Defining EPM: Sarcocystosis

blue day before oroquinInfection with Sarcocystis is called sarcocystosis. Equine sarcocystosis, or equine protozoal myeloencephalitis (EPM), is an infection by protozoa that results in inflammation of the nervous tissues.  These parasites can sometimes be found in the central nervous system (CNS) although inflammation can cause signs without the parasite entering the CNS.  Note that EPM is a syndrome, it is caused by infection and inflammation. Infection causes a variety of signs that include muscular disease and neurological dysfunction. Sarcocystosis can be chronic in horses, those that undergo treatment frequently relapse. Relapse is most likely due to re-exposure of the protozoa in the feed or environment.

There are two protozoa that infect horses, Sarcocystis neurona and Sarcocystis fayeri. The horse is a natural host for S fayeri and may be less inflammatory that S neurona.  The horse is not a natural host for S neurona, the infection is called aberrant. Both of these organisms can cause clinical signs that look like EPM. There are tests to detect infections and exposure to these organisms. 2016 S fayeri

Protozoal infection stimulates immunity in the horse.  Innate (cellular) responses that trigger specific defensive pathways are activated quickly. These pathways remain active as long as the infectious stimulus is present.  Sometimes, these pathways become chronic by creating a “feedback” loop.  The innate response stimulates the production of proinflammatory  molecules, these molecules feed a signal to initiate the inflammatory reaction again, hence the results of  starting inflammation can be a chronic cycle.  These pathways are not specific.  Any infection can stimulate the initial response. Normally, when the infection is treated effectively the protective responses turn off.  Chronic inflammation is a dysfunction of the immune system.

We test for the presence of proinflammatory molecules found in the blood stream.  This is useful and an adjunct to other tests that are specific.  In our laboratory we quantitate C-reactive protein (CRP) to identify the extent of the pro-inflammatory pathway.  Values are measured from 0-99.  An absolute value isn’t as valuable as evaluating a trend.  A value that is above 16 is abnormal.  Values that are above 39 are statistically significant and suggest the clinical signs are due to inflammation related to specific conditions that we can also detect.

Another type of immune response to protozoal infection is acquired immunity.  Acquired immune responses result in specific antibodies and memory cells that target the infection.  When the horse gets re-infected, memory cells are primed and ready to act faster that in the initial insult.  Re-infected horses are “experienced” with the infecting organism, whereas a horse with no experience is called “naïve”. Antibodies against S. neurona are used to link a causal agent with clinical signs seen in horses with EPM.  Similarly, S. fayeri  produces antibodies in horses.  We can use different tests to distinguish between S. neurona and S. fayeri  infections.

Opossum_03-HangingBranchThe horse acquires Sarcocystis neurona by eating hay or feed that is contaminated with neurona-infected opossum feces. Opossums are the definitive host.  Definitive hosts exclusively produce the infective stage of Sarcocystis.  The infectious “eggs” (sporocysts) hold sporozoites that are short-lived in the horses’ intestine. There are three serotypes of S. neurona that can cause sarcocystosis in horses.  Often, the opossum is infected with multiple serotypes!  Dogs are definitive hosts for S. fayeri . Horses are infected by eating hay or feed that is contaminated with fayeri-infected dog feces.  It was long thought that S. fayeri   infections in horses were benign, unless a horse was debilitated from starvation or another disease.  Up to one third of horses in the United States are infected with S. fayeri.

The horse is an unnatural host for S. neurona.  After the initial infection, the parasite goes through its life cycles: sporozoitesbovine produce 1st generation merozoites and this stage kills host cells. First generation merozoites mature and produce 2nd generation merozoites.  These second generation merozoites must enter muscle cells and turn into cysts.  The horse is an unfriendly host to neurona merozoites and S. neurona is unable to make cysts. The horse is very friendly to S. fayeri and the second generation fayeri merozoites encyst in muscles. The cysts eventually mature and die and this is when they release toxins that result in inflammatory reactions.

The horse responds to both Sarcocystis infections by innate immunity.  Elevated CRP levels are seen in both diseases. In fact, the horse can look normal and have an elevated CRP.  This is called sub-clinical inflammatory disease. Sporozoites of Sarcocystis don’t produce enough identifying molecules to simulate acquired immunity.  The acquired immune response to S. neurona is elicited by the merozoitesSometimes, as disease progresses or with some treatments, these organisms can hide the molecules that stimulate antibodies. However, if first generation merozoites are being produced from sporozoites, antibodies will be stimulated to the “new” infection, even if the infection doesn’t progress from the gut into the blood stream of the horse.

The foregoing is a description of the pathogenesis of sarcocystosis in horses and can be used to understand the results of testing.  The disease process, from infection to immunity, was used to form our three disease model of EPM which are: 1) S. neurona sarcocystosis, 2) S. fayeri sarcocystosis, and 3) post- treatment EPM inflammatory syndrome (PTEDS).  Pathologic PTEDS progresses into the treatable autoimmune polyneuritis or a condition known as polyneuritis equi.

An elevated CRP concentration indicates inflammation.  If there are no apparent clinical signs when the sample was taken, the horse has “sub-clinical” disease.  An elevated CRP value, found along with antibodies to a specific organism (S. neurona, S. fayeri, or Borrelia, Lyme)…indicates there is active disease.  We associate elevated CRP values in horses without Sarcocystis antibodies with pathologic, chronic inflammation that results in autoimmune polyneuritis.