Avian hepatitis-E-virus infection is a disease of broiler breeders and table-egg layers. Infections may be subclinical or associated with low mortality and mild decreases in egg production. This article is the first part of a two-part description in which the disease is described for the first time extensively.
By Dr Tahseen Aziz , Rollins Animal Disease Diagnostic Laboratory and Dr H. John Barnes, College of Veterinary Medicine, NC State University, both in Raleigh, North Carolina, USA
The clinical disease caused by avian hepatitis E virus is referred to as hepatitis-splenomegaly (HS) syndrome (first recognised in Canada in 1991) and as big liver and spleen (BLS) disease (first recognised in Australia in 1980). From mid-1993 to 2001, a disease similar to HS syndrome occurred in Canada and the USA and was referred to as necrotic hemorrhagic hepatitis-splenomegaly syndrome, necrotic hemorrhagic hepatomegalic hepatitis, hepatitis-liver hemorrhage syndrome, or chronic fulminating cholangiohepatitis. Recently, we also have seen lesions in dead backyard chickens with lesions consistent with HS syndrome.
The causative virus
Avian hepatitis E virus (avian HEV) is a species within a yet-to-be named genus in the family Hepeviridae. The other genus in this family is Hepevirus that includes the species Hepatitis E virus, which infects mammals and which will be referred to in this article as mammalian HEV. Currently, four major genotypes of mammalian HEV are recognised. Genotypes 1 and 2 cause hepatitis in humans, while genotypes 3 and 4 infect humans, pigs, and possibly other animals.
In 2001, a virus was first isolated in the USA from the bile of chickens with HS syndrome. Based on genome organisation and significant nucleotide sequence identities with human and swine hepatitis E viruses, the isolated virus was classified as avian HEV to distinguish it from mammalian HEV. Avian HEV shares common antigenic epitopes and approximately 50% nucleotide sequence identity with mammalian HEV.
In Australia in 1999, an infectious agent that was presumed to be a virus was detected in chickens with BLS disease. Based on the nucleotide sequence of a short region of the genome, the virus was found to be related to human HEV. The HS syndrome virus isolated in USA was found to share about 80% nucleotide sequence identity with BLS disease virus isolated in Australia. Thus, it seems HS syndrome in North America and BLS disease in Australia are caused by variant strains of avian HEV. Despite extensive variations in the nucleotide sequence between mammalian and avian HEVs, it appears there is only a single serotype of the virus.
Gene sequence and phylogenetic analyses revealed heterogeneity among avian HEVs. Those recovered from chickens with HS syndrome in four different states in the USA showed heterogeneity regardless of geographical origin. However, viruses recovered from clinically healthy chickens clustered together and were genetically related to, but different from, those recovered from chickens with HS syndrome. Additionally, avian HEV can be separated into at least three different genotypes: genotype 1 (Australia), genotype 2 (USA), and genotype 3 (Europe) based on phylogenetic analysis of genomic sequences of the regional HEVs.
During the 1980’s and 1990’s, BLS was considered the most economically significant disease of commercial broiler breeders in Australia due to egg production losses and mortality. At one time, 50% of the breeder flocks were thought to be affected, with an estimated loss of 8-10 eggs per hen during the egg-production cycle. The economic impact of avian HEV infection in the USA is unknown as only a few, sporadic cases of HS syndrome have been reported in broiler breeder and table-egg layer flocks.
Subclinical infection with avian HEV in the USA is probably widespread and common. About 71% of flocks and 30% of chickens tested in a seroprevalence study of avian HEV infection among commercial chicken flocks in five states had antibodies to avian HEV. Among seropositive chickens, 36% were adult and 17% were under 18 weeks of age. In another study, avian HEV was identified from seropositive, clinically healthy chickens. It was believed that avian HEV infection is dose-dependent and that only chickens infected with higher doses of the virus develop HS syndrome. The possibility of avirulent strains of avian HEV that cause subclinical infection has also been suggested.
Two outbreaks of a disease resembling BLS disease have been reported in broiler breeder flocks in Italy. In Hungary, avian HEV infection in broiler breeder flocks was associated with a disease that had clinical and pathological features of BLS disease and HS syndrome. Antibodies to HEV have been detected in chickens in the United Kingdom, Vietnam, China, and Spain. Further serologic surveys are needed to determine the occurrence, distribution, and significance of avian HEV in chickens flocks throughout the world.
Source of infection and transmission
Droppings from infected chickens are the most likely source of infection for other birds as large amounts of the virus were shed in the faeces of experimentally infected chickens. The virus is primarily transmitted between birds and spreads in a flock via the faecal-oral route via contaminated feed, water, and litter.
Transmission between flocks occurs through contaminated litter that is carried by people or on fomites (e.g. equipment). There is no field or experimental data to conclusively indicate vertical transmission of the virus from infected hens to their progeny. The role of backyard chickens as a potential reservoir of avian HEV is unknown.
Hepatitis E virus infection occurs in broiler breeders and table-egg layers. Although subclinical infection of HEV is common in chicken flocks in the USA and perhaps in other countries, clinical disease associated with infection is relatively infrequent. Natural infections in turkeys have not been identified, but they can be infected experimentally.
Hepatitis-splenomegaly syndrome. Disease in broiler breeders and table egg layers usually occurs between 30-72 weeks of age with the highest incidence between 40 and 50 weeks. Clinically, the syndrome is characterised by “above-normal” mortality for several weeks. Weekly mortality usually increases to 0.3% but may reach or exceed 1%. In some cases, increased mortality is associated with a drop in daily egg production of up to 20%. In the USA, infection with avian HEV has been associated with so-called “primary feather drop syndrome” in which flocks show a delay in sexual maturity, fall short of their peak production goal, and moult primary feathers.
Big liver and spleen disease. Although chickens of all ages are susceptible to infection, clinical cases have been seen only in hens over 24 weeks of age. As with hepatitis-splenomegaly syndrome, weekly mortality may increase up to 1% and daily egg production my decrease by up to 20% (usually 4-10%). A sudden, rapid drop in egg production may be the first indication of HEV infection in a flock. The egg production drop usually lasts 3-6 weeks with another 3-6 weeks before production returns to a near-normal level. Decreased egg production is more evident if the flock becomes infected after attaining peak production. If the flock is affected during the first few weeks of production, delayed sexual maturity and low peak production may be the first signs of infection. Small eggs with thin, poorly pigmented shells are seen, but hatchability is usually not affected. Individual birds in affected flocks are lethargic, anorexic, have pale combs and wattles, and soiled feathers around the vents (pasty vents). Many birds in the flock may exhibit loss of primary feathers resembling moulting.