Geographic and Temporal Variability of Hepatitis E Virus Circulation in the Russian Federation

Abstract

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.

Hepatitis E Virus Infection in Voluntary Blood Donors in the Russian Federation

“…In this study, we investigated the proportion of blood donors with viremic HEV infection to assess whether HEV RNA testing should be implemented for blood services in Russia. Previous studies have shown that the HEV epidemiology in Russia is similar to that observed in many industrialized countries which are of intermediate HEV endemicity, with rather high seroprevalence due to asymptomatic infections in the general population and increased seroprevalence rates in seniors, and zoonotic HEV-3 is the causative agent of autochthonous cases [ 14 ]. Thus, although TT-HEV cases have not been reported in Russia so far, they are expected to exist but are unrecognized and/or undiagnosed.…”

“…Two particular regions, Moscow and Belgorod, were chosen for this study, because the average anti-HEV IgG prevalence rate in the general population in the former is the same as the country’s average (4%), but it is four times higher in the latter, reaching 16.4% [ 14 ], which is indicative of a higher intensity of virus circulation. Indeed, the ratio of HEV RNA positivity among blood donors appeared to be 1.5 times higher in Belgorod than in Moscow (1:2936 and 1:4844, respectively), although this difference was not statistically significant.…”

“…All individual reactive plasma samples were subjected to supplementary amplification of the open reading frame 2 (ORF2) fragment of the HEV genome, as described elsewhere [ 14 ]. Both initial and follow-up plasma samples from donors positive for HEV RNA were tested for anti-HEV IgM and IgG antibodies using commercial enzyme immunoassay (EIA) tests: DS-EIA-ANTI-HEV-M and DS-EIA-ANTI-HEV-G, respectively (Diagnostic Systems, Nizhny Novgorod, Russia).…”

“…Seroprevalence studies have shown that HEV infection in the territory is much more widespread than previously assumed from the official registration data. The average prevalence of anti-HEV IgG antibodies in the Russian Federation is 4.6%, with significant variation between regions [ 14 ]. In the European part of the Federation, there are regions with increased intensity of HEV circulation, accompanied by increased incidence rates and a high prevalence of anti-HEV antibodies, such as the Belgorod region, a region in the European part of the Russian Federation located 600 km south of Moscow, close to the border with Ukraine [ 15 ].…”

“…In the European part of the Federation, there are regions with increased intensity of HEV circulation, accompanied by increased incidence rates and a high prevalence of anti-HEV antibodies, such as the Belgorod region, a region in the European part of the Russian Federation located 600 km south of Moscow, close to the border with Ukraine [ 15 ]. The data on the prevalence of anti-HEV IgM antibodies indicating current or recent infection in the general population of Russia also suggest widespread prevalence of infection; the value varies from 0.2% to 2.8%, depending on the surveyed region [ 14 ]. TT-HEV infection appears to be relevant for the Russian Federation, as the prevalence of anti-HEV IgM antibodies in blood donors was previously shown to be as high as 2.8–4.5%, depending on the region [ 16 ].…”