Equine protozoal myeloencephalitis or "EPM" is an infectious disease of horses caused by a microscopic protozoan parasite, which has been named Sarcocystis neurona, and is spread by the opossum. The opossum passes the organism in its feces, which are then ingested by horses when they eat contaminated feed, hay or water. This parasite gains access to the horse's brain and spinal cord where it causes inflammation and destruction of nerve tissues.
The incidence of EPM is high in many parts of the USA. It certainly represents one of the most common diagnoses for horses with neurological disease. Our knowledge about EPM changes frequently. In particular, recommendations regarding diagnostic testing, treatment options, and how to determine when to stop treatment change rather frequently as new information is learned about EPM.
Hopefully, increased awareness of EPM will lead to earlier disease recognition and treatment since treatment will likely be more successful when instituted early in the course of the disease.
How Infection Occurs
Horses become infected with S neurona by ingesting food material (grain, hay, grass) or drinking water which has been contaminated by the feces of the opossum. Bird droppings may also be an important source for the infective sporocysts. In the horse, the Sarcocystis neurona parasites migrate to the CNS (brain and spinal cord). *Not all infected horses develop recognizable symptoms of neurological disease.
Recent epidemiological surveys, using a blood test for Sarcocystis neurona, suggest that approximately 50 to 60 percent of all horses in the Midwest have been infected by, or exposed to, Sarcocystis neurona. Fortunately, only a relatively small number of those horses will actually ever develop neurological disease. Unfortunately, we do not presently know which exposed horses are likely to develop signs of EPM.
Sarcocystis neurona parasites set up tiny colonies in the CNS. The actual signs of abnormality depend on the location and the extent of these colonies. The parasites cause damage to nervous tissue and provoke an inflammatory response. When evident, signs of neurological dysfunction in affected horses are attributable to either the destruction of nerve tissue by parasites or interference with normal nerve impulse conduction by the horse's inflammatory reaction against the parasite.
What to Watch For
Essentially, EPM causes signs of neurological dysfunction in affected horses. EPM may cause any neurological sign or combination of signs: any neurological sign or combination of neurological signs could be due to EPM.
Signs of neurological dysfunction associated with EPM may be very minor and nonspecific, and include such problems as mild lethargy, relatively poor body condition, change of attitude, reduced exercise tolerance and/or difficulty with complex gaits. Alternatively, EPM may cause some rather striking and clear-cut neurological abnormalities such as:
It is important to recognize that EPM can cause ANY neurological abnormality or combination of abnormalities; therefore, EPM must be considered by the veterinary diagnostician whenever he/she is presented with equine neurological problems. It is also important to consider EPM because it is so common. However, it should be carefully noted that the diagnosis of EPM is commonly made without proper justification and/or consideration of other possibilities. It is easy to implicate this disease without a proper clinical evaluation. Lots of horses are treated for EPM when they are not actually affected with this disease.
Classically, EPM has been associated with the following three neurological features, and if these three features are evident, the affected horse is very likely affected with EPM:
The most common clinical manifestation of EPM is ataxia (incoordination) that arises from damage to the spinal cord.
EPM-affected horses are commonly presented to veterinarians for diagnosis of lameness. BUT, a diagnosis of EPM as a cause for lameness should not be made without first undertaking both a thorough lameness examination and a thorough neurological examination. Many of these horses have musculoskeletal problems, not a neurologic one.
Because it's a difficult lameness to figure out, it does not indicate the need to look for EPM. Incoordination (associated with EPM OR other causes of spinal dysfunction) might predispose to lameness because the affected horse is prone to falling or spraining joints. It might be difficult to determine whether "lameness" is due to musculoskeletal pain, neurological dysfunction or a combination of both.
In horses that are lame as a consequence of musculoskeletal pain, the lameness should be less pronounced during treatment with pain-relieving drugs such as phenylbutazone. Veterinarians often elect to use a short course of treatment with phenylbutazone to determine whether the observed problem is associated with pain, versus neurologic disease, which does not cause limb pain. If treatment with phenylbutazone causes a reduction in the severity of the lameness, it is less likely that the major problem is a neurological disease (such as EPM). Signs of limb dysfunction associated with EPM do not typically change during treatment with phenylbutazone.
This disease should be suspected whenever horses develop signs of neurological disease that cannot be readily explained by other obvious events. It must be remembered that EPM can produce any neurological abnormality or combination of abnormalities. Horses living (or that have lived) in areas in which the opossum is found are at the highest level of risk for EPM.
EPM was originally identified by J.R. Rooney in 1964. The first cases were recognized among horses returning to Kentucky from racetracks in the northeastern United States. Subsequent cases have been reported among native horses in most of the United States as well as in Canada and Mexico. At that time, it was not appreciated that the symptoms were due to a protozoan parasite, and the disease was known as "focal or segmental myelitis/encephalitis" (the cause was unknown - the disease was named for the pathologist's microscopic observations). Judging from the literature, EPM may not have been as common in those days.
