Equine Protozoal Myeloencephalitis (EPM)

This entry is part 1 of 2 in the series 2024 Series on EPM

For access to a recorded webinar on EPM that reviews this information and also includes more than an hour of Q & A from owners, click HERE

What is EPM?

EPM is a parasitic infection of the central nervous system caused by a single-celled microscopic organism called a protozoa (protozoa are not worms and are not killed by worming).  The protozoa associated with most EPM infections appears to be Sarcocystis Neurona (S. neurona).  Other protozoa also may be involved, including Neospora Hughesi (N. hughesi).

EPM in its non-infectious form is carried by cats, raccoons, skunks, and other animals but the protozoa have to pass through the body of an opossum in order to become infectious.  The infectious form is excreted in opossum feces that are ingested by the horse.  Infected feces are present anywhere the opossum travels.  This includes pastures as well as unsecured feed rooms and hay barns.

EPM cannot be transmitted from horse to horse; ONLY an opossum can infect a horse.

The life cycle of S. neurona: the non-infectious form of the protozoa can be carried by many animals but must pass through the body of an opossum to become infectious.  The infectious form is present in opossum feces and is ingested by the horse. (figure from https://www.ars.usda.gov/northeast-area/beltsville-md-barc/beltsville-agricultural-research-center/animal-parasitic-diseases-laboratory/docs/epmsarcocystis-neurona/)

What happens once the horse ingests the protozoa?

When the horse consumes the protozoa, they enter the digestive tract.  In response to the protozoa’s presence in the gut, the immune system (about 65% of which resides in the gut wall) begins to make antibodies.  These antibodies can be detected in a blood sample that is sent to the laboratory for testing; this procedure is called running an EPM blood titer.  A horse with a positive blood titer for EPM is said to have been EXPOSED to EPM.  “Exposure” means that the horse has ingested the protozoa and the immune system has been activated.  Exposure does NOT necessarily mean that the horse is infected with EPM.  In studies that measured blood titers in U.S. domestic horses, from 26% to 89.2% had positive EPM titers (Vardeleon et al., 2001; Bentz et al., 2003).  These data indicate that exposure to EPM is common.  Exposure, however, is not equivalent to infection.

Exposure vs. Infection

Exposure means that the horse has ingested the protozoa and the immune system is making antibodies BUT the horse does NOT have neurological symptoms because the protozoa are NOT present in the brain and spinal cord.


Infection means that the protozoa have escaped the gut, crossed the blood-brain barrier, and are now present and replicating in the brain and spinal cord.  The damaging actions of the protozoa in the nervous system CAUSE neurological symptoms.


What do titers measure?

Titers measure the response of the immune system to an invading organism.  Titers do NOT measure the organism itself.  EPM titers, therefore, measure the activity of the immune system in response to the protozoa; they do NOT measure the number of protozoa that are present.  EPM titers can be measured in blood or in cerebrospinal (CSF) fluid – the fluid that surrounds the spinal cord.  A blood titer is the most common titer run because it requires only a blood sample; CSF titers are less commonly performed because they require obtaining a sample of CSF which is a more invasive, risky, and costly procedure.

In an exposed only horse (who by definition has no symptoms), the blood titer will be positive — because the protozoa entered the gut and activated the immune system — but the CSF titer (if performed) will be negative because the protozoa have NOT crossed into the brain and spinal cord.  The exposed only horse does not have symptoms because there are no protozoa present in and damaging the nervous system.  


Asymptomatic, positive blood titer, negative CSF titer (if performed)

In an infected horse (who is symptomatic by definition), the blood titer will be positive — because the protozoa entered the gut and activated the immune system — and the CSF titer (if performed) will be positive because the protozoa have crossed into the brain and spinal cord and are replicating in the nervous system.  The infected horse has symptoms because the protozoa are present in and damaging the nervous system.  It is generally accepted that if a horse has a positive blood titer and has symptoms, then that horse is infected (assuming other possible causes of neurological symptoms have been ruled out).


