Equine Protozoal Myeloencephalitis (EPM): The signs and treatment

"Equine Protozoal Myeloencephalitis life cycle".
“Equine Protozoal Myeloencephalitis life cycle”. © Wikipedia

Equine Protozoal Myeloencephalitis (EPM) is a master of disguise. This serious disease, which attacks the horse’s central nervous system, can be difficult to diagnose because its signs often mimic other health problems in the horse and signs can range from mild to severe.

It is caused by an apicomplexan protozoan infection by Sarcocystis neurona, an intracellular parasite, and in parts of the United States virtually all horses are exposed, with a small proportion (< 0.5%) exhibiting neurological symptoms. Horses can come into contact with Sarcocystis neurona while grazing or eating feed or drinking water contaminated by opossum feces. Fortunately, not all horses exposed to the parasite develop the disease.

The clinical signs of EPM can be quite varied. Clinical signs are usually asymmetrical (not the same on both sides of the horse). Actual signs may depend on the severity and location of the lesions that develop in the brain, brain stem or spinal cord.

If left undiagnosed and untreated, EPM can cause devastating and lasting neurological damage. Use this checklist of symptoms when assessing your horse’s condition for the possibility of EPM:

  • Ataxia (incoordination), spasticity (stiff, stilted movements), abnormal gait or lameness.
  • Incoordination and weakness which worsens when going up or down slopes or when head is elevated.
  • Muscle atrophy, most noticeable along the topline or in the large muscles of the hindquarters, but can sometimes involve the muscles of the face or front limbs.
  • Paralysis of muscles of the eyes, face or mouth, evident by drooping eyes, ears or lips.
  • Difficulty swallowing.
  • Seizures or collapse.
  • Abnormal sweating.
  • Loss of sensation along the face, neck or body.
  • Head tilt with poor balance; horse may assume a splay-footed stance or lean against stall walls for support.

Current treatments for EPM

Contact your veterinarian immediately if you suspect your horse has developed EPM. The sooner treatment begins, the better the horse’s chances for recovery.

Because S. neurona can locate anywhere in the brain and spinal cord, the disease can mimic any neurological condition, and diagnosis can be challenging. EPM was first identified in the 1960s, with development of improved diagnostic tests in the 1990s. Since 2000, three Food and Drug Administration (FDA) approved treatments for EPM have been brought to market.

Treatment of EPM is challenging because S. neurona is an intracellular parasite and an expert in avoiding immune system attack. The three different anti-protozoal treatment modalities currently available work on entirely different pharmacological principles.

Traditionally, EPM was treated with combinations of pyrimethamine and a sulfonamide, one of the so-called “potentiated sulfonamides” used in classic anti-malarial therapy. These drugs act “in sequence” on nucleic acid synthesis. The sulfonamide directly inhibits the incorporation of para-amino benzoic acid (PABA) into folic acid, and pyrimethamine selectively inhibits dihydrofolate reductase. When present together in the brain at effective concentrations, these drugs produce a 1 to > 2 synergistic inhibition of nucleic acid metabolism. This combination was, for many years, the only known treatment for EPM, although the duration of treatment was often prolonged. Potentiated sulfonamide combinations have long been marketed by compounding pharmacies, and more recently, Phoenix Laboratories has brought to market an FDA-approved formulation of pyrimethamine and sulfadiazine, marketed as ReBalance.

Side effects that may be associated with pyrimethamine-sulfonamide combinations are related to inhibition of host nucleic acid metabolism. Animals on potentiated sulfonamide treatments should optimally be monitored for inhibition of red cell formation, leukopenia, and thrombocytopenia. Some of the earlier potentiated sulfonamide preparations were associated with reports of reduced spermatogenesis in stallions.

Another treatment, Marquis (ponazuril), is adapted from a widely used poultry coccidiostat, toltrazuril. These drugs act by directly attacking the “apicoplast” organelle of S. neurona. Apicoplasts are chloroplast-related organelles that were acquired by S. neurona millions of years ago. They are highly susceptible to specific attack by herbicide-related drugs such as ponazuril. Working with these drugs, University of Kentucky researchers showed that they are highly specific and effective treatments for EPM. Ponazuril is well absorbed orally, has a 4.5 day plasma half-life, and is virtually non-toxic to equines at clinically effective doses. Single daily dosing is effective, and in an extensive field study, no adverse responses could be linked to treatment.

The manufacturer’s suggested treatment period is 28 days. Because of its unique mechanism of action, Marquist is essentially specific for apicomplexans, and a positive response to treatment offers strong support for an EPM diagnosis. Marketed in 2001, Marquist was the first FDA-approved treatment for EPM.

"Equine Protozoal Myeloencephalitis". Licensed under Public Domain via Wikimedia Commons
Equine Protozoal Myeloencephalitis. © Wikipedia
Nitazoxanide (Navigator) is in a novel class of anti-infective drugs and is thought to act by inhibiting pyruvate-ferridoxin oxidoreductase in susceptible organisms. It has a broad spectrum of action, acting on enteric bacteria, protozoa, and viruses. In human medicine it has been approved as a broad spectrum anthelmintic and anti-viral drug.

The oral dose is carefully calculated, and treatment starts at a half daily dose for the first five days, increasing to the full dose of 22 mg/kg for the remaining 23 days. The principal adverse response in the horse relates to the drug’s broad enteric action, which can change equine intestinal flora and produce enteric problems. The addition of rice bran or corn oil to the diet helps to reduce the incidence of intestinal problems.

Horses on any long-term therapy for EPM should be monitored daily for adverse reactions and changes in clinical signs.

