Analyze Diet
Journal of veterinary internal medicine2024; 38(3); 1892-1905; doi: 10.1111/jvim.17016

Pharmacologic interventions for the treatment of equine herpesvirus-1 in domesticated horses: A systematic review.

Abstract: Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death. Objective: Does pharmacological therapy decrease either the incidence or severity of disease or infection caused by EHV-1 in domesticated horses? Methods: A systematic review was preformed searching AGRICOLA, CAB Abstracts, Cochrane, PubMed, Web of Science, and WHO Global Health Index Medicus Regional Databases to identify articles published before February 15, 2021. Selection criteria were original research reports published in peer reviewed journals, and studies investigating in vivo use of therapeutic agents for prevention or treatment of EHV-1 in horses. Outcomes assessed included measures related to clinical outcomes that reflect symptomatic EHV-1 infection or virus infection. We evaluated risk of bias and performed a GRADE evaluation of the quality of evidence for interventions. Results: A total of 7009 unique studies were identified, of which 9 met the inclusion criteria. Two studies evaluated valacyclovir or small interfering RNAs, and single studies evaluated the use of a Parapoxvirus ovis-based immunomodulator, human alpha interferon, an herbal supplement, a cytosine analog, and heparin. The level of evidence ranged between randomized controlled studies and observational trials. The risk of bias was moderate to high and sample sizes were small. Most studies reported either no benefit or minimal efficacy of the intervention tested. Conclusions: Our review indicates minimal or limited benefit either as a prophylactic or post-exposure treatment for any of the studied interventions in the mitigation of EHV-1-associated disease outcome.
Publication Date: 2024-02-21 PubMed ID: 38380685PubMed Central: PMC11099759DOI: 10.1111/jvim.17016Google 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.
  • Systematic Review
  • 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.

Overview

  • This research article systematically reviews existing studies to determine whether pharmacological treatments reduce the incidence or severity of equine herpesvirus-1 (EHV-1) infection in domesticated horses.
  • The review concludes that available pharmacologic interventions show minimal or limited benefit for preventing or treating EHV-1-related disease outcomes.

Background

  • Equine herpesvirus type 1 (EHV-1) is a significant pathogen in horses causing upper respiratory illness, neurological disease, abortions in pregnant mares, and death of newborn foals.
  • Due to the serious clinical consequences of EHV-1 infections, effective treatments to reduce disease severity or infection rates are needed.

Objective

  • The primary question was: Does pharmacological therapy decrease the incidence or severity of EHV-1 infection or related disease in domesticated horses?

Methods

  • A systematic literature search was conducted across multiple databases: AGRICOLA, CAB Abstracts, Cochrane, PubMed, Web of Science, and WHO Global Health Index Medicus Regional Databases.
  • Articles published before February 15, 2021, were considered.
  • Inclusion criteria:
    • Original research published in peer-reviewed journals.
    • Studies investigating in vivo use of therapeutic agents for prevention or treatment of EHV-1 infection in horses.
  • Outcomes assessed were clinical measures indicating symptomatic EHV-1 infection or virus presence.
  • Risk of bias in studies was evaluated, and the GRADE approach was used to assess the quality of evidence for interventions.

Results

  • From 7009 unique studies identified, only 9 met all inclusion criteria.
  • Interventions evaluated in these studies included:
    • Valacyclovir (antiviral drug) – 2 studies
    • Small interfering RNAs (siRNAs) – 2 studies
    • Parapoxvirus ovis-based immunomodulator – 1 study
    • Human alpha interferon – 1 study
    • Herbal supplement – 1 study
    • Cytosine analog (antiviral agent) – 1 study
    • Heparin (anticoagulant with potential anti-inflammatory effects) – 1 study
  • The types of studies included ranged from randomized controlled trials to observational trials.
  • Risk of bias assessment showed moderate to high risk, indicating potential limitations in study design or execution.
  • Most studies had small sample sizes, limiting the power to detect significant treatment effects.
  • The majority of studies either reported no benefit or only minimal efficacy of the pharmacologic agents tested in preventing or mitigating EHV-1 infection or disease severity.

Conclusions

  • Current pharmacologic interventions do not demonstrate strong or consistent evidence of effectiveness as either preventive or post-exposure treatments against EHV-1 in horses.
  • There is limited benefit observed from the tested drugs and immunomodulatory agents in controlling the clinical consequences of EHV-1 infection.
  • Further well-designed, larger-scale controlled studies are required to better evaluate potential therapeutic options.
  • Until such evidence emerges, management of EHV-1 infections relies primarily on supportive care and prevention strategies rather than pharmacologic treatment.

