LAWSONIA INTRACELLULARIS (PROLIFERATIVE ENTEROPATHY)
LEVELS: Highly unlikely: No controls necessary; Highly unlikely: No evidence of non-foodborne zoonotic transmission; Highly effective: Routine on-farm biosecurity measures are effective in preventing farm-to-farm transmission; Moderate: Clinical signs not unique but existing tests available at local/regional laboratory(s); Substantial: Unsustainable acute or chronic losses related to severe clinical signs in a high prevalence of animals; Negligible: Little or no market disruption when disease occurs on one or more farms; Minimal risk: Agent inherently unlikely to develop clinically important resistance to antibacterial or antiviral treatments; Minimal risk: Antibacterial or antiviral treatments rarely occur, or are typically limited to short-course individual animal therapy; 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; Not feasible: Eradication extremely unlikely
OVERVIEW
Lawsonia intracellularis is an obligately intracellular, gram-negative, microaerophilic bacterium that causes proliferative enteropathy (PE), also known as ileitis. The disease is characterized by thickening of the intestinal mucosa due to crypt epithelial cell proliferation directly associated with intracellular bacterial replication. Globally, approximately 96% of farm sites are infected, with approximately 30% of weaner-to-finisher pigs having lesions. Three clinical forms are recognized: acute proliferative hemorrhagic enteropathy (PHE) affecting young adults with bloody diarrhea and high mortality; chronic porcine intestinal adenomatosis (PIA) affecting weaned pigs 6-20 weeks with diarrhea and reduced growth; and subclinical infection causing reduced weight gain without overt diarrhea. Economic losses from reduced weight gain, poor feed conversion, and mortality are estimated at US$1-5 per affected growing pig, likely underestimated since subclinical cases are not included. L. intracellularis cannot be cultivated in cell-free media and requires dividing cells with specific microaerophilic conditions. Infection also occurs in horses, hamsters, and various other species, though species-adapted subtypes may exist. Prevention relies on hygiene, rodent control, AIAO management, and vaccination. Both modified-live oral and injectable killed vaccines are available with demonstrated efficacy.
FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL
Level: Highly unlikely: No controls necessary
L. intracellularis does not cause foodborne illness in humans. "There is no evidence of L. intracellularis infection in humans. A surveillance study in children living on European pig farms failed to find L. intracellularis DNA in their fecal samples."
NON-FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL
Level: Highly unlikely: No evidence of non-foodborne zoonotic transmission
L. intracellularis is not zoonotic. "Investigations of Crohn's disease and other mucosal inflammatory conditions of humans have consistently failed to find typical PE lesions or L. intracellularis." While the organism infects multiple animal species, no human infections have been documented.
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
Transmission is controllable through management: (1) Fecal-oral route: "Transmission is by the fecal–oral route from infected pigs or contaminated environments"; (2) Environmental survival limited: "L. intracellularis can remain viable in feces at 5–15 °C (41–59 °F) for 2 weeks"; (3) Disinfectant susceptibility: "Quaternary ammonium-based compounds have effective anti-Lawsonia disinfectant activities"; (4) Management controls effective: "Application of strict disinfection protocols and AIAO procedures is critical to decrease the prevalence of PE"; (5) Rodent control important: "Application of rodent control strategies is an important factor in controlling PE."
DIFFICULTY OF DETECTING AND CONFIRMING INFECTION
Level: Moderate: Clinical signs not unique but existing tests available at local/regional laboratory(s)
Diagnosis requires laboratory confirmation with specific challenges: (1) Cannot culture routinely: "The difficulty in routinely culturing L. intracellularis has led to several alternative methods"; (2) IHC gold standard: "Immunohistochemical staining using L. intracellularis-specific antibody has been the gold standard"; (3) PCR widely available: "PCR assays have been widely used to confirm L. intracellularis DNA in fecal or intestinal mucosal samples"; high sensitivity detecting <100 organisms/g feces; (4) PCR interpretation challenges: "Because of this high sensitivity, the mere demonstration of L. intracellularis in feces by PCR may not indicate economically significant PE"; (5) Ct value correlation: "Ct values of <20...were predictive of finding lesions of PE"; (6) Serology available: IPMA, ELISA, flow cytometry assays; (7) Broad differential: Must distinguish from coronaviruses, rotaviruses, Brachyspira, Salmonella, PCVAD, E. coli.
