JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC Accession #4048859): Four-week old male crossbred pig (Sus scrofa)
HISTORY: A respiratory disease in a pig herd quickly spread from the finishing unit to the growing and breeding units. The affected animals showed prostration with respiratory signs including sneezing. The disease disappeared two weeks after onset, except in the breeding unit. The presently examined pig was one of two in the breeding unit submitted for necropsy.
HISTOPATHOLOGIC DESCRIPTION: Lung: Affecting approximately 40% of this section, there are multifocal areas of atelectasis and consolidation centered around or adjacent to bronchi and bronchioles. Diffusely affecting the bronchioles, and to a lesser extent the bronchi, the epithelium is circumferentially either attenuated, degenerate and/or necrotic, sloughed and replaced by karryorhectic and cellular debris with infiltrating macrophages, neutrophils, lymphocytes, and plasma cells. This necrotic and inflammatory material variably fills bronchial and bronchiolar lumina which are mildly to moderately ectatic. The epithelium of less affected bronchi is often hyperplastic up to three cell layers thick, forming folds into the lumina or eroded and replaced by similar necrosis and inflammation which infiltrates through the lamina propria. Surrounding alveolar septa are diffusely thickened up to three times normal by lymphocytes, plasma cells, macrophages, and type II pneumocyte hyperplasia. Alveolar septa are often fragmented and necrotic with karryorhectic and cellular debris extending into the alveolar lumina which contain scattered neutrophils, macrophages, fibrin, and necrotic debris. There is mild perivascular and interlobular edema, and vessels often have hypertrophied endothelium.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, bronchointerstitial, necrotizing, multifocal, moderate, with type II pneumocyte hyperplasia, crossbred pig, porcine.
ETIOLOGIC DIAGNOSIS: Orthomyxoviral pneumonia
CAUSE: Swine orthomyxovirus (Influenza A virus)
CONDITION: Swine Influenza
- Single-stranded RNA orthomyxovirus: viral gene transcription in nucleus, viral protein production in cytoplasm, and virions bud from plasma membrane
- Causes outbreaks of severe nonfatal respiratory disease or as an endemic part of porcine respiratory disease complex
- Three genera of orthomyxoviruses
- Influenza A: Most significant; causes disease in swine, horses, humans and other species
- Influenza B: Human isolates only
- Influenza C: rare and cause mild to subclinical infections in humans and swine
- Genetic drift leads to point mutations and several genomic variants
- Antigenic variation of viral strains is dependent on 15 hemagglutinin (H) and 9 neuraminidase (N) envelope glycoproteins
- Used to track outbreaks and develop vaccine strains
- Swine act as hosts for reassortment among avian, porcine, and human influenza viruses because swine possess cell-surface receptors for avian and human viral strains
- Usually restricted to respiratory tract but may cause myocarditis, myositis, and encephalitis in carnivores and horses
- Spread by aerosol or contact with secretions and infect epithelial cells lining respiratory tract inducing necrotizing bronchitis/bronchiolitis
- Virulence proteins:
- Hemagglutinin binds to sialic acid (mammals: SAα2,6; birds: SAα2,3) and mediates fusion with host cell membrane
- Neuraminidase destroys receptors in mucus that mimic viral glycoprotein receptors, cleaving sialic acid and facilitating entry into host cells by degrading mucins
- Polymerases: direct cell processes towards viral replication
- PB1: catalyst for viral mRNA transcription
- PB2: most important in pathogenicity; removes 5’ caps from host pre-mRNA molecules (cap-snatching) for use as primers for viral mRNA production
- PA- assists w/ “cap snatching”
- NS1: Present only in host cell cytoplasm; interferes with host antiviral response by inhibiting apoptosis of viral infected cells and promoting it of cell that attack viral infected cells.
