|First Posted: Feb 8, 2007 |
Updated: Aug 6, 2013Apr 17, 2018
Equine Protozoal Myeloencephalitis (EPM)
by Debora Johnson
Update: Update: EPM in Horses The EPM Society endeavors to contribute to a greater understanding of equine protozoal myeloencephalitis, encourage cooperative EPM research, promote awareness of current EPM research and new developments in the field, and evaluate and disseminate guidelines for the diagnosis, treatment, and prevention of EPM.
The following wise quotes were written in an excellent article from theHorse: Is My Horse Neurologic or Lame?
Stephen Reed said, "The often simple sentence used to describe the difference...is that 'A lame horse is regularly irregular, and an ataxic horses is irregularly irregular."
"Equine protozoal myeloencephalitis (EPM) is the most common infectious cause of neurologic lameness. Rarer infectious causes include tetanus, botulism, Lyme disease, rabies, West Nile virus, equine encephalomyelitis, and equine herpesvirus-1."
NOTE: Protazil® (1.56% diclazuril) is the only FDA-approved alfalfa-based top dress antiprotozoal pellet for the treatment of EPM.
What Is EPM?
Update: January 10, 2012, my husband and I attended a seminar, "What Is Making My Horse Stumble? - Diagnosis for the Neurologic Horse" by Dr. Martin Furr. It was outstanding, as usual. At this seminar a new test for EPM was mentioned--the Peptide SAG ELISA Test.
Read more about this test: "This test is generally run on serum, but can be run on CSF... . It looks for the presence of antibodies specific to three surface antigens (SAG1, 5, and 6) created by the protozoa. Each of these SAG are exclusive to a phenotype, and the test will measure 100% of the strains of Sn. It does not use SAG2, 3, or 4, and will not detect antibodies to other Sarcocystis through these SAG's. There are no false positives with this test. It is a quantitative test, and the results will show the level of the antibodies, helping to sort out exposure from active infection. This test is machine read, and is objective in the titer. The results are read as a dilution, not as a negative or positive. The use of two serial tests is helpful to measure the change in titer. The change in titer can also indicate if treatment is working, or if the horse is relapsing. Knowing the strain that infects the horse is important to prognosis and treatment..." EPM Test Summary
EPM, Equine Protozoal Myeloencephalitis, is a disease of the central nervous system caused by protozoal parasites: Sarcocysis neurona and sometimes by Neospora hughesi. It is quite difficult to diagnose and treat. By a process of elimination the veterinarian can rule out other diseases. EPM causes signs of neurological problems much like wobbles.The EPM tests veterinarians currently use for diagnostics are most effective in determining if the horse does not have EPM. A positive EPM test only reveals that the horse has been exposed to the parasites but does not definitively diagnose that the horse has EPM. The medication presently used to treat EPM, pyrimethamine-sulfonamide combinations, only has a 70% effective rate to reduce the symptoms or resolve the signs. Often the symptoms return after treatment. There is a new drug treatment, (Marquis) ponazuril, by Bayer, that is now being used specifically for EPM in horses. It is an anti-protozoal drug.
What Is Known About EPM?
NEWS CAPSULE No. 31, July 2001
EPM Continues to Puzzle Scientists
The diagnosis of equine protozoal myeloencephalitis, or EPM, is a chilling moment for any horse owner. EPM, which is infectious, is now the most common neurological disease afflicting horses, accounting for more than 35 percent of all equine spinal cord disease in the United States. It can also affect the brain and brain stem.
EPM's most common signs are incoordination and weakness, but the initial signs may be low key and more vague, such as mild lethargy, attitude change, subtle gait changes, inability to exercise as well as before, and difficulty maintaining complex gaits. The more severe signs include incoordination, inability to stand, lameness, facial paralysis, stumbling, falling, and tremors. Although most common among young adult horses and yearlings in training or young racehorses, the disease can infect horses of any age.
