Search

2021 marks the 40th anniversary of the discovery of the hepatitis E virus by an outstanding Russian virologist, academician of the Russian Academy of Medical Sciences Mikhail Surenovich Balayan. This date is an occasion to remember this remarkable scientist and person, to analyze the current state of the problem of viral hepatitis E, to sum up the research results and to correct the prospects of scientific directions, the development of which is largely related to the basic foundations laid by M.S. Balayan.The scientific heritage of M.S. Balayan is associated with the study of poliomyelitis, hepatitis A and hepatitis E. The main contribution of Mikhail Surenovich Balayan to world science was the discovery of the hepatitis E virus. This is, in first place, associated with the significance of the results obtained and the high moral value of the experimental selfinfection with hepatitis E.The paper presents data on the study of virology, epidemiology, clinical course, diagnosis and prevention of hepatitis E. The main concepts and directions of studying hepatitis E are overviewed.

The problem of choosing a strategy to control hepatitis A in the Russian Federation remains relevant for the health care of our country. By strategy we mean a scientifically based program of action that defines the priorities and resources needed to effectively control hepatitis A.The aim of the work is to present a strategy to control hepatitis A in the Russian Federation, taking into account the realities of today. Based on the analysis of Russian and international studies, we present answers to the questions that should be addressed before the choosing a strategy to control hepatitis A in the Russian Federation. The low incidence of hepatitis A creates a false image of the favorable situation with this infection. The rationale is given to include vaccination against hepatitis A in the National Vaccination Schedule in the section of mandatory vaccinations. Routine vaccination of children aged 24 and 36 months will lay the foundation for future protection against this infection. We consider the creating a National Hepatitis A Vaccination Program as an important aim. The implementation of such a program will allow full control of hepatitis A in the Russian Federation.

Introduction. Hepatitis D (delta, 5) is caused by an RNA virus (hepatitis D virus, HDV) from genus Deltavirus, and is the most severe and difficult to treat disease among both viral hepatitis and infectious diseases in general. The development of HDV infection in the host organism is possible only in the presence of hepatitis B virus (HBV). Coinfection with HBV and HDV is associated with a more rapid progression of chronic viral hepatitis (CVH) to liver cirrhosis (LC) and an unfavorable outcome in comparison with HBV monoinfection. Data on the influence of clinical, biochemical and virological factors on the infectious process in patients with hepatitis D are limited due to the insufficient amount of research on this theme. The study aimed to determine demographic, clinical, biochemical, and virological factors influencing the course and progression of CVH D in patients followed during 10 years, residing in the territory of the Tuva Republic, one of the endemic regions of the Russian Federation. Material and methods . Changes in clinical and laboratory parameters were analyzed in dynamics in 121 HDV infected patients with a different course of the disease, who were under observation from 2009 to 2019. Three groups of patients were identified: group 1 - 61 patients with disease progression of chronic hepatitis to LC (Child-Pugh class B-C), group 2 - 49 patients with non-progressive chronic hepatitis, and group 3 - 11 patients with slowly progressive LC (class A). Demographic data, the presence of detectable HBV DNA, indicators of the functional state of the liver: alanine aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and total bilirubin content were analyzed. The severity of hepatic encephalopathy was assessed by the duration of the numbers connection test (NCT). Results. All patients belonged to the same ethnic group (Tuvinians), were infected with HDV genotype 1 and were positive for HDV RNA throughout the entire follow-up period. There were no significant differences in sex ratio and mean age at the time of inclusion in the study between the groups. In group 1, the average number of years from inclusion in the study to the formation of LC was 3.65 ± 2.3 years, years to the lethal outcome: 4.5 ± 3 years. Significantly higher levels of AST/GOT, ALP, GGT, total bilirubin (TB) and NCT grade were found in group 1 compared to group 2. ALT/GPT levels did not differ significantly in these groups. When comparing groups with disease progression and slowly progressive LC (groups 1 and 3), no significant differences were found in any of the clinical and biochemical parameters. ALT/GPT, GGT, TB and NCT values were significantly higher in patients with slowly progressive LC (group 3) compared to group 2. No differences in AST/GOT and ALP levels were found between these groups. Detectable HBV DNA was significantly more frequent in patients with progressive disease and with chronic viral hepatitis than in patients with slowly progressive LC. There were no significant differences in the frequency of HBV DNA detection in patients from groups 1 and 2. Conclusion. The results obtained on a relatively homogeneous cohort demonstrated that age and gender are not the factors influencing the progression of chronic viral hepatitis D to cirrhosis. The lack of detectable HBV DNA is associated with the slow progression of LC. The revealed differences in clinical and biochemical parameters reflect the degree of functional liver damage in chronic viral hepatitis D and HDV-associated cirrhosis.

