Similar scenes of realization have been played out often enough now to have made the cause out often enough now to have made the cause- equine protozoal myeloencephalitis (EPM) -all too familiar in many parts of the United States. Some southeastern horsemen are medicating their stables of uninfected racehorses in hopes of preventing infection, accepting the risk that the antiprotozoal treatment often produces anemia and occasionally triggers severe diarrhea. The University of Kentucky's Gluck Equine Research Center has set up an EPM pre-recorded information line to deal with calls from worried horsemen, and the university has set up a commercial laboratory to run EPM tests sent by equine practitioners. Auction buyers are demanding EPM-negative tests before they bid on horses. Research into the course and treatment of the disease is proliferating.

The cause of this uproar is a parasitic protozoan, a microscopic, single-celled animal called Sarcocystis neurona (although scientists now believe the protozoa is the same as one identified 100 years ago as Sarcocystis falcatula). Ingested by horses in their food and water, the protozoa sometimes find their way to a host horse's spinal cord, where inflammation and eventually nerve-cell damage most often produce a vague lameness mixed with incoordination and weakness.

The good news is that for all its deceptiveness, EPM is far from invincible:

When caretakers are aware of what to watch for, take swift action in response to these signs and conscientiously apply treatment, they can contribute to satisfactory recoveries of EPM-afflicted horses. But without prompt intervention, the victims can become progressively incapacitated until euthanasia is the only option.

THE INFECTION PROCESS

A "cousin" to the protozoan responsible for malaria, S. nerona probably between opossums and brown-headed cowbirds and grackles. The omnivorous marsupials feed on any and everything, including dead birds in whose muscles protozoa live; the birds consume the protozoa's infective state (sporocysts) in opossum feces. Scientists suspect that horses stumble into this cycle by ingesting food or water contaminated by feces from infected opossums. Horses are noncontagious "dead-end" hosts of the EPM protozoa, and scientists have concluded that they do not infect each other.

Once the protozoa enter equine hosts, they are usually disabled by the immune system, but in some horses, they penetrate blood-vessel walls to enter the spinal cord and brain. When the parasites mature, the nerve cells burst, causing a host of neurologic symptoms, including lameness, incoordination and muscle wasting. Once EPM has breached the central nervous system, early detection is crucial to horsešs recovery.

TROUBLE SIGNS

Every day that passes without antiprotozoal therapy for the infected horse increases the potential for irreparable nerve-cell destruction. The key to swift diagnosis lies in the handler's recognition of the subtle changes in the horse's stance and way of going. A rider may well notice this subtle incoordination or weakness before it becomes evident to viewers or examiners.

EPM SIGNS INCLUDE:
• subtle or marked incoordination, including toe dragging, especially when tired; often affects only one side;
• lameness, more often than not in the hind end, and/or back soreness that cannot be diagnosed with confidence, especially when coupled with incoordination;
• asymmetry or choppiness of gait;
• muscle atrophy, often asymmetrical, usually of the hindquarters but may involve the forelegs or face;
• facial paralysis, indicated by lips or ears drooping to one side, head tilting, protruding tongue and difficulty chewing, swallowing or blinking;
• standing or stepping awkwardly, indicating a loss of proprioception, the sense of where limbs are placed in space;
• tendency to lean to one side;

Signs frequently appear slight for long periods before suddenly becoming severe. This occurs in part because horses have a finite capacity to switch from failing neurologic circuits to healthy ones. "The body has an unbelievable capacity for compensation," explains University of Kentucky PhD candidate and EPM researcher Clara K. Fenger, DVM, Dip. ACVIM. "A lot of horses can compensate to a point, and then all of a sudden, it's night and day. The trainer thinks it started yesterday, whereas the horse really had the problem for a long time and then suddenly reached a point at which he could no longer compensate." This subtlety of the signs, coupled with their similarity to those of other ailments, particularly wobblers disease and hind-end lamenesses, means that for months victims may be mistakenly treated for orthopedic problems instead of the neurological disease. In some cases, slight incoordination causes horses to injure themselves repeatedly without handlers ever suspecting a connection with EPM. "There are those tough-luck horses that just keep getting little injuries here and there," says Fenger. "A lot of them have had EPM for a while. They're just a little uncoordinated, so when they get tired, they're more likely to take a bad step and injure something."

