Case-Control Study of Risk Factors for Acquired Hepatitis E Virus Infections in Blood Donors, United Kingdom, 2018-2019.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in England. Substantial yearly increases of autochthonous infections were observed during 2003-2016 and again during 2017-2019. Previous studies associated acute HEV cases with consumption of processed pork products, we investigated risk factors for autochthonous HEV infections in the blood donor population in England. Study participants were 117 HEV RNA-positive blood donors and 564 HEV RNA-negative blood donors. No persons with positive results were vegetarian; 97.4% of persons with positive results reported eating pork products. Consuming bacon (OR 3.0, 95% CI 1.7-5.5; p<0.0001), cured pork meats (OR 3.5, 95% CI 2.2-5.4; p<0.0001), and pigs' liver (OR 2.9, 95% CI 1.0-8.3; p = 0.04) were significantly associated with HEV infection. Our findings confirm previous links to pork products and suggest that appropriate animal husbandry is essential to reduce the risk for HEV infection.

Persistent Hepatitis E virus infection across England and Wales 2009-2017: Demography, virology and outcomes.

The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty-six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti-HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci-symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti-HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment.

Human-to-Human Transmission of Monkeypox Virus, United Kingdom, October 2018.

In September 2018, monkeypox virus was transmitted from a patient to a healthcare worker in the United Kingdom. Transmission was probably through contact with contaminated bedding. Infection control precautions for contacts (vaccination, daily monitoring, staying home from work) were implemented. Of 134 potential contacts, 4 became ill; all patients survived.

Epidemiology of Hepatitis E in England and Wales: A 10-Year Retrospective Surveillance Study, 2008-2017.

Indigenous, foodborne transmission of hepatitis E virus genotype 3 (HEV G3) has become recognized as an emerging problem in industrialized countries. Although mostly asymptomatic, HEV G3 infection has a range of outcomes, including mild illness, severe acute hepatitis, and, of particular concern, chronic progressive hepatitis in immunocompromised patients. Public Health England has monitored cases of acute HEV infection in England and Wales since 2003. Between 2010 and 2017, enhanced surveillance using 2 linked laboratory databases and questionnaires on clinical features and risk factors was conducted. There was a year-on-year increase in the number of infections from 2008 (183) through 2016 (1243). Then, in 2017, the number of infections declined (to 912). As reported previously, HEV G3 group 2 (also known as "G3 abcdhij") is the predominant cause of acute infections, and older men are most at risk. Consumption of pork and pork products was significantly higher among patients than in the general population, but other previously reported associations, such as consumption of shellfish, were not observed. Ongoing surveillance is required to monitor future trends and changes in the epidemiology of the virus. The changing methods of animal husbandry and processing and distribution of animal products needs to be further investigated.

Two cases of monkeypox imported to the United Kingdom, September 2018.

In early September 2018, two cases of monkeypox were reported in the United Kingdom (UK), diagnosed on 7 September in Cornwall (South West England) and 11 September in Blackpool (North West England). The cases were epidemiologically unconnected and had recently travelled to the UK from Nigeria, where monkeypox is currently circulating. We describe the epidemiology and the public health response for the first diagnosed cases outside the African continent since 2003.

Hepatitis E virus infection in Europe: surveillance and descriptive epidemiology of confirmed cases, 2005 to 2015.

Hepatitis E virus (HEV) is an under-recognised cause of acute hepatitis in high-income countries. The purpose of this study was to provide an overview of testing, diagnosis, surveillance activities, and data on confirmed cases in the European Union/European Economic Area (EU/EEA). A semi-structured survey was developed and sent to 31 EU/EEA countries in February 2016, 30 responded. Twenty of these countries reported that they have specific surveillance systems for HEV infection. Applied specific case definition for HEV infection varied widely across countries. The number of reported cases has increased from 514 cases per year in 2005 to 5,617 in 2015, with most infections being locally acquired. This increase could not be explained by additional countries implementing surveillance for HEV infections over time. Hospitalisations increased from less than 100 in 2005 to more than 1,100 in 2015 and 28 fatal cases were reported over the study period. EU/EEA countries are at different stages in their surveillance, testing schemes and policy response to the emergence of HEV infection in humans. The available data demonstrated a Europe-wide increase in cases. Standardised case definitions and testing policies would allow a better understanding of the epidemiology of HEV as an emerging cause of liver-related morbidity.

Virology, serology, and demography of hepatitis E viremic blood donors in South East England.

BACKGROUND: Hepatitis E virus (HEV) Genotype 3 (G3) in England comprises two principal phylogenetic groups (Group 1 and Group 2) and can be transmitted by transfusion. Unselected screening identified 79 viremic donors; 76 participated in a follow-up study. STUDY DESIGN AND METHODS: Viral RNA dynamics, phylogenetics, and seroconversion were characterized in the donors. Detailed demographic, travel, clinical, and lifestyle questionnaires were undertaken. RESULTS: The majority of viremic individuals (57/79) were seronegative at time of donation but all seroconverted. Viremia was short-lived, with a median of 6.5 weeks to confirmed viral clearance. All infections were acquired in the United Kingdom and were G3, with Group 2 viruses predominating (43/54; 80%). Infection was associated with some clinical symptoms both at and after donation (8/77; 10%). Viral loads and symptoms were more pronounced in Group 1 infections. There was no serologic evidence of reinfection. Donors were more commonly male (p = 0.002); both male and female donors were older than comparator donors. Animal contact was unlikely to be the source of infection. Consumption of chicken and pig meat was common to all infected donors; processed pig meat was most commonly purchased from one particular retail chain. CONCLUSION: Viremic donors represent primary infection in older members of the community and reflect a widespread zoonotic in the United Kingdom. The two phylogenetic groups of HEV G3 display different pathogenicity and the more common Group 2 appears less adapted to humans. There are no objective demographic criteria that can identify donors at enhanced HEV risk.

