Edema disease is a syndrome of peracute vasculitis causing facial swelling, enteritis and sometimes focal encephalomalacia in post-weaning pigs. The causative agent is F18+ E coli. The disease is characterized clinically by visible edema of the face and GI tract. Treatment is limited as the disease is rapidly fatal in most affected animals; prevention is aimed at vaccination and management strategies.
Edema disease is a peracute toxemia caused by a specific pathotype of Escherichia coli that affects primarily healthy, rapidly growing nursery pigs. Other names include “gut edema” and “bowel edema” because of the prominent edema of the submucosa of the stomach and mesocolon.
Edema disease may occur independently or accompanied by postweaning diarrhea in a single outbreak of E coli. Treatment is often ineffective because of the sudden onset and rapid course of disease. Oral medication with an antimicrobial may protect clinically unaffected pigs in a herd where positive cases have been detected, based on antimicrobial susceptibility results. Isolation of the causative E coli from the intestinal contents or feces and identification by PCR assay give a definitive diagnosis. However, these bacteria may no longer be present in the intestine at the time of death.
Etiology and Pathogenesis of Edema Disease in Pigs
Edema disease is caused by hemolytic E coli that produce F18 fimbrial adhesins and Shiga toxin 2e (Stx2e, also known as verotoxin 2e or VT2e). The F18 fimbriae have two major antigenic variants—F18ab and F18ac—both of which may be associated with the development of edema disease. The most common Shiga toxin–producing E coli serogroups implicated in edema disease are O138, O139, O141, and O147.
Pigs become infected initially via a contaminated environment or the sow. Transmission of infection among penmates is facilitated by the large numbers of Shiga toxin–producing E coli that are shed by colonized pigs. Some F18ab-positive and F18ac-positive strains of Shiga toxin–producing E coli also carry genes for enterotoxins; however, these strains are more commonly associated with diarrhea than with edema disease.
Ingestion of edema disease strains of E coli is followed by colonization of the intestine in pigs, where intestinal epithelial cells carry receptors for the F18 fimbriae. Expression of the receptors is age related, arising first around 10 days of age and increasing gradually to be highly expressed from ~3 weeks old; young piglets are therefore less susceptible to colonization than are older pigs.
Resistance/susceptibility is determined by a single locus with a dominant susceptibility allele and a recessive resistance allele. It is possible to select resistant pigs, which can be identified by a simple PCR test that indicates the 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 has been shown in Swiss Landrace pigs.(1) However, this association does not exist in all races of pigs.
Shiga toxin 2e produced in the intestine of colonized pigs is responsible for the major clinical signs and pathologic changes observed in edema disease. 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 receptors globotriaosylceramide and globotetraosylceramide.
Edema disease–causing 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. Stx2e binds readily to pig RBCs, which may transport the toxin to various sites in the body.
Sites highly susceptible to the toxin include the submucosa of the stomach, the mesocolon, 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, possibly due, at least in part, to the increased availability of substrates allowing the proliferation of the gut microbiota, including the edema disease strains of E. coli. Factors associated with weaning (eg, the stresses of pigs being mixed, dietary changes, and loss of milk antibodies) appear to be important elements that increase the susceptibility of recently weaned pigs to the disease.
References
Meijerink E, Fries R, Vogeli P, et al. Two alpha (1,2) fucosyltransferase genes on porcine chromosome 6q11 are closely linked to the blood group inhibitor (S) and Escherichia coli F18 receptor (ECF18R) loci. Mamm Genome 8, 1997;736–741.
Clinical Findings of Edema Disease in Pigs
Edema disease may be sporadic or may affect the whole herd. Possible clinical presentations include peracute death with no signs of illness, CNS involvement (ataxia, paralysis, recumbency), and visible edema of the face with generalized malaise. In subclinical edema disease, pigs are clinically normal but develop vascular lesions and may have a decreased growth rate.
A small proportion of pigs show chronic edema disease, lasting from a few days to several weeks after initial intestinal infection. The chronic form is characterized by failure to grow and signs of circling movements, twisting of the head, and limb muscle atrophy.
