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==Introduction==

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A progressive, infectious,<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>neurological disease of horses, endemic in the USA<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref> and only encountered elsewhere in equids that have travelled in the Americas.<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref>  Equine protozoal myeloencephalitis (EPM) is one of the most frequently diagnosed neurological conditions in the Western Hemisphere<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> and the principal differential for multifocal, asymmetric progressive central nervous system (CNS) disease.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>  The disease is not contagious.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''', (Third edition), ''SUDZ Publishing'', 245-250.</ref>

 

 

==Description==

A progressive, infectious,<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>neurological disease of horses, endemic in the USA<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref> and only encountered elsewhere in imported equids.<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref>  EPM is one of the most frequently diagnosed neurological conditions of the Western Hemisphere<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> and the principal differential for multifocal, asymmetric progressive central nervous system (CNS) disease.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>  As it can resemble any neurological disorder, EPM must be considered in any horse with neurological signs if it resides in the Americas or if it has been imported from that area<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref><ref name="EPM9">DEFRA, The Animal Health Trust, The British Equine Veterinary Association (2009) Surveillance: Equine disease surveillance, April to June 2009, ''The Vet Rec'', Oct 24:489-492.</ref>  The disease is not contagious.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''', (Third edition), ''SUDZ Publishing'', 245-250.</ref>

==Aetiology==

==Aetiology==

EPM results from infection of the CNS by the apicomplexan parasite ''Sarcocystis neurona'' or, less frequently, its close relative ''Neospora hughesi''.<ref>Dubey, J.P, Lindsay, D.S, Saville, W.J, Reed, S.M, Granstrom, D.E, Speer, C.A (2001)A review of ''Sarcocystis neurona'' and equine protozoal myeloencephalitis (EPM). ''Vet Parasitol'', 95:89-131. In: Pusterla, N, Wilson, W.D, Conrad, P.A, Barr, B.C, Ferraro, G.L, Daft, B.M, Leutenegger, C.M (2006) Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy.  ''Vet Rec'', Sep 9:''Papers & Articles''.</ref><ref>Wobeser, B.K, Godson, D.L, Rejmanek, D, Dowling, P (2009) Equine protozoal myeloencephalitis caused by ''Neospora hughesi'' in an adult horse in Saskatchewan.  ''Can Vet J'', 50(8):851-3.</ref>  These protozoans develop within neurons<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  causing immediate or inflammatory-mediated neuronal damage.  The organisms migrate randomly through the brain and spinal cord causing asymmetrical lesions of grey and white matter and thus multifocal lower and upper motor neuron deficits.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

EPM results from infection of the CNS by the apicomplexan parasite [[Sarcocystis|''Sarcocystis neurona'']] or, less frequently, its close relative [[Neospora|''Neospora hughesi'']].<ref>Dubey, J.P, Lindsay, D.S, Saville, W.J, Reed, S.M, Granstrom, D.E, Speer, C.A (2001)A review of ''Sarcocystis neurona'' and equine protozoal myeloencephalitis (EPM). ''Vet Parasitol'', 95:89-131. In: Pusterla, N, Wilson, W.D, Conrad, P.A, Barr, B.C, Ferraro, G.L, Daft, B.M, Leutenegger, C.M (2006) Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy.  ''Vet Rec'', Sep 9:''Papers & Articles''.</ref><ref>Wobeser, B.K, Godson, D.L, Rejmanek, D, Dowling, P (2009) Equine protozoal myeloencephalitis caused by ''Neospora hughesi'' in an adult horse in Saskatchewan.  ''Can Vet J'', 50(8):851-3.</ref>  These protozoans develop within neurons<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  causing immediate or inflammatory-mediated neuronal damage.  The organisms migrate randomly through the brain and spinal cord causing asymmetrical lesions of grey and white matter and thus multifocal lower and upper motor neuron deficits.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

==Epidemiology==

==Epidemiology==

In endemic areas of the United States, around a quarter of referrals for equine neurological disease are attributed to EPM.<ref>Reed, S.M, Granstrom, D, Rivas, L.J, Saville, W.A, Moore, B.R, Mitten, L.A (1994) Results of cerebrospinal fluid analysis in 119 horses testing positive to the Western blot test on both serum and CSF to equine protozoal encephalomyelitis.  In ''Proc Am Assoc Equine Pract'', Vancouver BC, AEEP, Lexington, KY, p199.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  According to the United States Department of Agriculture, the average incidence of the disease is 14 cases per 10,000 horses per year.  However, the challenges of obtaining a definitive diagnosis may mean this figure is an underestimate.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  The disease has been identified in parts of Central and South America, southern Canada and across most of the USA..<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> EPM is noted occasionally in other countries, in horses that have been imported from the Americas.<ref>Pitel, P.H, Pronost, S, Gargala, G, Anrioud, D, Toquet, M-P, Foucher, N, Collobert-Laugier, C, Fortier, G, Ballet, J-J (2002) Detection of ''Sarcocystis neurona'' antibodies in French horses with neurological signs, ''Int J Parasitol'', 32:481-485.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref><ref>Goehring, L.S (2001) Sloet van Oldruitenborgh-Oosterbaan MM: Equine protozoal myeloencephalitis in the Netherlands?  An overview, ''Tijdschr Diergeneeskd'', 126:346-351.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  It is likely that these animals underwent transportation carrying a silent but persistent infection.  There have been reports of EPM in horses that have not travelled to or from endemic regions,<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> although cross-reacting antigens on the immunoblot test may explain this discrepancy. <ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