Hepatitis B virus (HBV) is a partially double-stranded DNA virus that specifically targets hepatocytes. It is considered a major health issue due to its high prevalence and the life-threatening consequences of chronic infection, including liver cirrhosis and hepatocellular carcinoma. Despite widespread vaccination against HBV, millions of people live with chronic HBV infection. Existing antiviral therapies fail to achieve full HBV elimination, so most patients with the disease require lifelong treatment. The search for new antiviral therapy strategies is hindered by the limited availability of in vitro HBV infection models that are able to support the full HBV life cycle. Therefore, the development and optimization of cellular models are crucial to the search for drugs effective against HBV. In this study, we optimized an in vitro HBV infection model consisting of two cell lines: HepAD38 cells, which are able to produce infectious HBV; and HepG2-NTCP cells, which are susceptible to HBV infection. We showed that prolonged production of HBV in the "donor" cells and HBV inoculation of the "acceptor" cells simultaneously with seeding improves the established procedure. This modified protocol was proven effective in experiments involving compounds with known activity against HBV, suggesting its utility for future high-throughput screening. Keywords: HBV; HBV in vitro models; HepG2-NTCP; HepAD38.

Hepatitis D (delta, δ) virus (HDV) was discovered more than 40 years ago, but the understanding of its origin and evolution is poor. This is mainly due to the lack, until recently, of data on the existence of any viruses similar to HDV. The discovery in recent years of sequences of new delta-like agents in a wide range of vertebrate (Vertebrata) and invertebrate (Invertebrata) species has facilitated a revision of views on the origin of HDV and contributed to understanding the place of this unique virus among other animals’ viral agents. The purpose of this review is to analyze the latest published data on new delta-like agents and their biological characteristics.

Various deer species are infected with hepatitis E virus (HEV) and may be a source of zoonotic infection for humans. So far, HEV has not been isolated from reindeer and the role of this domesticated deer species in HEV transmission is unknown. We tested serum samples from 191 reindeer (Rangifer tarandus) and 86 adult reindeer herders from the circumpolar regions of Yakutia (Russian Federation) for anti-HEV and HEV RNA. Anti-HEV IgG prevalence was 12.0% (95% confidence interval [95% CI]: 8.1-17.5) in reindeer and 4.7% (95% CI: 1.5-11.7) in reindeer herders. The latter was similar to the positivity rate observed in adult residents of the city of Yakutsk, the capital of Yakutia, who do not have routine contact with reindeer (3.7% [19/519, 95% CI: 2.3-5.7]). No samples positive for HEV RNA were identified. The study provides evidence of HEV circulation in reindeer. Nevertheless, the low seroprevalence in reindeer herders indicate a low risk of zoonotic HEV infection.

The most significant processes of arbovirus evolution can be expected to occur in the territories where ticks of different species cohabitate and at the boundaries of virus occurrence, where the probability of the appearance of new virus variants is high due to the possible shift in the main vectors and/or vertebrate hosts. One of the most interesting regions in this regard is the Republic of Tuva. Since most of its territory is covered by mountain ranges and intermountain basins, we were able to study the distribution of vectors and viruses in geographically isolated areas at different altitudes and in various landscapes. From 2008 to 2017, we conducted six expeditions to Tuva and collected 3,077 adult ticks and 24 nymphs. The distribution of tick species was confined to specific landscapes, as follows: Dermacentor nuttalli occurred in steppes, D. silvarum inhabited forest-steppe areas, and Ixodes persulcatus inhabited mixed forests. All three species of ticks were collected on plains and mountain slopes. The range of D. silvarum was shown to be lower than 1300 m above sea level (a.s.l.). Only D. nuttalli and I. persulcatus were collected at higher altitudes. According to our observations, single nymphs of D. nuttalli appear on animals one month before larvae appear. This finding confirms the hypothesis that the immature forms of D. nuttalli are able to overwinter under favourable conditions. We isolated 9 strains and 3 isolates of tick-borne encephalitis virus (TBEV) from I. persulcatus, one strain from D. nuttalli and one strain from D. silvarum. The TBEV strain from D. nuttalli was isolated from the territory inhabited only by Dermacentor ticks. All isolated strains belong to the Siberian subtype of TBEV. TBEV was detected in ticks from all the investigated altitudes. There were no statistically significant differences in the virus prevalence between the Dermacentor and Ixodes ticks. The results of our work provide additional support for the hypothesis of the existence of TBEV foci in areas with an absolute dominance of D. nuttalli.

