Changes

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>

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>

*'''Sulfadiazine and pyrimethamine combination, ('RebalanceTM', 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.  ''Mode of action'': trimethoprim, sulfadiazine, and pyrimethamine all inhibit enzymes of folic acid synthesis.  ''Efficacy'': 61.5% improvement by one clinical grade.(98 in furr)''Potential adverse effects'': bone marrow suppression (mild anaemia, leucopenia, neutropenia, thrombocytopenia), fever, anorexia, depression, acute worsening of ataxiam altered reproductive performance in stallions (19 in IVIS 4), congenital defects(20 in IVIS 4) and abortion.  Folic acid deficiency may also cause gastrointestinal disturbances such as glossitis.(18 in IVIS 4) Blood dyscrazias are typically self-limiting and resolve on withdrawal of treatment. (Furr)

*'''Sulfadiazine and pyrimethamine combination, ('RebalanceTM', 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.  ''Mode of action'': trimethoprim, sulfadiazine, and pyrimethamine all inhibit enzymes of folic acid synthesis.  ''Efficacy'': 61.5% improvement by one clinical grade.(98 in furr)''Potential adverse effects'': bone marrow suppression (mild anaemia, leucopenia, neutropenia, thrombocytopenia), fever, anorexia, depression, acute worsening of ataxiam altered reproductive performance in stallions (19 in IVIS 4), congenital defects(20 in IVIS 4) and abortion.  Folic acid deficiency may also cause gastrointestinal disturbances such as glossitis.(18 in IVIS 4) 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> 

*'''Ponazuril (Marquis(R), 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(100 in Furr), clinical response within 10 days, 60% improvement by at least one clinical grade, 8% relapse within 90 days of stopping treatment(91 in Furr).  ''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.(101 in Furr)However, the manufacturer reports signs that may have been related to treatment including blisters on 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>

*'''Ponazuril (Marquis(R), 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(100 in Furr), clinical response within 10 days, 60% improvement by at least one clinical grade, 8% relapse within 90 days of stopping treatment(91 in Furr).  ''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.(101 in Furr)However, the manufacturer reports signs that may have been related to treatment including blisters on 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>

*'''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.(98 in Furr)  ''Potential adverse effects'': none found in one efficacy study.(Furr)  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>

*'''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.(98 in Furr)  ''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>

*'''Nitazoxanide, NTZ ('Navigator(R)', 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.(98 in Furr) ''Potential adverse effects'': adverse effects and death at high doses(98), fever, anorexia, diarrhoea, lethargy, depression and laminitis recorded at lower doses.  Toxic signs usally resolve upon cessation of treatment.(Furr)'''''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.'''''(IVIS 4)

*'''Nitazoxanide, NTZ ('Navigator(R)', 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.(98 in Furr) ''Potential adverse effects'': adverse effects and death at high doses(98), 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.'''''(IVIS 4)

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.(Furr)  A lack of response to treatment suggests that the diagnosis should be re-assessed.  Another month's worth of treatment is recommended for partial responders.(Furr)

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 treatment is recommended for partial responders.<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> 

===Ancillary medication===

===Ancillary medication===

*'''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(Furr).  Caution: DMSO may cause intravascular haemolysis(Pasq).

*'''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(Furr).  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>

*'''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(Pasq) and stress is a proposed risk factor for EPM.(Furr)

*'''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(Pasq) and stress is a proposed risk factor for EPM.(Furr)

*'''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 (110 in Furr).  IFN-γ is thought to be essential for the clearance of S neurona, thus PPOV may be useful in EPM.(Furr)

*'''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 (110 in Furr).  IFN-γ is thought to be essential for the clearance of S neurona, thus PPOV may be useful in EPM.(Furr)

*'''Multiple vitamin B supplement'''.(Pasq)

*'''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>

===Supportive management===

===Supportive management===