JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

November 2024

D-V20

 

SLIDE A: Signalment (JPC #4035678): 3 week old broiler chicken

 

HISTORY: There was a sudden onset of mortality affecting 10% of the flock. Sick birds adopted a crouching position with ruffled feathers and died within 48 hours. 

 

HISTOPATHOLOGIC DESCRIPTION: Liver: Randomly affecting 60% of the section, there is multifocal to coalescing disruption of the hepatic cord architecture characterized by hepatocellular degeneration and/or necrosis admixed with eosinophilic and karyorrhectic debris (lytic necrosis), edema, and fibrin. Hepatocytes within the affected areas exhibit one of the following changes: swollen with pale eosinophilic, vacuolated cytoplasm, often with one discrete cytoplasmic vacuole up to 15 µm in diameter (lipid change), hypereosinophilic and shrunken with rounded to angular cytoplasm and a shrunken, pyknotic nucleus (single cell necrosis), or are lost. Degenerate hepatocyte nuclei occasionally contain 10-20 µm, round to irregularly round, basophilic, smudgy, intranuclear inclusion bodies that fill and expand the nucleus and peripheralize the chromatin. Multifocally portal areas are expanded by low numbers of heterophils, lymphocytes, fewer macrophages, and plasma cells with admixed karyorrhectic debris. In some periportal regions there are granulocytic precursors (extramedullary hematopoiesis). Multifocally, sinusoids are expanded and congested by erythrocytes. The capsule is mildly undulant.

 

MORPHOLOGIC DIAGNOSIS: Liver: Hepatitis, necrotizing, multifocal to coalescing, random, acute, with numerous hepatocellular basophilic intranuclear viral inclusions, chicken, avian.

 

ETIOLOGIC DIAGNOSIS: Adenoviral hepatitis

 

CAUSE:  Fowl adenovirus

 

CONDITION: Inclusion body hepatitis (IBH); hydropericardium syndrome

 

SLIDE B: Signalment (JPC #4113523): 3-month-old male white turkey

 

HISTORY: Found weak but ambulatory. Rapidly became pale and unable to stand, and died abruptly. Hemorrhagic discharge from the anus was noted on physical examination. 

 

HISTOPATHOLOGIC DESCRIPTION: Intestine: The luminal mucosa is circumferentially markedly congested and there is necrosis of approximately 90% of the mucosal epithelium characterized by loss of architecture with replacement by eosinophilic cellular and karyorrhectic debris. There is abundant hemorrhage and fibrin with the lumen containing sloughed mucosal epithelial cells, hemorrhage and cellular debris. There are mats of cocci and rod bacteria enmeshed within the fibrin and necrotic cellular debris. The lamina propria is diffusely expanded by moderate infiltrates of macrophages, with fewer heterophils, lymphocytes and plasma cells. Inflammation surrounds and separates crypts that rarely contain luminal aggregates of cellular debris and inflammatory cells (crypt abscesses). Previously described inflamamtion occasionally infiltrates into the crypt and mucosal epithelium. Multifocally, low numbers of histiocytes have an enlarged nucleus which contains a single amphophilic to basophilic intranuclear viral inclusion. 

 

Spleen: Affecting approximately 95% of the spleen, the parenchyma, predominantly the white pulp, is expanded by numerous macrophages, lymphocytes and fewer heterophils and plasma cells which efface the normal architecture. Within the white pulp, there are increased numbers of macrophages that contain intracytoplasmic cellular and karyorrhectic debris (lymphocytolysis). Macrophages and lymphocytes often have an enlarged nucleus which contains a single amphophilic to basophilic intranuclear viral inclusion. 

 

MORPHOLOGIC DIAGNOSES: 1. Intestine: Enteritis, necrohemorrhagic, diffuse, severe, with intranuclear viral inclusion bodies, white turkey (Meleagris gallopavo), avian. 

