Equine Proliferative Enteropathy in Horses (Lawsonia intracellularis)

Equine Proliferative Enteropathy (EPE) is a disease of the small intestine caused by the obligate intracellular bacterium, Lawsonia intracellularis. EPE occurs predominantly in foals between 4-7 months of age. Lawsonia intracellularis infects enterocytes, particularly in the ileum, and causes proliferation of an abnormal population of enterocytes. The architecture of the intestinal mucosa is subsequently altered and the foal suffers from a decreased ability to absorb nutrients. Foals with EPE develop clinical signs of weight loss, diarrhea, hypoproteinemia and peripheral edema. EPE can be treated with antibiotics that have good intracellular penetration, such as oxytetracycline, macrolides and chloramphenicol. Commercial vaccines are currently not available, but research is underway.

Introduction to EPE in Horses

Equine Proliferative Enteropathy (EPE) is a relatively new disease of horses that was first described by Duhamel and Weeldon in 1982 as ‘intestinal adenomatosis’. In the 1930s, a similar disease had been described in pigs, called Porcine Proliferative Enteropathy (PPE), and was responsible for significant economic losses in commercial piggeries. Lawsonia intracellularis was not identified as the causative agent of PPE until 1993, and was then later found to also be the etiologic agent of EPE. Research has shown that the strains of L. intracellularis that affect pigs and horses appear to be species-specific (Pusterla 2009). L. intracellularis was named after the Scottish veterinarian, Gordon Lawson (McOrist 2005). L. intracellularis is not considered a zoonotic disease (Slovis 2014).

Etiology and Pathophysiology of EPE in Horses

L. intracellularis is a rod-shaped gram-negative obligate intracellular bacterium that invades host enterocytes, and uses the host intracellular mechanisms to assist in its own reproduction. L. intracellularis infects primarily the ileum, but infection can also spread to the jejunum and colon. Special stains are required to visualize bacteria in pathologic samples.

Inflammation is not a significant feature of EPE. Instead, infection of enterocytes by L. intracellularis causes proliferation and hyperplasia of the cells, particularly the rapidly dividing cells of the glandular crypt epithelium. These proliferating cells tend to be immature, and lack microvilli, which is the important surface across which nutrients are absorbed. Infected foals subsequently suffer from malabsorption of nutrients (Pusterla 2009; Slovis 2014).

Transmission of L. intracellularis is thought to occur by the fecal-oral route. Horses may be introduced to the bacteria by contact with wild or domestic animals. L. intracellularis has been detected in the feces of a large variety of animals, including rodents, rabbits, pigs, dogs, deer, ostriches, monkeys and giraffes. It is not yet know how much species-specificity there is among the various L. intracellularis strains (Slovis 2014).

L. intracellularis infection tends to affect foals when they are at the vulnerable age of 4-7 months; when maternal antibody concentrations are waning, when many foals are often going through the stress of weaning, and when the foals are highly susceptible to gastrointestinal parasitism. It is not yet known whether one, or all of these factors, play an important role in the development of EPE.

Infected foals usually shed the bacteria in their feces, and shedding may start 5-17 days before clinical signs develop. Shedding foals may transmit the bacteria to other foals, however not all foals exposed to the bacteria will necessarily develop EPE. Adult horses are also occasionally affected by L. intracellularis infections (Slovis 2014).

In North America, EPE has a seasonal distribution, and is usually only detected between the months of August to January (Slovis 2014). EPE has been reported to occur in many countries throughout the world.

Clinical Presentation of EPE in Horses

EPE can affect foals between the ages of 2-13 months, but occurs especially in foals in the 4-7 month age-bracket. L. intracellularis infections can be subclinical, or may cause subtle signs such as mild ill thrift and failure to ‘thrive’.

The classic clinical findings with EPE are as follows (Pusterla 2009; Slovis 2014):

Clinical symptoms:

  • Weight loss
  • Diarrhea – can vary from cowpat to watery.
  • Lethargy, depression, anorexia
  • Fever
  • Colic
  • Peripheral edema

Blood work:

  • Hypoproteinemia – usually < 50 g/l.
  • Profound hypoalbuminemia – usually < 20 g/l.
  • Electrolyte abnormalities – often decreased calcium, chloride and sodium
  • +/- Leukocytosis, neutropenia, anemia, elevated fibrinogen.
  • +/- Elevated muscle enzymes.

Ultrasound:

  • Thickening of the small intestinal wall (normal wall thickness is < 3mm)
  • +/- Free abdominal fluid – on abdominocentesis this fluid is usually a non-inflammatory transudate.

In rare cases, L. intracellularis can cause intestinal necrosis, and foals may then present with acute onset disease and rapid death (Page 2012).

Diagnosis for EPE in Horses

The diagnosis of EPE is based on the clinical findings, as described above, and on fecal analysis and serology.

