Changes

==Treatment==

==Treatment==

Antiprotozoals

===Antiprotozoals===

 

Sulphonamide drugs combined with pyrimethamine for synergism - FDA approved

Sulphonamide drugs combined with pyrimethamine for synergism - FDA approved

Sulfadiazine and pyriemthamine PO SID 'Re-Balance' no longer available? - 61.5% improvement by one clinical grade, tx for 90-270days (98 in frr)

Sulfadiazine and pyriemthamine PO SID 'Re-Balance' no longer available? - 61.5% improvement by one clinical grade, tx for 90-270days (98 in frr)

Use of sulfadizine in breeding animals controversial but one study showed no effect on pregnancy rates or EED

Use of sulfadizine in breeding animals controversial but one study showed no effect on pregnancy rates or EED

Sulfamethoxazole and pyrimethamine caused mild ataxia associated with mounting and ejaculation in a grp of pony stallions (99 in furr)

Sulfamethoxazole and pyrimethamine caused mild ataxia associated with mounting and ejaculation in a grp of pony stallions (99 in furr)

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)

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)

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.

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)

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.

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.

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.

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.

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

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

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

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 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

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

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

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)

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)

We had earlier identified triazine-based antiprotozoal agents for the treatment and prophylaxis of EPM, and on this basis, we elected to develop a highly bioavailable oral formulation, namely toltrazuril sulfone sodium salt (TSSS), that can be used for the treatment and prophylaxis of EPM.  Based on these data, repeated oral-mucosal administration of TSSS with or without feed will yield useful steady-state plasma and cerebrospinal fluid concentrations of toltrazuril sulfone for the treatment and prophylaxis of EPM. (IVIS)

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.

 

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)

Treatment is also challenging, because several medications are available and response to treatment is not consistent among horses.  There are four treatments currently approved by the Food and Drug Administration (FDA) for EPM, but only three have been commercially available: a sulfadiazine and pyrimethamine combination, ponazuril, and nitazoxanide. Diclazuril has been approved but not yet marketed. Recently (spring of 2009), the commercially available form of nitazoxanidea has been discontinued.

The FDA-approved combination is sulfadiazine and pyrimethamineb daily for a minimum of 90 days. If the FDA-approved combination is unavailable, some practitioners opt to use trimethoprimsulfa tablets q 12–24 h, PO) with pyrimethamine tablets (q 24 h, PO) because of availability or ease of administration.

However, this regimen constitutes extra-label/unapproved use. All three of the drugs (trimethoprim, sulfadiazine, and pyrimethamine) inhibit enzymes in the folic acid pathway and thereby, inhibit thymidine synthesis. The most common adverse reaction in one study was bone marrow suppression (anemia, leucopenia, neutropenia, and/or thrombocytopenia) .  Adverse effects attributed to treatment included fever, leucopenia, anorexia, depression, acute worsening of ataxia, mild anemia, and abortions.

In addition to blood dyscrasias, folic acid deficiency may lead to gastrointestinal disturbances such as glossitis.18 Stallions treated for 90 days with trimethoprim-sulfamethoxazole and pyrimethamine may have changes in copulatory form and agility along with altered pattern and strength of ejaculation.19 Three mares receiving sulfonamides, pyrimethamine (with or without trimethoprim), and folic acid delivered foals with congenital defects that died or were euthanized.20

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.

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.

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.

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.

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

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)

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)

Treatment duration using standard therapy (pyrimethamine and sulphadiazine) has been advocated until the patient becomes CSF immunoblot-negative (Fenger 1997). Our experience with horses that have received standard treatment suggests that many may remain CSF imunoblot-positive for long periods after successful treatment.  

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)

Based on these results, diclazuril has considerable potential as a primary treatment of selected horses with EPM that have been either refractory to or have relapsed after standard treatment.(EPM 1)

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.

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

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.

We had earlier identified triazine-based antiprotozoal agents for the treatment and prophylaxis of EPM, and on this basis, we elected to develop a highly bioavailable oral formulation, namely toltrazuril sulfone sodium salt (TSSS), that can be used for the treatment and prophylaxis of EPM.   Based on these data, repeated oral-mucosal administration of TSSS with or without feed will yield useful steady-state plasma and cerebrospinal fluid concentrations of toltrazuril sulfone for the treatment and prophylaxis of EPM. (IVIS)

Treatment is based on the use of antiprotozoal drugs which inhibit folic acid synthesis, the most commonly used being pyrimethamine and sulphadiazine. (EPM 8)

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

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, 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)

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 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)

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)

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)

This disease is curable if caught soon enough and treated with antiprotozoal drugs. There are currently three antiprotozoal treatments available: potentiated sulfonamide medications such as ReBalance, Marquis (ponazuril), and Navigator.(Wikipedia)

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)

==Prognosis==

==Prognosis==