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| EPM Equine Protozoal Myeloencephalitis |
| Equine Protozoal Myeloencephalitis (EPM) is a serious and often fatal neurologic disease 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) |