In endemic areas of the United States, around a quarter of referrals for equine neurological disease are attributed to EPM.<ref>Reed, S.M, Granstrom, D, Rivas, L.J, Saville, W.A, Moore, B.R, Mitten, L.A (1994) Results of cerebrospinal fluid analysis in 119 horses testing positive to the Western blot test on both serum and CSF to equine protozoal encephalomyelitis.  In ''Proc Am Assoc Equine Pract'', Vancouver BC, AEEP, Lexington, KY, p199.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  According to the United States Department of Agriculture, the average incidence is 14 cases per 10,000 horses per year.  However, the challenges of obtaining a definitive diagnosis may mean this figure is an underestimate.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  EPM has been identified in parts of Central and South America, southern Canada and across most of the USA.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> The disease is noted occasionally in other countries, in horses that have been imported from endemic regions.<ref>Pitel, P.H, Pronost, S, Gargala, G, Anrioud, D, Toquet, M-P, Foucher, N, Collobert-Laugier, C, Fortier, G, Ballet, J-J (2002) Detection of ''Sarcocystis neurona'' antibodies in French horses with neurological signs, ''Int J Parasitol'', 32:481-485.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref><ref>Goehring, L.S (2001) Sloet van Oldruitenborgh-Oosterbaan MM: Equine protozoal myeloencephalitis in the Netherlands?  An overview, ''Tijdschr Diergeneeskd'', 126:346-351.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  It is likely that these animals carried a silent but persistent infection during transportation.  There have been reports of EPM in horses that have not travelled to or from endemic regions,<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> although cross-reacting antigens in immunodiagnostic tests may explain this discrepancy. <ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

The route of infection remains unconfirmed,<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> but there is an increased risk associated with a young age (1-4 years)<ref>Saville, W.J.A, Reed, S.M, Granstrom, D.E, Morley, P.S (1997) Some epidemiologic aspects of equine protozoal

The route of infection remains unconfirmed,<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> but there is an increased risk associated with a young age (1-4 years)<ref>Saville, W.J.A, Reed, S.M, Granstrom, D.E, Morley, P.S (1997) Some epidemiologic aspects of equine protozoal myeloencephalitis.  ''Proceedings of the Annual Convention of the AAEP'', 43:6-7.</ref>and autumn months.<ref name="NAHMS">NAHMS (2000): ''Equine protozoal myeloencephalitis in the US'', Ft Collins, CO, USDA:APHIS:VS, CEAH, National Animal Health Monitoring System.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  The reported age range for EPM cases is currently 2 months<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref> to 24 years.<ref>MacKay, R.J, Davis, S.W, Dubey, J.P (1992) Equine protozoal myeloencephalitis, ''Compend Contin Educ Pract Vet'', 14:1359-1367.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Thoroughbreds, Standardbreds and Quarterhorses are most frequently affected across the US and Canada.<ref>Fayer, R, Mayhew, I.G, Baird, J.D, Dill, S.G, Foreman, J.H, Fox, J.C, Higgins, R.J Higgins, Reed, S.M, Ruoff, W.W, Sweeney, R.W, Tuttle, P (1990) Epidemiology of equine protozoal myeloencephalitis in North America based on histologically confirmed cases, ''J Vet Intern Med'', 4:54-57.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  This may relate to a breed predispostion or alternatively, managemental factors associated with these breeds.<ref>Boy, M.G, Galligan, D.T, Divers, T.J (1990) Protozoal encephalomyelitis in horses: 82 cases (1972-1986), ''J Am Vet Med Assoc'', 196:632-634.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Showing and racing have been linked to a greater risk of clinical disease.<ref>Saville, W.J.A, Reed, S.M, Morley, P.S (1999) Examination of risk factors for equine protozoal myeloencephalitis.  ''Proceedings of the Annual Convention of the AAEP'', 45:48-49.</ref> Increasing age and environmental temperature have been associated with an increased seroprevalence of ''S. neurona''.<ref>Tillotson, K, McCue, P.M, Granstrom, D.E, Dargatz, D.A, Smith, M.O, Traub-Dargatz, J.L (1999) Seroprevalence of antibodies to ''Sarcocystis neurona'' in horses residing in northern Colorado, ''J Equine Vet Sci'', 19:122-126.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Seroprevalence for this species is typically higher than for ''N. hughesi''.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>Other risk factors for EPM include the presence of opossums, rats, mice and woodland, increased population density of humans and horses, bedding horses on shavings or wood chips and the use of purchased grain.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>Case clustering may operate where all the risk factors occur, but the majority of cases appear in isolation.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

