Changes

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 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>  

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, 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'', 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>  

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

==Pathogenesis==

==Pathogenesis==

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.(24 in Furr)  Factors which promote disease develpoment include parasite dose (71 in Furr) and probably virulnece of the protozoal strain.  Stress induced by preganancy, travel, training, showing (25 in Furr) may have an immunosuppressive effect that encourages infection.  Indeed, it has been shown that stress affctes the severity of clincal sigsn seen in natural infections (74 in 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> Factors which promote disease development include parasite dose(71 in Furr) and, most probably virulence of the protozoal strain.  Stress induced by pregnancy, travel, training and showing (25 in Furr) may have an immunosuppressive effect that encourages infection.  Indeed, it has been shown that stress affcts the severity of clinical sigsn seen in natural infections.(74 in Furr)

The 'Trojan horse' hypothesis suggests that S.neurona meroziotes traverse the blood brain barrier encrypted within leucocytes that have pahgocytosed the parasite in the periphery.  Subsequent eggression and infection of other cells once inside the CNS, 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 and/or metabolites may have a considerable roel in porducign pathological changes.(EPM 6)  Althugh the protozoan may iduce 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-priveglie of the CNS prevents parasite clearance form this site (Furr). Placental trasnmission is conseiderd highly unlikely (Furr).

The 'Trojan horse' hypothesis suggests that S.neurona meroziotes traverse the blood brain barrier encrypted within leucocytes that have pahgocytosed the parasite in the periphery.  Subsequent eggression and infection of other cells once inside the CNS, 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 and/or metabolites may have a considerable roel in porducign pathological changes.(EPM 6)  Althugh the protozoan may iduce 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-priveglie of the CNS prevents parasite clearance form 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> Placental trasnmission is conseiderd highly unlikely.<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>

Both humoral and cell-mediated immune mechansism are likely to be significant in the host defecne agaisnt ''S.neurona''.  Antibodies are porduced soon after infection and offer some degree of protection (furr).  CD8 postivie T-cells and their production of IFN-gamma are likely to be pivtoal in the removal of intracellualr stages of the parasite (Furr).

Both humoral and cell-mediated immune mechansism are likely to be significant in the host defecne agaisnt ''S.neurona''.  Antibodies are porduced 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 postivie T-cells and their production of IFN-gamma are likely to be pivtoal in the removal of intracellualr 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>

==Signalment==

==Signalment==