In the 1970s, the protozoan parasite was seen in affected neural tissues obtained from EPM-affected horses. The disease was then described as equine protozoal myeloencephalitis for the first time, but the actual protozoan parasite was not identified. It was (incorrectly) thought that the protozoan was Toxoplasma gondii (leading to the incorrect name "equine toxoplasmosis"). Probably most, if not all, of the literature about neurological disease associated with toxoplasmosis in horses actually relates to EPM.
In the late 1970s and the early 1980s, evidence was accumulating to suggest that the protozoan parasite responsible for EPM belonged to the Sarcocystis group. In the late 1980s, the causative organism of EPM was finally isolated in the laboratory and determined to be a previously undescribed species of Sarcocystis; it was named Sarcocystis neurona. Soon after it had been isolated in the laboratory, it became possible to develop some useful diagnostic tests for EPM.
One of the persisting mysteries about Sarcocystis neurona had been its life cycle. After it was determined that the causative parasite was a Sarcocystis spp., a search for possible definitive hosts was undertaken. Logical candidate species included the raccoon, opossum and skunk. These animals were considered as possibilities because they are not found beyond the Americas, and EPM has only been described in North and South America, where these particular mammalian species exist. EPM has only been described outside of the Americas in horses that had previously been living in America. In North America, the distribution of the majority of cases of EPM almost exactly follows the population distribution of the opossum.
It has been shown that the definitive parasite host for Sarcocystis neurona is the opossum. Like other Sarcocystis spp, in order to complete its life cycle, the parasite must cycle between the opossum and an intermediate host (the intermediate host for Sarcocystis neurona is currently unknown). The horse is thought to be a dead-end or aberrant host; in other words, the horse does not transmit the disease.
Recently, in a small number of horses, EPM has been attributed to infection by Neospora hughesi (in California and Alabama), but whether Neospora hughesi is as epidemiologically important as Sarcocystis neurona has not yet been determined. In some parts of the United States where the opossum is NOT found, such as Arizona, horses that have always lived there may develop EPM and may have a positive blood test for EPM. It is possible that in those cases the disease may be associated with Neospora. Currently, it is believed that Neospora hughesi is not a very common cause of EPM in horses in the United States.
The life cycle of Sarcocystis parasites follows a well-defined life cycle. These parasites exist in two distinct forms: in one form, the parasite "lives" in the lining of the intestine of a carnivore (the "definitive" host). It reproduces at that location and passes infective sporocysts in the feces.
Recently, the carnivore host (in North America) for Sarcocystis neurona has been identified as the opossum (Didelphis virginiana). EPM is also seen in South America (associated with a different species of opossum). EPM is only seen in the Old World in those horses that have been imported from the USA.
All Sarcocystis parasites have an obligate predator-prey life cycle. Opossums are infected by eating sarcocyst-containing muscle tissue from an infected intermediate (prey) host and, after a brief prepatent period, (probably 10 days), infectious sporocysts are passed in the feces.
In order for the parasite to complete its life cycle, the intermediate host must ingest the infective sporocysts by way of a fecally contaminated food source. Once ingested, the sporocyst migrates to the skeletal muscles and can persist there (as a sarcocyst) for many years. The carnivore host (opossum) becomes infected (in its intestinal lining) by eating the skeletal muscles of the secondary host. Obviously, the secondary host has either been killed by the carnivore or has died for other reasons. Of the two classic Sarcocyst hosts, one is a predator, the other is prey.
Opossums eat almost anything, including dead birds and insects. It has been suggested that the intermediate host for Sarcocystis neurona could be a species of bird. It is not surprising that the feces of the opossum represent a rich source of nutrition for wild birds. By eating dead birds (or whatever other animal is shown to be the intermediate host), the opossum enables Sarcocystis neurona to complete its life cycle. Wild birds ingest sporocysts by eating opossum feces. Probably, neither the opossum nor the intermediate host are clinically affected in any way by the presence of a few Sarcocystis parasites - at least not seriously.
Horses may become infected with EPM by eating food material (grain, hay, grass) or drinking water (ponds, streams, water troughs) that has been contaminated by the feces of the opossum, containing infective sporocysts. The horse is infected in the same way as the intermediate host, by ingesting the infective sporocysts. However, unlike the intermediate host, in horses the infective "stages" of the parasite (merozoites are the tissue-invasive stage) migrate into the central nervous system. Even when an infected horse dies, it is unlikely that an opossum (or anything else) would ingest its brain or spinal cord; therefore, the horse is a dead-end host for this parasite. In other words, the horse is not needed for the completion of the parasite's life cycle. EPM is not contagious; Sarcocystis neurona parasites cannot be transmitted from the horse to other animals (including other horses).
