Porcine Proliferative Enteropathy

Introduction:  Porcine proliferative enteropathy (PPE), commonly referred to as ileitis, is caused by the obligate, gram-negative, intracellular bacterium Lawsonia intracellularis. Ileitis is an economically important disease that affects swine populations throughout the world.  Incidence ranges from 32.7% of farms with less than 2,000 head total inventory, 53.7% in medium sized farms (2,000-9,999), and 75% in large farms (10,000+).

Pathophysiology:  The pathogenesis of PPE develops as progressive proliferation of immature intestinal epithelial cells in the terminal ileum, and less commonly, the large intestine. L. intracellularis organisms enter dividing crypt cells via an entry vacuole.  The vacuole quickly breaks down, releasing bacteria into the cytoplasm where they rapidly multiply.  The mechanism by which infected crypt cells continue to divide, undergo mitosis, yet fail to mature is unclear.

  A less common acute form of the disease, known as proliferative hemorrhagic enteropathy (PHE), is characterized by widespread degeneration and desquamation of enterocytes with severe congestion of mucosal vasculature and hemorrhage from capillary beds.  Mucosal thickening may not be as marked as in traditional PPE.  The trigger for hemorrhagic crisis is not known.

Clinical signs:  The majority of PPE cases are subclinical infections characterized by decreased daily gains, poor feed efficiency, and increased days to market.  Clinical disease usually occurs in grower-finisher pigs between 2-6 months of age.  Affected pigs exhibit signs of anorexia, poor growth, and watery yellow-green diarrhea.  Most pigs recover, although some may progressively deteriorate and die.  The PHE form of disease usually affects older animals between the ages of 4-12 months.  Clinical signs are acute, including severe, dark brown-bloody watery diarrhea and sudden death.

Gross lesions:  Gross lesions are consistently observed in the terminal ileum, but less commonly occur in the distal jejunum, proximal spiral colon, and cecum.  The most characteristic gross lesion is thickening of the mucosa with an irregular nodular or folded appearance.  In most severe cases, the mucosa may be eroded with a granular appearance and adherent fibrinonecrotic debris.  Proliferative lesions are common to both forms of the disease, though, in the PHE form, a large amount of undigested blood is also observed within the lumen.

Histopathology:  Microscopic lesions of PPE are characteristic and often diagnostic.  Proliferation of immature crypt epithelial cells replaces the normal mucosal architecture and produces the thickened appearance observed grossly.  Crowded, immature epithelial cells populate proliferating crypts, which may become branched and extend to the mucosal surface.  Mitotic figures are common and goblet cells are absent from the abnormal epithelium.  Additionally, crypts may be dilated and contain necrotic debris and neutrophils.  L. intracellularis organisms are detected as small, curved, rod-shaped bacteria in the apical portion of immature crypt cells by Warthin-Starry silver staining.  In cases of PHE, bacteria may also be found free, in macrophages, and within capillaries and lymphatics.  In chronic cases of PPE, however, microscopic lesions are less diagnostic due to production of fibrous connective tissue throughout the mucosa.

Diagnostic Tests:  Because L. intra-cellularis does not grow in conventional cell-free media, bacterial culture is not employed for diagnostic testing.  The most commonly used diagnostic tests, in addition to histopathology, are serology and polymerase chain reaction (PCR) of fecal and tissue samples.  Fecal PCR has limited efficacy for determining exposure to L. intracellularis`and may be more useful to identify animals that are actively shedding the organism.  In one study, only 60% of pigs orally infected with L. intracellularis had positive fecal PCR results 3 weeks after challenge, which declined to 30% by 6 weeks post-infection.  Tissue PCR has nearly 100% specificity and sensitivity.  Serial samples collected from a large number of animals of different age groups will yield the best results.

Treatment:  Treatment of clinical PPE is often successful in the mid to late finisher.  Treatment of animals showing clinical signs must be immediate and aggressive.  Injectable tylosin and lincomycin are the antibiotics of choice.  Other treatments include oral antibiotics in the feed or water.  Examples of antibiotics with label claims include: Tylan (tylosin), Denagard (tiamulin), Lincomix (lincomycin), and BMD plus aureomycin.  Determining age of exposure by use of the previously outlined diagnostic tests will facilitate proper placement of oral antibiotics and reduce the economic impact of the disease.

Prevention:  Preventative measures to reduce the incidence of PPE in swine herds involve the implementation of proper sanitation, disinfection, and vaccination protocols.  Enterisol Ileitis, an avirulent live vaccine administered orally in the water, is currently available.  Although the vaccine has shown success, proper administration is essential to maintain efficacy.  For proper protection, the vaccine must be administered several weeks prior to exposure to the organism.   For example, if pigs are exposed to L. intracellularis in the early finisher, the vaccine should be placed in the middle nursery stage of production.  Additionally, no antibiotics should be added to feed or water for several days before and after administering the vaccine.

-by Tony Lahr,  Class of 2003

-edited by Dr. Kim Maratea, ADDL  Graduate Student

References

1. Marsteller TA, Armbruster G, Bane DP et al: 2002.  Monitoring the prevalence of Lawsonia intracellularis antibodies using serial sampling in growing and breeding herds.  Proc 33^rd AASV meeting, Kansas City, MO  85-86.

2. McOrist S and Gebhart, CJ: 1999.  Porcine Proliferative enteropathies. In: Straw BE, D’Allaire S, Mengeling WL, and DJ Taylor (Eds.  Diseases of Swine 8^th ed. Iowa State University Press, Iowa, 521-534.

3. Philips RC, Geiher JO and Karhoff K: 1998.  Evaluation of the use of Lawsonia intracellularis  indirect fluorescent antibody test (IFA) in a large production system.  Proceedings Leman Conference, Volume 25, pp 5-6.

4. Stevenson G: 2001.  Differential diagnosis of diarrhea in grow-finish swine.  Proceedings 32^nd AASV, Nashville, TN, 359-363.

5. USDA: 2002.  Part II: Reference of swine health and health management in the United States, 2000.  USDA:APHIS:VS, CEAH, National Animal Health Monitoring System, Fort Collins, CO, #N355.0202.