Ashish C. Shrestha

Hepatitis E virus and implications for blood supply safety, Australia.

To the Editor: Hepatitis E virus (HEV) is an emerging public health concern for industrialized countries (1). Although HEV infection has been associated with travel to countries where the virus is endemic, cases of autochthonous HEV are increasing (2). Detection of HEV RNA in blood donations in the United Kingdom, Germany, the Netherlands, Japan, and China and accumulating reports of HEV transmitted through blood transfusion highlight the potential risk this virus poses to blood supply safety (1–4). In Australia, where most HEV infections are associated with travel (5), an average of 25 HEV cases occurred each year during 1999–2013 (http://www9.health.gov.au/cda/source/rpt_3.cfm). HEV infection is nationally notifiable in Australia, but the presence of subclinical infections and the lack of recent seroprevalence studies have prevented the accurate estimation of HEV incidence and population exposure. Thus, we examined HEV seroprevalence in a cohort of Australian blood donors, assessed risk factors for exposure, and used the data to examine the effectiveness of current blood safety strategies for the management of HEV in Australia. Plasma samples (n = 3,237) were collected from donors during August–September 2013. Information on age, sex, state of residence, new/repeat donor status, and overseas travel disclosure was obtained. Details of any relevant blood donation deferral (malaria, diarrhea) applied on previous donation attempts were also collected. Application of a specific malaria deferral code is routine for donors disclosing travel to a malaria-endemic country, and a diarrhea deferral applies when a donor reports having had diarrhea (of viral or unknown cause) 1 week before any attempted donation. All samples were tested for HEV IgG by using the Wantai HEV-IgG ELISA (Beijing Wantai Biologic Pharmacy Enterprise Co., Ltd, Beijing, China). Positive samples were tested for HEV IgM by using the Wantai HEV-IgM ELISA and for HEV RNA by using a prototype transcription-mediated amplification assay (Hologic Inc., San Diego, CA, USA). Of 3,237 samples, 194 (5.99%) were positive for HEV IgG (95% CI 5.18–6.81). Compared with estimates from previous studies that used the Wantai ELISA (6–9), our estimate is comparable to those reported from Scotland (4.7%) and New Zealand (4.2%) but lower than those from the United States (18.8%) and southwestern France (52.5%). Considerable debate exists regarding the sensitivity and specificity of HEV detection methods (2,10); however, on the basis of studies in France and the United Kingdom (9,10), we believe that the measured seroprevalence in our study is accurate. Our findings showed an increased seroprevalence of HEV associated with previous malaria deferral, diarrhea deferral, and age (multivariate logistic regression) (Table), the latter of which is consistent with previous findings (9). IgG seropositivity was also higher (7.73%) in donors who had traveled to a malaria-endemic country. HEV is often endemic to malaria-endemic countries (http://wwwnc.cdc.gov/travel/yellowbook/2014); however, the HEV exposure status of travelers is unknown before departure, so the exact place of exposure cannot be determined. Furthermore, 3.37% of donors in our study had evidence of previous HEV exposure; these donors had not reported travel outside Australia, so they may have acquired HEV locally. Because subclinical HEV infection is possible, persons infected locally may not be identified by the current donor screening questionnaire and thus pose a potential risk to blood supply safety. Table HEV (IgG) seroprevalence, and risk factors for exposure, in Australian blood donors* Detection of HEV IgM in 4 (2.06%) of the 194 samples from IgG-positive donors indicates the donors had been recently exposed to HEV (95% CI 0.06–4.06). All 4 donors had traveled overseas; 3 reported travel to malaria-endemic countries. HEV RNA was not detected in any of the HEV IgG–positive samples. Although it is encouraging that HEV nucleic acid was not detected, the sample size is insufficient to accurately determine the true rate of HEV RNA carriage among donors in this study; a larger study is planned. Management strategies to safeguard the Australian blood supply against transfusion-transmitted HEV are based on donor selection guidelines. To identify donors with possible bacteremia/viremia, including HEV, blood donation staff members ask donors several medical, behavioral, and travel-based questions before donation. These include questions relating to general wellness, sex practices, gastric upset, diarrhea, abdominal pain, and vomiting within the previous week. In addition, for 4 months after a donor’s return from travel to a malaria-endemic country, donations are restricted to plasma for fractionation. Some protection against blood donations from HEV-infected persons may occur because HEV and malaria are co-endemic to many countries. Our findings showed a higher HEV seroprevalence among donors with prior malaria or diarrhea deferrals; thus, malaria- and diarrhea-related screening questions may reduce contributions from donors with travel-associated HEV infection. Our findings showed HEV exposure in travelers and nontravelers, suggesting the possibility of imported and locally acquired HEV in Australia. Prior HEV exposure was higher in donors who were temporarily excluded from donating blood on previous donation attempts, suggesting the current management strategy in Australia is partially effective in minimizing any risk of HEV transmission through blood transfusion. However, the presence of HEV IgG in donors who reported no overseas travel and/or no prior related deferrals, coupled with the knowledge that asymptomatic infection is possible, suggests that additional safety precautions may be warranted.

