EPM: The devil is in the diagnosis - DVM
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EPM: The devil is in the diagnosis


DVM360 MAGAZINE


Tests present challenges

Testing for EPM remains problematic, though, in that numerous problems and issues exist with just about every test available.

The serum antibody test for EPM is run on a sample of blood, and it detects circulating antibodies to S. neurona. A negative test means that the horse in question does not have EPM, unless it is early in the disease process and the body has not yet had time to make antibodies or if the disease is well localized in the central nervous system and the peripheral immune system has not been "exposed" to it yet.

This may be difficult to explain because the parasite must enter the body through the digestive system, and it would seem logical that on its way to the central nervous system some immune system stimulation and recognition should occur. But there are enough reports of initially tested EPM negative horses that became positive on retest to make this an important point to consider.

The horse in question also could be one of the small number of cases caused by N. hughesi or other protozoans. A positive serum antibody test often is seen as not very helpful because it is now known that 30 percent to 60 percent of all horses are exposed to S. neurona during their lifetime. The vast majority of these animals will make antibodies to this parasite, and their immune systems will mount a successful challenge so they will never develop EPM.

Studies indicate that only about one quarter of 1 percent of all horses (0.14 percent) will actually develop the disease. Crisman and Witonsky would suggest that it is precisely these statistics, however, that do make the serum antibody test a useful field diagnostic tool for EPM diagnosis.

If a high percentage of horses will have a positive serum titer for EPM yet a very small percentage of horses will actually have the disease, and if EPM generally causes at least some neurological signs in the truly affected horse, then the clinically diagnosed horse, based on a thorough physical examination, with a positive "high" serum titer, will have a very high likelihood of actually having EPM, while the horse with vague problems, no neurological signs and a positive titer will not.

Progression of signs

"In the field, I diagnose EPM horses based on clinical signs and a high titer," Witonsky says.

The progression of signs also can be a good diagnostic indicator, in that an examination done on the first visit when blood is taken for a titer can then be repeated a few days later when results (assuming a positive titer) have returned from the laboratory.

The EPM horse will very possibly show some neurological progression of signs between visits that can sometimes help the practitioner, especially if those neurological signs were not very apparent at the initial examination. Progression of signs (though common) is not required for EPM diag-nosis; however, many clinicians choose to progress to more advanced testing.

Western blot analysis of central spinal fluid (CSF) has been the "gold standard" in EPM diagnosis for years. This test verifies the presence of the protozoal parasite in the central nervous system, which is the classic definition of EPM disease. This testing methodology has been more rigorously evaluated than any other tests currently available.

While there are other tests out there (Polymerase chain-reaction [PCR] on spinal fluid, IgM ELISA, indirect fluorescent antibody testing [IFAT] and others), "the CSF western blot is the test that we know the most about," according to Witonsky, so it continues to be the standard even though there are issues about its interpretation.

"There is potential for peripheral blood contamination, some horses may have antibodies cross over from their serum to the CSF," explains Witonsky as she lists potential problems for western blot CSF analysis. "It is also possible that a horse could be very early in the disease process and not yet mount an antibody response in the CSF."

A University of Pennsylvania New Bolton Center study found that a few as eight red blood cells per microliter (roughly one millionth the concentration in peripheral blood and far too few to be seen in a CSF sample) can be enough to contaminate a spinal tap and cause a false-positive result. These problems, along with the additional risk to the horse and the financial cost, have led to a significant reduction in the number of CSF taps being done for EPM diagnosis.

"We used to do them (spinal taps for EPM) routinely, maybe three to four per week, but we are now down to maybe a few tests per month," says Crisman.

Newer tests

The newer tests show promise and may help because these tests, like the IFAT being run at the Diagnostic Laboratory of the College of Veterinary Medicine at the University of California-Davis and the SAG-1 ELISA (Antech/Ellison), may be able to give clinicians some idea about active infection rather than past exposure titers. The indirect fluorescent antigen test (IFAT) offered at UC- Davis uses whole merozoites from an S. neurona SAG-1 positive strain (SAG-1+) as the antigen. The laboratory reports a titer and an odds ratio that gives the clinician a likelihood of active EPM disease. The SAG-1 ELISA, developed by Ellison and run by Antech Diagnostic Laboratories, tests for antibodies to one specific protein of S. neurona (SAG-1). This test reports a quantitative result.

The advantage of these newer tests is that they do provide some idea of how high a titer or response the individual horse is making. A horse with a high titer and clinical signs of EPM is much more likely to actually have the disease.

The disadvantage of these tests is that they have not been in use long enough or used on enough horses to accurately evaluate their merits. More testing on larger numbers of horses is needed to show that these tests are indeed selective and specific enough to be consistent with or even better than the tests currently available.

An additional complication is the fact that we now know that there are SAG-1 + and SAG-1- strains of S. neurona. It is not yet known whether these SAG-5+ strains, which are SAG-1-, will cross-react on tests developed using SAG-1+ antigen or if these tests can identify a SAG-5+ infected horse. It is also unclear as to what percentage of EPM affected horses are infected with SAG-1+ or SAG-5+ strains.

Additional work must now be done in this area to clarify these concerns.

If the SAG-1+ vs. SAG-5+ issue can be resolved accurately, then these tests would fit nicely into the suggested work-up that is the best way for veterinarians to diagnose EPM infection in the horse.

"A complete history and thorough physical exam is absolutely critical," Witonsky says.

"It is important to have a complete list of differential diagnoses, considering signalment, clinical signs, vaccination history, localization of neurological signs and sometimes multiple diagnostic tests to rule in and rule out other causes of neurological disease."

All of this information, evaluations about disease progression and re-examination when necessary, and a positive "high" serum titer, especially a quantitative newer test titer (as opposed to the qualitative western blot test) showing "active" infection, may make EPM just a little bit easier to diagnose definitively.

Marcella is an equine practitioner in Canton, Ga.


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Source: DVM360 MAGAZINE,
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