POSSIBILITIES FOR PREVENTION

areas of the country the horse owner may not have access to veterinarians who feel comfortable doing a spinal tap in the field. Having a blood test that would be accurate enough would be very helpful.”

In the meantime, veterinarians sometimes rely on one other method when trying to determine whether a horse has EPM: Start him on antiprotozoal drugs and see how he responds---if he improves, EPM is likely. The diagnosis-through-treatment approach can work, says Pusterla, but requires caution: “A lot of horses who have EPM are also rested and given other types of medication such as anti-inflammatory drugs, and they get better,” he says. “But we don’t know whether clinical improvement was due to the antiprotozoal drugs or other drugs and rest.”

The bottom line is, despite advances in testing, veterinarians must still rely on traditional---even old-fashioned--methodology when diagnosing EPM, considering the big picture rather than relying mainly on lab results. “The serological tests help support a diagnosis, but we shouldn’t forget the horse’s history and clinical signs to conclude that a horse has EPM,” says Pusterla. “If a horse presents with asymmetrical and progressive clinical signs, this is worth looking into, versus a horse that presents with symmetrical neurological signs.”

TREATMENT OPTIONS

Three FDA-approved anti-protozoal drugs are now available to treat EPM:

• Ponazuril (tradename Marquis; generic name toltrazuril sulfone), an oral paste administered once daily for 28 days.

• Pyrimethamine and sulfadiazine (tradename Rebalance), an oral sus- pension administered once daily for as long as 120 days.

• Diclazuril (tradename Protazil), a pelleted, alfalfa-based top-dressing fed for 28 days.

These medications cross the bloodbrain barrier and enter the cerebrospinal fluid at levels high enough to either limit the reproduction of the protozoa or kill them outright. “All of the treatments have similar efficacy. Protazil [the newest of the three] has emerged as an alternative treatment but not necessarily a superior treatment,” says Johnson. “There is no one regimen or drug that is clearly superior to the others, but it is nice that owners and veterinarians have options. Part of the decision of which to use will depend on the owner and the horse, and the ease or reluctance of that horse taking oral medication.”

At the standard doses, it can take at least a few days for ponazuril to reach therapeutic levels in the CSF, but researchers are working to find ways to help the drug work faster. In 2009, a study from the University of Illinois showed that combining toltrazuril sulfone with DMSO (dimethylsulfoxide) helped the drug reach therapeutic lev- elsel three times faster than administeringad it without DMSO.DM “DMSO is very good at carrying many drugs throughthr physiological barriers,” says Johnson. “Some practitioners do this and some don’t.”

In more severe cases, or if the disease is progressing rapidly, a veterinarian may opt to start a course of ponazuril treatment with a “loading dose”---the administration of up to seven times the normal amount---before beginning the routine drug regimen. With this method, therapeutic levels of ponazuril in the CSF can be achieved much faster. “The initial loading dose that was published with the study in Illinois was seven times the label dosage,” says Johnson. “Thus, if you were using Marquis paste, you would give the whole

tube---atube a week’s worth of the drug---at once.”

However, follow-up work done at Rood and Riddle showed that using a smaller loading dose of ponazuril would yield the same results. “That study showed that giving just three times the daily dose---about half the tube---was sufficient to raise spinal fluid levels quickly,” says Johnson. “Many practitioners today, but not all, are using a loading dose at the beginning of treatment. Even if you don’t use it, spinal fluid levels will eventually reach the point they need to be; it just takes longer. Whether or not your veterinarian will use DMSO depends on practitioner preference; at this point there is not a consensus regarding treatment protocols.”

For now, the most effective way to protect your horse from EPM is to limit his exposure to the causal protozoa, but that is easier said than done (see, “Managing“Manaa to Prevent EPM,” page 50). R Researchers are hard at work on o other prevention measures.

For example, research is underway to determine whether therapeutic drugs, administered at a low dose, can be used to prevent EPM in healthy horses. Pusterla recently published a study in which diclazuril showed promise in protecting foals from S. neurona infection. (For a report on the study see “A Way to Prevent EPM?” Medical Front, page 14.)

No vaccine against EPM is currently available, and there probably won’t be one for some time. “It is very difficult to establish a vaccine for protozoa,” says Pusterla. “Not many vaccines have been developed for protozoal diseases in humans or animals. An EPM vaccine for horses with a conditional license [in 2001] was pulled off the market mainly because they were not able to establish a good animal model.”

Indeed, the lack of a good research model is one of the primary challenges EPM researchers must overcome--whether investigating treatments or potential vaccines: It is difficult to cause a horse to develop EPM in laboratory conditions.

“There are currently two models,” says Reed. “One is oral feeding of the protozoan sporocysts to the horses. That model requires maintaining a colony of raccoons, to be fed to the opossums. Then you sacrifice the opossums to get the sporocysts to feed to the horses. This model was a pretty good one for studying the disease, but it takes a lot of effort to maintain it. The other model involves collecting white blood cells from a horse and co-incubating them with the protozoa. Then horses are infected with intravenous injections, but this skips several stages of natural infection, which may mean that research findings might not apply in natural settings.”

Researchers have tried alternatives but, says Reed, “each model has its shortcomings. We looked at whether there are any small mammals, besides mice, that might serve as models,