While West Nile virus continues to dominate headlines when it comes to equine health, researchers are working to unlock the mysteries of that other, not-quite-so-new disease--equine protozoal myeloencephalitis (EPM). High on the list is understanding the life cycle of the disease.
"Knowing about the life cycle is important because it would allow us to more effectively test treatment methods, to test preventive methods like vaccines, and to have a model to study exactly why one horse gets the disease and another horse doesn't," explains EPM researcher Martin Furr, DVM, PhD, Dipl. ACVIM, associate professor of internal medicine at the Virginia-Maryland Regional College of Veterinary Medicine's Equine Medical Center.
Researchers are also investigating diagnoses, treatments, and prevention, all in the hope of getting a better handle on addressing EPM.
Know Thy Enemy
An equine challenge model is being developed at The Ohio State University (OSU) by William Saville, DVM, PhD, Dipl. ACVIM, an extension epidemiologist and large animal internist who has been researching EPM since 1993. In May, he confirmed that his team was able to induce clinical neurologic signs of EPM within seven to eight days after introducing a certain dose of parasite into the horse, with positive antibodies appearing in the blood within two to three weeks and in the cerebrospinal fluid within four weeks.
"What's important is we know the dose of the parasite, and when it was given, so we're using samples from those horses to work on new diagnostic testing," states Saville. "This may help us to understand the pathophysiology of the disease by knowing how the parasite causes the disease and what changes the body goes through once it's infected. It's important to have an animal model."
Furr's research team also recently completed some challenge studies; however, that data isn't yet available to the public.
On another front, researchers from the University of Florida, Virginia-Maryland Regional College of Veterinary Medicine, the University of Missouri, Ohio State, and the USDA Agricultural Research Service have learned there are several intermediate hosts for Sarcocystis neurona, the protozoal parasite that causes EPM in horses.
"The opossum is considered to be the definitive host," explains Michel Levy, DVM, Dipl. ACVIM, associate professor of large animal medicine at Purdue University. "For a while, several species of birds were thought to be the intermediary hosts, but this hypothesis was set aside. Most new information relates to the recognition of new intermediary hosts--the cat, armadillo, skunk, raccoon, and sea otter. Consequently, researchers now believe that a number of species can serve as intermediate hosts, with other candidates likely to be discovered in the future."
Treatment and Prevention
Currently, two new drug compounds are awaiting FDA approval--diclazuril and nitazoxanide (NTZ). "The effectiveness of diclazuril is expected to be about the same as Marquis, the only drug approved by the FDA for treatment of EPM," says Furr. "The data I've see for NTZ suggests the same effectiveness, but there is some concern about the safety, that it tends to make some of the horses not feel very well."
These drugs have been used in field trials with positive results, and Furr expects that both drugs will be approved.
Studies were recently completed seeking ways to eliminate the protozoal parasite in barns. Reports OSU's Saville, "We tested different disinfectants regularly used in veterinary medicine, but none of them did anything to the parasite; it was still viable. Only one compound (100% ammonia hydroxide) inactivated the organism, but the compound was so strong that it would likely damage the barn!"
More successful were the heat treatment studies: "Steam cleaning is one of the few ways to reduce contamination of the barn facility," stated Saville. "A heat treatment of 131°F (55°C) for 15 minutes or 140°F (60°C) for one minute or more renders the organism non-infective."
Another prevention option for many diseases is, of course, vaccination. Studies continue at several equine clinics regarding vaccine efficacy. Notes Andrews, "Fort Dodge is sponsoring a multi-center clinical trial looking at the effectiveness of their vaccine. It's a three-year trial; we are at the end of the second year."
In terms of other kinds of prevention, a trial was conducted on the use of daily pyrantel tartrate to prevent S. neurona infection in horses. Says Hal Schott, DVM, PhD, Dipl. ACVIM, associate professor of equine medicine at Michigan State University, "In vitro studies showed that pyrantel tartrate is lethal to S. neurona merozoites (a stage of the parasite that is found in neural tissue of affected horses). Twenty-four mixed-breed weanling horses were randomized into two groups. Group A received pyrantel tartrate (Strongid C 2X) at the label dose, and group B received a placebo. Ten adult horses testing negative for antibodies to S. neurona were monitored as untreated, uninfected controls."
