Equine Protozoal Myeloencephalitis (EPM): Debunking the Myths
- Jun 1, 2009
"The EPM story is truly a success story for modern veterinary research. Twenty-five years ago we became aware of an enigmatic parasitic infection of the nervous system of the horse. Since then, veterinary and affiliated scientists have determined the cause of the illness, worked out a complicated life cycle, described the epidemiology of the disease, developed specific tests to diagnose infection, and developed pharmaceutical agents to treat the infection. This highlights the importance of research in all aspects of an illness, and research's contribution toward the final goal of effective means of prevention or treatment in individual animals."--Excerpt from an article written by Martin Furr, DVM, PhD, Dipl. ACVIM, professor and Adelaide C. Riggs Chair in Equine Medicine at Virginia Tech's Marion duPont Scott Equine Medical Center (on behalf of the Equine Research Coordination Group www.aaep.org/equine_research_co_group.htm) published by TheHorse.com in January (article #13462).
While Furr succinctly summarizes the tremendous advances that the equine industry has enjoyed in the field of EPM research, there is much to be learned regarding this potentially fatal neurologic disease in horses. Further, there remains a great deal of controversy--even among the EPM experts--pertaining to basic EPM facts. Among owners/trainers and equine practitioners, myths continue to be perpetuated about the "best way" to diagnose, treat, and prevent the disease.
Rather than review the basic facts of EPM and recapitulate the multitude of deficiencies in our knowledge of EPM, we instead asked five veterinarians, all board-certified in internal medicine, "In your opinion, what is the most misunderstood issue surrounding EPM?"
While each of the interviewees acknowledged that treatment and prevention are important areas in need of further research, the resounding response to the question was: "Diagnostics!"
Experts currently recommend a horse only be diagnosed with EPM if:
- He has clinical signs consistent with the disease;
- The veterinarian has ruled out all other neurologic diseases that are similar to EPM; and
- You have a positive EPM test result.
According to Steve Reed, DVM, Dipl. ACVIM, from Rood & Riddle Equine Hospital in Lexington, Ky., "Ruling out other neurological diseases includes performing a neurological examination, localizing the disease to the spinal cord, especially to the cervical (neck) region, and taking cervical radiographs."
Reed says that most, if not all, practitioners are willing to perform the neurologic examination, but taking cervical radiographs and running one or more diagnostic tests, even on serum (not necessarily cerebrospiral fluid, the fluid that surrounds the brain and spinal cord, or CSF), is becoming less commonplace.
"Instead, many equine veterinarians are electing to simply treat the horse for EPM and monitor response to treatment," explains Reed.
The five internists we interviewed for this article agree that even with the persistent problems associated with EPM testing, diagnosing by assessing response to treatment is not ideal, and the above-described diagnostic plan is still the best way to proceed.
The Biggest Loser: Diagnostics
"The principal hurdle with EPM lies in our inability to accurately diagnose the disease," says Noah Cohen, VMD, MPH, PhD, Dipl. ACVIM, professor of medicine in Texas A&M University's Department of Large Animal Clinical Science.
Furr concurs with Cohen and adds, "EPM can look like a number of different conditions and affects performance in a variety of ways. It is important for practitioners to always carefully look for the more common causes of poor performance and neurological disease first and rule them out before EPM is considered. EPM is very hard to diagnose. We still do not have the best tools to work with, and the ones we do have (which are good) are not well-understood."
There are currently four tests available for diagnosing EPM caused by either Sarcocystis neurona or Neospora hughesi, both protozoan parasites.
Western blot (Immunoblot) The Western blot detects antibodies to S. neurona in either blood (serum) or CSF. A positive Western blot merely means the horse has been exposed to the parasite and has developed antibodies to S. neurona. A positive test does not necessarily mean the horse is actively infected. In contrast, a negative test suggests the horse is not infected with S. neurona.
Serum indirect fluorescent antibody test (IFAT) This test measures the level of antibodies (i.e., a titer) against either S. neurona or N. hughesi in the serum of horses. Like the Western blot, a positive result simply indicates exposure to the parasite, but it does not necessarily mean the horse is actively infected.
Enzyme-linked immunosorbent assay (ELISA or SAG1 test) This assay measures antibodies to the primary surface antigen (SAG1) of S. neurona. (An antigen is a disease-causing substance that stimulates the immune system.) Titers of 1:100 and greater indicate exposure to S. neurona and (according to the laboratory) possibly active disease if associated with clinical signs of EPM.
Polymerase chain reaction (PCR) Veterinarians perform the PCR assay on CSF and neural tissue to identify DNA fragments of S. neurona. The assay is run on CSF samples only with a concurrent positive EPM SAG1 antibody ELISA result. With this test a negative result does not necessarily mean that the horse does not have EPM, as the horse might have antibodies to another surface antigen. For example, if the horse's immune system has cleared the disease-causing parasite, then the test will be negative; however, the parasite could have caused substantial damage to the horse's spinal cord and brain that continues to cause neurologic deficits.
