Diclazuril for Sale—Purchasing the Right Formulation for Horses
Diclazuril is a triazinone antiprotozoal that is effective for treating equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona. It is also used in treating infections caused by Isospora spp., Toxoplasma gondii, and Eimeria spp,1 and as a coccidiostat in chickens and turkeys.2
Equine Protozoal myeloencephalitis (EPM) is the leading infectious neurologic disease of American horses. EPM is classified as a “New World disease,” and is the most common infectious neurological disease of horses in the Western hemisphere. The “apicomplexan” parasite which causes EPM (S. neurona) cycles naturally between opossums and birds. The horse is an aberrant host, becoming exposed when it consumes infectious material from opossum feces. In the horse, S. neurona makes its way to the brain and spinal cord, where it proliferates and causes clinical disease.3 In the U.S., diclazuril is has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of EPM in horses, and as a coccidiostat in broiler chickens.4
The epidemiology and economic significance of S. neurona infection is substantial. In endemic areas in the U.S., over 40% of horses tested are seropositive. Of these, a small percentage are clinically affected. Of animals clinically affected, 30—40% reportedly fail to respond to current therapy, and some of these animals die. Better and more effective prophylactic and therapeutic modalities are required. The economic loss in performance horse breeding is likely more substantial than these figures (which refer only to clinically observable infections) suggest.3
Clinical Pharmacology
In a target animal safety study, 1.56% diclazuril antiprotozoal pellets were administered to 24 horses (12 males and 12 females, ranging from 2 to 8 years of age). Three groups of 4 horses/sex/group received 0, 1, or 5 mg diclazuril/kg body weight/day for 42 days as a topdress on the grain ration of the horse. The variables measured during the study included physical examinations, body weights, food and water consumption, hematology, and serum chemistry. The effectiveness of diclazuril in inhibiting merozoite production of S. neurona and S. falcatula in bovine turbinate cell cultures was studied. Diclazuril inhibited merozoite production by more than 80% in cultures of S. neurona or S. falcatula treated with 0.1 ng/mL diclazuril and greater than 95% inhibition of merozoite production was observed when infected cultures were treated with 1.0 ng/mL diclazuril.5
EPM Infection Rates
Approximately 1% of horses which encounter S. neurona will develop neurologic disease but the seroprevalence of S. neurona antibodies ranges from 15-89% of tested horses The seroprevalence variance is influenced by geographic region and presences of sera antibodies merely indicates exposure to S. neurona and not clinical neurologic disease. The high exposure rate but relatively low incidence of neurologic disease, most likely indicates that most exposed horses elicit the required immune response to prevent clinical neurologic disease.2 The immunopathogenesis of EPM is not completely understood and a better understanding would improve diagnostic tests and treatment options of EPM. The current EPM immunopathogenesis knowledge has mostly been acquired by employing immunocompromized mouse models.5
Purchasing the Right Formulation
Due to its wide range of clinical applications across species, there are numerous formulations of diclazuril available. At present, diclazuril is available from dozens of suppliers, and there are at least as many commercially-available (branded) formulations for livestock. Dosage forms of diclazuril mainly contain pre-mixing agents, suspension powders, binders, etc.6 Available in powder, pellets, pastes, liquid, gels, oil suspensions and injectable forms, for the prevention of EPM, powders or pellets are generally used as a top dressing in the horse’s feed.
In studies, the oral administration of single doses of diclazuril 10 mg/kg yielded a mean peak plasma concentration of 4.5 µg/ml with no signs of toxicity. The apparent plasma half-life of toltrazuril was approximately 55 h. The oral administration of a single dose of diclazuril 5 mg/kg yielded a peak plasma concentration of 1 µg/ml after 24 h and declined with an apparent plasma half-life of 50 h.7
The duration of treatment with diclazuril is determined by resolution of clinical signs. A horse might experience a relapse once a drug has stopped and/or in instances of stress. Relapse rates are estimated at 10-20%. Horses that seem refractory to one medication might be switched to another or could receive a combination of medications with improved results. In general, failures in treatment are usually because a horse is not actually infected with EPM, has been infected for a long time before treatment is started, and/or the degree of neurologic damage is beyond recovery.3
Preventive Strategies—The Best Bet
Considering EPM, aside from prophylactic dosing with diclazuril, prevention would be the preferred objective since not only is it difficult to identify that a horse has EPM in the early stages, but also because even with aggressive treatment, lingering neurologic deficits can remain. The best route to EPM prevention is to manage any possible contamination of horse feed or water from the primary reservoir host, the opossum. Skunks, raccoons, sea otters and even cats also can be protozoal sources. Feed containers should be locked away in vermin-proof containers and rooms.
When possible, feeding horses from the ground should be avoided, and spilled feed should be removed and disposed of immediately to deter attracting wildlife and rodents. Water sources should be cleaned and freshened frequently. Keeping wildlife away from where horses graze—an admittedly difficult proposition—should at least be attempted.
1Papich, M. DVM, MS, DACVCP, Diclazuril: Pharmacology and mechanism of action. In: Saunders Handbook of Veterinary Drugs (Fourth Edition), 2016.
2Alexander, J., et. al. Cross-contamination of non-target feedingstuffs by diclazuril authorised for use as a feed additive. The EFSA Journal (2008) 716, 1-31.
3Granstrom, David E. and Tobin, Thomas, Formulations and Methods to Treat and Prevent Equine Protozoal Myeloencephalitis (1999).Veterinary Science Faculty Patents.
4Plumb’s Veterinary Drugs.
5Reed, S. M., M. Furr, D. K. Howe, A. L. Johnson, R. J. Mackay, J. K. Morrow, and S. Witonsky. 2016. Equine protozoal myeloencephalitis: An updated consensus statement with a focus on parasite biology, diagnosis, treatment, and prevention. Journal of Veterinary Internal Medicine 30: 491–502.
6Merck Animal Health.
7Grandstrom DE, McCrillis S, Tobin T, et al. Diclazuril and equine protozoal myeloencephalitis, in Proceedings. 43rd Annu Conv Am Assoc Equine Practnr 1997;13–14
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