Researchers inoculated experimental horses with EPM sporocysts (the stage of the parasite that the horse ingests) and administered pyrantel tartrate to the horses in group A immediately following dosing with sporocysts. Both groups subsequently tested positive to antibodies to S. neurona in the serum and spinal fluid tests, with no significant difference found between the groups.
"We conclude that daily administration of pyrantel tartrate does not prevent infection with S. neurona in horses when given according to label instruction," says Schott.
One bit of knowledge that has been gained in prevention concerns common sense management. "Because the opossum is a scavenger that can feed on dead animals, it's now thought that one of the steps in the prevention of the transmission of the parasite to horses is to remove and dispose of dead animals when found on pastures," Levy says. (For more on EPM research, see page 18.)
Retraining the EPM Horse
Through rehabilitation, most EPM horses can regain muscle strength, balance, and coordination--but to what degree is a matter of how quickly the horse received treatment and how severe the disease was.
Some affected horses can return to their previous levels of fitness and competition, while others remain too unsteady and weak to be safely ridden.
"The biggest problem is that many--if not most--horses retain some degree of neurologic deficit," explains Janice Sojka, VMD, MS, Dipl. ACVIM, associate professor of large animal medicine at Purdue University. "This makes most of the severely affected horses unsuitable for use except as breeding stock. The prognosis for full recovery must always be considered guarded."
Adds Steve Adair, DVM, MS, Dipl. ACVS, associate professor of equine surgery at the University of Tennessee's College of Veterinary Medicine, "We grade a horse's neurologic status from 1-5, with 1 barely perceptible, very minimal neurologic deficits, up to a grade 5, which is a horse that's recumbent (down). Successful therapy usually achieves only an improvement of one or two grades. What happens is the parasite eventually kills nerve tissue. Medication kills the parasite, but it takes a long time for the nervous system to heal and for the other neurons in the spine and in the brain stem to compensate for the dead nerve tissue. The improvement you see is the horse's ability to compensate from other nerves, the neurons rerouting themselves, and the horse adapting to its condition."
The horse which has had neurologic signs for several months to a year will likely have permanent neurologic deficits, states Frank M. Andrews, DVM, MS, Dipl. ACVIM, professor and section chief of large animal medicine at the University of Tennessee's College of Veterinary Medicine. However, he says, "If the horse has only been neurologic for a week or two, there is a good likelihood the horse will improve significantly with treatment."
Overall, treating and rehabilitating the EPM horse is a slow process. The first step is killing the parasite; the usual treatment is a 28-day round of Marquis. The second step is rehabilitation therapy, which is often a slow process that can take several months to a year before obtaining maximum results. Depending on the severity of clinical signs, retraining can begin as early as 14 days into medical treatment with a grade 1-3 horse. Grade 4-5 horses need to be able to stand and walk on their own in the stall before beginning an exercise regimen.
Starting Out--Prior to and during very early stages of retraining, horses should not be turned out. "A lot of these neurologic horses feel okay, so when they're turned out, they start running," warns Andrews. "Most neurologic horses can run pretty fast, but they can't stop. Once they get to the stage where they're exercising and are very stable, then they can be turned out to get exercise in a pasture or small paddock."
Although the length and frequency of sessions and speed of the horse's progress will depend on the individual horse, in general, horses should start each level of exercise with a five- to 10-minute session, once or twice a day for a week or two. When the horse can handle that amount of work in a steady, stable, and relatively strong manner, increase session length by adding a minute a day to each session until the horse is up to 15- to 20-minute sessions twice or three times daily.
"It may take three or four weeks to do that," Adair says.
Once the horse is steady, stable, and able to comfortably handle a particular exercise, the animal should be re-evaluated by a veterinarian before proceeding on to the next level of training.
