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, and several countries in Central and South America. In other countries, EPM is seen sporadically.
Etiology and Epidemiology
Most cases of EPM 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. All Sarcocystis spp have an obligate predator-prey life cycle. The definitive (predator) host for S neurona 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 wk), 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. A few cases of EPM, both in the Americas and Europe, are associated with Neospora hughesi, an organism that is closely related to S neurona. The natural host(s) of this organism have not yet been identified.
Because the protozoa may infect any part of the CNS, almost any neurologic sign 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 caudal 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.
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.
Postmortem diagnosis is confirmed by demonstration of protozoa in CNS lesions on the basis of distinctive morphology or by immunohistochemical staining. Immunoblot (Western blot) and indirect fluorescent antibody (IFAT) tests for S neurona are used as aids to antemortem diagnosis. In horses with neurologic signs, demonstration of specific antibody in CSF by either technique is suggestive of EPM. A positive immunoblot test in serum only indicates exposure to S neurona; however serum IFAT titers >1:100 correlate well with the presence of EPM. Conversely, a negative immunoblot result or low IFAT titer, in either serum or CSF, tends to exclude the diagnosis of EPM. In a few horses with EPM, CSF analysis reveals abnormalities such as mononuclear pleocytosis and increased protein concentration.
Depending on the clinical signs, differential diagnoses may include cervical stenotic myelopathy, trauma, aberrant metazoan parasite migration, equine degenerative myeloencephalopathy, myeloencephalopathy caused by equine herpesvirus 1, equine motor neuron disease, neuritis of the cauda equina, arboviral (Eastern or Western equine, West Nile) encephalomyelitis, rabies, bacterial meningitis, and leukoencephalomalacia.
The FDA-approved treatments for EPM are ponazuril (5 mg/kg, PO, sid for 28 days), nitazoxanide (25 mg/kg for 5 days, then 50 mg/kg, PO, sid for 23 days), and a combination of sulfadiazine and pyrimethamine (20 mg/kg and 1 mg/kg, respectively, for at least 90 days). Diclazuril is also approved, but no product has been marketed. The bioavailability of ponazuril and nitazoxanide is improved by concurrent PO administration of an ounce of corn oil with each treatment. The sulfadiazine/pyrimethamine product must be given at least 1 hr before or after hay is fed. Anemia may develop after prolonged treatment with sulfadiazine/pyrimethamine and is best prevented by providing high quantities of green forage. About 60% of horses improve with each treatment, but <25% recover completely. Relapses occur commonly up to 2 yr after discontinuation of antiprotozoal therapy. Because EPM may be associated with immunosuppression, immunostimulants (eg, mycobacterial cell-wall derivative or levamisole) 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 March 2008 and it is no longer offered. There is interest in using antiprotozoal drugs for prevention; however, evidence-based protocols are not yet available. The source of infective sporocysts is probably 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.
Last full review/revision July 2011 by Robert J. Mackay, BVSc, PhD