EQUUS - - Eq Medical Front -

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

EHV-1 in­fec­tion typ­i­cally causes res­pi­ra­tory ill­ness in young horses and abor­tions in preg­nant mares.

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.”

The re­searchers found that treat­ment with vala­cy­clovir did not make it less likely that horses in­fected with EHV-1 would de­velop neu­ro­log­i­cal signs, but it did re­duce the sever­ity of their im­pair­ment.


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