Evaluation of orally administered valacyclovir in experimentally EHV1-infected ponies.
Abstract: The purpose of the current study was to investigate the therapeutic efficacy of valacyclovir against EHV1 in a controlled study. Eight naïve Shetland ponies were inoculated with 10(6.5) TCID(50) of the neuropathogenic strain 03P37. Four ponies were treated with valacyclovir at a dosage of 40mg/kg bodyweight, 3 times daily, for 5 (n=2) or 7 (n=2) consecutive days, while the other four ponies served as untreated controls. The treatment regimen started 1h before inoculation. Ponies were monitored daily for clinical signs. At 0, 1, 2, 3, 4, 5, 7, 9, 11, 14, 17 and 21 days post inoculation (d pi), a nasopharyngeal mucus sample was taken to determine viral shedding. At the same time points, blood was collected and peripheral blood mononuclear cells (PBMC) were isolated to determine viremia. During the treatment, blood samples were collected 6 times daily, i.e. just before valacyclovir administration and 1h later, to determine the concentration of acyclovir in plasma. Also a nasopharyngeal swab was taken to measure the acyclovir concentration in nasal secretion. No differences could be noticed between valacyclovir-treated and untreated ponies. The clinical signs, the viral shedding and the viremia were similar in both the groups. Plasma acyclovir concentration could be maintained above the EC(50)-value of EHV1 during 50% of the entire treatment period in valacyclovir-treated ponies. Acyclovir could be detected in nasal swabs at concentrations varying from 50% to 100% of the corresponding plasma concentration. Although sufficiently high acyclovir levels could be reached in plasma and nasal mucus, no effect was seen of the treatment with valacyclovir on clinical signs, viral shedding and viremia of EHV1-infected ponies.
Publication Date: 2008-09-21 PubMed ID: 18986780DOI: 10.1016/j.vetmic.2008.09.062Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research primarily focuses on the effectiveness of valacyclovir, an antiviral medication, in treating Equine Herpes Virus-1 (EHV1) in ponies. Despite administering the expected therapeutic level of the medication to experimentally infected ponies, the study found no noticeable differences in infection symptoms, virus shedding, or bloodstream virus presence between treated and untreated animals.
Research Design and Methodology
- The research used eight Shetland ponies that had never been exposed to EHV1. These ponies were experimentally infected with a neuropathogenic strain of EHV1.
- A dosage of 40mg/kg of valacyclovir was administered three times daily to half of the ponies (four out of eight) for either 5 or 7 consecutive days. The treatment began 1 hour prior to infecting the ponies with EHV1. The remaining four ponies were utilized as controls and did not receive any treatment.
- All the ponies were observed daily for clinical signs of illness. They were also tested regularly post-infection to monitor viral shedding (the process through which a virus is expelled and can infect new hosts) through nasopharyngeal mucus samples and to detect the presence of the virus in their blood.
Key Findings
- The study revealed that there were no differences in clinical symptoms, virus shedding, and the presence of the virus in the bloodstream (viremia) between the valacyclovir-treated ponies and the untreated ones.
- In the treated ponies, the researchers marked that the plasma concentration of acyclovir, the active form of valacyclovir, remained above the suggested effective concentration against EHV1 for 50% of the treatment period.
- They also noticed the presence of acyclovir in the nasal secretions of the treated ponies, with concentrations ranging from 50% to 100% of the corresponding plasma concentration.
Conclusion
- The study concluded that despite the placebo-controlled design and the achievement of therapeutically relevant concentrations of acyclovir in plasma and nasal secretions, no effect was observed on the progression or control of EHV1 infection in the treated ponies.
- This implies that while valacyclovir can achieve expected therapeutic concentrations in plasma and nasal secretions, it might not be effective in reducing symptoms, controlling viral shedding, or lowering viremia in ponies affected by EHV1.
Cite This Article
APA
Garré B, Gryspeerdt A, Croubels S, De Backer P, Nauwynck H.
(2008).
Evaluation of orally administered valacyclovir in experimentally EHV1-infected ponies.
