Equine Protozoal Myeloencephalitis

Description

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

Equine protozoal myeloencephalitis, or EPM, is a disease cause by a protozoal infection of the central nervous system of horses.

EPM was discovered in the 1960s by Dr. Jim Rooney. The disease is considered rare, though recently, an increasing number of cases have been reported. Research at the University of Kentucky has labeled the opossum as the definitive host of the disease. . 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.

EPM is caused by the parasite Sarcocystis neurona. In order to complete its life cycle this parasite needs two hosts, a definitive and an intermediate. In the laboratory, raccoons, cats, armadillos, skunks, and sea otters have been shown to be intermediate hosts. The oppossum is the definitive host of the disease. Horses most commonly contract EPM from grazing or watering in areas where an opossum has recently defecated. However, horses cannot pass the disease among themselves. That is, one horse cannot contract the disease from another infected horse. The horse is the dead-end, or aberrant, host of the disease.[1]

Pathogenesis

The actual method by which the Sarcocystis neurona infects a horse is still unknown, however it is thought to preferentially infect leukocytes (white blood cells) in order to cross the blood brain barrier.

Diagnosis

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.

History

Usually an insidious onset ataxia, but the presentation may be acute and severe.

Clinical exam

Typically normal, although focal muscle atrophy may be observed.

Clinical signs

The protozoa can cause lesions sporadically in any part of the CNS which makes the clinical presentation highly variable. The three characteristic 'As' of EPM (ataxia, asymmetry, atrophy) suggest multifocal or diffuse disease, but are not pathognomonic. It has been suggested that rapidly progressive presentations reflect brainstem lesions. Spinal cord signs are most commonly seen and may include:

• asymmetric or symmetric paresis, spasticity and ataxia of one to four limbs
• focal or general muscle atrophy
• apparent lameness
• upward fxation of the patella
• back pain
• loss of condition
• cauda equina signs
• focal regions of inappropriate sweating, loss of reflexes or cutaneous anaesthesia

Lesions of the brainstem, cerebrum or cerebellum are less frequently recognized:

• depression
• head tilt
• dysphagia
• tongue or massetter paralysis
• massetter atrophy
• laryngeal hemiplegia
• dorsal displacement of the soft palate (DDSP)
• seizures (may be the only clinical sign)
• abnormal menace response
• behavioural abnormalities
• head shaking

Without treatment, progression to recumbency and death is likely. This deterioration may occur smoothly or spasmodically over hours to years.

Pathology

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.

Treatment

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.

This disease is curable if caught soon enough and treated with antiprotozoal drugs. There are currently three antiprotozoal treatments available: potentiated sulfonamide medications such as ReBalance, Marquis (ponazuril), and Navigator.

Control of this disease includes a recently released vaccine against the parasite and control of opposums in an area. The vaccine, however, has only been conditionally approved by the USDA until efficacy tests are available.

References

• • Necrotising encephalomyelitis affecting the grey and white matter of the CNS
  • Caused by Sarcocystis neurona
  • Opossum thought to be the definitive host
  • Horses thought to be accidental hosts
  • Natural intermediate hosts currently unknown
  • Western Blotting shows 50% of horses in the USA are seropositive
  • Risk factors poorly understood