DIAGNOSTIC TESTS

Diagnosis is performed using a Western blot test, a technique that detects antibodies to the protozoa in blood serum or spinal-fluid samples. Blood testing is a simple, inexpensive procedure, but it is in no way a definitive diagnostic tool for EPM, as it reveals only that the horse has been exposed to the protozoa but not necessarily that the protozoa have passed into the central nervous system. Spinal taps require local or general anesthesia, depending upon whether the fluid drawn from between vertebrae in the loin area or from just behind the skull, and call for a degree of experience and skill to assure that no blood gets into the spinal-fluid sample to possibly confuse the results. Consequently, some practitioners prefer to have the procedure performed at referral clinics where spinal taps are commonplace. Despite the expense and greater risk of the spinal tap, it is the only sure way to find out if the protozoa have breached the blood-brain barrier and reached the central nervous system. Yet other diagnostic difficulties occur when a horse infected in the previous week or two has not yet produced the antibodies identifiable by the Western blot test or when antibody reaction has waned in long-entrenched cases. In both instances, an infected horse may test negative. To fill these diagnostic gaps, Fenger recently developed a test that reveals the presence of A. neurona DNA in spinal fluid. Because it will detect the organism itself even when antibody response is low, this test is a useful adjunct to the Western blot procedure.

TREATMENT

EPM treatment consists of the antiprotozoal drugs pyrimethamine (Daraprim®) and trimethoprim-sulfa (several trade names exist, including tribrissen®) coupled with nonsteroidal anti-inflammatories. (Administration of corticosterois anti-inflammatories suppresses the horse's natural defenses against infectious agents and can worsen the condition.) The standard medication protocol has been to continue treatment uninterrupted for three to four weeks beyond the time the horse appears to have fully recovered/improved.

Fenger estimates, however, that between one-third and one-half of today's EPM patients relapse within three weeks after treatment ends. Based on a recent study of 11 EPM patients on a Kentucky farm, she believes that the post-recovery medication probably needs to continue until the patient's spinal fluid tests negative to the protozoa, which, in the study horses, took an average of four months. To date, none of the 11 horses has relapsed. Other researchers also support the practice of testing before stopping medication: "We're starting to recommend that you treat until they are negative," says Robert MacKay, BVSc, PhD, associate professor of large animal medicine at the University of Florida. "It gives you an objective end point."

On average, the medications cost $400 to $800 per month, making long-term treatments expensive propositions. In rare cases, horses require medication indefinitely to control replication of a drug-resistant protozoal strain that can't be completely eradicated. In successful cases, these permanently medicated horses are perfectly normal and can continue their training and competition schedules unhindered. (Drug relations in some performance sports or particular jurisdictions may restrict participation of horses receiving antiprotozoal medications.) Additional expenses arise from monitoring and treating the common side effects of the drugs: many practitioners run complete blood counts during the course of treatment to check for anemia and decreased white blood cell counts. Supplementation of folic acid, the B vitamin depleted by the medications, and plenty of green grass and alfalfa in the horse's diet are the usual prescriptions for patients rendered anemic by the treatment. Because Daraprim has affected fetal development in research animals, some practitioners are concerned about using the drug in pregnant mares. Yet they stress that this does not mean that broodmare owners should forego treatment "If you don't treat," says EPM researcher David Granstrom, DVM, PhD, associate professor of parasitology at the University of Kentucky, "you don't have a horse, and you don't have a baby. We recommend the standard dose of Tribrissen®, half the daily dose of Daraprim and folic-acid supplementation" for pregnant mares.

THE PROGNOSIS

A successful course of medication destroys only the existing infection and inflammation-produced signs but can do nothing to restore damaged or destroyed nerve cells. Consequently, the outlook for each affected horse is directly related to the stage at which EPM has been diagnosed and treated. Researchers estimate that between 75 and 90 percent of horses whose infections are caught early make full recoveries, but those whose infections go untreated for months, even years, or who are treated incompletely and inconsistently face at least a lifetime of medication if not increasing disability.