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Indigenous HEV infection in the UK: a hazard for blood donation?. Samreen Ijaz Virus Reference Department Health Protection Agency. Female. 50-59 yrs. Genotype 3 UK strains. >60 yrs. Male. Genotype 1& 2 Endemic strains. GENDER. AGE. MOLECULAR ANALYSIS.
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Indigenous HEV infection in the UK: a hazard for blood donation? Samreen Ijaz Virus Reference Department Health Protection Agency
Female 50-59 yrs Genotype 3 UK strains >60 yrs Male Genotype 1& 2 Endemic strains GENDER AGE MOLECULAR ANALYSIS HEV Infections in England and Wales (2005 study) HEV seropositive samples with no travel history identified from 1996-2003 at CPHL
40% 1991 35% 30% 25% Prevalence 20% 15% 10% 5% 0% 1-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 Age group (years) HEV seroprevalence in England(year 1991)
40% 1991 2004 35% 30% 25% Prevalence 20% 15% 10% 5% 0% 1-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 Age group (years) HEV prevalence by age-group1991 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 ~62 000 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
Post transfusion hepatitis in the UK 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 2 Patient 1 INFECTED UNINFECTED • HEV infection in the recipient related to dose?
Post-transfusion hepatitis • 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 62 000 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?
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) 25 20 15 % 10 5 0 17 - 29 30 - 39 40 - 49 50 - 59 > 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