Aim. The development of the hepatitis E virus (HEV) genotype 3 recombinant capsid protein. Materials and methods. E.coli strains, plasmid vectors, serological and clinical samples, ELISA reagent kits, molecular biological, bioinformatic, biotechnological, biochemical and serological methods. Results. Using viruscontaining material from pigs of Belgorod region (Russian Federation) we made E.coli strains producing recombinant capsid protein, containing C-terminal of viral ORF2 protein fragment fused to E.coli β-galactosidase. Recombinant protein ORF2 had been isolated from the bacterial inclusion bodies and purified by size exclusion chromatography. Antigenic specificity of the recombinant polypeptide was confirmed by ELISA and Western blotting with sera of hepatitis E patients and reference groups (healthy donors, patients with hepatitis A, B, C, infectious mononucleosis, cytomegalovirus infection and HIV-infected patients). Conclusion. HEV genotype 3 ORF2 recombinant antigen had been developed, and the possibility to use it in diagnostic tests had been experimentally shown.

Aim. Design аис1 construction of the hepatitis E virus (HEV) genotype 3 full-size ORF3 recombimnt polypeptide. Materials and methods. Escherichia coli strains, ptasmid vectors, serologiral and biological amples, molecular biological, bioinformatic, biotechnological, biochemical and serological methods.Results. RNA was isolated from pig fecal extracts collected on Belgorod farms and was used in RT-PCR to obtain the fragment of the orf3 gene of the hepatitis E virus genotype 3. Using A/T-cloning a recombinant plasmid was obtained with insertion of a DNA fragment (230 bp) encoding the N-terminal region of the ORF3 protein. The primary structure of the missing C-terminal region of the ORF3 VGE of the genotype 3 was calculated by bioinformatics methods. Codon optimization of the sequence for biosynthesis in E.coli cells was performed. For constructing the recombinant plasmid a chemically synthesized DNA fragment encoding the fulllength ORF3 protein had been used. E.coli strain producing full-size recombinant protein ORF3 fused to E.coli beta-galactosidase was developed. Recombinant protein ORF3 had been isolated from the inclusion bodies of the E.coli biomass and purified by size exclusion chromatography. Antigenic specificity of recombinant polypeptide had been confirmed in immunochemical reactions (ELISA, Western blot) with sera from patients with hepatitis E and control groups of patients. Conclusion. HEV genotype 3 ORF3 recombinant antigen had been designed, and itfs applicability in diagnostic tests had been experimentally confirmed.

Since August 2012, universal single-dose vaccination in children aged at least three years has been implemented in the Republic of Tuva, which was previously the region most affected by hepatitis A in Russia. The objective of this cross-sectional study was the assessment of the immunological and epidemiological effectiveness of vaccination program five years following its implementation. In the pre-vaccination period, anti-HAV antibody detection rates in Tuva was 66.0% [95% CI: 56.3&ndash, 74.6%] in children aged 10&ndash, 14 years and reached a plateau (&gt, 95%) by age 20&ndash, 29 years. Annual incidence rates in children under 18 years of age peaked at 450&ndash, 860 per 100,000 in pre-vaccination years but dropped to 7.5 per 100,000 in this age group and to 3.2 per 100,000 in the total population one year after the start of vaccination. Since 2016, no cases of hepatitis A has been reported in Tuva. Serum anti-HAV antibodies were quantified in samples from healthy children following single-dose vaccination. Protective anti-HAV antibody concentrations (&ge, 10 mIU/mL) were detected in 98.0% (95% CI: 96.2&ndash, 99.0% (442/451)) of children tested one month after single-dose immunization, in 93.5% (95% CI: 91.0&ndash, 95.4% (477/510)) and in 91.1% (95% CI: 88.2&ndash, 93.4% (422/463)) of children one year and five years after single-dose immunization, respectively. Anti-HAV antibody geometric mean concentrations were similar in sera collected one month, one year, and five years following single-dose vaccination: 40.24 mIU/mL, 44.96 mIU/mL, and 57.73 mIU/mL, respectively (p &gt, 0.05). These data confirm that single-dose vaccination is an effective method of bringing hepatitis A under control in a short period of time in a highly endemic region.