Although the exact species that acts as the intermediate host for S. neurona is not currently known, numerous other species (including birds) may assist in the dispersion of infective sporocysts in the environment. Some infective sporocysts may also be passed through the intestinal tract in birds' feces unchanged. Therefore, bird droppings should also be regarded as potentially infective for horses; if this is true, birds are acting as mechanical vectors for dispersion of the infective sporocysts. It has also been suggested that certain insect species (such as cockroaches) might also aid in the mechanical dispersion of infective sporocysts.
The blood test for EPM is not very useful since approximately 50 percent of horses in endemic areas have a positive blood test. A negative blood test provides evidence that the horse may not have been exposed to EPM (but it is not a guarantee). A positive blood test result does not confirm a diagnosis of EPM.
It is necessary to make a thorough effort to rule out other causes of neurological disease in horses, in order to support a diagnosis of EPM (especially to rule out cervical vertebral malformation in young male horses - the "wobbler" syndrome).
The best test currently available requires the collection of a cerebrospinal fluid (CSF) sample that is tested for the presence of antibodies against Sarcocystis neurona; this test is called the western immunoblot, and relies on the fact that, during active EPM disease, antibodies are being produced against S neurona within the spinal cord and brain and can be detected in the CSF. However, an effort must be made to prove that the spinal fluid has not been contaminated with blood. It only takes a tiny quantity of blood contamination to turn a negative CSF test in to a positive ("false positive").
A positive CSF western immunoblot test result is strong evidence that EPM may be the problem if the tested horse if truly demonstrating signs of neurological dysfunction. A positive CSF western immunoblot test result is NOT evidence that EPM is present in horses in which neurological dysfunction cannot be demonstrated. Therefore, it is not recommended that "normal" horses be tested using the western blot on CSF.
All too commonly, neurological symptoms are contrived in order to support the diagnosis of EPM in the face of a positive spinal test result. Although EPM is common in specific geographical locations, the diagnosis must be supported by proper interpretation of the horse's clinical situation and the diagnostic tests that are currently available. There are no logical reasons at the current time to test CSF for EPM in horses that are not demonstrating any signs of neurological dysfunction. A positive CSF test in a non-neurological horse is meaningless.
Collection of CSF can be done at two locations: the lumbo-sacral tap is done in the standing horse at a point just behind where the saddle is located. This procedure requires a specific technique for which veterinarians have been trained. Alternatively, the horse can be anesthetized, and a CSF sample obtained from the cisterna magna, close to the head. The CSF must be stored carefully and submitted promptly to the laboratory. The CSF must arrive in the laboratory in the beginning of the week when it can be processed fresh; it should not be mail-delayed, as the sample might deteriorate.
Both serum and spinal fluid can be frozen to help in submitting the sample to the laboratory.
It is also possible to test CSF for the DNA (genetic material) of S neurona using a PCR test. A positive PCR test is very strong evidence of EPM. However, a negative PCR test does not rule-out EPM. Unfortunately, most cases of EPM tested using PCR are negative.
Another important aspect to establishing the diagnosis includes ruling out other possible causes of similar neurological signs. It should also be remembered that EPM might occur simultaneously with other neurological diseases. The response to treatment (for EPM) might lend further support to the diagnosis of EPM.
Ultimately, an accurate diagnosis of EPM can often be made after an affected horse has died. The veterinary pathologist is able to examine the spinal cord and the brain under the microscope and identify either the protozoal parasites or the characteristic effects of parasite damage. In some cases following death, it is even possible to culture the Sarcocystis neurona parasite from the CNS tissues but this method is not routinely available.
There are three treatment strategies when faced with horses that are likely affected with EPM:
It should be noted that approximately 10 percent of EPM-affected horses become more severely affected immediately following initiation of treatment. This is attributed to the death of parasites and an increase in the immune reaction to dead parasites. This worsening phase, known as a treatment crisis, is usually transient. The veterinarian might use specific anti-inflammatory drugs at this time to minimize the worsening phase.
Currently, there is no evidence that one anti-protozoal drug strategy is better than any other. Certainly, if one strategy has failed to cause any improvement over the course of four weeks, the strategy might be changed or the diagnosis should be re-considered.
Horses should be treated for at least six months. In our experience, the western immunoblot test rarely becomes negative within eight months. If the signs of neurological dysfunction disappear, it is recommended that treatment be continued for at least another four weeks. The treatment may not eliminate the Sarcocystis neurona parasite; it might only constrain the organism until the body is able to neutralize it. Some horses are not able to eliminate the organism, and their problems probably improve because the parasite is inhibited, but they are at risk for further problems if their immune system is compromised again in the future.
