EPM: Diagnostics Have Evolved, But Cure Remains Elusive by Denise Steffanus|07.30.2019|12:16pm In the 1990s, equine protozoal myeloencephalitis (EPM) was regarded by horsemen as the greatest threat to the health of American horses. In response to their concerns, a group of researchers into the disease formed the EPM Society to consolidate their efforts to develop effective diagnostics and find a cure. Twenty years later, improved diagnostics can effectively identify antibodies to the disease in the cerebrospinal fluid, and antiparasitic drugs can kill the organism. But a cure is still elusive. “We're better at diagnosing it, and there have always been good antiprotozoal treatments that kill the parasite,” said Dr. Dan Howe, a microbiologist at the University of Kentucky's Gluck Equine Research Center and longtime researcher into the organisms that cause EPM. “The key thing is whether this is done in a timely fashion so that when you treat and kill the parasitism, you don't have a lot of parasitic damage.” The question many horsemen ask is whether the symptoms they see in a horse are because of an active infection or parasitic damage from an old infection that has been resolved by treatment. Symptoms of the disease are a result of brain and spinal cord damage by the protozoans. In severe cases, horses will drag one hind leg and lose coordination. Common signs in earlier stages of EPM include loss of muscle tone and decreased sensation in the hindquarters, loss of tail-muscle tone, and uneven wear on hind shoes. Howe said one of the big improvements in diagnosis is the ability to identify effectively and accurately an active infection in the central nervous system. He credits this work to Dr. Martin Furr of Oklahoma State University, a founding member of the EPM Society. “It requires doing a spinal tap and collecting spinal fluid,” Howe said. “You then measure the amount of antibody in the spinal fluid, and you measure the amount of antibody in the serum, or blood. Based on the ratio of antibody in spinal fluid versus serum, you can pretty much identify a horse that's producing antibodies in the central nervous system, indicating an active infection. And that's key.” Three medications used to treat horses with EPM are: ReBalance, a combination of pyrimethamine and sulfadiazine produced by PRN Pharmacal; Protazil, a diclazuril drug manufactured by Merck Animal Health; and Marquis by Merial, which contains ponazuril. Dr. David Granstrom pioneered EPM research while he was at the Gluck Center in the 1990s. Granstrom now is assistant executive vice president of the American Veterinary Medical Association. Granstrom developed the first EPM diagnostic, the Western blot test, which was considered the gold standard for many years. “A highly sensitive and specific recombinant ELISA developed a few years ago made it possible to reliably demonstrate the presence of Sarcocystis neurona-specific antibody production in the spinal fluid, which is associated with active infection,” Granstrom said in an email. “However, that doesn't necessarily mean that concurrent neurologic clinical signs are the result of the infection. Certainly, it's a strong indicator of clinical EPM when combined with a thorough neurologic exam and appropriate additional diagnostics to work through the list of differential diagnoses, but timing is an important consideration.” Dr. Robert MacKay, professor of large animal clinical sciences at the University of Florida, also was one of the early researchers. He said he's been pleased with treatment over the past decade because more than half the horses treated for EPM improve, and half of those improved horses return to normal function. “I think the future is all about prevention and very early detection rather than treatment,” he said. “Diagnostics are much better, so we can identify it much earlier and treat it early.” Originally, the protocol for diagnosing EPM was first to test the serum (blood) for the presence of antibodies. Most horses during their lifetime are exposed to EPM and mount an antibody attack. A negative serum test was the gold standard that the horse didn't have EPM. If the serum test came back positive, the clinician would perform a spinal tap to sample the cerebrospinal fluid for antibodies to confirm the EPM diagnosis. But that thinking has since changed. “Although it's not common, you can have a case where a horse would have no antibody or very low serum antibody and yet be an EPM horse,” Howe said. “The converse is that there are a lot of EPM horses out there that have surprisingly high antibody titers and they're not diseased. My own personal opinion is that the serum test alone is not very informative.” When trying to figure out if the symptoms are an active infection or lingering neurological damage, an accurate history of the horse is essential. “The clinical history should give you an idea whether it's a new problem or an old problem,” MacKay said. “If it's an old lesion that isn't active, you wouldn't expect it to get worse. If it was EPM that had been treated successfully, and you were still seeing residual signs, that's one thing. But if it was treated, and you thought successfully but it got worse again, that would be an indication that the infection was active again.” Interestingly, Howe said it is possible that what an owner perceives is a “24-hour bug” in a horse actually might be an EPM infection that resolves on its own. “Maybe when they get a low-grade infection, there are some subtle signs that are never seen,” he said. “I wouldn't want to rule that out. But it's also possible that the horse gets infected, the infection is very quickly controlled by the immune response, and while antibodies are produced, there is really no disease, no signs at all. So either scenario is very possible. “What is really one of the issues with EPM is that you can presume to have a really effective result, and after a couple of years it could get bad again and show similar signs. That makes us think we didn't completely kill it. I'd say that issue is unresolved at this moment. Whether or not you can totally stamp out every last vestige with treatment is not known. It may be that we actually can do that, but the horse that does get EPM may be unusually susceptible to that parasite, and even if you kill it, that horse might get another round of the same disease. That's still unknown.” Researchers have never been able to develop an effective vaccine against EPM. In 2017, Dr. William Saville led two studies at the Ohio State University to assess the current vaccine attempt. Saville and his colleagues concluded: “In these two studies, vaccination with the S. neurona vaccine failed to prevent development of clinical neurologic deficits.” Vaccinated horses in one study actually developed worse neurologic signs. Saville, who devoted decades of his career to investigating this troubling disease, characterizing himself as a “bulldog who just won't quit,” died unexpectedly in 2018, shortly after completing these studies. He was 71.