The purpose of study was to establish risk group on hepatitis C in conditionally healthy population of the Belgorod oblast. Total 2025 conditionally healthy inhabitants aged between 1 and 99 were surveyed and serum samples from them were tested. There were eight age groups: 1-14 years (12.3%), 15-19 years (13.1%), 20-29 years (12.7%), 30-39 years (12.8%), 40-49 years (12.8%), 50-59 years (11.8%), 60-69 years (8.6%) and over 70 years of age (15.7%). Overall, 44.6% of the examined persons were male. 41.3% (ranging from 6.5 to 72.1%) of respondents reported surgery in their anamnesis, 5.1% (ranging from 0.8 to 12.6%) had blood/blood products transfusion, 10.3% (ranging from 1.7 to 57.9%) ear/nose piercing and 2.96% (ranging from 0.8 to 6.6%) tattoos. There were no people who injected drugs. The piercing was significantly higher in age groups 15-19 years and 20-29 years than other age groups (p-value

Overall incidence of toxocariasis in Russia is low and varies between 1.6 and 2.7 per 100,000, while in several hyper-endemic regions, such as Altay, Kurgan, Perm and Udmurtia, it reaches 43 per 100,000. The seroprevalence of toxocariasis in published references was on average 16% and varied across the regions of Russia from negligible in North Siberia to 40% in southern regions of West Siberia. Seroprevalence in adults in five regions of Russia identified in this study was on average 20%, and varied from 3% in Yakutia (north of East Siberia) to 36% in Rostov-on-Don, South Russia. There was no correlation between seroprevalence and reported incidence of toxocariasis; however, the pattern of seroprevalence variation could be linked to Toxocara prevalence in dogs. Toxocariasis seroprevalence has more than doubled over the last 20 years. Diagnostic antibody titres (1:800 or more) were found in 3.6% of sera, suggesting about five million of acute Toxocara invasions per year.

Introduction . Belgorod region is the territory with the highest incidence of hepatitis E in the Russian Federation. The aim of the study was to comprehensively characterize the circulation of hepatitis E virus (HEV) in the Belgorod region, including the study of population immunity to the virus, determining the prevalence of infection among the pig population and analysis of the genetic diversity of HEV from patients and animals. Material and methods . Serum samples of a conditionally healthy population ( n = 2027) of all age groups were tested for anti-HEV IgG and IgM by ELISA with commercial assays. HEV RNA was determined in fecal samples from pigs aged 2–4 months (n = 526), in sewage samples from pig farms ( n = 10), as well as in stool samples from patients with hepatitis E ( n = 6) using reverse transcription polymerase chain reaction (RT-PCR). Phylogenetic analysis was performed for an amplified 300 nt fragment corresponding to HEV open reading frame 2. Results and discussion . The prevalence of anti-HEV IgG in general population averaged 16.4% (95% CI: 14.8–18.1; 332/2027). The proportion of individuals who had both anti-HEV IgM and IgG averaged 2.8% (95% CI: 2.2–3.6; 57/2027). The incidence rate of anti-HEV IgG increased with age, from 2.8% (95% CI: 1.3-5.8) in children aged 1–14 years to 40.1% (95% CI: 34.9-45.6) in people 70 years or older. The detection rate of HEV RNA in pigs was 20% (95% CI: 16.8-23.6; 105/526). HEV RNA was detected in 2 out of 10 sewage samples. The HEV sequences isolated from patients with hepatitis E, pigs, and sewage samples in Belgorod region belonged to the HEV genotype 3, had a 95-100% homology, and formed common clusters on a phylogenetic tree. Conclusions. The high prevalence of HEV in pigs population has led to the formation of an endemic territory in the Belgorod region, which is the center of pig breeding. Measures aimed at reducing the circulation of HEV among pig population and decontamination of sewage from pig farms are necessary to control HEV infection.

The Hepatitis E (HE) is a viral liver disease that is common on all continents at different rates and very frequently is not symptomatically distinguishable from other viral hepatitis, such as hepatitis A, B and C, as well as from other infectious diseases referred to as "acute jaundice syndrome". The GE-anthroponosis (in the case of infection caused by genotypes 1 or 2 of hepatitis E virus) or anthropozoonosis (in the case of infection caused by 3 or 4 viruses) is predominantly propagated through fecal-oral transmission. The article presents the general characteristics of VGE, human risk factors and means of prevention. The particular attention is paid to the development of complex of anti-epidemic, hygienic and veterinary sanitary measures in the Belgorod Oblast.