myeloencephalitis.  ''Proceedings of the Annual Convention of the AAEP'', 43:6-7.</ref>and autumn months.<ref>NAHMS (2000): ''Equine protozoal myeloencephalitis in the US'', Ft Collins, CO, USDA:APHIS:VS, CEAH, National Animal Health Monitoring System.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  The reported age range for EPM cases is currently 2 months<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref> to 24 years.<ref>MacKay, R.J, Davis, S.W, Dubey, J.P (1992) Equine protozoal myeloencephalitis, ''Compend Contin Educ Pract Vet'', 14:1359-1367.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Thoroughbreds, Standardbreds and Quarterhorses are most frequently affected across the US and Canada.<ref>Fayer, R, Mayhew, I.G, Baird, J.D, Dill, S.G, Foreman, J.H, Fox, J.C, Higgins, R.J Higgins, Reed, S.M, Ruoff, W.W, Sweeney, R.W, Tuttle, P (1990) Epidemiology of equine protozoal myeloencephalitis in North America based on histologically confirmed cases, ''J Vet Intern Med'', 4:54-57.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  This may relate to a breed predispostion or alternatively, managemental factors associated with these breeds.<ref>Boy, M.G, Galligan, D.T, Divers, T.J (1990) Protozoal encephalomyelitis in horses: 82 cases (1972-1986), ''J Am Vet Med Assoc'', 196:632-634.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Showing, racing and stress<ref name="Saville">Saville, W.J, Reed, S.M, Morley, P.S, Granstrom, D.E, Kohn, C.W, Hinchcliff, K.W, Wittum, T.E (2000) Analysis of risk factors for the development of equine protozoal myeloencephalitis in horses.  ''J Am Vet Med Assoc'', 217:1174-1180.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> have been linked to a greater risk of clinical disease.<ref>Saville, W.J.A, Reed, S.M, Morley, P.S (1999) Examination of risk factors for equine protozoal

myeloencephalitis.  ''Proceedings of the Annual Convention of the AAEP'', 45:48-49.</ref>  

 

Increasing age and environmental temperature have been associated with an increased seroprevalence of ''S. neurona''.<ref>Tillotson, K, McCue, P.M, Granstrom, D.E, Dargatz, D.A, Smith, M.O, Traub-Dargatz, J.L (1999) Seroprevalence of antibodies to ''Sarcocystis neurona'' in horses residing in northern Colorado, ''J Equine Vet Sci'', 19:122-126.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Seroprevalence for this species is typically higher than for ''N. hughesi''.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>Other risk factors for EPM include the presence of opossums, rats, mice and woodland, increased population density of humans and horses, bedding horses on shavings or wood chips and the use of purchased grain.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>Case clustering may operate where all the risk factors occur, but the majority of cases appear in isolation.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

==Life Cycle==

==Life Cycle==

[[Image:Equine_Protozoal_Myeloencephalitis_life_cycle.jpg|600px|thumb|centre|''' Life cycle diagram of ''Sarcocystis neurona''.  Created by the ''Agricultural Research Service, the research agency of the United States Department of Agriculture'', July 2005.  ''Sourced from the USDA Agricultural Research Service page on EPM/Sarcocystis neurona, located via WikiMedia Commons.'' ''']]

[[Image:Equine_Protozoal_Myeloencephalitis_life_cycle.jpg|600px|thumb|centre|''' Life cycle diagram of ''Sarcocystis neurona''.  Created by the ''Agricultural Research Service, the research agency of the United States Department of Agriculture'', July 2005.  ''Sourced from the USDA Agricultural Research Service page on EPM/Sarcocystis neurona, located via WikiMedia Commons.'' ''']]

See [[Sarcocystis|here]] for further details of the life cycle of ''Sarcocystis neurona''.

Infective sporocysts are passed in the faeces of the definitive host and must be ingested by the horse for infection to occur.  See [[Sarcocystis|the ''Sarcocystis'' page]] for further details of the life cycle of ''S.neurona''.

The causative pathogen(s) have been isolated from species other than the horse including zebra, domestic cat, Canadian lynx, sea otter, straw-necked ibis, mink, raccoon and sunk. (Furr)

 

Immune clearance of ''S.neurona'' must be, in the large part, very effective, since less than 1% of horses exposed to the protozoan suffer from EPM.<ref name="NAHMS">NAHMS (2000): ''Equine protozoal myeloencephalitis in the US'', Ft Collins, CO, USDA:APHIS:VS, CEAH, National Animal Health Monitoring System.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Both humoral and cell-mediated immune mechanisms are likely to be significant in the host defence against ''S.neurona''.  Antibodies are produced soon after infection and offer some degree of protection.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  CD8 positive T-cells and their production of IFN-γ are likely to be pivotal in the removal of intracellular stages of the parasite.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>Factors which promote disease development include parasite dose<ref>Sofaly, C.D, Reed, S.M, Gordon, J.C, Dubey, J.P, Oglesbee, M, Njoku, D, Grover, C, Saville, W.J.A (2002) Experimental induction of equine protozoal myeloencephalitis (EPM) in the horse: effect of ''Sarcocystis neurona'' sporocyst inoculation dose on the development of clinical neurological disease, J Parasitol, 88:1164-1170.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>and, most probably virulence of the protozoal strain.  Stress induced by pregnancy, travel, training and showing<ref name="Saville">Saville, W.J, Reed, S.M, Morley, P.S, Granstrom, D.E, Kohn, C.W, Hinchcliff, K.W, Wittum, T.E (2000) Analysis of risk factors for the development of equine protozoal myeloencephalitis in horses.  ''J Am Vet Med Assoc'', 217:1174-1180.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> may have an immunosuppressive effect that encourages infection.  Indeed, it has been shown that stress affects the severity of clinical signs seen in natural infections.<ref>Njoku, C.J, Saville, W.J, Reed, S.M, Oglesbee, M.J, Rajala-Schultz, P.J, Stich, R.W (2002) Reduced levels of nitric oxide  metabolites in cerebrospinal fluid are associated with equine protozoal myeloencephalitis, ''Clin Diagn Lab Immunol'', 9:605-610.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

