear clinical signs in 67.3% cases, and, in 80% cases, it ischaracterized by enlargement of intrathoracic lymphatic nodes as based on radiologic data, thus arranging a risk group for tuberculosis morbidity in children. Appropriate recommendations for these patients include a fullscale phthisiatric assessment and administration of well justified and adequate therapy.

Therapy in pregnant women with tuberculosis always presents certain difficulties and sets regarding not only the status of the mother, but also that of her baby. Tuberculosis and pregnancy have been mostly recently considered to be incompatible. The presented clinical case provides evidence that therapy can be performed during pregnancy and can yield a good clinical result in the course of a specific process in the mother and in the adequate intrauterine development in the baby. There is a need for adequate combination therapy with regard to the susceptibility of isolated Mycobacterium tuberculosis, the status of the mother and the baby, and the constant patient monitoring by a phthisiatrician and an obstetrician/gynecologist.

Simple Summary: Bioinformatic analysis of molecular mimicry is an important step in predicting the development of autoimmunity. The checking of microbial peptides for possible cross-reactivity can be useful for the development of safe vaccines and more effective immunotherapy. When analyzing autoantibodies in patients with pulmonary tuberculosis, we found a high level of antibodies to modified citrullinated vimentin (anti-MCV compared to other antibodies. Patients also had high levels of antibodies to C3 fragments of complement and rheumatoid factors in the absence of any rheumatic or autoimmune diseases. Some common pentapeptides are related to immunoreactive epitopes of Mtb antigens. We found that the bioinformatic data correlate with our earlier studies of the levels of relevant autoantibodies in the sera of tuberculosis patients. Our findings on cross-reactivity and sequence similarity between the Mtb proteins and human autoantigens provide support for the role of antigen mimicry in TB-related autoimmunity. Comorbidities in tuberculosis patients are increasing annually. Autoimmune pathology may influence the diagnosis and treatment of tuberculosis (TB). However, the molecular mimicry between Mycobacterium tuberculosis (Mtb) and human autoantigens is an important provocative factor in the development of autoimmunity on one hand. Mtb has already been widely discussed as a provocateur of autoimmunity in humans. The aim of this study was to determine whether molecular mimicry exists between Mtb antigens and human autoantigens previously demonstrated as targets of autoimmunity. Materials and Methods: We analyzed the level of antibodies in 19 patients with pulmonary tuberculosis. In all cases ELISA assays was used. Also, in parallel, we identified 29 similar pentapeptides between key Mtb antigens and human autoantigens. Bioinformatic methods were used in this study. All amino acid sequences of MT antigens and human autoantigens were obtained from the UniProt database, and similar epitopes between Mtb antigens and human autoantigens were identified using the original "Alignmentaj" program. The immunoreactivity of the shared pentapeptides in Mtb antigens was evaluated with use of the IEDB database. Results: The high level of antibodies to modified citrulinated vimentin (anti-MCV) was most frequently detected (57%) in comparison with other antibodies. Elevated levels of antibodies to C3 complement fragments (47%) and rheumatoid factors (21%) in the absence of any rheumatic or autoimmune diseases are noteworthy. Several of the shared pentapeptides belong to the immunoreactive epitopes of Mtb antigens. The bioinformatic data correlated with our earlier studies of the levels of corresponding autoantibodies in the sera of TB patients. Conclusion: Our findings on cross-reactivity and sequence similarity between the Mtb proteins and human autoantigens provide support for the role of antigen mimicry in TB-related autoimmunity. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic inflammatory disease with an unknown etiology and a wide range of clinical manifestations. The incidence of sarcoidosis ranges from approximately 1 to 15 cases per 100,000 individuals per year worldwide. The significant variability in clinical presentations and target organs, as well as concomitant diseases, greatly complicates diagnosis. We analyzed articles in PubMed, Scopus, Cochrane Library, and Embase, where databases were searched using the keywords "chronic sarcoidosis", "diagnosis of sarcoidosis", "course of sarcoidosis", "pulmonary sarcoidosis", "cardiac sarcoidosis", "skin sarcoidosis", "neurosarcoidosis", "ocular sarcoidosis", and "autoimmune inflammation". Studies on the course and diagnosis of sarcoidosis with a deep search of ten years were included. In this review, we present an analysis of publications on the course and diagnosis of chronic sarcoidosis, as well as a clinical case. We have noted that the diagnosis of chronic sarcoidosis is particularly difficult due to the lack of specific biomarkers or their combination. The development and introduction of new diagnostic criteria for this disease will contribute to increasing the level of efficiency, not only of the diagnostic complex, but also the prognosis of the development and course of the pathological process. Conclusion: For the most accurate diagnosis and determination of prognosis, the existence of a single immunological or imaging marker with sufficient sensitivity and specificity is necessary. [ABSTRACT FROM AUTHOR]