Cite This Article

APA
Goehring L, Dorman DC, Osterrieder K, Burgess BA, Dougherty K, Gross P, Neinast C, Pusterla N, Soboll-Hussey G, Lunn DP. (2024). Pharmacologic interventions for the treatment of equine herpesvirus-1 in domesticated horses: A systematic review. J Vet Intern Med, 38(3), 1892-1905. https://doi.org/10.1111/jvim.17016

Publication

ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 38
Issue: 3
Pages: 1892-1905

Researcher Affiliations

Goehring, Lutz
  • University of Kentucky, College of Agriculture, Food and Environment, Maxwell H. Gluck Equine Research Center, 1400 Nicholasville Road, Lexington, Kentucky 40546-0099, USA.
Dorman, David C
  • College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA.
Osterrieder, Klaus
  • Institut für Virologie, Freie Universität Berlin, Robert-von-Ostertag-Str. 7, 14163 Berlin, Germany.
Burgess, Brandy A
  • College of Veterinary Medicine, University of Georgia, 2200 College Station Road, Athens, Georgia 30602, USA.
Dougherty, Kelsie
  • College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA.
Gross, Peggy
  • College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA.
Neinast, Claire
  • College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA.
Pusterla, Nicola
  • School of Veterinary Medicine, University of California, Davis, One Garrod Drive, Davis, California 95616, USA.
Soboll-Hussey, Gisela
  • College of Veterinary Medicine, Michigan State University, Veterinary Medical Center, Room G331, 784 Wilson Road, East Lansing, Michigan 48824, USA.
Lunn, David P
  • School of Veterinary Science, University of Liverpool, Leahurst Campus, Chester High Road, Neston CH64 7TE, United Kingdom.

MeSH Terms

  • Animals
  • Horses
  • Herpesvirus 1, Equid / drug effects
  • Horse Diseases / drug therapy
  • Horse Diseases / virology
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / drug therapy
  • Antiviral Agents / therapeutic use
  • Valacyclovir / therapeutic use