 

The 'Trojan horse' hypothesis suggests that ''S.neurona'' meroziotes traverse the blood brain barrier encrypted within leucocytes that have phagocytosed the parasite in the periphery.  Once inside the CNS, eggression and infection of other cells results in encephalitis.<ref>Lindsay, D.S, Mitchell, S.M, Yang, J, Dubey, J.P, Gogal, R.M, Jr, Witonsky, S.G (2006) Penetration of equine leukocytes by merozoites of ''Sarcocystis neurona''.  ''Vet Parasitol'', 15:138(3-4):371-6</ref>  Other theories include haematogenous spread or direct passage of parasites via the cytoplasm of endothelial cells into the CNS.  However, despite extensive histological lesions, few organisms are typically visible in the neural tissues of affected horses.  This implies that cytokines may have a considerable role in producing pathological changes.<ref>Pusterla, N, Wilson, W.D, Conrad, P.A, Barr, B.C, Ferraro, G.L, Daft, B.M, Leutenegger, C.M (2006) Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy, ''Vet Rec'', 159:341-346.</ref>  Although the protozoan may induce some degree of immunosuppression in the host<ref>Spencer, J.A, Ellison, S.E, Guarino, A.J, Blagburn, B.L (2004) Cell-mediated immune responses in horses with equine protozoal myeloencephalitis.  ''J Parasitol'', 90(2):428-30.</ref><ref>Yang, J, Ellison, S, Gogal, R, Norton, H, Lindsay, D.S, Andrews, F, Ward, D, Witonsky, S (2006) Immune response to Sarcocystis neurona infection in naturally infected horses with equine protozoal myeloencephalitis.  ''Vet Parasitol'', 138(3-4):200-10.</ref>, it is likely that the immune-privilege of the CNS prevents parasite clearance from this site.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>.  The methods by which ''S.neurona'' and ''N.hughesi'' cause EPM is still debated.

==Signalment==

==Signalment==

==Diagnosis==

==Diagnosis==

===Differential Diagnoses===

===Differential Diagnoses===

The protozoan can migrate to any region of the CNS<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref>, thus the differential list comprises almost all diseases of this system.

''S.neurona'' can migrate to any region of the CNS<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Rec'', 149:269-273.</ref>, thus the differential list comprises almost all diseases of this system.

{| cellpadding="10" cellspacing="0" border="1"  

{| cellpadding="10" cellspacing="0" border="1"  

|Plain lateral radiography of C1 to T1<ref name="Hahn">Hahn, C.N (2010) ''Cervical Vertebral Malformation'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, myelography. <ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>

|Plain lateral radiography of C1 to T1<ref name="Hahn">Hahn, C.N (2010) ''Cervical Vertebral Malformation'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, myelography. <ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>

|-

|-

|West Nile encephalitis

|[[West Nile Virus|West Nile encephalitis]]

|Systemically ill, pyrexia.  Difficult to differentiate if horse is afebrile and has no excessive muscle fasciculations.<ref name="Long">Long, M.T (2010) ''Flavivirus Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Systemically ill, pyrexia.  Difficult to differentiate if horse is afebrile and has no excessive muscle fasciculations.<ref name="Long">Long, M.T (2010) ''Flavivirus Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Leukogram, CSF analysis, IgM capture ELISA, plaque reduction neutralization test (PRNT),<ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>absence of mosquito vectors.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

|Leukogram, CSF analysis, IgM capture ELISA, plaque reduction neutralization test (PRNT),<ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>absence of mosquito vectors.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

|Leukogram, IgM ELISA<ref>Bertone, J.J (2010) ''Viral Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|Leukogram, IgM ELISA<ref>Bertone, J.J (2010) ''Viral Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|-

|-

|Equine herpesvirus-1 myeloencephalopathy  

|[[Equine Herpesvirus 1|Equine herpesvirus-1 myeloencephalopathy]]

|Sudden onset and early stabilization of neurological signs, multiple horses affected, recent fever, respiratory disease, abortion.<ref>Wilson, W.D, Pusterla, N (2010) ''Equine Herpesvirus-1 Myeloencephalopathy'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Dysuria not often seen in EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|Sudden onset and early stabilization of neurological signs, multiple horses affected, recent fever, respiratory disease, abortion.<ref>Wilson, W.D, Pusterla, N (2010) ''Equine Herpesvirus-1 Myeloencephalopathy'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Dysuria not often seen in EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|CSF analysis, buffy coat, nasal swab PCR.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref><ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>

|CSF analysis, buffy coat, nasal swab PCR.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref><ref name="Seino">Seino, K.K (2010) ''Spinal Ataxia'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 3.</ref>

|-

|-

|Rabies

|[[Rabies]]

|Rapid progression<ref name="Sommardahl">Sommardahl, C.S (2010) ''Rabies'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, behavioural alterations, depression, seizure, coma.<ref name="Long">Long, M.T (2010) ''Flavivirus Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Rapid progression<ref name="Sommardahl">Sommardahl, C.S (2010) ''Rabies'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, behavioural alterations, depression, seizure, coma.<ref name="Long">Long, M.T (2010) ''Flavivirus Encephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Post-mortem fluorescent antibody testing of brain required for definitive diagnosis.<ref name="Sommardahl">Sommardahl, C.S (2010) ''Rabies'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Post-mortem fluorescent antibody testing of brain required for definitive diagnosis.<ref name="Sommardahl">Sommardahl, C.S (2010) ''Rabies'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  