Symptomatic, positive blood titer, positive CSF titer (if performed)

In a minority of cases, a symptomatic horse has a negative blood titer.  In this situation, the only way to rule EPM in or out is to perform a CSF titer.  If the CSF titer is positive, then the interpretation is that the horse is infected.  If the CSF titer is negative, then other potential causes of neurological symptoms should be pursued.  These include spinal arthritis, “kissing spine,” “wobblers,” equine motor neuron disease (EMD), and neurological Lyme disease.  However, note that it is possible for a horse to have been infected with EPM, developed symptoms, and then cleared the infection.  In this case, the blood and CSF will be negative for protozoa antibodies but the damage caused by the protozoa to the nervous system remains and the horse remains symptomatic.

What do titer numbers mean?

Titers measure the response of the immune system to an invading organism; they DO NOT measure the number of invading organisms present in the body.  A high titer number reflects a strong immune response.

In the asymptomatic EXPOSED horse, the numbers reported in the titer reflect only the robustness of the immune response to ingestion of the protozoa.

In the symptomatic horse, the higher the titer number, then the more likely the horse is to be INFECTED with EPM – meaning that the protozoa have breached the blood-brain barrier and are now in the brain and spinal cord.  However, there are exceptions to this principle.  Horses with weak immune systems (i.e., older horses, horses in poor condition, malnourished horses, horses with other medical issues such as ulcers or metabolic conditions, chronically stressed horses, horses co-infected with Lyme) may not mount a strong titer response to an invading organism, resulting in a relatively low titer.  In addition, when horses are co-infected with another organism such as the spirochete that causes Lyme disease, then the titer to one or both infections may be relatively low.  If the horse has neurological symptoms, and other causes of symptoms have been excluded, then infection is likely.

Damage to the spinal cord from EPM; from Henker et al., 2020; Pathological, immunohistochemical, and molecular findings of equine protozoal myeloencephalitis due to Sarcocystis neurona infection in Brazilian horses; Tropical Animal Health and Production 52(6)

What are neurological symptoms?

Neurological symptoms include changes in your horse’s posture, gait, strength, balance, coordination, proprioception, reactions, body condition and/or mood that suggest that the nervous system is not working normally.  Your veterinarian can perform a formal neurological exam.  For detailed technical information about the neurological exam, how it is performed, and the meaning of findings, see here: https://aaep.org/sites/default/files/issues/proceedings-10proceedings-z9100110000331.pdf

This exam assesses:

  1. the horse’s mental state
  2. the connections between the brain and the cranial nerves; these nerves control smell, vision, hearing, swallowing, the ability to move the tongue, lips, muzzle, eyes, and ears
  3. spinal reflexes, including tail and anal tone, as well as skin sensation and abnormal sweating responses
  4. gait and posture, including walking/trotting in a straight line, walking in serpentines, walking with elevated head, walking while pulling the tail, spinning in circles, walking backward, and walking on uneven ground or up and down a hill

In addition, owner observations about changes in mood, posture, gait, and body condition are important contributions to understanding possible neurological symptoms.

What types of symptoms are observed in EPM horses?

EPM can result in an enormous range of symptoms.  These include:

Posture abnormalities:

  • Standing with feet in abnormal positions
    • Feet too far apart – spread abnormally wide from side to side or too far forward or too far back
    • Feet too close together
  • Unable to stand straight or square
  • Unable to stand without leaning on a fence or wall
  • Standing with the head tilted

Gait abnormalities:

Ataxia – lack of coordination

  • Cannot walk in a straight line
  • Cannot back up in a straight line
  • Tightrope walking (front or back or both)
  • Constantly changing the spacing between feet
  • Unable to consistently track hind feet behind front feet while walking
  • Spasticity – stiff, awkward movements
  • Disorganized gaits
    • Front and back legs not synchronized
    • Tripping or stumbling
    • “Bunny hop” canter – both hind legs come down togethe
  • Lameness without apparent cause
  • Circling behavior
  • Ataxia – lack of coordination
    • Cannot walk in a straight line
    • Cannot back up in a straight line
    • Tightrope walking (front or back or both)
    • Constantly changing the spacing between feet
    • Unable to consistently track hind feet behind front feet while walking
  • Spasticity – stiff, awkward movements
  • Disorganized gaits
    • Front and back legs not synchronized
    • Tripping or stumbling
    • “Bunny hop” canter – both hind legs come down togethe
  • Lameness without apparent cause
  • Circling behavior

