History

Equine protozoal myeloencephalitis was originally identified in the 1960's by Dr. Jim Rooney, although protozoa were first identified in the lesions in 1974. This disease has been considered to be sporadic and rare, but recently, researchers have begun to learn the extent of distribution of this disease. Until recently, we had no idea which species of animal actually spread the disease. However, recent research efforts at the University of Kentucky have implicated the opossum as the definitive host of the EPM organism.

Clinical Signs

EPM is an infection of the central nervous system of horses. The neurological signs that it causes are most commonly asymmetric incoordination (ataxia), weakness and spasticity, although they may mimic almost any neurological condition. Clinical signs among horses with EPM include a wide array of symptoms that may result from primary or secondary problems. Some of the signs cannot be distinguished from other problems, such as lameness. Airway abnormalities, such as laryngeal hemiplegia (paralyzed flaps), dorsal displacement of the soft palate (snoring), or airway noise of undetermined origin may result from protozoa infecting the nerves which innervate the throat. Apparent lameness, particularly atypical lameness or slight gait asymmetry of the rear limbs are commonly caused by EPM. Focal muscle atrophy, or even generalized muscle atrophy or loss of condition may result. Secondary signs also occur with neurological disease. Upward fixation of the patella (locking up of the stifle) is among the most common findings among horses with neurological disease. Another common side effect of EPM is back soreness, which can be severe. Even typical racing injuries may ultimately be caused by EPM, because horses which are uncoordinated are much more likely to "take a bad step" in racing or training. Therefore, any horse with these signs should be carefully evaluated for the presence of neurological disease.

Life Cycle

The organism that causes EPM was tentatively named Sarcocystis neurona in 1990, because we did not have a positive identification of the species. However, since the opossum has been identified as the definitive host, DNA testing and infection studies have shown that the organism is closely related to the protozoan Sarcocystis falcatula, a species that cycles in nature between two host species, birds and opossums. This protozoan can cause a severe life-threatening disease in some of its natural intermediate hosts, such as budgerigars, but may cause few clinical signs in others, such as pigeons. Subsequent research performed at the University of Florida and Cornell University has demonstrated that S. falcatula and S. neurona are not the same species. In the normal life cycle, the parasite is ingested (fecal-oral transmission) in the form of a sporocyst by the intermediate host, undergoes asexual reproduction in the blood vessels of the liver, lungs and muscles and then encysts in the intermediate host's muscle tissue, without traveling to the central nervous system. When this tissue is eaten by the opossum, the organism undergoes sexual reproduction in the intestinal cells, and forms the infective sporocysts, which are passed in the feces. The opossum does not become sick, but may shed the parasites for months.

Horses represent an aberrant host of S. neurona. Sporocysts are ingested, but never encyst in the tissues of the horse. Instead, they migrate to the central nervous system, where they continue to undergo asexual reproduction intracellularly in neurons, without forming tissue cysts. Horses cannot transmit the organism to other horses, or even to opossums. Horses probably eat the opossum sporocysts inadvertently while eating grass, hay or grain.

In a recent research study (Fenger et al., 1997), we were able to reproduce the disease by feeding opossum-derived sporocysts to horses. The horses had detectable serum antibodies at about 3 weeks after infection, and all of the horses that ultimately developed EPM had spinal fluid antibodies about a week later. Those that did not develop EPM never had antibodies in the spinal fluid, even as long as 4 months later.

Opossums

This disease may be preventable by some simple measures. Anything that may attract opossums into barns should be tightly covered, or put away, especially at night. This includes cat food, garbage and grain. Opossums are particularly fond of cat and dog food. Feed should not be left out at night for the morning, or even during the day to attract birds. The opossum population should be kept under control on farms and stables, where possible. Mesh wire or chain link fencing with "hot wire" around the outside may keep opossums out, since they can climb, but they do not dig. The processes of steam-crimping and pelleting grain kills off the sporocysts, so using processed grains can also decrease the exposure to EPM.

Epidemiology

Exposure of horses to EPM occurs at an average rate of about 50%, but approaches 80-90% among some groups of horses. It is impossible to predict which exposed horses will develop fulminant disease. Some horses with active disease may be able to clear the organism without treatment. Currently, the only approach to control of EPM is early detection of incoordination, gait or other abnormalities, definitive diagnosis of the disease by cerebrospinal fluid (CSF) analysis, and appropriate treatment. The disease probably requires a minimum of two weeks and up to two years to develop from the time of exposure to the development of marked clinical signs. The disease can increase in intensity when the equines immune system is challenged. Exposure rates (but not disease rates) for different farms or training facilities may vary from zero to 100% of the horses at a given location. Premises with very high seroprevalence appear also to have a high prevalence of clinical disease. Most horses probably ingest the sporocysts, mount an immune response, and clear the organisms before they reach the central nervous system. Alternatively, they may be persistently infected in the central nervous system, but are able to combat the organism sufficiently to prevent the development of clinical signs. There is no "dormant" stage, and there is no "remission".

Diagnosis

The current testing methods are limited in that cerebrospinal fluid (CSF) is required for the diagnosis. Falsely positive or negative tests are unlikely in spinal fluid, but common when only the blood is tested. Therefore, any horses that are considered candidates for EPM should have CSF tested for the presence of antibodies to this parasite.

Treatment

The most exciting new development in the area of EPM research is the advent of new and different alternatives for treating EPM. There are no FDA approved drugs for the treatment of this disease, but a number of drugs have been used off-label, or imported from other countries for treating EPM. The most common treatment is still a combination therapy of pyrimethamine (1.0 mg/kg daily), in combination with sulfadiazine (20 mg/kg daily), most commonly available from compounding pharmacies . New treatments and medications, along with vaccinations are being developed regularly. Ask your veterinarian for the best direction in diagnosis and treatment to date. Horses should remain on both drugs for the duration of treatment, because protozoa have been shown to become resistant to pyrimethamine in the absence of sulfas. Trimethoprim is not recommended, and probably should be avoided, if possible, because it is likely to add to the toxicity of the pyrimethamine, without adding to the efficacy Beware of compounding pharmacies that compound a combination product with trimethoprim, pyrimethamine and sulfadiazine, because the trimethoprim is contraindicated. Ideally, CSF should be obtained and determined to test negative by immunoblot before the treatment is discontinued although this approach is likely to be extremely conservative, and many horses may actually continue to test positive for several months after the protozoa is killed.

Anti-inflammatory therapy is indicated in acute EPM cases. This may include treatment with phenylbutazone or banamine (1.1 mg/kg 1-2 times daily for 3-7 days), as well as the addition of DMSO (1 g/kg in a 10% solution) administered either intravenously or by nasogastric tube. Corticosteroids may be used if necessary. Anti-inflammatory drugs are occasionally necessary at other times during the first six weeks of treatment. Some horses actually get worse during treatment, presumably because of a reaction to the dying parasites. Supplementation with vitamin E, folic acid and thiamine may be helpful adjunct treatment. Some recent evidence has put the use of folic acid supplementation into question. However, it is probably safe and recommended for most performance horses, but not recommended for use in pregnant animals.

Horses testing positive and treated have been able to go on to live normal lives where others may always show some sort of symptom. Each case should be viewed individually with keeping in mind the possibilities of behavior issues due to the physical factors of the disease.

UPDATE 02/14/2008