Aim. The development of the hepatitis E virus (HEV) genotype 1 recombinant capsid protein. Materials and methods. Escherichia coli strains, plasmid vectors, serological and clinical samples, ELISA reagent kits, molecular biological, bioinformatic, biotechnological, biochemical and serological methods. Results. Using HEV genotype 1 DNA copy of subgenomic virus RNA we made E.coli strains producing recombinabt capsid protein, containing C-terminal fragment of ORF2 protein fused to E.coli beta-galactosidase. Recombinant protein ORF2 had been isolated from the inclusion bodies of the E.coli biomass and purified by size exclusion chromatography. By Western blotting it had been shown specific interaction of the recombinant polypeptide with anti-HEV IgG from pool of positive sera. Antigenic specificity of the recombinant polypeptide had been confirmed by enzyme-linked immunosorbent assay with sera of hepatitis E patients and reference groups: healthy donors, patients with hepatitis А, В, C, infectious mononucleosis and cytomegalovirus infection, HIV-infected patients. Conclusion. HEV genotype 1 ORF2 recombinant antigen had been developed, and its possible use in diagnostic tests had been experimentally shown.

Aim. Experimental reproduction of HEV-infection in mini-pigs and comparative analysis of virological and immunological characteristics of experimental infection. Materials and methods. Wiesenauer minipigs (2 females and 4 males, age 50 - 60 days, weight 5-10 kg) were infected by HEV genotype 3 strain isolated from swine feces in Belgorod region in 2013. The virus was administered as a 10% clarified feces extract (800 pi). Blood (weekly) and feces (daily) were sampled from the animals for 49 days. Anti-HEV IgG were determined in sera samples using DS- ElA-ANTI-HEV-G (Diagnostic Systems) system, HEV RNA in samples of feces extracts and blood sera - RT-PCR. Results. Wiesenauer minipigs were sensitive to HEV genotype 3 infection, infection developed in all the animals after administration of the virus, that was accompanied by the presence of HEV RNA in feces for 2 weeks and seroconversion by anti-HEV. Comparative analysis of virological characteristics of experimental H EV-infection in mini- and standard pigs has shown, that the duration of the infection in mini-pigs is shorter, and seroconversion by anti-HEV occurs earlier. Conclusion. Sensitivity to HEV genotype 3 and lower weight make mini-pigs a comfortable alternative to standard swine and primates for modelling HEV infection in vivo.

Aim. To determine of the prevalence of viral hepatitis A, E, B, C and D markers in migrant workers. Materials and methods. Blood serum samples from 1,333 migrant workers recently arrived in Russia from Uzbekistan (n = 464), Tajikistan (n = 415), Ukraine (n = 308) and Moldova (n = 146) were analyzed. Anti-HAV IgG, anti-HEV IgM and IgG, HBsAg, anti-HBV and anti-HCV were tested using commercial ELISA tests. Results. The frequency of HBsAg detection was significantly higher among migrants from Tajikistan and Uzbekistan (5,3% and 5,2%, respectively) compared to migrants from Ukraine (1,0%) and Moldova (3,4%). No anti-HDV was detected in any positive HBsAg sample. The rate of anti-HCV detection was high regardless of the country of origin: 4,5% (Uzbekistan), 4.8% (Tajikistan), 3,9% (Ukraine), 4,8% (Moldova). Anti-HEV IgG was significantly higher in migrants from Uzbekistan and Tajikistan compared to those from Ukraine and Moldova (25,4% and 43,1%, vs. 7,8% and 12,3%, respectively, p

Background Age cohort screening for hepatitis C virus (HCV) might be an effective strategy if the majority of undiagnosed cases are concentrated in a particular age group. The objective of this study was to determine HCV prevalence in different age cohorts of the general population in the Central European part of Russia and second, to assess feasibility of HCV antigen testing for community screening programs. Methods Sera from 2027 volunteers were tested for anti-HCV (Architect Anti-HCV, Abbott Laboratories). All anti-HCV reactive samples were confirmed in an immunoblot and tested for HCV Ag (ARCHITECT HCV Ag, Abbott Laboratories), HCV RNA and HCV viral load. Results Out of 31 individuals with anti-HCV reactive result, 22 (71%) were confirmed by immunoblot, six were false positives and three were indeterminate. Active infection was observed in 73% of anti-HCV confirmed positives. Five out of 16 individuals had low HCV-RNA levels (

