A long held belief is that a horse with EPM has antibodies to Sarcocystis neurona. Along with that idea is that spinal fluid (CSF) can improve the diagnosis of EPM--logic says if one detects antibody made in the CNS then organisms must be there. The antibodies are a response to local infection. The discussion quickly proceeds to the antigens used to detect antibodies--which are are most useful? Not up for debate is the question of active versus past infections. We already know that no antibody test can make that distinction. And that is because Equine Protozoal Myeloencephalitis is a disease, a syndrome, with infection and inflammation and both need to be recognized and treated.
We know, by experiment, that using CSF along with serum antibodies does not enhance the diagnosis of clinical EPM. In several randomized, controlled, masked studies (using horses) we determined that there was no statistical significance when CSF was used to diagnose disease. We used serial serum and CSF tested by SAG 1 ELISA (we used a SAG 1 challenge so that is our gold standard), and western blot (EBI, Lexington KY). Western blot was the test de jour and we added it to our testing to be complete. We have discussed that topic in prior posts.
Another factor affecting antibody as a diagnostic aid is the horses’ prior history. If a horse is naïve (the first infection) the antibody titer will be low and get higher as the infection continues. An experienced horse, this is usually an older animal, develops a higher titer in a shorter period of time. Antibody is detected by day 17 after infection. These observations were statistically significant in randomized, controlled, masked studies (using horses). We also know, and have discussed, that treatment (with triazine drugs) will delay an antibody response, again observed in randomized, controlled, masked studies. It takes very little drug to delay an antibody response, the serum levels are posted on our archived web page. We suspect that other antiprotozoal drugs have the same quelling effect on antibody (but not clinical signs) but the data has not been published. These confounding factors (an animals exposure and treatment history) change our diagnostic decision tree.
The first factor we look at is the exposure to antiprotozoal drugs. Classically, the animal would not have a treatment history (and that would have to include no other animal served as an environmental contaminator). When we look at submission forms a treatment history is included, but we are unsure of low level drug exposure. The next most important factor is the presence of clinical signs. If there are no antibodies (on our test a titer of <8) we look for a treatment response and recheck the horse at the end of treatment. If there is a treatment response and no rise in titer we give a tentative diagnosis treatment-responsive inflammation. Horses that respond to treatment a fourfold rise in titer increases the probability signs were due to active S. neurona.
Of course our diagnostic job is easier if the horse starts with an antibody titer (on our test >8). If we see a response to treatment we just like to look for antibody again in 6-8 weeks to make sure the levels are <2 (on our test). If we get a partial--or no response to treatment we look to inflammatory disease or seek other causes of the clinical signs. A young horse (<2 would be a candidate for neck radiographs while an old horse would be a candidate for vitamin E treatment for equine motor neuron disease). The expertise of the field veterinarian is important here.
The other half of our decision tree deals with inflammatory disease. We use C-reactive protein, and in some instances serum IL6, to decide what the treatment steps are going forward. A response to treatment indicates treatment-responsive inflammation--with or without S. neurona infection. This is when an antibody response is useful developing a treatment plan. When there is a treatment response and the CRP is falling to normal levels (we need serial testing to determine this) our follow up treatment if there are more issues.
The situation in which there is no response to treatment, the gait score is >2 and deteriorating, with a serum CRP concentration of >16 micrograms per ml further drastic measures are in order. The first thing we try is using a treatment for encysted small strongyles that has good efficacy for this stage of parasite and rechecking the CRP in 7 days after de-worming. In a few cases treating for Lyme, despite a negative test run at Cornell, has improved horses clinical signs. Sadly, in the other cases, we hit a dead end. These cases are rare for us .03% of the submissions. It may be useful to do a standing nerve biopsy. A pre-mortem diagnosis can confirm untreatable disease in some of these horses.
What makes our approach to analysis of a case different is our first question—treatment--we don’t start our analysis with antibody—the confounding factors are too complex. We start with treatment history and move to treatment response. The serum testing is invaluable and is in our analysis so testing is critical and adds to our analysis. The CRP is useful, it changes our treatment decisions in many cases.