Natal'YA V. Vlasenko

Relevance. Mass immunization of the population is the most reliable way to prevent infectious diseases, but its effectiveness depends on a number of conditions, both objective and subjective. One of the main subjective factors should be considered the attitude of the population towards the question of the expediency and safety of mass vaccination. Aim. of the study is to assess the state of public opinion regarding the immunoprophylaxis of infectious diseases in different population groups. Materials and methods. A survey of Moscow residents (N=1035) was conducted in order to determine their attitude to the problem of specific prevention of infectious diseases. To analyze the data obtained, a distribution was made based on the presence/absence of higher education and the age of the respondent – up to 40 years and over 40 years. The method of parametric standardization of indicators was used to compare the values of unequal samples. Results. It was found that 83.0 % of respondents have a positive attitude towards mass vaccination, 17.0 % have a negative attitude towards it. It is shown that 86.0 % of people under the age of 40 approve of mass vaccination, while only 76.8 % over the age of 40 approve. The main sources of information for respondents of all groups were: the attending physician, visual campaigning in medical institutions, as well as official information posted on the websites of the Ministry of Health and Rospotrebnadzor. The importance of the media in shaping public attitudes towards mass immunization is relatively small. The media was mentioned by 8.4 % as a source of information, regardless of its orientation. Conclusions. The results of the sociological survey indicate that society does not sufficiently assess the relevance of the problem of infectious diseases and the importance of mass immunization as the main tool for its prevention. Despite the availability of evidence base and official recommendations, 17% of respondents expressed distrust of vaccination and consider it dangerous, while 9.6% indicated that they were not interested in this topic. These data indicate a lack of public awareness, which may contribute to a decrease in vaccination coverage and, as a result, an increased risk of outbreaks of vaccine-preventable disease.

Aim: determination of alleles of HLA genes associated with autoimmune hepatitis (AIH) and overlap syndrome (OS) in the Russian population.Materials and methods. The study included 160 adult patients with a verified diagnosis of AIH or OS. The control group consisted of 320 conditionally healthy participants. A custom NGS panel was used to type the alleles of the HLA class I and II genes. The statistical analysis was carried out using Pearson’s χ² test with multiple FDR correction (p < 0.05). A logistic regression model was used to evaluate HLA alleles as predictors of the disease.Results. Alleles and haplotypes which frequencies have statistically significant difference in the study and control groups were identified. In the study group, alleles HLA-A*01:01:01 (OR = 2.15; 95 % CI: 1.43–3.23), HLA-B*08:01:01 (OR = 3.38; 95 % CI: 2.10–5.44), HLA-C*07:01:01 (OR = 1.90; 95 % CI: 1.30–2.78), HLA-DPB1*01:01:01 (OR = 3.22; 95 % CI: 1.58–6.55), DQB1*02:01:01 (OR = 3.11; 95 % CI: 2.06–4.70), HLA-DRB1*03:01:01 (OR = 3.03; 95 % CI: 2.02–4.55) were more common. Frequency of occurrence of the DQB1*03:01:01 allele in the study group was lower than in the control group (OR = 0.49; 95 % CI: 0.34–0.71). A logistic regression model was built, which was characterized by an accuracy of 0.688, a sensitivity of 0.487, and a specificity of 0.887.Conclusion. Alleles and haplotypes of HLA genes associated with AIH and OS were identified in a representative sample of the Russian population.

Literature data suggest that HLA alleles may be associated with the development of Sjögren's syndrome (SS) and the production of autoantibodies against the Ro/SSA and La/SSB antigens. However, such studies have not been conducted in Russia.Objective: to study the association between alleles of the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and the risk of developing SS and the production of autoantibodies.Material and methods. The study included 80 patients with SS or Sjögren's disease (SD). All patients met the ACR/EULAR criteria, 2016. AntiRo/SSA and anti-La/SSB autoantibodies were detected in 67 patients (83.8%), 37 patients had the combination anti-Ro/SSA/anti-La/SSB, 30 patients had only anti-Ro/SSA, and 13 patients did not have these antibodies. The control group consisted of 160 healthy blood donors without autoimmune diseases and without a family history of autoimmune diseases, who were comparable in gender and age to the patient group. High-throughput sequencing of the alleles of the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes was performed on the Illumina MiSeq platform using the MiSeq Reagent Kit v3. To amplify the exons of the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes, 56 specially designed primers containing Illumina adapters at the 5’ ends for subsequent indexing were used. Statistical data processing, including comparison of the frequencies of HLA alleles in the group of patients with SS/SD and in the control group, was performed in the Python software environment using the Numpy, Pandas and scikit-learn libraries.Results and discussion. In the group of patients compared to the control group we observed an increase in frequency for the alleles HLA-A*01:01:01 (OR=3.28, 95% CI [1.90–5.67], p Conclusion. A statistically significant association was found between several HLA alleles/haplotypes belonging to ancestral haplotype 8.1 (AH 8.1) as markers of susceptibility to SS and the production of Ro/SSA and La/SSB autoantibodies.

