Equine protozoal myeloencephalitis (EPM) is a disease that affects the central nervous system of horses. It is caused by a protozoal infection that is brought about by the

apicomplexa The Apicomplexa (also called Apicomplexia; single: apicomplexan) are organisms of a large phylum of mainly parasitic alveolates. Most possess a unique form of organelle structure that comprises a type of non-photosynthetic plastid called an ap ...

n parasites '' Sarcocystis neurona'' or '' Neospora hughesi''. Most cases are caused by ''S. neurona''. The lifecycle and transmission of ''N. hughesi'' is not well understood. The parasites create lesions in both the brain and spinal cord of the affected horses leading to neurological issues. Most horses infected with ''S. neurona'' do not exhibit neurological symptoms consistent with EPM.

Causes

EPM is caused primarily by the

parasite Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted str ...

''Sarcocystis neurona.'' To complete its lifecycle, ''S. neurona'' requires two

host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places * Host, Pennsylvania, a village in Berks County * Host Island, in the Wilhelm Archipelago, Antarctica People * ...

s: a definitive host, and an intermediate host. The definitive host is the opossum. In North America, the definitive host is the

Virginia opossum The Virginia opossum (''Didelphis virginiana''), also known as the North American opossum, is a member of the opossum family found from southern Canada to northern Costa Rica, making it the northernmost marsupial in the world and the only marsup ...

(''Didelphis virginiana''); South American opossums can also act as the definitive host. A number of mammals can serve as intermediate hosts. In the laboratory,

raccoon The raccoon ( or , ''Procyon lotor''), sometimes called the North American, northern or common raccoon (also spelled racoon) to distinguish it from Procyonina, other species of raccoon, is a mammal native to North America. It is the largest ...

cat The cat (''Felis catus''), also referred to as the domestic cat or house cat, is a small domesticated carnivorous mammal. It is the only domesticated species of the family Felidae. Advances in archaeology and genetics have shown that the ...

armadillo Armadillos () are New World placental mammals in the order (biology), order Cingulata. They form part of the superorder Xenarthra, along with the anteaters and sloths. 21 extant species of armadillo have been described, some of which are dis ...

skunk Skunks are mammals in the family Mephitidae. They are known for their ability to spray a liquid with a strong, unpleasant scent from their anal glands. Different species of skunk vary in appearance from black-and-white to brown, cream or gi ...

s, and

sea otter The sea otter (''Enhydra lutris'') is a marine mammal native to the coasts of the northern and eastern Pacific Ocean, North Pacific Ocean. Adult sea otters typically weigh between , making them the heaviest members of ...

s have been shown to be intermediate hosts of ''S. neurona''. The opossum passes the parasite through feces. Horses contract EPM from contaminated feed or water. Horses cannot pass the disease among themselves; that is, one horse cannot contract the disease from another infected horse. The horse is a dead-end, or aberrant, host of the parasite. Although all horses are believed to be susceptible to EPM the disease is usually found in younger horses typically around three to six years of age. EPM does not typically correlate with other factors such as poor nutrition or other diseases. A study conducted in the US found there was no correlation to the genders of the horses infected nor was there a correlation with the time of year. Six subspecies of ''S. neurona'' can be identified by surface antigens (SAG). Equine EPM is caused by the parasites that exhibit SAG1, SAG5, and SAG6. SAG1 and SAG5 are responsible for the majority of EPM cases in horses. Horses produce antibodies to these surface

antigens In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. An ...

. Serum antibody testing is available that measures levels of these antibodies in the blood of horses, which is helpful in diagnosing EPM in an ataxic horse. Serial blood levels are helpful in guiding treatment. In experimentally infected horses it takes 14 days from infection to positive antibody tests. 80% of horses with EPM have positive antibody tests. A negative antibody test in the presence of EPM results if testing is done before 17 days or if the horse has been treated with antiprotozoal drugs which delays antibody production.

