Friday, September 21, 2012

What Does a Low EPM Titer Mean?

Red's EPM ELIZA peptide antigen blood test results came back:

SAG 1 - 2
SAG 5 - 2
SAG 6 - 2.

This is essentially a zero antibody result.  In a horse who's had an active EPM infection (neurological symptoms and a previously high titer), it likely means that the horse has had EPM and the infection has cleared - this usually will result in significant improvement in neurological symptoms.  This was Red's status after his first bout of EPM and treatment.  At that point he made a full recovery and had no neurological symptoms at all - he was completely sound and rideable.

At this point, he has clear neurological symptoms, not just lameness in one leg (with no heat/swelling or any other indication of residual mechanical injury).  So what does this zero result tell us? - it turns out that, as more is learned about the disease and its mechanisms, particularly about early stages of the disease, there are a number of possible answers.  There are apparently other horses out there with low or marginal titers who do have neurological symptoms - so what's up with that?

Here are the possibilities as I understand them, from reviewing information on Dr. Ellison's web site, published papers, and talking to my vet, who has had experience with a significant number of horses with EPM.  Please remember that I am not a vet, and some of what I'm going to say is speculation at this point regarding the disease process and what may be going on with Red, so please do not attribute what I'm saying to anyone other than me - any errors are mine.  Ongoing research is being done on some of these possibilities, and Red's case may be clarified in a couple of weeks as we're planning to do a follow up blood test.

We are going ahead and treating him with the ten days of Oroquin-10 paste (decoquinate/levamisole) and follow-on 90 days of low-dose decoquinate feed top dressing - the reasons for this will become clear as we review the possible explanations.  So, here are the possibilities:

1.  Red has another neurological condition than EPM.  Although we did do a blood test for Lyme (results not back yet) my vet thinks this is unlikely.  His symptoms are much more consistent with EPM than with any other cause of neurological symptoms, although we may be missing something.  If something else is going on, treatment for EPM will likely not change his symptoms, and his titers will stay low on retest.

2.  He has not been infected with a new strain of EPM (his prior infection was with strain 5), but rather is having an exacerbation of symptoms due to inflammatory processes - some horses who've had, and cleared, EPM appear to remain susceptible to inflammatory redevelopment of symptoms, which can be triggered by a number of things, including recent vaccination or other illnesses that stimulate the immune system. (Some of these cases may have previously been attributed to "relapses".) Red has not been recently vaccinated nor has he been otherwise ill or stressed.  If this is the case, the levamisole that's in the paste treatment should help reduce this inflammation, and his symptoms should abate.  In this case, titers will stay low on retest.

3.  He's had a low-grade infection for a while with a new strain - likely strain 1 - but the low-dose feed top dressing treatment he was on from June through August (intended to prevent infection) held the organisms to a low enough level that he did not produce a robust antibody response, although he did develop symptoms.  If this is the case, the levamisole in the paste treatment is there in part to stimulate a robust immune response, and if that happens and his titers go up in two weeks, we'll know that he's got an active infection.  It is also likely in this case that the treatment will improve his symptoms.  In this case, some of his symptoms back in the summer may have been attributable to EPM.  This is possible, but I don't have a clear understanding of the mechanisms that might be involved so I don't know how likely it is.

4.  The symptoms in the summer were primarily mechanical in nature, and have since healed - he was making a good recovery by the end of August and was improving.  He started to get worse again, and the symptoms became more clearly neurological, by the middle of September.  He finished up the 90 days of low-dose (preventative) treatment at the end of August.  It may be that he has subsequently developed a new infection with strain 1, since the end of August - it may be that he couldn't develop an infection while he was on the low-dose powder.  (Pie had an infection with strain 5, cleared it after treatment, and had a subsequent infection with strain 1, also treated and cleared, and remains symptom-free, so these sequential infections are possible.  This also might have been characterized as a "relapse" before the ability to accurately characterize the strain causing the infection.) Apparently a robust antibody response may not develop in the first three weeks or so of infection, although symptoms do appear in that time frame.  Although this explanation has more moving parts, and I would otherwise be suspicious of it, it fits the facts and timing quite well.  If this is the case, then treatment should improve his symptoms, and it is also likely that we'll see an increased titer on a retest in two weeks.

In summary, in both possibilities 3 and 4, we should see abatement of symptoms as well as possibly an increase in titers at two weeks.  It otherwise won't be possible to distinguish between these two explanations, although based on the timing and nature of his symptoms, I think 4 is a more consistent explanation, although if he's treated effectively it won't matter.  In possibility 1, there would be no abatement of symptoms and titers would stay low.  In possibility 2, symptoms should improve but titers would stay low - this would also be effective treatment of the inflammatory process, due to the levamisole, although we'd need to keep a good eye on him in the future in case he has other episodes that require treatment.

Time will tell - Red will be having his fourth paste treatment today, and I'll be doing a recheck on his neurological symptoms soon to see if anything is changing.

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