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
PE causes substantial economic losses globally: (1) High prevalence: "Globally, it is estimated that 96% of farm sites are infected, with approximately 30% of weaner-to-finisher pigs having lesions"; (2) Reduced performance: "Chronically affected pigs have an average reduction in daily weight gain of 6–20%"; (3) Economic estimates: "Economic losses...totaling from US$1 to US$5 per affected growing pig"; (4) Likely underestimated: "The impact is likely higher since estimates are based on clinical cases and do not include subclinical cases"; (5) Subclinical losses: "infected pigs have less extensive lesions that are associated with a commensurate reduction in growth rates"; (6) Multiple impacts: "negative impacts on slaughter weight, feed conversion efficiency, and space utilization, as well as breeding problems and morbidity and mortality."
EFFECT ON DOMESTIC OR EXPORT MARKETS
Level: Negligible: Little or no market disruption when disease occurs on one or more farms
No trade implications: (1) Not regulated: PE is not a reportable or trade-restricted disease; (2) Endemic worldwide: "PE is endemic in domesticated swine herds"; (3) Production disease: Impact is on individual farm economics, not trade.
PATHOGEN'S ABILITY TO DEVELOP AND SPREAD RESISTANCE
Level: Minimal risk: Agent inherently unlikely to develop clinically important resistance to antibacterial or antiviral treatments
No acquired antimicrobial resistance documented: "Acquired resistance by L. intracellularis to these active drug groups has not been demonstrated." The obligately intracellular nature of the organism limits opportunities for resistance gene acquisition through horizontal transfer.
AMR DEVELOPMENT DRIVEN BY DISEASE MANAGEMENT
Level: Minimal risk: Antibacterial or antiviral treatments rarely occur, or are typically limited to short-course individual animal therapy
PE management does not significantly drive AMR: (1) Vaccines available: "A modified live vaccine has been widely used with demonstrated effectiveness"; injectable killed vaccine also available; (2) Vaccination reduces antimicrobial use: "vaccination has resulted in reduced antibiotic usage in PE-affected herds"; (3) Management alternatives: Hygiene, AIAO, rodent control provide non-antimicrobial options; (4) No resistance development: Effective antimicrobials remain effective.
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 effective when properly administered: (1) Effective drug classes: "macrolides and pleuromutilins are the most effective antibiotics, when given at an adequate dosage rate"; (2) Quinoxalines: "In the United States, quinoxalines (such as carbadox) are also available and effective"; (3) Tetracyclines: "medication via water using tetracycline and its derivative, doxycycline, demonstrated reduction in fecal shedding"; (4) Dosage critical: "Apparent medication failures with antimicrobials known to be effective are most likely due to sub-therapeutic dosages"; (5) Ineffective drugs: "Antimicrobials known to be ineffective...include the penicillins, bacitracin, aminoglycosides, virginiamycin, and ionophores."
AVAILABILITY OF EFFECTIVE VACCINES OR BACTERINS
Level: Available but uncertain efficacy: Commercial or autogenous vaccines exist in the US but protection may be inconsistent
Two vaccine types are available with demonstrated efficacy: (1) Modified-live oral vaccine: "A modified live vaccine has been widely used with demonstrated effectiveness in preventing PE"; "provided protection against subsequent challenge with virulent heterologous L. intracellularis"; (2) Injectable killed vaccine: "an injectable killed vaccine became commercially available in the United States" in 2016; "reduced PE lesions and fecal shedding of L. intracellularis in vaccinated pigs"; (3) Field efficacy: "Field studies confirm that vaccination results in improved rate-of-gain and economic benefits"; (4) Antimicrobial interaction: "Temporary removal of most medications from feed is recommended at least 3 days before and 3 days after vaccination" for live vaccine; (5) Breeding stock: "Vaccination is particularly important in nucleus herds and for the introduction of replacement breeding stock."
FEASIBILITY OF ERADICATING THE DISEASE FROM THE US
Level: Not feasible: Eradication extremely unlikely
Eradication is not feasible due to endemic nature and multiple reservoirs: (1) Near-universal prevalence: "96% of farm sites are infected"; (2) Multispecies host range: Infection documented in hamsters, rabbits, ferrets, horses, deer, birds, and many other species; (3) Wildlife reservoirs: "Presence of L. intracellularis in fecal samples of various wild species, such as jackrabbits, skunks, opossums, raccoons, and coyotes, has also been reported"; (4) Rodent reservoir: "rodents in particular may have a critical role in the introduction and maintenance of L. intracellularis in swine herds"; (5) Subclinical carriers: "The absence of clinical PE in conventional swine herds...is no guarantee of freedom from L. intracellularis infection"; (6) Feral swine: "PE is endemic in domesticated swine herds and has also been described in feral swine populations worldwide."