JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2286508): Grower pig
HISTORY: One of a herd of several hundred 3 to 6-month-old grower pigs experiencing high mortality.
HISTOPATHOLOGIC DESCRIPTION: Lung: Diffusely, alveoli are filled with many foamy alveolar macrophages, low to moderate numbers of degenerate neutrophils, few lymphocytes, occasional colonies of 2 um coccobacilli, eosinophilic beaded to fibrillar material (fibrin), and pale eosinophilic homogenous material (edema). Multifocally and frequently centered upon bacterial colonies, leukocytes are degenerate with streamed nuclei (oat cells). Alveolar septa are frequently necrotic, characterized by loss of architecture and replacement with eosinophilic cellular and karyorrhectic debris. Diffusely, alveolar septa, interlobular septa, and the pleura are expanded by fibrin, necrotic debris, few inflammatory cells, occasional large colonies of coccobacilli, ectatic lymphatics and increased clear space (edema). Within bronchioles and bronchi, there is loss of epithelium with replacement by a mat of necrotic debris and fibrin. The lumina contain sloughed epithelial cells, necrotic debris, fibrin, macrophages and degenerate neutrophils. Bronchiolar and bronchial walls are expanded by edema, fibrin, necrosis, necrotic leukocytes, macrophages, lymphocytes and plasma cells. Multifocally, arteries have endothelial cell loss; absence of the internal elastic lamina; expansion of the walls by neutrophils, macrophages, fibrin, edema, and necrotic debris (necrotizing vasculitis) and often contain fibrin thrombi. Multifocally, there are mats of fibrin adherent to the pleural surface.
MORPHOLOGIC DIAGNOSIS: Lung: Pleuropneumonia, fibrinonecrotic, histiocytic and neutrophilic, subacute, diffuse, severe, with necrotizing vasculitis, fibrin thrombi, and large colonies of coccobacilli, breed unspecified, porcine.
ETIOLOGIC DIAGNOSIS: Pulmonary actinobacillosis
CAUSE: Actinobacillus pleuropneumoniae
CAUSE SYNONYMS: Formerly Haemophilus pleuropneumoniae, Haemophilus parahaemolyticu
CONDITION: Porcine contagious pleuropneumoni
SYNONYMS: Porcine actinobacillus pleuropneumoni
- One of the most common and important respiratory diseases of growing pigs
- Can cause disease without a primary viral infection
- Severe, often fatal fibrinohemorrhagic necrotizing pneumonia with accompanying fibrinous pleuritis
- All ages of swine are susceptible; however disea se is more common in pigs 6-weeks to 6-months of age, with peak mortality between 10‑16 weeks of age
- Peracute, acute, and subacute to chronic forms of the disease are recognized
- Actinobacillus pleuropneumoniae is an encapsulated, non‑motile, non-sporeforming, facultative anaerobic gram‑negative pleomorphic coccobacillus which requires an exogenous source of nicotinamide adenine dinucleotide (NAD)
- There are two biovars based on capsular antigens; biovar 1 has twelve serotypes and is NAD-dependent; biovar 2 has three serotypes and is NAD-independent
- Serovars are defined by their antigenic variation in capsular polysaccharide and cell wall lipopolysaccharides; serotypes 1,5,9 and 11 secrete both Apx I and II toxins and cause more severe disease
- Transmission via direct contact or aerosol droplets >colonization of the tonsil and adherence to the alveolar epithelium
- Organisms produce fimbriae that facilitate adherence
- Organisms adhere to or are phagocytized by alveolar macrophages
- Virulence factors include:
- 4 cytotoxins of the RTX (repeats in toxin) family (Apx I, II, III and IV), which cause cytolysis of porcine neutrophils, alveolar macrophages, erythrocytes, endothelium, and epithelium; lysis of leukocytes releases toxic materials e.g. reactive oxygen species (ROS), resulting in damage to host tissues
- Lipopolysaccharide (LPS) induces macrophage activation and secretion of neutrophil chemoattractants, procoagulant activity and complement activation
- Capsule impairs phagocytosis and may inhibit complement activation
- Additional virulence factors include fimbrial adhesins, outer membrane proteins, iron-binding proteins, metalloproteinase and urease
- Organism produces a variety of antioxidant enzymes including superoxide dismutase, catalase and hydrogen peroxide reductase that facilitate survival in the milieu of released cytotoxins and ROS
- The organism-produced cytotoxins and macrophage-elaborated cytokines (IL‑1, IL-6, IL‑8, TNF-alpha) and proteins (inducible-NOS) are responsible for lesion development
