EPM Continues to Puzzle Scientists

Photo: Rosettes of the protozoan organisms that cause EPM can be grown inside cells under laboratory conditions. (Photo courtesy of Dwight Bowman.)

EPM's most common signs are incoordination and weakness, but the initial signs may be low key and more vague, such as mild lethargy, attitude change, subtle gait changes, inability to exercise as well as before, and difficulty maintaining complex gaits. The more severe signs include incoordination, inability to stand, lameness, facial paralysis, stumbling, falling, and tremors. Although most common among young adult horses and yearlings in training or young racehorses, the disease can infect horses of any age.

EPM, which is becoming more and more commonly diagnosed, can be life threatening. Veterinary scientists are still puzzled over many aspects of the disease, says Dwight Bowman MS, PhD, an associate professor of parasitology, who has been studying the disease since it was identified in 1991.

"Veterinarians are perhaps more puzzled now than they were just a few years ago when they thought the various pieces had come together to explain the method by which horses became infected and why disease developed," he says.

In the late 1970s, researchers found a microscopic protozoan in the nervous tissue of horses with signs of neurologic disease. In the early 1980s, it was suggested that these organisms were similar to the Sarcocystis group of parasites that characteristically have two hosts: a final carnivorous host in which the parasites live in the intestinal mucosa and produce transmission stages that are passed in the feces, and an herbivorous intermediate host that ingests the fecal stage and develops cysts in their tissues. In the early 1990s, the parasite was isolated from horses that had developed severe signs of EPM, and the isolated organism was given the name Sarcocystis neurona.

To find the host of the disease, researchers looked at potential final hosts whose geographical distributions overlapped those of the reported cases of EPM. EPM, they found, followed the distribution pattern of the common opossum, and indeed, using molecular tools, the opossum was identified as the natural final host of this organism. When researchers went to the literature, they matched the newly identified Sarcocystis neurona with one described a hundred years ago as Sarcocystis falcatula.

"This led to a fairly well-grounded and acceptable hypothesis that the EPM organism was S. falcatula and that it was cycling between a sarcocyst stage (cysts in the muscle tissue) in birds and a sporocyst stage spread throughout the environment in opossum feces," Bowman explains. "In this scenario, horses are infected by eating or drinking material contaminated with sporocysts shed by opossums."

Several newer studies, however, including one conducted at Cornell, have shown that feeding uninfected horses up to 60 million sporocysts from the feces of infected opossums does not cause the signs of the disease or any immunological changes in the horses' blood. In some cases, horses fed sporocysts have developed neurologic signs, but neither organisms nor the DNA of organisms have been recovered from these horses at necropsy. Also, it has been recently shown that the organisms isolated from horses are morphologically different from those considered to be the avian parasite Sarcocystis falcatula.

"Thus it appears that the initial jubilation over having discovered the source of equine infection has been misplaced and we find ourselves almost exactly where we were when the organism was first described in 1991," says Dr. Bowman. "Now the possibilities seem twofold. One possibility is that the actual identity of the species of Sarcocystis cycling in wildlife has not been determined and, therefore, the experimental infection of horses does not induce disease. A second possibility is that some other factor or agent predisposes horses to develop disease or causes an existing infection with Sarcocystis neurona to change from a latent to a lethal condition.

Bowman recently received a grant from the Harry M. Zweig Memorial Fund to obtain information relative to the first of these two possibilities. The hypothesis continues to be that the causative organism in EPM sheds sporocysts in the feces of an animal that is indigenous to the Americas because EPM has not been observed in Europe, Africa, or Asia. He also believes that cysts that serve to infect these carnivores are present in muscles in small vertebrates such as birds or rodents.

"We know there are many species of Sarcocystis in wildlife that are either not described or very poorly known. Basically, we will reproduce the work that led to the choice of the opossum-bird model with other carnivore and omnivore-prey systems," explains Bowman. "Although we still do not know what the source of infection is for the horse, we now have a much greater ability to look for it than we did in the early 1990s," he says.

Bowman's laboratory now has the expertise to maintain Sarcocystis species in culture. He also has a bird model in the parakeet that allows easier isolation of organisms in cell cultures and the development of muscle cysts that can be fed to potential final hosts. His lab has the technology to distinguish the various Sarcocystis species molecularly, and work is progressing collaboratively with Dr. Antoinette Marsh at the University of Missouri and Dr. J. P. Dubey at the U.S. Department of Agriculture in Beltsville, Maryland.

"Our goal is to isolate and identify an organism from wildlife hosts that is identical to the EPM organism we find in diseased horses and is capable of inducing the disease in horses. Work by others and ourselves has indicated that the opossum is host to several Sarcocystis species, and one of these may be Sarcocystis neurona."

Bowman plans to isolate various Sarcocystis sporocysts from the feces of wild carnivores such as opossums, raccoons, skunks, foxes, and coyotes and, perhaps, some raptors and vultures that will be used to infect parakeets and mice. From the parakeets and mice, Bowman and his colleagues will harvest organisms to initiate their growth in cell culture. Since each carnivore probably is a host to more than one species of Sarcocystis, the researchers will try to develop techniques to identify specific isolates.

Treatment and Prevention

Thomas Divers DVM, Dipl ACVIM, a professor of medicine who is the coinvestigator on this project, has been wrestling with the treatment of this disease for years.

"Once horses become infected with the culprit species of Sarcocystis, probably by ingesting grain or other food or drinking water that has been contaminated, the parasites migrate to the central nervous system, including the spine and brain," he says.

Recent studies have shown that about 50 to 60 percent of horses in areas with high rates of EPM, such as the Midwest and Northeast, seem to have been exposed to Sarcocystis, though only a small percentage actually develop neurological symptoms. Researchers believe that symptoms develop from the body's inflammatory response to the parasite causing structural damage in the central nervous system.

The disease is difficult to diagnose without a full battery of tests that includes a spinal fluid sample to look for antibodies against the parasite. Early treatment is important for recovery. Treatment, which typically lasts one to four months, involves parasite-killing drugs and sometimes anti-inflammatories and immune system-boosting medication. While most horses improve with treatment, only about 10 to 20 percent of treated horses seem to make a full recovery. About 70 percent partially recover, and about 10 percent must be euthanized. If left untreated, most horses tend to deteriorate.

"At present, the best way to prevent this disease is to protect horses from exposure to potential sources of feed contaminated with the feces of wildlife," Bowman says. "Try to keep opossums, raccoons, and other carnivores out of horse barns. Keep grain for horses in containers with tight-fitting lids. It is important to keep watering troughs as clean as possible. It is of course impossible to prevent infection when animals are at pasture, but maintaining a tidy pasture with minimal trash or surrounding undergrowth will be likely to preclude the activity of most of these hosts."