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[[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.'' ''']]

Infective sporocysts are passed in the faeces of the definitive host and must be ingested by the horse for infection to occur.(Furr) 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|here]] for further details of the life cycle of ''Sarcocystis neurona''.

 

==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.<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<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 (25 in Furr) 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>

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<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 (25 in Furr) 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 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>

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> Placental transmission is considered 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.<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>

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>

==Signalment==

==Signalment==