HEV infection and blood safety

Recently, chronic infection with hepatitis E virus (HEV) was detected in several immunosuppressed, poly-transfused patients in the Netherlands. In the past, acute hepatitis E predominantly occurred in persons returning from HEV-endemic countries, and the HEV seroprevalence in the Netherlands was low. More recently, the incidence of locally acquired HEV has increased in industrialized countries, which seems to be linked to HEV-genotype 3 infection among pigs. Reports show that many pig farms in the Netherlands are infected with HEV and that viral RNA can be detected in pig meat. Several studies showed that HEV can be transmitted by blood. 

The increased HEV incidence raises concern about the safety of blood and blood products. A large project, aiming to determine the incidence and seroprevalence of HEV infection among blood donors, has been proposed. To facilitate the study, sensitive HEV PCR and genotyping assays are being developed. 

Q fever among blood donors

In 2007, 2008 and 2009 outbreaks of Q fever occurred in the Netherlands with increasing magnitude, caused by the release of large amounts of Coxiella burnetii spores in the environment. The 2009 outbreak with 2,354 reported cases is the largest human Q fever outbreak ever recorded. 

To assess the extent of infection and the safety of donated blood, we tested local blood donations for presence of C. burnetii-antibodies and -DNA. Starting May 2009, over 40,000 serum samples were collected from all consenting blood donors in the areas with high Q fever incidence. A PCR for detection of C. burnetii DNA was developed. The 1,004 samples from the areas with the highest number of reported cases were tested for presence of C. burnetii DNA. Seroprevalence and incidence were determined using ELISA and immunofluorescence assays (IFAs) in the subset of 543 donors, of whom a follow-up sample was available. 6/1,004 donor samples tested reactive for C. burnetii DNA. 

Confirmatory testing (IFA) on the index and follow-up samples demonstrated seroconversion in 2 donors; high-level pre-existing antibodies in 1 donor and no seroconversion in 3 donors. Thus, 3/1,004 blood donations were proven to contain C. burnetii DNA. IgG testing of the 543 serum pairs showed that 66 (12.2%) were reactive in the latest sample, of which 10 represented seroconversions. The ten seroconversions result in an incidence of 5.7% per year, which is more than 10-fold higher than the local number of reported clinical cases (0.47% per year)

Residual risk

The transmission of classical blood-borne infections is largely prevented by donor selection, donor screening, and the removal and inactivation of infectious agents. A small residual risk remains because in some of these infections the viremia is below the limit of detection. Two additional types of residual risk exist. Some agents, which probably are present among our blood donors, may or may not cause infection via blood transfusion (e.g.: chronic infection with Coxiella burnetii, vCJD and HTLV). In addition, some agents which are known to cause infection through blood transfusion, may or may not be silently imported by traveling blood donors (e.g.: West Nile Virus). 

Far-reaching safety measures have been implemented to decrease the three types of residual risk, although the cost-benefit ratios involved may be very high or unknown. The departmentt of Blood-borne Infections has started a study on the definition and management of the residual risk of transfusion-transmitted infections.

Key publications

• Slot E, Zaaijer HL, Molier M, Van den Hurk K, Prinsze F, Hogema BM. Meat consumption is a major risk factor for hepatitis E virus infection. PLoS One. 2017 Apr 27;12(4):e0176414
• van de Laar TJ, Bezemer D, van Laethem K, Vandewalle G, de Smet A, van Wijngaerden E, Claas EC, van Sighem AI, Vandamme AM, Compernolle V, Zaaijer HL. Phylogenetic evidence for underreporting of male-to-male sex among human immunodeficiency virus-infected donors in the Netherlands and Flanders. Transfusion. 2017 May;57(5):1235-1247.
• Kramer K, Zaaijer HL, Verweij MF.The Precautionary Principle and the Tolerability of Blood Transfusion Risks. Am J Bioeth. 2017 Apr;17(4):W4-W6.
• de Vos AS, Janssen MP, Zaaijer HL, Hogema BM. Cost-effectiveness of the screening of blood donations for hepatitis E virus in the Netherlands. Transfusion. 2017 Feb;57(2):258-266.
• Kramer K, Verweij MF, Zaaijer HL. Are there ethical differences between stopping and not starting blood safety measures? Vox Sang. 2017 Jul;112(5):417-424.