Porcine proliferative enteritis (PPE) is an enteric disease characterized by hyperplasia of crypt enterocytes with inflammation and sometimes ulceration or hemorrhage. Lesions always include thickening of the mucous membrane of part of the small intestine and/or large intestine. Lesions vary considerably by location, extent, and duration. Many terms have been used to describe this disease, including: proliferative hemorrhagic enteropathy (PHE), porcine intestinal adenomatosis (PIA), porcine proliferative enteritis (PPE), necrotic enteritis (NE), regional or terminal ileitis (RI), ileitis, and garden-hose gut.
Porcine proliferative enteritis (PPE) occurs worldwide. Disease is categorized pathologically as a severe acute form (proliferative hemorrhagic enteropathy or PHE) that is more common in young adults, and a chronic or necrotic form which occurs much more frequently, usually during the grower phase.
The disease occurs primarily in growing/finishing pigs but may also occur in pigs as young as 3 weeks, in market weight hogs and adult swine. Disease often appears to be more severe with, and occurs at an increased incidence in, age-segregated herds. Similar signs and lesions occur in other mammals (hamsters, ferrets, guinea pigs, foxes, horses, lambs, rabbits, rats, dogs, white-tailed deer, emus) with no detectable differences in the genotype of the causative organism. Hamsters have been used in research and are readily infected by the porcine organism.
The first report of PPE was published in 1931. Neither that nor another report in 1935 stimulated much interest. In the 1970s there was a renewed interest as marked losses from PPE became more apparent. In 1993, a method of cultivation of the confirmed etiologic agent (Lawsonia intracellularis) in tissue culture was reported. The agent has now been used to reproduce the disease in conventional, susceptible pigs.
Bent, rod-shaped, Gram-negative bacteria in crypt enterocytes of swine with PPE were recognized long ago. However, the organism could not be grown on cell-free media and was not identified until 1993. The obligate intracellular organism, Lawsonia intracellularis(Li) is considered to be a novel taxonomic genus and species. It is related to certain anaerobic, sulfate-reducing bacteria.
Lawsonia intracellularis can be grown in a rat enterocyte cell line and inoculation of susceptible pigs with pure culture of the organism reproduces PPE. All isolates examined from different host species and from different geographical locations appear to be quite similar. Polymerase chain reaction (PCR) has been useful for characterization of the organism and has ruled-out involvement of Campylobacter spp. in the disease
The incubation, recovery, and carrier phase of L. intracellularis infection is quite long in some pigs, probably months. Undoubtedly, there are carrier swine that disseminate L. intracellularis in their feces to susceptible pigs by fecal-oral route. Infection often results in subclinical disease. Research also shows that L. intracellularis from experimentally infected pigs spreads to naive sentinel pigs penned with them or penned separately in the same enclosed area.
Carrier dams have been demonstrated to infect their litters as early as six days of age, a likely reason for failure of segregated early weaning techniques to control disease. The incubation period is at least two weeks, perhaps much longer. Outbreaks often have been associated with a variety of stresses. Lateral transmission of infection has been demonstrated but not all pigs within a population are necessarily infected simultaneously.
L. intracellularis infects epithelial cells and survives intracellularly. When enterocytes undergo mitosis, each cell retains some of the bacteria, and enterocytes fail to mature. The resulting hallmark lesion is a proliferation of immature enterocytes. Whether the organism stimulates greater proliferation, retards maturation, or both is not known. Microscopically, organisms are visible within the apex of crypt epithelial cells. Responses to the bacteria include crypt elongation, epithelial cell hyperplasia, degeneration and necrosis of enterocytes, fewer goblet cells, and an inflammatory response.
Other details of pathogenesis are speculative. Variations in the reported syndromes may correlate with different stages in lesion development or different responses to infection, perhaps modulated by predisposing factors, stresses and saprophytic organisms. Seroconversion occurs two weeks after infection, although lesions may not develop for three to four weeks post-infection. The protected, intracellular environment afforded the organism probably requires a cell-mediated response to eliminate infection. Resolution of lesions starts approximately four weeks after infection.
