Defining EPM in Horses
Research continues regarding the epidemiology (how the disease originates, develops and spreads) of EPM. Before researchers can develop effective treatment and diagnostics, scientists must first define the current parameters of this elusive disease. Dr. Ian Gardner is leading the epidemiology group, including graduate student Paulo Duarte and collaborators who are currently conducting the longest and most in-depth study following a group of horses on several California breeding farms from birth through four years old (which includes these horses in race training). They are investigating 1) the percentage of equine neurological disease that can be attributed to EPM, 2) the geographic distribution of the disease, 3) the risk factors or management factors that are associated with clinical infection, 4) the possibility of fetuses contracting the disease while in the womb, and 5) the age at which horses are more likely to be exposed to the EPM parasites under field conditions.

Though the studies are still in progress, early results indicate that despite its relatively low incidence in the general population (14 new cases per 10,000 horses a year), approximately 23 percent of the horses with neurological signs that died and were examined at the California Animal Health and Food Safety Laboratory (headquartered at UC Davis) had S. neurona in their central nervous systems. More information on risk factors for EPM should be available within the next six to 12 months.

Dr. Duarte said, "We are trying to identify risk factors associated with natural exposure to the EPM parasites. We hope this information can be used to develop more specific preventive measures against exposure and therefore reduce the risk of disease."

Developing a Physiological Profile of the EPM Parasites
Another integral piece of the EPM puzzle is a complete physiological profile of the EPM parasites, including their life cycles, methods of reproduction and modes of environmental distribution. This information is vital to developing effective diagnostics and treatments.

Though the opossum remains the only identified definitive host for the EPM parasites, a number of other potential intermediate hosts have been identified including armadillos, skunks, raccoons and the domestic cat. It appears that the opossums may eat the dead skunks or other infected animals, however, the importance of these hosts for the spread of EPM in horses has not been established. Birds were investigated but it was determined that they do not serve as intermediate hosts for S. neurona. Research is continuing on the life cycle and mode of transmission for this parasite in horses.

How EPM Develops in Horses
At this point in time, we simply do not know enough about how these protozoa invade the horse's body and cause illness. A large percentage of horses carry antibodies to S. neurona indicating exposure, yet only a fraction of these horses ever develop clinical signs of EPM. What happens in these horses? Is the parasite eliminated or only encysted somewhere in the body to be reactivated at a later time? For horses that do develop clinical signs of disease, how long does it take for the organism to enter the central nervous system and cause damage that results in symptoms?

Dr. Rob MacKay and his associates at the University of Florida are working on these questions and more, but one of the biggest obstacles is not being able to experimentally cause infection in horses. Dr. Bill Saville and his associates at the Ohio State University are developing an experimental infection model of S. neurona. This information should help further define EPM in horses, and allow critical evaluation of the efficacy of vaccines and drug treatments.

Developing Accurate and Reliable Diagnostic Testing
As mentioned earlier, the current diagnostics for EPM remain less than optimal because they are based on the presence of antibodies to the causative parasites and antibodies only indicate that the horse has been exposed to these organisms at some point in their lives. Also, vaccinating against EPM will result in a positive test for EPM. UC Davis researchers Drs. Barbara Daft, Bradd Barr and associates have spent a considerable amount of time and effort trying to improve the diagnostic methods. Up to this point, most of their studies have identified the pitfalls in the antibody-based tests.

One of the most important findings from an extensive study by Dr. Barbara Daft is that a negative Western blot test on a blood sample is a reliable indicator that the horse does not have EPM. If the test comes back positive, however, then a second Western blot is run on a sample of cerebral spinal fluid and used as a confirmation of the disease. The cerebral spinal fluid samples are difficult to obtain and their diagnostic reliability is also being reexamined. The complexities of the horse's immune response to the protozoa and problems with sample contamination are the main issues. UC Davis researchers also determined that polymerase chain reaction (PCR) tests, which use DNA analysis to detect the protozoa's presence in the spinal fluid, were not as useful as hoped and are not being recommended for use in EPM diagnostics.

At the UC Davis Veterinary Medical Teaching Hospital, it appears that fewer horses are being diagnosed with EPM but this may not necessarily mean that EPM is less apparent than it was over the last decade. Dr. David Wilson said, "The lower number of diagnosed cases may not necessarily mean that there are fewer cases of EPM. It may be more that our diagnostics have gotten more specific. We can rule out EPM with more accuracy than before. Plus, we are better with interpreting the current diagnostics because we have identified the pitfalls (false positives, etc.) I think a lot of suspect horses were previously being diagnosed with EPM and with our current knowledge, these same horses are not being diagnosed with EPM."

An indirect fluorescent antibody test (IFAT), another antibody-based test being investigated by Dr. Patricia Conrad and other UC Davis researchers, is showing promise as a more specific test that can better differentiate between actual infection and mere exposure. The test is being further evaluated in the field to verify its accuracy. More research is required in this area to improve EPM diagnostics.

Dr. Gregory Ferraro said, "We will never be able to positively diagnose EPM with antibody tests alone. We need a test that can detect current infection of the parasites alone. Our group is currently working on the development of a Stage Two test that detects the presence of parasite antigens circulating in the cerebral spinal fluid and serum of infected horses. Our hope is that this novel approach to the diagnosis of EPM will overcome many of the limitations of antibody detection tests. Unlike the tests based on detecting antibodies, this antigen-based test could also be used to diagnose neurologic infections in vaccinated animals."