Actinobacillus pleuropneumoniae (APP) in Pigs: Fibrinohemorrhagic Pleuropneumonia and Diagnosis

Etiology

Actinobacillus pleuropneumoniae (APP) is a Gram-negative, facultatively anaerobic, pleomorphic coccobacillus belonging to the family Pasteurellaceae. The organism is a primary bacterial pathogen of swine and the causative agent of porcine pleuropneumonia, a disease characterized by fibrinohemorrhagic and necrotizing lung lesions. APP requires nicotinamide adenine dinucleotide (NAD, V factor) for in vitro growth, a trait that distinguishes it from other Pasteurellaceae members such as Pasteurella multocida (see Fowl Cholera in Poultry: Pasteurella multocida Pathogenesis, Clinical Signs, Prevention, Control, and WOAH Classification for comparative pathogenesis). The bacterium produces a polysaccharide capsule and expresses a range of virulence factors, most notably the Apx exotoxins (ApxI, ApxII, ApxIII, and ApxIV). These repeats-in-toxin (RTX) proteins are hemolytic and cytotoxic, causing pore formation in host cell membranes, lysis of alveolar macrophages and neutrophils, and the release of proinflammatory mediators that drive the characteristic fibrinohemorrhagic exudation.

Eighteen serotypes (1 through 18) have been described based on capsular polysaccharide and lipopolysaccharide antigens. Serotypes 1, 5, 9, and 11 are considered highly virulent, while others show moderate to low virulence. Cross-protection between serotypes is limited, complicating vaccine strategies. The Apx toxin profile varies by serotype: serotype 1 produces ApxI and ApxII; serotype 2 produces ApxII and ApxIII; serotype 5 produces ApxI and ApxII; and serotype 3 produces only ApxII and ApxIII. ApxIV is produced by all virulent strains and is used as a target for serological differentiation between infected and vaccinated animals (DIVA strategy).

Epidemiology

APP is distributed worldwide in swine-producing regions. Transmission occurs primarily via direct contact between pigs through respiratory droplets and aerosols. Carrier animals, often subclinically infected, serve as the main reservoir. The bacterium can persist in the upper respiratory tract (tonsils and nasal cavities) for months. Stressors such as crowding, poor ventilation, temperature fluctuations, and concurrent infections (e.g., with Mycoplasma hyopneumoniae or porcine reproductive and respiratory syndrome virus) precipitate clinical outbreaks. Morbidity can reach 40-60% in naive herds, and mortality ranges from 10-30% in acute cases. The disease is most common in growing-finishing pigs (8-16 weeks of age) but can affect all ages.

Clinical Signs

The clinical presentation of Actinobacillus pleuropneumoniae APP pigs fibrinohemorrhagic pleuropneumonia varies from peracute to chronic forms.

Peracute form: Sudden death without premonitory signs. Pigs may be found dead with cyanotic extremities and bloody froth from the nostrils.

Acute form: High fever (41-42 degrees C), severe dyspnea, open-mouth breathing, coughing, anorexia, and reluctance to move. Affected pigs often adopt a dog-sitting posture to facilitate respiration. Auscultation reveals harsh lung sounds, crackles, and pleural friction rubs. Cyanosis of the ears, snout, and extremities is common. Death occurs within 24-48 hours if untreated.

Subacute and chronic forms: Milder respiratory signs, intermittent cough, reduced growth rate, and poor feed conversion. Chronic cases may develop pulmonary abscesses, sequestra, and fibrous pleural adhesions. These animals remain carriers and shed the organism intermittently.

Pathology

Gross lesions are predominantly in the lungs and pleura. In acute cases, the lungs show bilateral, multifocal to coalescing areas of fibrinohemorrhagic necrosis, often affecting the diaphragmatic and cardiac lobes. Affected tissue is dark red to black, firm, and sharply demarcated from adjacent normal parenchyma. A characteristic feature is the presence of a thick, yellow fibrin layer covering the pleural surface, often with adhesions to the parietal pleura. The pleural cavity may contain serosanguinous fluid mixed with fibrin clots. Cut surfaces of the lung reveal a mottled pattern of hemorrhage, necrosis, and fibrinous exudate.

Histologically, the lesions consist of coagulative necrosis of alveolar septa, massive infiltration of neutrophils and macrophages, fibrin deposition, and thrombosis of pulmonary vessels. The Apx toxins induce apoptosis and necrosis of alveolar epithelial cells and endothelial cells, leading to vascular leakage and hemorrhage. In chronic cases, fibrous encapsulation of necrotic foci (sequestra) and pleural fibrosis are observed.

Diagnostics

Accurate diagnosis of Actinobacillus pleuropneumoniae APP pigs fibrinohemorrhagic pleuropneumonia requires a combination of clinical, pathological, and laboratory methods. The following table summarizes the main diagnostic approaches.

