EQUINE PROTOZOAL MYELOENCEPHALITIS


EPM Treatment Summary

Once a diagnosis of EPM is established, treatment of the horse should start immediately.  A delay in treatment allows the disease to progress, potentially causing additional permanent damage to the central nervous system.  Treatment is usually with drugs known to kill or retard the reproduction of the protozoa S. neurona.  None of the drugs kill 100% of the protozoa.  The drugs reduce the protozoa population to a level where the horse's immune system kills the rest.  It is important to help the horse rebuild the immune system while treatment is ongoing.

This web site is based upon information found in veterinary journals and clinical studies.  Drugs or remedies which have not been studied in a clinical trial are not covered here.  The FDA has approved four drugs for the treatment of EPM, and there is one field drug trial in progress (as of 5/11). 

© Johny Day phtograph 'Beard Trimming'
   © Johny Day  Beard Trimming
All of the medications listed below require a prescription by a licensed veterinarian.  Some veterinarians stock the medications, and will sell them to the owner.  Other veterinarians will issue a prescription for the drug.  The drugs are available on the internet, with a prescription.  The laws concerning who may order the drug, the owner or the veterinarian, vary depending on the state where the pharmacy is located.

The veterinarian may also prescribe the use of an anti-inflammatory, immune stimulant, and/or vitamin E during treatment.  Most veterinarians will suggest that the horse not be ridden or worked for some time, dependant on the severity of symptoms.  Giving the horse time off will help keep its stress to a minimum, and allow the immune system to heal.  Read the page on Other Therapies for items to accompany the treatment drugs.

About EPM Drugs

All of the drugs require a minimum number of days to build the concentration of drug in the cerebrospinal fluid to a level that will kill or impede the protozoa.  It is important that the horse receives the medication every day and generally at the same time of day.  All listed medications are given orally.

All four FDA drugs fall within the range 57% to 61% success rate, based upon clinical studies.  Two major differences between the drugs are cost and possible side effects.  A successful treatment is deemed one in which the neurological symptoms are reduced by 1 on the Mayhew Scale.  This is not very comforting to an owner with a horse at 4 on the Mayhew Scale.  A successful treatment under this definition may leave the horse safe for pasture only.  The trial drug has been tested in 200 horses and early reports are 94% efficacy.

There is disagreement between researchers over the effectiveness of longer or stronger drug protocols.  Some veterinarians may suggest the use of ponazuril or diclazuril at higher than label doses.  Longer/stronger doses are not FDA approved, are off-label, and have no published studies to document efficacy.  Recent information indicates that longer/stronger doses are not as important as an anti-inflammatory.  There is only one way to know when to stop treatment:  when a blood antibody test shows a significant drop in Sn antibodies.  This may be as soon as two weeks after beginning treatment.

Drug Trial for Oroquin-10

This field drug trial opened in May 2011.  This drug is a combination of decoquinate and levamisole.  Both drugs are FDA approved individually for other animals, but not combined for use in horses.  Oroquin-10 has started through the FDA review process.  Decoquinate has an in-vitro efficacy study completed for EPM, and a safety trial in horses.  Oroquin-10 is a ten-day dose of oral paste medication.  An antibody test is required before and after the medication.  Your vet has to fill out and submit the form, with either a blood sample for the Peptide ELISA, or by sending a positive Multiplex Sn strip.  Prescription information will be sent to your veterinarian.  There is no cost to enter the trial, the antibody blood tests total $78 (plus 2-day shipping) and the drug is about $150. 

Oroquin-10 Field Trial Description - Open pdf

Peptide ELISA submission form - Open pdf

Sulfadiazine - Trimethoprim - Pyrimethamine Combination

February 2011 Cost for compounded drug $72-190/month, ReBalance N/A

This drug, in different combinations is one of the first drugs used to treat EPM.  The FDA approval was issued to ReBalance for a sulfadiazine-pyrimethamine combination.  As of January 2012 Rebalance was not on the market, but may return.  It should be pointed out that Sulphadiazine/Trimethoprim is the human anitbiotic Septra, and this formula will not kill protozoa.  Sulpha/Pyrameth also appears to treat the cyst-forming S. falcatula and S. fayeri; however, little information is available.

This drug acts on S. neurona by limiting folic acid uptake by the protozoa, inhibiting its ability to reproduce.  The Freedom of Information NADA (below) for Rebalance indicates that it does kill the protozoa invitro, and has a better kill rate that the 'zuril' drugs.  It must be given long enough to limit reproduction until the horse's immune system can complete the kill, three to seven months.  This drug also limits folic acid uptake by the horse.  “Because of the greater frequency and severity of bone marrow suppression at the 2X dose level, REBALANCE Antiprotozoal Oral Suspension should be administered at the labeled 1X dose level.”  It should be given according to an accurate animal weight.  Supplementation with folic acid to avoid anemia is controversial.  This drug must be given at least one hour before food.  The horse should be monitored monthly by blood tests for anemia, as 22% of the horses in the clinical study became anemic.

