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Journal of veterinary internal medicine2018; 32(5); 1763-1767; doi: 10.1111/jvim.15230

Effect of valacyclovir on EHV-5 viral kinetics in horses with equine multinodular pulmonary fibrosis.

Abstract: Equine herpesvirus-5 is commonly isolated from the lungs of horses with EMPF, suggesting an etiological link. Valacyclovir is used empirically to treat EMPF; however, no data is available concerning its impact on EHV-5 viral kinetics. Objective: To determine the effect of oral administration of valacyclovir on EHV-5 viral load measured by qPCR in blood, nasal secretions (NS) and BALF in horses with EMPF. Methods: Six horses diagnosed with EMPF. Methods: A prospective clinical trial was performed. Horses received 10 days of PO administered valacyclovir (loading dose 30 mg/kg, maintenance dose 20 mg/kg). Blood, NS, and BALF were collected for EHV-5 viral kinetics analyses during treatment. Blood and NS were collected every other day. BALF was collected on day 0 and day 10. Results: There was no statistical difference in median EHV-5 viral load between day 0 and day 10 for all samples tested. In blood median EHV-5 viral load was 7676 (range 575-39 781) on day 0 and 6822 (range 1136-18 635) glycoprotein B (gB) gene copies per million cells on day 10. For NS median EHV-5 viral load was 2.944 × 10 (range 184 691-3.394 × 10 ) on day 0 and 8.803 × 10 (range 251 186-9.868 × 10 ) gB gene copies per million cells on day 10. For BALF median EHV-5 viral load was 59,842 (range 61-315 655) on day 0 and 185 083 (range 3562-542 417) gB gene copies per million cells on day 10. Conclusions: Valacyclovir might not be an effective short-term antiviral treatment but efficacy in treatment of EMPF is unknown.
Publication Date: 2018-09-17 PubMed ID: 30221792PubMed Central: PMC6189341DOI: 10.1111/jvim.15230Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article

Summary

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The research evaluates the impact of the antiviral medication, Valacyclovir, on the viral load of Equine herpesvirus-5 (EHV-5) in horses diagnosed with equine multinodular pulmonary fibrosis (EMPF). The study found no significant difference in viral load before and after treatment suggesting that Valacyclovir may not be effective for short-term antiviral treatment of EMPF.

Research Objective

  • The main goal of the research was to determine the effect of the oral administration of Valacyclovir on EHV-5 viral load in horses diagnosed with EMPF. The sample included six horses and the viral load was measured using quantitative Polymerase Chain Reaction (qPCR) analysis in blood, nasal secretions (NS), and Bronchoalveolar lavage fluid (BALF).

Methods

  • A prospective clinical trial was conducted where the six diagnosed horses were given an oral loading dose of 30 mg/kg of Valacyclovir, followed by a maintenance dose of 20 mg/kg for 10 days.
  • Blood and NS samples were collected every other day, while BALF was collected on the first (day 0) and last (day 10) days of the experiment.
  • The viral load, in terms of glycoprotein B gene copies per million cells, was then analysed in these samples.

Results

  • The study found no statistically significant difference in the median EHV-5 viral load between day 0 and day 10 for all samples tested.
  • The viral load in the blood was 7676 on day 0 and decreased slightly to 6822 on day 10.
  • In NS, the viral load was around 2.944 x 10 on day 0 and increased considerably to 8.803 x 10 by day 10.
  • For BALF, the median viral load significantly increased from 59,842 on day 0 to 185,083 on day 10.

Conclusion

  • The research concluded that the administration of Valacyclovir appears to have negligible effects on short-term EHV-5 viral kinetics in horses with EMPF. There was no significant reduction in viral load in the tested samples, with some even showing considerable increase.
  • While Valacyclovir is commonly used to treat EMPF based on perceived associations between the disease and EHV-5, its efficacy for this particular purpose remains uncertain. More research is required to evaluate the drug’s long-term effects and potential utility in treating EMPF.

