They shouldn't be there; it's not where they normally live. And when they do invade, they can be innocuous, or insidious. Sarcocystis neurona is not a parasite whose life cycle includes the horse. When horses ingest the protozoan appanantly passed on by some kind of wildlife, the resulting neurologic disease is treatable, but often is fatal.
When the protozoan Sarcocystis neurona is ingested by a horse, it penetrates the bowel and eventually makes its way to the brain or spinal cord, where is can cause extensive damage, said Dr. David Granstrom of the Gluck Equine Research Center at the University of Kentucky. The disease, know as equine protozoal myeloencephalitis (EPM) is not contagious from horse to horse, and the protozoan does not mature and reproduce in the horse. The horse is a dead-end host and thus unable to spread the disease.
EPM can mimic a number of neurologic diseases depending on what part of the brain or spinal cord it damages. Clinical signs can range from mild to severe...from dragging a toe to seizures and collapse. Often one side of the body is affected worse than the other.
Granstrom developed the first test able to detect the presence of Sarcocystis neurona in a living horse. Using an immunoassay known as an immunoblot (or Western blot), immunity to Sarcocystis neurona can be tested in blood or spinal fluid samples. This test specifically determines whether the horse has been exposed to Sarcocystis neurona, as opposed to other Sarcocystis organisms, such as S. Fayeri, which don't cause neurologic disease in the horse.
Nationwide, an estimated 30% of the horses have been exposed to the organism, but only a small fraction will ever show clinical signs. Some areas would have more horses test positive than other areas because of exposure to infected wildlife.
Since a large number of horses may test positive for exposure using a blood sample, testing blood alone is of limited value in determining the cause of a central nervous system disease, said Granstrom. However, "if you test spinal fluid and it's positive, then it's highly correlated with the diagnosis of EPM at postmortem," said Granstrom.
More than 90% of the time the immunoblot testing of spinal fluid was correct. False positives can occur if blood gets in the spinal fluid sample or if the blood-brain barrier has been compromised or damaged. (The capillary walls in the central nervous system are tightly joined and antibodies can't pass through them unless there is damage.)
Since starting to test blood and spinal fluid samples routinely in January of 1992, Granstrom's lab had processed more than 6,000 tests through the end of May. There was greater than 60% positives among these tests. However, Granstrom warned that horse owners should not panic over the numbers, but keep in mind that many of these samples were submitted by veterinarians who suspected EPM in horses with neurologic signs. About a third probably had EPM.
"With 1,400 spinal fluid samples, there were more than 35% positives," he said. "When we looked at serum and spinal fluid from the same horse (about 1,100 horses), we saw about the same percentage (35%) of positives."
He added that in those 1,100 horses with both blood and serum samples, less than one-half of one percent, or three horses, were seronegative from blood but had positive spinal fluid. "We're not missing them with the blood, but the spinal fluid is more specific," Granstrom said.
The lab currently is conducting about 200 tests for EPM each week from across North America. Sarcocystis neurona appears to be limited to the Western Hemisphere and is not known to affect horses native to Europe, said Granstrom.
"We've received a lot of blood to test from racetracks nationwide, and there appears to be a higher number of positives than on the farms," he said. "We don't know if it has something to do with feed sources or travel and exposure, or tracks that have wildlife problems."
CHAIN OF EVENTS
Sarcocystis organisms are spread by a predator-prey or scavenger-carrion route, said Granstrom. The predator (or scavenger) eats the tissues of the prey (or carrion). In the muscles the Sarcocystis organisms Oocysts form in the lining of the predator's bowel, rupture, and release sporocysts into the environment through droppings. These sporocysts are eaten by a specific host animal.
In the appropriate intermediate host, the Sarcocystis organisms penetrate the bowel and replicate in blood vessel walls. Sarcocystis organisms eventually end up in the muscles, where they can remain until they are eaten by the appropriate predator or scavenger.
The horse enters the life cycle when the predator sheds the Sarcocystis organisms in its feces and they are picked up and eaten. However, since the organisms cannot reproduce, the parasite cannot be spread to another horse or be infectious to a carnivore that might eat the infected horse.
Finding the host animal is important in determining the life cycle of Sarcocystis neurona, said Granstrom. Wildlife in Central Kentucky have been captured and tested, and so far, skunks are the only animals that have tested positive for Sarcocystis neurona.