Hepatitis E virus RNA in Australian blood donations

Hepatitis E virus (HEV) poses a risk to transfusion safety. In Australia, locally acquired HEV is rare and cases are mainly reported in travelers returning from countries endemic for HEV. The risk posed by HEV to transfusion safety in Australia is unknown; therefore, we aimed to measure the rate of current HEV infection in Australian blood donations.

A Comparative Study of Assay Performance of Commercial Hepatitis E Virus Enzyme-Linked Immunosorbent Assay Kits in Australian Blood Donor Samples

Hepatitis E virus (HEV) is transfusion-transmissible and therefore poses a risk to blood transfusion safety. Seroprevalence studies are useful for estimating disease burden and determining risk factors. Considerable variability in the sensitivity of HEV antibody detection assays exists. This study aimed to compare the performances of commercially available HEV enzyme-linked immunosorbent assays (ELISA) in Australian blood donor samples. Plasma samples that tested positive (n = 194) or negative (n = 200) for HEV IgG (Wantai HEV IgG ELISA) were selected. Of the 194 HEV IgG positive samples, 4 were positive for HEV IgM (Wantai HEV IgM ELISA). All samples were tested with the MP Diagnostics: HEV IgG ELISA, total (IgG, IgM, and IgA) HEV antibody ELISA, and HEV IgM ELISA. Of the 194 Wantai HEV IgG positive samples, 92 (47%) tested positive with the MP Diagnostics HEV IgG ELISA (κ = 0.47) and 126 (65%) with MP Diagnostics total HEV antibody assay (κ = 0.65). There was poor agreement between Wantai and MP Diagnostics HEV IgM assays. This study demonstrated poor agreement between the assays tested. These observations are consistent with previous reports demonstrating significant variability between HEV ELISAs, highlighting that results of HEV serology should be interpreted with caution.

Hepatitis E virus: do locally acquired infections in Australia necessitate laboratory testing in acute hepatitis patients with no overseas travel history?

Summary Hepatitis E virus (HEV) is emerging as a global public health threat. Water-borne HEV outbreaks are common in developing countries and are associated with genotypes 1 and 2. In industrialised countries, sporadic cases of zoonotic transmission associated with genotypes 3 and 4 are increasingly being reported. Transfusion- and transplantation-transmitted HEV have been documented, although ingestion of contaminated food is thought to be the major transmission route. Severe disease is possible and chronic hepatitis infection occurs in solid-organ-transplant recipients and in patients with immunosuppressive disorders. In Australia, HEV cases are mainly travellers returning from disease endemic countries. Indeed, there are few reported cases of locally acquired HEV. Pigs in Australia have been shown to be infected with HEV, which indicates the possibility of zoonotic transmission. The extent of locally acquired infection is not known, however it may be greater than expected and may necessitate laboratory testing in patients reporting no overseas travel.

