Diclazuril for the Prevention and Treatment of EPM
Veterinarians first described the set of symptoms that would come to be known as equine protozoal myeloencephalitis (EPM) in 1968.1 In the 1970s, researchers determined that this this devastating neurologic illness was caused by a protozoan, although they did not identify Sarcocystis neurona as the specific protozoan involved until the 1990s. S. neurona is a member of the phylum Apicomplexa, a broad group of pathogens found globally. This classification includes the protozoans that cause malaria and toxoplasmosis in humans via zoonotic transmission.
EPM is endemic to the Americas (North, South and Central America), and has only been found in horses that reside in these areas, or those which have spent time in these areas. The literature maintains that more than 50 percent of all horses in the United States may have been exposed to the S. neurona organism. The infective stage of the organism (sporocysts) is passed in the feces of an intermediate host, after which the horse comes into contact with the infective sporocysts while grazing or eating contaminated feed or drinking water.
EPM can present in a multitude of ways, from weakness and loss of coordination in the horse, to facial paralysis and difficulty swallowing.1 The literature maintains that more often than not, when a horse ingests the S. neurona protozoan (usually via the feces of an intermediate host), its immune system eliminates the threat and the horse does not become ill. In some cases, however, the organisms cross the blood-brain barrier and attack the central nervous system, causing a wide range of neurological problems.2
EPM Symptoms and Diagnosis
EPM isn’t grabbing headlines as often as it did when it was first identified, but this debilitating neurological disease remains a threat to horses all over the Americas. Fortunately, researchers and veterinarians continue to amass all of the information they can regarding the disease syndrome and the S. neurona organism, and research is ongoing in many areas. One of the aspects that continues to confound is the fact that while most U.S. horses have been exposed to the pathogen, just a fraction of them develop clinical disease. Researchers are also examining how coinfections with different pathogens may influence the onset and severity of clinical EPM disease.
No two horses with EPM will present in exactly the same fashion, which is one of the factors that make an accurate EPM diagnosis frustratingly difficult for the veterinarian. Another aspect is that there are several diseases of the central nervous system of the horse that present in similar fashion to EPM, especially in the early stages of the disease. “Finally, there is no single “test” that can be done, which is 100 percent accurate in the live horse that can tell us if a particular animal is suffering from EPM. There are tests that can be utilized by your veterinarian, and these are used to support his or her diagnosis of EPM as well as to rule out other diseases, which may look like EPM.”3 In order to diagnose a horse with clinical EPM, it should be both CSF positive for S. neurona antibodies and show a history and clinical signs consistent With EPM. Other non S. neuronal-based causes of neuropathy must also be excluded.
EPM Prevention and Treatment with Diclazuril: Then and Now
As with any diagnostic effort, the treatment of EPM should only be done under the direct supervision of a veterinarian. Once the horse has been definitively diagnosed as having EPM, treatment should begin immediately, as this will increase the horse’s chances are for recovery. 60% to 70% percent of EPM cases aggressively treated show significant or complete reversal of symptoms, with many horses being able to return to normal activity.3
Although there have been drug combinations available to treat EPM for quite some time, there are now proprietary anti-protozoal drugs specifically labeled by the U.S. Food and Drug Administration (FDA) to treat the disease. Research conducted in the 1990s utilized diclazuril daily for three weeks to treat horses with severe neurological impairment due to EPM. This treatment resulted in significant clinical improvement. Based on this encouraging preliminary evidence of bioavailability, selective toxicity and clinical efficacy, clinical investigations of the efficacy of diclazuril for the treatment of EPM were conducted.4 These also showed promising results, and diclazuril was well on its way to becoming a staple for the prevention and treatment of EPM.
The chemical formulation of diclazuril is based upon an herbicide, and attacks the chloroplast function of the protozoa. It is non-toxic at higher doses in mammals, and had no reportable side effects when the drug was in trials. In the non-injectable forms, diclazuril may be given with or without food. Diclazuril was labeled at 1mg/kg body weight, but was shown in a study to have higher relapse rates at that level than other drugs. More recently, compounded diclazuril rates run from 5.0 to 15.0 mg/kg body weight.3
Diclazuril pelleted for the top-dressing of feed was approved by the FDA in March 2007, and became available in February of 2011. Liquid or paste diclazuril is available through veterinary compounding pharmacies. The injectable form is also available through compounding pharmacies for cases where clinical EPM is present and an aggressive treatment regimen is prescribed.
1Church, S. Update: EPM in Horses. The Horse, May 2019.
2Hackstein, J.H., Mackenstedt, U., Melhorn, H., Meijerink, J.P.,Schubert, H. and Leunissen, J.A. (1995) Parasiticapicomplexans harbor a chlorophyll a-D1 complex, thepotential target for therapeutic triazines. Parasitol. Res.81,207-216.
3MacKay, R., DVM. Equine Protozoal Myeloencephalitis. J. American Association of Equine Practitioners, March 2019.
4Bentz, B.G., et. al. Diclazuril and equine protozoal myeloencephalitis (EPM): a clinical report. Equine vet. Educ. (2000) 12 (4) 195-200.
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