Managing infectious equine neurological disease (Proceedings)
Aug 01, 2010
CVC IN KANSAS CITY PROCEEDINGS
Equine Protozoal MyelitisEtiological Agent. Many horses likely encounter myelitis-causing protozoal organisms, Sarcocystis neurona or Neospora hughesi, at some point in their life without developing detectable neurologic disease (asymptomatic infection). However little is known about why one horse gets EPM and the other does not. Recent studies indicate that once challenged orally, the parasite is rapidly disseminated in horses and can be isolated from the mesenteric lymph nodes, lung, and liver between 1 and 7 days after infection. Recent studies also indicate that this organism is highly pleomorphic and has antigenic variation which likely accounts for our difficulties in development of diagnostic tests.
Clinical Signs. Clinical signs in affected horses vary from mild muscle wasting or vague lameness to recumbency, convulsions, and death. The variability of clinical signs due to S. neurona makes clinical identification without ancillary testing at times difficult. The protozoa infect the CNS of the horse in low numbers, diffusely, and in several areas, causing insidious and multifocal or diffuse disease. These organisms appear in gray and/or white matter, brain and/or spinal cord. Although onset may be slow and insidious, many horses develop acute neurological dysfunction. Cranial nerve involvement reflects its predilection for the hindbrain in horses. Spinal ataxia can be present and can be symmetrical or asymmetrical. Weakness and muscle atrophy in one or more limbs is common. Muscle atrophy is also associated with cranial nerve dysfunction and most often occurs with temporal-masseter muscle atrophy associated with involvement of the 5th cranial nerve.
Diagnosis. In the original NAHMS study, neurological disease caused by equine protozoal myeloencephalomyelitis (EPM) diagnosis was based on clinical signs alone and no ancillary testing whatsoever was done in 60% of these horses41. Diagnosis and treatment of this disease has only been moderately improved since isolation of the organism Sarcocystis neurona in 1991. Most horses test positive in their serum for EPM, but relatively few actually develop signs of EPM. Irrespective of assay, a positive test from the serum of a horse with clinical signs of EPM does not diagnose the disease. Likewise, cerebrospinal fluid (CSF) can test positive after exposure to disease and these horses may or may not develop signs of EPM. Many false positive tests occur; in fact horses that are vaccinated by EPM vaccine become CSF positive. Acupuncture points have also been proven to be unreliable for diagnosis of EPM. Recent studies have indicated a wider geographic range for Neospora hughesi (or caninum) as a cause of EPM, thus testing for this organism is also necessary to completely rule out EPM as a cause of clinical signs. Other reports indicated that S. neurona can change its major surface proteins thus making testing based on certain of these proteins could be unreliable. The latest information indicates that Elisa's based on the SAG2 protein have a 95.5% and a 92.9% sensitivity and specificity, respectively. Potentially, various other isotype formats such as IgM may indicate acute infection vs. previous exposure.
Treatment. The triazine family of medications, ponazuril (Marquis); dial doser at 5 mg/kg for 28 days. Two months of treatment is recommended. Recent reports indicate that intermittent therapy with ponazuril every 7 days will decrease production of antibodies in the CNS and anectdotal reports indicate that 10 mg/kg is needed. This indirectly indicates the use of this drug as either a preventative therapy for high risk horses (e.g. young horses in training) or 2) possible prevention of recurrence in previously, diagnosed, at risk horses. Folic acid inhibitors are a second option consisting of a combination of trimethoprim-sulfamethoxazole (30 mg/kg) and pyrimethamine at 2.0 mg/kg, SID for 3 days then TMS at 30 mg/kg and pyrimethamine at 1.0 mg/kg for 90 to 180 days depending on response to therapy. Perform CBC every 2-4 weeks to monitor for bone marrow aplasia. Other anti-protozoals consist of nitazoxanide (25 mg/kg for the first week, then 50 mg/kg for the next 3 weeks). This lower dose is recommended because of development of severe diarrhea in some horses that are initially placed on the higher dose. Recent publications have examined intermittent treatment for EPM which include NTZ at 25 mg/kg for 2 days per week or ponazuril at 20 mg/kg once per week. Very low prolonged intermittent dosing at 2.5 mg/kg or 5.0 mg/kg reduced the incidence in a population study.