Evaluating the risks posed by hepatitis E virus to blood supply safety

Abstract

Transfusion is an important field of clinical medicine, responsible for saving the lives of millions of people. However, concerns remain for patients’ safety from adverse reactions and transfusion transmissible infections (TTIs). While risks from well-known TTIs (such as human immunodeficiency virus, human T-lymphotrophic virus, hepatitis B virus, hepatitis C virus and Treponema pallidum) have been reduced in developed nations, developing countries struggle to maintain the minimum screening requirements for these infections. Introduction of stringent donor questionnaires and sensitive screening tests are strategies to minimise risk, however, there is a threat to the safety of the blood supply from emerging infectious diseases. In 2005, the global annual disease burden for hepatitis E virus (HEV) was estimated to be 20.1 million incident infections, which resulted in an estimate of 3.3 million symptomatic cases, 70,000 deaths and 3,000 still births. This study represented 71% of world’s population and was associated with genotype 1 and 2. An improved epidemiological understanding of autochthonous HEV through the adoption of improved tests and testing practices, together with evidence of the virus in blood donors and cases of transfusion transmitted HEV (TT-HEV), have raised concern for transfusion safety. Increasing HEV awareness in recent years in Australia, and limited prevalence and incidence data in the blood donor population, warranted investigation of the risk posed by this virus to the Australian blood supply. This study therefore aimed to evaluate HEV risk to blood safety. Firstly, this study provided evidence that 5.99% of Australian blood donors had been exposed to HEV. HEV IgG was detected in international travellers (6.38%) and non-travellers (3.37%), indicating the possibility of both imported and locally-acquired HEV in Australia. The study also demonstrated prior HEV exposure was higher in donors with prior donation restrictions in relation to malaria and/or diarrhoea. This suggests the current blood donor management strategy in Australia in relation to malaria and diarrhoea are partially effective in minimizing risk of TT-HEV. The rate of HEV RNA positivity among 14,799 blood donations was then assessed, with one donation testing positive. The risk of collecting an HEV infectious donation was estimated to be 1 in 14,799 donations (95% CI: 1 in 2,657 to 1 in 584,530). The one HEV positive sample was HEV genotype 3, which suggests either the donor was infected overseas in a developed country where this genotype occurs, or within Australia via zoonotic transmission. The viral load in the HEV RNA positive sample was estimated to be 15,000 IU/ml. Viral loads between 400 and 250,000 IU/mL have been associated with TT-HEV in the United Kingdom, however, as this study was de-linked, risk of transfusion transmissibility from this donation was unable to be determined. In addition, countries at higher risk for travel related HEV exposure were identified through a retrospective study of notified HEV cases in Australia. This analysis allowed an assessment of whether the current travel based considerations used by the Australian Red Cross Blood Service adequately manage this risk. This study demonstrated that the majority of notified overseas-acquired HEV infections in Australia were in travellers returning from South Asia, namely India, Bangladesh and Nepal. These countries are endemic for HEV as large water-borne outbreaks occur sporadically. The majority of these countries are also endemic for malaria. This study estimated that countries for which blood donations are restricted following travel due to malaria-risk accounted for 94%of overseas-acquired HEV cases in Australia. HEV prevalence was also measured in Nepal, a developing nation endemic for HEV, allowing for a comparison between an endemic and presumed non-endemic country (Australia). This study measured HEV IgG prevalence of 41.90% in Nepalese blood donors. Current and recent HEV infection occurred in Nepalese donors, based on 0.11% and 2.98% of donors having HEV antigen and HEV IgM, respectively. Though the water-borne mode of HEV transmission is common in Nepal, this study suggests other modes of transmission including zoonotic transmission may occur in Nepal. HEV infection results in a relatively high mortality rate in pregnant women and can cause chronic infection in immunocompromised individuals. Hence a safe blood supply for these risk groups should also be of concern in developing countries. Priorities for safe blood transfusion vary between Australia and Nepal, based on how common infectious agents are in these countries, as well as the maturity of blood transfusion services, and the cost-effectiveness of screening. This research has provided an evidence based assessment of the risk HEV currently poses to the safety of the blood supply in Australia. The research findings from this study will be utilised to develop strategies for managing blood transfusion safety and form the basis of policies to manage the potential threat of TT-HEV. Prevalence and incidence data are also of importance to public health authorities to supplement existing data sets to assist with assessing the current burden of HEV infection in Australia.