Weakness/Proprioceptive deficits

  • Difficulty lifting feet, resulting in toe-dragging
  • Difficulty turning
  • Difficulty going up or downhill; may drift to one side
  • Difficulty getting up or down
  • Difficulty backing up

Body condition changes

Muscle atrophy (loss)

  • Most typically loss of topline and hindquarter muscling
  • May have asymmetrical muscle loss
  • Can have full body muscle wasting

Other Physical Symptoms

  • Facial paralysis, including drooping eyelids, ears, or lips
  • Difficulty chewing, moving food with the tongue, or difficulty swallowing
  • Missing tail reflex, anal reflexes, or skin reflexes
  • Odd sweating patterns
  • In extreme cases: Seizures, loss of vision, loss of hearing

Mood symptoms

  • In horses who are not usually reactive, the emergence of anxiety, fearful behavior, spookiness, explosiveness
  • Dissociated behavior

What causes neurological symptoms?

Neurological symptoms are caused by damage to the brain, the spinal cord, and the individual nerves that control body structures (especially muscles and organs) and relay information about the body back to the brain.  More specifically, the protozoa can damage:

  • Pathways that route information from the brain to the various parts of the body such as the legs, with the consequence that the horse cannot control his/her body
  • Pathways that route information from the body back to the brain, especially information about where the legs and feet are in space, with the consequence that the horse does not know where his/her feet/legs are (proprioceptive deficits)
  • Nerve fibers that run through the musculature, with the consequence that the muscles become weak and may shrink (muscle wasting); when nerves that run through muscles do not fire normally, then the muscle fibers wither
  • Specific structures in the brain that control balance, vision, hearing, and mood, and that integrate information about the environment

Predictors of Recovery

Intensity of infection: the number of protozoa that have infiltrated the nervous system

  • The more protozoa that are present in the nervous system, the more damage will occur (symptoms are the result of damage)
  • With greater damage, more support is needed and recovery takes longer
  • It is IMPOSSIBLE TO KNOW how many protozoa are present in the nervous system; remember that titers reflect the activity of the immune system in response to the protozoa – not the number of protozoa
  • Although it is generally accepted that higher titers in a symptomatic horse indicate a heavier infection, immunocompromised horses may not mount a strong titer response; clinically, some of the most symptomatic horses seen have had low titers.

Duration of infection: how much time passed before EPM was diagnosed

  • When infection is diagnosed quickly, the protozoa have less time to replicate and damage the nervous system; full recovery is more likely and easier to accomplish
  • In horses who were undiagnosed for months or years, damage continues to accumulate during that period; these horses may have a substantial backlog of damage that has to be addressed; recovery will take longer and require more support

Location of infection:  the location of infection in the brain or spinal cord is the location of damage

  • The location of damage is revealed by the type of symptoms
  • Localized symptoms such as one weak hind leg resolve more quickly than more complex symptoms consistent with brain inflammation/damage such as circling behavior or seizures

Presence of other conditions:

  • Recovery is usually straightforward in otherwise healthy horses with no other underlying conditions
  • The presence of any condition that suppresses the immune system or promotes inflammation complicates and lengthens recovery
    • Other infections such as Lyme disease
    • Metabolic conditions such as insulin resistance (IR), Cushing/pituitary pars intermedia dysfunction (PPID), overweight
    • Gut inflammation – diarrhea, fecal water, colic, ulcers
  • Chronic stress from inadequately managed pain, frequent travel and competition

Age and size of horse:

  • Recovery can take longer in older horses who lack the physiological resilience of younger horses
  • Recovery can take longer in larger horses who have more nervous system to repair

Why does treatment fail to return many horses to normal function?

This is the most misunderstood aspect of EPM recovery:  the EPM medications stop the protozoa from replicating but they DO NOT (and cannot) repair the nervous system damage left behind.  Some horses recover on their own over time but many cannot recover without targeted support for inflammation control and nervous system regeneration.

Treatments for EPM

FDA-approved medications:

There are three FDA-approved medications for the treatment of EPM.  These medications fall into two categories:
  • Direct anti-protozoals: these medications directly inhibit protozoa replication and interfere with protozoa metabolism, resulting in a rapid reduction in the number of protozoa in the body. These medications are —
    • Marquis – generic or compounded as ponazuril
    • Protazil – generic or compounded as diclazuril
  • Indirect anti-protozoal: This medication inhibits folic acid synthesis which indirectly and slowly (over many months) reduces the number of protozoa in the body. This medication is Rebalance – generic or compounded as pyrimethamine + sulfadiazine.