Some horses are so severely affected with EPM that they are unable to stand up, even with treatment. Many of these horses are clearly suffering and it is unlikely that, even if they could eventually stand up, they would be able to recover sufficiently to ever be ridden again. It is not possible to treat some horses because the disease has affected the horse's ability to swallow. For those reasons, euthanasia may be considered for those horses.
Note of Caution
It should be strongly cautioned that there are numerous treatments for EPM, many tried unsuccessfully, which have not been tested and have gained popularity simply because they sound "logical." The period that elapses during these unsuccessful treatments allow time for the parasite to do more damage. There is no strong evidence that any one treatment is more effective than another, although one treatment might be better than another in a specific horse. If one treatment selection is ineffective, another drug might be selected by the veterinarian who is managing and monitoring the case.
The prognosis for horses with EPM is variable. Although early diagnosis and prompt therapy help to ensure a good response, irreversible damage to the brain or spinal cord is more likely to occur if the parasite has been present for long periods of time.
Most horses improve with treatment, but relatively few make a complete recovery. Some horses do not respond to treatment at all, and without treatment, many horses eventually deteriorate to the point that they are unable to stand up. A significant number of horses eventually relapse and develop further active EPM.
Some have suggested that 70 percent of EPM-affected horses can return to their original level of work upon completion of treatment.
If treated horses do respond favorably, it appears that they may still be at risk for recurrence of EPM (relapse rate is higher for horses that have been treated for less than three months). The reason for relapse is unknown. Possibly, the anti-protozoal treatment fails to eliminate the parasite but allows the immune system to suppress the parasite. If the immune system is compromised again in the future, further EPM symptoms may develop. Alternatively, for whatever reason the individual horse developed EPM in the first place, there might be an underlying inherent predisposition to this disease that enables the same horse to become affected if challenged again in the future.
Early diagnosis and prompt therapy help to ensure a favorable response. If the horse does not respond to treatment, it is appropriate to also re-consider other possible neurological diseases. If improvement is not noted after four to six weeks of therapy, the prognosis for recovery is relatively poor.
To prevent EPM, every effort should be made to lessen the chances that opossums might interact closely with horses. Certainly, opossums (and birds) should never be tolerated inside barns, in places where horse feed is stored and especially at locations where horses are fed. In addition, minimize vermin and insects (cockroaches), which may potentially act to spread the infective sporocysts.
Horses that are allowed to graze adjacent to or in wooded areas (opossum habitat) are at higher risk. Therefore, whenever possible, this type of land should not be used for horse accommodation.
Opossums might be trapped and removed to distant locations. It is easy to catch opossums in live traps. Two to four traps should be placed around the barn, and the traps can be baited with just about anything. Canned cat food, especially the seafood type, probably works the best.
After trapping opossums, they may be destroyed, or they may be driven miles away and released. Opossums live in a home range of 10 to 50 acres, and they spend their entire lives within that range. Females bear two or three litters per year, usually with two young per litter. Thus, per female, there will be four to six new opossums per year. Please note that trapping and killing opossums might be subject to local law enforcement regulations, so check with local wildlife authorities prior to undertaking a catching and moving operation. The local Department of Conservation will likely be very helpful in this regard.
In addition, the following can also be done to help:
Other possible food sources for opossums include fruit trees, fallen fruit, spoiled meat and garbage. Dead animals should be disposed of expeditiously and not allowed to rot. Food material should NOT be available to opossums in areas where horses are kept. In order to reduce the number of opossums that might be attracted to a horse farm or barn, all uneaten and discarded animal feed should be picked up and cleaned away, spilled grain should not be allowed to accumulate, animal cadavers should be disposed of in an expeditious manner, and fallen fruit should be picked up quickly. Grain, sweet feed, and pelleted feed intended for horses should be thoroughly inspected for possible contamination by opossum feces and stored in air-tight containers (grain bins).
Heat-treated commercial horse rations (such as steam-flaked, pelleted, or extruded feeds) represent a safe source of feed because the infective sporocysts are destroyed by the high temperature. It has not been determined whether cold-processed commercial horse feed is free of sporocysts.
It is fortunate that, although a majority of horses are exposed to Sarcocystis neurona in certain parts of the United States and Canada (leading to a positive blood test for EPM), only a small number of exposed horses actually develop neurological signs. At this time, highly effective preventive measures (such as vaccination) have not been designed and the strategies suggested here are simply logical approaches to management which are largely based on what little we know about the natural history of this parasite and the opossum.
Interestingly, EPM does not appear to affect either donkeys or mules. Out of concern for the problem, horse owners are electing to replace their horses with donkeys and mules.
A vaccine manufacturer has recently announced that a vaccine targeted against Sarcocystis neurona will be available shortly. It should be noted that, at this time, the company has not yet demonstrated that this vaccine is able to protect horses against EPM.