The level at which a horse begins retraining depends on the severity of his disease, Adair emphasizes. A horse which has been down, but has improved to the point of moving around steadily in the stall, should start out with hand-walking in the barn aisle for five or 10 minutes once a day for a week or two. More stable horses can start out being ponied in straight lines at a walk or trot (hill work is especially beneficial for strengthening rear limb muscles) or longeing in each direction; do not work an incoordinated horse in tight circles as he can lose his balance and fall.
"If the horse can longe in both directions for a total of 45-60 minutes in a day--that may be divided in multiple sessions--then we are able to progress farther," says Adair.
To build up strength for carrying a rider, Andrews recommends working the horse with a saddle, then adding sacks of feed or weights as the horse gets stronger.
"If a horse is barely neurological, I may have the rider on them most of the time," Adair states. "Ridden exercises consist strictly of flat work; no jumping or gymnastics. Use big serpentines and walking/trotting transitions, and make sure they warm up and cool down very well.
"Once the horse is being ridden and the veterinarian judges the horse to be stable and safe, we need to start working on improving the horse's coordination," continues Adair. "This may be accomplished by starting with longeing the horse over ground poles in various configurations. Start with a single ground pole and work up to more complex arrangements. Once the horse is performing well on the longe line, then he can be ridden over ground poles. Again, start out with simple arrangements and proceed to more complex arrangements. Once they are comfortable/stable being ridden over ground poles, then other, more strenuous exercise may be introduced. The key is to go slow and do not put the handler, rider, or horse in danger."
EPM remains a difficult disease to understand, and it presents some continuing difficulties in diagnosis. Fortunately, researchers are moving ahead in their efforts to learn more about the disease, developing more sensitive diagnostics, and producing effective preventions and treatments.
BRINGING THE EPM HORSE BACK
Once horses have been treated medically and are showing signs of neurologic recovery from EPM, specific rehabilitation and complementary therapies might be indicated on an individual basis, depending on the presence, duration, and severity of the neurologic damage and secondary muscular compromise or compensation.
Rehabilitation for Muscle Atrophy
Physical therapists often use electrical muscle stimulation to help weak or injured muscles contract and to prevent loss of muscle mass when the nerves to the muscle have been injured. Two to four pads are placed over the affected muscle and specific electrical signals are applied to induce muscle contractions. The frequency and strength of the muscle contraction can be controlled by the operator, and are tailored for the specific muscle involved or desired treatment outcome. Electroacupuncture can also be applied in the same manner using acupuncture needles inserted into the affected muscle.
For horses with severe or long-standing muscle atrophy and fibrosis, electrical muscle stimulation will tend to be less effective in helping the muscles regain their original size and strength capabilities. If horses are having difficulty moving due to muscle weakness, muscle stimulation can provide an effective means to induce muscle contraction and support muscle rehabilitation without much exertion or conscious muscular effort from the horse. Caution should be used with electrical muscle stimulation since some horse do not tolerate the stimulation well or will get frightened by the unusual sensation of having their muscles contract involuntarily without having any control over the contractions.
Rehabilitation for Ataxia and Loss of Coordination
One of the most important factors to consider when returning horses with EPM to athletic function is the loss of coordination or awareness of where the horse's limbs are in space (proprioception). Nerve signals from the brain to the feet are disrupted with the disease, and horses are not able to control placement of their feet, resulting in toe-dragging, stumbling, tripping, and sometimes falling down. Similar problems occur in people with spinal cord injuries or after strokes.
Simple walking, backing, and ground pole exercises are immediately recommended to help develop or stimulate these injured nerve pathways. In severely affected horses, hand walking with two lead ropes and a third person holding into the tail to stabilize the hind end might be required. In milder cases, one might use progressively more difficult exercises designed to help develop impaired coordination, such as walking in straight lines, then big circles, then figure-eights, then serpentine movements around cones, then going up and down an incline or hill.
