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Equine protozoal myeloencephalitis, or EPM, is a disease cause by a protozoal infection of the central nervous system of horses. EPM is one of the most commonly diagnosed neurological diseases of the Western Hemisphere, accounting for around a qaurter of equine neurological cases admitted to two referrral centres in the United States; 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. (Merck) EPM is one of the most commonly diagnosed neurological diseases of the Western Hemisphere, accounting for around a qaurter of equine neurological cases admitted to two referrral centres in the United States; 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. (Furr)

First descrobed 1964 by Dr. Jim Rooney, called segmental myelitis, focal myelitis encephlaitis, toxoplasma-like encephalitis. 1976 Dubey suggested caused by Sarcocystis member.  S.neurona was eventually cultured form spinal cord of affected horse and so namedbecuase it developed within neurons.  This and similar organsism have been cultured form several ataxic horses, zebra, domestic cat, Canadian lynx, sea otter, straw-nekced ibis, mink, raccoon and sunk.  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.

First descrobed 1964 by Dr. Jim Rooney, called segmental myelitis, focal myelitis encephlaitis, toxoplasma-like encephalitis. 1976 Dubey suggested caused by Sarcocystis member.  S.neurona was eventually cultured form spinal cord of affected horse and so namedbecuase it developed within neurons.  This and similar organsism have been cultured form several ataxic horses, zebra, domestic cat, Canadian lynx, sea otter, straw-nekced ibis, mink, raccoon and sunk. (Furr)  

Neospora hughesi has recently been shown to also cause EPM in the horse but is probably reltively unimportant.

 

Neospora hughesi has recently been shown to also cause EPM in the horse but is probably reltively unimportant.(Furr)

====Aetiology and Epidemiology====  

====Aetiology and Epidemiology====  

The average incidence of EPM according ot the United Sattes Department of Agroiculture is around 14 cases per 10,000 horses per year.  The true incidecne is porbbaly underestimated due to the complexity of the clincial dx and difficulty in finding conclusive CNS lesions.  Racing and showing animals have been shown to be at higher risk than beeding and pleasure horses.  EPM is a disease of the Western Hemisphere, with cases outside of the Americas havign spendt time in endemic regions.  The diseas ehas been reporetd in England among horses imported from the Eastern US an din an Arbaian horse in South Africa imported from the US.  The cases demonstarte the porbbaility of persitent, subcliicsal, latent infections.  But a few reports exist of neurological horses with consistent cx, positivew immunoblot test results and no hx of travel in the American continent.  This may be due to cross-reactign Ags.  TBs, SBs and Quarterhorses are most commonly affected across the US and Canada.  this may refelct managemetn, env or use of these breeds rather than an innate breed charcterisitic.

The average incidence of EPM according ot the United Sattes Department of Agroiculture is around 14 cases per 10,000 horses per year.  The true incidecne is porbbaly underestimated due to the complexity of the clincial dx and difficulty in finding conclusive CNS lesions.  Racing and showing animals have been shown to be at higher risk than beeding and pleasure horses.  EPM is a disease of the Western Hemisphere, with cases outside of the Americas havign spendt time in endemic regions.  The diseas ehas been reporetd in England among horses imported from the Eastern US an din an Arbaian horse in South Africa imported from the US.  The cases demonstarte the porbbaility of persitent, subcliicsal, latent infections.  But a few reports exist of neurological horses with consistent cx, positivew immunoblot test results and no hx of travel in the American continent.  This may be due to cross-reactign Ags.  TBs, SBs and Quarterhorses are most commonly affected across the US and Canada.  this may refelct managemetn, env or use of these breeds rather than an innate breed charcterisitic.(Furr)

Most cases of EPM are caused by an Apicomplexan protozoan, [[Sarcocystis|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.

Most cases of EPM are caused by an Apicomplexan protozoan, [[Sarcocystis|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. (Merck)

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]

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](Wikipedia)

====Life Cycle====

====Life Cycle====

====Pathogenesis====

====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.

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. (Wikipedia)

====Signalment====

====Signalment====

Hx (age), Cx (asymmetric multifocal ataxia & weakness), CNS Cx plus positive Western blot of CSF highly suggestive.  Presumptive: treat and rul out others.  Western blot serological test for CSF and serum, 50% horses positive serum.  CSF taps: normal or maybe increased protien & monocytes (pleocytosis).  Post multiple sections of spinal cord: multifocal & asymmetrci, gross: grey-brown dicsoloration, with H+, swelling & liquefaction, histo: nonsuppurative inflammatory focal malacia & H+, perivasucalr cuffing, gliosis, astrocytosis, neuronal necrosis & gitter cell proliferation, multinucleated giant cells.  Parasite in CNS defintiive, schizonts & merozoites at perhoepry of lesions, but may not be demonstarted (Pasq)

Hx (age), Cx (asymmetric multifocal ataxia & weakness), CNS Cx plus positive Western blot of CSF highly suggestive.  Presumptive: treat and rul out others.  Western blot serological test for CSF and serum, 50% horses positive serum.  CSF taps: normal or maybe increased protien & monocytes (pleocytosis).  Post multiple sections of spinal cord: multifocal & asymmetrci, gross: grey-brown dicsoloration, with H+, swelling & liquefaction, histo: nonsuppurative inflammatory focal malacia & H+, perivasucalr cuffing, gliosis, astrocytosis, neuronal necrosis & gitter cell proliferation, multinucleated giant cells.  Parasite in CNS defintiive, schizonts & merozoites at perhoepry of lesions, but may not be demonstarted (Pasq)

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.   

