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Summer 2004 Newsletter

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 Equine Protozoal  Myeloencephalitis   

Introduction and Etiology:  Equine protozoal myeloencephalitis (  EPM) is a progressive, degenerative neurological disease of the central nervous system that has been described in horses for over 30 years. The disease is one of the most commonly diagnosed neurological disorders of horses in the United States.  A recent USDA study revealed an incidence of 14 new cases of EPM diagnosed per 10,000 horses per year in the United States.  While great strides have been made throughout the last decade in an effort to understand EPM, many questions remain unanswered concerning its etiology, pathogenesis, occurrence, treatment, and diagnosis.

  Sarcocystis neurona is by far the most commonly implicated agent in cases of EPM; however, recent investigation implies that the syndrome, in rare cases, can be caused by Neospora caninum and/or Neospora hughesi infections as well.  Unfortunately, infection with these other protozoan species is clinically indistinguishable from infection with Sarcocystis neurona. For the purpose of this paper, only infection with Sarcocystis neurona as a causative agent of EPM will be described.

Pathogenesis:  The definitive host of Sarcocystis neurona is the opossum.  Infected opossums shed sporocysts in feces which are in turn infective to the intermediate host when ingested.  Many intermediate hosts are currently recognized in the life cycle of this protozoan, and the full range of hosts has yet to be identified.  Current species implicated include cats, armadillos, skunks, raccoons, and sea otters.  Once the intermediate host is infected, it goes on to develop sarcocysts in its skeletal muscle.  When this muscle is ingested by the opossum, the life cycle is completed.

  The horse is considered an aberrant or dead-end host of Sarcocystis neurona. While the horse is presumably infected by ingestion of sporocysts in contaminated feed and water, there are many unanswered questions concerning the pathogenesis of this protozoan once it actually infects the horse.  It is suggested that sporozoites released from the ingested sporocysts are able to penetrate the intestinal wall and enter arterial endothelial cells.  Schizonts then develop in these cells until they rupture releasing merozoites into the bloodstream.  This stage of the life cycle may be repeated several times producing large amounts of merozoites.  At this point, the infection can be cleared leading to seropositivity but no clinical signs or the protozoan can progress to the central nervous system.  It is unknown how S. neurona enters the CNS in horses.  It has been suggested that merozoites enter the CNS via infected leukocytes or through the cytoplasm of endothelial cells.  Once the merozoite has gained access, schizonts form in one or more areas of the central nervous system including the cerebrum, the cerebellum, the brainstem, cranial nerves, and/or the spinal cord.  Schizonts and daughter merozoites in the neural tissue remain uninfective and, therefore, transmission from the infected horse to other animals is not possible.

  Recent studies suggest that anywhere between 22-65% of horses in the United States are seropositive with S. neurona antibodies, depending on the geographic location.  Although several theories have been developed concerning why only some horses develop clinical disease, the reason is unknown.  Theoretical contributing factors to the development of this disease include stress and other unrelated health events that occur before the onset of clinical EPM.  In addition, little is known concerning the incubation period between exposure to the protozoan and development of clinical disease.

Clinical Pathology and Necropsy Findings:  No characteristic changes are seen in the hemogram or serum chemistries found in horses affected with equine protozoal myeloencephalitis.  Cytological examination of cerebral spinal fluid typically does not reveal significant changes.  Gross pathological changes are apparent in the affected portions of the brain and spinal cord, and include multifocal areas of hemorrhage and malacia or both grey and white matter.  Gross changes of muscular atrophy may also be seen in the skeletal muscle of affected horses.  Histological examination of affected nervous tissue reveals neuronal necrosis and loss in addition to marked mononuclear perivascular cuffing.  Infiltration of monocytes, lymphocytes, some eosinophils, and rare neutrophils can also be observed.  Direct visualization of the organism is often not achieved because they are often present in very low numbers.  This is especially true if the animal has been previously treated with antiprotozoal medications.

Diagnosis:  A definitive diagnosis of EPM in a live horse is challenging.  Simple seropositivity toward S. neurona antigen is inadequate for diagnosis since the protozoan must enter the central nervous system from the systemic blood circulation in order to cause the disease.  In other words, a seropositive horse has been exposed to the organism, but may or may not have EPM.  While there are several tests available to diagnose EPM, all of them are problematic.

  The most recent major advance in diagnosis is the introduction of the immunoblot test for detection of IgG antibodies against Sarcocystis neurona.

Antibodies detected in the cerebral spinal fluid (CSF) provide support for a diagnosis of EPM.  However, if the CSF is accidentally contaminated with blood during the procedure, a false positive can result. For this reason, it is recommended that only CSF samples with less than 50 RBCs/μL be submitted for immunoblot testing.  It has also been suggested that limited antibody movement into the CSF can occur without the presence of CNS disease.  This could also result in a false positive immunoblot test result.

  Although the immunoblot test is reported to have a sensitivity and specificity of 89%, a recent study by Daft et al determined that the specificity of the Western blot test (a type of immunoblot test is between 44-60%.  These results, as well as the risk of a false positive test, suggest that the use of immunoblot analysis is most useful in ruling out EPM rather than diagnosing the disease.

  Other diagnostic tests for EPM include polymerase chain reaction (PCR) testing, the albumin quotient test, and the IgG index test.  While PCR testing can detect minute amounts of protozoan DNA, the rapid destruction of DNA in the CSF environment and the possibility that DNA may not be present in the CSF makes the sensitivity of this test questionable.  The albumin quotient test was developed to detect contamination of the CSF sample with blood. Unfortunately, the test does not decipher whether the contamination is iatrogenic or a simple “leakage” of protein through the blood-brain barrier.  The IgG index test was developed to detect the production of IgG in the CSF. However, subsequent studies have found little difference between index values of EPM-affected horses and normal control horses.

