Inclusion body hepatitis as a primary disease

According to Dr Holly Sellers, professor of Virology at the Poultry Diagnostic and Research Center (PDRC), University of Georgia, US, there has been a significant increase in IBH case submissions coming into the PDRC lab. The number of case submissions in 2018 doubled compared to the previous 4-5 years, when requests for IBH diagnostic testing were sporadic. The number of IBH case submissions in 2021 tripled relative to 2018. These submissions to the PDRC lab have been from numerous companies in different geographic regions of the US.

Breaking down the adenoviruses

Dr Sellers adds that the surge in the IBH problem doesn’t appear to be solely a domestic issue in the US, as she has also noticed an increase in international case submissions to the PDRC. Taking a closer look at the breakdown of the adenoviruses that were isolated or detected with polymerase chain reaction (PCR), we can see a shift: with the pre-2018 case submissions, FAdV group E serotype 8a, or FAdV group D serotype 11 both used to be isolated. Since 2018 the primary adenoviruses are FAdV group E serotype 8b.

Data presented by Dr Davor Ojkic, adjunct faculty virologist and immunologist at the Animal Health Laboratory, at the University of Guelph, Canada, concurs with these findings. Positive diagnostic submissions of IBH have been on the rise in Canada since 2016 with the FAdV 8b serotype forming the majority of positive cases.

IBH – a global problem

Dr Guillermo Zavala, senior consultant at Avian Health International, LLC and former professor of Poultry Medicine at the University of Georgia, US, also holds that IBH is a global problem in the poultry industry and can be seen in just about every area of the world – from the Americas to Europe, Africa, Central Asia and Southeast Asia. And that serotype 4 of FAdV continues to be present but not as prevalent as it was in the 1980s. He adds that serotype 8b is now by far the most prevalent serotype, globally. He also maintains that although traditionally FAdVs were considered opportunistic pathogens that take advantage of immunosuppression caused primarily by infectious bursal disease (IBD) and Marek’s disease, as well as chicken anaemia virus (CAV), in recent years there has been considerable evidence that FAdV 8b is also a primary pathogen that can cause IBH in chickens in the absence of IBD or other predisposing immunosuppressive factors. However, it is important to note that the clinical presentation of IBH can be exacerbated by immunosuppression. Other non-infectious immunosuppressive factors in the field, including mycotoxins and other stressors, should not be ignored and must also be accounted for in the diagnostic process.

IBH explained

Inclusion body hepatitis (IBH) is a viral disease that is commonly diagnosed in commercial chickens worldwide. The disease is caused by fowl avian adenovirus (FAdV) group I, which is a member of the Adenoviridae family of viruses. The disease is characterised by the presence of intranuclear inclusion bodies in the liver, spleen and kidney of affected birds.

IBH is an acute disease that typically occurs in broiler chickens between 2-6 weeks of age. In commercial poultry farms this disease is most commonly seen in large flocks with high stocking densities. The virus is transmitted vertically and horizontally, and is spread via the faecal-oral route with infected birds shedding the virus in their faeces​. When the disease is transmitted vertically, clinical symptoms and mortality usually appear between 16-18 days of age, while when it is transmitted horizontally, it usually presents after 25-26 days of age​.

There are 5 different species of FAdV (A to E) with different genotypes and 12 serotypes (1 to 8a, 8b to 11). Some geno or serotypes are known to induce hepatitis hydropericardium syndrome (HHS) (known to be caused by serotype 4 – common in some parts of the world), inclusion body hepatitis (IBH) and adenoviral gizzard erosion (AGE). Anti-FAdV antibodies can be measured either by enzyme-linked immunosorbent assay (ELISA) (broad cross-detection) or by neutralization assay (serotype specific)​. Clinical symptoms of IBH include depression, appetite loss, diarrhoea and decreased water intake. The liver is frequently swollen, enlarged, with a yellowish discolouration and many pale and/or red (hemorrhagic) foci. Occasionally the kidneys may be involved. Mortality rates can range from 0% to 30%, depending on the severity of the outbreak.