"This suggests that the skunk is involved" in the life cycle, said Granstom. "but the skunk might be inadvertently infected, like the horse. We'll continue to look until we find a host or hosts with the stage that's infective to the horse."
Dr. Clara Fenger, working in Granstrom's laboratory at the Gluck Center, has developed a test used on a research basis that is able to detect the parasite's DNA in spinal fluid or blood. From a research standpoint, this test is useful in helping screen wildlife to determine where the horses are getting the parasite.
"It probably won't replace the immunoblot in testing horses, but it's an important adjunct in some cases," said Granstrom. "It's extremely specific and sensitive. In theory, it can detect a single parasite, if the DNA is available in the sample."
Granstrom noted that birds and insects have been shown to transport Sarcocystis among other animals and might be a minor source of parasites for horses.
TREATMENT
"It appears from talking to veterinarians and from histories we receive that about half of the horses, or more, respond to treatment," said Granstrom. "Many of them don't improve enough to return to the same level of competition as before, but you may be able to salvage the horse for breeding or pleasure. It's not always hopeless. Some of them do quite well."
The key to successful treatment is quick diagnosis and immediate therapy.
"If you get to the horse quickly and get treatment started, then he should have a better chance," he said. "The longer the parasite stays in the brain and spinal cord, the more opportunity it has to do irreversible damage."
The two drugs that are primarily used are Trimethoprim sulfa (several brands are available) and pyrimethamine (trade name Daraprim). Both are anti-protozoal drugs (sulfa also is an antibiotic). DMSO, a rapid-acting anti-inflammatory, also is recommended, as are banamine and bute (non-steroidal anti-inflammatories). Granstrom said he did not recommend using corticosteroids because they are know to suppress the immune system.
"You want to arrest the parasite and allow the horse to get rid of it," explained Granstrom. "But it is possible to eliminate the parasite and have significant damage remain."
PROTECTION
There are no vaccinations available against Sarcocystis neurona. Since horses have to ingest the parasite, the best way to prevent EPM is to control wildlife around horses. Protect sweet feeds and grain products in tightly sealed containers. Keep the population of mice and rats down in the barn. Try to reduce contact with wildlife such as skunks and raccoons.
"We've not found any positive cats yet," said Granstrom, "but we are continuing to look at them as a possible host. We can't eliminate any carnivore until we find the appropriate one or ones. However, cats are abundant in horse barns in Europe, and apparently there is no EPM there."
The knowledge that EPM can mimic numerous neurologic processes makes
it difficult to spot the problem, but awareness and the ability to test
for Sarcocystis neurona gives veterinarians a chance to diagnose the problem
early and start treatment that could very well save the animal's life.
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Equine Protozoal Myelitis 1994 Clara K. Fenger, DVM, MS, Dipl. ACVIM |
Equine protozoal myelitis (EPM) is a neurologic disease of horses which most commonly results in asymmetric incoordination (ataxia), weakness and spasticity, although it may mimic almost any neurologic condition. In the most mild cases, the only clinical sign may be an ill-defined rear limb lameness, and in the most severe cases, horses may be unable to swallow or stand. This disease is easy to mistake for wobbler disease (cervical vertebral myelopathy). The causative organism is Sarcocystis neurona, which is a protozoal parasite. The clinical signs are caused by direct neuronal damage by the parasite, and damage secondary to the mononuclear inflammatory infiltrate.
The life cycle and mode of transmission of this parasite to horses has not yet been determined, however several conclusions can be made based on our knowledge of related organisms. Sarcocystis spp have an obligate 2-host species life cycle, including an herbivorous (prey species) intermediate host and a carnivorous (predator or scavenger species) definitive host. The parasite is ingested (fecal-oral transmission) in the form of a sporocyst by the intermediate host. The organism then undergoes asexual reproduction in the intermediate host and encysts in the host tissue. When this tissue is eaten by the definitive host, the organism undergoes sexual reproduction in the intestinal cells, and forms the infective sporocysts, which are passed in the feces. These sporocysts are picked up in the feed of the intermediate host, and undergo an asexual stage in this host. This consists of a replicative cycle in the blood vessels, and possibly in the white blood cells. Eventually, the parasites find their way to the muscle, and encyst, forming a sarcocyst, which contains quiescent protozoa called bradyzoites. When the secondary host is killed, or dies and is eaten, these cysts are activated in the GI tract of the primary host, and the cycle starts again.
