I thought I would devote this week's page to Equine Protozoal Myeloencephalitis (EPM), a frightening disease that we in the horse community MUST learn more about to dispell the myths surrounding it.
WHAT IS EPM?
Dr. Jim Rooney originally identified EPM in the 1960's, although it was not until 1974 that protozoa were found in the lesions and discovered to be the culprits of the disease. EPM is an infection of the equine central nervous system. It is NOT contagious, as the horse is a "dead end host" i.e. the protozoa that cause the illness are NOT passed out in the horse's saliva, feces, urine, blood, or semen.
WHAT CAUSES EPM?
EPM is caused by a protozoan organism called Sarcocystis neurona . It has been positively identified using DNA testing and infection studies of opossums who are infected with the protozoan. It is closely related to a protozoan that cycles between birds and opossums in nature called Sarcocystis falcatula In the life cycle of these protozoa in the case of birds, they are ingested at the sporocyst stage by fecal-oral transmission. The intermediate host (in this case, the bird) provides an environment for the sporocyst to asexually reproduce in the tissues of its liver, lungs, and muscles. The muscle tissue then becomes the area where the sporocyst encysts. It is important to note that in the bird, the sporocyst does NOT attack the central nervous system. In some birds, such as pigeons, the protozoan infestation will cause little if any clinical problems or signs, but in other species it can be particularly devastating. The opossum then consume the tissue of the infected bird. Within the opossum's intestinal cells, the protozoan undergoes sexual reproduction and forms the infective sporocysts that the opossum then deposits in the environment through its fecal material. It is important to note that the opossum itself does not become sick from the infection by the protozoan, but it can shed these dangerous parasites for months following an infestation in their gastrointestinal tract. Once in the horse's central nervous system, the protozoa destroy the fatty layer of insulation around nerves called myelin. This reduces conductivity of the neuron and reduces the level, number, and accuracy of firing of action potentials from the neuron to transmit impulses necessary for coordinated movement and balance. Think of an electric fan. As long as it has a plastic coating (akin to the myelin in the horse's nervous system) around its wires, it will run smooth and steady with the electrical current being insulated from the outside environment and going straight to the motor of the fan. However, if we remove a section of that plastic coating, the fan now has serious trouble operating properly if at all. THIS IS WHAT HAPPENS TO A HORSE WITH EPM!
HOW DO HORSES CONTRACT THE DISEASE?
The horse is an aberrant host (a "dead end" host if you will) of the protozoa. Sarcocystis neurona sporocysts are ingested by the horse inadvertently while foraging for grass, or while eating their ration of hay or grain. The reason the horse is a "dead end" host is because the sporocysts which cause the infection never encyst in the tissues of the horse as they do in the bird and opossum. They migrate to the central nervous system. In the horse's central nervous system, the sporocysts reproduce asexually intracellularly in neurons (the cells that make up the central nervous system and conduct electrical impulses through the horse's body). They do this without forming tissue cysts. It is interesting to note that as reported by a study by Fenger et al., 1997, the disease condition was reproduced by feeding opossum-derived sporocysts to horses. Detectable serum antibodies (markers produced by the immune system that indicate that an animal/person has been infected with a particular organism) will appear at about three weeks post infection. All horses that developed EPM in the study had antibodies in their spinal fluid approximately 7 days after being fed the sporocysts. The horses that did not develop EPM never developed those antibodies in their spinal fluid.
HOW COMMON IS EPM?
About 50% of horses will be exposed to EPM, though in some groups the rate of exposure (which does not necessarily lead to infection of all horses in the group) is closer to 80-90%. Veterinary medicine currently does not have the capability to predict which horses will develop the full blown disease. Some horses who contract the active disease are able to clear the protozoa from their system without treatment. It is hypothesized that the disease takes a minimum of two weeks but possibly as long as two YEARS to develop from the time of exposure until the horse owner notices signs that something is amiss with his/her horse. There is no "dormant stage" or "remission" with EPM. Most horses ingest the sporocysts, an immune response is mounted, and the organisms ar cleared from the body before reaching the central nervous system. Another scenario is that the horse may have a persistent infection in the central nervous system of the protozoa, but the horse is able to keep the number of protozoa low enough by an immune response to keep the clinical signs of the disease from becoming apparent.
WHAT ARE THE SYMPTOMS OF EPM?
There are many signs of EPM. When I managed Cranwell Farms there was a mare there who had the disease. She had been pulled off of her medication after her first round of treatment (see treatment philosophies below) and she first started showing a lack of balance and she would put her head to the ground as if looking for the ground when she was walked from her stall as though she was experiencing vertigo. Ataxia (asymmetric incoordination), muscle weakness, muscle spasticity, lameness, airway abnormality (laryngeal hemiplegia or roaring, dorsal displacement of the soft palate or snoring, or an airway noise that is of an undetermined origin or of undetermined cause can all indicate that the protozoa have attacked neurons which innervate the muscles and structures of the throat). A horse with EPM will often show atypical lameness, or a SLIGHT asymmetry of the rear limbs. Focal (very localized in one location) or generalized atrophy of muscle and loss of condition can also be an indicator of EPM. Locking of the stifle joint in the hind legs (upward luxation of the patella) is also a common finding in horses with EPM as well as other neurologic diseases. Back soreness (at times severe) is also a red flag for EPM.
