Horse owners with EPM horses often have questions about alternative treatments, new diagnostic tests and the status of research into EPM. We asked Dr. David Granstrom, a pioneer of EPM research and a world-recognized expert, for help understanding this debilitating disease.
How long have you been involved in EPM research and what types of studies have you done’
I began working on sarcocystosis in cattle as a graduate student at Kansas State University in 1983. I joined the faculty at the University of Kentucky in late 1988 to study EPM. At that time, Sarcocystis was believed to be the primary cause, but it hadn’t been proven. Initially, I used reagents developed to study cattle sarcocystosis in my work at UK. I used antibodies against cattle Sarcocystis to demonstrate the presence of similar parasites in the brain and spinal cord of horses that had died due to EPM.
I was attempting to culture the causative organism from postmortem tissues when Dr. J. P. Dubey and his colleagues at the USDA cultured S. neurona. I was able to collaborate with them by demonstrating that antibodies against cattle Sarcocystis cross-reacted with S. neurona. This led to a long and productive collaboration with Dr. Dubey and others that resulted in the standard Western blot test for EPM, established regional seroprevalence, identified the opossum as the definitive host of S. neurona, developed the initial EPM infection model, and the first FDA-approved treatment for EPM.
How many different organisms have now been identified as capable of causing EPM’ Is there any estimate of how many cases may be caused by organisms other than Sarcocystis neurona’
Neospora hughesi also infects the central nervous system of horses resulting in the same clinical signs observed with S. neurona infection. Although other protozoal organisms may be able to infect the equine central nervous system, none have been identified as a cause of clinical EPM.
Are there any clinical signs exhibited by EPM horses that help put it higher on the list of possible causes when a horse has neurological symptoms’
EPM may produce clinical signs commonly associated with almost any equine neurologic disease. However, incoordination or ataxia that affects one side more than the other has been most commonly associated with EPM. Similarly, muscle wasting or atrophy on one side that is not mirrored on the opposite side has been more commonly associated with EPM than other equine neurologic diseases.
Many people seem to believe EPM can be diagnosed solely on the basis of an abnormal neurological exam, and that cerebral spinal fluid (CSF) testing is too prone to error to be of any use. Do you agree’
A thorough neurologic exam, done by an experienced clinician, provides the primary basis for an EPM diagnosis. However, serology and CSF testing continue to serve as useful adjuncts for the accurate diagnosis of EPM. Due to the relatively high-exposure rate to S. neurona and dramatically lower incidence of clinical disease, positive serology is of little value. However, negative serology effectively rules out EPM from the list of possible causes. The situation is somewhat different for CSF, but the end result is similar. Positive CSF increases the likelihood that EPM is present, however, negative CSF effectively rules it out. The accurate diagnosis of equine neurologic disease often requires a process of elimination utilizing a combination of multiple diagnostic techniques.
In the scenario of a horse with compatible neurological signs and positive Western Blot test on the CSF, does PCR testing help make the diagnosis more definitive’
The PCR test was designed to detect S. neurona DNA in CSF. Although the assay is technically sound, detectable amounts of parasite DNA rarely appear in the CSF of affected horses. A positive test would be definitive, but a negative test wouldn’t rule out EPM. There have been some cases with positive PCR even though CSF was negative on Western blot. This would be most likely to occur very early in the course of initial infection, before the affected horse had time to mount a detectable antibody response.
Blood-contaminated CSF samples can’t be tested reliably for the presence of parasite-specific antibody. Since PCR testing is not affected by blood contamination, it provides a less-sensitive alternative when blood is present in the CSF sample.
Our readers have asked us about the ELISA antibody testing being offered by Antech Diagnostics, which gives a quantitative titer against some surface antigens (SAG1). What are the pros and cons of this compared to Western Blot’ How does it compare to the ELISA SAG2, and the ELISA directed at IgM and the SNUCD-1 antigen’
The Western blot test has been in continuous use for over 15 years. None of the other tests have undergone extensive clinical testing in the field. The SAG2 and IgM capture ELISAs are not available commercially. It remains to be seen how they will perform using routine clinical samples. Recombinant ELISAs depend on a small number of, hopefully, very specific antigens. Unfortunately, horses don’t produce antibodies that react with every antigen. Some horses are simply incapable of ”seeing” the antigens used, and some strains of S. neurona may fail to produce sufficient antigen to induce a detectable response. In both cases, the affected horses will test negative.
The most effective recombinant ELISAs will need to include a cocktail of highly specific antigens in order to approximate the sensitivity of the Western blot in actual practice. These do not. The small number of defined control serum and CSF samples used to validate these tests do not approach the amount of variability encountered among hundreds of thousands of clinical samples from the general equine population.
