Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-I infection in horses

Lara K. Maxwell, Bradford G. Bentz, Lyndi L. Gilliam, Jerry W. Ritchey, Nicola Pusterla, R. Eberle, Todd C. Holbrook, Dianne McFarlane, Grant B. Rezabek, James Meinkoth, Chase Whitfield, Carla L. Goad, George P. Allen

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Abstract

OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differen-tially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 µg/ mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1–infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.

Original languageEnglish (US)
Pages (from-to)1126-1139
Number of pages14
JournalAmerican Journal of Veterinary Research
Volume78
Issue number10
DOIs
StatePublished - Oct 1 2017

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valacyclovir
Herpesviridae Infections
Horses
horses
infection
Equid Herpesvirus 1
Equid herpesvirus 1
Acyclovir
Viremia
viremia
virus replication
fever
Therapeutics
Fever
placebos
myeloencephalopathy
Placebos
Virus Shedding
viral shedding

ASJC Scopus subject areas

  • veterinary(all)

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Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-I infection in horses. / Maxwell, Lara K.; Bentz, Bradford G.; Gilliam, Lyndi L.; Ritchey, Jerry W.; Pusterla, Nicola; Eberle, R.; Holbrook, Todd C.; McFarlane, Dianne; Rezabek, Grant B.; Meinkoth, James; Whitfield, Chase; Goad, Carla L.; Allen, George P.

In: American Journal of Veterinary Research, Vol. 78, No. 10, 01.10.2017, p. 1126-1139.

Research output: Contribution to journalArticle

Maxwell, LK, Bentz, BG, Gilliam, LL, Ritchey, JW, Pusterla, N, Eberle, R, Holbrook, TC, McFarlane, D, Rezabek, GB, Meinkoth, J, Whitfield, C, Goad, CL & Allen, GP 2017, 'Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-I infection in horses', American Journal of Veterinary Research, vol. 78, no. 10, pp. 1126-1139. https://doi.org/10.2460/ajvr.78.10.1126
Maxwell, Lara K. ; Bentz, Bradford G. ; Gilliam, Lyndi L. ; Ritchey, Jerry W. ; Pusterla, Nicola ; Eberle, R. ; Holbrook, Todd C. ; McFarlane, Dianne ; Rezabek, Grant B. ; Meinkoth, James ; Whitfield, Chase ; Goad, Carla L. ; Allen, George P. / Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-I infection in horses. In: American Journal of Veterinary Research. 2017 ; Vol. 78, No. 10. pp. 1126-1139.
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abstract = "OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differen-tially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 µg/ mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1–infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.",
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AU - Bentz, Bradford G.

AU - Gilliam, Lyndi L.

AU - Ritchey, Jerry W.

AU - Pusterla, Nicola

AU - Eberle, R.

AU - Holbrook, Todd C.

AU - McFarlane, Dianne

AU - Rezabek, Grant B.

AU - Meinkoth, James

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N2 - OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differen-tially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 µg/ mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1–infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.

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