Antiviral drug shows promise against EHV-1

A new study shows that the antiviral drug valacyclovir can significantly reduce the severity of neurological problems brought on by equine herpesvirus type 1 (EHV-1) and may limit the spread of the virus to other horses.

One of nine types of equine herpesvirus, EHV-1 infection typically causes respiratory illness in young horses and abortions in pregnant mares. In some cases, the virus leads to muscle weakness and incoordination, a condition called equine herpesvirus myeloencephalopathy (EHM). EHV-1 is also highly contagious, and outbreaks in a barn can last for weeks.

Researchers at Oklahoma State University recent investigated the efficacy of valacyclovir, a medication developed to treat herpes infections in people, in treating EHM. “Valacyclovir is a prodrug for acyclovir, meaning that the body converts valacyclovir to its active form, which is acyclovir,” explains Lara Maxwell, DVM, PhD. “Acyclovir is transported to the inside of the horse’s cells, which is where the virus replicates. In the cell, acyclovir is modified by viral and cellular enzymes to an active form that interferes with DNA synthesis. Therefore, acyclovir works by inhibiting viral replication. It cannot actually kill the virus, but it reduces viral replication and so buys time for the horse’s immune system to more directly attack the virus and virally infected cells.”

Acyclovir and valacyclovir have been used to treat other viral diseases in horses, including equine multinodular pulmonary fibrosis (EMPF) associated with EHV-5.

For the study, the researchers selected 18 healthy mares aged 20 or older—a cohort known to be particularly susceptible to EHM —and inoculated them with EHV-1. The mares were divided into three groups: The first began receiving valacyclovir one day before being exposed to EHV-1, the second group was started on the drug only after developing a fever, indicating infection, at one to two days after inoculation, and the third group was given a placebo treatment to serve as controls. In the first phase of the study, which involved half the horses, the valacyclovir treatments were continued for one week. In the second phase of the study, using the remaining horses, valacyclovir treatments continued for two weeks.

Throughout the study period, researchers monitored each horse’s temperature twice daily, and a specialist performed daily neurological evaluations, documenting any observable ataxia (lack of muscle coordination).

The researchers found that treatment with valacyclovir did not reduce the likelihood that neurological signs would develop but it did seem to have a positive effect: “Valacyclovir significantly reduced severity of neurological disease,” explains Maxwell. Horses treated prior to being inoculated with EHV-1 showed the least severe ataxia, suggesting a benefit to treating all horses in a barn during an outbreak, not just those already showing clinical signs.

Maxwell says her findings indicate that the earlier treatment with the antiviral drug is started, the better: “Valacyclovir therapy should be administered early for the best chance of sparing the horse from debilitating disease,” she says. “Once the virus has impacted the central nervous system [CNS] and caused ataxia and other neurological signs, damage to the neurons has occurred, and that may or may not be reversible in that individual horse.”

In addition to drawing blood from horses daily to determine the circulating levels of virus (viremia), the researchers swabbed their nasal secretions throughout the study period to monitor viral shedding, which is how EHV spreads from horse to horse.

“Although shedding is from the nose, EHV-1 moves around the body through the blood,” says Maxwell. “It is theorized that the virus reaches the horse’s CNS by moving from the nose to the brain and spinal cord via the blood. Therefore, we are interested in viremia as a marker of how much EHV-1 could reach the CNS through the blood.”

The data revealed that horses started on valacyclovir prior to the development of fever had lower levels of nasal shedding and viremia. Although this alone is not proof that the drug could help curb outbreaks, the researchers believe it supports the idea of early treatment: “It would be a logical expectation that lower viral shedding in treated horses would decrease the chance of infecting other horses,” says Maxwell. “However, we don’t know what viral dose is necessary for infection and whether reduction (but not elimination) of shedding would really decrease the chance of infecting other horses.”

Maxwell says that ongoing studies are exploring other treatments that may be more effective later in the course of EHV-1 infection, but based on this study, “I’d recommend that any horse documented to have an active EHV-1 infection, or recent exposure to an infected horse, could potentially benefit from early treatment with valacyclovir. However, valacyclovir is most likely to be efficacious if therapy begins well before the development of neurological signs.”

This article was originally published in EQUUS 486, March 2018




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