Equine protozoal myeloencephalitis (EPM) continues to frustrate North American horse owners and veterinarians as one of the most common neurologic diseases in horses--and one of the most challenging to diagnose and treat. At the 2011 Western Veterinary Conference, held Feb. 20-24 in Las Vegas, Nev., Steve Reed, DVM, Dipl. ACVIM, of Rood & Riddle Equine Hospital in Lexington, Ky., delivered an overview of the disorder and discussed diagnostic and treatment options.
Background
Reed explained that EPM was first noted in Kentucky and Pennsylvania in the 1970s, and the causative organism (a protozoon called Sarcocystis neurona) was first identified in the 1980s. Later, researchers determined that S. neurona has a two-host life cycle. To complete its life cycle, this organism requires a definitive host (the opossum), which feeds on the muscles of a dead intermediate host (such as a raccoon, skunk, cat, or armadillo) containing S. neurona sarcocysts. Once ingested by the opossum these sarcocysts mature to their infective stage (sporocysts), which the opossum passes in its feces.
Horses, which are generally considered "dead-end hosts" (meaning they typically can't pass the protozoa on to other animals), contract the disease by ingesting infected matter, often grass or hay contaminated with opossum feces containing S. neurona sporocysts.
Traditionally, the prognosis for EPM has been poor, with many cases ending in euthanasia of the affected horse. Although some horses with EPM have irreparable damage that therapy can't fix, researchers have developed several treatment options that can ease the effects of the disease and allow many affected horses a longer, healthier life.
Diagnosis
Once infected, horses generally begin to display clinical signs, many of which are consistent with other neurologic diseases, Reed said. These signs include:
- Asymmetric muscle atrophy (wasting);
- Cranial nerve dysfunction;
- Ataxia (incoordination); and
- Dysphagia (difficulty swallowing).
Although the disease was first recognized more than 30 years ago, veterinarians have not yet found one single test that presents 100% diagnostically accurate results, Reed noted. Veterinarians generally begin their diagnosis process with a neurologic exam. A presumptive diagnosis can be made with the neurologic exam alone; however most veterinarians continue the process by running a blood or cerebrospinal (CSF) test to detect an antibody response against the parasite, he said. A blood test, Reed cautioned, will only determine whether the horse has been exposed to the causative agent. At this point, no test is able to render a 100% positive diagnosis of EPM, nor distinguish between a previous and recent exposure.
Reed said that one of the most commonly used EPM tests is a quantitative indirect fluorescent antibody test (IFAT), which identifies the immune response to S. neurona's surface antigens (SAG). The IFAT produces a quantifying number, or titer, that expresses the concentration of antibodies circulating in the horse’s blood, he explained. Comparative titers taken a few weeks apart show if a horse’s antibody level is changing, he added; If the horse has clinical signs of neurologic disease and the titer is rising, then the test might indicate active infection, he explained. The IFAT is interpreted as a probability of whether a horse has EPM; however, the claim is based on a small number of necropsies in an area of the country that has a low frequency of positive EPM cases, Reed cautioned.
Older testing methodologies using Western blot are still used but are only semi-quantitative, Reed explained: “The (Western blot) gives a reading of positive or negative as to the presence of antibodies in the serum or CSF, but it does not quantify the extent.”
Another quantitative test uses an enzyme-linked immunosorbent assay format (ELISA) to measure the antibody response to the surface antigen SAG1. Some strains of the S. neurona organism do not contain this surface antigen, generating false negative results.
Reed also discussed a recently developed by researchers at the University of Kentucky Gluck Equine Research Center in Lexington: an ELISA test that determines the antibody concentration in response to the surface antigens SAG2, 3, and 4. This test appears to be very accurate and highly diagnostic when blood and CSF titer values are compared and a ratio of the titers determined, he noted. A normal concentration of antibodies is expected in CSF based on the antibody concentration found in the blood. When the amount in CSF is greater than would be expected, based on this ratio, it can be assumed that the antibody production in the CSF is a result of primary infection in the nervous system.
Finally, Reed discussed a study that examined this new test in more than 300 paired blood and CSF samples from horses presenting with clinical signs suggestive of EPM. After analyzing the test and necropsy results, the team noted that horses with higher CSF titer levels, but more significantly, with serum to CSF titer ratios less than 100 were much more likely to have EPM.
Treatment
Only a handful of treatment options are available for horses with EPM, Reed noted, adding that several previously available choices have been removed from the market. Two FDA-approved products are currently available for use in treating EPM: ponazuril and diclazuril.
Reed explained that ponazuril (marketed under the trade name Marquis), a paste administered orally over a 28-day period, has been effective in treating EPM in horses. Additionally, few side effects have been noted in treated horses, he noted.
For treatment to be effective the medication must reach a certain detectable level in the blood; Reed noted that in his experience some horses do not reach that blood level until 11 days following the beginning of treatment, and in a typical 28-day course, this means the horse receives just over half the benefit of a full course of treatment. He suggested that a loading dose of the medication (which is not currently within the labeled instructions) might aid in boosting the blood level sooner, and he indicated that the medication's manufacturer is investigating this possibility.
Reed also discussed a newly released EPM treatment: diclazuril (marketed under the trade name Protazil). He said he believes that this recently FDA-approved pelleted form of an existing EPM treatment will prove very helpful to EPM horses. The recommended dosage for protazil is 1mg/kg body weight fed over a 28-day course, like ponzuril, and its alfalfa-based pellet used as a top-dressing on the horse's normal grain ration makes it more amenable to some horses than a paste or injection. He also added that it might one day be possible to use pelleted diclazuril as a preventive EPM treatment, but he stressed that no studies have been completed to test this hypothesis.
He also noted that some veterinarians use the injectable medications diclazuril and toltrazuril to treat EPM. Other medications used to aid EPM horses with their clinical signs, but not treat the root cause, are dexamethazone, flunixin meglumine (Banamine), and dimethyl sulfoxide (DMSO). Reed noted that adding natural vitamin E (not synthetic, as he noted it is not absorbed well) to an EPM horse's diet could help reduce neurologic signs.
Prevention
Reed suggested veterinarians encourage their clients to try to prevent EPM rather than treat it. He suggests the following measures to keep horses from consuming infected material:
- Protect feed and bedding supplies from exposure to wildlife;
- Remove carcasses of small wildlife on the property; and
- Trap and relocate small wildlife away from the property.
Reed does not believe there is any justification to "relocating opossums to heaven," as he put it; however, rehoming them away from horses will likely reduce horses' risk of contracting EPM.
Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.