RESUMEN
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.
Asunto(s)
Aciclovir/análogos & derivados , Antivirales/uso terapéutico , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1 , Enfermedades de los Caballos/tratamiento farmacológico , Valina/análogos & derivados , Aciclovir/uso terapéutico , Animales , Femenino , Fiebre/tratamiento farmacológico , Fiebre/veterinaria , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/fisiopatología , Enfermedades de los Caballos/fisiopatología , Caballos , Premedicación/veterinaria , Valaciclovir , Valina/uso terapéutico , Viremia/veterinaria , Replicación Viral/efectos de los fármacosRESUMEN
The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between each treatment. Serum samples were obtained for acyclovir assay using reversed-phase, high-performance liquid chromatography with fluorescence detection. Deproteinated serum was injected onto a C18 column, and elution occurred under isocratic conditions. The limit of quantification was 0.04 microg/mL. The assay exhibited suitable accuracy, precision, and recovery. The IV data were analyzed by a 3-compartment model, and oral data were analyzed noncompartmentally. Intragastric acyclovir administration at either dose was associated with high variability in serum acyclovir-time profiles, low Cmax, and poor bioavailability. The dosage of 20 mg/kg was associated with mean (+/- SD) Cmax of 0.19 +/- 0.10 microg/mL, and bioavailability was 2.8%. Inhibition of equine herpesvirus has been reported to require significantly higher acyclovir concentrations than those obtained here. The results of this study do not support a therapeutic benefit for the oral administration of acyclovir up to doses of 20 mg/kg.
Asunto(s)
Aciclovir/farmacocinética , Antivirales/farmacocinética , Caballos/metabolismo , Aciclovir/administración & dosificación , Aciclovir/sangre , Administración Oral , Animales , Antivirales/administración & dosificación , Antivirales/sangre , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Femenino , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1 , Enfermedades de los Caballos/tratamiento farmacológico , Inyecciones Intravenosas/veterinaria , MasculinoRESUMEN
A sampling of equids from the state of Oklahoma produced an estimate of seroprevalence of antibody to Sarcocystis neurona to be about 89.2%. This figure represents the highest currently reported regional seroprevalence of antibody to this organism. Regional differences in seroprevalence were found in the western quadrants of the state relative to the eastern quadrants of the state, with a significantly higher seroprevalence in the eastern regions. Thoroughbreds were found to exhibit a statistically significant lower seroprevalence as a breed group when compared with other breeds sampled.
Asunto(s)
Anticuerpos Antiprotozoarios/análisis , Enfermedades de los Caballos/epidemiología , Sarcocystis/inmunología , Sarcocistosis/veterinaria , Animales , Femenino , Enfermedades de los Caballos/inmunología , Enfermedades de los Caballos/microbiología , Caballos , Immunoblotting , Masculino , Oklahoma/epidemiología , Sarcocystis/patogenicidad , Sarcocistosis/epidemiología , Sarcocistosis/inmunología , Estudios SeroepidemiológicosRESUMEN
A 4-year-old Thoroughbred stallion was referred for signs of mild to moderate colic, anorexia, and decreased water intake of 3 weeks' duration. Ultrasonographic examination revealed an intussusception, the most common of which would be a cecal inversion or ileocecal intussusception. Surgical exploration identified an ileocecocolic intussusception with extension of the intussusceptum into the right ventral colon; however, the cause of the intussusception could not be identified. The intussusception could not be surgically corrected, and the horse was euthanatized. A side-to-side jejunocecostomy that had been performed previously was identified at necropsy. The ileal stump had intussuscepted into the right ventral colon and become hypertrophied, causing partial obstruction of the cecocolic orifice and clinical signs of colic. In horses requiring an ileocecal or jejunocecal anastomosis, the ileal stump may be left to slough within the cecum as part of the treatment for an irreducible ileocecal intussusception or intentionally inverted into the cecum when the ileal stump is necrotic and cannot be exteriorized and resected. Efforts should be made to minimize the size of the ileal stump to reduce the liklihood of intussusception.