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 40 references
  1. Oladunni FS, Horohov DW, Chambers TM. EHV‐1: a constant threat to the horse industry.. Front Microbiol 2019;10:2668.
    pmc: PMC6901505pubmed: 31849857
  2. Lunn DP, Davis‐Poynter N, Flaminio MJBF. Equine herpesvirus‐1 consensus statement.. J Vet Intern Med 2009;23:450‐461.
    pubmed: 19645832
  3. Reed SM, Toribio RE. Equine herpesvirus 1 and 4.. Vet Clin North Am Equine Pract 2004;20:631‐642.
    pubmed: 15519823
  4. Dunowska M. How common is equine herpesvirus type 1 infection?. Vet Rec 2016;178:67‐69.
    pubmed: 26769811
  5. Patel JR, Heldens J. Equine herpesviruses 1 (EHV‐1) and 4 (EHV‐4)—epidemiology, disease and immunoprophylaxis: a brief review.. Vet J 2005;170:14‐23.
    pubmed: 15993786
  6. Pusterla N, Mapes S, Akana N. Prevalence factors associated with equine herpesvirus type 1 infection in equids with upper respiratory tract infection and/or acute onset of neurological signs from 2008 to 2014.. Vet Rec 2016;178:70.
    pubmed: 26607427
  7. Dunowska M. A review of equid herpesvirus 1 for the veterinary practitioner. Part a: clinical presentation, diagnosis and treatment.. N Z Vet J 2014;62:171‐178.
    pubmed: 24597778
  8. Dunowska M. A review of equid herpesvirus 1 for the veterinary practitioner. Part B: pathogenesis and epidemiology.. N Z Vet J 2014;62:179‐188.
    pubmed: 24597839
  9. Pusterla N, Hussey GS. Equine herpesvirus 1 myeloencephalopathy.. Vet Clin North Am Equine Pract 2014;30:489‐506.
    pubmed: 25300635
  10. Pusterla N, David Wilson W, Madigan JE, Ferraro GL. Equine herpesvirus‐1 myeloencephalopathy: a review of recent developments.. Vet J 2009;180:279‐289.
    pubmed: 18805030
  11. Goehring LS, van Maanen C, Sloet van Oldruitenborgh‐Oosterbaan MM. Neurological syndromes among horses in The Netherlands. A 5 year retrospective survey (1999–2004).. Vet Q 2005;27:11‐20.
    pubmed: 15835280
  12. Garre B, Gryspeerdt A, Croubels S. Evaluation of orally administered valacyclovir in experimentally EHV1‐infected ponies.. Vet Microbiol 2009;135:214‐221.
    pubmed: 18986780
  13. Henninger RW, Reed SM, Saville WJ. Outbreak of neurologic disease caused by equine herpesvirus−1 at a university equestrian center.. J Vet Intern Med 2007;21:157‐165.
    pubmed: 17338164
  14. Maxwell LK, Bentz BG, Gilliam LL. 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;78:1126‐1139.
    pmc: PMC6440545pubmed: 28945127
  15. Awan AR, Field HJ. Effects of phosphonylmethoxyalkyl derivatives studied with a murine model for abortion induced by equine herpesvirus 1.. Antimicrob Agents Chemother 1993;37:2478‐2482.
    pmc: PMC192413pubmed: 8285638
  16. Gibson JS, Slater JD, Field HJ. The activity of (S)‐1‐[(3‐hydroxy−2‐phosphonyl methoxy) propyl] cytosine (HPMPC) against equine herpesvirus‐1 (EHV‐1) in cell cultures, mice and horses.. Antiviral Res 1992;19:219‐232.
    pubmed: 1332605
  17. Rollinson EA. Comparative efficacy of three 2′‐fluoropyrimidine nucleosides and 9‐(1,3‐dihydroxy‐2‐propoxymethyl)guanine (BW B759U) against pseudorabies and equine rhinopneumonitis virus infection in vitro and in laboratory animals.. Antiviral Res 1987;7:25‐33.
    pubmed: 3026244
  18. Higgins JPT, Lopez‐Lopez JA, Becker BJ. Synthesising quantitative evidence in systematic reviews of complex health interventions.. BMJ Glob Health 2019;4:e000858.
    pmc: PMC6350707pubmed: 30775014
  19. Hooijmans CR, Rovers MM, de Vries RB. SYRCLE's risk of bias tool for animal studies.. BMC Med Res Methodol 2014;14:43.
    pmc: PMC4230647pubmed: 24667063
  20. Guyatt GH, Oxman AD, Schunemann HJ. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology.. J Clin Epidemiol 2011;64:380‐382.
    pubmed: 21185693
  21. Worrall G. Herpes labialis.. BMJ Clin Evid 2009;2009:2009‐2031.
    pmc: PMC2907798pubmed: 21726482
  22. Sullivan SL, Whittem T, Morley PS, Hinchcliff KW. A systematic review and meta‐analysis of the efficacy of furosemide for exercise‐induced pulmonary haemorrhage in Thoroughbred and Standardbred racehorses.. Equine Vet J 2015;47:341‐349.
    pubmed: 25291214
  23. National Academies of Sciences, Engineering, and Medicine, Division on Earth and Life Studies, Board on Environmental Studies and Toxicology, Committee on Endocrine‐Related Low‐Dose Toxicity. Application of Systematic Review Methods in an Overall Strategy for Evaluating Low‐Dose Toxicity from Endocrine Active Chemicals.. Washington, DC: The National Academies Press; 2017.
    pubmed: 28896009
  24. Office of Health Assessment and Translation (OHAT). Handbook for Conducting a Literature‐Base Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration.. Bethesda, MD, USA: National Institute of Environmental Health Sciences; 2019.
  25. 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;147:176‐181.
    pmc: PMC7114471pubmed: 19896512
  26. Ons E, Van Brussel L, Lane S. Efficacy of a Parapoxvirus ovis‐based immunomodulator against equine herpesvirus type 1 and Streptococcus equi equi infections in horses.. Vet Microbiol 2014;173:232‐240.
    pubmed: 25153651
  27. Perkins GA, Van de Walle GR, Pusterla N. Evaluation of metaphylactic RNA interference to prevent equine herpesvirus type 1 infection in experimental herpesvirus myeloencephalopathy in horses.. Am J Vet Res 2013;74:248‐256.
    pubmed: 23363350
  28. Seahorn TL, Carter GK, Martens JG. Effects of human alpha interferon on experimentally induced equine herpesvirus‐1 infection in horses.. Am J Vet Res 1990;51:2006‐2010.
    pubmed: 1964771
  29. Verma S, Tewari SC, Yadav MP. Use of polyherbal immunomodulator in conjunction with inactivated vaccine against equine herpes virus‐1.. Indian J Virol 1999;15:63‐67.
  30. Walter J, Seeh C, Fey K, Bleul U, Osterrieder N. Prevention of equine herpesvirus myeloencephalopathy – is heparin a novel option? A case report.. Tierarztl Prax Ausg G Grosstiere Nutztiere 2016;44:313‐317.
    pubmed: 27652372
  31. Adams J, Hillier‐Brown FC, Moore HJ. Searching and synthesising ‘grey literature’ and ‘grey information’ in public health: critical reflections on three case studies.. Syst Rev 2016;5:164.
    pmc: PMC5041336pubmed: 27686611
  32. Osterrieder K, Dorman DC, Burgess BA. Vaccination for the prevention of equine herpesvirus‐1 disease in domesticated horses: a systematic review and meta‐analysis.. J Vet Intern Med 2023.
    doi: 10.1111/jvim.16895pmc: PMC11099739pubmed: 37930113google scholar: lookup
  33. Marenzoni ML, De Waure C, Timoney PJ. Efficacy of vaccination against equine herpesvirus type 1 (EHV‐1) infection: systematic review and meta‐analysis of randomised controlled challenge trials.. Equine Vet J 2022;55:389‐404.
    pubmed: 35946376
  34. Alpi KM, Vo TA, Dorman DC. Language consideration and methodological transparency in “systematic” reviews of animal toxicity studies.. Int J Toxicol 2019;38:135‐145.
    pubmed: 30791753
  35. Di Girolamo N, Giuffrida MA, Winter AL. In veterinary trials reporting and communication regarding randomisation procedures is suboptimal.. Vet Rec 2017;181:195.
    pubmed: 28487452
  36. Leung V, Rousseau‐Blass F, Beauchamp G, Pang DSJ. ARRIVE has not ARRIVEd: support for the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines does not improve the reporting quality of papers in animal welfare, analgesia or anesthesia.. PloS One 2018;13:e0197882.
    pmc: PMC5967836pubmed: 29795636
  37. Rufiange M, Rousseau‐Blass F, Pang DSJ. Incomplete reporting of experimental studies and items associated with risk of bias in veterinary research.. Vet Rec Open 2019;6:e000322.
    pmc: PMC6541106pubmed: 31205725
  38. Hooijmans CR, de Vries R, Leenaars M, Curfs J, Ritskes‐Hoitinga M. Improving planning, design, reporting and scientific quality of animal experiments by using the Gold Standard Publication Checklist, in addition to the ARRIVE guidelines.. Br J Pharmacol 2011;162:1259‐1260.
    pmc: PMC3058159pubmed: 21091655
  39. Thieulent CJ, Sutton G, Toquet MP. 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;11:539‐556.
    pmc: PMC9148010pubmed: 35631060
  40. Tan YJ, Crowley RJ, Ioannidis JPA. An empirical assessment of research practices across 163 clinical trials of tumor‐bearing companion dogs.. Sci Rep 2019;9:11877.
    pmc: PMC6695388pubmed: 31417164