Other medications:

  • Toltrazuril.  Toltrazuril is usually given in DMSO to enhance absorption.  It is metabolized in the horse’s body to ponazuril, which is Marquis.  There are many published scientific papers on the effective use of toltrazuril to treat EPM.  Toltrazuril is also available on some websites without the need for a prescription. NOTE:  if the drug is not obtained from a reputable pharmacy (which requires a script), then there is no way to know if the drug is the correct drug or if it is in the correct concentration.  There are major safety concerns when using medications that did not come through a pharmacy.
  • Decoquinate with levamisole.   This drug combination is marketed as Orogin.  Decoquinate is the anti-protozoal component; levamisole is a nervous system anti-inflammatory.  The evidence for its efficacy is extremely limited.
  • Other drug combinations.  There are currently many compounded drug combinations offered for the treatment of EPM.

Alternative approaches:

Many non-medicinal products are marketed for the treatment of EPM.  There is no evidence that any of these preparations work with the exception of the EPM treatment kits offered by Earthsong Ranch (www.earthsongranch.com).  These kits combine homeopathy and herbs; Earthsong Ranch has documented successful treatment in several thousand horses.

How Long Should My Horse Be Treated?

The original recommendation for treatment with the FDA-approved direct anti-protozoals (Marquis and Protazil) was 28 days.  This is the length of the trial used to obtain FDA approval.  The 28 day period was selected based on the finding that drug concentrations in the CSF are adequate by about Day 15 to inhibit the protozoa.  Remember that the protozoa are in the spinal cord and brain – for a drug to be effective it must be present in the CSF at a concentration that is adequate to stop the protozoa.

In practice, however, many vets treat for 60-90 days if the symptoms are moderate to severe or if the infection may have been present for many months or years.  Similar protocols are reasonable with toltrazuril (another direct anti-protozoal).  In the FDA trials, Rebalance required from 6 to 9 months to clear the protozoa – a substantially longer treatment duration.  Treating with Rebalance for shorter durations is likely to lead to a horse who is not definitively treated and continues to have an active infection.  Although there is one published paper suggesting that Orogin can be used for only 10 days, the data supporting this assertion are extremely weak and were inadequate to obtain FDA approval.  There is no evidence base for other compounded drug combinations but the 30 to 90 day treatment range is reasonable as long as a direct anti-protozoal is part of the combination (ponazuril, diclazuril, or toltrazuril).

What is “Successful” Treatment?

By “successful” treatment, owners mean that their horse is back to normal in terms of physical function, body condition, and mood.  It is often noted that Marquis and Protazil were approximately 60% effective in the FDA trials (Rebalance was approximately 42% effective).  It is critical to understand, however, that the definition of success in the FDA trials was NOT the return of the horse to normal.  Instead, success was defined as the improvement of one neurological grade on a 6-point scale.  That scale is below.

Neurologic Grading Scale
0Normal, no deficit detected
1Deficit just detected at normal gait
2Deficit easily detected and is exaggerated by backing, turning, swaying, loin pressure or neck extension
3Deficit very prominent on walking, turning, loin pressure or neck extension
4Stumbling, tripping, and falling down spontaneously
5Recumbent, unable to rise

Here are possible successes:

  • A horse who began the study unable to rise (grade 5) and finished the study able to rise but stumbling, tripping and falling (grade 4) is a treatment success.
  • A horse who began the study with grade 4 deficits and at study end had difficulty walking, with loin pressure and neck extension (grade 3) is a treatment success.
  • A horse who began the study with grade 3 problems and finished with deficits easily detected and exaggerated by backing, turning, swaying, pressure or neck extension (grade 2) is a treatment success.
  • A horse who begins the study with grade 2 issues and finishes with deficits detected at normal gaits (grade 1) is a treatment success.

No horses returned to normal function (grade 0) in these studies.