EPM, which is becoming more and more commonly diagnosed, can be life threatening. Veterinary scientists are still puzzled over many aspects of the disease, says Dwight Bowman MS, PhD, an associate professor of parasitology, who has been studying the disease since it was identified in 1991.
"Veterinarians are perhaps more puzzled now than they were just a few years ago when they thought the various pieces had come together to explain the method by which horses became infected and why disease developed," he says.
In the late 1970s, researchers found a microscopic protozoan in the nervous tissue of horses with signs of neurologic disease. In the early 1980s, it was suggested that these organisms were similar to the Sarcocystis group of parasites that characteristically have two hosts: a final carnivorous host in which the parasites live in the intestinal mucosa and produce transmission stages that are passed in the feces, and an herbivorous intermediate host that ingests the fecal stage and develops cysts in their tissues. In the early 1990s, the parasite was isolated from horses that had developed severe signs of EPM, and the isolated organism was given the name Sarcocystis neurona.
To find the host of the disease, researchers looked at potential final hosts whose geographical distributions overlapped those of the reported cases of EPM. EPM, they found, followed the distribution pattern of the common opossum, and indeed, using molecular tools, the opossum was identified as the natural final host of this organism. When researchers went to the literature, they matched the newly identified Sarcocystis neurona with one described a hundred years ago as Sarcocystis falcatula.
"This led to a fairly well-grounded and acceptable hypothesis that the EPM organism was S. falcatula and that it was cycling between a sarcocyst stage (cysts in the muscle tissue) in birds and a sporocyst stage spread throughout the environment in opossum feces," Bowman explains. "In this scenario, horses are infected by eating or drinking material contaminated with sporocysts shed by opossums."
Several newer studies, however, including one conducted at Cornell, have shown that feeding uninfected horses up to 60 million sporocysts from the feces of infected opossums does not cause the signs of the disease or any immunological changes in the horses' blood. In some cases, horses fed sporocysts have developed neurologic signs, but neither organisms nor the DNA of organisms have been recovered from these horses at necropsy. Also, it has been recently shown that the organisms isolated from horses are morphologically different from those considered to be the avian parasite Sarcocystis falcatula.
"Thus it appears that the initial jubilation over having discovered the source of equine infection has been misplaced and we find ourselves almost exactly where we were when the organism was first described in 1991," says Dr. Bowman. "Now the possibilities seem twofold. One possibility is that the actual identity of the species of Sarcocystis cycling in wildlife has not been determined and, therefore, the experimental infection of horses does not induce disease. A second possibility is that some other factor or agent predisposes horses to develop disease or causes an existing infection with Sarcocystis neurona to change from a latent to a lethal condition."
Bowman recently received a grant from the Harry M. Zweig Memorial Fund to obtain information relative to the first of these two possibilities. The hypothesis continues to be that the causative organism in EPM sheds sporocysts in the feces of an animal that is indigenous to the Americas because EPM has not been observed in Europe, Africa, or Asia. He also believes that cysts that serve to infect these carnivores are present in muscles in small vertebrates such as birds or rodents.
"We know there are many species of Sarcocystis in wildlife that are either not described or very poorly known. Basically, we will reproduce the work that led to the choice of the opossum-bird model with other carnivore and omnivore-prey systems," explains Bowman. "Although we still do not know what the source of infection is for the horse, we now have a much greater ability to look for it than we did in the early 1990s," he says.
Bowman's laboratory now has the expertise to maintain Sarcocystis species in culture. He also has a bird model in the parakeet that allows easier isolation of organisms in cell cultures and the development of muscle cysts that can be fed to potential final hosts. His lab has the technology to distinguish the various Sarcocystis species molecularly, and work is progressing collaboratively with Dr. Antoinette Marsh at the University of Missouri and Dr. J. P. Dubey at the U.S. Department of Agriculture in Beltsville, Maryland. "Our goal is to isolate and identify an organism from wildlife hosts that is identical to the EPM organism we find in diseased horses and is capable of inducing the disease in horses. Work by others and ourselves has indicated that the opossum is host to several Sarcocystis species, and one of these may be Sarcocystis neurona."