2. Spleen, white pulp: Hyperplasia, diffuse, severe, with lymphocytolysis and intranuclear viral inclusion bodies. 

 

ETIOLOGIC DIAGNOSIS: Adenoviral enteritis and splenitis

 

CAUSE: Turkey hemorrhagic enteritis virus

 

CONDITION: Hemorrhagic enteritis, Marble spleen disease

 

 

GENERAL DISCUSSION:

• Five genera of adenovirus (double-stranded DNA viruses) are currently recognized: Aviadenovirus, Mastadenovirus, Atadenovirus, Ichtadenovirus, and Siadenovirus; possibly a sixth (Testadenovirus)
• Aviadenoviruses are widely distributed throughout the world and can infect all age groups of domestic birds 
• Three avian adenovirus genera cause disease in birds; there are various serotypes within each genera:
  • Aviadenovirus (previously group I)
    • Fowl Adenovirus (FAdV) species represented as FadV A-E 
      • Multiple serotypes with each species represented as FAdV-1, FAdV-2, etc. (1-11) under each species
    • Turkey Adenovirus B
  • Siadenovirus (previously group II)
    • Turkey Adenovirus A – hemorrhagic enteritis virus
  • Atadenovirus (previously group III)
    • Duck Adenovirus A – egg drop syndrome
• Fowl adenovirus (FAdV) species D and E (serotypes 12 and 8 respectively) are associated with IBH; cause a sudden increase in mortality of young chickens

 

PATHOGENESIS:

• Transmission: Fecal, aerosol (rare), oral, and transovarian
• Virus exposure via GI, conjunctival, or nasal routes > primary replication in nasopharynx and intestine > viremia with dissemination to secondary sites of replication (hepatocytes, enterocytes, respiratory epithelial cells) > virus replication and shedding (especially into feces)
• More severely affects < 5 week old chicks, does not tend to cause disease in older animals. 
• Pathogenicity varies with strain and is enhanced by immunodeficiency, coinfection with chicken infectious anemia virus, infectious bursal disease, and/or avian leucosis
• Viral persistence and reactivation may occur
• Infection often latent; can reactivate with stress (peak egg production)
• No cross protection among serotypes

 

TYPICAL GROSS FINDINGS:

• Skin: Pale, possible icterus; petechial and ecchymotic hemorrhages in skeletal muscle of legs
• Liver: Swollen and pale; friable; petechial and ecchymotic hemorrhages
• Heart: Hydropericardium
• Gizzard: Erosions within the koilin layer
• Kidney: Enlarged, pale or mottled
• Bursa of Fabricius: Atrophy
• Rarely, can cause wrinkled eggs in ostriches. 

 

TYPICAL MICROSCOPIC FINDINGS:

• Liver: Diffuse hepatocellular degeneration and multifocal necrosis with basophilic to amphophilic intranuclear inclusion bodies; lymphocytic infiltrates with few heterophils; may progress to granulomatous response with fibrosis and biliary hyperplasia
• Rare inclusions may be present in the surface epithelium of the gizzard and epithelial cells of the small intestine
• Pancreas: Necrosis, rare inclusions may be present in the acinar cells
• Kidney: Glomerulonephritis; cortical tubular degeneration and necrosis is less common
• Heart: Myocarditis and hemorrhage

 

ULTRASTRUCTURE:

• Intranuclear viral particles are arranged in a paracrystalline array 
• Non-enveloped, double stranded DNA virus, 80-100 nm

 

ADDITIONAL DIAGNOSTIC TESTS:

• Serology, virus isolation 
• IHC against FAV
• PCR – detection of FAdV from liver
• ELISA for FAdV serotypes 4, 7, and 8 (L, J Vet Diagn Invest., 2020; Xie, J Vet Diagn Invest, 2021)

 

DIFFERENTIAL DIAGNOSIS: 

• Common coinfections with Aviadenovirus
  • Infectious bursal disease (birnavirus): May precede IBH; edema, hemorrhage, necrosis of bursa of Fabricius in chicks 3-5 wks old
  • Chicken infectious anemia (circovirus): Disease of young chickens causing severe (aplastic) anemia, hemorrhages in proventriculus, subcutaneous tissue and muscle, thymic and bone marrow atrophy
  • Infectious bronchitis (coronavirus)
  • Avian vibrionic hepatitis (Campylobacter jejuni): Myeloid hyperplasia
• Toxicities causing hemorrhage/anemia
  • Sulfas: Hemorrhages in skin, muscle, internal organs; thrombocytopenia, blood dyscrasias; folate inhibitors; no long common
  • Mycotoxins: Tricothecene-producing Fusarium sp.; acute lethal toxic levels associated with visceral and hepatic hemorrhages

