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Tuesday, April 29, 2008

EHV-1 the neuropathogenic strain

by Natalie Carrillo, MV, DVM, Dip ACVIM-LA

Recent outbreaks of myeloencephalopathy caused by equine herpesvirus (EHV-1) have generated new research that provides better information about diagnosis, treatment and outbreak management. The objective of this article is to summarize this information in a practical and applicable manner.

Clinical signs

The onset of EHV-1 myeloencephalopathy is characterized by a biphasic fever. In several outbreaks2 it has been observed that only horses younger than 5 years displayed fevers and respiratory signs, whereas the older horses were febrile, but had no signs of respiratory disease. It has also been observed that older horses develop neurologic deficits more frequently and of greater severity than younger horses (<5> 2. The reason for this bias is unknown, but may be explained by the role the horse’s immune system plays in the extent and severity of vasculitis and vascular thrombosis2.

The neurologic deficits appear approximately 4-6 days after the onset of fever2 and develop as the result of vasculitis, thrombosis and secondary ischemic degeneration of the neuropil1. The neurologic signs reflecting spinal cord involvement range from mild ataxia to recumbency, the pelvic limbs are more frequently involved and bladder atony is common. The brainstem may also be affected and therefore deficits of the cranial nerves may also be observed.

Epidemiology and outcome

The clinical signs are of rapid onset, but they also stabilize quickly. Most non recumbent animals do well, but the prognosis for recumbent horses is poor. In an outbreak of EHV-1 approximately 20-30 % of horses will be affected by the neuropathogenic strain, and of these the mortality will be approximately 30%1, 2.

Diagnosis

If you suspect a horse has EHV-1 due to an unexplained fever after being at an event, for example. A nasal swab and an EDTA purple top tube should be collected and submitted on ice packs overnight for real-time TaqMan® PCR on both samples to diagnose and differentiate the neuropathogenic vs non neuropathogenic strains. Results will be ready in 24h post arrival3. (See references for mailing addresses).

Outbreaks and treatment

In the event of a suspected outbreak there are guidelines on the AAEP website http://www.aaep.org/control_guidelines_nonmember.htm that pertain to biosecurity and quarantine. They are to extensive to cover, and are not the objective of this article. What I do want to incur into are treatment guidelines.

On the onset of fever of a suspected animal:

First implement biosecurity measures including stall confinement. Collect pertinent samples for diagnosis and then initiate therapy with NSAIDs such as flunixin meglumine 1.1 mg/kg or phenylbutazone 4.4mg/kg to manage the fevers.

Once the disease is confirmed or clinical signs of the disease progress to a working diagnosis of EHV-1, then more aggressive therapy and prophylaxis of surrounding animals should be initiated. All animals possibly exposed should be treated with Valacyclovir (Valtrex®) 205-403 mg/kg PO every 8 hours. Acyclovir despite clinical reports of effectivity2 has shown not to reach adequate serum levels to inhibit viral replication6 therefore should not be the first drug of choice. Valtrex® is an expensive drug and this option should be thoroughly discussed with the owner.

Management for the horses displaying clinical signs of the neuropathogenic form of EHV-1:

NSAIDs - continue flunixin meglumine 1.1mg/kg for 10 d (monitor serum creatinine every 3-5d depending on hydration status of the horse).

DMSO (if you are a believer) 1g/kg at 20% sol IV every 24h for 3 days, as a free radical scavenger.

Valacyclovir (Valtrex®) 205-403 mg/kg PO every 8 hours for 10 days or until clinical signs stabilize.

Vitamin E 10.000 IU PO every 24h for 10 days7 as an antioxidant.

Dexamethasone 0.1 mg/kg IV for 3 days then taper for a total of 10d. This therapy is controversial. On one hand it is a potent anti-inflammatory, but on the other it does suppress the immune system at these doses. And never forget the potential for laminitis. I would reserve this choice of therapy for horses showing neurological deficits, I would not administer to horses with just a fever, even if it is a confirmed case.

If at any point a horse should become recumbent or needs assistance standing, or in general deteriorates to the point of requiring constant monitoring please talk to the client about referral to a hospital with facilities for critical care.

Vaccination in an outbreak

From http://www.vetmed.ucdavis.edu/ceh/topics-EHV-1-vaccinations.htm

On premises with confirmed clinical EHV-1 infection, booster vaccination of horses likely to be exposed is not recommended.

Non-exposed horses or horses that have to enter the premises should have a booster vaccination if they have not been vaccinated within the past 90 days. This does not guarantee protection against the disease; the hope is that reduced nasal shedding of infectious EHV-1 by these horses will help reduce the magnitude of challenge experienced by other horses and potentially help reduce spread.

A current publication8 showed that recent vaccination with Rhinomune (modified live vaccine) may provide some protection against EHV-1 myeloencephalopathy. These results should be interpreted with caution because the number of animals used in the study was small.

Vaccines that provide the highest levels of viral neutralizing titers are Pneumabort, Prodigy, Calvenza and Rhinomune. The high levels of antibodies have been shown to reduce viral shedding. It is important to warn clients of the potential side effects of the modified live vaccine such as swelling of the injection site, fever and swelling of the limbs.

I hope this article has been helpful, if you should have any further questions about a case please do not hesitate to contact me.

References:

1.- Julia H. Kydd and K.C. Smith, Equine Herpesvirus Neurologic Disease: Reflections from across the pond. J Vet Intern Med. 2006 May-June;20(3):467-68.

2.- Henninger RW, et al, Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center. J Vet Intern Med. 2007 Jan-Feb;21(1):157-65.

3.- Allen GP, Development of a real-time polymerase chain reaction assay for rapid diagnosis of neuropathogenic strains of equine herpesvirus-1.J Vet Diagn Invest. 2007 Jan;19(1):69-72. M.H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546.

4.- Garré B, et al, Pharmacokinetics of acyclovir after intravenous infusion of acyclovir and after oral administration of acyclovir and its prodrug Valacyclovir in healthy adult horses. Antimicrob Agents Chemother. 2007 Dec;51(12):4308-14. Epub 2007 Sep 10.

5.- BG Bentz, et al, Pharmacokinetics of Valacyclovir in the adult horse. Abstract #108 J Vet Intern Med. 2007 May-June;21(3):601.

6.- BG Bentz et al, Pharmacokinetics of Acyclovir after Single Intravenous and Oral Administration to Adult Horses. J Vet Intern Med. 2006 May-June;20(3):467-68.

7.- J.K. Higgins, et al, Vitamin E levels in serum and cerebrospinal fluid of healthy horses following oral supplementation. Abstract #340 J Vet Intern Med. 2007 May-June;21(3):666.

8.- Goodman LB, et al, Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type 1 (EHV-1).

Vaccine. 2006 Apr 24;24(17):3636-45. Epub 2006 Feb 13.

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