A serious problem on the way to creating population immunity is the anti-vaccination movement and medical diversions from immunization. The increase in the number of parental refusals to vaccinate is due to a number of reasons, one of which is the passive position of medical workers in promoting vaccination among the population, which is the result of insufficient awareness of this issue. In addition, the active activity of a mass and aggressive media campaign about the dangers of vaccinations also deals a blow to the creation of collective immunity. The purpose of the study: to identify the causes that affect the negative attitude of the population and medical workers to vaccination work and to evaluate measures aimed at an adequate attitude to vaccination. As part of the European Immunization Week, a survey of the population on immunoprophylaxis was conducted. It has been found that health workers are more committed to immunization for themselves and their children. At the same time, it is noted that persons with medical education can conduct subjective overdiagnosis, identifying unjustified contraindications to vaccination and signs of adverse reactions in themselves and their children. When comparing the causes of negative attitudes towards vaccination among medical workers and the population without medical education, it was revealed that for doctors the main causes are adverse reactions and post — vaccination complications that may appear after vaccination or have already been observed in the respondents. Thus, the conducted research made it possible to characterize the factors influencing the commitment of the Moscow population to immunoprophylaxis and identify priority areas for overcoming the formation of public opinion aimed at refusing preventive vaccinations.

Hepatitis B (HB) remains one of the serious medical and social health problems, and to assess the epidemiological situation, it is necessary to analyze the state of population immunity by collecting information on its intensity during serological studies. The aim of the work is to assess the level of population immunity against HB in the population of the Russian Federation in 2017 to 2022. Materials and methods. The results of serological monitoring for the presence of anti-HBs, provided by territorial laboratories of medical institutions of each subject of the Russian Federation in 2017 to 2022, were analyzed. The cohort of subjects in each subject of the Russian Federation consisted of persons in the age groups 3–4, 16–17, 20–29, 30–39, 40–49 years old, numbering at least 100 people each. The analysis of the obtained data for 6 years (2017–2022) was carried out using averaged data for every two years – 2017–2018, 2019–2020 and 2021–2022. The number of study cohorts during these time intervals was 88,151, 84,166 and 97,274 people, respectively. Results and discussion. The average values of the proportion of persons with immunity against HB were 69.0% in 2017–2018, 66.2% in 2019-2020 and 61.3% in 2021–2022. The highest proportion of people with protective immunity against hepatitis B was observed in the age group of 20-29 years. The proportion of children 3-4 years old who had anti-HBs detected at a concentration exceeding 10 IU/l was 65.8–72.5%, and 16–17 years old – 49.6–64.9%. The intensity of post-vaccination immunity against HB in children 16-17 years old should be considered insufficient. Conclusion. An analysis of serological studies results for the period from 2017 to 2022 showed that the potential of vaccine prevention of hepatitis B, carried out since 2006 within the framework of the priority National Project «Health», is not fully realized.

