Reprinted
with permission of U C Davis
Equine
Protozoal Myeloencephalitis, or EPM as it is commonly referred to,
remains one of the most challenging and exasperating diseases in
horses, not only for veterinary scientists, but for horse owners
as well. If a horse shows signs of neurologic problems, the veterinarian
must begin a process of elimination to determine what isn't causing
the signs.
The
EPM tests veterinarians currently use for diagnostics are most effective
at determining if the horse does not have EPM. If an EPM test comes
back positive, the only fact it definitively reveals is that the
horse has been exposed to the parasites that cause EPM. The test
doesn't reliably show if the horse has an active infection by those
parasites or if the parasites are the cause of the neurologic problems.
To
make matters worse, if a horse is diagnosed as most likely having
EPM, there's no guarantee that the treatment will be 100 percent
successful. The newest medication can only offer a 70 percent chance
of improvement or resolution of signs. So where does this leave
the horse owner with an EPM horse?
The
only place to turn is back to the scientific drawing board. Two
decades of research and a substantial amount of funding may not
have solved the EPM puzzle, but it has helped scientists fill in
some of the gaps. Here's what veterinary scientists have discovered
so far.
- EPM is
a neurological disease that occurs when protozoal parasites
infect and invade the central nervous system.
- At least
two protozoal parasites cause EPM: Sarcocystis neurona
and less commonly, Neospora hughesi.
- EPM infection
results in characteristic lesions in the brain and spinal cord
that are evident during necropsy. The presence of these lesions
correlates well with the clinical signs generally attributed
to EPM (incoordination, muscle atrophy, etc).
- The horse
is considered a dead end host for S. neurona, meaning
that it cannot transmit the disease to other horses.
- Opossums
have been identified as the definitive host for S. neurona
and they shed the infective egg-like stages (sporocysts) in
their feces. Horses become infected by ingesting food or water
that has been contaminated with opossum feces containing the
infective sporocysts.
- Once ingested
by a horse, the sporocysts migrate from the intestinal tract
into the bloodstream and cross the blood/brain barrier. There,
they begin to attack the horse's central nervous system.
- The onset
of the disease may be slow or sudden and the signs vary depending
on the type of damage to the central nervous system. If left
undiagnosed and untreated, EPM can cause devastating and lasting
neurological deficits.
- Most current
diagnostic tests are based on the presence of antibodies to
the parasites that cause EPM. The presence of antibodies only
means that the horse has been exposed to these organisms. Not
all horses that are exposed actually come down with the disease
as some horses mount an immune response and are not affected
by the organisms.
In
1998, UC Davis assembled an EPM task force to address the many questions
that remain surrounding this disease. The team, headed by Dr. Patricia
Conrad, an expert on protozoal parasites, includes world-renowned
researchers and clinicians from various departments within the UC
Davis School of Veterinary Medicine: Drs. W. David Wilson, Bradd
Barr, Ian Gardner, Barbara Daft, Andrea Packham, Paulo Duarte, and
Center for Equine Health Director Dr. Gregory Ferraro. This task
force meets on a regular basis to discuss and plan future research
strategies for EPM. The group also utilizes the skills and talents
of interested postgraduate researchers and collaborates with other
scientists throughout the country.
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."
Treating
EPM
Treating EPM is not an easy task either. Treatment regimens previously
thought to be curative for the disease now appear to provide only
temporary relief of the symptoms. Researchers believe that the previously
recommended medication, pyrimethamine-sulfonamide combinations,
though successful in some cases, may have only been effective in
depressing the parasite's viability, temporarily enabling the horse's
immune system to control the infection during the treatment period.
When the treatment stops and the horse returns to work or is otherwise
stressed, the signs of the disease often recur.
A
new FDA-approved drug is now available that is made specifically
for EPM in horses. Marquis® (ponazuril), by Bayer, is showing promise
as an effective treatment. It is an anti-protozoal drug that is
recommended for a shorter period of time compared to the traditional
EPM treatment. The UC Davis Veterinary Medical Teaching Hospital
has been using it since August of 2001. UC Davis' Dr. Gary Magdesian
reports, "Marquis® is meant to be administered once daily for 28
days or more, depending on the severity and clinical signs. We have
started using it at the hospital but it is still relatively new.
It does not appear to be 100 percent effective, but in my opinion,
it is an excellent therapeutic for many horses with EPM." Bayer
reports the drug to be safe and effective.
One
of the main challenges with treating this disease is to begin treatment
early on. If the parasite is destroyed, the clinically affected
horses are still left with the damaged central nervous system and
therefore, compromised performance. The earlier treatment begins,
the better the horse's chances are to recover. Of course, that brings
us back to the problems with diagnosis.
An
EPM vaccine was conditionally licensed in the United States in 2000.
The efficacy of the vaccine under field conditions is currently
under investigation. There also remains the problem that once your
horse is vaccinated against EPM, the current diagnostic tests will
then report positive, which can be confusing.
Where
Do We Go From Here?
For researchers, the ultimate goal must be to eliminate and/or prevent
the parasite that causes EPM from invading the horse's brain and/or
spinal cord. Researchers must also find more accurate and reliable
testing methods to determine if a horse has an active infection.
The EPM puzzle can only be solved through a collaborative and multi-faceted
research effort. The Center for Equine Health will continue to make
this a top priority in the coming months and years ahead.
The
Horse Report is Copyrighted © 2001-2003 by the Regents of the University
of California. Use of this material for re-publication is allowed
only by permission of the Center for Equine Health.
