HEPATITIS E

frederik wid en

National Veterinary Institute (SVA) and Swedish University of Agricultural Sciences, Uppsala, Sweden

Hepatitis E virus belongs to the family Hepeviridae, which contains two genera: one named Hepevirus and one unnamed.

In the genus Hepevirus the gt land 2 infect only humans and are known to cause epidemic outbreaks under poor hygienic conditions in developing countries. The gt 3 and

4 are frequently present in pigs and wild boar and cause sporadic infections in humans. The detection of HEV in rabbits has led to the proposal of a fifth genotype of this genus, as it is only approximately 75% similar to the other genotypes(²).

The unnamed genus contains avian HEV, which has been found in poultry and is only 50% similar to the viruses in the Hepevirus genus. It can be further divided into three genotypes. There are no indications that these genotypes could infect mammals, including humans.

Furthermore, HEV detected in brown rats (Rattus nor- vegicus) appears to differ substantially from the genus Hep- evirus, with which it only is 60% similar, and from Avian HEV, with which it shares 50% sequence similarity.

Hepevirus has also been detected in other wild animals in Europe, including brown rats in Germany¹-¹⁰) and roe deer ( Capreolus capreolus) and red deer ( Cervus elaphus) in Hungary⁽⁷⁾. Elsewhere, detection of hepevirus has been reported in mongooses (Herpestes javanicus) and Sika deer (Cervus nippon) in Japan, and in oysters and farmed rex rabbits in China. There are also reports on the detection of hepevirus in Asian black bears (Selenarctos thibetanus), clouded leopards (Neofelis nebulosa), cattle, sheep and horses in China, but confirmation by further investiga­tions are warranted.

Infectious Diseases of Wild Mammals and Birds in Europe, First Edition. Edited by Dolores Gavier-Widen, J. Paul Duff, and Anna Meredith. © 2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd. Material authored by Paul Duff remains Crown Copyright.

This virus is not known to cause overt disease in wild animals, and little is known about the epidemiology. In domestic pigs the virus is most frequently detected in pigs of 3—4 months of age when maternal antibodies are waning and piglets from different sows are mixed. The fact that wild boar tend to live in family groups may have an influ­ence on how HEV is spread in this species, resulting in a different epidemiological situation to that of domestic pigs. Infection with HEV is self- limiting in mammals, including humans and pigs. Excretion in pig faeces lasts for 3—7 weeks⁽¹¹⁾ and viraemia for 1—2 weeks.

Infection with HEV occurs by the oral route.

Antibodies to HEV have been detected in several animal species such as dogs, cats, sheep, cattle and goats, as well as in non- human primates, but confirmation by direct virus detection methods is lacking and the presence of HEV in these animals has therefore not been confirmed. Another reason for caution is the difficulty of achieving consistent results for HEV antibody detection by enzyme- linked immunosorbent assays (ELISA) in different animal species.

The clinical signs in infected pigs are either inapparent or mild, and although this may also be true for wild boars it has not been studied. In humans, the clinical outcome of the infection is apparently dose-dependent⁽¹⁾; it may be sub-clinical or may cause mild to grave clinical symptoms and lead to death in approximately 0.5—4% of infected individuals due to hepatic failure. The mortality in preg­nant women is significantly higher and may reach 25%.

As wild animals infected with HEV probably do not display signs of disease, similar to domestic pigs, the diag­nosis is based on laboratory findings. Direct diagnostic methods include reverse transcription polymerase chain reaction (RT-PCR) or real-time RT-PCR for detection of HEV RNA in samples of faeces, liver or bile, whereas indirect methods such as ELISA can be used for detection of antibodies to HEV. Isolation of virus in cell culture is currently not possible. Although one research team⁽¹²⁾ report successful replication in vitro, others have not been able to reproduce the results.

At present, detection of HEV infection in animals is not notifiable, whereas infection in humans is notifiable in many countries. Infection with HEV is not possible to treat but it is self- limiting in animals and humans, although a few reports suggest the possibility of persistent infection in immunosuppressed humans. Vaccines for animals are not available. Vaccines have been developed for humans but are not yet commercially available.

Several studies have demonstrated that HEV from infected humans can be highly similar to HEV detected in pigs and wild boars, indicating that the infection is zoonotic and can be transmitted to humans by a food- borne route from these animals. The strongest evidence of such a route of infection comes from Japan, where human infection has been linked to the consumption of under­cooked pig and wild boar liver, as well as venison, and from Corsica, France, where human infection has been linked to the consumption of lightly smoked sausage con­taining pig liver and pig meat⁽¹³⁾. However, so far the routes of infection from animals to humans have not been sufficiently clarified.