  The detection of characteristic lesions on necropsy is considered the gold standard of diagnosis by some.  Due to the small number of organisms needed to cause the disease, however, the diagnosis can be missed even with a full neurologic necropsy.  In general for the live animal, a clinical diagnosis is best established in horses with neurological disease consistent with EPM and a positive immunoblot test or an uncontaminated CSF sample.  Another clue for diagnosis is an improvement of clinical signs in response to treatment of EPM.  Overall, it is imperative that the diagnosis be based not only on test results, but in conjunction with a thorough diagnostic examination that rules out other causes of neurological disease.

Treatment and Prognosis:  Treatment of equine protozoal myeloencephalitis is expensive, and even mildly affected horses can require prolonged therapy.  The standard treatment for many years has been combinations of antifolate drugs including sulfadiazine and pyrimethamine with or without trimethoprim.  The use of folic acid supplements in conjunction with this therapy has been recommended by some in an effort to reduce the risk of folic acid deficiency.  A recent case report showed that supplementation failed to prevent the development of folic acid deficiency, however.  The use of nonsteroidal anti-inflammatory medi-cations in conjunction with traditional therapy has been routinely used for many years.  Supplementation with various vitamins has been recommended by some as well as the use of acupuncture in an effort to treat EPM; however, the efficacies of these practices have not been proven in clinical trials.

  The most recent breakthrough in the treatment of EPM is the development of triazine-derivative drugs.  These medications were initially developed as herbicides and have historically been used as coccidiostats in poultry and swine.  Ponazuril (Marquis™) is a member of this family, and is the first approved medication for the treatment of EPM.  Other drugs in this class include diclazuril and toltrazuril.  Ponazuril is a primary metabolite of toltrazuril, and has shown anticoccidial activity against several parasites, including Sarcocystis neurona.  Treatment regimen requires once a day dosing for 28-56 days.  While studies show ponazuril can effectively rid horses of S. neurona, it does not improve the CNS damage that occurs before treatment begins.

  Studies estimate that clinical improvement can be seen in 70% of treated horses, but fewer than 25% return to original function.  Relapse of disease occurs in approximately 5-28% of horses when treatment is discontinued.  The mechanism of this relapse is unknown, but reemergence of a latent stage parasite, persistence of a small focus of infection despite treatment, and reexposure to S. neurona have all been proposed.

Prevention and Control:  Due to the lifestyle and eating habits of the definitive host of Sarcocystis neurona (the opossum), prevention and control of EPM are potentially problematic.  Current recommendations include preventing access of opossums to hay, grain, pasture, and water sources.  This may be difficult, especially if food and water are in short supply for the opossum.  The most reasonable and simple precaution for horse owners to take is to deny access of stored hay and grain bins to the opossum.

  The opossum is considered a scavenger and will consume whatever is available to it, including road-kill.  Recommendations to prevent EPM commonly include picking up road-kill in the immediate area.  This suggestion may be somewhat ineffective, however, since there are likely many other unknown intermediate hosts that are perpetuating the lifecycle.

  A killed vaccine against Sarcocystis neurona has been developed using merozoites.  No clinical evidence  supports the efficacy of the vaccine and little research has been completed to date, however.  Overall, there are few suggestions to aid in the prevention of Sarcocystis neurona exposure.

-by Katherine Gilmor, Class of 2004

-edited by Dr. Theresa Boulineau, ADDL  Graduate student


  1. Cook AG, Maxwell VB, Donaldson LL et al: 2002.  Detection of antibodies against Sarcocystis neurona in cerebro-spinal fluid from clinically normal neonatal foals.  JAVMA 220: 208-211.

  2. Daft BM, Barr BC, Gardner IA et al: 2002.  Sensitivity and specificity of western blot testing of cerebrospinal fluid and serum for diagnosis of equine protozoal myeloencephalitis in horses with and without neurologic abnormalities.  JAVMA  221:1007-1013.

  3. Furr M, MacKay R, Granstrom D et al: 2002.  Clinical diagnosis of equine protozoal myeloencephalitis.  J Vet Internal Med 16:618-621.

  4. Jones WE: 2002.  EPM Update.  J Equine Vet Sci 22:528-534.

  5. Lech PJ: 2002.  Ponazuril.  Compendium 24:484-485.

  6. Morley S, Traub-Dargatz J, Saville W et al: 2001. Equine protozoal myeloencephalitis.  J Equine Vet Sci 21: 262-270.

  7. Piercy RJ, Hinchcliff KW and Reed SM: 2002.  Folate deficiency during treatment with orally administered folic acid, sulphadiazine and pyrimethamine in a horse with suspected equine protozoal myeloencephalitis.  Equine Vet J 34: 311-316.

  8. Radostits OM, Gay CC, Blood Dc and Hinchcliff KW: 2000.  Vet Medicine: A Textbook of the Diseases of Cattle, Sheep, Pigs, Goats, and Horses, 9th ed.  WB Saunders, London.  1322-1324.

  9. Saville W: 2001.  Equine protozoal myeloencephalitis: 2001.  In: Smith BO, Large Animal Internal Medicine, 3rd ed. Mosby, ST. Louis 908-914.

  10. loencephalitis.  AAEP Proceedings 48: 181-185.


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