Edema disease is a peracute toxemia caused by specific pathotypes of Escherichia coli that affects primarily healthy, rapidly growing nursery pigs. Other names for edema disease include “gut edema” or “bowel edema,” due to the prominent edema of the submucosa of the stomach and mesocolon.
Etiology and Pathogenesis
Edema disease is caused by hemolytic E coli that produce F18 pili and Shiga toxin 2e (Stx2e, also known as verotoxin 2e or VT2e). The F18 pili have 2 antigenic variants, F18ab and F18ac; F18ab is characteristic of edema disease strains, and F18ac is associated primarily with enterotoxigenic E coli. The Shiga toxin-producing E coli implicated in edema disease most commonly belong to 4 specific serotypes: O138:K81:NM, O139:K12:H1, O141:K85a,b:H4, and O141:K85ac:H4. However, other serotypes of E coli may be implicated and strains of serogroup O147 have been dominant in parts of the USA in recent years. These O147 strains typically carry the H17 flagella but some have H14 or H19.
Pigs become infected initially by contaminated environment or the sow. Spread of infection among penmates is facilitated by the large numbers of pathogenic E coli that are shed by colonized pigs. Some strains of E coli that cause edema disease also carry genes for enterotoxins and can cause diarrhea as well as edema disease. Ingestion of edema disease strains of E coli is followed by colonization of the intestine in pigs in which intestinal epithelial cells carry receptors for the F18 pili. Expression of the receptors is age-related, so younger pigs are less susceptible to colonization than older pigs. Some pigs carry a specific mutation in a gene required for expression of the receptors and are thereby resistant to infection.
Resistance/susceptibility is determined by a single locus with a dominant susceptibility allele and a recessive resistant allele; it is possible to select resistant pigs, which can be identified by a simple PCR test that identifies presence or absence of the specific mutation. Some concern about selection for resistance to F18+ E coli has been expressed because a very high association between presence of the marker for resistance to F18+ E coli and presence of the marker for stress susceptibility was shown in Swiss Landrace pigs. However, this association does not exist in Belgian pigs.
Shiga toxin 2e produced in the intestine of colonized pigs is responsible for the major clinical signs and pathology that are observed. This cytotoxin inhibits protein synthesis, leading to cell death. The toxin is absorbed from the intestine and targets vascular endothelium in specific sites believed to have high concentrations of the toxin receptor globotetraosyl ceramide. A recent study has shown that edema disease strains of E coli may colonize the mesenteric lymph nodes and produce Stx2e there. This may be an additional site from which the toxin is absorbed into the bloodstream. The Stx2e toxin binds readily to pig RBC, which may transport the toxin to various sites in the body. Sites that are highly susceptible to the toxin include the submucosa of the stomach, the colonic mesentery, the subcutaneous tissues of the forehead and eyelids, the larynx, and the brain. Damage to vascular endothelium results in edema, hemorrhage, intravascular coagulation, and microthrombosis.
High-protein diets increase the susceptibility of pigs to the disease. Factors associated with weaning, including the stresses of mixing pigs, changes in diet, and the loss of milk antibodies from the intestine, appear to be important elements in enhancing the susceptibility of weaned pigs to the disease.
Clinical signs range from peracute death with no signs of illness to CNS involvement with ataxia, paralysis, and recumbency. Edema disease usually occurs 1–2 wk after weaning and typically involves the healthiest animals in a group. The disease is seen occasionally in nursing pigs or in adult pigs. The average morbidity is 30–40%, and the mortality among affected pigs is often as high as 90%. Periocular edema, swelling of the forehead and submandibular regions, dyspnea, and anorexia are common.
Edema disease is primarily a disease of the vasculature, and gross lesions consist of subcutaneous edema and edema in the submucosa of the stomach, particularly in the glandular cardiac region. The edema fluid is usually gelatinous and may extend into the mesocolon. The edema may be accompanied by hemorrhage. Fibrin strands may be found in the peritoneal cavity, and serous fluid may be found in both the pleural and peritoneal cavities. Microscopically, a degenerative angiopathy affecting arteries and arterioles and necrosis of the smooth muscle cells in the tunica media are present. Lesions of focal encephalomalacia in the brain stem are characteristic and thought to result from vascular damage, leading to edema and ischemia.
A clinical history of peracute death in healthy, well-conditioned, recently weaned pigs, along with observation of periocular edema and extensive edema of the stomach and mesocolon, are helpful in diagnosis. There may be a characteristic squeal due to edema of the larynx. Diarrhea may precede the signs of edema disease if the E coli responsible also possesses genes for enterotoxins. Characteristically, the stomach is full of dry feed. Diagnosis is easily made in an outbreak in which the full range of clinical signs and pathologic features are likely to occur. It is more difficult when only a few animals are affected or when the disease occurs in an atypical age group. Isolation and characterization of the E coli are required for a definitive diagnosis. Culture of the small intestine and colon typically yields a heavy growth of hemolytic E coli, but in some cases the organism may no longer be present in the intestine at the time of death. Demonstration that the hemolytic E coli isolated is an edema disease strain may be done by PCR amplification of the genes for the F18 pili and Stx2e. Serotyping of the isolate is useful for tracking the persistence of a particular type of the organism on a farm. However, the F18 pili are not readily expressed in vitro and they may not be detected on organisms that are cultured routinely.
Treatment and Control
Because the onset of disease is often sudden and the course rapid, treatment is often ineffective. Oral medication via the drinking water may be used to protect clinically unaffected pigs in a herd in which cases of the disease have been detected. Antibiotic sensitivity should be determined on the isolate from an affected pig; medication should be changed if the initial choice was ineffective. Control is also difficult. Several experimental approaches have been shown to be effective, but none are economical to date. These methods include feeding a high fiber and low protein diet, reducing the amount of feed given to weaned pigs, vaccination by a systemic route with Stx2e toxoid, oral vaccination with an F18+ nontoxigenic E coli, passive systemic immunization with antitoxin, and passive oral immunization with anti-F18 antibodies. Mucosal immunization with purified F18 fimbriae has been investigated but proved to be ineffective, possibly because the portion of the F18 fimbria that binds to the intestine is a small fraction of the total fimbrial structure. Recently, incomplete protection has been reported following vaccination of pigs with the receptor portion of the F18-fimbriae conjugated with F4 fimbriae.
Last full review/revision March 2012 by Carlton L. Gyles, DVM, PhD, FCAHS