Managing infectious equine neurological disease (Proceedings)


Managing infectious equine neurological disease (Proceedings)

Aug 01, 2010

Table 1. Diagnostic Testing for Equine Neurological Diseases Current Diagnostics for Equine Neurological Diseases.
Neurological disease represents 0.3% (affecting between 0.2 and 0.5% of horses depending on age) of all health problems identified by owners in the latest 2005 Equine National Animal Health and Monitoring Study (NAHMS).14 Likely this is much higher given losses in young horses due to non-infectious neurological causes, in all ages of horses from underreporting of encephalitis, and misdiagnoses of these diseases as lameness and trauma. The actual contribution of neurological impairment to the health of US equids overall is actually unknown due to poor diagnostic tools, loss of animals to post-mortem testing if destroyed, and reporting mechanisms that emphasize diseases only of human significance. In fact, while owners in the 2005 NAHMS study only identified 5.0% of the non-ambulatory horses as neurological, another 30.6% were due to a "lameness" problem which may have been incorrectly categorized. Neurological impairment in the horse, even more so than lameness or trauma, is more apt to foreshorten the animal's athletic career, result in permanent deficit, monetary investment by the owner for treatment, and ultimately destruction of the animal. Sixty-one percent of those horses were rendered unusable in the 1998 NAHMS data on EPM, either these horses relapsed, did not respond to treatment, were destroyed or sold due to the original diagnosis. If one estimates for 2010 that approximately 6M equids reside in the US and if one uses an overall estimate of 0.3% population incidence of neurological disease, at least 180,000 cases of some sort of neurological disease occur annually in horses. If a conservative 50% of those animals do not survive, then this represents a loss of 90,000 horses per year to neurological impairment. In direct value, utilizing the AHC data, we performed a survey during the WNV outbreak (unpublished data) and based on client reporting, the direct value of the horses averaged $1500/horse thus a loss of 90K horses represents 270M in livestock loss alone. We further estimated based on American Horse Council statistics that each horse represents $14K/year in combined direct and indirect benefits to the economy. Thus the loss due to equine neurological impairment just from mortality is conservatively 1.2B per year.

Table 2. Summary of CSF Findings in Infectious Neurological Diseases
Antemortem testing for the cause of equine neurological disease is still more art than science. Causes of neurological diseases in the horse are infectious (RNA viruses, DNA virus, parasitic, bacterial and fungal) and noninfectious (cervical vertebral malformation, various congenital malformation, degenerative, toxic, and trauma).13 Given the substantial loss due to equine neurological disease, evidence-based identification of the causes of equine neurological diseases poses a constant challenge and this is estimated at 60% for a confirmed diagnosis (based on our database of over 2900 post mortem cases of neurological disease) while less than 30% are found to have had the etiology identified ante-mortem.14-16 Furthermore, the CNS is an immunologically privileged site which is difficult to access in the standing normal or neurologically impaired horse, thus "organ-specific" diagnosis is a challenge without invasive procedures. Although the singlemost valuable test one can obtain is a CSF analysis, many times this procedure is difficult to perform for a variety of circumstances in the neurological horse.

Equine Protozoal Myelitis

Etiological 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.

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