|Bacterial meningoencephalitis

|Bacterial meningoencephalitis

|Stiff neck.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

|Stiff neck.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

|

|CSF analysis and culture.  '''NB: CSF collection contraindicated if clinical signs suggest high intracranial pressure'''

|-

|-

|CNS abscessation due to 'bastard strangles'<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|CNS abscessation due to [[Streptococcus equi subsp. equi|'bastard strangles]]'<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|History of ''Streptococcus equi subsp. equi'' infection.<ref name="Byrne">Byrne, B. A (2010) ''Diseases of the Cerebellum'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|History of [[Streptococcus equi subsp. equi|''Streptococcus equi subsp. equi'']] infection.<ref name="Byrne">Byrne, B. A (2010) ''Diseases of the Cerebellum'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|CSF analysis (severe, suppurative inflammation), culture of CSF.<ref name="Byrne">Byrne, B. A (2010) ''Diseases of the Cerebellum'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|CSF analysis (severe, suppurative inflammation), culture of CSF.<ref name="Byrne">Byrne, B. A (2010) ''Diseases of the Cerebellum'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

|-

|-

|-

|-

|''Sorghum'' cystitis/ataxia<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

|''Sorghum'' cystitis/ataxia<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

|Posterior ataxia or paresis, cystitis, history of grazing ''Sorghum'' species<ref>Talcott, P (2010) ''Toxicoses causing signs relating to the urinary system'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 22.</ref>

|Posterior ataxia or paresis, cystitis, history of grazing ''Sorghum'' species<ref name="Talcott">Talcott, P (2010) ''Toxicoses causing signs relating to the urinary system'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 22.</ref>

|Demonstration of cystitis or pyelonephritis by laboratory methods, but not specific.<ref>Talcott, P (2010) ''Toxicoses causing signs relating to the urinary system'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 22.</ref>

|Demonstration of cystitis or pyelonephritis by laboratory methods, but not specific.<ref name="Talcott">Talcott, P (2010) ''Toxicoses causing signs relating to the urinary system'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 22.</ref>

|}

|}

[[Image:Equine_Protozoal_Myeloencephalitis.jpg|600px|thumb|left|''' Sarcocystis neurona stages and lesions.  

 

[[Image:Equine_Protozoal_Myeloencephalitis.jpg|600px|thumb|right|''' Sarcocystis neurona stages and lesions.  

(A). Cross section of spinal cord of horse with focal areas of discoloration (arrows) indicative of necrosis. Unstained.  

(A). Cross section of spinal cord of horse with focal areas of discoloration (arrows) indicative of necrosis. Unstained.  

==Treatment==

==Treatment==

===Antiprotozoals===

===Antiprotozoals===

Ponazuril (Marquis, Bayer Animal Health) - 1st FDA-approved drug for EPM, well absorbed PO, achieves steady state therapeutic concentration in 3days in CSF of horses (100 in Furr).  In filed efficacy study improvement bny at least one clincal gradein 60%, 8% relase after 90days of stopping treatment (91 in Furr), resposne wihtin 10days. V safe, no sstemci toxicity even at high doses (101 in Furr), use in pregannt animals is off-label, feeding corn oil immediately prior to admin may enahcne absrobption of durg (103 in Furr)

The Food and Drug Administration (FDA) has approved four treatments for use in horses with EPM, but not all of these are commercially available:<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis). ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

Ponazuril is a triazinetrione antiprotozoal drug that targets the “apicoplast” organelle and inhibits energy metabolism (respiratory chains). The label dosage regimen PO daily for 28 days.  A multi-center field study - no adverse effects were noted.  However, information provided by the manufacturer reports “unusual daily observations” in eight animals that may have been related to treatment including blisters on nose and mouth, skin rash or hives, loose stools, mild colic, and a seizure.(IVIS 4)

Protocols involving intermittent administration of ponazuril may have application in prevention of EPM. (Mackay, R.J, Tanhauser, S.T, Gillis, K.D, Mayhew, I.G, Kennedy, T.J (2008) Effect of intermittent oral administration of ponazuril on experimental Sarcocystis neurona infection of horses.  Am J Vet Res, 69(3):396-402.

Treatment with ponazuril minimizes, but does not eliminate, infection and clinical signs of EPM in horses. (Furr, M, McKenzie, H, Saville, W.J, Dubey, J.P, Reed, S.M, Davis, W (2006) Prophylactic administration of ponazuril reduces clinical signs and delays seroconversion in horses challenged with Sarcocystis neurona.  J Parasitol, 92(3):637-43.