Cite This Article

APA
Easton-Jones CA, Madigan JE, Barnum S, Maxwell LK, Taylor SD, Arnesen T, Pusterla N. (2018). Effect of valacyclovir on EHV-5 viral kinetics in horses with equine multinodular pulmonary fibrosis. J Vet Intern Med, 32(5), 1763-1767. https://doi.org/10.1111/jvim.15230

Publication

ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 32
Issue: 5
Pages: 1763-1767

Researcher Affiliations

Easton-Jones, Charlotte A
  • Willian R Pritchard Veterinary Medical Teaching Hospital, University of California Davis, California.
Madigan, John E
  • Department of Medicine and Epidemiology, University of California, Davis, California.
Barnum, Samantha
  • Department of Medicine and Epidemiology, University of California, Davis, California.
Maxwell, Lara K
  • Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma.
Taylor, Sandra D
  • Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana, IN.
Arnesen, Terry
  • Stillwater Equine Veterinary Clinic, Stillwater, Minnesota.
Pusterla, Nicola
  • Department of Medicine and Epidemiology, University of California, Davis, California.

MeSH Terms

  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use
  • Bronchoalveolar Lavage Fluid
  • DNA, Viral
  • Dose-Response Relationship, Drug
  • Female
  • Gammaherpesvirinae
  • Herpesviridae Infections / drug therapy
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / virology
  • Horse Diseases / drug therapy
  • Horses
  • Male
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / veterinary
  • Pulmonary Fibrosis / virology
  • Valacyclovir / administration & dosage
  • Valacyclovir / therapeutic use
  • Virus Replication / drug effects

Grant Funding

  • University of California, Davis Center for Equine Health with funds provided by the State of California satellite wagering fund and contributions by private donors.

