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HEPATITIS E VIRUS (HEV) INFECTION IN ESTONIA Valentina Tefanova Tatjana Tallo, Irina Reshetnjak, Elina Shatova National Institute for Health Development, Tallinn, Estonia The Public Health Agency of Sweden, Stockholm, Sweden XI Annual Conference of The Network against Life-threating viral infections April 24-27, 2014, Vilnius, Lithuania Epidemiological patterns of HEV Hepatitis E virus is an important public–health concern as a major cause of enterically transmitted hepatitis worldwide. Hepatitis E occur sporadically and in large outbreaks causing significant morbidity, mortality and disruption of trade and tourism. It is estimated that 2.3 billion people are infected globally. Hepatitis E in developed countries is more common than previously recognised. Pigs are presumed reservoirs for HEV transmission to humans suggesting that hepatitis E is a zoonotic infection. Four major routes of HEV infection transmission are known: fecal-oral, due to contamination of drinking water – the most common route food-borne transmission blood-born through the transfusion of infected blood products vertical transmission HEV characteristics HEV - the sole member of the genus Hepevirus, family Hepeviridae. HEV genome: spherical, non-enveloped, single-stranded, positive-sense RNA virus 7.2-kb in length; contains 3 open reading frames (ORF). Four major HEV Gts are recognized with numerous subtypes (at least 24), a single serotype. Gts 1 and 2 only infect humans; transmission via contaminated water. Gts 3 and 4 have been isolated from humans and infected animals (domestic pigs, wild boars, deers). Transmitted to humans via consumption of animal products. HEV distribution HEV seroprevalence rates differ significantly from 0.3% to 53% depending on wold region and studied population. HEV gt 1 – prevalent in endemic countries; the main cause of sporadic and epidemic cases gt 2 – circulates in Mexico, West and South Africa gt 3 – prevalent worldwide, including Europe gt 4 – circulates in developed regions of East and Southeast Asia HEV geographic distribution (According to CDC data). Hepatitis E manifestations In the majority of cases, hepatitis E is acute self-limiting and asymptomatic infection. Young adults, 15 to 40 years of age, are the main targets of infection. Genotype HEV-1 infection can cause epidemics as well as the fulminant hepatitis in pregnant women with mortality rates up to 25%. Chronic genotype HEV-3 infection is an emerging problem in immunosupressed pts, including organ transplant pts. HEV gts 1 and 3 have been associated with severe extrahepatic manifestations: neurological symptoms, including meningoencefalitis, hematological disorders and kidney injury. Prevention: by improving the sanitary infrastructure, providing of clean drinking water, avoiding eating of undercooked meat. Two candidate HEV vaccines have been investigated in clinical trials. HEV infection in Estonia: background In Estonia decision to notify hepatitis E cases has been made by the Ministry of Social Affairs in 1997. However, HEV diagnostics are still not performed on a routine bases. To establish a starting point for further studies on HEV infection a retrospective study on HEV prevalence in Estonia was conducted in 2011*. Totally 1253 serum samples collected from 494 males and 759 females 20 to 91 yrs between 1994 and 2006 were tested. The prevalence of anti-HEV IgG - 3.2%, being up to 6% in people aged 60 yrs and older. • Highest HEV prevalence - in healthy people (6.0%) followed by dialysis patients (5.1%). • Out of all, 1.04% were anti-HEV IgM pos. • No significant difference in HEV seroprevalence between males and females was found. The first 2 cases of acute hepatitis E with clinical presentation (48 yrs old men, with no identified any common for HEV risk factors)**, and 32 yrs old man with history of travel to India were diagnosed and laboratory confirmed at our depart. anti-HEV positivity by studied groups 6.0* % 5.1 *Financial support: Estonian Health Board **Prükk, 2013 3.2 2.5 2.4 0 acute VH nAnC n=763 dial.pts n=176 HCW n=163 healthy people n=151 HEV in Estonia: current study Aim: to study HEV seroprevalence in people under the risk for HEV infection and in animals as pigs and wild boars in Estonia. Material: Totally 468 serum samples were collected between 2007 and 2012 from 251 males and 217 females aged 17 to 63 yrs. From those: 205 samples - from injection drug users (IDUs) 105 – from patients with chronic hepatitis C (CHC) 158 – from non-swine veterinarians (VT). 380 serum samples from pigs below 1.5 years of age were collected from 14 Estonian swine farms across country. 471 heart meet-juice samples from wild boars collected from 14 out of the 15 Estonian counties, including continental and island parts of Estonia. Methods: Human serum samples have been tested for the presence of HEV IgG and HEV IgM Abs using recomWell HEV IgG/IgM ELISA kit (Mikrogen, Denmark). For confirmation, positive sera were tested with an immunoblot assay (recomLine HEV IgG/IgM, Mikrogen). Swine and wild boars samples were screened with PrioCHECK® HEV Ab porcine ELISA (Prionics AG, Switzerland) for specific antibodies against HEV. HEV RNA was detected using real-time PCR and qScript™ One-Step Fast qRT-PCR Kit, ROX™ (Quanta BioSciences, USA) and Applied Biosystems 7500 (Applied Biosystems, USA) instrument platform. Results The overall anti-HEV IgG seroprevalence in studied people was 1.7%, being 2.4% (5/205) and 1.9% (3/158) among IDUs and veterinarians, respectively. None one patients with CHC were found positive for HEV antibodies. 62% (234/380) of serum samples collected from pigs were positive for antiHEV antibodies, ranging from 27% to 100%, depending on farm. 17.2% (81/471) of heart meet-juice samples from wild boars were positive for anti-HEV antibodies. In none of the tested serum samples from people and pigs HEV RNA could be detected. 2.8% (13/471) of the meet-juice samples from wild boars were HEV RNA positive indicating the presence of ongoing HEV infection. Conclusions Based on our previous and current serological data, HEV infection does occur in the adult Estonian population and is widespread among the Estonian domestic and wild animals. Thus, HEV can be a possible causative agent of acute hepatitis in Estonia. Circulation of HEV in animals may sustain hepatitis E virus in the environment or as a part of the food chain. Since HEV diagnostic is not still performed in Estonia, there are urgent needs for introduction of robust protocol for diagnostics of HEV infection. Acknowledgment Estonian Health Board, Tallinn Jevgenija Epstein, Kuulo Kutsar, Tiiu Aro Estonian University of Life Sciences, Tartu Brian Lassen, Kaisa Velström, Pikka Jokelainen, Arvo Viltrop National Institute for Health Development, Department of Virology Anna Ivanova, Irina Golovljova This work was supported by the European Regional Development Fund programme TerVe/ZoonRisk 3.2.1002.11-0002. Thank you for attention!