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.  (merck)

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.

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. (Merck)

====Differential Diagnoses====

====Differential Diagnoses====

Verminous encephaltiis

Verminous encephaltiis

Bacterial meningitis

Bacterial meningitis

CNS abscessation

CNS abscessation (Furr)

====History====

====History====

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

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

====Clinical exam====

====Clinical exam====

Typically normal, although focal muscle atrophy may be observed.  

Typically normal, although focal muscle atrophy may be observed. (Wikipedia)

====Clinical signs====

====Clinical signs====

*behavioural abnormalities

*behavioural abnormalities

*head shaking

*head shaking

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

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

====Laboratory tests====

====Laboratory tests====

====Biopsy====

====Biopsy====

====Pathology====

====Pathology====

CNS lesions in the horse often extesnive.  Mutlifocal areas of H+ to light discoloration of brain or spinal cord may be visble on gross exam.  Lesions may be microscopic to several cm wide.  Brasintem and spinal cord affected most often but lesions have been seen in perpheral nerves.  Microscopically lesions are focal to diffuse areas of nonsuppurative inflammation and necrosis with perivascualr infiltration of mononclear cells, including lymphocuytes, macs and plasma cells.  Giant cells, eosinphils and gitter cells are also present in inflamatory infiltrates.  Grey or white matter or both affected.  organsisms have been ofund in neurons, leukocytes and vascualr endothelium, but tend to devlop most often in neurons.

CNS lesions in the horse often extesnive.  Mutlifocal areas of H+ to light discoloration of brain or spinal cord may be visble on gross exam.  Lesions may be microscopic to several cm wide.  Brasintem and spinal cord affected most often but lesions have been seen in perpheral nerves.  Microscopically lesions are focal to diffuse areas of nonsuppurative inflammation and necrosis with perivascualr infiltration of mononclear cells, including lymphocuytes, macs and plasma cells.  Giant cells, eosinphils and gitter cells are also present in inflamatory infiltrates.  Grey or white matter or both affected.  organsisms have been ofund in neurons, leukocytes and vascualr endothelium, but tend to devlop most often in neurons. (Furr)

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.

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.(Merck)

====Treatment====

====Treatment====

Use of sulfadizine in breeding animals contorverisla but one study showed no effect on preganncy rates or EED

Use of sulfadizine in breeding animals contorverisla but one study showed no effect on preganncy rates or EED

Sulfamthoxazole and pyrimethaine caused mild ataxia associated with mounting and ejaculation in a grp of pony stallions

Sulfamthoxazole and pyrimethaine caused mild ataxia associated with mounting and ejaculation in a grp of pony stallions

Ponazuril (Marquis, Bayer Animal Health) - 1st FDA-approved drug for EPM, well absorbed PO, achieves steady state theraeutic concentration in 3days in CSF of hroses treated with 5mg/kg

Ponazuril (Marquis, Bayer Animal Health) - 1st FDA-approved drug for EPM, well absorbed PO, achieves steady state theraeutic concentration in 3days in CSF of hroses treated with 5mg/kg (Furr)

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.  

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. (Merck)

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.   

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.  (Merck)

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.

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.(Wikipedia)

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.

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. (Wikipedia)

====Prognosis====

====Prognosis====

====Prevention====

====Prevention====

Control difficult becasue of widespread distirbution of parasite and variety of intermediate hosts.  Monitor high risk grousp (young and old horses) closely for evidence of neurologic disease to help dtect EPM early.  Neuro disease in wamrer months suspiciois.  Wildlife such as opossums and pests should be denied access to feed, use rodent-proof contianers, protect forages in enclosed faciltiies.  Early diagnosis aided by close monitoring of brrodmares close to foaling and hoirses that dvelop major illness or injury.  Prophylaxis with pronazuril has reduced the incidence and sevrity of cx in one study.  Probably not financially viable but may vbe useful before and during persistentyl stressful events to redcue risk of illness.  Interval tx may also be an option.

Control difficult becasue of widespread distirbution of parasite and variety of intermediate hosts.  Monitor high risk grousp (young and old horses) closely for evidence of neurologic disease to help dtect EPM early.  Neuro disease in wamrer months suspiciois.  Wildlife such as opossums and pests should be denied access to feed, use rodent-proof contianers, protect forages in enclosed faciltiies.  Early diagnosis aided by close monitoring of brrodmares close to foaling and hoirses that dvelop major illness or injury.  Prophylaxis with pronazuril has reduced the incidence and sevrity of cx in one study.  Probably not financially viable but may vbe useful before and during persistentyl stressful events to redcue risk of illness.  Interval tx may also be an option.(Furr)

====References====

====References====