Vet Microbiol, 135(3-4), 214-221.
https://doi.org/10.1016/j.vetmic.2008.09.062 Publication
Researcher Affiliations
- Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. barbara.garre@ugent.be
MeSH Terms
- Acyclovir / analogs & derivatives
- Acyclovir / blood
- Acyclovir / therapeutic use
- Animals
- Antiviral Agents / blood
- Antiviral Agents / therapeutic use
- Body Temperature / drug effects
- Dose-Response Relationship, Drug
- Fever / drug therapy
- Fever / veterinary
- Herpesviridae Infections / drug therapy
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / drug effects
- Herpesvirus 1, Equid / isolation & purification
- Horse Diseases / drug therapy
- Horse Diseases / virology
- Horses
- Valacyclovir
- Valine / analogs & derivatives
- Valine / blood
- Valine / therapeutic use
- Virus Shedding / drug effects
Citations
This article has been cited 17 times.- Thieulent CJ, Sutton G, Toquet MP, Fremaux S, Hue E, Fortier C, Pléau A, Deslis A, Abrioux S, Guitton E, Pronost S, Paillot R. Oral Administration of Valganciclovir Reduces Clinical Signs, Virus Shedding and Cell-Associated Viremia in Ponies Experimentally Infected with the Equid Herpesvirus-1 C(2254) Variant. Pathogens 2022 May 4;11(5).
- Vandenberghe E, Boshuizen B, Delesalle CJG, Goehring LS, Groome KA, van Maanen K, de Bruijn CM. New Insights into the Management of an EHV-1 (Equine Hospital) Outbreak. Viruses 2021 Jul 22;13(8).
- Lecollinet S, Pronost S, Coulpier M, Beck C, Gonzalez G, Leblond A, Tritz P. Viral Equine Encephalitis, a Growing Threat to the Horse Population in Europe?. Viruses 2019 Dec 24;12(1).
- Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Couck L, Van den Broeck W, Azab W, Nauwynck HJ. Equine Herpesvirus 1 Bridles T Lymphocytes To Reach Its Target Organs. J Virol 2019 Apr 1;93(7).
- Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Soboll Hussey G, Maes RK, Nauwynck HJ. Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense. Front Cell Infect Microbiol 2018;8:312.
- Tallmadge RL, Žygelytė E, Van de Walle GR, Kristie TM, Felippe MJB. Effect of a Histone Demethylase Inhibitor on Equine Herpesvirus-1 Activity In Vitro. Front Vet Sci 2018;5:34.
- 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. Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-1 infection in horses. Am J Vet Res 2017 Oct;78(10):1126-1139.
- Hue ES, Richard EA, Fortier CI, Fortier GD, Paillot R, Raue R, Pronost SL. Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment. Vaccines (Basel) 2017 Sep 19;5(3).
- Zhao J, Poelaert KCK, Van Cleemput J, Nauwynck HJ. CCL2 and CCL5 driven attraction of CD172a(+) monocytic cells during an equine herpesvirus type 1 (EHV-1) infection in equine nasal mucosa and the impact of two migration inhibitors, rosiglitazone (RSG) and quinacrine (QC). Vet Res 2017 Feb 27;48(1):14.
- Toishi Y, Tsunoda N, Kirisawa R. Occurrence of equine coital exanthema (ECE) in stallions in Japan and effectiveness of treatment with valacyclovir for ECE. J Vet Med Sci 2017 Mar 23;79(3):632-635.
- Laval K, Favoreel HW, Poelaert KC, Van Cleemput J, Nauwynck HJ. Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells. J Virol 2015 Nov;89(21):10912-23.
- Carmichael RJ, Whitfield C, Maxwell LK. Pharmacokinetics of ganciclovir and valganciclovir in the adult horse. J Vet Pharmacol Ther 2013 Oct;36(5):441-9.
- Brosnahan MM, Damiani A, van de Walle G, Erb H, Perkins GA, Osterrieder N. The effect of siRNA treatment on experimental equine herpesvirus type 1 (EHV-1) infection in horses. Virus Res 2010 Feb;147(2):176-81.
- Fulton A, Peters ST, Perkins GA, Jarosinski KW, Damiani A, Brosnahan M, Buckles EL, Osterrieder N, Van de Walle GR. Effective treatment of respiratory alphaherpesvirus infection using RNA interference. PLoS One 2009;4(1):e4118.
- Normand C, Thieulent CJ, Fortier C, Sutton G, Senamaud-Beaufort C, Jourdren L, Blugeon C, Vidalain PO, Pronost S, Hue ES. A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response. Viruses 2024 May 8;16(5).
- Goehring L, Dorman DC, Osterrieder K, Burgess BA, Dougherty K, Gross P, Neinast C, Pusterla N, Soboll-Hussey G, Lunn DP. Pharmacologic interventions for the treatment of equine herpesvirus-1 in domesticated horses: A systematic review. J Vet Intern Med 2024 May-Jun;38(3):1892-1905.
- Pusterla N, Dorman DC, Burgess BA, Goehring L, Gross M, Osterrieder K, Soboll Hussey G, Lunn DP. Viremia and nasal shedding for the diagnosis of equine herpesvirus-1 infection in domesticated horses. J Vet Intern Med 2024 May-Jun;38(3):1765-1791.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