Horses represent an aberrant host of S neurona. Sporocysts are probably 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. Therefore, horses cannot transmit S neurona to other horses. The definitive host is unknown, but must be an animal which commonly has access to horse's grain or hay, and can therefore shed sporocysts into the feed. Domestic animals have not been implicated, and therefore, the source of equine exposure is probably wildlife, such as raccoons or skunks. The parasite has a sexual life cycle in the intestinal cells of the primary host, and forms oocysts which are passed in the feces.
Our laboratory has been performing a laboratory procedure which tests for the presence of an immune response by the horse against Sarcocystis neurona. This test is called a Western blot, and can be used to determine if a horse has been exposed to the organism by evaluating horse serum for the presence of antibodies. Exposure as determined by a blood test DOES NOT indicate active disease. Active production of antibodies in the cerebrospinal fluid, however, does indicate disease. Therefore, the diagnostic test of the greatest value in EPM is the evaluation of antibodies in spinal fluid. A positive test on a clean (un-blood contaminated) sample of CSF reflects active intrathecal production of anti-S. neurona antibodies, and is therefore highly correlated to clinical disease. This is currently the most sensitive antemortem test available for EPM. Theoretically, a negative test is possible in affected horses which fail to mount an humoral immune response, but the majority of EPM affected horses have a positive test on CSF.
We have been testing serum from horses for several years, and based on our tests, have concluded that exposure to this organism is widespread in the New World. No cases of EPM have been identified abroad, except in horses which have been imported from North or South America. The disease probably requires a minimum of two months to develop from the time of exposure to the development of marked clinical signs, and may be present for as long as two years before becoming severe. Some horses with active disease may clear the organism without treatment. Exposure rates for different farms or training facilities may vary from zero to 80% of the horses on a given premise, even though few, if any, actually have the disease. This probably means that most horses ingest the sporocysts, mount an immune response, and clear the organism before it reaches the central nervous system. Alternatively, they may be persistently infected, but are able to combat the organism sufficiently to prevent the development of clinical signs.
Using the western blot technique, we have tested many different wildlife and domestic species in an attempt to identify the carrier definitive host. These include: dogs, cats, rats, raccoons, skunks, badgers, woodchucks and opossums. The only animal to test positive has been the skunk. This could mean that (a) the skunk is the definitive host, (b) the skunk is the intermediate host, (c) the skunk is an aberrant host, like the horse, or (d) the antibodies against the "normal" skunk Sarcocystis, Sarcocystis rileyi cross react with those from Sarcocystis neurona. These possibilities are currently under investigation in our laboratory.
Most EPM-affected horses are treated with anti-protozoal drugs for at least 2 months, and improve 1-2 grades in neurologic symptoms. Current maintenance dosage recommendations for trimethoprim-sulfamethoxazole are 15-30 mg/kg combined dose (7-15 DS tablets for 1000 lb horse) twice daily, and 0.5-1.0 mg/kg of daraprim (10-20 tablets) once daily. Some horses fail to respond to the lower dosages of daraprim and respond at the higher doses. Horses should remain on both drugs for the duration of treatment, because protozoa have been shown to become resistant to daraprim in the absence of sulfas. Anti-inflammatory therapy is indicated in acute cases. This may include continued treatment with phenylbutazone and banamine, as well as the addition of DMSO administered intravenously. Supplementation with MSM and vitamin E may be helpful adjunct treatment. Corticosteroids should be avoided if possible.
Questions regarding this disease may be directed to us at the above address,
by e-mail at drfenger@ukcc.uky.edu.
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LOOKING FOR ANSWERS ABOUT EPM Thoroughbred Times 9/9/95, Written by Glenye L. Cain, News Editor Reprinted by permission |
"Despite its widespread occurrence in the United States, equine protozoal myeloencephalitis remains mysterious, and sometimes misunderstood.
Some researchers have estimated that 50% of the horsesd blood-tested in the United States would test positive for EPM (equine protozoal myeloencephalitis, or equine protozoal myelitis).
