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Equine Protozoal Myeloencephalitis (view source)

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*'''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>

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*'''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>

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*'''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>

*'''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>

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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, switching to a different chemical class if this fails.<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 efficacy of currently approved antiprotozoals against ''N.hughesi'' is unknown.(Furr)~~

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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>

===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.<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>

*'''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>

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*'''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>

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*'''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>

*'''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>

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