“The combination of pyrimethamine, and sulfa may cause anemia, decreased platelets, decreased white blood cell counts, and suppress bone marrow. Pyrimethamine should be used with extreme caution in animals with blood dyscrasias or bone marrow suppression,” indicates Wedgewood Pharmacy.

In Compendium Equine Jan/Feb 2008, Dr. Robert MacKay suggests using this drug simultaneously with diclazuril or ponazuril to treat relapses, however, this is not FDA-approved, and there is no efficacy study.  It is available from many compounding pharmacies including:

Wickliffe Pharmacy   (888) 934-5678  

Wedgewood Pharmacy  888-678-1967

Diclazuril (Protazil)

Feb 2011 Protazil $562/28 days to the vet, $750 online; compounded cost $150-$300

Protazil pelleted top-dress, FDA approved March 2007, became available in Feb 2011.  However, many large retailers don't stock it.  Liquid or paste diclazuril is available through veterinary compounding pharmacies.  This drug is based upon an herbicide, and attacks the chloroplast function of the protozoa.  It is considered non-toxic at higher doses in mammals, and had no reportable side effects in trials.  This drug may be given with or without food, and it is not known if supplemental fat (corn oil) increases absorption.  Protazil was labeled at 1mg/kg body weight, but was shown in a study to have higher relapse rates at that level, than other drugs.  Commonly compounded diclazuril rates are 5.0 to 15.0 mg/kg body weight.  In Compendium Equine Jan/2008, Dr. Robert MacKay suggests treating relapses using diclazuril at 7mg/kg body weight; however, this protocol is not FDA-approved and has no efficacy study.  The author questions how you use Protazil if the horse won't eat the top-dress pellets. 

There is an interesting point in the Freedom of Information Summary.  The study authors indicate 67% of the horses improved by one grade after treatment.  The board certified neurologists, blinded to the trial, indicated that only 42% of the horses improved by one grade. 

Compounded diclazuril is available from the following compounding pharmacies:

Axtell Rite Value Pharmacy    903-564-3216

Ponazuril (Marquis)

Feb 2011 Marquis $672/28 days to the vet, $780 online, compounded N/A.

Ponazuril is in the same class of drugs as diclazuril.  It is not available compounded in the US; a close drug Baycox or toltrazuril is available in Canada.  This drug is also based upon an herbicide, and attacks the chloroplast function of the protozoa.  It is considered non-toxic at higher doses in mammals, and has minor side effects including rash and mouth blisters.  This drug may be given with or without food, and immediately giving additional fat (corn oil) will help absorption.  Marquis is labeled at 5mg/kg body weight, and is given once per day for 28 days.  In Compendium Equine Jan/2008, Dr. Robert MacKay suggests treating relapses using Marquis at 35mg/kg body weight per day for the first four days, then 5mg/kg for 28 days.  This protocol is not FDA-approved, and has no efficacy study.  This protocol will very effectively empty your bank account.

A 2010 study on Sea Otters indicates that Ponazuril will not treat encysted forms.  It most likely will not treat S. falcatula and S. fayeri encysted infections in the horse.

Nitazoxanide (Navigator)

February 2009 IDEXX Labs stopped making Navigator, stock no longer available

Navigator generally cost more than Marquis, and according to the package insert, had potentially serious side effects such as enterocolitis, laminitis, anorexia, fever, and lethargy.  It was toxic at levels above the labeled use, and an accurate animal weight was necessary for proper administration.  In two field studies 27% and 31% of horses had adverse reactions while on the drug.  A not-yet-published manuscript indicates that IDEXX is testing a new formulation of NTZ without the nitrogen.

January 2012

References:

Rebalance Freedom of Information Summary Open PDF

Protazil Freedom of Information Summary  Open PDF

Marquis Freedom of Information Summary Open PDF 

Navigator Freedom of Information Summary Open PDF

Navigator package insert:  Insert is no longer available on IDEXX website.  Information is contained in FOI above.

Pyrimethamine
http://www.wedgewoodpharmacy.com/monographs/pyrimethamine.asp

“EPM: Managing Relapses”, Compendium Equine Jan/Feb 2008
Click here to open pdf.

AAEP Proceedings, Vol 54, 2008

Eq Vet ED, vol 12, #4, June 2000, 195-200.

Clin Tech Equine Pract 5:9-16 2006

Navigator and new compound J Vet Para.2009.03.22

 

Photograph 'Mail Wagon 1905''Mail Wagon 1905'

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