Understandably, that kind of exposure rate for a disease which can cause debilitating nerve damage and wobbler-type symptoms has put horsemen on guard. It is easy to see why: EPM is most effectively treated when it is recognized early, but it can be overlooked or misdiagnosed because it may look like any of a variety of ailments, from vague hind-end lameness to wobbler syndrome. And once you have determined a horse does have it, treatment can last 4 1/2 months or beyond at an estimated monthly cost of $800. Some buyers of Thoroughbreds have considered requiring negative EPM tests before they will bid - a nightmare for consignors, since mere exposure to the disease can cause a blood positive, even if the horse never comes down with clinical symptoms.
Fear and loathing - and better testing procedures - have made EPM one of the most talked-about diseases in the United States. It is hard to know whether the disease is actually occurring more or if we just recognize it more readily, but there is no doubt that horsemen throughout the country are asking more questions. In Response, the University of Kentucky's Gluck Equine Research Center in April established an EPM information hotline for phone queries. But even as awareness has risen, EPM remains elusive for researchers and veterinarians, who have tried for years to unlock the basic mystery of its cause and life cycle.
'When we know who the culprit is, we can actually do experiments on how to prevent it,' said Clara Fenger, a Ph.D candidate at the Gluck Center who specializes in the study of EPM and is working with EPM expert Dr. Dave Granstrom. 'There are a number of compelling ideas, like coming up with some kind of a feed supplement, or some kind of safe low-level drug, that you can put directly on the horses' feed for life and prevent them from ever becoming infected. And of course a vaccine is something we'd like to have eventually.'
SEARCH FOR THE CULPRIT
Researchers and horsemen hope a break in the case - identification of the animal that carries and transmits the disease to horses - will come soon. It is widely believed that possums - which, like EPM, are native to the Americas and do not naturally occur in Europe - are the culprits. Although that commonly held suspicion has not yet been tested and confirmed scientifically, many horsemen are stepping up anti-possum, pigeon, raccoon, and rat measures in their barns and pastures.
'There are some simple things that can be done' to minimize the possibility of EPM exposure, said Fenger. 'Everybody has barn cats, which are necessary...but if you feed your cats in the barn, cat food attracts a lot of critters. Feed in the day and put the food away at night, when they come out. Cover your trash cans with tight-fitting lids. Don't set your feed at night for the following day, and cover your feed tubs so animals can't get into them.'
Anything you can do to get rid of birds, which may help spread the disease, probably also will help, Fenger added.
But until the parasite's carrier and life cycle is determined, true understanding of how the disease progresses will be hampered.
A PARTLY KNOWN PARASITE
What is known about EPM is that it is caused by a malaria- related parasite known as "sarcocystis neurona", which are passed on in the carrier's feces and then ingested by the horse, which promptly mounts an antibody campaign against the organism, resulting in a blood-positive state. The parasite replicates as it travels to the horse's immune response - including dangerous swelling of the spinal cord- ultimately is triggered as the organism invades and damages nerve tissue.
The horse is a dead-end source, meaning that it cannot transmit the parasite to other animals or people, but the damage carcocystis neurona can wreak on a single victim can be devastating if the disease is not recognized in time. Veterinarians primarily confirm the disease in one of two ways - by Western blot blood test or by analysis of spinal fluid.
The blood test may be simpler from the horseman's standpoint but is limited:
A positive blood test indicates only that the horse has been exposed to the parasite, so even an individual who has successfully developed antibodies against it and is free of the organism will still test positive. Analysis of spinal fluid - which can determine that damage to the central nervou system has occurred - is considered far more precise, but the necessar spinal tap requires a certain amount of delicacy to prevent the fluid sample from including false-positive blood.
Recently, researchers have developed a third test which identifies the parasite directly by detecting the presence of specific parasite DNA in spinal fluid. This sensitive procedure is believed to enhance early detection capability.
EPM can cause some dramatic changes, but its multifocal tendencies and often vague early symptoms can throw even an astute observer off track. Even more obvious clinical signs can be mistaken for other problems, like wobbler syndrome.