Citations

This article has been cited 6 times.
  1. Durán MC, Suazo M, Maturana A, Vargas MP, García A, Ahumada C, Pezoa A, Goehring LS, Lara F. First Equine Herpes Myeloencephalopathy (EHM) Outbreak in Chile.. Animals (Basel) 2025 Aug 11;15(16).
    doi: 10.3390/ani15162344pubmed: 40867672google scholar: lookup
  2. Pusterla N, Lawton K, Barnum S, Flynn K, Hankin S, Runk D, Mendonsa E, Doherty T. Management of an Equine Herpesvirus-1 Outbreak During a Multi-Week Equestrian Event.. Viruses 2025 Apr 24;17(5).
    doi: 10.3390/v17050608pubmed: 40431620google scholar: lookup
  3. Pusterla N, Lawton K, Barnum S, Ross K, Purcell K. Investigation of an Outbreak of Equine Herpesvirus-1 Myeloencephalopathy in a Population of Aged Working Equids.. Viruses 2024 Dec 21;16(12).
    doi: 10.3390/v16121963pubmed: 39772269google scholar: lookup
  4. Hu Y, Zhang SY, Sun WC, Feng YR, Gong HR, Ran DL, Zhang BZ, Liu JH. Breaking Latent Infection: How ORF37/38-Deletion Mutants Offer New Hope against EHV-1 Neuropathogenicity.. Viruses 2024 Sep 16;16(9).
    doi: 10.3390/v16091472pubmed: 39339948google scholar: lookup
  5. Li L, Li S, Ma H, Akhtar MF, Tan Y, Wang T, Liu W, Khan A, Khan MZ, Wang C. An Overview of Infectious and Non-Infectious Causes of Pregnancy Losses in Equine.. Animals (Basel) 2024 Jul 2;14(13).
    doi: 10.3390/ani14131961pubmed: 38998073google scholar: lookup
  6. Lunn DP, Burgess BA, Dorman DC, Goehring LS, Gross P, Osterrieder K, Pusterla N, Soboll Hussey G. Updated ACVIM consensus statement on equine herpesvirus-1.. J Vet Intern Med 2024 May-Jun;38(3):1290-1299.
    doi: 10.1111/jvim.17047pubmed: 38497217google scholar: lookup