EPM Continues To Defy Logic

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A small fraction of the horse population is susceptible to EPM (equine protozoal myelitis), and no one knows why. This presents the twin problems of making it difficult to induce the disease in test horses for study and to determine which horses are susceptible and which aren’t. Attempts to cause EPM by feeding the organisms failed to induce the disease, although those horses did develop EPM antibodies.

More recently, researchers at Virginia-Maryland Regional College of Veterinary Medicine (Virginia Tech), wanting subjects for testing drugs, inoculated horses with the life stage found in cells of the nervous system (the merozoites) of horses with natural infections. The organisms were injected directly into the subarachnoid space, bypassing the tissues of the blood brain barrier and getting right into the cerebrospinal fluid (CSF). However, after 4 ?? months, none of the five test horses developed EPM. Prior to the test, all five horses were confirmed negative for EPM antibodies. After the inoculation, all five converted to positive blood and CSF antibody levels, despite never showing the disease. They therefore had false-positive CSF tests — results that indicated exposure but not disease.

One of the working theories to explain why some horses get EPM and others don’t is that there must be some weakness in the normal barriers to the disease, such as the gut lining or the blood brain barrier. The Virginia Tech findings, however, suggest even bypassing these natural defenses is not enough to cause EPM. Work is continuing at Ohio State, under the direction of Dr. William Saville, on developing a method of administration of organisms that will predictably result in EPM. A paper updating their progress is in the works.

One theory to explain why the direct nervous system inoculation did not produce the disease is that it may be necessary for the organisms to travel through the tissues before they can produce the disease. That’s possible, but it’s unlikely. The major observable change in the organisms as they go from the gut to the tissues is in the life stage they represent. Since the organisms injected were in the form known to invade the cells of the brain and nervous system and tissues, tissue effects were less likely.

Some people are also suggesting the researchers didn’t wait long enough for symptoms to develop. Again, nothing is impossible with EPM, but 4 ?? months is an awfully long time. Foals as young as two months of age have been diagnosed with EPM. Additionally, the researchers did postmortem examinations and cultures on the CSF from two of the test horses and were unable to find any evidence of invasion, and cultures remained negative as well.

These findings reinforce the fact that it may be impossible to diagnose EPM with 100% laboratory certainty in a living horse. A positive CSF tap is still the most suggestive finding (positive PCR being more suggestive than positive antibody levels in the CSF), but this study again shows you can even have the organism in the spinal fluid without having EPM. The odds of a horse just happening to have protozoa in his cerebrospinal fluid and having a neurological disease of another type are probably pretty small, so if the horse is showing clear neurological signs compatible with EPM, the chance of a positive result being false are low. On the other hand, if the symptoms are vague and EPM is just one of the things on the list, positive CSF findings are not sufficient justification to stop looking for other causes.

Unfortunately, we are no closer than before to understanding why about 1% of the horse population is susceptible to EPM, but the others are not. Your best bet remains building your horse’s immune system.

Reference: Vet Parasitol 2000 Sep 20;92(2):157-63, from Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Drs. Lindsay et al.

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