Fecal Analysis

Fecal culture is not a practical test for EPE, as the bacterium requires a special cell-culture in order to be grown (Pusterla 2009).

Polymerase Chain Reaction (PCR) analysis can detect L. intracellularis DNA in fecal samples. PCR testing has a high specificity for L. intracellularis detection, but the sensitivity of the test varies depending on the quality of the fecal sample (Pusterla 2009).

Fecal samples should be immediately refrigerated, as the overgrowth of some bacteria can inhibit the test. Rectal swabs can be used for PCR analysis if no fecal samples are available (Slovis 2014).

In advanced disease, L. intracellularis may no longer be shed in feces. L. intracellularis may also not be detectable if the foal has previously been treated with antibiotics (Slovis 2014).

Serology

Serology can detect antibodies (IgG) against L. intracellularis. In the early stage of disease serology results may be negative because antibodies have yet to develop. Serology is often used in combination with fecal PCR testing. For example, if a foal has clinical signs, but is fecal PCR negative, then a positive serology result would indicate that infection with L. intracellularis is likely. Several types of serologic tests are available, however the immunoperoxidase monolayer assay (IPMA) has been found to be the most accurate (Slovis 2014).

It is important to rule out other causes of protein loss in foals – i.e. kidney disease, intestinal parasites, right dorsal colitis etc. – by performing urinalysis, and examining the plural and peritoneal cavities (Slovis 2014).

Treatment for EPE in Horses

L. intracellularis infections can be treated with antibiotics, and normally foals will show a rapid response to treatment. The response will depend on the severity of disease, and whether there are complicating factors (such as severely compromised bowel) or concurrent disease (i.e. respiratory infections or gastric ulcers). Hypoalbuminemia may take a few weeks to resolve (Slovis 2014).

Recommendations for treatment include:

  • Antibiotics administration for 2-3 weeks. Antibiotics are selected based on their ability to penetrate the enterocyte cytoplasm.
    Recommended antibiotics include:

    • Macrolides (azithromycin, clarithromycin) +/- Rifampicin
      • Macrolides are not recommended in adult horses and should be avoided in older foals, as they can cause colitis (Slovis 2014; Pusterla 2009).
    • Tetracyclines (oxytetracycline, doxycycline).
    • Chloramphenicol.
  • Intravenous plasma to treat hypoalbuminemia. Plasma improves the colloid osmotic pressure and subsequently decreases the tissue edema. Synthetic colloids like Hetastarch can also be used, but plasma is preferred.
  • Supportive care, as needed. This may include:
    • Intravenous fluids.
    • Parenteral nutrition.
    • Non-steroidal anti-inflammatory medications (NSAIDs).
    • Polymixin B.
  • Anti-coagulation medications such as heparin, clopidogrel or aspirin may need to be considered, as bowel infarction is a small risk. EPE can induce a state of hypercoagulation in foals, because hypoproteinemia can cause a decrease in the production of antithrombin (Slovis 2014).

Prevention of EPE in Horses

Foals most at risk of infection are usually living in herd environments, where exposure to contaminated feces becomes more likely. Slovis (2014) made the following recommendations for prevention of EPE:

  • Minimize stress at weaning.
  • Implement good parasite control.
  • Attempt to restrict access of other animals to the herd.
  • Separate infected horses, and suspect horses, from the rest of the herd, until the shedding status is confirmed by fecal PCR.
  • Monitor the herd for infection by monitoring the foals for clinical signs, and systematically testing blood protein/blood albumin concentrations, serology, and fecal PCR.

The test results on healthy appearing horses may be interpreted as follows:

  1. If blood protein levels are normal, but serology is positive (titer ≥ 60 for the IPMA test), the horse should be considered to have had past exposure, with subclinical disease.
  2. If blood work shows hypoproteinemia (< 5.0 g/dl) or hypoalbuminemia (< 3.0 g/dl), and the serology is either positive, or negative, the horse should be tested further, including hematology, abdominal ultrasound, urinalysis, and fecal PCR.

Vaccinations against L. intracellularis are being developed and tested, but are not yet available commercially.

References

McOrist, S. et al. (2005) The Discovery of Lawsonia intracellularis. European Enterisol® Ileitis Symposium, Barcelona. Boehringer Ingelheim.

Page, A.E. et al. (2012) Acute Deterioration and Death with Necrotizing Enteritis Associated with Lawsonia intracellularis in 4 Weanling Horses. J Veterinary Internal Medicine, 26: 1476–1480.

Pusterla, N. et al. (2009) Equine proliferative enteropathy caused by Lawsonia intracellularis. Equine Vet Educ 21:415-419.

Slovis, N.A. (2014) Lawsonia intracellularis Proliferative Enteropathy in Foals. AAEP Focus on the First Year of Life Proceedings. http://www.aaep.org