Symptoms

The onset of EPM can come on suddenly or gradually however once the lesion is created it is extremely hard to reverse the damage. The most common symptoms of EPM are

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

, general weakness with muscle spasticity. However, this is not specific to EPM and is common in many other neurological disorders. Clinical signs among horses with EPM include a wide array of symptoms that may result from primary or secondary problems. Apparent lameness, particularly atypical lameness or slight gait asymmetry of the rear limbs are commonly caused by EPM. Focal

muscle atrophy Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakne ...

, or even generalized muscle atrophy or loss of condition may occur. Secondary signs also occur with neurologic disease. Airway abnormalities, such as laryngeal hemiplegia, snoring, or airway noise of undetermined origin may result from damage to the nerves which control the throat, although this is quite uncommon. In experimentally infected horses, very early signs included loss of appetite, decreased tongue tone, facial paresis, altered mental status, generalized weakness, and lameness. ''Sarcocystis neurona'' is thought to not need to enter the CNS to cause disease, in some cases ''S. neurona'' has been found in the CNS, but usually not. In cases where ''S. neurona'' is found in the CNS,

white blood cells White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

probably play a role in the parasite's penetration of the blood-brain barrier.

Diagnosis

Diagnosing EPM can be challenging because the signs can vary significantly from horse to horse, and the symptoms can be similar to those of other CNS diseases. The only way to definitively diagnose EPM is through post-mortem testing, but there are ways to exclude other diseases and establish a basis for the EPM diagnosis. One method is a neurological examination that assesses the CNS function of the horse. Another option is a cervical radiograph, which can identify any compression in the spinal cord that may cause a horse to lose coordination. A veterinarian can also draw blood and spinal fluid and send it to a lab to confirm if a horse has been exposed to opossum feces. Labs can perform immunodiagnostic testing on spinal fluid to evaluate the production of antibodies that fight against these parasites.

Treatment and prevention

EPM is treatable, but irreversible damage to the nervous system is possible. Identifying the disease as early as possible and beginning treatment with antiprotozoal drugs is important. Currently, three FDA approved treatments are available in the US: ReBalance (

sulfadiazine Sulfadiazine is an antibiotic. Used together with pyrimethamine, a dihydrofolate reductase inhibitor, it is the treatment of choice for toxoplasmosis, which is caused by a protozoan parasite. It is a second-line treatment for otitis media, pr ...

and

pyrimethamine Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...

), Marquis ( ponazuril), and Protazil ( diclazuril). These drugs minimize the infection, but do not kill the parasite. The use of anti-inflammatory agents such as banamine, corticosteroids, or phenylbutazone are often used to help reduce inflammation and limit further damage to the CNS. Antioxidants, such as vitamin E, may help promote the restoration of nervous tissue. Response to treatment is often variable, and treatment may be expensive. Recently, antiprotozoal treatments that kill the parasite and clear the infection have shown promise. The inflammatory component is thought responsible for the symptoms of EPM; anti-inflammatory drugs that target the IL-6 pathway have been particularly effective at reversing symptoms. However, there is no vaccine to cure EPM. There are several ways that horse owners can potentially lessen the chances of their horse(s) getting EPM. Some of these preventative measure include proper storage of hay and feed, if possible, not feeding on the ground, reducing wildlife access to stalls and pastures, thoroughly cleaning the horse’s water source often, and prompt disposal of animal carcasses.

History

In the 1960s, a syndrome dubbed "segmental myelitis" was first reported in horses in the US by Rooney and colleagues. Later, in the 1970s, it was recognized by Mayhew and colleagues that the syndrome was associated with an infection by protozoa, and the current name of the disease, "equine protozoal myeloencephalitis", was coined. In 1991, a morphologically distinct parasitic agent was identified in samples taken from horses across the US which had EPM; the parasite was tentatively named ''Sarcocystis neurona''. That same year, ''S. neurona'' was isolated from tissue taken from three infected horses. Following identification of the cause of EPM, in 1993 the first test was developed which could identify antibodies to ''S. neurona'' in the serum of horses. In 1995, the opossum ''Didelphis virginiana'' was first associated with EPM when genetic sequences from ''S. neurona'' were found in the opossum's intestinal contents. The term EPM refers to the clinical neurologic symptoms caused by the parasite, not infection itself.

Causes

Symptoms

Diagnosis

Treatment and prevention

History

References

Further reading