Conversion of cerebrospinal fluid (CSF) on Western blot from antibody-positive to antibody-negative also was measured for all three drugs and was considered a sign of success in the Protazil and Rebalance studies.

However, horses that converted to negative did not improve neurologically and most horses did not become negative during the studies, including those that did improve.

In other words, successfully clearing the protozoa did not result in improvement and horses that did improve did not have negative titers.

The role of inflammation in provoking and maintaining neurological symptoms is generally underestimated.  Inflammation is the reason why early in treatment some horses will experience worsening symptoms as the protozoa die-off provokes even higher levels of inflammation (known as a Herxheimer effect).  This is why a neurologically impaired horse can test negative on a CSF Western blot as reviewed in the drug trials above – there may be no more sign of the protozoa’s presence but the inflammation and associated destruction remain.  This is also why a horse without symptoms can have a positive Western blot – in this case, the horse is managing the inflammation.  In the absence of actions to control the inflammation (which inhibits repair) and support the nervous system in repairing itself, the disability may linger and, in some horses, it may never resolve.

Neurological relapse — a return of symptoms after a period of recovered functioning — is a different issue and may be the result of incomplete treatment, re-infection, failure to support nervous system healing, and/or inflammation that has not been adequately addressed to allow full recovery and minimize the chance of re-infection.

Bottom line:

  1. Titers are not a reliable predictor of function
  2. Treatment does not mean that titers return to zero


What are the medication “success” rates?

Bearing in mind that success was defined as the improvement of one neurological grade – not as return to normal function – it is also important to appreciate that success rates depended on whether the evaluations were made by the clinical investigators (the veterinarians who carried out the study; higher rates) or by outside independent experts not associated with the study (lower rates).

  • For Marquis, study veterinarians reported an improvement of one neurological grade in 60% of horses after 28 days of treatment; however, independent vets who examined study data noted that only 41.8% of horses had improved by one neurological grade.
  • For Protazil, study veterinarians reported an improvement of one neurological grade in 59.5% of horses after 28 days of treatment; the independently verified rate was 24.3%.
  • For Rebalance, study veterinarians reported that 42.3% had improved by one neurological grade after 6 to 9 months of treatment; the independently verified rate was 34.6%.

Feeding to Restore Neurological Function

Clinical experience in hundreds of horses diagnosed with EPM has suggested that a custom protocol that aligns with the following principles support the most rapid and complete recovery.

  1. Inflammation blocks healing and exacerbates symptoms.  Inflammation can be produced by pro-inflammatory foods as well as by events such as extreme weather changes, stressors (e.g., hauling, change in herd members, change of barns, etc.), vaccinations, and in some cases worming with chemical wormers.  Controlling inflammation by adjusting the diet and avoiding/minimizing stress supports recovery.
  2. Feeding an anti-inflammatory diet that covers foundational nutrition needs (especially trace minerals) is a central component to EPM recovery.  Some horses will improve by one neurological grade simply in response to the change in diet.  The ideal diet should be customized to the horse, taking into account other existing conditions as well as age and breed.  This diet:
    1. Eliminates pro-inflammatory food constituents such as soy, corn, wheat middlings, and excess sugar (e.g., sweet feed)Eliminates or minimizes toxin/contaminant exposure (pesticides in soy, extremely high iron levels and aluminum contamination in beet pulp)Includes high levels of omega-3 (anti-inflammatory) fatty acids and low levels of omega-6 (pro-inflammatory) fatty acids
    2. Includes high levels of omega-3 (anti-inflammatory) fatty acids and low levels of omega-6 (pro-inflammatory) fatty acids
  3. Restore neurological function from the INSIDE OUT using nutrients, herbs, and nutraceuticals.  The selection and dosing of specific supplements depends on the individual horse, its medical history, and the severity and type of current symptoms.  These substances:
    1. Stimulate release of nerve growth factor – the chemical signal to the nervous system to engage in repairs
    2. Control inflammation in the nervous system that can block healing and make symptoms worse;
    3. Optimize gut function – because a well-functioning gut helps to control inflammation and strengthen the immune system
    4. Optimize immune function to support protozoa clearing and the prevention of re-infection or infection by other organisms
    5. Optimize liver and kidney function to maintain efficiency of detoxification processes
  4. Restore neurological function and strength from the OUTSIDE IN using
    1. Exercises to strengthen weakened muscles
    2. Strategies to improve proprioception (awareness of where the body is in space):
      • Exercises/movement
      • Balance pads (e.g., Murdoch pads)
      • Wearable rehabilitation system – the Eagle Pro-Six (www.eagleprosix.com); this is a system of stretchy straps that can be worn for long periods once the horse is acclimated.  It encourages balanced body use, reduces compensation, and improves proprioception by giving the horse constant input about where his/her body and legs are.  This attribute is especially helpful for horses who are having trouble walking in a straight line or have to lean on fences or walls in order to stand.  Improvements usually occur within the first 30 min of wearing the Pro-Six.