Bowman plans to isolate various Sarcocystis sporocysts from the feces of wild carnivores such as opossums, raccoons, skunks, foxes, and coyotes and, perhaps, some raptors and vultures that will be used to infect parakeets and mice. From the parakeets and mice, Bowman and his colleagues will harvest organisms to initiate their growth in cell culture. Since each carnivore probably is a host to more than one species of Sarcocystis, the researchers will try to develop techniques to identify specific isolates.
Treatment and Prevention
Thomas Divers DVM, Dipl ACVIM, a professor of medicine who is the co investigator on this project, has been wrestling with the treatment of this disease for years.
"Once horses become infected with the culprit species of Sarcocystis, probably by ingesting grain or other food or drinking water that has been contaminated, the parasites migrate to the central nervous system, including the spine and brain," he says.
Recent studies have shown that about 50 to 60 percent of horses in areas with high rates of EPM, such as the Midwest and Northeast, seem to have been exposed to Sarcocystis, though only a small percentage actually develop neurological symptoms. Researchers believe that symptoms develop from the body's inflammatory response to the parasite causing structural damage in the central nervous system.
The disease is difficult to diagnose without a full battery of tests that includes a spinal fluid sample to look for antibodies against the parasite. Early treatment is important for recovery. Treatment, which typically lasts one to four months, involves parasite-killing drugs and sometimes anti-inflammatories and immune system-boosting medication. While most horses improve with treatment, only about 10 to 20 percent of treated horses seem to make a full recovery. About 70 percent partially recover, and about 10 percent must be euthanized. If left untreated, most horses tend to deteriorate.
"At present, the best way to prevent this disease is to protect horses from exposure to potential sources of feed contaminated with the feces of wildlife," Bowman says. "Try to keep opossums, raccoons, and other carnivores out of horse barns. Keep grain for horses in containers with tight-fitting lids. It is important to keep watering troughs as clean as possible. It is of course impossible to prevent infection when animals are at pasture, but maintaining a tidy pasture with minimal trash or surrounding undergrowth will be likely to preclude the activity of most of these hosts."
"The next topic Reed discussed is equine protozoal myeloencephalitis (EPM), which is viewed as a serious parasitic disease with neurologic consequences. The opossum, identified as the definitive host, eats the flesh of an intermediate host (skunk, armadillo, sea otter, or domestic cat) that has encysted stages of the protozoan parasite Sarcocystis neurona. Then the opossum excretes parasitic oocysts in its feces, which are inadvertently eaten by horses in contaminated feed or pasture. Opossums tend to be opportunistic feeders, especially on forest edges. If separate sources of water are available for horses and wildlife so horses drink separately from opossums, there is lessened chance of infection.
Horse ingestion of contaminated feces might result in parasitic development in the horse's central nervous system (CNS), leading to asymmetric ataxia with muscular atrophy. Horses might be exposed to S. neurona, but they might not necessarily develop clinical disease. Therefore, blood testing is fraught with false positives.
A positive response in the CSF (cerebral spinal fluid) indicates that S. neurona entered the CNS and evoked an immune response; however, any blood contamination of the CSF tap can produce false positive results. False negatives are rare on blood or CSF, but they have been observed in the first seven to 10 days post-infection. The most important consideration is to rule out all other possible causes of ataxia.
With treatment, a horse is 50 times more likely to survive if there is notable improvement in clinical signs. Prevention is important and most effective and involves keeping wild animals away from horses, removing carcasses of intermediate hosts, keeping definitive hosts (opossums) away from horse feed and water sources, and by decreasing risk factors of stress and transport as much as possible."