References

This article includes 32 references
  1. Williams KJ, Maes R, Del Piero F, Lim A, Wise A, Bolin DC, Caswell J, Jackson C, Robinson NE, Derksen F, Scott MA, Uhal BD, Li X, Youssef SA, Bolin SR. Equine multinodular pulmonary fibrosis: a newly recognized herpesvirus-associated fibrotic lung disease.. Vet Pathol 2007 Nov;44(6):849-62.
    pubmed: 18039898doi: 10.1354/vp.44-6-849google scholar: lookup
  2. Wong DM, Belgrave RL, Williams KJ, Del Piero F, Alcott CJ, Bolin SR, Marr CM, Nolen-Walston R, Myers RK, Wilkins PA. Multinodular pulmonary fibrosis in five horses.. J Am Vet Med Assoc 2008 Mar 15;232(6):898-905.
    pubmed: 18341449doi: 10.2460/javma.232.6.898google scholar: lookup
  3. Williams KJ, Robinson NE, Lim A, Brandenberger C, Maes R, Behan A, Bolin SR. Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.. PLoS One 2013;8(10):e77754.
  4. Williams KJ. Gammaherpesviruses and pulmonary fibrosis: evidence from humans, horses, and rodents.. Vet Pathol 2014 Mar;51(2):372-84.
    pubmed: 24569614doi: 10.1177/0300985814521838google scholar: lookup
  5. Wilkins PA. Equine multinodular pulmonary fibrosis: Diagnosis and treatment.. Equine Vet Educ 2013;25:393–397.
  6. Hart KA, Barton MH, Williams KJ. Multinodular pulmonary fibrosis, pancytopenia and equine herpesvirus‐5 infection in a Thoroughbred gelding.. Equine Vet Educ 2008;20:469–476.
  7. Dunkel B. Pulmonary fibrosis and gammaherpesvirus infection in horses.. Equine Vet Educ 2012;24:200–205.
  8. Belgrave RL. Review of the diagnosis, treatment, and managment of equine multinodular pulmonary fibrosis (Five Cases).. AAEP Proc 2009;55:304–306.
  9. Spelta CW, Axon JE, Begg A, Diallo IS, Carrick JB, Russell CM, Collins NM. Equine multinodular pulmonary fibrosis in three horses in Australia.. Aust Vet J 2013 Jul;91(7):274-80.
    pubmed: 23782020doi: 10.1111/avj.12072google scholar: lookup
  10. Niedermaier G, Poth T, Gehlen H. Clinical aspects of multinodular pulmonary fibrosis in two warmblood horses.. Vet Rec 2010 Apr 3;166(14):426-30.
    pubmed: 20364010doi: 10.1136/vr.b4811google scholar: lookup
  11. Schwarz B, Schwendenwein I, van den Hoven R. Successful outcome in a case of equine multinodular pulmonary fibrosis (EMPF) treated with valacyclovir.. Equine Vet Educ 2013;25:389–392.
  12. Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis.. Lancet 2017 May 13;389(10082):1941-1952.
    pubmed: 28365056doi: 10.1016/s0140-6736(17)30866-8google scholar: lookup
  13. Yonemaru M, Kasuga I, Kusumoto H, Kunisawa A, Kiyokawa H, Kuwabara S, Ichinose Y, Toyama K. Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis.. Eur Respir J 1997 Sep;10(9):2040-5.
    pubmed: 9311499doi: 10.1183/09031936.97.10092040google scholar: lookup
  14. Schooley RT, Carey RW, Miller G, Henle W, Eastman R, Mark EJ, Kenyon K, Wheeler EO, Rubin RH. Chronic Epstein-Barr virus infection associated with fever and interstitial pneumonitis. Clinical and serologic features and response to antiviral chemotherapy.. Ann Intern Med 1986 May;104(5):636-43.
    pubmed: 3008616doi: 10.7326/0003-4819-104-5-636google scholar: lookup
  15. Doran P, Egan JJ. Herpesviruses: a cofactor in the pathogenesis of idiopathic pulmonary fibrosis?. Am J Physiol Lung Cell Mol Physiol 2005 Nov;289(5):L709-10.
    pubmed: 16214821doi: 10.1152/ajplung.00235.2005google scholar: lookup
  16. Rempe S, Hayden JM, Robbins RA, Hoyt JC. Tetracyclines and pulmonary inflammation.. Endocr Metab Immune Disord Drug Targets 2007 Dec;7(4):232-6.
    pubmed: 18220943doi: 10.2174/187153007782794344google scholar: lookup
  17. Wong DM, Maxwell LK, Wilkins PA. Use of antiviral medications against equine herpes virus associated disorders.. Equine Vet Educ 2010;22:244–252.
  18. 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.
    pmc: PMC6440545pubmed: 28945127doi: 10.2460/ajvr.78.10.1126google scholar: lookup
  19. Maxwell LK, Bentz BG, Bourne DW, Erkert RS. Pharmacokinetics of valacyclovir in the adult horse.. J Vet Pharmacol Ther 2008 Aug;31(4):312-20.
  20. Pusterla N, Mapes S, Wademan C, White A, Hodzic E. Investigation of the role of lesser characterised respiratory viruses associated with upper respiratory tract infections in horses.. Vet Rec 2013 Mar 23;172(12):315.
