Etiology:  Transmissible gastroenteritis (TGE) in swine is known to be one of the most significant diarrhea-produceing diseases in young pigs.  The causative agent, TGE virus (TGEV) belongs to the genus Coronavirus of the family Coronaviridae.  TGEV is very stable when stored frozen, but labile at room temperature or above.  TGEV is vulnerable to sunlight and various disinfectants such as sodium hypochrolite or iodines

  To understand an overall picture of TGE, it is necessary to describe a deletion mutant of TGEV, porcine respiratory coronavirus (PRCV).  PRCV appeared in the 1980s and has become prevalent worldwide, including the United States.  PRCV replicates primarily in the respiratory tract and, to a minimal extent, in small intestinal epithelial cells.  Usually, no clinical disease is produced or, uncommonly, mild respiratory disease is observed.  PRCV does not produce clinical enteric disease.  PRCV typically forms an endemic infection in intensely managed swine herds and infected pigs produce neutralizing antibodies which also neutralize TGEV.  Therefore, when pigs already affected by PRCV get infected by TGEV, these pigs develop a less severe clinical form of TGE.

Epidemiology:  Epidemiologically, TGE can be classified as epidemic or endemic form.

  Epidemic TGE occurs in herds in which most of the pigs are TGEV/PRCV-seronegative and susceptible, and is observed most often in winter.  As a reservoir during summer months, non-porcine hosts (e.g. cats, dogs, birds) or mechanical vectors (e.g. houseflies) have been postulated.  Morbidity is high in this form of TGE and pigs under 2-3 weeks of age tend to show severe diarrhea and rapid dehydration, which often result in death.  The mortality rate is usually less than 10-20%.  Diagnosis of endemic TGE in suckling or recently weaned piglets can be difficult and should be differentiated from infection with other diarrhoegenic pathogens such as rotavirus, E. coli, Clostridium spp. and Isospora suis.

Pathogenesis:  The major route of transmission of TGEV is fecal-oral.  The incubation period for TGEV is from 18 hours to 3 days.  At initial exposure, the pig swallows the virus which then travels to the small intestine, binds to receptors and is internalized into absorptive enterocytes.  The virus replicates within enterocytes and then lyses them to enter the intestinal lumen, resulting in villous atrophy.  Intestinal crypts are spared during TGE and become hyperplastic, therefore, secretion continues.  However, absorption is partially impaired by enterocyte lysis and villous atrophy (malabsorption).  At the same time, osmolarity in the intestinal lumen increases because of the presence of undigested material (maldigestion), which results from decreased enzymatic activity in the damaged intestinal mucosa.  This increased osmolarity causes a pull of fluid into the intestinal lumen.  Eventually, malabsorption and maldigestion lead to net increase in intestinal mucosal secretion and clinical manifest diarrhea.  The ultimate cause of death is likely associated with dehydration and metabolic acidosis.

  TGEV impacts younger pigs more because their enterocytes are not able to be replaced as quickly as those of an older animal.  Another reason of the higher morbidity/mortality in younger pigs is that the compensatory fluid absorption takes place in the large intestine of older pigs, compared with younger pigs.

Clinical signs:  In the epidemic form of TGE, typical clinical signs include transient vomiting, watery, yellow diarrhea which may contain undigested milk, weight loss, dehydration, and high morbidity/mortality, especially in pigs less than two weeks of age.  One of the most notable signs is the smell of the diarrhea - foul steatorrhea (excess fat in feces) due to maldigestion.  Many pigs older than three weeks of age will survive but are likely to remain stunted.  Growing and finishing pigs with epidemic TGE may show inappetance, diarrhea, agalactia, or vomiting of variable period of time.

  Clinical signs for endemic TGE are similar but are less severe than those seen in seronegative pigs of the same age.

Lesions:  Gross examination of carcasses of pigs that have suffered from TGE will reveal evidence of dehydration (sunken eyes, increased skin turgor) and diarrhea (soiled perianal/perineal skin with watery material, lack of formed feces in the large intestine).  The small intestine will have very thin, translucent walls with congested mesenteric vessels.  Mesenteric lymphatics may be devoid of chyle, since there is malabsorption of fat in the small intestinal mucosa.  The stomach and small intestine may contain a milk curd and bile-stained fluid, respectively.  The small intestine will show villous atrophy if the mucosa is examined by a hand lens.

  The most striking microscopic lesion is severe villous atrophy evidenced by decrease of villus-crypt ratio (about 1:1 in affected pigs, 7:1 in normal pigs) in the jejunum and, less commonly, in the ileum.  Inflammatory reaction is usually minimal.  Compensatory hyperplasia of crypts develops.  Villi may be lined by attenuated epithelium with irregular nuclear polarity and indistinct brush border.  Since lesions can be patchy, multiple sections should be examined.  Although rotavirus infection can also cause villous atrophy, it is not usually as severe or extensive as in TGE.

Diagnosis:  If TGE is suspected based on clinical signs and macro-/microscopic lesions, the diagnosis of TGE can be confirmed by 1) detection of viral antigen, 2) detection of nucleic acid, 3) microscopic detection of virus at high magnification by electron microscopy, 4) isolation and identification of virus, and/or 5) detection of a significant titer increase for TGE.  Methodologies apply to each testing are listed below.  Importantly, because of overlapping of clinical signs and lesions among different etiologies responsible for porcine diarrhea, a combination of different test methods provides more accurate diagnosis than when a single test methodology is employed.  Please contact the pertinent section of ADDL or visit our website(www.addl.purdue.edu) for more detailed information regarding methodology, recommended tissue and timing of sampling, price, etc.