Universal hepatitis B vaccination of newborns was implemented in Russia starting from 1998. From 1998 to 2019, the incidence of acute hepatitis B reduced from 43.8 to 0.57 cases per 100,000 population. Here, we assessed the timely coverage of newborns with the birth dose (HepB-BD), second dose (HepB-2nd), and three vaccine doses (HepB3) in two remote regions of Russia with low (Belgorod Oblast) and high (Yakutia) levels of hepatitis B virus (HBV) endemicity. Vaccination data were obtained from the medical records of 1000 children in Yakutia and 2182 children in Belgorod Oblast. Sera of healthy volunteers from Belgorod Oblast (n = 1754) and Yakutia (n = 1072) across all age groups were tested for serological markers of HBV to assess the infection prevalence and herd immunity. Average HepB-BD coverage was 99.2% in Yakutia and 89.4% in Belgorod Oblast (p &lt, 0.0001) and in both regions varied significantly, from 66% to 100%, between medical centers. The principal reason for the absence of HepB-BD was parent refusal, which accounted for 63.5% of cases of non-vaccination (83/123). While timely HepB-2nd coverage was only 55.4%&ndash, 64.7%: HepB3 coverage by the age of one year exceeded 90% in both study regions. HBV surface antigen (HBsAg) prevalence in the 1998&ndash, 2019 birth cohort was 0.2% (95% CI: 0.01&ndash, 1.3%) in Belgorod Oblast and 3.2% (95% CI: 1.9&ndash, 5.2%) in Yakutia. The proportion of persons testing negative for both antibodies to HBsAg (anti-HBs) and antibodies to HBV core antigen (anti-HBc) in the 1998&ndash, 2019 birth cohort was 26.2% (125/481) in Belgorod Oblast and 32.3% (162/501) in Yakutia. We also assessed the knowledge of and attitude towards vaccination among 782 students and teachers of both medical and non-medical specialties from Belgorod State University. Only 60% of medical students knew that hepatitis B is a vaccine-preventable disease. Both medical and nonmedical students, 37.8% and 31.3%, respectively, expressed concerns about safety and actual necessity of vaccination. These data indicate the need to introduce a vaccine delivery audit system, improve medical education with respect to vaccination strategies and policies, and reinforce public knowledge on the benefits of vaccination.

Aim. Determine spread of hepatitis C vims genotypes, circulating in Moscow Region over the last decade. Materials and methods. The presence of HCV RNA, genotype and subtype of the vims were determined in blood sera samples obtained in 2006 - 2014 from 2847 individuals with the presence of HCV infection, who had or did not have injectable dmg administration in anamnesis. Results, lb and 3a remain the main subtypes, circulating in the population over the last decade. A notable reduction of la subtype circulation took place among injectable dmg users (IDU). Recombinant form RFl_2k/lb of hepatitis vims is present only among this risk group and constitutes 2% of the overall amount of subtypes in both 2007 and 2014. Genotype 4d was detected in 2014, that is not typical for Russian Federation. Genotype 3a is dominant in IDU age groups of 20 - 29 and older than 40, and in the 30 - 39 group the main - subtype lb. Phylogenetic analysis has shown the lack of certain genetic variants of subtypes lb and 3a, characteristic for IDU, that gives evidence on a wide circulation of the main subtypes of the vims in the whole population of individuals, infected by HCV. Conclusion. Spread of main genotypes/subtypes of HCV in the overall population and among IDU in Moscow remains stable over the last decade.

Aim. Description of the first documented case of imported hepatitis E, associated with genotype 4 of HEV and introduced from southern France. Materials and methods. Clinical, epidemiologic and laboratory analysis of the imported case of disease of hepatitis E was carried out. Phylogenetic analysis of nucleotide sequences of HEV isolate, taken from the patient, was carried out. Results. Epidemiologic analysis allowed to assume imported character of the detected case of HEV-infection. Comparative analysis of nucleotide sequences of regions of the open reading frame 2 (300 nt) and open reading frame 1 (721 nt) of HEV genome, isolated from the patient, showed identity of this isolate with variants of genotype 4 HEV, isolated in France in 2009 - 2011 from patients with autochthonous hepatitis E. Conclusion. The results obtained confirm the case of import into Russia of genotype 4 HEV from south-eastern France (Corsica), where spread of this virus genotype is observed in recent years.

We developed a model of hepatitis E virus infection in common marmosets (Callithrix jacchus) and determined optimal route of infection, duration, clinical and virological characteristics of infection in laboratory animals. Using this model, we demonstrated that replication of hepatitis E virus primarily occurs in the liver, while virus replication presumed to take place in the intestine was not confirmed in this experiment.

Objective of the study is to analyze the influence of vaccination against hepatitis A on the corresponding morbidity rates in the Republic of Sakha (Yakutia). Materials and methods: statistical data contained in the statutory forms of the State statistical reporting on infectious diseases and preventive vaccination against hepatitis A in Yakutia, dated 1992 to 2015. Results and conclusions. Following selective immunization of high-risk groups, performed during the last 14 years in the Republic of Sakha, the incidence of hepatitis A has decreased by 38 times. According to the results of 2015, registered were 15 cases of infection, the rate being 1.6 per 100 thousand of the population, which was below the national average by 2.8 times. Assessment of the long-term dynamics has demonstrated the impact of preventive vaccination on the epidemic process of hepatitis A. Morbidity rates fall down with the increment of the numbers of immunized persons. Effect of the vaccination among the age group of 7 to 14 years is especially strong.