Diclazuril po, SID, chemically similar to ponazuril, one study imorvment in 58% cases if gven for 28days (98 in Furr), approved by FDA for use as top-dress tablet but not comemrically avialable, no adverse effects in effciacy study.(Furr)

*'''Sulfadiazine and pyrimethamine combination, ('Rebalance™', Antiprotozoal Oral Suspension, IVX Animal Health)''': administered PO daily for a minimum of 90 days. Due to availability and ease of administration, some use an off-label regimen of trimethoprimsulfa tablets with pyrimethamine tablets.  Pyrimethamine must be given at least 1 hr before or after hay is fed.<ref name="Merck">Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial</ref>  ''Mode of action'': trimethoprim, sulfadiazine, and pyrimethamine all inhibit enzymes of folic acid synthesis.  ''Efficacy'': 61.5% improvement by one clinical grade.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>''Potential adverse effects'': bone marrow suppression (mild anaemia, leucopenia, neutropenia, thrombocytopenia), fever, anorexia, depression, acute worsening of ataxia and altered reproductive performance in stallions<ref>Bedford, S.J, McDonnell, S.M (1999) Measurements of reproductive function in stallions treated with trimethoprim-sulfamethoxazole and pyrimethamine. ''J Am Vet Med Assoc'', 215:1317–1319.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>, congenital defects<ref>Toribio, R.E, Bain, F.T, Mrad, D.R, Messer, N.T, Sellers, R.S, Hinchcliff, K.W (1998) Congenital defects in newborn foals of mares treated for equine protozoal myeloencephalitis during pregnancy. ''J Am Vet Med Assoc'', 212:697–701.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>and abortion.  Folic acid deficiency may also cause gastrointestinal disturbances such as glossitis.<ref>Piercy, R.J, Hinchcliff, K.W, Reed, S.M (2002) Folate deficiency during treatment with orally administered folic acid, sulphadiazine and pyrimethamine in a horse with suspected equine protozoal myeloencephalitis (EPM). ''Equine Vet J'', 34:311–316.  In: Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis). ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>Blood dyscrazias are typically self-limiting and resolve on withdrawal of treatment.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Feeding high quantities of green forage should reduce the risk of anaemia after prolonged treatment. <ref name="Merck">Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial</ref>

Diclazuril is a triazinetrione antiprotozoal agent similar to ponazuril with an unknown (but possibly similar) mechanism of action.  A multi-center clinical field study was performed.  Reported adverse reactions were not clearly linked to drug administration and included worsening neurologic status and laminitis. Results of efficacy studies were surprisingly similar for each of the four approved therapies when similar methodologies and means of assessing improvement were used. Regardless of drug, _60% of treated horses improved by at least one neurologic grade or became negative on CSF WB. Based on reported side effects, ponazuril and diclazuril seem to have the fewest reported adverse effects. (IVIS 4)

NTZ (Navigator, Idexx Pharmaceuticals) member of 5-notrothiazol class of antimicrobials ad currently approved for tx of EPM, succes rate of about 60% in FDA-regulated study (98 in Furr). Adverse effects and death at high doses (98),, diarrhoea, depressiona and lamninits recorded at lower doses. {Poor completion rate and study compliance sugegts unreproted toxicity.  Toxci signs usally resolve oin withdrawl of tx, no longer availbale in US.

*'''Ponazuril (Marquis®, Bayer Animal Health)''': PO daily for 28 days, use in pregnant animals is off-label.  ''Mode of action'': ponazuril is a triazinetrione that targets the “apicoplast” organelle and inhibits the respiratory chain.  ''Efficacy'': well absorbed PO, achieves steady state therapeutic concentration in CSF within 3 days<ref>Furr, M, Kennedy, T (2001) Cerebrospinal fluid and serum concentrations of ponazuril in horses.  ''Vet Ther'', 2:232-237.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>clinical response within 10 days, 60% improvement by at least one clinical grade, 8% relapse within 90 days of stopping treatment.<ref>Furr, M, Kennedy, T, MacKay, R, Reed, S, Andrews, F, Bernard, B, Bain, F, Byars, D (2001) Efficacy of ponazuril 15% oral paste as a treatment for equine protozoal myeloencephalitis. ''J Vet Ther'', 2:215-222.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> ''Potential adverse effects'': none in a multi-centre field study<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>, no systemic toxicity even at high doses.<ref>Kennedy, T, Campbell, J, Selzer, V (2001) Safety of ponazuril 15% oral paste in horses. ''Vet Ther'', 2:223-231.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>However, the manufacturer reports signs that may have been related to treatment including blisters on the nose and mouth, skin rash or hives, loose stools, mild colic, and a seizure.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

Even successfully treaed cases may remian immunoblot positive for long periods so trying ot treat unitl seronegatvie not relasiitc. Triaxine based rugs (ponazuril, diclazruil, NTZ) licensed to be used oinly for 28days.  Longer tx often needed as determined by repeat exam after 1mth.  No reposnee sugegsts misdx and case should be re-evaluated. If some resposne bt rmeiansabnromal, continue tx for another mth.(Furr)

Paste no longer commercially available. This drug is a 5-nitrothiazole antiparasitic drug that inhibits the pyruvate:ferredoxin oxidoreductase (PFOR) enzymedependent electron transfer reaction essential for anaerobic energy metabolism. Reported side effects in these studies included inappetence and depression.

Two field studies for efficacy and safety were conducted during the approval process for nitazoxanide.

The most common adverse reactions were fever, anorexia/reduced appetite, and lethargy/depression.

