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
Am J Vet Res. 2017 Oct;78(10):1126-1139. doi: 10.2460/ajvr.78.10.1126.
OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differentially 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.
目的 确定预防性给予盐酸伐昔洛韦与在发热开始时开始治疗相比，是否能不同程度地保护马匹免受1型马疱疹病毒（EHV-1）感染所致的病毒复制和临床疾病影响。动物 18匹成年母马。程序 将马匹随机分配接受口服安慰剂（对照）、发热时治疗或预防性治疗（在病毒攻击前1天开始），然后经鼻接种EHV-1的神经致病株。在接种EHV-1或检测到发热后，口服安慰剂或伐昔洛韦7天或14天（每组3匹马）。评估治疗对病毒复制和临床疾病的影响。评估血浆阿昔洛韦浓度和病毒血症，以确定伐昔洛韦的抑制浓度。结果 与对照马匹相比，给予伐昔洛韦可减少病毒脱落和病毒血症。预防性接受2周伐昔洛韦治疗的马匹直肠温度和临床疾病评分低于对照马匹。给予伐昔洛韦可降低共济失调的严重程度，但不降低其风险。当稳态谷血浆阿昔洛韦浓度>0.8μg/mL时，病毒血症降低，支持阿昔洛韦的时间依赖性活性。结论和临床意义 伐昔洛韦治疗可显著降低EHV-1感染马匹的病毒复制和疾病体征；在病毒接种前开始治疗时效果最佳，但在接种后2天开始治疗也有效。在马疱疹病毒脑脊髓炎爆发期间，抗病毒治疗可在感染的各个阶段在马匹中开始，包括尚未出现病毒疾病体征的马匹。
