In the case from Singapore, the recipient was a 48-year-old man with chronic HBV and multifocal hepatocellular carcinoma that was outside of the eligibility criteria for liver transplantation in Singapore. The donor procured a commercial deceased donor liver graft in 2009 (country not reported), and was deeply jaundiced on returning to Singapore 3 weeks later for follow-up. Serology and NAT were positive for EBV and HEV-3, and acyclovir was commenced. Magnetic resonance imaging suggested an anastomotic biliary stricture and a biliary stent were successfully inserted; however, despite regular stent changes and good bile outflow, the patient's liver tests did not improve and he remained jaundiced. A liver biopsy 1 month after transplantation showed moderate acute cellular rejection, which responded well to pulse methylprednisolone, yet his liver function continued to deteriorate and 6 months posttransplant he was admitted to hospital with jaundice, ascites, peripheral edema, and constitutional symptoms, and he died shortly after from graft failure with disseminated bacterial and fungal infection. HEV RNA was still detectable at the time of death. In this case, it is not certain whether HEV was donor-derived, or whether the patient acquired it from eating contaminated meat shortly after transplantation.
In June 2017, the British Transplantation Society published guidelines for HEV detection and management in transplantation recipients, prompted by surveillance data from England indicating a recent rise in indigenous G3 HEV infection. Seroprevalence of HEV in the general English population is estimated to be as high as 13%, and data from the NHS Blood and Transplant selective screening program indicated that 1 in 2500 blood donations were HEV RNA-positive as of February 2017. A study of recipients of HEV-containing blood products found that 42% developed HEV infection, thus the approximate risk of transfusion-related HEV infection in England is 1 in 5000. On this basis, universal screening of blood components for HEV is now recommended by the UK Advisory Committee for the Safety of Blood, Tissues and Organs. The recommendations of the British Transplantation Society with regard to donor screening and management of HEV in solid organ transplant recipients are summarized in Table 25.
In summary, HAV and HEV pose a threat to transplantation in their acute phase, although outbreaks occur rarely in Australia. HDV is of greater concern, as coinfection/superinfection with HBV may seriously affect the outcome of transplantation and effective treatment is currently unavailable; however, measures to prevent HBV transmission to the recipient will prevent HDV transmission. Accordingly, the European Guide to the Quality and Safety of Organs for Transplantation states that organs from donors with HDV are usually not accepted, whereas organs are accepted regardless of the anti-HAV IgG/anti-HEV IgG status of the donor, except in cases of acute HAV/HEV infection. Other international guidelines do not include specific recommendations with respect to HAV, HDV, or HEV. An algorithm for the treatment of HEV-3 infection in transplant recipients has been developed in the event of donor-derived disease transmission or infection posttransplant (see Table 26). Australia and New Zealand are not endemic areas for HEV; therefore, there is no requirement for routine donor screening. HEV transmission is a risk only in the acute phase, so testing for this virus using NAT needs to occur only in donors with clinical suspicion (eg, acute hepatitis) and epidemiological risk for HEV infection.
Arboviruses refer to any viruses transmitted by arthropod vectors (eg, mosquitoes, ticks, sandflies). Arboviruses endemic to Australia include the flaviviruses Murray Valley encephalitis virus, the Kunjin lineage of WNV, and Japanese encephalitis virus, and the alphaviruses Ross River virus and Barmah Forest virus. Rates of infection are seasonal, peaking between approximately January and May when mosquitoes are most active, although seasonal trends vary between and within States and Territories according to differences in local mosquito vectors, hosts and climate. Ross River fever is the most common mosquito-borne disease of humans in Australia (6920 notifications in 2017), followed by Barmah Forest virus (449 notifications in 2017). Symptoms of Ross River virus most commonly include arthralgia, and less commonly rash and fever; however, up to 75% of Ross River virus infections are asymptomatic. Symptoms of Barmah Forest virus similarly include arthralgia, rash, fatigue, and flu-like symptoms, although again many people infected will be asymptomatic. Ross River virus and Barmah Forest virus infections have been reported in all Australian states (including Tasmania), with the highest notification rates occurring in Queensland, tropical Western Australia and the Northern Territory. The number of Ross River virus notifications in each State and Territory from 2007 to 2017 is shown in Figure 10. It should be noted, however, that there are known issues with unreliability of serological tests for Ross River virus and Barmah Forest virus, leading to overdiagnosis particularly in the off-season.