Co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors in Kathmandu, Nepal

Background: HIV, HBV, Syphilis and HCV share common modes of transmission. Objective: The study was aimed to determine the co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified blood donors. Methods: The study was conducted on blood samples screened as HCV seropositive at Nepal Red Cross Society, Central Blood Transfusion Service, Kathmandu, Nepal. HCV seropositive samples were further tested for HIV, HBV and Syphilis. Results: Eight co-infections were observed in 139 HCV seropositives with total co-infection rate of 5.75% (95% CI = 2.52-11.03). Conclusion: Co-infection of HIV, HBV and Syphilis with HCV is prevalent in the healthy looking blood donors of Kathmandu, Nepal.

Hepatitis E virus infections in travellers: assessing the threat to the Australian blood supply.

BACKGROUND In many developed countries hepatitis E virus (HEV) infections have occurred predominantly in travellers to countries endemic for HEV. HEV is a potential threat to blood safety as the virus is transfusion-transmissible. To minimise this risk in Australia, individuals diagnosed with HEV are deferred. Malarialdeferrals, when donors are restricted from donating fresh blood components following travel toanareain which malaria is endemic, probably also decrease the HEV risk, by deferring donors who travel to many countries also endemic for HEV. The aim of this study is to describe overseas-acquired HEV cases in Australia, in order to determine whether infection in travellers poses a risk to Australian blood safety. MATERIALS AND METHODS Details of all notified HEV cases in Australia from 2002 to 2014 were accessed, and importation rates estimated. Countries in which HEV was acquired were compared to those for which donations are restricted following travel because of a malaria risk. RESULTS Three hundred and thirty-two cases of HEV were acquired overseas. Travel to India accounted for most of these infections, although the importation rate was highest for Nepal and Bangladesh. Countries for which donations are restricted following travel due to malaria risk accounted for 94% of overseas-acquired HEV cases. DISCUSSION The vast majority of overseas-acquired HEV infections were in travellers returning from South Asian countries, which are subject to donation-related travel restrictions for malaria. This minimises the risk HEV poses to the Australian blood supply.

Hepatitis E virus seroepidemiology: a post-earthquake study among blood donors in Nepal

BackgroundAs one of the causative agents of viral hepatitis, hepatitis E virus (HEV) has gained public health attention globally. HEV epidemics occur in developing countries, associated with faecal contamination of water and poor sanitation. In industrialised nations, HEV infections are associated with travel to countries endemic for HEV, however, autochthonous infections, mainly through zoonotic transmission, are increasingly being reported. HEV can also be transmitted by blood transfusion. Nepal has experienced a number of HEV outbreaks, and recent earthquakes resulted in predictions raising the risk of an HEV outbreak to very high. This study aimed to measure HEV exposure in Nepalese blood donors after large earthquakes.MethodsSamples (n = 1,845) were collected from blood donors from Kathmandu, Chitwan, Bhaktapur and Kavre. Demographic details, including age and sex along with possible risk factors associated with HEV exposure were collected via a study-specific questionnaire. Samples were tested for HEV IgM, IgG and antigen. The proportion of donors positive for HEV IgM or IgG was calculated overall, and for each of the variables studied. Chi square and regression analyses were performed to identify factors associated with HEV exposure.ResultsOf the donors residing in earthquake affected regions (Kathmandu, Bhaktapur and Kavre), 3.2% (54/1,686; 95% CI 2.7–4.0%) were HEV IgM positive and two donors were positive for HEV antigen. Overall, 41.9% (773/1,845; 95% CI 39.7–44.2%) of donors were HEV IgG positive, with regional variation observed. Higher HEV IgG and IgM prevalence was observed in donors who reported eating pork, likely an indicator of zoonotic transmission. Previous exposure to HEV in Nepalese blood donors is relatively high.ConclusionDetection of recent markers of HEV infection in healthy donors suggests recent asymptomatic HEV infection and therefore transfusion-transmission in vulnerable patients is a risk in Nepal. Surprisingly, this study did not provide evidence of a large HEV outbreak following the devastating earthquakes in 2015.