Indigenous hepatitis E in England and wales from 2003 to 2012: evidence of an emerging novel phylotype of viruses.

BACKGROUND: Enhanced surveillance and molecular characterisation studies of hepatitis E virus (HEV) in England and Wales have been undertaken since 2003. The dynamics of hepatitis E have changed recently with an increase in the number of indigenous cases and an observed viral shift. METHODS: HEV antibody and RNA data were analysed to ascertain the annual number of acute infections, the HEV genotype disposition and viral phylogeny. These data were investigated in the context of collected travel history and demographic data. RESULTS: In total, 2713 acute hepatitis E cases were diagnosed, of which 1376 were indigenous infections. Travel associated cases remained steady and mainly associated with Genotype 1 infections. In contrast, major fluctuations were noted in indigenously-acquired cases with a dramatic year on year increase during 2010-2012. Molecular characterisation demonstrated indigenous infections to cluster into two distinct phylogenetic groups with the emergence of a novel group of Genotype 3 viruses coinciding with the recent increase in cases. CONCLUSIONS: HEV infection rates are dynamic in England and Wales, influenced by changing trends in indigenously-acquired cases. The recent increase in indigenous cases and the emergence of indigenous viruses not commonly circulating prior to 2010 suggest that the risk of acquiring HEV has changed.

Hepatitis E outbreak on cruise ship.

In 2008, acute hepatitis E infection was confirmed in 4 passengers returning to the United Kingdom after a world cruise. Epidemiologic investigation showed that of 789 persons who provided blood samples, 195 (25%) were seropositive, 33 (4%) had immunoglobulin [Ig] M levels consistent with recent acute infection (11 of these persons were symptomatic), and 162 (21%) had IgG only, consistent with past infection. Passenger mean age was 68 years. Most (426/789, 54%) passengers were female, yet most with acute infection (25/33, 76%) were male. Sequencing of RNA from 3 case-patients identified hepatitis E virus genotype 3, closely homologous to genotype 3 viruses from Europe. Significant association with acute infection was found for being male, drinking alcohol, and consuming shellfish while on board (odds ratio 4.27, 95% confidence interval 1.23-26.94, p = 0.019). This was probably a common-source foodborne outbreak.

Standardising surveillance of hepatitis E virus infection in the EU/EEA: A review of national practices and suggestions for the way forward.

BACKGROUND: Hepatitis E virus (HEV) infection is not notifiable at EU/EEA level, therefore surveillance relies on national policies only. Between 2005 and 2015, more than 20,000 cases were reported in EU/EEA countries. HEV testing is established in 26 countries and 19 countries sequence HEV viruses. OBJECTIVE AND STUDY DESIGN: WHO's European Action plan for viral hepatitis recommends harmonised surveillance objectives and case definitions. ECDC's HEV expert group developed minimal and optimal criteria for national hepatitis E surveillance to support EU/EEA countries in enhancing their capacity and to harmonise methods. RESULTS: The experts agreed that the primary objectives of national surveillance for HEV infections should focus on the basic epidemiology of the disease: to monitor the incidence of acute cases and chronic infections. The secondary objectives should be to describe viral phylotypes or subtypes and to identify potential clusters/outbreaks and possible routes of transmission. Seventeen of 20 countries with existing surveillance systems collect the minimal data set required to describe the epidemiology of acute cases. Eleven countries test for chronic infections. Twelve countries collect data to identify potential clusters/outbreaks and information on possible routes of transmission. DISCUSSION: Overall, the majority of EU/EEA countries collect the suggested data and meet the outlined requirements to confirm an acute case.

Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15.

BACKGROUND: Hepatitis E virus (HEV) is endemic in EU/EEA countries, but the understanding of the burden of the infection in humans is inconsistent as the disease is not under EU surveillance but subject to national policies. STUDY: Countries were asked to nominate experts and to complete a standardised questionnaire about the epidemiological situation and surveillance of HEV in their respective EU/EEA country. This study reviewed surveillance systems for human cases of HEV in EU/EEA countries and nominated experts assessed the epidemiology in particular examining the recent increase in the number of autochthonous cases. RESULTS: Surveillance systems and case definitions across EU/EEA countries were shown to be highly variable and testing algorithms were unreliable. Large increases of autochthonous cases were reported from Western EU/EEA countries with lower case numbers seen in Northern and Southern European countries. Lack of clinical awareness and variability in testing strategies might account for the observed differences in hepatitis E incidence across EU/EEA countries. Infections were predominantly caused by HEV genotype 3, the most prevalent virus type in the animal reservoirs. CONCLUSION: Discussions from the expert group supported joint working across countries to better monitor the epidemiology and possible changes in risk of virus acquisition at a European level. There was agreement to share surveillance strategies and algorithms but also importantly the collation of HEV data from human and animal populations. These data collected at a European level would serve the 'One Health' approach to better informing on human exposure to HEV.