- Subtypes H1N1, H3N2, and H1N2 are common in North America
- More virulent viruses express three characteristics:
- Higher or more prolonged levels of virus replication
- Induction of a strong proinflammatory response (cytokine storm) àincreased permeability
- Replication in the lower respiratory tract
- IgA and IgG are maximally elevated 1-4 weeks after exposure
- Virus shed for 5-7 days but cleared from lung 72 hours after infection
- Infection maintained in swine population by continuous exposure of naïve animals, no evidence of long-term carriers
TYPICAL CLINICAL FINDINGS:
- Acute, rapid spread to all ages of pigs
- Coughing, fever, stiffness
- Pigs recover in 5-14 days with low mortality
- Endemic form:
- Pigs develop secondary bacterial pneumonia from subclinical influenza infection
- Signs not specific for influenza and require further diagnostics for confirmation
TYPICAL GROSS FINDINGS:
- Cranioventral lobular distribution of atelectasis, sharply demarcated from normal lung
- Affected lobules are red, firm, and collapsed
- Adjacent lobules may be emphysematous
- Mediastinal and bronchial lymph nodes are enlarged and edematous
- Secondary bacterial pneumonia may obscure lesions
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Hallmark lesion is necrotizing bronchitis/bronchiolitis
- Alveolar epithelium may also be necrotic, attenuation of bronchiolar epithelial cells
- Exudate in bronchiolar lumina composed of necrotic debris and neutrophils
- Atalectasis, peribronchiolar, perivascular and interstitial lymphocytes and plasma cells
- Hyperplasia of airway epithelium in later lesions, +/- bronchiolitis obliterans
- Virions bud from respiratory epithelial cell surface
ADDITIONAL DIAGNOSTIC TESTS:
- Selecting tissue from cranioventral areas early in course of disease is critical for histologic and virologic diagnosis
- PCR of fresh lung
- ELISA on nasal or bronchial swabs
- IHC on fixed tissue (to type A nucleoproteins)
- Virus isolation
- PCV-2 (PMWS): Granulomatous interstitial to bronchointerstitial pneumonia and lymphadenopathy
- Proliferative and necrotizing pneumonia: Severe acute disease; entire lung may be affected, alveolar luminal exudate and septal thickening with type II pneumocyte hyperplasia; generalized lymphadenopathy; etiology unclear, may be related to multiple viruses including PRRSV, PCV-2, H1N1, H3N2 influenza
- Pseudorabies (Suid herpesvirus-1): Lung lesions inconsistent; cranioventral distribution of scattered throughout the lung; bronchointerstitial pneumonia with necrosis and sloughing bronchiolar epithelium; intranuclear inclusions
- Nipah virus (paramyxovirus): Lymphocytic and/or fibrinoid vasculitis; lymphoid necrosis; syncytial cells and intracytoplasmic viral inclusion bodies
- Porcine reproductive and respiratory syndrome virus: Interstitial pneumonia with necrotic alveolar macrophages and aggregates of free chromatin; lymphadenopathy; lymphocytic infiltrates in multiple organs (often perivascular)
- Inhaled toxic gases: rare in animals; water-soluble gases (eg sulfur dioxide and ammonia)àupper respiratory injury; less soluble gases (eg nitrogen dioxide)à bronchiolar and alveolar injury, massive mortality in cattle, pigs, and chickens with pulmonary edema, congestion, necrosis of bronchial and bronchiolar epithelium, alveolar hemorrhage, and fibrin exudation
- Also affects feral swine and wild boar
- Waterfowl serve as reservoir of nearly all influenza A viruses
- Poultry: High and low path avian influenza (see D-V25)
- LPAI: amino acid adjacent to hemagglutinin cleavage site is only susceptible to proteases found in the GI and respiratory tracts
- HPAI: has a sequence of multiple basic amino acids that allows cleavage by furin-like proteases that are present in many tissuesàsystemic infection
- Equine influenza: H3N8, high morbidity/low mortality, mainly in foals; foci of consolidation separated by unaffected to hyperinflated lung; similar histo to swine influenza, tracheitis is common
- Canine: H3N8: self-limiting upper respiratory tract disease; tracheobronchial epithelial cell necrosis with a unique lesion that similarly affects the bronchial glands; H3N2: much more severe subtype, death common
- Feline: No unique virus, but susceptible to human H1N1 and avian H5N1 and H7N7; ingestion of H5N1 infected chicken liver induces systemic infection with targeting of endothelial cells
- Influenza A virus H1N2 identified in mink
- Influenza A virus H1N1 identified in cats as the first known case of lethal respiratory disease associated with 2009 pandemic
- Caswell JL, Williams KJ. Respiratory system. In: Maxie MG. ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2017:526-527, 567, 577, 587.
- Constable PD, Hinchcliff KW, Done SH, Grünberg W. Veterinary Medicine: A Textbook of the Diseases of Cattle, Horses, Sheep, Pigs, and Goats. 11th ed. St. Louis, MO: Elsevier; 2017:1075-1085.
- Detmer SE, Gramer MR, Goyal SM, Torremorell M. In vitro characterization of influenza A virus attachment in the upper and lower respiratory tracts in pigs. Vet Pathol. 2012;50(4):648-658.
- Janke BH. Influenza A virus infections in swine: Pathogenesis and diagnosis. Vet Pathol. 2014;51(2):410-426.
- Löhr CV, et al. Pathology and viral antigen distribution of lethal pneumonia in domestic cats due to pandemic (H1N1) 2009 influenza A virus. Vet Pathol. 2010; 47(3): 378-386.
- Sutherland-Smith M. Suidae and tayassuidae (wild pigs, peccaries). In: Miller RE, Fowler ME. eds. Fowler’s Zoo and Wild Animal Medicine. 8. St. Louis, MO: Elsevier Saunders; 2015:576.
- Watson CE, Bell C, Toohey-Hurth K. H3N2 canine influenza virus infection in a dog. Vet Pathol. 2017;54(3):527-530.
- Yoon KJ, Schwartz K, Sun D, Zhang J, Hildenbrandt H. Naturally occurring influenza A virus subtype H1N2 infection in Midwest United States mink (Mustela vison) J Vet Diagn Invest. 2012; 24(2): 388-391.
- Zachary JF. Mechanisms of microbial infections. In: Zachary JF. ed. Pathologic Basis of Veterinary Disease. 6th ed., St. Louis, MO: Elsevier; 2017:207, 210.