Primary vs secondary IBH

A study was carried out in 2006 in Saskatchewan, Canada, to examine a possible association between IBH and infectious bursal disease virus (IBDV) and chicken infectious anemia virus (CAV) infections in Western Canada, and to identify the adenoviruses involved in outbreaks. The results of polymerase chain reaction (PCR) and sequencing identified high percentages of the virus FAdV-7, FAdV-8a, FAdV-8b and FAdV-11. ELISA serology titers showed that antibody response to vaccinations against IBDV and CAV was at expected levels in all broiler flocks, and therefore IBH outbreaks in the flocks were not due to inadequate levels of antibodies against IBDV and CAV​​. Moreover, the researchers did not find a correlation between occurrences of IBH outbreaks in broilers and their IBD or CAV titers at the time of processing​. Another study in Ontario​ demonstrated that pathogenic genotypes of FAdV serotypes FAdV-02, FAdV-08 and FAdV-11 constituted 39.38% of the isolates and similarly showed that there was no significant association between flock exposure to FAdV and exposure to CAV or IBDV.

Historical data

Historically speaking, in the decades that followed the initial discovery of an avian adenovirus in 1949, adenoviruses were isolated from both healthy and sick birds in various geographical locations​. The ability of IBDV and CAV to aggravate the clinical symptoms of FAdV was later demonstrated​. The primary pathogenicity of FAdVs was initially questioned because of the sporadic incidence of IBH, the widespread prevalence of FAdVs in chicken flocks and the importance of immunosuppression in inducing IBH. Based on initial field data and experimental infections, the general perception for a long time was that co-infection with an immunosuppressive virus (either IBDV or CAV, or both) was needed for a clinical FAdV-induced disease to manifest, mainly IBH and HHS.

Re-evaluating virulence

However, more recent laboratory and field reports from several regions in the world, including Canada, Australia, the Middle East, Japan and elsewhere, have demonstrated the primary role of FAdV, arguing for the need to re-evaluate the virus’s virulence​​ although earlier reports had also pointed in the same direction​.

Virulence of a specific FAdV strain

Moreover, experimental studies have shown that the outcome of an infection is mostly influenced by the virulence of a specific FAdV strain rather than the additive effects of concurrent infections​​. This is corroborated by a comparison of various infection studies that have been conducted using FAdVs of the same serotype, as significant differences in virulence between strains has been observed​.

Certain strains play a key aetiological role

This has been demonstrated in the field by the growing problems associated with FAdV, and several studies on the pathogenicity of the virus following outbreaks have confirmed that certain strains play a key aetiological role in distinct clinical disorders​. As previously mentioned, 2 Canadian studies demonstrated no statistically significant correlation between flocks exposed to FAdV and co-infected with CAV or IBDV​, indicating that the prevalence of FAdV does not correspond with the presence of IBDV or CAV.

FAdVs: Primary pathogens

Two findings from a 2021 study in Spain have suggested that FAdVs seem to be primary pathogens in the vast majority of IBH cases: (1) opportunistic CAV and IBDV have been successfully controlled in commercial meat-type poultry in the country by vaccination of broiler breeders; and (2) IBH-suspected cases have also been screened for CAV, with consistently negative results. These observations build upon existing evidence that FAdV may be a primary pathogen of IBH​.

FAdVs: Primary aetiologic agents

The emergence of hepatitis hydropericardium syndrome (HHS) and adenoviral gizzard erosion (AGE) in Europe, on the other hand, has also raised awareness of FAdVs as primary aetiologic agents, highlighting the importance of FAdV infections particularly in young chickens, especially broilers. There have also been more frequent reports of IBH outbreaks in various parts of the world over the last 2 decades​.

Immunosuppression is still a significant trigger

It is important, however, to note that although strains from the same serotype can vary in their pathogenicity​, immunosuppression is still a significant trigger for IBH, HHS and AGE and therefore particular care should be taken to protect birds accordingly​. FAdVs are frequently isolated from chickens that have suffered from immunosuppression due to infectious agents such as IBDV, CAV, Marek’s disease and, less commonly, reovirus or parvovirus​. Several researchers have also reproduced FAdV diseases of greater severity following experimental immunosuppression with chemicals or mycotoxins​. The role of physical and other types of stressors (e.g. suboptimal temperatures, stocking density, etc.), increased risk. Raising chickens in brand new barns, short downtimes between flocks, high viral load in the barn, poor litter management, the co-existence of other infectious diseases, like necrotic enteritis, also need to be considered​.

Emergence of recombinant FAdVs

A tendency towards more epidemic, rather than sporadic, FAdV outbreaks has been seen in many countries, especially over the past 2 decades. The most recent evidence on the emerging potential of the disease is currently provided by mounting reports of severe adenoviral outbreaks in China​. This change may be explained by more recent reports indicating the emergence of recombinant FAdVs in the field which, in turn, may explain the appearance of more pathogenic strains of FAdV within serogroups (e.g. 4 or 8b) which are capable of causing primary disease.