Advanced exercises include obstacle courses made of ground poles, cones, or barrels with increasingly difficult arrangements or increased heights such as half-cavaletti, then full cavaletti at three, six, nine, or 12 inches. All work is initially done in-hand at a walk, then at a trot as able, then in a round pen or longe line, then ridden at a walk, then at a trot and canter. If horses are not able to do the more advanced exercises, go back to the easier exercises until the horse is comfortable with them. Exercises should be successfully completed without any toe-dragging, stumbling, or fatigue.
Rehabilitation for Muscle Tightness and Stiffness
A horse with weakness or muscle loss in one part of his body often needs to compensate in other areas of his body. This results in overworked muscle groups or stiffness if an altered body position or disuse has been present for a long time. Low-level laser therapy and acupuncture are indicated for areas of secondary muscle hypertonicity (increased rigidity, tension, and spasticity of the muscles). If joint stiffness is perceived as the primary problem, then chiropractic care and stretches are most likely indicated.
A horse with muscle weakness or atrophy in his pelvic region might have to use the front half of his body more in order to compensate, which can result in neck, withers, or back stiffness. Stretches using carrot treats to encourage the horse to flex or bend his neck and back will help to promote spinal flexibility. Gentle leg stretches will help restore leg flexibility if the horse's legs are stiff or if he is not bearing weight evenly on all four legs. Gentle tail pulling exercises (side-to-side) force the horse to contract his croup muscles and engage his hindquarters, which is one of the most common areas affected and important skills lost in horses with EPM.--Kevin K. Haussler, DVM, DC, PhD, of the vet school at Cornell University
DIAGNOSING EQUINE PROTOZOAL MYELOENCEPHALITIS IN HORSES
Laboratory testing provides a useful adjunct to clinical examination for the diagnosis of equine protozoal myeloencephalitis (EPM). However, it cannot provide a diagnosis in and of itself. A thorough neurologic examination remains the single most important part of an effective diagnostic plan for EPM.
Serum and cerebrospinal fluid (CSF) samples can be collected and tested for a number of factors that might be useful for differentiating equine neurologic diseases. The presence of Sarcocystis neurona-specific antibody in serum and cerebrospinal fluid (CSF) is the basis of the standard EPM test (Western blot or immunoblot). Immunoblot testing of equine serum and CSF provides veterinarians with valuable information regarding exposure to S. neurona. It has now been shown that samples from horses with Neosporosis do not cross-react in the standard EPM test.
Another EPM test was introduced by a group at Michigan State University in 2000. At least one of the proteins used in this test appears to cross-react with S. fayeri, a similar, non-pathogenic (doesn't cause disease) parasite that commonly infects horses. A recently published comparison of the tests indicated that the new test did not perform as well as expected.
Recently, two additional tests were introduced that produce approximate estimates of the amount of anti-S. neurona antibody present in equine serum samples. Both assays rely on whole parasites rather than individual parasite proteins to detect the presence of anti-S. neurona antibodies. The developers of the S. neurona direct agglutination test (SAT) have claimed approximately 90% agreement with the standard EPM test, but the work has not been published for peer review.
The indirect fluorescent antibody test (IFAT) uses fluorescence to detect antibodies. Initial results published using this technique compared favorably with the standard EPM test and even suggested greater specificity. However, the number of horses tested was very limited.
The parasite has proven its ability to cause disease months after initial exposure. Presumably, serum antibodies rise following each exposure and begin to fall shortly after the parasite is eliminated or crosses the blood-brain barrier. An exposure rate of 45% indicates that horses probably ingest sporocysts on a fairly routine basis. Therefore, it makes little difference if serum (or CSF) antibody concentration is high or low; it is most important to know whether antibodies are present or not; that is, does the sample test positive or negative? An increasing concentration of specific antibody indicates recent exposure, which may or may not be relevant to the current disease problem.
Without question, further improvement of EPM testing methods are needed, and laboratories across the United States are working on new diagnostic tests using a variety of formats. (For more information on EPM testing, see article #4555 online.)--David Granstrom, DVM, Dipl. ACVIM
About the Author
Marcia King is an award-winning freelance writer based in Ohio who specializes in equine, canine, and feline veterinary topics. She's schooled in hunt seat, dressage, and Western pleasure.
POLL: Tack Shopping Choices