21 August 2015 Samreen Ijaz Virus Reference Department Health Protection Agency Indigenous HEV infection in the UK: a hazard for blood donation?

HEV Infections in England and Wales (2005 study) HEV seropositive samples with no travel history identified from at CPHL Male Female GENDER yrs >60 yrs AGE Genotype 3 UK strains Genotype 1& 2 Endemic strains MOLECULAR ANALYSIS

0% 5% 10% 15% 20% 25% 30% 35% 40% Age group (years) Prevalence 1991 HEV seroprevalence in England (year 1991)

HEV prevalence by age-group 1991 vs 2004 Temporal shift

Seroprevalence rates vs clinical disease 13% seroprevalence high compared to the low rate of clinically evident disease Incidence estimates between 1991 and 2004 indicate that ~ cases of HEV occurred per year Mathematical modelling suggests that incidence does not vary with age group Shared risk factors common to all age groups

Indigenous HEV in England and Wales Routes of transmission in the non-travellers could not be ascertained from this study Specific risk factors for acquiring indigenous HEV infections currently remains undefined The detection of HEV Abs and RNA in swine and subsequently in several other animals has led to suggestions of a potential zoonosis with animals acting as reservoirs for HEV infection in humans 85% of UK pigs are anti-HEV pos. Recommended that indigenous HEV be considered a level 2 zoonosis (potential zoonosis), thus requiring enhanced surveillance in the UK

Parenteral transmission of HEV? Higher HEV Ab levels reported in: paid blood donors positive for other blood borne viruses repeatedly transfused haemodialysis patients Subsequent reports of transfusion transmitted HEV from France, Japan and Saudi Arabia Studies from Japan have demonstrated that a small but significant proportion of their blood donors were viraemic and potentially able to cause transfusion-associated HEV in the absence of elevated ALT and signs or symptoms of hepatitis When characterised, the strains involved in the cases from Japan were shown to be indigenous viruses

Post transfusion hepatitis in the UK UK blood donor: 14 days after his donation he became ill with a ‘flu-like’ illness 10 days later he became jaundiced Blood donor reported illness to the blood service but components of his donation had already been used Testing for viral markers HAV, HBV, HCV, CMV and EBV negative HEV IgM and IgG positive HEV RNA positive – genotype 3

Blood Donation platelets red cells Pool from 4 donors which is resuspended using plasma from one of the donors (not the HEV pos donor) Would contain 20-30mls of the donor’s plasma Patient 1 Patient 2 UNINFECTED INFECTED Post transfusion hepatitis in the UK HEV infection in the recipient related to dose?

Post transfusion hepatitis in the UK is now a relatively rare event with enhanced surveillance through the Serious Hazards of Transfusion (SHOT) reporting system Approximately cases occur each year Suggests that there are a significant number of subclinical HEV infection Current screening policy in the UK does not include HEV testing Should we worry? Post-transfusion hepatitis

Initial studies to look at UK blood donors HEV IgG testing on: 262 samples from ‘ordinary’ blood donors 339 samples from donors with a history of jaundice (all anti-HBc negative) > 60 Age (yrs) %

HEV seroprevalence in UK blood donors HEV seroprevalence trend similar in blood donors to general population Similar seroprevalence rates between ordinary and jaundice history donors HEV unlikely to be responsible for donors reporting history of jaundice History of jaundice not accurate screening method for excluding at risk donors Further HEV IgM & RNA testing carried out on all donors 4 HEV IgM pos 0 HEV RNA pos EVIDENCE OF RECENT HEV INFECTION IN DONOR POPULATION

Further work Evidence of seroconversion in the blood donor panel Evidence of HEV RNA in minipools Concern of post transfusion hepatitis in transplant recipients and the immunosuppressed

Acknowledgements Richard Tedder Mathew Beale Kate Tettmar Roger Eglin NHS Blood and Transplant