Data about efficacy of conducting of routine vaccination of children against Hepatitis A are presented in the article. The results of realization such strategy of vaccine prevention of Hepatitis A in selected regions of Russian Federation are evaluated. The perspectives of using this experience in other regions of the country is discussed.

Two tests for measurements of hepatitis B virus DNA in human serum and plasma, VERSANT HBV 3.0 (based on the use of branched DNA chains) and Biotitre-B (a real-time PCR variant), were compared. Serum specimens from patients (n=56) with documented viral hepatitis were tested. For specimens with DNA values in the linear range in both tests the correlations were evaluated by Pearson's method. The sensitivity of the two tests, and reproducibility of the results of HBV DNA measurements were evaluated using a panel of recombinant virus DNA dilutions with a step of 1 lg HBV DNA copies per ml (from 7 to 3 lg). Three measurements for each concentration of the reference sample were carried out in each test. Clinical specificity of the two tests was evaluated by the analysis of HBV-negative serum samples, collected from donors not reactive by HBsAg and anti-HBc (n=60). Of 56 samples with documented infection, the results of testing by VERSANT HBV 3.0 and Biotitre-B did not agree in 4 (7.1%) samples. Pearson's correlation coefficient of for results obtained in VERSANT HBV 3.0 and Biotitre-B in linear range for both tests was 0.712. Evaluation of reproducibility of the tests using a panel of recombinant HBV DNA showed higher reproducibility of VERSANT HBV 3.0 test with coefficient of variations from 0.79 to 2.79% vs. 2.39-10.69% for Biotitre-B reference test. All 60 serum samples from donors areactive by HBsAg and anti-HBc were negative by HBV DNA when tested by VERSANT HBV 3.0 and Biotitre-B. Hence, clinical specificity of both tests was 100%. The results indicate high specificity of both tests and good agreement of their results, the reproducibility of VERSANT HBV 3.0 test being higher.

Enterovirus 71 (EV71) is an emerging human pathogen causing massive epidemics of hand, foot and mouth disease with severe neurological complications in Asia. EV71 also circulates in Europe, however it does not cause large outbreaks. The reason for distinct epidemiological patterns of EV71 infection in Europe and Asia and the risk of EV71 epidemic in Europe and Russia remain unknown. Seroepidemiology of EV71 and molecular epidemiology of occasional EV71 isolates were studied to explore circulation of EV71 in Russia. In six regions of Russian Federation, seroprevalence of EV71 in sera collected in 2008 ranged from 5% to 20% in children aged 1–2 years and from 19% to 83% in children aged 3–5 years. The seroprevalence among elder children was significantly higher (41–83% vs. 19–27%) in Asian regions of Russia. EV71 strains identified in Russia in 2001–2011 belonged to subtypes C1 and C2, while genotype C4 that was causing epidemics in Asia since 1998 emerged in 2009 and became dominant in 2013.

Summary. Antibody to hepatitis E virus of IgG class (anti-HEV IgG) is regularly detected in industrialized countries, where HEV is non-endemic, at levels not exceeding 2–3%; seropositive individuals are often found in certain groups of patients and professionals exposed to an increased risk of blood-borne infections. The present study was aimed at the identification of anti-HEV IgG in patients with human immunodeficiency virus (HIV) infection, including acquired immune deficiency syndrome (AIDS), living in Russia and Belarus, an area of low anti-HEV prevalence with a moderate spread of HIV infection and AIDS. In Russia, 13 out of 117 HIV-infected patients (11.1%) were found to be anti-HEV seropositive. This differed significantly from the frequency observed in the normal population (1.7%) but not from the frequency in a matching control, high-risk group consisting of male prisoners (8.0%). No difference in the frequency of anti-HEV IgG seropositivity was found between groups of HIV-infected men subdivided by sexual orientation. The rate of anti-HEV seropositivity increased with the progression of HIV infection, reaching 43.3% in AIDS patients and 38.1% in those who died from AIDS. In Belarus, anti-HEV IgG seropositivity was not found among 20 HIV-infected subjects nor among individuals from the control risk group, which consisted of 25 intravenous drug users. In conclusion, HEV infection may have common transmission mechanisms (risk factors) with HIV infection rather than represent an additional opportunistic infection in AIDS.

