The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.

Age and Gender Trends in the Prevalence of Markers for Hepatitis E Virus Exposure in the Heterogeneous Bulgarian Population.

The prevalence of hepatitis E virus (HEV) in the Bulgarian population remains underestimated. The aim of the present study was to evaluate age and gender trends in HEV prevalence in the heterogeneous Bulgarian population. Stored serum samples from blood donors and different patient sub-populations-kidney recipients (KR), patients with Guillain-Barre syndrome (GBS), Lyme disease (LD), patients with liver involvement and a clinical diagnosis other than viral hepatitis A and E (non-AE), hemodialysis (HD) and HIV-positive patients (HIV)-were retrospectively investigated for markers of past and recent/ongoing HEV infection. The estimated overall seroprevalence of past infection was 10.6%, ranging from 5.9% to 24.5% for the sub-populations evaluated, while the seroprevalence of recent/ongoing HEV infection was 7.5%, ranging from 2.1% to 20.4%. The analysis of the individual sub-populations showed a different prevalence with respect to sex. In regard to age, the cohort effect was preserved, as a multimodal pattern was observed only for the GBS sub-population. Molecular analysis revealed HEV 3f and 3e. The type of the population is one of the main factors on which the anti-HEV prevalence depends, highlighting the need for the development of guidelines related to the detection and diagnosis of HEV infection with regard to specific patient populations.

Varicella zoster virus infection in neurological patients in Bulgaria.

The clinical manifestations of neurological complications associated with varicella zoster virus (VZV) are non-specific and indistinguishable from those of other viral infections. Therefore, the definite diagnosis requires evidence of VZV infection in cerebrospinal fluid (CSF). The aim of this study was to determine the frequency of VZV DNA detection in CSF of patients with neurological diseases in order to obtain information concerning involvement of VZV infection in neuropathology in the country. This study is a retrospective survey of test results obtained from January 2015 to October 2019. During this period, 411 CSF specimens were tested for the presence of VZV DNA by nested PCR. Fisher's exact test was used to test for statistically significant difference in the frequency of VZV DNA positivity of CSF specimens from different groups. Of all 411 tested CSF samples, 11.2% were positive for VZV DNA. The highest VZV prevalence was detected in CFS from patients with meningitis-18.2%, followed by patients with cranial neuritis (15.4%), encephalitis (12.2%), Guillain-Barré syndrome (11.1%), myelitis (10%), and with other neurological syndromes (8.2%). The difference of VZV prevalence in CSF of patients according to the gender and age was not statistically significant. Our results indicated that VZV is a frequent causative agent of neurological diseases, suggesting an important role of VZV infection for neuropathology in the country. Therefore, efforts for wider application of VZV identification in CSF to facilitate faster onset of antiviral treatment and further strategies concerning varicella zoster virus vaccines in the country are needed.

Seroprevalence of Hepatitis E Virus Infection in Pigs from Southern Bulgaria.

Hepatitis E virus (HEV) has been isolated from humans and several animals' species. During the last years, the knowledge of HEV infection dramatically changed and enriched. The aim of this study was to estimate the seroprevalence of HEV in industrial pigs in different districts of Southern Bulgaria. Three hundred sixty swine serum samples were tested for anti-HEV IgG antibodies. The samples were collected from four industrial farms from three districts of Southern Bulgaria. HEV-specific antibodies in porcine serum were detected by enzyme-linked immunosorbent assay (PrioCHECK HEV Ab porcine). The overall HEV seroprevalence was 60.3%. The seropositivity varied widely depending on age groups and investigated farms. The overall prevalence in weaners was 25%, in fattening pigs 75.8%, and in group of sows was found the highest HEV positivity of 80%. The occurrence of HEV positivity in sows and fattening pigs presented odds ratio (OR) = 17.200 (95% confidence interval [CI]: 8.8-33.7) and OR = 11.342 (95% CI: 6.1-21.0), respectively, compared to weaners. The study indicated that HEV is widespread in industrial farms in Bulgaria and presented high seroprevalence in pigs. The results found that HEV seropositivity showed age dependency. The National Health Authorities should raise awareness of HEV and its zoonotic potential.

Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013-2015.

BACKGROUND: In industrialized areas of the world, including Europe, Hepatitis E Virus (HEV) is considered an emerging pathogen. In fact, autochthonous cases caused by HEV genotype 3 (HEV-3) are increasingly reported. Several studies described the human HEV-3 subtypes and strains circulating in West Europe countries; in contrast, very little is known about the HEV strains responsible for acute hepatitis E in countries of East Europe/Balkans, such as Bulgaria. METHODS AND FINDINGS: Anti-HEV IgM positive serum samples (n = 103) from acute hepatitis cases (2013-2015) from all over Bulgaria were analysed for HEV RNA by Real-Time PCR. Viremia was detected in 90/103 samples. A fragment of the viral genome (ORF-2 region) was amplified by nested PCR from 76/90 viremic samples, leading to a sequence in 64 of them. Genotyping by phylogenetic analysis with standard reference sequences showed HEV-1 in 1/64 cases, HEV-3 in 63/64. Subtyping of HEV-3 sequences showed 3e (39/63, 62%), 3f (n = 15/63, 24%) and 3c (n = 8/63, 13%) subtypes; in one case the sequence subtype was uncertain and classified as 3hi. In the phylogenetic tree, most 3e sequences grouped in two well distinct clusters (A and B), each one with very low intragroup genetic distances. In contrast, 3f and 3c were interspersed with reference sequences and showed lower tendency to cluster and/or higher intragroup distances. Geographically, while 3f and 3c were scattered throughout the country, 3e was restricted to the South-West area, with most cases in two towns about 40 kilometres apart from each other. CONCLUSIONS: Most acute hepatitis E cases in Bulgaria are caused by HEV-3, subtypes 3e, 3f and 3c. Circulation of 3e appears quite different from 3f and 3c, with 3e restricted to the South-West area while 3f and 3c diffused over the country. The factors underlying the observed molecular and geographical differences remain to be investigated.

Mediterranean spotted fever in children in the Pazardjik region, South Bulgaria.

The objective of the present study was to analyze the clinical pattern of contemporary Mediterranean spotted fever in children and to compare it with the clinical pattern in adults. The research involved 257 children. The more common symptoms in children were severe onset, fever, rash, "tache noire," swelling of lymph nodes and enlarged liver or spleen.