Following warning: “administration of nitazoxanide can disrupt the normal microbial flora of the gastrointestinal tract leading to enterocolitis.  Deaths due to enterocolitis have been observed while administering the recommended dose in field studies.”a(IVIS 4)

Relapse rate u to 25% with sulfadiazien and pyrimethamine reporetd (104).  Relpases should be treated wth same drug for longer period, authoir recommmnds 2mths ponaxuril then min 90 days sulfadiaizen -pyrimethamine.  Failure of longher ocurse of ponazuril prmpts swewitch to diffeent chemical class (furr)

*'''Diclazuril''': PO, daily for 28 days, approved by FDA for use as top-dress tablet but not commercially available.  ''Mode of action'': chemically similar to ponazuril but mechanism of action unknown.  ''Efficacy'': one study reported clinical improvement in 58% of cases.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  ''Potential adverse effects'': none found in one efficacy study.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> Reported problems in a multi-centre field study included worsening neurologic status and laminitis but these were not proven to be related to treatment.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

Dirikolu, L, Lehner, A.F, Hughes, C, Karpiesiuk, W, Tobin, T () New therapeutic approaches to equine protozoal myeloencephalitis: pharmacokinetcis of toltrazuril sulfone sodium salt in the horse

*'''Nitazoxanide, NTZ ('Navigator®', Idexx Pharmaceuticals)''': no longer commercially available in the US.  ''Mode of action'': a member of the 5-nitrothiazole class of antiparasitics that inhibits the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction essential for anaerobic energy metabolism.<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>  ''Efficacy'': 60% success rate in an FDA-regulated study.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> ''Potential adverse effects'': adverse effects and death at high doses<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>, fever, anorexia, diarrhoea, lethargy, depression and laminitis recorded at lower doses.  Toxic signs usally resolve upon cessation of treatment.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  '''''Caution: 'administration of nitazoxanide can disrupt the normal microbial flora of the gastrointestinal tract leading to enterocolitis.  Deaths due to enterocolitis have been observed while administering the recommended dose in field studies.'''''<ref name="Johnson">Johnson, A.L (2009) Evidence-based review of diagnosis and treatment of ''Sarcocystis neurona'' infection (Equine Protozoal Myeloencephalitis).  ''Proceedings of the Annual Convention of the AAEP'' - Las Vegas, NV, USA, 55:172-176.</ref>

The only FDA-approved treatments for EPM are ponazuril (PO, SID for 28 days) and nitazoxanide (PO, sid for 28 days), both as paste formulations. An alternative approach is the use of antifolate drugs, eg, sulfadiazine, or sulfamethoxazole (PO, sid-bid) in combination with pyrimethamine (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 months. Anaemia 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)

Prolonged, off-license treatment is often instigated after 1 month, based on repeated clinical examination.  Even successfully treated cases may remain immunoblot positive for long periods, thus aiming for seronegativity is unrealistic.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  A lack of response to treatment suggests that the diagnosis should be re-assessed. Another month's worth of the same treatment is recommended for partial responders, with switching to a different chemical class if this fails. The efficacy of currently approved antiprotozoals against ''N.hughesi'' is unknown.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

Combo of antifolate drugs - trimethoprim sulfa (PO q12hrs, 4-8wks) plus pyrimethamine (Darapem(R) malaria drug) (PO q12h, 3 d then PO q24h 4-8wk), blood count every 2wk during therapy because may cause folate deficiency (leukopenia, thrombocytopenia & anaemia, rare) - discontinue and give folate, folate supplement - potential toxicity in mares, (Pasq)

 

No studies ahve  been condicted to determine effectiveness of currently aspproved antiprotozoals vs N hughesi(Furr)

===Ancillary medication===

===Ancillary medication===

NSAIDs in severe cases or to avoid 'tx cirsis' where it is is prosped that parasite kill transiently worsens inflmamtrion

*'''NSAIDs''': DMSO IV as 10% solution, thought to reduce CSF pressure and improve clinical status.  Recommended for severe cases of EPM or to avoid worsening inflammation that may be induced by parasite kill.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Caution: DMSO may cause intravascular haemolysis.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

*DMSO IV as 10% solition - may lower CSF prfessure and imporve clinical status

*'''Corticosteroids''': a short course of dexamethasone may be beneficial whilst waiting for antiprotozoals to take effect.  However, use is controversial because cell-mediated immunity is required to control parasites<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> and stress is a proposed risk factor for EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

Cortcosteroids - use debated, concern over immunsupprressions and that stress is risk factor for ePM, short course ofdex may help stabilize patient until antiprotoxoals take effect

*'''Immunomodulators''': '''Levamisole''' influences T-cell mediated immunity and enhances phagocytosis.  '''Parapox ovis virus (PPOV)''' immunomodulator (Zylexis, Pfizer Animal Health, Kalamazoo, Mich).  This vaccine has been shown to upregulate the secretion of cytokines including IFN-γ in several species.<ref>Frieb, A, Siegling, A, Friederichs, S, Volk, H-D, Weber, O (2004) Effects of inactivated parapoxvirus ovis (orf virus) on human peripheral immune cells: induction of cytokine secretion in monocytes and Th1-like cells.  ''J Virol'', 78:9400-9411.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>IFN-γ is thought to be essential for the clearance of ''S.neurona'', thus PPOV may be useful in EPM.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

Immunomodulators to boost immue resopsne: levemaisole influecnes t-cell mediated immunity and enahcnes pahgocytosis, parapox ovis virus immunomodulator (Zylexis, Pfizer Animal HEalth, Kalamazoo, Mich) intende dto aid in tx of EHV-1 and 4, an upregulate secretion of IFN-gamma (110) in number of species, believed to be ciritcal for clearnace of S neurona, inclsuion of PPOV vaccien in tx of EPM may be logical (Furr)

*'''Multiple vitamin B supplement'''.<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref>