Vaccination of newborns against hepatitis B (HB) was introduced in Russia in 1998. Since then the incidence of acute HB has rapidly declined. However, prevalence of chronic HB remains stable. The aim of this study was to estimate the effect of vaccination on HBV-associated morbidity, and to assess the prevalence of HBV immune escape variants after 10 years of vaccination. Methods 6,217 sera samples collected from volunteers in six epidemiologically different regions of Russia were tested for serological and molecular markers of HBV infection. A mathematical model developed by the U.S. Centers for Disease Control and Prevention was used to estimate the effect of vaccination and birth dose coverage on the incidence of HB and adverse outcomes of infection. Results Prevalence of HBsAg in the study population varied from 1.2% to 8.2%; anti-HBc detection rates were 13.0–46.2%. HBsAg detection rates in epidemiologically significant cohorts were 0.6–10.5% in women of childbearing age; 0–2.4% in children ≤5 years old; 1.9–8.1% in adults ≥30 years old. Mathematical modeling demonstrated that the current 96.1–99.6% level of birth dose coverage increased the effectiveness of vaccination 10–21 times compared to 50% and 0% birth dose coverage scenarios. HBV DNA was detected in 63 sera samples. The frequency of amino acid substitutions in HBsAg was 38% (24/63). Only in 3% (2/63) the mutations were within the a-determinant of HBsAg (M133T and G145S, one case each). None of the identified mutations eluded HBsAg detection, since all these samples tested positive for HBsAg by commercial ELISA. Conclusion Despite a significant decline in acute HB incidence after the introduction of universal vaccination, many undiagnosed potential sources of infection remain. Low prevalence of HBV immune escape variants is a favorable predictor of vaccine effectiveness in the future.

It is generally understood that hepatitis B and hepatitis C may be sexually transmitted. During the last decade there was a sharp growth of hepatitis B and C in Russia. In comparison to 1992 the incidence of hepatitis B in Russia rose two-fold and in 1999 there were 43.31 cases per 100,000 of population (in some cities up to 150/100,000 and even more). The incidence of hepatitis C in 1999 (19.31 per 100,000 of population) rose to six times more than in 1994. At the same time there was a dramatic growth in syphilis and other sexually transmitted infections in Russia. The proportion of sexual transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) compared with other routes of transmission increased. According to the data from Moscow City Centre of Epidemiology during the last two years, up to 40% cases of HCV and HBV were sexually transmitted. The most dramatic growth of registered cases of hepatitis was seen among the sexually active population aged 14-29. Confirmation of the sexual route of transmission of HBV and HCV in teenagers was seen when the results of the study showed various markers of HBV and HCV to be significantly more common among sexually active (n=45) than sexually inactive (n=341) teenagers (13.33% vs. 4.39% for HBsAg; 46.67% vs. 12.61% for HBsAg+anti-HBs+anti-HBc; 9.47% vs. 3.95% for anti-HCV, respectively).

Hepatitis E is a major cause of acute icteric disease widespread in tropical and sub-tropical regions but rarely occurring in industrialized countries. Recently solid-phase enzyme immunoassays with recombinant antigens have been introduced for diagnosis of this infection.The aim of this study was to evaluate the diagnostic potential of a newly developed Abbott test for the detection of IgG class antibodies to hepatitis E virus (anti-HEV IgG) in hepatitis patients and 'normal' individuals.Sera taken from hepatitis patients and individuals without liver disorders in endemic (Kirghizstan and Uzkbekistan) versus non-endemic (Moscow) areas were investigated. In parallel IgG class antibodies to hepatitis A virus (anti-HAV IgG) were determined by an enzyme immunoassay with native HAV antigen.In five groups comprising altogether 86 suspected hepatitis E patients from endemic area the rate of anti-HEV IgG seropositivity varied from 85% to 17%. In Moscow anti-HEV IgG was found in one patient (who also had acute hepatitis B) out of 19. Anti-HEV IgG persisted in an experimentally infected volunteer for at least 12 years after the acute disease. Among the individuals without liver disorders eight out of 173 (4.6%) showed anti-HEV IgG seropositivity in Kirghizstan while there was only one seropositive out of 165 (0.6%) in Moscow. In contrast, anti-HAV IgG were frequently present in the residents of both areas: in Kirghizstan over 90% of individuals from young age groups already had these antibodies; in Moscow the rate of anti-HAV IgG seropositivity constantly increased from 31% in the youngest age group to almost 85% in the oldest one.Prevalence of anti-HEV antibodies was unexpectedly low in endemic area; in Moscow anti-HEV IgG was found only in single cases. Anti-HEV IgG seropositivity in a single serum sample could be of certain diagnostic value in non-endemic areas.