Diagnostic Workflow

The following Mermaid diagram illustrates a decision tree for laboratory diagnosis of APP in a suspect outbreak.

flowchart TD
    A[Clinical signs: acute dyspnea, fever, sudden death], > B[Postmortem examination]
    B, > C{Gross lesions: fibrinohemorrhagic pleuropneumonia?}
    C, >|Yes| D[Collect lung tissue and pleural fluid]
    C, >|No| E[Consider other causes: Mycoplasma hyopneumoniae, PRRSV, swine influenza]
    D, > F[Perform bacterial culture on chocolate agar + NAD]
    F, > G{Growth of NAD-dependent Gram-negative coccobacilli?}
    G, >|Yes| H[Identify by MALDI-TOF or biochemical tests]
    G, >|No| I[Perform real-time PCR for apxIV directly from tissue]
    H, > J[Serotype by multiplex PCR or coagglutination]
    I, > J
    J, > K[Report serotype and antimicrobial susceptibility]
    K, > L[Implement control measures: vaccination, biosecurity, antimicrobial therapy]

For herd-level surveillance, serological testing using ApxIV-based ELISA is recommended. This assay detects antibodies against the ApxIV toxin, which is expressed only during active infection and not in pigs vaccinated with subunit vaccines lacking ApxIV. This DIVA (Differentiating Infected from Vaccinated Animals) capability is critical for monitoring eradication programs.

Differential diagnoses include other causes of acute respiratory disease in swine: Mycoplasma hyopneumoniae (enzootic pneumonia), Pasteurella multocida (secondary pneumonia), Streptococcus suis (meningitis and pneumonia), Haemophilus parasuis (Glasser's disease), and viral pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus. Coinfections are common and can exacerbate clinical severity. For comparative respiratory pathology in other species, see Mannheimia haemolytica and Ovine Pneumonic Pasteurellosis and Mycoplasma bovis in Feedlot Cattle.

Treatment

Antimicrobial therapy is most effective when initiated early in the acute phase. The drug of choice depends on local susceptibility patterns, but commonly used classes include:

• Beta-lactams (ceftiofur, amoxicillin)
• Tetracyclines (oxytetracycline, doxycycline)
• Fluoroquinolones (enrofloxacin, marbofloxacin)
• Macrolides (tulathromycin, gamithromycin)
• Florfenicol and tiamulin

Injectable formulations are preferred for acutely ill pigs due to anorexia. Water or feed medication may be used for group treatment during outbreaks. However, antimicrobial resistance is an emerging concern, particularly against tetracyclines and some beta-lactams. Susceptibility testing (disk diffusion or broth microdilution) should guide therapy. For a broader discussion of resistance in livestock pathogens, see Antimicrobial Resistance in Livestock-Associated Staphylococcus aureus.

Supportive care includes providing a stress-free environment, adequate ventilation, and non-steroidal anti-inflammatory drugs (e.g., flunixin meglumine) to reduce fever and inflammation.

Control and Prevention

Control of APP relies on a combination of biosecurity, management, and vaccination.

Biosecurity: All-in/all-out production systems, strict quarantine of incoming stock, and separation of age groups reduce transmission. Carrier pigs should be identified and culled in eradication programs. Rodent and bird control is important as mechanical vectors.

Vaccination: Commercial bacterins (killed whole-cell vaccines) and subunit vaccines containing Apx toxins and outer membrane proteins are available. Bacterins provide serotype-specific protection and reduce clinical severity but do not prevent colonization. Subunit vaccines offer broader cross-protection but require booster doses. Autogenous vaccines can be tailored to the circulating serotype(s) in a herd. The DIVA capability of ApxIV-based vaccines allows serological monitoring.

Eradication: Herd depopulation and repopulation with APP-free stock is the most effective method but is economically prohibitive. Partial depopulation combined with medication and vaccination has been used with variable success.

Management: Optimize ventilation, reduce stocking density, and minimize environmental stressors. Control concurrent infections (e.g., PRRSV, Mycoplasma hyopneumoniae) through vaccination and management.

For related respiratory disease control in other livestock, refer to Necrotic Enteritis in Broiler Chickens: Clostridium perfringens Virulence Factors for an example of bacterial pathogenesis in poultry, and Listeria monocytogenes: Circling Disease in Ruminants for a comparative perspective on bacterial infections in livestock.

References

[1] World Organisation for Animal Health (WOAH). Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Chapter 3.8.1: Actinobacillus pleuropneumoniae. Paris: WOAH.

[2] Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW, Zhang J, editors. Diseases of Swine. 11th ed. Hoboken: Wiley-Blackwell.

[3] Gottschalk M. Actinobacillus pleuropneumoniae. In: Gyles CL, Prescott JF, Songer JG, Thoen CO, editors. Pathogenesis of Bacterial Infections in Animals. 4th ed. Ames: Blackwell Publishing; 2010. p. 319-332.

[4] Bosse JT, Janson H, Sheehan BJ, Beddek AJ, Rycroft AN, Kroll JS, et al. Actinobacillus pleuropneumoniae: pathobiology and pathogenesis of infection. Microbes Infect. 2002;4(4):449-460.

[5] Frey J. Virulence in Actinobacillus pleuropneumoniae and RTX toxins. Trends Microbiol. 1995;3(7):257-261.