There have been no cases of transmission of Ross River virus or Barmah Forest virus infection by organ transplantation reported to date, although the potential for donor-derived transmission presumably exists given the ubiquity of these alphaviruses in Australia and 1 report in the literature of a case of Ross River virus transmission via blood transfusion occurring in Western Australia in 2014. The blood donor developed fatigue and arthralgia 2 days after giving blood and was subsequently diagnosed with Ross River virus infection; however, some of the components had already been transferred to a patient before the recall of the affected donation. The recipient was receiving regular blood transfusions due to myelodysplastic syndrome associated with chronic fatigue and joint pains, and had reported a worsening of symptoms in the months after the transfusion of the infected blood. Serological tests were positive for Ross River virus; however, the recipient experienced no further symptoms or sequelae. The potential outcomes in the event of transmission to an immunosuppressed organ transplant recipient are unknown.
In contrast to endemic alphaviruses, notifications of the Kunjin lineage of WNV and Murray Valley encephalitis virus are infrequent and mostly sporadic, with approximately 10 cases in recognized outbreak years, generally affecting residents of and visitors to the Kimberley region of Western Australia or the Northern Territory. However, despite the low notification rate, it is recognized that for every clinical case of there may be hundreds of asymptomatic infections, because the vast majority of Kunjin virus and Murray Valley encephalitis virus infections are asymptomatic. Anecdotal evidence suggests Kunjin virus causes symptomatic disease more often than Murray Valley encephalitis virus, with symptoms of Kunjin including arthralgia, myalgia, fever, headache, and occasionally, a rash. When Murray Valley encephalitis virus does cause clinical disease, symptoms are generally more than severe than for Kunjin virus: an estimated 1 in 1000 infections with Murray Valley encephalitis virus results in clinical encephalitis. Encephalitis is less common in cases of Kunjin virus infection. To date, there have been no cases of Kunjin virus or Murray Valley encephalitis virus transmission via blood transfusion or organ donation; however, precautions may be warranted particularly in regions where there are active outbreaks of disease.
Other nonendemic arboviruses of public health importance to Australia include dengue virus, chikungunya virus, and Zika virus. Nonendemic arboviruses are of concern primarily in the case of donors whose recent travel history includes south and southeast Asia, tropical Africa, or the Pacific Islands. Imported cases of dengue fever are relatively common among travellers returning from endemic areas, in particular India, Sri Lanka, southeast Asia, and the Pacific Islands (see Table 26).
In New Zealand, virtually all notified cases of arboviral infections to date have occurred in overseas travellers, although a local case of sexual transmission of Zika virus was reported in 2016. Only 1 arbovirus is endemic to New Zealand-the Sindbis-like alphavirus Whataroa virus which is established in bird populations on the West Coast of the South Island; however, human infection has only ever been documented serologically (absent of disease). There are 3 mosquito species established in New Zealand that have the potential to be vectors for human diseases: Culex quinquefasciatus (a potential vector for encephalitis viruses), Aedes notoscriptus (a vector for dengue virus), and Aedes australis (a vector for dengue and Whataroa viruses). All 3 are potential vectors for Ross River virus, by none are particularly effective arboviral vectors are would be unlikely to support endemic transmission of arboviruses in New Zealand.
In 2016, there were 191 cases of dengue virus infection (4.1 per 100 000) in New Zealand, 28 cases of chikungunya virus infection (0.6 per 100 000 population), 100 cases of Zika virus infection (2.1 per 100 000 population), and 4 cases of Ross River virus infection. Countries of acquisition included Indonesia (dengue), Fiji (dengue, chikungunya, Ross River, Zika), Tonga (Zika virus), Samoa (dengue, Zika), Thailand (dengue), India (chikungunya), Brazil (chikungunya), and Australia (Ross River virus).