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Testing the horse with suspect EPM should yield values that assist in treatment decisions.  The IFAT shown in the photo is a positive result.  That doesn’t necessarily mean this horse should be treated with anti-protozoal medications!  Our study that defined relapses attributed to EPM categorized three diseases that have three different treatments. The diseases warrant different treatment because horses may have a one-time exposure or  be chronically exposed. Post-disease conditions that leave the animal with signs due to inflammation are also treated differently.

Sarcocystosis can be caused by S. neurona or S. fayeri.  Some horses are chronically exposed to Sarcocystis in the environment and continued exposure will result in new disease.  These cases are often interpreted as relapses. Disease in horses can be managed and prevented if the correct process is recognized.  The reagents we use to measure S. neurona allow us to determine if a horse has active disease, relapsing disease due to chronic exposure, or signs due to another condition.

Similarly, disease due to S. fayeri can be resolved and prevented if there is suspected environmental exposure.  About thirty percent of horses have S. fayeri and it is usually harmless, horses don’t show disease.  However, some horses do have disease or sub-clinical disease associated with S. fayeri.  We measure the toxin associated with disease-causing fayeri cyst and associate disease with the CRP test.  The CRP allows us to give significance to the presence of S. fayeri  toxin and determine if the infection is due to re-exposure.

The most important criteria in evaluating a horse before, during, and after treatment is the gait score or the presence of signs that indicate disease.  Lab values are important and give insight into the disease process.  The trend. obtained from repeating lab testing, has the most significance in long term case management.  Combined, signs and test results are a valuable method to manage horses.

Quick reference for sarcocystosis testing in a horse that improved with treatment:

S. neurona antibody declined after treatment, CRP trending to normal: indicates that the horse does not have repeat exposure to S. neurona in the environment.  MONITORING THE HORSE FOR CLINICAL SIGNS IS SUFFICIENT.

S. neurona antibody declined after treatment, CRP elevated: indicates that the horse does not have repeat exposure to S. neurona in the environment and there is another disease process. FURTHER TESTING TO DEFINE THE DISEASE PROCESS IS NEEDED.  TESTING FOR S. FAYERI TOXIN, LYME, OR AUTOIMMUNE DISEASE IS USEFUL. DEWORMING TO REMOVE ENCYSTED SMALL STRONGYLES IS USEFUL IN A FEW CASES.

S. neurona antibody increased within 1 month after treatment, CRP trending to normal: indicates that the horse may not have repeat exposure in the environment and responded to the elimination of parasites. A RISE IN TITER IS NOT UNUSUAL, ANTIBODIES WILL REMAIN FOR 5-8 MONTHS. RETESTING THE S. NEURONA SAG’S AT 6-9 MONTHS IS USEFUL.

S. neurona antibody increased after treatment, CRP elevated: indicates that the horse does have repeat exposure in the environment or there is another disease process. FURTHER TESTING TO DEFINE THE DISEASE PROCESS IS NEEDED.  TESTING FOR S. FAYERI TOXIN, LYME, OR AUTOIMMUNE DISEASE IS USEFUL. DEWORMING TO REMOVE ENCYSTED SMALL STRONGYLES IS USEFUL IN A FEW CASES.

S. fayeri antitoxin declined after treatment, CRP trending to normal: indicates that the horse does not have repeat exposure in the environment.   MONITORING THE HORSE FOR CLINICAL SIGNS IS SUFFICIENT.  If the horses was treated for 6 months for S. fayeri the horse can discontinue treatment.

S. fayeri antibody declined after treatment, CRP elevated: indicates that the horse does not have repeat exposure to S. fayeri in the environment and there is another disease process. FURTHER TESTING TO DEFINE THE DISEASE PROCESS IS NEEDED.  TESTING FOR S. FAYERI TOXIN, LYME, OR AUTOIMMUNE DISEASE IS USEFUL. DEWORMING TO REMOVE ENCYSTED SMALL STRONGYLES IS USEFUL IN A FEW CASES.

In our testing/treatment protocol we will not see an increase in S. fayeri antibody after treatment to indicate acute disease was resolved. The anti-toxin is a response to cysts that produce toxin. The CRP is the indicator of disease.

The last disease process that is related to sarcocystosis is inflammation.  Chronic neuromuscular inflammation is polyneuritis.  Pathologic inflammation can be related to new or old disease.  That will be the final topic in this series.  Stay tuned.

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.

“A lie told often enough becomes the truth”. --Vladimir Lenin

If you’re not talking about inflammation, then-- by exclusion-- you’re lying about equine protozoal myeloencephalitis.  Reviewing only the causative agents (protozoa), life-cycle of the parasite, antibody testing, and treatment perpetuates misunderstanding.  Old ideas (EPM is enzootic and effectively untreatable, most horses are doomed to relapse) repeated often enough become a self-fulfilling prophesy.

Instead of viewing EPM as a population of horses infected with S. neurona containing a sub-group of untreatable, relapsing horses, chew on this.  View the population of ataxic horses as the whole pie (data set).  Ataxia is ubiquitous in horses and ataxia has several etiologies.  Sometimes ataxia in horses is caused by S. neurona.  Our data associates ataxia and S. neurona  in 54% of ataxic horses.

The ideas are very similar, however the practical difference between the views is that we can treat the latter group successfully—we are all too familiar with the treatment success of the former group.  Treating inflammation appropriately is key.  Understanding and managing the two components of EPM, inflammation and infection, are important to long term success.  The successful management of a horse with EPM will not be achieved by treatment alone, management takes an understanding the disease process.  It takes some work and it isn’t hard.

We make the association based on a gait assessment score, GAS, and the presence of specific serum antibody to the predominant surface antigens of S. neurona-SAG 1, 5, or 6.  A GAS of >1 and an ELISA SAG 1, 5, or 6 titer >8 attributes the ataxia to S. neurona.  A response to treatment supports the diagnosis.

Horses that do not have antibodies to S. neurona, with a positive GAS, are considered the rest of the pie, 46%. Just for arguments sake, call this group of animals IE-- disease due to inflammatory encephalitis.

If licensed anti-protozoal drugs are used for treatment the treatment efficacy is (published) 58%.  The difference in treating inflammation along with an anti-protozoal in suspect cases of EPM is 35%.  Are we just treating IE horses with an effective immune modulator or is there reason to think S. neurona played a role in disease? That is an experimental question for scientists, horse owners and veterinarians want results.

When horses show signs after "EPM" treatment they are called “relapses”.  Relapses are attributed to ineffective killing of anti-protozoals or re-infection.  The relapse rate with conventional antiprotozoal drugs are reported as 25% (ReBalance) and 20% (Triazines)—all of these drugs decrease the detectable antibodies in serum leaving, on average, 17% of horses in the IE category—ataxic with no antibodies--these are post-treatment IE cases but are attributable to S. neurona.  The rate of relapse (inflammation post-treatment) is three times higher in horses in which the inflammation was not addressed at the time of protozoal killing. Seventy one percent of ataxic horses with a presumptive diagnosis of EPM (no alternate diagnosis) had a root cause of inflammation that was most likely due to S. neurona infections.  This should be the topic of conversation about EPM.

The math leaves us to believe that 22% of horses with IE are horses with inflammation with an undetermined cause.  In some cases, we detect the effectiveness treatment for IE by serum CRP.  The anticipated treatment failure rate of treating inflammation and ignoring the inciting infectious cause, including S. neurona, would be high.  Our data indicates that S. neurona is a significant cause of IE in horses and should be a top consideration in treatment options.  Our research indicates that inflammation is the larger issue.  When treatment fails other obvious causes of IE should be investigated.