ACTINOBACILLUS PLEUROPNEUMONIAE (APP)
LEVELS: Rarely occurs: Requires significant failure at one or more control points for transmission to humans; Highly unlikely: No evidence of non-foodborne zoonotic transmission; Highly effective: Routine on-farm biosecurity measures are effective in preventing farm-to-farm transmission; Easy: Distinct clinical signs and/or existing test(s) available at local/regional laboratory(s); Substantial: Unsustainable acute or chronic losses related to severe clinical signs in a high prevalence of animals; Temporary disruption: Measureable negative effect on demand for less than a month when disease occurs on one or more farms; Moderate risk: Evidence of development of clinically important resistance to antibacterial or antiviral treatments, or that development of such resistance is likely to occur over time; High risk: Antibacterial or antiviral treatments commonly used on affected groups, or for prophylaxis; Available but with uncertain efficacy: Limited treatments available in US or are only effective in some situations; Available but uncertain efficacy: Commercial or autogenous vaccines exist in the US but protection may be inconsistent; Possible: Eradication possible but likely to require major changes into logistic systems, regulatory environment, infrastructure, and producer behaviors
OVERVIEW
Actinobacillus pleuropneumoniae (APP) is a small, gram-negative, encapsulated coccobacillus that causes porcine pleuropneumonia, one of the most important bacterial respiratory diseases of swine worldwide. APP is classified into two biotypes based on NAD (nicotinamide adenine dinucleotide) requirement for growth: biotype I (NAD-dependent) and biotype II (NAD-independent). Nineteen serotypes have been described, with virulence varying remarkably among serotypes and even within the same serotype across geographic regions. The most virulent strains can rapidly induce fatal fibrinohemorrhagic and necrotizing pleuropneumonia in pigs of all ages, with experimental infections causing death within 6 hours of inoculation. Survivors often develop chronic lung lesions with bacteria-laden sequestra. The major virulence factors are the RTX (repeats-in-toxin) exotoxins ApxI, ApxII, ApxIII, and ApxIV, with different serotypes producing different combinations. Serotypes 1, 5, 7, and 9/11 are generally most virulent in North America and Europe. APP resides primarily in the tonsils of carrier pigs, and many conventional herds harbor multiple strains, including highly virulent strains that may remain subclinical until environmental stressors or concurrent infections trigger outbreaks. Economic losses result from mortality, reduced growth, veterinary costs, and slaughterhouse condemnations. High mortality outbreaks are now less frequent in North America but remain problematic in Latin America, Asia, and Europe.
FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL
Level: Rarely occurs: Requires significant failure at one or more control points for transmission to humans
APP does not typically infect humans and poses minimal public health risk. The chapter states: "APP does not usually infect humans and poses no public health risk." Only isolated incidents have been documented: "necrosis from needlestick injury with live APP vaccine (non-virulent strain for pigs)" and "isolation of an APP serotype 5 strain from a poorly healing wound of a swine producer after being bitten by a boar." These represent rare occupational exposures rather than foodborne transmission. There is no evidence of foodborne transmission risk from consumption of pork products.
NON-FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL
Level: Highly unlikely: No evidence of non-foodborne zoonotic transmission
Human infections are exceptionally rare and limited to specific occupational accidents. The documented cases involve direct inoculation (needlestick with live vaccine, bite wound contamination) rather than respiratory or contact transmission typical of APP's spread among pigs. These incidents represent isolated cases rather than a pattern of zoonotic transmission. APP's host specificity is notable: "APP is widely distributed and only infects pigs" with swine being the "primary reservoir." This host restriction makes human infection unlikely through normal occupational contact.
EFFECTIVENESS OF ON-FARM BIOSECURITY IN PREVENTING FARM-TO-FARM TRANSMISSION
Level: Highly effective: Routine on-farm biosecurity measures are effective in preventing farm-to-farm transmission
APP transmission can be controlled through rigorous biosecurity: (1) Primary transmission route: "Transmission between herds occurs mainly through the introduction of carrier animals"; (2) Short-range spread: "The main route of spread is by direct nose-to-nose contact or by droplets within short distances"; (3) Limited environmental survival: "Survival of the organism in the environment is of short duration, especially in warm, dry conditions"; survives only days when protected by organic matter; up to 30 days in clean water at 4°C; (4) Effective disinfection: "Common disinfectants are effective against APP when organic matter is first removed by thorough washing"; (5) Airborne transmission limited: "Kristensen et al. reported that airborne transmission between closely located pig units is possible, but uncommon." However, some recent outbreaks suggest biosecurity gaps (shared rendering trucks) can facilitate spread. Standard biosecurity practices—controlled introductions, serological testing, quarantine—can prevent APP introduction and spread.
