Equine Protozoal Myeloencephalitis: Introduction

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 is assumed to undergo early asexual multiplication (schizogony) in extraneural tissues before parasitizing the CNS. Because infectious sarcocysts are not 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 believed to be 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 ωκ), 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.

Clinical Findings:

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 response, or behavioral abnormalities. Without treatment, EPM often progresses to cause recumbency and death. Progression to recumbency occurs over hours to years and may occur steadily or in a stop-start fashion.

Lesions:

There is focal discoloration, hemorrhage, and/or malacia of CNS tissue. Histologically, protozoa are 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 cases, protozoa are not seen on H&E-stained sections, and the diagnosis is made on the basis of characteristic focal or multifocal inflammatory change.

Diagnosis:

Postmortem diagnosis is confirmed by demonstration of protozoa in CNS lesions. An immunoblot (Western blot) test for S neurona is used as an aid to antemortem diagnosis. In horses with neurologic signs, demonstration of specific antibody in CSF (by immunoblot) is highly suggestive of EPM. A positive immunoblot test in serum only indicates exposure to S neurona . Conversely, a negative immunoblot result, 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.

Treatment and Control:

The only FDA-approved treaments for EPM are ponazuril (5 mg/kg, PO, sid for 28 days) and nitazoxanide (50 mg/kg, PO, sid for 28 days), both as paste formulations. An alternative approach is the use of antifolate drugs, eg, sulfadiazine, or sulfamethoxazole (15-25 mg/kg, PO, sid-bid) in combination with pyrimethamine (1 mg/kg, PO, sid). The sulfonamide can be given with or without trimethoprim. Pyrimethamine must be given at least 1 hr before or after hay is fed. Treatment is usually continued for 6 mo. Anemia may develop after prolonged treatment with antifolate drugs and is best prevented by provision of high quantities of green forage. At least 60% of horses improve with treatment, but <25% recover completely. Relapses are common in horses that remain positive on immunoblot and rare in those that become negative.

No proven preventive is available. A conditionally approved vaccine is marketed, and its efficacy continues to be evaluated. 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.