- Cytokine production > edema and congestion of alveolar walls, dilated lymphatics with fluid, fibrin and inflammation > platelet and neutrophil accumulation in damaged septa > thrombosis, vessel wall necrosis > infarct
TYPICAL CLINICAL FINDINGS: PERACUTE/ACUTE
- Anorexia; fever (105‑106oF); severe respiratory distress, cyanosis of skin on nose, ears and legs, coughing, dyspnea; +/- slight diarrhea and vomiting
- High morbidity and mortality; sometimes death with no preceding clinical signs
- Survivors of acute disease may become carriers
- Survivors of acute phase often become chronically ill, with low or no fever, intermittent cough, and loss of appetite
- +/- extrapulmonary manifestations such as arthritis, endocarditis, hepatitis, and lymph node abscesses
TYPICAL GROSS FINDINGS:
- Serofibrinous pleuritis, fibrinosuppurative bronchopneumonia and necrotizing hemorrhagic pneumonia
- Lesions are most commonly dorsocaudal with concentration around major bronchi near the hilus but may be anywhere in the lung, and are usually bilateral
- Blood‑tinged fluid in the thoracic cavity
- Foamy, blood-tinged, mucous exudate in the trachea and bronchi in rapidly fatal cases
- Fibrinous pleuritis and abscess‑like nodules surrounded by a thick connective tissue capsule are present most often in the diaphragmatic lobes
- Sequestra that develop from large foci of coagulative necrosis
- Rarely, granulomatous lymphadenitis and hepatitis
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Fibrinous and necrotizing pneumonia/pleuropneumonia
- Necrosis, hemorrhage, thrombosis, vasculitis, edema, fibrin deposition, and neutrophilic and histiocytic infiltration
- Extrapulmonary vascular lesions (thrombosis and fibrinoid necrosis) possible, especially in the kidney
- Degenerate alveolar leukocytes (oat cells) bordering areas of coagulative necrosis
- Large colonies of bacteria
- Macrophage infiltration, marked fibrosis around areas of necrosis, and fibrous pleuritis
- Fimbriae measure 0.5-2 nm in diameter and 60-450 nm in length
- ADDITIONAL DIAGNOSTIC TESTS:
- Gram‑stain of lung smears
- Serologic testing
- Salmonella choleraesuis: Fibrinonecrotic or hemorrhagic pneumonia; multifocal necrotizing hepatitis, splenomegaly, disseminated lymphadenopathy, and colitis
- Haemophilus parasuis (Glasser's Disease): Occasionally suppurative bronchopneumonia; usually fibrinous meningitis, polyserositis, and/or polyarthritis
- Pasteurella multocida: Suppurative bronchopneumonia with or without pleuritis; usually no vasculitis
- Salmonella choleraesuis: Interstitial pneumonia with hemorrhage and necrosis; interlobular edem
- Actinobacillus suis: Difficult to differentiate; causes pneumonia and septicemia in swine
- Streptococcus suis: Occasionally associated with bronchopneumonia
- Arcanobacterium pyogenes: Chronic suppurative bronchitis, bronchiolitis, and pulmonary abscesses in sheep, cattle and swine
- Swine influenza virus: Causes extensive bronchiolar necrosis
- Actinobacillus pleuropneumoniae only affects swine.
- Actinobacillus equuli in foals
- Most common cause of embolic suppurative nephritis in foals
- May also cause hepatitis, interstitial pneumonia, and fibrinous mesenteric lymphadenitis and peritonitis
- Actinobacillus lignieresii in cattle
- Causes deep glossitis (wooden tongue) and/or stomatitis
- 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 Limited; 2016:532-533.
- Gottschalk M, Taylor DJ. Actinobacillus pleuropneumoniae. In: Straw BE, Zimmerman JJ, D'Allaire S, Taylor DJ, eds. Diseases of Swine. 9th ed. Ames, IA: Blackwell Publishing; 2006:563-576.
- Lopez A, Martinson A. Respiratory system, mediastinum and pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. St. Louis, MO: Elsevier; 2017:543-544.
- Oh Y, Ha Y, Han K, et al. Expression of leucocyte function-associated antigen-1 and intercellular adhesion molecule-1 in the lungs of pigs infected with Actinobacillus pleuropneumoniae. J Comp Pathol. 2013; 148:259-265.
- Ohba T, Shibahara T, Kobayashi H, et al. Multifocal granulomatous hepatitis caused by Actinobacillus pleuropneumoniae serotype 2 in slaughter pigs. J Comp Pathol. 2008; 139:61-66.
- Ohba T, Shibahara T, Kobayashi H, et al. Granulomatous lymphadenitis associated with Actinobacillus pleuropneumoniae serotype 2 in slaughter barrows. Can Vet J. 2010; 51:733-737.
- Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. St. Louis, MO: Elsevier; 2017:172-173.