Relevance. It is known that the immune response to the administration of immunobiological drugs is variable and depends on the individual characteristics of the organism. Host immunogenetic factors have a significant impact on the effectiveness of vaccination. In this study, the frequencies of alleles of the HLA class I (HLA-A, B, C) and class II genes (HLA-DRB1, DPB1, DQB1) were studied in groups of participants with different levels of antibodies (anti-HBs) after vaccination against viral hepatitis B. Aims of the work was to determine the possible relationship between alleles of HLA genes and the intensity of post-vaccination immunity against hepatitis B. Materials and methods. The study included 271 apparently healthy adults who were divided into 3 groups depending on the specific concentration of post-vaccination antibodies (anti-HBs) using ELISA. All calculations were made relative to the groups anti-HBs >100 mIU/ml (n=82), 10-100 mIU/ml (n=98) (protective antibody level) and anti-HBs 2 goodness-of-fit test using the FDR multiple correction method with an initial target of p < 0.05. Results. When typing the six genes studied, the total number of alleles identified at least once was 189 variants that were distinct from each other. We identified 3 alleles (B*38:01:01, DQB1*06:03:01 and DRB1*13:01:01), which were significantly more common (FDR p < 0.05) in the group with a protective level of anti-HBsS. Also in this group there was an increased frequency of occurrence of alleles A*26:01:01, A*32:01:01, C*12:03:01, DPB1*04:01:01 and haplotypes DQB1*06:03:01 -DRB1*13:01:01 and B*38:01:01-C*12:03:01. In the group of seronegative patients, alleles A*02:01:01, A*03:01:01, B*44:02:01, B*44:27:01, C*07:04:01, DPB1*04 were more common :01:01, DQB1*05:01:01, DRB1*01:01:01 and DRB1*16:01:01. It was shown that the identified associations were more significant in the group of individuals with a concentration of post-vaccination anti-HBs above 100 mIU/ml. Conclusion. The results obtained indicate that the HLA alleles we identified may influence the level of anti-HBsS production, and that the genetic factor may, to a greater extent, determine whether the antibody level exceeds 100 mIU/ml. defined as an anti-HBS level of 10 mIU/ ml. The development of an integrated approach to the organization of vaccine prevention, including the determination of genetic markers, will improve the quality of immunization of the population. Information about the association of HLA gene alleles can be used to develop predictive scenarios for the development of the hepatitis B epidemic process.

Introduction. Hepatitis B virus (HBV) remains a pressing global public health concern. The clinical course of the disease, particularly its tendency towards chronicity and response to therapy, is significantly influenced by the HBV genotype and specific mutations. There is an imperative need for a straightforward, highly sensitive, and dependable method for whole genome sequencing of HBV. Objective. Development and testing of an amplification panel for HBV whole-genome sequencing. Materials and methods. We introduce an NGS amplification panel designed for genome sequencing of HBV on the Illumina platform. A panel consisting of 54 primers, divided into 2 pools and amplifying overlapping regions of the HBV genome up to 300 bp in length, was tested on 246 HBV DNA samples. Results. The studied samples represented a genotypic diversity of the virus, with a pronounced predominance of the genotype specific to the Moscow region: 216, 27, 2, and 1 sample were identified as genotype D, A, B, and E, respectively. Five samples contained at least one mutation associated with antiviral therapy resistance, and twenty-three samples contained at least one mutation associated with vaccine escape described in the literature. Conclusion. The present paper describes the stages of whole-genome sequencing of HBV, provides a laboratory protocol, nucleotide sequences of the primers and an approach to the data analysis. Using a list of clinical samples as example, the reliability of the panel is shown. The HBV panel holds immense potential for utilization in scientific research, epidemiological monitoring, and advancement of personalized medicine approaches.

Introduction. The design of studies aimed at finding the association between the genetic factor and the studied feature (disease) involves a comparison of the ratio of genotypes or allelic proportions in the study group with those in the control group. At the stage of determining the ratio of genotypes of the studied polymorphisms in the reference group, researchers meet a number of problems, which are the subject of the present work. Aim of the work is to provide scientific rationale for the feasibility of creating a national information system comprising genetic data of the relatively healthy population of Russia, incorporating its ethnic diversity. Materials and methods. The study group, total 1020 people, was genotyped for a number of single nucleotide polymorphisms of human genes. A comparative characteristic of the frequency distribution of the studied polymorphisms with those presented in international databases as reference data was carried out using χ2 index. Results. The frequency of SNP rs4986790 of the TLR4 gene significantly differs from the EUR population (p = 0.032) and the CEU subpopulation (p = 0.047). The allele frequencies of the rs1800795 (IL6) and rs1800896 (IL10) polymorphisms in the study population differ from the CEU subgroup (p = 0.030 and 0.012, respectively). The frequency of SNP rs2295119 (HLA-DPA2) in the study group is significantly different from the EUR population (p = 0.034). Conclusion. The analysis carried out in this work confirms the need to create a domestic information system containing data on the occurrence of SNP alleles and genotypes for a conditionally healthy population and in subgroups with various pathological conditions.