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 < 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%–64.7%: HepB3 coverage by the age of one year exceeded 90% in both study regions. HBV surface antigen (HBsAg) prevalence in the 1998–2019 birth cohort was 0.2% (95% CI: 0.01–1.3%) in Belgorod Oblast and 3.2% (95% CI: 1.9–5.2%) 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 1998–2019 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.

The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics of the HEV. The anti-HEV IgG antibody detection rates in the general population increase significantly with age, from 1.5% in children and adolescents under 20 years old to 4.8% in adults aged between 20 and 59 years old to 16.7% in people aged 60 years and older. HEV seroprevalence varies between regions, with the highest rate observed in Belgorod Region (16.4% compared with the national average of 4.6%), which also has the country’s highest pig population. When compared with the archival data, both increases and declines in HEV seroprevalence have been observed within the last 10 years, depending on the study region. Virus shedding has been detected in 19 out of the 21 pig farms surveyed. On one farm, the circulation of the same viral strain for five years was documented. All the human and animal strains belonged to the HEV-3 genotype, with its clade 2 sequences being predominant in pigs. The sequences are from patients, pigs, and sewage from pig farms clustered together, suggesting a zoonotic infection in humans and possible environmental contamination. The HEV-3 population size that was predicted using SkyGrid reconstruction demonstrated exponential growth in the 1970s–1990s, with a subsequent decline followed by a short rise around the year 2010, the pattern being similar to the dynamics of the pig population in the country. The HEV-3 reproduction number (Re) that was predicted using birth–death skyline analysis has fluctuated around 1 over the past 20 years in Russia but is 10 times higher in Belgorod Region. In conclusion, the HEV-3 circulation varies both geographically and temporally, even within a single country. The possible factors contributing to this variability are largely related to the circulation of the virus among farm pigs.

Amino acid substitutions R70Q/H and L91M in HCV subtype 1b core protein can affect the response to interferon and are associated with the development of hepatocellular carcinoma. We found that the rate of R70Q/H in HCV 1b from Russia was 31.2%, similar to that in HCV strains from Asia (34.0%), higher than that in the European (18.0%, p=0.0010), but lower than that in the US HCV 1b strains (62.8%, p<0.0001). Substitution L91M was found in 80.4% of the Russian HCV 1b isolates, higher than in Asian isolates (43.8%, p<0.0001). Thus, a significant proportion of Russian HCV 1b isolates carry the unfavorable R70Q/H and/or L91M substitution. In silico analysis of the epitopic structure of the regions of substitutions revealed that both harbor clusters of T-cell epitopes. Peptides encompassing these regions were predicted to bind to a panel of HLA class I molecules, with substitutions impairing peptide recognition by HLA I molecules of the alleles prevalent in Russia. This indicates that HCV 1b with R70Q/H and L91M substitutions may have evolved as the immune escape variants. Impairment of T-cell recognition may play a part in the negative effect of these substitutions on the response to IFN treatment.

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: 56.3–74.6%] in children aged 10–14 years and reached a plateau (>95%) by age 20–29 years. Annual incidence rates in children under 18 years of age peaked at 450–860 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 (≥10 mIU/mL) were detected in 98.0% (95% CI: 96.2–99.0% (442/451)) of children tested one month after single-dose immunization, in 93.5% (95% CI: 91.0–95.4% (477/510)) and in 91.1% (95% CI: 88.2–93.4% (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 > 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.

РАСПРОСТРАНЕННОСТЬ ВИРУСА ГЕПАТИТА С СРЕДИ УСЛОВНО ЗДОРОВОГО НАСЕЛЕНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ

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.