By Rob MacKay, BVSc (Dist), PhD, DACVIM and Kenton Morgan, DVM, DACT 

Equine protozoal myeloencephalitis (EPM) is a disease of horses that affects the central nervous system. Equine obviously refers to the horse, protozoal refers to the type of organism that causes the disease and myeloencephalitis refers to that portion of the animal, which is damaged. “Myelo” refers to the spinal cord and “encephalitis” refers to an infection/inflammation of the brain. So, EPM is a disease of the brain and/or spinal cord of the horse, which is caused by a protozoan organism. 

What Is A Protozoa? 

Protozoa are the smallest and most simplistic members of the animal kingdom. They are single-celled organisms. The name given to the protozoan organism shown to be the primary causative agent for EPM is Sarcocystis neurona. Sarcocystis refers to the type of protozoan parasite and neurona refers to the nervous system where this organism was first isolated. 

The disease was described in the 1960s as segmental myelitis. By 1974 we determined this disease was caused by a protozoan organism. In 1976 it was concluded that some type of Sarcocystis organism was the culprit. This organism (Sarcocystis neurona) was first isolated from the spinal cord of a horse with clinical signs of EPM in the early 1990s. In the late 1990s, another organism called Neospora hughesi was shown to also cause EPM in horses. This organism is widely distributed in the United States but, compared to S. neurona, is a relatively rare cause of EPM. EPM is a disease primarily of the Western Hemisphere and is not commonly seen in other parts of the world. We find this disease in horses that reside in North or South America or in horses that once spent time in the Americas. 

We do know that many horses are exposed to the S. neurona parasite. We know this is true by doing specific testing on blood samples taken from horses around the country. The blood sample is evaluated to determine if it contains antibodies specific to the S. neurona organism. If the sample contains these antibodies, then we know the horse has been exposed to this parasite and has mounted an immune response. We say the horse is “seropositive” with antibodies against S. neurona. It does not tell us if the horse has or will ever have EPM, it just tells us the horse has been exposed. Most horses in the United States will demonstrate this antibody in their blood. In some areas of the country over 90 percent of horses can be seropositive. By comparison, horses with antibodies specific to N. hughesi have been found in 21 states and, in some locations, up to 20% of horses may be seropositive to this organism.  Luckily, only a very small percentage of horses seropositive to either parasite ever develop the disease we call EPM. 

The actual disease rate or incidence is difficult to estimate. Results from a very large equine survey completed by the USDA in the 1990s estimated the actual disease incidence to be approximately 0.14 percent in the general equine population, excluding horses at racetracks. This finding provides evidence for the notion, stated above, that even though the majority of the equine population is exposed to these parasites, only a very small percentage ever develops clinical disease. 

Parasite Life Cycle 

Although much has been learned in recent years with respect to the life cycle of S. neurona, there is still much we do not know. Sarcocystis neurona has a complex, two-host life cycle. This life cycle includes both a definitive host and several possible intermediate hosts. For clarification, the definitive host is that animal which sheds in its feces an infective form of the parasite, S. neurona. The intermediate host is that animal, which does not shed an infective form but is a host where the parasite resides and is necessary for the parasite to complete its life cycle. 

In 1995, the opossum was determined to be the definitive host of this parasite (there may possibly be other definitive hosts for this organism and we have just not yet identified them). The opossum sheds the infective form of the parasite in the feces; we call this infective form a “sporocyst.” The sporocyst is then ingested (eaten) by the horse. Once inside the horse, there is much that we do not know regarding what occurs next. The parasite does go through a maturation or reproductive phase and eventually produces a form of the parasite we call “merozoites.” Eventually (in only a very small percentage of horses) the merozoites reach the central nervous system, damage this vital area and create the disease condition we call EPM. 

As for intermediate hosts, there are several; currently we know that skunks, armadillos, raccoons, cats and sea otters can serve as intermediate hosts for the S. neurona parasite. This list undoubtedly will continue to grow as we learn more about this protozoan parasite. Since we do not believe the horse is a “normal” host for this parasite, we refer to the horse as an aberrant, intermediate host. Although considered extremely unusual, it has been shown that the horse can serve as a true intermediate host for this parasite in certain circumstances. 

Neither the definitive nor the intermediate host(s) for N. hughesi have been identified.

What Does EPM Look Like? 

Since EPM is a disease of the central nervous system (brain and spinal cord) and it can affect multiple locations within the brain and spinal cord, the signs and severity of this disease can vary dramatically. Though EPM can affect both the brain and spinal cord, it is more common for the signs of disease to be associated with damage to the spinal cord, but we can and do see insult to the brain. 

We typically refer to the 3 “A”s of this disease: Asymmetry, Ataxia and Atrophy. 

1. Asymmetry is a term we use to describe a symptom that is worse on one side of the body than on the opposite side. In other words, with EPM, the signs are generally worse on the left side than on the right or visa versa. 

2. Ataxia is a term we use to describe incoordination or the inability of the horse to know exactly where its legs are, resulting in inability to move its legs and trunk normally. 