    pubmed: 23423483doi: 10.1136/vr.100943google scholar: lookup
  21. Pusterla N, Mapes S, Wilson WD. Use of viral loads in blood and nasopharyngeal secretions for the diagnosis of EHV-1 infection in field cases.. Vet Rec 2008 May 31;162(22):728-9.
    pubmed: 18515763doi: 10.1136/vr.162.22.728google scholar: lookup
  22. Wilkins PA, Papich M, Sweeney RW. Pharmacokinetics of acyclovir in adult horses.. JVet Emerg Crit Care 2005;15:174–178.
  23. Bentz BG, Maxwell LK, Erkert RS, Royer CM, Davis MS, MacAllister CG, Clarke CR. Pharmacokinetics of acyclovir after single intravenous and oral administration to adult horses.. J Vet Intern Med 2006 May-Jun;20(3):589-94.
  24. Garré B, Shebany K, Gryspeerdt A, Baert K, van der Meulen K, Nauwynck H, Deprez P, De Backer P, Croubels S. Pharmacokinetics of acyclovir after intravenous infusion of acyclovir and after oral administration of acyclovir and its prodrug valacyclovir in healthy adult horses.. Antimicrob Agents Chemother 2007 Dec;51(12):4308-14.
    pmc: PMC2167972pubmed: 17846132doi: 10.1128/aac.00116-07google scholar: lookup
  25. Fortier G, van Erck E, Pronost S, Lekeux P, Thiry E. Equine gammaherpesviruses: pathogenesis, epidemiology and diagnosis.. Vet J 2010 Nov;186(2):148-56.
    pubmed: 19766026doi: 10.1016/j.tvjl.2009.08.017google scholar: lookup
  26. Hoshino Y, Katano H, Zou P, Hohman P, Marques A, Tyring SK, Follmann D, Cohen JI. Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers.. J Virol 2009 Nov;83(22):11857-61.
    pmc: PMC2772668pubmed: 19740997doi: 10.1128/jvi.01005-09google scholar: lookup
  27. Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis.. Am J Respir Crit Care Med 2011 Feb 15;183(4):431-40.
    pubmed: 20935110doi: 10.1164/rccm.201006-0894cigoogle scholar: lookup
  28. Aiello M, Bertorelli G, Bocchino M, Chetta A, Fiore-Donati A, Fois A, Marinari S, Oggionni T, Polla B, Rosi E, Stanziola A, Varone F, Sanduzzi A. The earlier, the better: Impact of early diagnosis on clinical outcome in idiopathic pulmonary fibrosis.. Pulm Pharmacol Ther 2017 Jun;44:7-15.
    pubmed: 28257817doi: 10.1016/j.pupt.2017.02.005google scholar: lookup
  29. Back H, Ullman K, Leijon M, Söderlund R, Penell J, Ståhl K, Pringle J, Valarcher JF. Genetic variation and dynamics of infections of equid herpesvirus 5 in individual horses.. J Gen Virol 2016 Jan;97(1):169-178.
    pubmed: 26518010doi: 10.1099/jgv.0.000332google scholar: lookup
  30. King TE Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis.. Lancet 2011 Dec 3;378(9807):1949-61.
    pubmed: 21719092doi: 10.1016/s0140-6736(11)60052-4google scholar: lookup
  31. Selman M, Carrillo G, Estrada A, Mejia M, Becerril C, Cisneros J, Gaxiola M, Pérez-Padilla R, Navarro C, Richards T, Dauber J, King TE Jr, Pardo A, Kaminski N. Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern.. PLoS One 2007 May 30;2(5):e482.
  32. Pusterla N, Magdesian KG, Mapes SM, Zavodovskaya R, Kass PH. Assessment of quantitative polymerase chain reaction for equine herpesvirus-5 in blood, nasal secretions and bronchoalveolar lavage fluid for the laboratory diagnosis of equine multinodular pulmonary fibrosis.. Equine Vet J 2017 Jan;49(1):34-38.
    pubmed: 26639080doi: 10.1111/evj.12545google scholar: lookup

Citations

This article has been cited 2 times.
  1. Hardefeldt L, Thomas K, Page S, Norris J, Browning G, El Hage C, Stewart A, Gilkerson J, Muscatello G, Verwilghen D, van Galen G, Bauquier J, Cuming R, Reynolds B, Whittaker C, Wilkes E, Clulow J, Burden C, Begg L. Antimicrobial prescribing guidelines for horses in Australia. Aust Vet J 2025 Dec;103(12):781-889.
    doi: 10.1111/avj.70003pubmed: 40903020google scholar: lookup
  2. Craven A, Todd-Donato A, Stokol T, Liepman R, Glasberg I, Wilkins P, Luethy D, Wong D, Schoster A, van den Brom-Spierenburg AJ, Tomlinson JE. Clinical findings and outcome predictors for multinodular pulmonary fibrosis in horses: 46 cases (2009-2019). J Vet Intern Med 2024 May-Jun;38(3):1842-1857.
    doi: 10.1111/jvim.17084pubmed: 38619130google scholar: lookup