1. Detection of viral antigen: fluorescent antibody assay (FA), immunohistochemistry (IHC), Figure 1.

2. Detection of nucleic acid: reverse-transcriptase polymerase chain reaction (RT-PCR)

3. Microscopic detection of virus: electron microscopy (EM)

4. Isolation and identification of virus: cell culture

5. Detection of a significant antibody response: serology

  With regard to serology testing, the diagnosis may be complicated due to antigenic similarity between TGEV and PRCV.  A blocking enzyme-linked immunosorbent assay (ELISA) can overcome this shortcoming and differentiate between these two viruses.  In order to determine whether endemic TGE or PRCV is prevalent in a herd, serum samples from pigs of 2-6 months old can be tested for presence of antibodies.  At this age, maternal antibodies should be absent, thus the positive results suggest endemic TGEV or PRCV.  Evaluation of the results of serology testing always requires careful comparison of disease history and serological status of the herd.

Treatment:  The treatment of choice is supportive care, although it may not be practical under farm conditions.  It is recommended to provide pigs with warm (above 89°F), dry, and draft-free environment.  Make water, nutrient, or rehydration solution accessible because intestinal absorptive mechanism is intact despite severe damage to the epithelium.  Oral fluid intake will help alleviate severe dehydration especially in pigs that are infected at older than 3-4 days of age.  For 2- to 5-week old pigs, antibiotic therapy may be helpful if there is concurrent infection by bacterial pathogens.

Prevention and control:  In order to prevent TGE from entering into a sero-negative herd, it is important to acquire new animals from a TGE-free source which are also sero-negative.  The incoming animals should be quarantined for 2-4 weeks and tested negative for TGEV before they are introduced into the new herd.  Maintenance of a TGEV-negative herd is based on disciplined biosecurity.  Structure of buildings should exclude all potential animal vectors (rodents, cats, dogs, birds, etc).  Human traffic should be minimized and shower-in shower-out facilities are ideal.  Other fomites (tracks, tools, supplies, etc.) should be carefully monitored.  For more information, please refer to chapter 68 of Diseases of Swine (reference #5).

  The basis of control of TGE in infected herds is to allow the sows to acquire IgA and continually pass along immunoglobulin-A (IgA) in their milk to provide passive immunity to the neonatal/suckling pigs.  IgA secreting lymphocytes primarily result from uptake of viral antigens into the M cells in the Peyer's patches of the intestine rather than from lymphocyte stimulation by a parenteral vaccine source.  Active, protective immunity develops after infection by virulent TGEV and lasts 6-18 months.  Parenteral vaccines typically result in mainly IgG and IgM production.  IgA is stable within the gastrointestinal tract while IgG and IgM are both destroyed by the digestive process.  Since TGEV is transmitted orally and it targets the enterocytes, it is important to have IgA functional within the intestinal lumen.

  In the event of a TGE outbreak in a naïve herd with no vaccination history,  a later epidemic in the farrowing house appears inevitable.  It is important to begin control at the pre-farrowing level.  If sows are two weeks or less to farrowing, it is important to farrow them off-site or in a non-TGEV exposed area and keep the young pigs free from exposure for at least three weeks.  If the sows are greater than two weeks away from farrowing, the "feed-back" method may be used to advertently expose the sows to TGEV and boost their IgA production which will be passed along in colostrums and milk.  To accomplish this, the small intestines from acutely affected young pigs will be ground up and fed back to the sows.

  In the case of endemic TGE, in addition to all-in/all-out flow and farrowing in non-TGEV exposed units if available, it is important to use a live attenuated vaccine to boost immunity of sows prior to farrowing in order to provide a longer duration of passive immunity to the neonates.  This will likely decrease the morbidity and mortality.  The key to the parenteral vaccine boosters and maintaining immunity is the previous exposure to virulent TGEV.  Parenteral vaccination with an attenuated vaccine in a sero-negative pregnant sow may not significantly raise IgA levels and thus will not initiate adequate passive immunity for the neonatal pigs.  Finally , some research indicates that multiple exposures of sows to PRCV resulted in high anti-TGEV IgA in milk and provided a high degree of protection to TGEV challenge.

-by Dr. Megan Potter, Class of 2007

-edited by Dr. Ikki Mitsui, ADDL Graduate Student and Dr. Roman Pogranichniy, Head of Virology/Serology

References

1. Dewey CE, Carman S, Hazlett M, van Dreumel T, Smart NE:1999.  Endemic transmissible gastroenteritis: Difficulty in diagnosis and attempted confirmation using a transmission trial.  Swine Health Prod 7:73-78.

2. Gelberg HB: 2007.  Alimentary system - Transmissible gastroenteritis.  IN: Pathologic Basis of Veterinary Disease.  4^th ed., McGavin MD, Zachary JF eds.  Mosby-Elsevier, St. Louis, MO.  p. 375.

3. Moeser AJ, Blikslager AT: 2007.  Mechanism of porcine diarrheal disease.  JAVMA 231:56-67.

4. Murphy FA, Gibbs EPJ, Horzinek MC, Studdert MJ: 1999.  Coronaviridae.  In: Veterinary Virology, 3^rd ed. Academic Press, San Diego, Ca.  pp 495-508.

5. Saif LJ, Sestak K: 2006.  Transmissible gastroenteritis and porcine respiratory coronavirus.  In: Diseases of Swine, 9^th ed. Straw BE, Zimmerman JJ, D'Allaire S, Taylor DJ eds. Blackwell Publishing, Ames, IA.  Pp 489-516.