There has been much confusion related to nomenclature, lesions, and clinical signs of PPE, primarily due to the variation that exists in clinical signs, age of pig affected, and gross lesions. In addition, a syndrome (hemorrhagic bowel syndrome or HBS) of sudden death with blood in the intestinal tract (which is not PPE) is often confused with this condition. Acute cases of PPE are most frequently observed in late finishing pigs and young breeding stock (PHE). Acute diarrhea with brownish to black unclotted blood, pallor, weakness, and rapid death are common; lesions include mucosal proliferation and hemorrhage. Subacute to chronic cases occur more frequently in the grower stages, manifested by sporadic diarrhea, wasting, and variation in growth rate; lesions often include necrotic enteritis and can be easily confused with salmonellosis. Morbidity and mortality with either presentation is variable. Some pigs may have quite severe proliferation of mucosa of terminal small intestine yet can be clinically asymptomatic.
Lesions vary in severity and location but usually include gross thickening of some part of the mucosa of the small and/or large intestine. The ileum is commonly affected, often with a hose-like thickening of the mucosa of terminal ileum. A cerebriform pattern (resembling the external fissures and convolution of the brain) of intestinal thickening is visible from serosal surface. Peyer’s patches may be hyperplastic. Bloody intestinal content, perhaps with frank blood clots, may be present, especially in PHE. Lesions occasionally are present only in the large intestine. In these instances, the mucosa of the cecum and/or colon is thrown into thick folds, plaques or polyps, may be covered by inflammatory exudate, and vaguely resembles lesions of swine dysentery, trichuriasis, or salmonellosis. Healing lesions of PPE in many slaughtered hogs suggest that some affected swine may show few or no signs and recover spontaneously.
In conventionally stained histologic sections there is severe intestinal crypt cell hyperplasia; in silver stained sections or with immunohistochemistry, curved to rod-shaped bacteria usually can be demonstrated in the apex of some enterocytes.
A tentative diagnosis often can be made on the basis of clinical signs along with the presence of characteristic gross and microscopic lesions, although some cases of porcine circovirus type 2 (PCV2) enteritis can present themselves clinically very similar to PPE. Laboratories use silver stains, immunohistochemistry, or fluorescent antibody tests on histologic sections to confirm the presence of the organism within lesions. Polymerase chain reaction (PCR) testing on samples of affected mucosa or feces is also available. PCR performed on feces from clinically affected pigs is diagnostic but negative tests do not rule out carrier status. Serology has limited availability and unknown sensitivity. Antibody specific for L. intracellularis appears to have low magnitude and duration but testing can be useful on a herd basis to determine if the herd is infected and when infection may be occurring.
Prevention by elimination is difficult; segregated rearing has been largely unsuccessful. There is no certainty that exposure of swine to L. intracellularis can be avoided. More information is needed on survival of the organism under field conditions and the role other animals may play in transmission and/or reservoirs. Presently there is no widely available way to screen large numbers of apparently normal, suspected carriers. Serologic tests eventually may be useful for identifying infected herds. Although PCR is not yet widely available, it can identify Lawsonia intracellularis in fecal samples from clinically affected pigs but lacks sensitivity to identify inapparent carriers.
Outbreaks sometimes appear to be stress related. Environmental and other stresses, including transportation, sorting, or commingling, often precipitate outbreaks and should be minimized.
Various antibiotics often are added to feed for several weeks during or after periods of stress and during outbreaks in order to control and treat PPE. Experimental PPE can be controlled using tylosin, tetracyclines, lincomycin, tiamulin, and carbadox. Various medication strategies have been used, including pulse dosing and continuous medication. Medication failures are common in breeding stock where animals are not fed ad libitum, hence receive subtherapeutic doses of antimicrobials that might otherwise be effective. Control of PPE has been a major reason for use of feed-grade antimicrobials in grow-finish swine.
An avirulent live vaccine is widely available and appears to have very good efficacy when properly administered via water or orally. Vaccination of growing pigs as well as breeding gilts during acclimatization has been very successful in reducing or eliminating clinical signs of PPE. In some herds, vaccination has allowed the elimination of continuous administration of feed-grade antimicrobials.
See the table Diseases Associated with Hemorrhage in Intestine