Pick a Test, Any Test
While each test possesses specific attributes that make it an excellent choice for practi tioners, none of these tests is able to definitively diagnose EPM.
So, which test do you order?
Many researchers and clinicians, including Reed, currently recommend the Western blot test for EPM, but they emphasize that even the results from this test must be interpreted in conjunction with the physical and neurologic examination findings.
"With strong evidence of neurological disease and after having ruled out all other possibilities, even a positive serum Western blot (not just a positive Western blot on CSF) provides adequate evidence that the horse has EPM and should be treated," attests Reed.
Nicola Pusterla, DVM, PhD, Dipl. ACVIM, associate professor in the Department of Medicine and Epidemiology at the University of California, Davis, School of Veterinary Medicine, believes differently. He says, "I strongly recommend the use of a quantitative serologic test (i.e., the IFAT or ELISA test). The IFAT offered by the immunology lab at the William R. Pritchard Veterinary Medical Teaching Hospital (at UC Davis) tests for both EPM-causing pathogens--S. neurona and N. hughesi. The titer is associated with a calculated probability of disease, which makes the interpretation of the test results easier."
According to Pusterla, the fact that you can test for both organisms using IFAT is important because, "Approximately 15% of the EPM caseload (at UC Davis) is due to N. hughesi, an organism not recognized very often in other parts of North America (perhaps because it is not often tested for). We have actually done work on this pathogen and described clinical cases and its epidemiology."
Playing the devil's advocate, William Saville, DVM, PhD, Dipl. ACVIM, chair of the Department of Veterinary Preventive Medicine at The Ohio State University's College of Veterinary Medicine, doesn't believe that a gold standard EPM test exists.
"With any of the available tests, the chance of getting a positive result when the horse is EPM-negative is pretty high," he says. "In addition, there are just too many false negative test results. So horses that are actually EPM-positive are testing negative."
With so much controversy even among the experts, is it any wonder why practitioners are abandoning testing altogether?
One viable option available to practitioners is the "EPM panel" offered by the UC Davis Veterinary Medical Teaching Hospital's immunology/virology laboratory. This panel tests for S. neurona via Western blot, and it tests for both S. neurona and N. hughesi using IFAT. All three tests cost approximately $145 to run, and results are returned within seven to 14 business days of submission date (instructions for submitting samples are available at www.vetmed.ucdavis.edu/vmth/small_animal/laboratory/pdfs/epmsample.pdf).
"From my perspective, I think that the most pressing need with respect to EPM is a test that accurately detects active infection and disease," concludes Cohen. Saville agrees fully.
"Our job would be a lot easier if the parasite would work with us," jokes Saville. "What we need is an IgM (a protective protein manufactured by lymphocytes, or types of white blood cells) antibody test, like the one that has been designed for testing for West Nile virus. An IgM test is a better indicator of a current EPM infection than the IgG (another type of protective protein) antibody tests (like the current Western blot test for EPM)."
Interestingly, Saville and his colleagues have developed an IgM test for EPM that could help solve the industry's problems.
"As we reported back in 2006, the IgM-ELISA (for S. neurona) works very well in experimentally infected horses, but now needs to be tested in field samples," says Saville. The other problem, he confides, is they just can't get the test marketed.
Until this or an alternate EPM test better able to diagnose active infections is developed, sources strongly encourage veterinarians to use one or more of the currently available tests, as long as all other neurologic diseases have been ruled out and the horse is actually showing overt neurologic signs.
The Final Tally
If it looks like EPM and smells like EPM ... it probably isn't. EPM remains a rare cause of neurologic disease in horses--less than 0.5% of horses are diagnosed with EPM annually in the United States.
"Most horses have been exposed to the parasites that cause EPM and will, therefore, have antibodies against S. neurona and potentially N. hughesi," says Saville. "S. neurona, in particular, is ubiquitous in the environment, but only rarely does it cause disease in horses."
However, if you do the math, 0.5% of all the horses residing in the United States still amounts to several thousand horses diagnosed with EPM each year.
"I have seen a lot of horses with EPM in my career," states Reed.
He says that EPM is likely quite rare in the subset of horses that have no overt neurologic signs and only a history of "poor performance."
"There are a lot of horses on racetracks, for example, that are on EPM medications," says Reed. "Do they all have EPM? No. But, the trainers are adamant that the horses race better when they are being treated with ponazuril (the drug used most often to rid a horse of the causative parasite)."
Saville states: "It just makes no sense to treat horses for poor performance with EPM medications without performing a full work-up."
The take-home message from all five internists can't be repeated often enough. Only diagnose (and treat) for EPM if:
- The horse has clinical signs consistent with the disease;
- A veterinarian has ruled out all other neurologic diseases that are similar to EPM; and
- You have a positive EPM test result.
About the Author
Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.