3. Atrophy describes a condition where the muscles shrink from their normal size. With EPM, this results from damage to the nerves that normally control or “innervate” these muscles. Muscle atrophy is not seen in all cases of EPM, so it is not as consistent a sign of disease as is the asymmetrical ataxia. 

So, with this disease we will see horses that are incoordinated and this incoordination is usually worse on one side of the body as compared to the other side. These horses may or may not develop muscle atrophy. It is also common to see muscle weakness in these horses. Some horses may display abnormal gaits, lameness and loss of sensation along the face, neck or body. Paralysis of the muscles of the eyes, face or mouth may occur and this will be evident by drooping eyes, ears or lips. Horses may also demonstrate a head tilt, poor balance and difficulty in swallowing or vocalizing. On rare occasion even seizures and collapse may occur. This disease may progress rapidly or very slowly. Horses generally deteriorate over time but some animals may “level off” or plateau for a period of time only to worsen days, weeks or even months later. Most horses afflicted with this debilitating disease continue to have a bright, alert temperament. 

How Do We Diagnose EPM? 

As you can see from the preceding discussion, clinical signs of this disease can vary significantly, and no two horses with EPM will look exactly the same. That is one of the factors that make the accurate diagnosis of this disease such a challenge. Another factor is that there are several diseases of the central nervous system of the horse that can look very similar to EPM, especially in the early stages of the disease process. Finally, there is no single “test” that can be done, which is 100 percent accurate in the live horse that can tell us if a particular animal is suffering from EPM. There are tests that can be utilized by your veterinarian, and these are used to support his or her diagnosis of EPM as well as to rule out other diseases, which may look like EPM. It is important to remember that we can never be absolutely sure a particular horse has EPM. 

The most important evaluation done by your veterinarian as he or she begins the diagnostic work-up for a suspected case of EPM is the neurologic examination. This is a specialized exam that is done to evaluate the function of the central nervous system of the horse. It may also be necessary that radiographs be taken of the neck region of the horse. This is done to determine if there is a problem with the spine that might cause compression on the spinal cord. Clinical signs from pressure on the spinal cord of the horse can look very much like EPM. This type of condition has several names but the most common term used is “wobblers.” This is an important “rule out” when evaluating a horse for EPM. Your veterinarian may also draw blood during the examination process. In some cases, he or she may decide to collect spinal fluid from the horse by doing a spinal tap. The most accurate of the currently available EPM tests require submission of both blood and spinal fluid to the diagnostic lab. Analyses of blood and spinal fluid samples both support the diagnosis of EPM and also help rule out other diseases of the central nervous system. 

EPM is a challenging diagnosis to make, and in certain cases treatment of the horse may be part of this diagnostic process. In other words, a horse may be treated for EPM with only minimal diagnostic efforts expended. If the animal improves, then it is concluded that the horse did have EPM. If the horse does not improve, then further diagnostic efforts may be necessary. This approach should only be considered after careful consultation with your veterinarian.

How Do We Treat EPM? 

Just as with our diagnostic efforts, treatment of EPM should only be done under the direct supervision of your veterinarian. With all types of life-threatening disease, it is important that you recognize, diagnose and treat early for the best possible outcome. Currently, there are three FDA-approved treatments for EPM available for use in the United States. These are prescription drugs and can be used only by or on the order of a licensed veterinarian. 

• The first is a product called Marquis, which is manufactured by Merial. The active ingredient is ponazuril. This product is a paste formulation and is given once daily for 28 consecutive days including a higher “loading” dose on the first day of treatment. The drug has demonstrated effectiveness in treating horses with EPM and has a very favorable safety profile. 

• The second is a product called PROTAZIL Antiprotozoal Pellets manufactured by Merck Animal Health. The active ingredient is diclazuril. This is a pelleted product designed to top dress feed.  Protazil has safety and effectiveness profiles similar to Marquis and is also to be given once daily for 28 consecutive days. 

• The third is ReBalance, which is manufactured by PRN Pharmaceuticals. The active ingredients are sulfadiazine and pyrimethamine.  The product is a liquid suspension given by mouth for 90 to 270 days. ReBalance must be given on an empty stomach for optimal absorption. The drug is generally safe, although overdoses can cause serious toxicity and it generally is not recommended for pregnant mares. Effectiveness is comparable to Marquis.

Veterinarians have actually used the combination of sulfadiazine and pyrimethamine (SDZ/PYR), since the early days of EPM treatment and it previously could be obtained as a compounded drug.  Because there is now an FDA-approved product (ReBalance) other forms of this drug combination should not be given.

It is also common for veterinarians to use other supportive or ancillary drugs while treating EPM. These treatments can include anti-inflammatory products such as corticosteroids, bute, Banamine, DMSO and others. Some practitioners may also supplement with vitamin E while treating neurologic disease. Others may try to stimulate the immune system by using one of several immune-modulating products on the market. It is also recommended that horses be removed from stressful environments and activities while receiving treatment for EPM. 

It is important to remember that successful treatment may eliminate the parasite, but the effects from damage to the central nervous system by the parasite can be permanent. Another important issue to keep in mind is that some horses that have responded favorably to treatment may be affected again, often with similar signs, at a later time.

