Equine protozoal myeloencephalitis (EPM) is a common neurologic disease of horses in the Americas; it has been reported in most of the contiguous 48 states of the USA, southern Canada, Mexico, and several countries in Central and South America. In other countries, EPM is seen sporadically in horses that previously have spent time in the Americas.
Etiology and Epidemiology
Most cases of equine protozoal myeloencephalitis are caused by an apicomplexan protozoan, Sarcocystis neurona. Horses are infected by ingestion of S neurona sporocysts in contaminated feed or water. The organism undergoes early asexual multiplication (schizogony) in extraneural tissues before parasitizing the CNS. Because infectious sarcocysts are only rarely formed, the horse is considered an aberrant, dead-end host for S neurona. Like other Sarcocystis spp, S neurona has an obligate predator-prey life cycle. The definitive (predator) host for S neurona in the USA is the opossum (Didelphis virginiana). Opossums are infected by eating sarcocyst-containing muscle tissue from an infected intermediate (prey) host and, after a brief prepatent period (probably 2–4 weeks), infectious sporocysts are passed in the feces. Nine-banded armadillos, striped skunks, raccoons, sea otters, Pacific harbor seals, and domestic cats have all been implicated as intermediate hosts; however, the importance in nature of each of these species is unknown.
Sporadic cases of EPM are associated with Neospora hughesi, an organism closely related to S neurona. The natural host(s) of this organism have not yet been identified. Transplacental protozoal transmission with the birth of infected foals has been documented for N hughesi but not for S neurona.
Because the protozoa may infect any part of the CNS, almost any neurologic sign of equine protozoal myeloencephalitis is possible. The disease usually begins insidiously but may present acutely and be severe at onset. Signs of spinal cord involvement are more common than signs of brain disease. Horses with EPM involving the spinal cord have asymmetric or symmetric weakness and ataxia of one to all limbs, sometimes with obvious muscle atrophy. When the sacrocaudal spinal cord is involved, there are signs of cauda equina syndrome. EPM lesions in the spinal cord also may result in demarcated areas of spontaneous sweating or loss of reflexes and cutaneous sensation. The most common signs of brain disease in horses with EPM are depression, head tilt, and facial paralysis. Any cranial nerve nucleus may be involved, and there may be seizures, visual deficits including abnormal menace responses, or behavioral abnormalities. Without treatment, EPM may progress to cause recumbency and death. Progression to recumbency occurs over hours to years and may occur steadily or in a stop-start fashion.
With EPM, there is focal discoloration, hemorrhage, and/or malacia of CNS tissue. Histologically, protozoa may be found in association with a mixed inflammatory cellular response and neuronal destruction. Schizonts, in various stages of maturation, or free merozoites commonly are seen in the cytoplasm of neurons or mononuclear phagocytes. Also parasitized are intravascular and tissue neutrophils and eosinophils and, more rarely, capillary endothelial cells and myelinated axons. Merozoites may be found extracellularly, especially in areas of necrosis. In at least 75% of clinical cases, protozoa are not seen on H&E-stained sections.
Based on neurologic signs, elimination of competing diagnoses, and serology
Postmortem diagnosis of equine protozoal myeloencephalitis is confirmed by demonstration of protozoa in CNS lesions on the basis of distinctive morphology or by immunohistochemical staining. Testing for S neurona–specific antibody is the basis for presumptive antemortem diagnosis of EPM. Serologic tests for specific antibodies against whole S neurona or N hughesi (eg, indirect fluorescent antibody test) or protozoal surface antigens provide evidence of current or previous exposure to the organism; thus, low or negative serum titers tend to exclude the diagnosis of EPM. Conversely, positive or high serum S neurona titers have limited diagnostic utility in that such titers do not clearly distinguish horses with subclinical extraneural infections from those with EPM. In horses with neurologic signs, serum:CSF antibody titer ratios of <1:100 or C-ratios >1 are indicative of production of S neurona antibody in the CNS and are highly supportive of the diagnosis of EPM. In a few horses with EPM, CSF analysis reveals abnormalities such as mononuclear pleocytosis and high protein concentration.
Depending on the clinical signs, differential diagnoses may include:
cervical vertebral stenotic myelopathy
aberrant parasite migration
equine herpesvirus 1 myeloencephalopathy
equine motor neuron disease
cauda equina neuritis
arboviral (Eastern or Western equine, West Nile) encephalomyelitis Overview of Equine Arboviral Encephalomyelitis Equine encephalitides can be clinically similar, usually cause diffuse encephalomyelitis ( see Meningitis, Encephalitis, and Encephalomyelitis) and meningoencephalomyelitis, and are characterized... read more
Antiprotozoal drugs and immunomodulators
The FDA-approved treatments for EPM are ponazuril (5 mg/kg/day, PO, for 28 days), diclazuril (1 mg/kg/day, PO, for 28 days), and a combination of sulfadiazine and pyrimethamine (20 mg/kg and 1 mg/kg, respectively, for at least 90 days). The bioavailabilities of ponazuril and diclazuril are improved by concurrent PO administration of corn oil or DMSO. A loading dose of ponazuril (15 mg/kg, PO) may be given on the first day of treatment to rapidly attain therapeutic blood levels. The sulfadiazine/pyrimethamine product must be given at least 1 hour before or after hay is fed. Anemia Anemia in Animals Anemia is an absolute decrease in RBC numbers, hemoglobin concentration, or PCV. Signs include pale mucous membranes, increased heart rate, and hypotension. Diagnosis can be made by CBC, but... read more may develop after prolonged treatment with sulfadiazine/pyrimethamine and is best prevented by providing folate-rich green forage such as alfalfa hay or green pasture.
Approximately 60% of horses improve with each type of treatment, but <25% recover completely. Relapses occur commonly up to 2 years after discontinuation of antiprotozoal therapy. Because immunosuppression/immunodeficiency may be a risk factor for EPM, immunomodulators (eg, mycobacterial cell-wall derivative, levamisole, killed parapoxvirus ovis, or transfer factor) are sometimes given as ancillary therapy.
Prevention and Control
No proven preventive is available. A conditionally approved vaccine was marketed, but the license lapsed in 2008, and the vaccine is no longer offered. There is interest in using antiprotozoal drugs for prevention, and it has been shown that daily diclazuril prevents foals from seroconverting against S neurona and N hughesi. Evidence-based protocols for preventive use of antiprotozoal drugs are not yet available. The source of infective sporocysts is opossum feces, so it is prudent to prevent access of opossums to horse-feeding areas. Horse and pet feed should not be left out; open feed bags and garbage should be kept in closed galvanized metal containers, bird feeders should be eliminated, and fallen fruit should be removed. Opossums can be trapped and relocated. Because putative intermediate hosts cannot be directly infective for horses, it is unlikely that control of these populations will be useful in EPM prevention.
EPM is a common cause of neurologic disease of horses in the Americas.
Diagnosis is based on a combination of neurologic signs and serologic tests.
Antiprotozoal drugs improve clinical signs in most horses, but complete recovery occurs less commonly, and clinically recovered horses may suffer relapses.
There is no vaccine for EPM.
For More Information
Also see pet health content regarding equine protozoal myeloencephalitis Equine Protozoal Myeloencephalitis Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses that occurs in endemic form in the Americas and sporadically in other countries. The endemic form is caused by ingesting... read more .