Numerous adjunctive therapies for EPM are also used. Anti-inflammatory therapy can help reduce inflammatory responses to the protozoan and may be useful in “treatment crisis” (transient worsening of clinical signs early in treatment) reported in some severe cases receiving an anti-protozoal medication. Use of corticosteroids in EPM cases is controversial among veterinarians.

Immune stimulants have also been recommended and include products such as Propionibacterium acnes administration, mycobacterial cell wall extracts, oral levamisole, and alpha-interferon. Additionally, a commercially available chemically inactivated vaccine of merozoites of S. neurona with an adjuvant has been suggested to further stimulate cell-mediated immunity.

Clinical experience suggests that rehabilitation is facilitated by mild to moderate unmounted, controlled exercise. The exercise level is dictated by the stability of the horse and the opinions of both the examining veterinarian and the owner. Complete recovery (to neurological normalcy) may not be possible, but rehabilitation and strengthening of affected horses can maximize the clinical outcome.

Based on information provided by the AAEP, Bayer Animal Health, and David Granstrom, Dan Howe, Brad Bentz, Levent Dirikolu, and Thomas Tobin at the Maxwell H. Gluck Equine Research Center. Treatment information reprinted courtesy of Dr Thomas Tobin, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky.

This information was first published on Horsetalk.co.nz in March, 2007.

14 thoughts on “Equine Protozoal Myeloencephalitis (EPM): The signs and treatment

  • July 30, 2015 at 10:15 am

    Just wondering if there’s a vaccine for this. I have been both a horse and opossum rescuer for any years. In the U.S., the opossum is our only marsupial and many of us treasure them for their unique natures. They have been terribly mistreated here for the lack of understanding. As a rescuer of equine, this is especially disturbing. I have heard about the danger of opossums from a few vets in the past, but this is the first comprehensive report I’ve seen. So, if there is a vaccine that equine owners can get for their horses in places with both species exist, what it it?

    • January 21, 2017 at 2:09 pm

      The best way to ensure that horses do not get EPM is to ensure that possums are not in your barn The opossum is a necessary part of he wild environment but like many animals they can gravitate to man made environments. A good plan is to keep wild animals wild and not habituated to human contact.

  • May 9, 2017 at 2:55 am

    Would a possible indication of the disease be the loss of motility in the tail…looks like the tail had a “block” and skin irritation under the tail.

    • May 18, 2017 at 10:55 pm

      My horse had asymmetrical position of tail as early sign.

  • September 16, 2017 at 11:53 am

    Would a horse leaning to the right in the hind end be a sign? She walks, trots, canters perfect but when she is standing, she is leaning very far to the right in the hind end, her tail actually touches the ground about 3 inches outside her right hind leg. It just started today and is very odd.

  • June 19, 2018 at 1:26 pm

    Putting my 20 year old mare down tomorrow. EPM from a possum or two that have been in our barn. Hoping the other 2 horses don’t get it yet. 🙁

    • August 28, 2018 at 7:11 am

      I am so vary sorry for your loss!! Could you please tell me the Symptoms your mare had before you put her down??

    • September 19, 2018 at 12:49 pm

      I am so sorry for your loss.. I too had to put my boy down due to EPM last April. I was devistated and have been so worried about my other horse coming down with it..

  • December 27, 2018 at 9:54 am

    The vet thinks my mare has EPM. Drew blood, awaiting results. The only obvious symptom was her inability to hold a canter. Previously had a beautiful canter. I had two equine chiropractors and a body work practitioner and nobody could find a musculoskeletal reason. I was still thinking soft tissue injury when I called the vet. I feel like the wind has been knocked out of me. What are the success rates with treatment? I’ve only known three horses with EPM and all three died.

  • July 31, 2019 at 2:12 am

    My mares blood work shows epm level 500. Still waiting on rest of results. Symptoms her whole rear end off when riding. Lack of energy no trot. No loss of appetite.

  • August 14, 2019 at 6:15 am

    I haven’t seen any opposums, and I noticed that all comments were mares .Is this a gender disease ???
    My mare has stiff hindquarters….. and very wobbly really bad… she is 22 and I’m not sure what to do

    • August 25, 2019 at 1:53 am

      I have a friend that had 2 gelding with rpm at different times.

  • August 29, 2019 at 4:56 am

    For ours it started out he wasn’t eating all of his food, thought maybe with him being as thick as he was it might just be the heat, put him in the barn with a fan on him – he ate hay and nibbled on alfalfa, wasn’t interested in feed or water, thought it might be anhidrosis because he wasn’t sweating enough; Vet pulled blood, came back as high enzymes in his intestines and liver, he was super stiff in his hind end movements, wouldn’t pull all the way up in his sheath, and seemed to be confused about where he was supposed to be; we started treatment for EPM that day, gave him probiotics, electrolytes, walked him and used the hose to help him get water in him, he was still nibbling grass so we had hope; the last day, his nervous system was in total shutdown, couldn’t swallow, his nerves in his intestines were shut down so he couldn’t go, it was the most awful thing imaginable for him to go through, he didn’t make it, We just buried our beautiful boy this past Saturday –

  • November 7, 2019 at 8:49 am

    Our horse crossed his back legs when he walks. Hes a Tennessee walking horse and he is a rescue. Hes had no butt muscles since we got him and we just had his teeth floated because he was not putting on weight. We put him on a grass pasture and he was slowly putting it on but from the amount we were feeding him he should have been as big as a house by now. The vet said they suspect EPM but I’ve had a horse that was diagnosed (blood test) with wpm and she had a severe case. Couldn’t stand or walk. Constantly spinning circles, it was horrible. We had to have her put down it was so severe


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