EPM and the Immune System; A clinical perspective

Do you have a horse or know of one impacted by EPM? Equine Protozoal Myeloencephalitis (EPM) is unfortunately a common disease in the horse, impacting hundreds, if not thousands every year.  The outcomes for each case can vary dramatically, resulting in a huge expenditure for the owner and an uncertain future for the horse.  Give the huge variability in outcomes despite newer treatment options, one is left asking 'why' and what more can be done to aid in prevention and therapy to help increase the success rates. Maybe it is time to rethink our approach to these cases in order to maximize the outcome.

If we were to take 100 horses and expose them to the parasite known to cause EPM or equine protozoal myeloencephalitis, (S. neurona), we would find that all horses would develop an antibody response or become seropositive within a short period of time, but out of those 100 horses, likely only ten would develop clinical disease. That is 10%, but is still significant. Given this information, one would be inclined to ask why this is and if there is something we can do to expand to help change the course of the disease?  Is there a genetic predisposition on some level or is there potentially an immune component that is helping to protect those horses who did not develop clinical disease?

Experience and Thoughts on Equine Protozoal Myeloencephalitis in Practice

For the 18 years that I clinically managed EPM cases, it was interesting to me to see the variability in the responsiveness to the treatments.  Over the course of my career, the medication regimens changed from sulfa-based antibiotics in combination to the use of powdered medication used in the poultry industry (diclazuril) that we would have imported for use in certain cases.  In today's treatment world, we still have the older and well used regimens for the horse, but have now at our disposal more user friendly preparations.  Despite these changes in approaches, we have not seen, at least in my opinion, a dramatic shift in the recovery rate and remissions of disease.

As a practicing veterinarian, I was often witness to cases that relapsed, often within 1-2 months of therapy, while others would completely recover.  I had always believed there was a direct connection with the immune response and made it a standard to evaluate various white blood cell lines and levels in our cases.  Evaluating cases over the years, it became readily apparent that there was a direct connection with the immune response.  Those cases that seemed more responsive to treatment with fewer relapses demonstrated a normal level of a white blood cell called the Lymphocyte in pre-treatment bloodwork, while those that were more difficult to manage and relapsed had below normal lymphocyte counts.  Was this a cause and effect type of scenario, meaning did the low lymphocyte count predipose the horse to infection or was the lowered lymphocyte count a result of the infection?  Given the difference in lymphocyte values in infected horses, some normal, some not, one would have to conclude that it was not a result of the parasite but more a dysfunction in the animal that may have led to the infection.

It was just my opinion after all, but this back in the late 1990's when immune function was not a highly questioned topic in the horse.  Despite this, my intention was to improve patient outcomes and so we began to couple traditional therapies with immunotherapy, hoping to boost immune function and improve outcomes.  We began to use a cattle dewormer called Levamisole on a specific regimen and noted that in those cases in which it was used, the horses responded better, had fewer side effects and had a reduced relapse rate.  After many years, we began to incorporate other therapies, including various medicinal mushrooms, which seemed to actually produce an even better response.

Was it all theory and opinion or was there something to this observation?

Based on research information and input from many high level EPM researchers, the debate could go either way.  It has been noted that the parasite, S. neurona, could potentially inflict suppression of the immune response on the host as this is a common finding with other protozoal type infections. However, it has also been noted that horses under higher levels of stress or strain, including pregnancy, training and competition, seem to be at a higher risk of disease development.  This last fact seems to favor the concept of a compromised immune response contributing to an increased susceptibility to clinical disease.(1)

To be more specific, research has indicated that EPM affected horses actually seem to have an altered immune response, resulting in increased expression of a protein called IL-4 from lymphocytes, which resulted in an unfavorable response to the invading parasite.  In murine models, the ideal response is an increase in CD4 Th1 and CD8 lymphocytes with increased expression of interferon-gamma. (1)

So, going back to our example of 100 horses with one developing clinical signs, we could hypothesize that the remaining 99 horses were immune competent and able to defend themselves from active infection.  Going one step further, we could also theorize that the one horse that developed clinical disease may have had a defect in either the CD4 Th1 or CD8 cell lines, which led to an increased risk of infection; whether if that was due to genetics, diet or other influences is uncertain.

Intuition tells us there is a variable that exists that predisposes one horse to infection over another and now, we have actual science that backs up that opinion.  There is a difference and now we know it, but what can we do to minimize the impact?

Influences on Horse Immune Health

Immune function is dependent on many variables ranging from genetics to diet, but also includes environmental influences including stress. Immune function is also impacted negatively by elevated levels of inflammation, which is common in the stressed and competing equine athlete.  I think that in order for us to maximize the outcome in all of the cases, we have to take all of these variables into consideration.  It is by far much easier and cheaper to prevent any clinical disease through improved health than it is to treat when the disease arises.

Stress and the influences by training and competition is to me one of the biggest factors as most of the horses we have seen and consulted with were actively competiting.  Despite realizing this, it is hard to reduce the stress in many instances or at least persuade the owner or trainer of the importance of reducing stress.  All too often, we would initiate therapy in a patient and begin to witness results, but then the horse would be placed back in to training and resume the influences of stress....which often led to increased rates of relapse. In most situations, this resulted in a retreatment period for the horse and more expenses for the owner with a still uncertain outcome.

I believe, as a veterinarian and holistic practitioner, that we can modify the impact of stress upon the body.  We can use herbs and nutrients to decrease the impact of cortisol, help calm anxiety and support immune function. We can use herbs to reduce systemic inflammation and the impact on the immune response and cellular health. There is no doubt in my mind of their effectiveness, but we have to understand that one shoe does not fit all feet, meaning that each situation is different.  With an increased level of stress comes increased metabolic and nutritional demands on the body, plain and simple.  We can't feed each horse in training the same or supplement them all identically and expect the same results in each.  Every horse is an individual and each horse needs to be catered to for the best outcome.

I feel it is important to not only address the immune dysfunction that may be present, but also help to promote a healthy inflammatory response, as this is often tied in, creating ongoing damage and oxidative stress.  This is done through a combination approach in most cases.

EPM can be a devastating diagnosis for any horse owner to hear, but we have to realize that this diagnosis is not the end.  Medications are warranted in most cases, but we also have to remember what potentially opened that door for infection to occur and to manage each horse individually and in a supportive fashion.

If we take the 'complete' approach, I do believe that better outcomes can be reached. For further information regarding EPM and the horse, please read this article.

In another article, I have discussed Immune Support and concepts relating to the horse.

All my best,

Tom Schell, D.V.M.

Nouvelle Research, Inc.

1. Witonsky, S. et al. Horses experimentally infected with Sarcocystis neurona develop altered immune responses in-vitro, J. Parisitology, 94(5), 2008, 1047-1054