Is Parasite Resistance a Concern With EPM Treatments?

A veterinarian explains why antiprotozoals are unlikely to cause resistance among the protozoan parasites that cause EPM in horses.

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There is likely no danger of protozoan parasites developing a resistance to Protazil. | Photo:

Q: My horse was recently treated for equine protozoal myeloencephalitis (EPM). As a preventive measure, my veterinarian recommended a once weekly dose of Protazil (1.56% diclazuril). Is there a danger of creating treatment-resistant protozoan parasites, as has happened with internal parasites?

Laura, via email

A:  This is a question I often get and find particularly puzzling. While the equine industry faces challenges with antimicrobial and anthelmintic resistance, concern about antiprotozoals inducing resistant parasites can likely be crossed off the list.

There are two primary reasons. First, for resistance to develop, antiprotozoal drugs would need to be overused, selecting hardier organisms for survival. In my mind, that is not happening in the equine industry. Second, the life cycle of Sarcocystis neurona—the primary causative organism of EPM—shows us that even if resistance is selected, the parasite will die with the host. The rare exception would be if opossums scavenged the horse. Let’s take a closer look.

Biology of S. neurona makes resistance highly improbable

Sarcocystis neurona has a two-host life cycle—a definitive host, the opossum, and several intermediate hosts, with skunks, raccoons, armadillos, and cats among the most common. Opossums are commonly infected with S. neurona and are a major source of infection for horses. The horse is a dead-end host and becomes infected with S. neurona by ingesting food or water contaminated with opossum feces. S. neurona cannot be transmitted horizontally between horses, nor can it be spread by nonequine intermediate hosts.

Although limited evidence exists that the horse could serve as a natural intermediate host for S. neurona, it is unlikely that horses are normal intermediate hosts that contribute to the parasite’s life cycle. This is because S. neurona sarcocysts typically are not found in the tissue of horses, and equine carcasses are rarely accessible to opossums.

Hence, a horse treated with an antiprotozoal drug is highly unlikely to harbor resistant forms of S. neurona that can then be ingested by opossums, completing the parasite’s life cycle. Furthermore, all drugs that are FDA-approved for the treatment of EPM have been shown to yield concentrations at steady state that are in excess of what is needed to inhibit S. neurona growth. There are likely strains of S. neurona that are less susceptible to antiprotozoals, but that does not make them resistant. 

What happens in the horse stays and dies in the horse

Resistance is often a result of product overuse (or incorrect use), as we’ve seen with antibiotics and deworming compounds. However, the same comparison cannot be made with EPM treatments. Not only is overuse of EPM treatments unlikely, but the biology of the inciting parasite makes resistance highly improbable.

Some additional notes on the dosing regimen you describe: The once-a-week diclazuril preventive treatment has the goal to prevent reinfection but not flare-ups since we are not reaching minimum inhibitory concentration levels in the central nervous system. Further, the preventive treatment should only be used during the “risky” season (i.e. spring to fall and/or during the show season when the horse is more likely to be stressed).


Written by:

Nicola Pusterla, DVM, PhD, Dipl. ACVIM, is currently an associate professor of equine internal medicine at the University of California, Davis, School of Veterinary Medicine, as well as chief of large animal medicine and section head of equine medicine and dentistry. Pusterla’s research focuses on selected aspects of equine infectious diseases with an emphasis on epidemiology, clinical disease understanding, diagnostics, prevention, and treatment.

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