A horse is considered a dead-end host since it cannot transmit the disease to other horses. The definitive host is the opossum,
shedding the infected egglike sporocysts into the environment via feces, which are consumed by horses grazing in parasite-infected
pasture or in feed or water. Intermediate hosts, which complete the two-host life cycle of S. neurona, include domestic cats, raccoons, skunks, armadillos and passerine birds.
The CNS, including the brain and spinal cord, is infected when the sporocysts migrate from the gastrointestinal tract into
the bloodstream to cross the blood-brain barrier. Once infected, horses may show neurologic signs fairly soon after exposure,
though most horses similarly exposed do not show signs since their immune response will ward off the disease. Other infected
horses may harbor the organism and develop signs at a later time.
Nicola Pusterela, DVM, PhD, Dipl. ACVIM, associate professor in the Department of Medicine and Epidemiology at the School
of Veterinary Medicine at UC-Davis, notes, "It's only speculation whether the horse will develop immunity to the protozoal
organism without developing disease, develop disease soon after exposure to the parasite or develop it at a later time. We
don't know. Horses will develop neurologic disease shortly after being experimentally infected, but what may happen under
natural conditions, nobody knows. We assume most horses become exposed and mount an immune response, and the organism never
gets into the CNS.
"And then there's a small percentage of horses, less than 1 percent, in which the organism will—probably not freely, but bound
to white blood cells—enter the CNS and then undergo different cycles of replication within the neuronal cells, leading to
inflammation and clinical disease," Pusterela continues.
Robert MacKay, BVSc, PhD, Dipl. ACVIM, professor of large-animal medicine at the University of Florida College of Veterinary
Medicine, notes, "As far as we know, for every horse that develops neurologic signs we can see, there are at least 50 that
are infected without [visible] neurologic signs. It's typical for the horse to become infected, develop an immune response
and never develop neurologic signs. The exposed horse that's infected and develops neurologic signs is an unusual situation.
The horse is relatively resistant to that kind of disease. That represents the tip of the iceberg of infections."
The factors that make one horse in 50 develop disease where others don't are unknown, says MacKay. Retrospective studies have
looked at populations of horses and identified some risk factors, such as age, previous adverse or stressful events and exposure
to environments rich in opossums. "Presumably, there's also a genetic component, which hasn't been thoroughly investigated
as to why some horses appear to be susceptible and most horses aren't," he says.
The fact that almost half of horses are exposed to the parasite but less than 1 percent are affected and show clinical signs
may be due to variations in the parasite's potency or a horse's ability to effectively mount an immune response. Stephen Reed,
DVM, from Rood & Riddle Equine Hospital, Lexington, Ky., thinks the answer is probably both. "But in reality, I would say
the horse's immune system is probably more important than the pathogenicity of organism, though we don't have the knowledge
to definitively say it's one or the other.
"In all the areas where we have the definitive host—the opossum—you see a large percentage of antibodies in the [horses']
bloodstream, indicating they've been infected and are making antibodies," Reed continues. "Because only a few of them get
neurologic signs, you have to believe they're able to clear the organism on their own. But there are some who argue it's only
infection with the very rare, highly pathogenic strain that causes clinical EPM. There's most likely truth to both sides.
I feel very comfortable that the role of the immune system is really critical."
No one knows if there are genetic factors between horses that affect their immunity. Jennifer Morrow, PhD, co-owner of Equine
Diagnostic Solutions (EDS) laboratory, Lexington, Ky., says, "There are certainly different strains of the parasite across
the country, so horses aren't becoming infected with the exact same strain of the parasite. There must be factors on both
sides that result in the fact that, while many horses are exposed, very few develop clinical EPM disease. Why that is is currently
Variations in the clinical neurologic signs of disease leading to deficits depend on where the parasite does its damage anatomically
within the CNS (i.e., brain, spinal cord or peripheral nerves) and how severe the damage is. The severity also depends on
several other factors, namely, the host, pathogen strain and, possibly, environment. "It's very complicated, and we really
don't understand it," says Pusterela.