The IgM capture ELISA represents an interesting approach that has worked fairly well to detect initial exposure to a number of infectious organisms in a variety of animal species. This is because IgM is the class or type of antibody produced by the body upon initial exposure to an infectious agent.
Subsequent exposure typically results in a class switch to IgG antibody (detected by the other tests). Therefore, IgM capture assays are most useful for the diagnosis of diseases with low serologic prevalence. Horses in the U.S. appear to be exposed to S. neurona repeatedly, which helps explain the high serologic prevalence in much of the U.S. Seroprevalence also increases with age. Therefore, an IgM capture ELISA may aid in the diagnosis of EPM in horses under one to two years of age that test negative on the Western blot. It remains to be seen if good correlation exists between recent exposure and the onset of clinical disease. Certainly, some cases result from acute exposure, but the vast majority appear to develop over time.
Given that many horses are never necropsied so we really don’t know, do you think that EPM is either over or under-diagnosed’
I believe EPM was under-diagnosed before it became the disease de jour in the early ’90s. It probably was over-diagnosed in the mid-’90s, but much has changed over the l ast 10 years. We know much more about EPM and other equine neurologic diseases today. Greater appreciation for the limitations of EPM testing, the introduction of West Nile Virus across the U.S., and the recent emergence of EHV-1 have altered the diagnostic landscape. Differentiating equine neurologic diseases remains one of the most difficult diagnostic challenges in clinical practice, but the veterinary community constantly strives to apply the latest information and techniques to keep the quality of care moving forward.
What is the current estimate of the percentage of the equine population nationwide that is suffering from EPM, and how does this change regionally’
The incidence of clinical EPM remains quite low. The estimate is well below 1% of the equine population.
In looking at the efficacy data on the new drug applications submitted to the FDA, all the current treatment regimens seem to have fairly equivalent results in terms of clinical improvement. Is any type of treatment truly better’
Veterinarians use professional judgment to develop an optimal therapeutic plan based on available information and experience. Each of the three approved drugs has particular strengths and weaknesses, but all have been shown to help horses recover.
Veterinarians develop preferences based on experience. Typically, they initiate therapy with the drug or combination of drugs they believe provide the best chance for recovery. If that approach fails, another drug may be substituted. Experiments that led to the first FDA-approved drug for the treatment of EPM (Marquis) were done while I was at the University of Kentucky. I’ve been pleased with the effectiveness of the drug when used in an appropriate therapeutic plan.
What results from treatment should an owner reasonably expect’
The vast majority of affected horses improve with treatment. The amount of improvement depends on a number of factors. I think most clinicians would agree that early diagnosis and treatment is the single most important factor for a good outcome. The likelihood of irreversible CNS damage increases over time. Mildly affected horses, treated early, have the best chance for full recovery. It has been estimated that approximately 25% of affected horses make a full recovery.
From time to time we hear of treatments such as intensive ivermectin dewormings, tubing horses with single- or double-dose of high-dose Baycox, herbals or even serial injections with the EPM vaccine supposedly curing EPM. Is there any basis at all for those claims’
Baycox contains toltrazuril, the precursor of ponazuril, which is the active ingredient of Marquis. However, this formulation has not been subjected to clinical trials required to establish an optimal dose or receive FDA approval. I am unaware of any controlled experimental trials that substantiate the effectiveness of ivermectin, herbal medications, or homeopathy for the treatment of EPM. In my opinion, none of these approaches provide a viable alternative to current FDA-approved therapeutic agents.
If a horse is treated with one of these things and his symptoms improve, is it safe to assume the problem wasn’t EPM in the first place’
It’s difficult to control all the variables associated with an experimental trial under the best of conditions. Any number of factors can confound results and preclude drawing a meaningful conclusion. It’s probably best not to assume anything.
What about colloidal silver as a treatment’
I am unaware of any controlled experimental trials that have substantiated the effectiveness of colloidal silver for the treatment of EPM.
What are the controversies surrounding the EPM vaccine’
Whether or not the vaccine actually prevented clinical disease was never firmly established, but it did induce an antibody response that interfered with interpretation of diagnostic testing.
With such a small percentage of exposed horses ever developing EPM, how could this vaccine ”prove” itself in the field’
A large multi-center trial comprised of large referral centers around the country was established at Texas A&M a number of years ago to help establish field efficacy. The small number of cases referred and limited vaccine use severely limited progress.
Has any progress been made in determining why some exposed horses develop EPM and others don’t’
Nothing definitive has been established. Recent completion of the equine genome sequence should accelerate the process.
What are some practical measures owners can use to reduce the risk of EPM for their horse’
Prevent the access of opossums to feed and water. Keep the area clean. Opossums eat anything. Observe best management practices, e.g., adequate nutrition, vaccinations, de-worming, safe environment, regular exercise, preventive dental care, etc.