 

COMPARATIVE PATHOLOGY:

Avian Adenoviruses:

• Aviadenovirus
  • Quail bronchitis virus (FAdV A)
    • Conjuctivitis, tracheitis with mucus, air sacculitis, hepatitis, and gaseous distention of the intestine
      • Pinpoint foci of necrosis in the liver
      • Mottling and enlargement of the spleen
    • Basophilic intranuclear inclusion bodies in the liver

• Adenoviral gizzard erosion (FAdV A)
  • Distended gizzard with hemorrhage and multiple erosions/ulcerations within the koilin layer. 
• Hydropericardium-hepatitis syndrome (FADV C serotype 4)
  • Hydropericardium with accumulation of gelatinous material in the pericardium. With myocardial edema with degeneration and necrosis
  • Within the liver lesions are similar to IBH, but more severe
    • Chick embryo lethal orphan (CELO) virus
  • Hemorrhagic enteritis virus (HE, turkeys > 4 weeks of age)
    • Diffuse hemorrhagic enteritis
    • Mottled spleen (necrosis), enlarged unless severe blood loss
    • Intranuclear inclusion bodies in spleen and GI within macrophages and lymphocytes
  • Marble spleen disease (MSD, pheasants, H-V08)
    • Respiratory signs (edema, congestion, dyspnea, and death)
  • Avian adenovirus splenomegaly (AAS, chickens) 

• Atadenovirus 
  • Egg drop syndrome (Duck adenovirus 1)
    • Eggs with no shell (vs. soft-shell eggs seen with infectious bronchitis virus (coronavirus)) 
    • The natural host of this virus is ducks and geese which may be asymptomatic; the virus causes outbreaks of egg drop syndrome in chickens and quail where it infects the oviduct and shell gland resulting in abnormal thin shelled or soft shelled eggs
• Fatal adenovirus infections are commonly reported in falcons and more rarely hawks (Torii, J Vet Diagn Invest, 2022), as well as in lovebirds (acute conjunctivitis, hepatic necrosis, pancreatitis), Senegal parrots (hepatitis in nestlings; Psittacine Adenovirus-1), budgerigars (budgerigar adenovirus-1) and Gouldian finches (a novel adenovirus).

 

Mammalian Adenoviruses (mastadenovirus):

• Bovine adenovirus: One of many suspected agents for Bovine Enzootic pneumonia 
• Canine adenovirus 1 (D-V19): Infectious canine hepatitis
• Canine adenovirus 2 (P-V21): Can cause upper respiratory disease and/or conjunctivitis
• Equine adenovirus: Can cause pneumonia in SCID (Arab) foals
• Porcine adenovirus: Typically asymptomatic but known to cause pneumonia and enteritis
• Simian adenovirus: Typically asymptomatic but can cause pneumonia and gastroenteritis, conjunctival and corneal lesions, most often in immunocompromised individuals, and is also associated with pancreatitis and less commonly hepatitis
• Human adenoviruses cause acute respiratory disease and keratoconjunctivitis 
• Hamsters: Adenovirus can experimentally cause tumors in hamsters
• Adenovirus hemorrhagic disease of deer: Endotheliotropic, causes endothelial damage leading to ischemic necrosis; lesions primarily seen in lungs and GI tract
• California sea lion adenovirus-1: Unique form of canine adenovirus 1, can cause necrotizing hepatitis

 

Reptilian Adenoviruses: Most are atadenoviruses

• Chelonian Adenovirus (Siadenovirus; the only reptilian non-atadenovirus)
• Sulawesi tortoise adenovirus-1 (only reptilian adenovirus within the Siadenovirus genus): Necrotizing enterocolitis, hepatocellular necrosis, myeloid necrosis and splenic necrosis with INIBs.
• Lacertilia (lizard) adenovirus: Reported in many lizards, overrepresented in bearded dragons (Agamid adenovirus 1)

• Histo lesions similar to other species to include INIB within hepatocytes and often other cell types (e.g. bile duct epithelium, enterocytes, endothelium, and renal tubular epithelium) 
• Gross lesions are often not seen
• Clinically variable, none to wasting, anorexia, CNS signs

 

REFERENCES:

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