Equine Protozoal Myeloencephalitis
of horses. The causative agent of EPM is Sarcocystis neurona, a protozoan parasite which
appears to have a predilection for the central nervous system. The classic presentation of the
disease is an asymmetrical ataxia with focal muscle atrophy. The disease may be focal or
multifocal in nature with atypical manifestations such as head tilts, facial paralysis, and
sometimes seizures. The horse is an aberrant host in that the asexual stage of S. neurona is
the only stage of the parasite which has been detected. This is also confirmed by the inability to
detect sarcocysts in the muscle of the horse.
Diagnosis
The only methods of definitive antemortem diagnosis presently available are the Western blot
for detection of antibodies to S. neurona in cerebrospinal fluid (CSF) and the detection of
species-specific DNA with the aid of polymerase chain reaction (PCR). Additional tests that are
used to aid in diagnosis of EPM are called the CSF Indices. They help to determine whether
the CSF sample was contaminated with serum at the time of collection or whether there is
intrathecal production of antibody. These calculations along with the cytology of the sample
and the Western blot analysis may help clarify the treu disease status of the horse.
Epidemiology
EPM has only recently been recognized in horses, and as a result our knowledge of the
pathogenesis and epidemiology of this disease are limited. Available information suggests that
EPM is a disease of the Americas but that there may be geographic differences in the
prevalence of infection. There were reports of cases of this myeloencephalitis from Canada,
California and Brazil. While cases were reported from England only horses born in the U.S. were
affected. S. neurona was cultured from both the gray and white matter of the spinal cord of a
horse born in Panama. Another case of EPM was reported from the Republic of South Africa in
a young Arabian horse that was imported from the US a few months before onset of clinical
signs.
It has been suggested that the distribution of EPM may be limited to North, Central and South
America because of indigenous wildlife which likely serve as definitive and intermediate hosts.
An organism that is very similar to S. neurona was found in the brain of 2 raccoons which led to
some speculation that this host species may be involved in the life cycle of the disease. Reports
on the disease indicated that the most likely species involved in the life cycle of S. neurona are
skunks, raccoons, and opossums.
The skunk is the only species that has been serologically positive, but may be incidentally
infected like the horse. In 1995, results of PCR analysis provided strong evidence that the
opossum is the definitive host of Sarcocystis neurona . This study revealed a 99.89% homology
with the opossum sporocyst, Sarcocystis falcatula . These results have been corroborated by
others. Experimental induction of EPM has just been completed by investigators at the
University of Kentucky, which further corroborates that the opossum is the definitive host for this
organism. The opossum is indigenous to North, Central and South America which coincides with
the fact that no cases of EPM have been reported in horses other than those born there.
Unlike most Sarcocystis spp., S. neurona or S. falcatula (aberrantly) infects a large number of
intermediate hosts such as it does in the horse. Reports in the literature indicate infection with
this organism in cats, mink, raccoons, a striped skunk, a golden eagle, rhesus monkeys and
chickens. The natural intermediate hosts for S. falcatula are cowbirds and grackles, however
earlier work suggests that the organism may form sarcocysts in the muscle of many species of
birds from the Orders Passeriformes, Psittaciformes and Columbiformes. This wide host range
is atypical for Sarcocystis spp., however, this behavior is similar to Toxoplasma gondii which
may be phylogenetically similar. This would suggest the possibility of more than 1 species of S.
falcatula or perhaps there are subspecies. Recent work generated by the University of Florida
would suggest that S. neurona is distinct from S. falcatula and that the natural intermediate host
for S. neurona is not the cowbird or grackle. It would appear that the opossum does harbor
more than one species of Sarcocystis. More recent evidence would suggest that the Opossum
harbors 3 species of Sarcocystis. The three species likely include S. neurona, S. falcatula and
a S. neurona-like organism. This information was generated using nude mice and
gamma-interferon knockout mice, therefore, further research is needed to determine the effect
of all three species in the horse. More research is needed to determine the exact life cycle of
this organism.