What Can I do to Help Prevent or Minimize the Risk of EPM? 

Horse owners can take advantage of some basic husbandry practices and good common sense to help reduce the risk factors that can contribute to disease incidence. One thing that all of us can do is to keep our feed storage areas neat and clean. Untidy areas with spilled feed invites unwanted guests such as opossums. 

• Keep your feed in sealed or closed containers.
• Cover your hay storage area if possible.
• Keep rodents under control on your property.
• Discourage visits by opossums.
• Check with local authorities with respect to trapping and relocating opossums or eliminating them.
• Properly dispose of any animal carcasses that you may see on or near your property.
• Clean your equine water sources on a regular basis.
• Do not feed on the ground.
• When transporting horses, make them as comfortable as possible. Transportation stress can be a contributing factor for EPM. 

Currently there are no USDA approved vaccines available for use in horses to aid in the prevention of this disease.  

Equine Protozoal Myeloencephalitis (EPM) Summary Points 

General comments:

• EPM is an abbreviation for Equine Protozoal Myeloencephalitis
• Disease of the brain and/or spinal cord in the horse
• Caused by protozoan parasites, the most of important of which is transmitted by the opossum
• Difficult to accurately diagnose
• Early diagnosis and treatment very important
• Sarcocystis neurona and Neospora hughesi are the protozoan pathogens of EPM
• No horse-to-horse transmission
• Circulating antibodies to S. neurona or N. hughesi indicate the horse has been exposed to the parasite, but does not indicate active disease (we call this seropositive)
• In some geographic locations, over 90 percent of horses may be seropositive, in others far less
• A large equine survey indicated only about 0.14 percent of horses will develop clinical disease

Life Cycle of Sarcocystis neurona 

• S. neurona has a complex, two-host life cycle
• The opossum has been identified as a definitive host of S. neurona
• The opossum ingests sarcocysts in muscle tissues of scavenged carcasses of intermediate hosts
• The parasite undergoes a form of sexual reproduction within the opossum which produces the sporocyst
• Sporocysts are shed in the feces of the opossum
• Sporocysts can survive in the environment for several months
• The horse is an aberrant, intermediate host
• The horse is exposed by ingesting feed or water contaminated with opossum feces that contain sporocysts
• The parasite undergoes a form of asexual reproduction in the horse and eventually gains access to the brain and spinal cord 

 Intermediate host 

• The armadillo, striped skunk, cat, raccoon and sea otters can serve as intermediate hosts
• Recent work has demonstrated sarcocysts in a horse; therefore, the horse may serve as a true intermediate host
• The intermediate host picks up the parasite from ingesting sporocysts
• The parasite goes through an asexual reproduction stage and produces tissue sarcocysts (cysts in the muscle tissue)
• This stage then is the source of infection for the opossum, which ingests these infected tissues containing sarcocysts) and the life cycle is completed 

 Clinical Signs 

• Progressively debilitating disease affecting the CNS (brain and spinal cord)
• Can be sudden or gradual onset
• Disease may involve brain, brain stem, spinal cord or any combination thereof
• Disease may progress very rapidly or slowly
• Disease may stabilize only to resume progression days, weeks or months later
• Horses are usually bright and alert during course of disease
• Horses typically do not have high temperatures (fevers) 

Signs may include any of the following: 

• Subtle lameness
• Weakness
• Ataxia (incoordination)
• Usually asymmetrical, one to all limbs
• Muscle atrophy
• Head tilt
• Head shaking
• Cranial nerve signs, such as asymmetrical facial paralysis, head tilt or swallowing difficulties
• Behavioral abnormalities, seizures
• Recumbency

 Diagnosis 

• A thorough physical and neurologic exam is the most important part of the diagnostic process
• Radiographs of the neck region if indicated by your veterinarian
• Blood work if indicated by your veterinarian
• Spinal tap if indicated by your veterinarian

Differential Diagnosis (Rule outs)

• Any instability or abnormality of the vertebrae of the neck, such as “wobblers”
• Equine Herpesvirus infection of the spinal cord and brain
• Other viral disease of the brain and spinal cord such as rabies, EEE, WEE, West Nile virus
• EMND (equine motor neuron disease)
• Injury/trauma of the spinal cord or brain
• EDM (equine degenerative myeloencephalopathy)
• Polyneuritis Equi (PNE, including cauda equina)
• Tumor, abscess, cyst, granuloma, or hematoma of the brain or spinal cord

FDA Approved Treatments currently available 

Marquis oral paste

PROTAZIL pellets 

ReBalance oral suspension

Prevention 

• Decrease presence of opossums
• Keep grain stored and feed area clean
• Keep water sources clean
• Keep hay covered if possible
• Rodent control
• Do not feed on the ground
• Immediately remove and bury carcasses of skunks, armadillos, cats and raccoons whenever possible
• Currently, there are no USDA approved vaccine products available to aid in the prevention of EPM 

*A commercial FDA-approved product containing SDZ/PYR was marketed for several years, but was later withdrawn from the market.

 

Reviewed by Infectious Disease Committee in 2020.