What are the indicators of recovery?

The best indicators of recovery from EPM are FUNCTIONAL:

  • A return to normal balance, coordination, and movement
  • A return to normal mood and affect
  • A return to normal body condition
  • A return to normal energy level


Protozoa titers may remain elevated for months or years after the horse appears to be normal (Dubey et al., 2015).  Checking titers is unlikely to be helpful in knowing whether the horse has recovered.  This is especially true if the horse is in an environment in which protozoa exposure is ongoing.  Every time the horse ingests the protozoa the immune system will activate and make antibodies which will be measurable on a titer.  However, making antibodies does not mean that the horse is re-infected; infection requires infiltration of the protozoa into the nervous system.

What is an EPM relapse?

By a “relapse,” owners usually mean that the symptoms exhibited by the horse during active EPM infection have returned or, if the horse is still symptomatic, that symptoms have become worse.

When symptoms re-appear or worsen, it does not necessarily mean that the horse has been re-infected.  Return of symptoms or symptom exacerbation can occur in the absence of a new infection but in response to weather changes (e.g., extreme heat, extreme cold, rapid temperature swings), stressors (e.g., hauling, showing, competing, change of barns, changes in herd members), vaccines, and, in some cases, chemical worming.  These environmental conditions and events can precipitate inflammation that reveals unhealed nervous system damage.  Horses, as prey animals, are masters of compensation; they can appear to be essentially normal while masking low levels of symptoms.  However, when an inflammatory event occurs, the ability to compensate for the decrease in function may be inadequate – and symptoms can return or worsen.

How can you tell if the horse has been re-infected?  It is difficult to know for certain because protozoa titers do not behave like other titers (e.g., Lyme) and do not reliably decrease as treatment progresses.  In addition, if the horse is in an environment where re-exposure can occur (because possums are present), then the immune system will respond to re-exposure by making antibodies – resulting in titers that stay elevated even though the horse is not necessarily re-infected.  Remember that infection by definition requires infiltration of the protozoa into the brain and spinal cord.

Key steps are to manage inflammation, continue nervous system support to achieve full healing, and consider re-treating if symptom return or exacerbation is prolonged.


Bentz, B.G., Ealey, K.A., Morrow, J., et al.  Seroprevalence of antibodies to Sarcocystis neurona in equids residing in Oklahoma.  J Vet Diagn Invest; 15; 2003; 597-600.

Dubey, J.P., Howe, K.K., Furr, M., et al.  An update on Sarcocystis neurona infections in animals and Equine Protozoal Myeloencephalitis (EPM). Veterinary Parasitology; 2015; 209; 1-42.

New Animal Drug Application (NADA) 141-188; Freedom of Information Summary; Marquis (15% w/w ponazuril) anti-protozoal oral paste; Sponsor: Bayer Corporation (https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/698)

New Animal Drug Application (NADA) 141-268; Freedom of Information Summary; Protazil antiprotozoal pellets 1.56% diclazuril oral pellets horses; Sponsor: Schering-Plough Animal Health Corporation (https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/829)

New Animal Drug Application (NADA) 141-240; Freedom of Information Summary; Rebalance antiprotozoal oral suspension (sulfadiazine and pyrimethamine); Sponsor: Animal Health Pharmaceuticals, LLC (https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/787)

Vardeleon, D., Marsh, A.E., Thorne, J.G., Loch, W., Young, R., Johnson, P.J. Prevalence of Neospora Hughesi and Sarcocystis neurona antibodies in horses from various geographical locations.  Vet Parasitol.; 95(2-4); 2001; 273-82.


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