Diclazuril and equine protozoal myeloencephalitis (EPM): a clinical report

Equine protozoal myeloencephalitis (EPM) is a nervous system disease caused by the protozoan Sarcocystis neurona. The clinical syndrome caused by the disease can have a variety of presentations. Classically, horses present with asymmetric ataxia and weakness defined by multifocal central nervous system lesions. Successful management of this disease has been frustrated by failure of treatment success and by relapse after withdrawal of therapy. Diclazuril is a triazine derivative used in the prophylaxis of coccidiosis in poultry and experimentally in lagamorphs for coccidiosis (Vanparijs et al. 1988, 1989; McDougald et al. 1991). It has been evaluated for the treatment of isosporiasis and cryptosporidiosis in AIDS patients (Kayembe et al. 1989; Menichetti et al. 1991; Limson-Pobre et al. 1995) It has also been used, to a limited extent, to treat experimentally induced Toxoplasma gondii encephalitis in mice (Lindsay et al. 1995). These observations suggest that triazine derivatives may be useful in the treatment of diseases such as EPM that are caused by similar organisms. The chemical structure of diclazuril is shown with other triazine derivatives in Figure 1. The triazine ring is present in all of the compounds; a benzeneacetonitrile group (benzene ring with an acetonitrile group attaching it to the centre ring structure) in all compounds except toltrazuril; and all compounds are correctly termed triazinones due to the presence of the ketone groups on the triazine ring structure (Fleeger 1997). Recent research utilised oral diclazuril (Clinacox) daily for 3 weeks to treat a horse with severe neurological impairment. This treatment resulted in significant clinical improvement (Granstrom et al. 1997). Research found that a closely related compound, toltrazuril, was well absorbed after oral administration to horses (Tobin et al. 1997). Recent research suggests that triazines may be selectively toxic for apicomplexans due to a chlorophyll a D1 complex that serves as the target site for such agents (Hackstein et al. 1995). This site is thought to be conserved in apicomplexans and to be absent in mammals (Hackstein et al. 1995). Therefore, triazine derivatives may exhibit selective toxicity to these parasites while causing few or no appreciable side effects in an equine patient. Based on encouraging preliminary evidence of bioavailability, selective toxicity and clinical efficacy, a clinical investigation of the efficacy of diclazuril for the treatment of EPM was initiated. The purpose was to: 1) evaluate the clinical efficacy of this compound in the treatment of EPM; 2) establish an effective daily dosage and treatment duration; 3) estimate the rate of relapse at 6 months; and 4) provide preliminary information on the occurrence of adverse effects associated with treatment.