Despite the achievements of modern medicine, tuberculosis remains one of the leading causes of mortality globally. The difficulties in differential diagnosis have particular relevance in the case of suspicion of tuberculosis with other granulomatous diseases. The most similar clinical and radiologic changes are sarcoidosis. The aim of this study is to apply mathematical modeling to determine diagnostically significant immunological parameters and an algorithm for the differential diagnosis of tuberculosis and sarcoidosis. Materials and methods: The serum samples of patients with sarcoidosis (SD) (n = 29), patients with pulmonary tuberculosis (TB) (n = 32) and the control group (n = 31) (healthy subjects) collected from 2017 to 2022 (the average age 43.4 ± 5.3 years) were examined. Circulating 'polarized' T-helper cell subsets were analyzed by multicolor flow cytometry. A symbolic regression method was used to find general mathematical relations between cell concentrations and diagnosis. The parameters of the selected model were finally fitted through multi-objective optimization applied to two conflicting indices: sensitivity to sarcoidosis and sensitivity to tuberculosis. Results: The difference in Bm2 and CD5−CD27− concentrations was found to be more significant for the differential diagnosis of sarcoidosis and tuberculosis than any individual concentrations: the combined feature Bm2 − [CD5−CD27−] differentiates sarcoidosis and tuberculosis with p < 0.00001 and AUC = 0.823. An algorithm for differential diagnosis was developed. It is based on the linear model with two variables: the first variable is the difference Bm2 − [CD5−CD27−] mentioned above, and the second is the naïve-Tregs concentration. The algorithm uses the model twice and returns "dubious" in 26.7% of cases for patients with sarcoidosis and in 16.1% of cases for patients with tuberculosis. For the remaining patients with one of these two diagnoses, its sensitivity to sarcoidosis is 90.5%, and its sensitivity to tuberculosis is 88.5%. Conclusions: A simple algorithm was developed that can distinguish, by certain immunological features, the cases in which sarcoidosis is likely to be present instead of tuberculosis. Such cases may be further investigated to rule out tuberculosis conclusively. The mathematical model underlying the algorithm is based on the analysis of "naive" T-regulatory cells and "naive" B-cells. This may be a promising approach for differential diagnosis between pulmonary sarcoidosis and pulmonary tuberculosis. The findings may be useful in the absence of clear differential diagnostic criteria between pulmonary tuberculosis and sarcoidosis. [ABSTRACT FROM AUTHOR]

Histiocytoses are rare diseases characterised by infiltration of affected organs by myeloid cells with a monocyte or dendritic cell phenotype. Symptoms can range from self-resolving localised forms to multisystemic lesions requiring specific treatment. To demonstrate extremely rare cases of CD68-negative cardiac histiocytosis with expression of SARS-CoV-2 antigen in infiltrate cells. We demonstrated a case of Erdheim–Chester disease in a 67-year-old man with pericardial involvement and positive dynamics with vemurafenib treatment, an autopsy case of xanthogranulomatous myopericarditis in a 63-year-old man, surgical material of xanthogranulomatous constrictive pericarditis in a 57-year-old man, and an autopsy case of xanthogranulomatosis in a 1-month-old girl. In all cases, xanthogranuloma cells expressed CD163, many of them spike protein SARS-CoV-2, while CD68 expression was detected only in single cells. In this article, we demonstrated four cases of extremely rare CD68-negative cardiac xanthogranulomatosis in three adults and one child with expression of the spike protein SARS-CoV-2 in M2 macrophages. This potential indirect association between COVID-19 and the development of histiocytosis in these patients warrants further investigation. To substantiate this hypothesis, more extensive research is needed. [ABSTRACT FROM AUTHOR]