In addition to the predator-prey life cycle, which occurs in all Sarcocystis, there is some
speculation there are transport vectors which may play a role in this disease. One of the
species suspected of serving as such a vector is the cockroach. Others speculate that since so
many birds (pigeon, finch, canary, grosbeak, budgerigar), will form sarcocysts after ingestion of
the sporocysts of S. falcatula, there is a possibility some of these birds may be acting as
transport vectors as well.
Life Cycle
The life cycle was determined in 1995 when the research determined that the Opossum is likely
the definitive host and the grackle and cowbird are putatively the natural intermediate hosts. In
addition there are likely numerous other intermediate hosts which will hopefully be determined in
the future. The issue of transport vectors is still undecided, however, there is speculation about
cockroaches, birds and a potential for the orbatid mite. To see life cycle link (click HERE)
Treatment
The current method of treatment recommended is potentiated sulfonamides in combination with
pyrimethamine, an antimalarial medication. The efficacy of the treatment as indicated by short
term survival and response to therapy has been reported to only be 55% or 60%, although
there are indications it may be higher.
In addition to the anti-protozoal medications, it is recommended that horses undergoing
treatment for this disease be supplemented with Vitamin E up to 9,000 IU per day. We also
recommend your horse's blood be checked monthly for folic acid levels and a CBC every other
week to examine for signs of anemia. This is to attempt to prevent folic acid deficiency as both
sulfonamides and pyrimethamine are anti-folate medications and may cause folic acid
deficiency. Folic acid supplementation is not recommended at this time, particularly in pregnant
mares with EPM.
Additional therapies are also being used by some clinicians. These therapies include the use of
immune stimulants such as Eqstim, Equimune, alpha-interferon, or levamisole. These
compounds may boost non-specific cell-mediated immunity. Cell-mediated immunity is
necessary to rid the body of these parasites. The efficacy of these compounds has been
established in humans with leishmaniasis.
A new therapy (Diclazuril) has been receiving a lot of press recently and has been under study
by the University of Kentucky. This new compound is a triazine derivative that has been used
as a coccidiostat in other countries for a number of years. The site at which these compounds
exert their effect is called a chloroplast which do not exist in mammals. For this reason, the
compound should not be toxic to mammals, however, the toxicity studies have not been
completed to date. The efficacy of this compound is very similar to the standard therapy
discussed above, however, the treatment period is much shorter (4 weeks) and therefore less
costly. This compound has been used primarily in horses that have relapsed after the standard
therapy with reasonably good success. This compound is available through the AAEP and the
FDA by special permit. An additional triazine derivative (Toltrazuril) is available through the
same sources as the Diclazuril. Current clinical trials are being performed at several sites
throughout the US to establish efficacy against Sarcocystis neurona.
A new therapy called Nitazoxanide (NTZ) is being investigated by Blue Ridge Pharmaceuticals.
NTZ is a thiazolide derivative that demonstrates a wide spectrum of activity against bacteria,
protozoa, and intestinal helminths. The drug is in development for humans to treat parasitic
infections that are common in developing countries and to treat immunocompromised patients
afflicted with cryptosporidiosis. Veterinarians may obtain more details on NTZ. The area is
password protected. Please call 800-870-4264 to obtain the password to enter this area. We
will need your name, your clinic address, your state veterinary license number, and your DEA
number.
More Epidemiology
A multi-center descriptive study indicated that there was not a preferred geographic location nor
a breed predilection. The study involved ten centers throughout North America with follow-up
periods ranging from three to eleven years. Another study from the University of Pennsylvania
Veterinary Teaching Hospital suggested that the incidence was higher in Standardbreds and
male horses. These two studies are the only epidemiologic studies undertaken but had
conflicting conclusions and did not identify risk factors for disease which could be used to
design control programs
All information on this page was obtained from EPM Research Performed at Ohio State University (OSU ).
For an extended version or further articles on EPM CLICK HERE
(The Extended version is printable)
 |
 |