DIFFICULTY OF DETECTING AND CONFIRMING INFECTION
Level: Easy: Distinct clinical signs and/or existing test(s) available at local/regional laboratory(s)
Multiple well-validated diagnostic methods are available: (1) Clinical and gross pathology: Typical lesions allow presumptive diagnosis; (2) Culture: "It is relatively easy to demonstrate APP by culture in pneumonic lesions from freshly dead animals" on blood agar with staphylococcal nurse streak; (3) Rapid identification: CAMP phenomenon, urease activity, MALDI-TOF MS; (4) Molecular detection: Species-specific PCR tests, multiplex PCR for serotyping all 19 serotypes; direct detection from FTA cards; (5) Serology: LPS-ELISA for serotype/serogroup-specific detection; ApxIV ELISA for species-specific detection; multiplex fluorescent microbead-based immunoassays. The main diagnostic challenges are: detecting tonsillar carriers in subclinically infected herds, differentiating from A. suis (biotype II), and identifying serotypes of atypical strains. Chronic cases may require serology rather than culture due to difficulty isolating from old lesions.
FINANCIAL IMPACT ON FARM'S COST OF PRODUCTION
Level: Substantial: Unsustainable acute or chronic losses related to severe clinical signs in a high prevalence of animals
APP causes substantial economic losses through multiple mechanisms: (1) Mortality: "The most virulent strains can rapidly induce fatal fibrinohemorrhagic and necrotizing pleuropneumonia in pigs of all ages"; peracute death can occur within 6 hours; up to 25% mortality reported in recent serotype 15 outbreak in US; (2) Reduced growth: "reduced growth" and "impact on average daily gain" documented though variable; (3) Veterinary costs: Antimicrobials, vaccinations, diagnostic testing; (4) Slaughterhouse condemnations: Chronic pleuritic adhesions result in condemnations; "high prevalence of dorsocaudal pleuritis at slaughter is very suggestive of previous APP pleuropneumonia"; (5) PRDC component: APP contributes to porcine respiratory disease complex with additive effects from coinfections; (6) Endemic herd losses: "Most conventional herds are infected with one or more serotypes." The chapter emphasizes that "APP remains a significant cause of economic loss to the swine industry." While high mortality outbreaks are now "rather infrequent" in North America, they "remain a problem in Latin American, Asian, and European countries."
EFFECT ON DOMESTIC OR EXPORT MARKETS
Level: Temporary disruption: Measureable negative effect on demand for less than a month when disease occurs on one or more farms
APP status affects trade in breeding stock and high-health animals: (1) Seedstock purchases: "Seedstock should be purchased from herds with a history of absence of clinical sign and APP-compatible lesions, and serological results must be negative for all known APP serotypes if animals are to be introduced in an APP-free herd"; (2) SPF/high-health programs: European SPF programs include APP-free status; introduction of positive animals into negative herds requires careful management; (3) Regional serotype considerations: "it is critical when testing imported pigs to select diagnostic tests targeting the most important virulent serotypes present in their region or country of origin"; (4) Slaughter plant findings: Chronic pleuritic adhesions affect carcass value. APP is not a WOAH-listed disease triggering international trade restrictions, but serological status is a significant consideration for genetic stock movement and high-health herd certification.
PATHOGEN'S ABILITY TO DEVELOP AND SPREAD RESISTANCE
Level: Moderate risk: Evidence of development of clinically important resistance to antibacterial or antiviral treatments, or that development of such resistance is likely to occur over time
APP shows variable antimicrobial resistance patterns: (1) Generally susceptible: "APP is rarely resistant in vitro to cephalothin, ceftiofur, florfenicol, tilmicosin, tiamulin, spectinomycin, or tildipirosin"; (2) Some resistance observed: "highest frequency of resistant isolates was found for gentamicin, penicillin, and tetracycline"; North American data showed "high level of resistance to chlortetracycline (88.4%) and oxytetracycline (90.7%)"; (3) Variable susceptibility: "Susceptibility to amoxicillin and enrofloxacin was high or intermediate, depending on the reports and the countries"; (4) Geographic variation: Resistance patterns differ by region; (5) No serotype association: "there is no clear correlation between the distribution of the antibiotic resistances and the serotypes of APP." Regular susceptibility monitoring is recommended.