Update: The following is a direct quote from the Atlanta Equine Clinic. There is no copyright on their website: Article: " Antigen Types for EPM"/The Atlanta Equine Clinic
"Multiple Antigen Types for EPM
Pathogenes Inc. (Fairfield, Florida) is a company which has recently identified multiple antigen types for EPM. This is in contrast to our recent belief that only one antigen type (known as SAG 6) existed. Pathogenes' discovery carries great clinical significance because our medical approach has been historically directed at diagnosing and treating disease caused by the SAG 6 antigen type only.
In addition to SAG 6, Pathogenes has identified two other antigen types: SAG 1 and SAG 5. They have also developed Elisa tests for each one.
Horses testing negative for the SAG 6 antigen type (via the Western Blot method) were previously considered to be free of EPM infection. During this test, potential positive titers for one or more of the other antigen types (SAG 1 and/or SAG 5) would have gone undetected, thereby producing false negative results.
Moreover, horses which tested positive for the SAG 6 antigen type and did not respond to treatment (such as Marquis® administration) may have had concurrent infection with one or more of the other antigen types (which may not respond to Marquis®). In these cases, residual neurologic deficits were erroneously considered to be permanent and irreversible.
The current knowledge that multiple antigen types for EPM exist enables veterinarians to more accurately diagnose and more effectively treat this disease.Pathogenes: Diagnosis of EPM
Pathogenes used experimental and confirmed cases of EPM to determine that SAG 1, 5, and 6 ELISA titers detect the organism shortly after the parasite enters the blood stream.
The disease, EPM, is a sequela of Sarcocystis neurona infection.
An advantage to the SAG ELISA test is the ability to determine therapy choice. The Peptide ELISA detects antibodies to the 3 antigen types of S. neurona and the test result is reported as a titer. These three titers indicate reaction to different proteins that identify the three antigenic types of S. neurona causing the infection. The total cost for the test (revealing all three Elisa titers) is $60.
Pathogenes found no advantage in using cerebral spinal fluid (CSF) to detect infections.What Do the Results Mean?
Mixed infections are the most common situation. Pathogenes does not have false positive results due to the specificity of the antigens although the presence of one cross-reactive phenotype can confound other testing.
Any titer (to any of the three antigens) that is less than 4 means the animal has no response to active parasites or it is too early in the infection (less than 15 days) to have a measurable response. If the titer is negative and the horse has a presumptive diagnosis of EPM a second titer should be obtained two weeks later.
Any titer to the three antigens that is greater than 4 means the animal has had experience with the parasite and may or may not have an active infection. Two tests, performed two to four weeks apart can determine if the infection is currently active. The titer should increase (2 to 4 fold) with progression of the disease or decrease with disease regression or elimination.
Titers at 16 or greater are supportive of active EPM infection. [Bold added by me.]
The best use of the test is in conjunction with neurological examination. The test is indicated for cases in which the horse is exhibiting clinical signs consistent with neurologic disease that could be attributed to S. neurona infection. Screen testing in normal horses is rarely advised.Pathogenes: Treatment of EPM
Horses do show ataxia and inflammatory responses to all three phenotypes of S. neurona. The best drug for treatment should be based on knowledge of the antigen type of the S. neurona causing the infection.
Pathogenes recommends treatment for EPM based on the 3 antigen titers reported.
A field trial using Oroquin-10, a 10-day drug treatment for EPM, is currently available. This non-toxic drug is absorbed quickly and kills intracellular pathogenic protozoa that can evade other treatments (which leads to relapse conditions). Oroquin-10 is non-toxic to animals and is formulated to stimulate protective immunity during treatment. The in vitro efficacy against SAG 1 and SAG 5 phenotypes has been established. Challenge trials are ongoing. The drug is safe in horses at 10 times the prescribed dose. No side effects have been reported. The cost of Oroquin-10 treatment is approximately $200.
In our experience, the testing and treatment protocols offered by Pathogenes are more accurate, effective, and economical than current strategies that use Western Blot titers for testing and treatment with medications such as Marquis®."
For More Information:
The Many Faces of EPM
EPM and other Reactive Points on Equine/Video
Equine Emerging Diseases Reviewed