HOW IS EPM DIAGNOSED?
Neurological testing and the early detection of incoordination, gait, or other signs listed above can point your veterinarian in the right direction. However, the ONLY definitive way to tell if your horse HAS the disease (as opposed to having been exposed to the disease, which can be detected in the blood which could result in a false positive if your horse has no antibodies in its cerebrospinal fluid) is by an antibody immunoblot test of the cerebrospinal fluid (CSF) of your horse via a spinal tap.
WHAT IS THE TREATMENT FOR EPM?
There are no FDA approved drugs for treating EPM, though a number of drugs have been used "off-label" and have been imported to treat the disease. The most common combination of drugs, pyrimethamine (1.0 mg/kg daily) and sulfadiazine (20 mg/kg daily) work by depriving the protozoa of folic acid, which is a necessary component for the survival of the protozoa and the cell wall of the organism remaining intact. It should be noted that the horse is also subsequently deprived of folic acid during the course of treatment. Studies in 1997 by Fenger et al. suggested that supplementing the horse with vitamin E, folic acid, and thiamine may be helpful in addition to the drug therapy in treating horses with EPM. However, recent evidence has called folic acid supplementation into question particularly in pregnant mares. The original concern was that if the mare was deficient in folic acid during pregnancy, there could be an increase of neural tube defects in foals and a reduction of foal crop survival. However, it turned out that oversupplementation with folic acid not only had no effect on neural tube defects of foals, it substantially increased foal death due to anemia. At this time, it is NOT recommended that you supplement a pregnant mare who is on drug therapy for EPM with folic acid. However, it should be safe to do for performance horses in which pregnancy status is not an issue. It should also be noted that the two drugs previously mentioned should be taken TOGETHER, as the protozoa are more likely to become resistant (and therefore untreatable) if pyrimethamine is used without sulfas. Trimethoprim is contraindicated, as it tends to increase the toxicity of pyrimethamine without adding to the efficiency and efficacy of pyrimethamine. There are two schools of thought on when it is acceptable and safe to discontinue treatment of the horse with EPM. One school of thought says to discontinue treatment when symptoms disappear. However, as I noted in my earlier symptoms section, that is not always effective and is believed by some to increase the risk of the development of resistant strains of the protozoa. The other more conservative school of thought is that treatment should be continued until the cerebrospinal fluid is determined to test negative by immunoblot. It should be noted that many horses will continue to test positive for several months after all protozoa have been killed and eliminated from the horse's system. Antiinflammatory therapy is necessary and indicated in cases of acute EPM. Phenylbutazone or banamine (1.1mg/kg b.i.d. for 3-7 days), as well as DMSO (1g/kg in a 10% solution) via I.V. or nasogastric administration. Corticosteroids may also be used if needed. Some horses will appear to get worse during the course of treatment, which is thought to be a reaction to the dying parasites. The antiinflammatory medications should help diminish this problem. Use caution with phenylbutazone in pregnant mares for an extended period of time, as it can cause placental thickening and premature placental separation if utilized for long time periods in high dosages. If you're at all unsure, be certain to ask your veterinarian to advise you. Physical therapy and massage as well as the use of an equine chiropractor has been shown to be quite beneficial to the horse who is recovering from EPM. The horse will likely NEVER be "what he or she once was" in terms of performance, but can still be a valuable, loyal, and loving companion. Also be aware that EPM and laminitis (founder) tend to go hand in hand due to the metabolically devastating effects that the protozoa have on the horse's body. Monitor your EPM horse's deep digital pulses DAILY and pay special attention to their feet. I learned this when the afore mentioned mare foundered.
HOW DO I PREVENT EPM?
Currently the only preventative against EPM is to control the access of opossums to your horse's environment. It is therefore crucial that ANYTHING that may attract opossums into your barn such as cat food, dog food, garbage, and grain should be tightly covered in airtight/sealable/plastic containers or put away entirely, particularly at night when opossums (nocturnal creatures by nature) are active. Also try to control the bird population in your barn. Do NOT leave feed out at night for the morning, and do NOT leave feed out during the day to attract birds. If possible, try to control the opossum population on your farms and around your stables. Mesh wire with a "hot wire" around the outside may help to keep opossums out of your pastures, as opossums are quite skilled at climbing, but do not posess the talent for heavy digging to get under fences. Sporocysts are killed during the steam-crimping and pelleting processes in grain mills, so the use of processed feeds and grains for your horse may help reduce the horse's exposure to the protozoa that cause EPM. A drug manufacturer has developed a vaccine against EPM according to what I have been told by veterinarians at the Virginia-Maryland Regional College of Veterinary Medicine. However, I was STRONGLY advised NOT to use the new vaccine for at LEAST a year or two because in the rush to get it to market, testing may not have been as complete as it could be which could result in some unfortunate, unforseen side effects. (I'm sure all the horse owners who rushed to have their horses vaccinated against leptospirosis when it became the fad despite limited trials who now have horses with the autoimmune manifestation of equine recurrent uveitis can testify to that.)