AMR DEVELOPMENT DRIVEN BY DISEASE MANAGEMENT
Level: High risk: Antibacterial or antiviral treatments commonly used on affected groups, or for prophylaxis
APP management frequently involves population-level antimicrobial use: (1) Outbreak treatment: "During outbreaks of pleuropneumonia on APP infected farms, the priority must be to control mortality by treating affected individuals, usually including all contact animals in the affected pen"; (2) Feed/water medication: "Feed and water medication can be used as prophylactic antimicrobial therapy to prevent acute outbreaks in highly infected herds" where allowed; (3) Strategic medication: "strategic medication may be targeted at periods of risk"; (4) Documented collateral effects: "a single treatment event with enrofloxacin significantly increased the occurrence of quinolone-resistant Escherichia coli in the herd, even years after treatment." The chapter notes that endemic infection in many conventional herds creates ongoing pressure for antimicrobial use.
AVAILABILITY OF EFFECTIVE TREATMENT OPTIONS
Level: Available but with uncertain efficacy: Limited treatments available in US or are only effective in some situations
Antimicrobial treatment is generally effective when initiated early: (1) Multiple effective agents: Ceftiofur, florfenicol, tilmicosin, tiamulin, enrofloxacin, tulathromycin, lincomycin/spectinomycin shown effective; (2) Critical timing: "Antibiotic therapy is effective only in the initial phase of the disease when it can reduce mortality"; "success of therapy depends mainly on early detection of clinical signs and on rapid intervention"; (3) Route matters: "Antibiotics should be given parenterally (subcutaneously or intramuscularly) and in high dosage, as affected animals may not eat or drink"; (4) Limitations: Treatment does not eliminate carrier state—"antibiotic therapy does not eliminate infection in a herd and carrier animal may persist for a long time"; late treatment results in "chronic damage, which will leave the animal with compromised respiratory function"; (5) Susceptibility testing recommended: MIC testing and pk/pd considerations should guide antibiotic selection.
AVAILABILITY OF EFFECTIVE VACCINES OR BACTERINS
Level: Available but uncertain efficacy: Commercial or autogenous vaccines exist in the US but protection may be inconsistent
Multiple vaccine types are available with documented efficacy but notable limitations: (1) Commercial vaccine types: Killed organisms (bacterins), subunit toxin-based vaccines (ApxI, II, III), toxin-expressing bacterins; (2) Documented benefits: "vaccines can basically reduce clinical signs, treatments, and lung lesions"; improve daily weight gain and feed conversion; reduce slaughterhouse condemnations; (3) Serotype limitations: "Vaccination with bacterins is serotype-specific"—must match infecting serotype; (4) Carrier state persists: vaccines are "poorly effective in eliminating the carrier stage"; "presence of antibodies (either natural or vaccine induced) will not eliminate the carrier state"; (5) Maternal antibody interference: "first dose should not be administered during the first 7–8 weeks of age"; (6) Variable field performance: "It is extremely hard to predict which type of vaccine is working better in a given situation, and this seems to depend on the farm and the strain involved"; (7) Autogenous vaccines: Used when commercial products don't match local serotypes. Subunit and toxin-expressing bacterin vaccines provide broader cross-protection against multiple serotypes.
FEASIBILITY OF ERADICATING THE DISEASE FROM THE US
Level: Possible: Eradication possible but likely to require major changes into logistic systems, regulatory environment, infrastructure, and producer behaviors
Eradication is achievable at herd level but would be extremely challenging nationally: (1) Successful herd-level eradication documented: Multiple methods have succeeded including depopulation/repopulation, medicated early weaning, partial depopulation with antimicrobial treatment; (2) SPF programs exist: European countries maintain APP-free breeding herds through health schemes; (3) Barriers to national eradication: High prevalence in conventional herds ("Most conventional herds are infected with one or more serotypes"); subclinical carriers difficult to detect; tonsillar carriage persists despite vaccination or treatment; wild boar populations are infected; (4) Serotype complexity: 19 serotypes with varying virulence; some serotypes are highly infective making eradication difficult; (5) Recontamination risk: Aerosol transmission between nearby herds documented; biosecurity gaps allow reintroduction. Herd-level eradication of specific virulent serotypes is feasible with significant resources; national eradication would require massive coordinated effort and may not be economically justified given subclinical carriage in most herds.