Edema disease usually occurs 1–2 weeks after weaning and typically affects the healthiest animals in a group. The disease occurs 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.
Lesions
Edema disease is primarily a disease of the vasculature. 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, 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 brainstem are characteristic and thought to result from vascular damage, leading to edema and ischemia.
Diagnosis of Edema Disease in Pigs
Characteristic clinical signs: facial edema, peracute death, concurrent diarrhea in the group
Necropsy findings
Confirmation by culture and identification of E coli that are positive for Stx2e and F18
A clinical history of peracute death in healthy, well-conditioned, recently weaned pigs, along with the observation of periocular edema and extensive edema of the stomach and mesocolon, are findings which are helpful in the diagnosis of edema disease. A characteristic squeal may result from edema of the larynx. Diarrhea may precede the clinical signs of edema disease if the E coli responsible also possesses genes for enterotoxins.
Edema disease is easily diagnosed in an outbreak, in which the full range of clinical signs and pathologic features are likely to occur. Diagnosis 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; in some cases, however—eg, those of subacute or chronic edema disease—the organism may no longer be present in the intestine at the time of death.
PCR amplification of the genes for the F18 pili and Stx2e can be used to demonstrate that the hemolytic E coli isolated is an edema disease strain. Serotyping of the isolate is useful to track the persistence of a particular type of the organism on a farm. The F18 fimbriae are not readily expressed by E coli grown in culture; however, the genes that encode them are easily detected by PCR assay.
Treatment and Control of Edema Disease in Pigs
Treatment: oral antimicrobial prophylaxis in affected pens, based on antimicrobial sensitivity testing
Control: feed management, passive immunity, and vaccination
Antimicrobial treatment of pigs clinically affected with edema disease is often ineffective because of the sudden onset and rapid course of the disease, and because the Stx2e toxin has already bound to receptors by the time clinical signs become visible.
Oral medication with antimicrobials may be administered via the drinking water to protect clinically unaffected pigs in a herd in which cases of the disease have been detected. Antimicrobial sensitivity should be determined on the isolate from an affected pig; medication should be changed if the initial choice is ineffective.
Control of edema disease is also difficult. Feed management strategies include feeding a high-fiber, low-protein diet and decreasing the amount of feed given to weaned pigs. Various strategies involving passive immunity, including systemic immunization with antitoxin, and oral immunization with anti-F18 antibodies, have been used with varying success.
Several commercial vaccines are now available for the prevention of edema disease. There are three general approaches to vaccination:
For the passive immunization of piglets to decrease clinical signs and mortality in pigs up to 21 days old, certain E coli bacterins for vaccinating sows and gilts
For the immunization of pigs against F4-positive and F18-positive pathogenic E coli, live bivalent F4 and F18 nonpathogenic E coli vaccines administered in the drinking water or by oral drenching
For the immunization of young pigs to decrease clinical signs and mortality due to edema disease, injectable vaccines containing genetically modified recombinant Stx2e
New approaches are currently being explored and show promise as future vaccines for the prevention of edema disease, such as:
Multiepitope fusion antigen technology using a backbone such as the enterotoxin LT for presentation of F18
Use of E coli probiotic strains as vectors for delivery of F18
Lettuce-based expression of Stx2e for production of an oral vaccine
Key Points
Edema disease is a peracute toxemia due to a specific pathotype of Escherichia coli that affects primarily healthy, rapidly growing nursery pigs.
Clinical signs range from sudden death to paralysis and typically include prominent edema of the submucosa of the stomach and mesocolon.
Treatment is often ineffective because of the sudden onset and rapid course of the disease. Oral administration of an antimicrobial may protect clinically unaffected pigs in a herd where positive cases have been detected.
Isolation of the causative E coli from the intestinal contents or feces and identification by PCR assay give a definitive diagnosis.
Prevention is difficult but centers on feed management, passive immunity, and vaccination. Several commercial vaccines are now available.
For More Information
Fairbrother JM, Nadeau E. Colibacillosis. In: Straw BE, Zimmerman JJ, D’Allaire S, Taylor DJ, eds. Diseases of Swine. 11th ed. Blackwell Publishing; 2019:807-834.