'As a general rule, they're clinically indistinguishable,' Fenger said of EPM
horses and wobblers. 'Most commonly, EPM causes an asymmetric ataxia (lack of coordination) which is worse on the rear end than the front. In general, wobbler disease causes symmetric ataxia, which is worse in the rear end than the front. If the horse is only slightly asymmetric, you're not going to be able to tell the difference. Wobbler disease affects them in the neck, so where the damage occurs is quite predictable. However, EPM can be multifocal, and while it appears to occur most commonly in the neck, it can occur anywhere.'
COSTLY TREATMENT
Standard treatment for the disease is an intensive - and costly - course of medication with the anti-protozoal medications Darapri (pyrimethamine) or trimethoprim-sulfa, which is available under several trade names. These often are administered in careful conjunction with anti-inflammatories such as Bute, Banamine, or DMSO to combat the horse's own inflammatory response to nervous system damage.
'Daraprim is the only treatment we have available,' said Fenger, who added that one problem with Daraprim treatment is that the parasites ca become immune to it, particularly if the horse's treatment is stopped an restarted according to evidence of clinical signs, or if he is given an amount smaller than 20 tablets (one milligram per kilogram of bod weight) per day.
Cases vary, with some horses able to continue training during treatment and others requiring nearly five months off while receiving medication. The success rate for returning EPM-affected horses to the racetrack, however, can be quite high - provided the disease is caught and identified early - and EPM victims have been known to take up rewarding careers after bouts with the disease.
Until the EPM carrier is identified and the parasite's complete life cycle is charted and understood, progress toward more effective prevention and treatment will be slow. Until those keys unlock the mystery of EPM, researchers encourage veterinarians and horsemen to be vigilant.
'Right now, all we can do is identify it and treat it,' Fenger concluded.
'The prognosis is excellent if the horse is caught early and treated long
enough, but very few horses are caught early and treated long enough.'
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| EPM UPDATE & FACTS 9/17/95 |
Scientists have apparently zeroed in on the source of equine protozoal myeloencephalitis, and horsepeople want straight talk on how to deal with EPM. How long should treatment last? Should a horse be treated if he has a positive blood test but no clinical signs? Can a mare transmit EPM to her unborn foal?
These were among the questions posed at an EPM forum at Keeneland on 9/9/95 sponsored by The Horse magazine. Dr. David Granstrom of the University of Kentucky's Gluck equine Research Center talked about how EPM occurs, how to identify it, and how to treat it.
EPM, a neurological disease, can incapacitate and kill a horse, has caused widespread alarm in the Thoroughbred industry, particularly in central Kentucky where it appears to be more prevalent, but actually, Granstrom said, is not. He said EPM is one of the most common neurological diseases in horses throughout North America. It also occurs in South America. The common link, researchers are almost certain, is the opossum. There is "very, very strong evidence," Granstrom said, that the opossum is the key player in the life cycle of the parasitic protazoan that causes EPM.
Horses apparently contract the disease when eating feed or drinking water that has been contaminated by an infected opossum's feces. "Possums become infected by eating dead birds and re-contaminating the environment in a cyclical manner," Granstrom said. The horse, however, cannot pass on the disease because it is a "dead-end host."
Once ingested by the horse, the parasite has an incubation period of anywhere from several weeks to several years. When it hatches, the parasite ultimately makes its way to the horse's spinal column, brain stem, or brain. "It can infect anywhere up and down the tract," Granstrom said.
The most common Symptom of EPM is progressive incoordination on one side. It can manifest itself in toe dragging, muscle atrophy, and a sore back. Grandstrom said EPM is particularly confounding because it can mimic almost any neurological disease.
A blood test is of limited use because the exposure rate to EPM is so high; an estimated 40-45% of horses in the eastern half of the United States have been so exposed, Granstrom said.
Granstrom recommends testing fluid from a spinal tap, or a DNA test. Once EPM is confirmed, treatment is fairly straightforward: a daily combination of pyrimethamine (Daraprim) and trimethoprim-sulfa. Anti-inflammatory medications such as DMSO and Bute also can be used as part of the treatment, which Granstrom said should continue 30 days after the horse appears to have recovered or as he puts it "stops getting better."
Approximately 70% of EPM-affected horses recuperate. "With adequate, aggressive treatment and with early diagnosis," Granstrom said, "It's not a death sentence. They can respond. They can get better."
| Granstrom said: |
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It does not appear that an EPM - positive mare can infect her foal,
although it is not definitive.
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