NSAIDS, not steroids (because of need for cell mediated immunity to control parasites) DMSO IV to decrease inflammation in 5% dextrose - given without difficulty but causes intravsacular haemolysis so haemoglobinuria or haematuria, variable positive or negative response time - insurance require 6wk before euthanise, monitor CBC every 10-14d, folate inhibitors, can get pancytopenia, marked platelet drop, cut back dose, multiple B vitamin supplement, stall rest, Diclazuril & Toltrazuril: antiprotozoal disease, need testing, euthanize if don't respond. (Pasq)

===Supportive management===

===Supportive management===

Stall with deep bedding and good footing for v ataxic animasl, turnout in leve grassy fueld with no obstacles, care re turnotu with herd matyes, recumebvnt animals need additional care (FUrr)

Box rest with deep bedding and good footing or turn out in a flat, grassy field.  Ensure all obstacles are removed and avoid turning out ataxic animals with dominant herd mates.  Recumbent horses will require dedicated support and a sling if available.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

==Prognosis==

==Prognosis==

Depends on duration and severity of neurological signs<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref> but clinical resolution is more likely if the condition is diagnosed and treated early.<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Record'', 149:269-273.</ref>    With standard therapy, involving 6-8months of ponazuzril or pyrimethamine-sulfadiazine (V), there is a recovery rate of around 25% and an improvement in 60-75% of cases.<ref>MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> A good prognosis might be expected if there is an improvement in clinical signs within two weeks of commencing anti-protozoal and anti-inflammatory treatment (V).  The prognosis will be guarded to poor<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> for a horse with severe irreversible neuronal damage or one that has not been diagnosed or treated appropriately (V).

Depends on duration and severity of neurological signs<ref name="EPM3">Vatistas, N, Mayhew, J (1995) Differential diagnosis of polyneuritis equi.  ''In Practice'', Jan, 26-29.</ref> but clinical resolution is more likely if the condition is diagnosed and treated early.<ref name="EPM8">Gray, L.C, Magdesian, K.G, Sturges, B.K, Madigan, J.E (2001) Suspected protozoal myeloencephalitis in a two-month-old colt.  ''Vet Record'', 149:269-273.</ref>    With standard therapy, there is a recovery rate of around 25% and an improvement in 60-75% of cases.<ref name="MacKay">MacKay, R.J (2006) Equine protozoa myeloencephalitis: treatment, prognosis and prevention.  ''Clin Tech Equine Pract'', 5:9-16.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref> A good prognosis might be expected if there is a response to treatment within two weeks.  The prognosis will be guarded to poor<ref name="Pasq">Pasquini, C, Pasquini, S, Woods, P (2005) '''Guide to Equine Clinics Volume 1: Equine Medicine''' (Third edition), ''SUDZ Publishing'', 245-250.</ref> for a horse with severe, irreversible neuronal damage.

==Prevention==

==Prevention==

===Prophylaxis===

===Prophylaxis===

A killed vaccine, developed using ''S.neurona'' merozoites, was conditionally licensed for use in horses.<ref>Saville, W.J.A, Reed, S.M, Dubey, J.P (2002) Prevention of equine protozoal myeloencephalitis

A killed vaccine, developed using ''S.neurona'' merozoites, was conditionally licensed for use in horses.<ref name="Saville1">Saville, W.J.A, Reed, S.M, Dubey, J.P (2002) Prevention of equine protozoal myeloencephalitis(EPM). ''Proceedings of the Annual Convention of the AAEP'', 48:181-185.</ref>  The vaccine proved to be ineffective in the prevention of EPM and has since been removed from the market.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  There is evidence to suggest that the antiprotozoal, ponazuril, may be useful prophylactically to reduce the incidence and severity of clinical signs.<ref>Furr, M, MacKenzie, H, Dubey, J.P (2006) Pretreatment of horses with ponazuril limits infection and neurologic signs resulting from S.neurona.  ''J Parasitol'', 92:637-643.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Implementing such a regime prior to and during stressful events may be beneficial, although the cost is likely to be prohibitive.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>Protocols involving intermittent administration of ponazuril may also show promise in the prevention of EPM.<ref>Mackay, R.J, Tanhauser, S.T, Gillis, K.D, Mayhew, I.G, Kennedy, T.J (2008) Effect of intermittent oral administration of ponazuril on experimental ''Sarcocystis neurona'' infection of horses.  ''Am J Vet Res'', 69(3):396-402.</ref>

(EPM). ''Proceedings of the Annual Convention of the AAEP'', 48:181-185.</ref>  The vaccine proved to be ineffective in the prevention of EPM and has since been removed from the market.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  There is evidence to suggest that the antiprotozoal, ponazuril, may be useful prophylactically to reduce the incidence and severity of clinical signs.<ref>Furr, M, MacKenzie, H, Dubey, J.P (2006) Pretreatment of horses with ponazuril limits infection and neurologic signs resulting from S.neurona.  ''J Parasitol'', 92:637-643.  In: Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>  Implementing such a regime prior to and during stressful events may be beneficial, although the cost is likely to be prohibitive.<ref name="Furr">Furr, M (2010) ''Equine protozoal myeloencephalitis'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), ''Saunders'', Chapter 12.</ref>

 

 

 

 

 

==References==

==References==

[[Category:Tissue_Cyst_Forming_Coccidia]][[Category:Horse]]

[[Category:Expert_Review]]

[[Category:To_Do_-_Nina]]

[[Category:Neurological Diseases - Horse]]