Inclusion Body Hepatitis and Hepatitis Hydropericardium Syndrome in Poultry

The etiological agents of inclusion body hepatitis (IBH) and hepatitis hydropericardium syndrome (HHS) in poultry are fowl adenoviruses (FAdVs), which are nonenveloped linear double-stranded DNA viruses belonging to the genus Aviadenovirus of the family Adenoviridae.

Adenoviruses are widespread throughout all avian species. Most adenoviruses cause no or only mild disease (adenoviruses or their antibodies may be found in healthy birds); however, some are associated with specific clinical conditions.

FAdVs have been classified into 5 species (A–E), with each species containing 1 or more of 12 known serotypes (1–7, 8a, 8b, and 9–11). However, binomial nomenclature is now the official format for naming virus species in viral taxonomy.

• Aviadenovirus gallinae (FAdV-2 and FAdV-11) and A hepatitidis (FAdV-8a and FAdV-8b) have been associated with IBH in broiler chickens.

• A hydropericardii (FAdV-4 and FAdV-10) is the main etiological agent of HHS in chickens as well as in ducks.

• In chickens, a syndrome referred to as adenoviral gizzard erosion has also been linked to A ventriculi (FAdV-1) in several countries.

Variable levels of cross-protection have been reported between viruses belonging to different serotypes or genotypes. Analyses of the whole genome sequence from a large number of FAdVs have revealed recombination events between FAdV strains, reflecting a complex cross-protection relationship.

Inclusion body hepatitis primarily affects commercial broiler chickens. IBH-like disease caused by various members of the genus Aviadenovirus has also been reported in other poultry species, including turkeys, farmed pigeons, and geese, as well as various other birds (including parrots, kestrels, and a merlin).

IBH has been reported in Southeast Asia, Europe, the Middle East, Australia, New Zealand, North America, Central America, and South America. HHS has been reported in China, Pakistan, Japan, Korea, Iraq, Mexico, Peru, Ecuador, and Chile.

Horizontal and vertical transmission play an important role in IBH and HHS. Vertical transmission has been documented in progeny from breeder flocks infected with FAdV-4 and FAdV-8. Horizontal transmission, leading to peracute disease and death, has also been demonstrated in young chicks placed in contact with infected chicks.

Infection with some strains of FAdVs may result in minimal hepatic disease; however, if birds have been infected with other immunosuppressive viruses, clinical signs of disease are exacerbated.

Sudden increase in daily mortality from IBH and HHS is usually observed in chickens < 6 weeks old and can occur in chicks as young as 4 days old (see flock mortality graph).

Mortality rates normally range from 2–40% with IBH and from 20–80% with HHS. Mortality rates also vary depending on the pathogenicity of the virus and concurrent infection with other viral or bacterial agents.

Flock mortality pattern, inclusion body hepatitis, chickens

Image

Courtesy of Dr. Amir H. Noormohammadi.

Clinical signs associated with diseases caused by other pathogens (eg, bacteria, fungi, or viruses) commonly occur if birds are immunosuppressed.

In flocks affected with IBH or HHS, sudden death often occurs, and individual chickens may show nonspecific clinical signs such as lethargy, huddling, ruffled feathers, and yellowish-green mucoid droppings, due to excess bile (see image of droppings, IBH). Affected birds show these clinical signs for 2 days before they die or recover. Elevated mortality rate usually lasts for 5 days with IBH and longer with HHS.

Droppings, inclusion body hepatitis, bird

Image

Courtesy of Dr. Amir H. Noormohammadi.

With IBH and HHS, the liver is often swollen and enlarged, with yellowish discoloration and multiple pale or red (hemorrhagic) foci (see hepatitis and hydropericardium image).

In cases of HHS, as much as 10 mL of a straw-colored transudate may be in the pericardial sac. Histopathological lesions in the liver include acute hepatocytic degeneration, necrosis, mononuclear cell infiltration, and rare to widespread basophilic intranuclear inclusion bodies. Lesions in the heart include myocardial edema and necrosis.

Hepatitis and hydropericardium, poultry

Image

Courtesy of Dr. Pedro Villegas.

• Tentative diagnosis: mortality pattern and gross lesions

• Definitive diagnosis: histological examination or PCR assay

A tentative diagnosis of IBH or HHS is usually based on a pattern of spiking mortality and typical gross lesions (see images of gross lesions, IBH and HHS).

The diagnosis is confirmed by microscopic examination of the affected tissues and detection of typical lesions, especially intranuclear inclusion bodies (see microscopic lesions photomicrographs), or by PCR assay. The latter can also be used in combination with nucleotide sequencing or high-resolution melt curve analysis of the amplified DNA for virus classification. This information is useful for epidemiological investigations and for developing an effective vaccination strategy.

Virus isolation and serological testing are rarely used for routine diagnosis but are useful tools for research and disease monitoring, respectively. Among serological assays, ELISA is considered the test of choice for monitoring host antibody responses.

Gross hepatic lesions, inclusion body hepatitis, chickens

Image

Courtesy of Dr. Amir H. Noormohammadi.

Microscopic hepatic lesions, inclusion body hepatitis, poultry

Image

Courtesy of Dr. Amir H. Noormohammadi.

• Vaccination

• Antimicrobials to prevent secondary disease

As with many other viral diseases, there is no treatment for IBH or HHS. Antimicrobials may help prevent secondary bacterial infections.

Given the ubiquitous and highly transmissible nature of FAdVs, biosecurity practices have little value for the prevention of IBH and HHS. In fact, rigorous biosecurity practices in the poultry industry have been hypothesized to contribute to disease transmission by generating immunologically naive breeding stocks. Therefore, control and prevention strategies should consider poultry flock immunity through vaccination. The exception is specific pathogen-free (SPF) flocks, where biosecurity is important because vaccination is not an option.

Various vaccines are used to control IBH and HHS in many countries. Available vaccines include the following:

• Killed virus vaccines against IBH and HHS

• Live virus vaccines against IBH or HHS, containing one or multiple FAdV serotypes

Both live virus vaccines and killed virus vaccines, comprising only one serotype (monovalent) or a combination of serotypes (multivalent), are available. Recombinant, vectored, and subunit vaccines have also been described but are primarily used in experimental settings.

The FAdVs most frequently used to prepare commercial vaccines belong to serotypes 4, 8b, and 11. Primary poultry breeders with stringent biosecurity practices sometimes use autogenous killed virus vaccines to ensure the transfer of maternal immunity from breeding flocks to their progeny. In Australia, a live virus vaccine is given via drinking water (contrary to the ocular route recommended by the manufacturer) to breeders between 10–14 weeks old. In other countries, including Mexico, Pakistan, and many countries in South America, killed virus vaccines are routinely used to vaccinate breeders and broilers. When breeders are properly vaccinated, antibodies generated by the vaccine are transmitted to the progeny, providing protection against field infections and clinical disease.

In some countries, broilers are occasionally vaccinated at < 10 days old when either their parents do not have serotype-specific adenovirus antibodies or maternal antibody transmission is erratic because of improper vaccination procedures.