Feline Herpesvirus Type 1

Feline Herpesvirus type 1 (FHV-1) is believed to be the most common cause of ocular disease in cats.  Multiple cat households, catteries, kittens and cats from pet stores, and feral kittens and cats are most prone to develop active FHV-1 as the disease process usually manifests itself in poorly conditioned felines as well as those that are experiencing stressful living conditions. 

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HERPES IS ‘FOREVER’ ……..  What is currently being used to ‘Manage’ feline Herpesvirus type 1 (FHV-1)?
Steve Dugan, DVM, MS, Diplomate of the ACVO

Feline Herpesvirus type 1 (FHV-1) is believed to be the most common cause of ocular disease in cats.  Multiple cat households, catteries, kittens and cats from pet stores, and feral kittens and cats are most prone to develop active FHV-1 as the disease process usually manifests itself in poorly conditioned felines as well as those that are experiencing stressful living conditions.  FHV-1 is associated with keratoconjunctivitis, corneal sequestration, eosinophilic keratoconjunctivitis, KCS, loss of corneal sensation, symblepharon, anterior uveitis, rhinitis, stomatitis, and ulcerative facial and nasal dermatitis.  Alpha Herpesviruses such as FHV-1 cause disease by two distinctly different mechanisms: 1) cytolytic (cell-rupturing) disease which involves active viral replication and destroys the epithelial cells of the cornea and conjunctiva causing ulceration; and, 2) immune-mediated disease results from the deposition of viral antigen in subepithelial tissues.  FHV-1 establishes latency in the trigeminal ganglia and can travel back to the eye via anterograde axonal transport.  Latency will develop in approximately eighty percent of infected cats and approximately fifty percent of latently infected cats will have spontaneous and stress-related reactivation and shedding of the virus.  If recurrent, severe  FHV-1 induced disease develops frequently in a cat, then laboratory testing to rule in or rule out various diseases that may decrease a cat’s immune competence and as such predispose the patient to frequent recurrences should be considered (e.g., FeLV, FIV, FIP etc).

Positive FHV-1 test results (virus isolation, immunofluorescence techniques, and conventional PCR assays) do not differentiate subclinically infected cats from those with clinical disease as a result of FHV-1 infection.   In addition, PCR assays also detect vaccine strains of FHV-1.  It was recently shown by Low et al that increased copy numbers of FHV-1 DNA as determined by PCR could not be identified in cats with conjunctivitis compared to cats without conjunctivitis.  Because of the difficulty in establishing a definitive diagnosis of FHV-1 as the cause of ocular disease in most cats, presumption of cause is usually based upon clinical signs (particularly recurrent episodes of keratoconjunctivitis and/or the presence of respiratory signs) and response to treatment.  Immunity from vaccination against FHV-1 is incomplete and temporary whether parenteral or intranasal vaccination is administered.

No consistently effective primary treatment exists for chronic viral diseases in cats.  In addition, the antiviral agents currently used are virostatic versus virocidal and thus are unable to eradicate latent viral infection.  Because stress is an important trigger of viral shedding and reactivation, treatment that is noninvasive and palatable is paramount to therapeutic success.  Because FHV-1 can induce tissue injury directly as a result of viral cytolysis or indirectly through immunopathologic processes mediated by inflammatory cells, treatment of FHV-1 keratoconjunctivitis involves: 1)  prevention of viral replication; 2) immunomodulation; and, 3) prevention of secondary bacterial infection.

Medications currently used to prevent viral replication include: l-lysine (Viralys); trifluridine (Viroptic); idoxuridine; interferon alpha; famciclovir (Famvir); and, cidofovir (Vistide).   L-lysine, a competitive inhibitor of arginine which is necessary for the replication of FHV-1, is believed to moderate disease in severe or chronically recurring cases, is safe, inexpensive, available as a paste, powder, or pills, and is typically administered at 250 to 500 mg per os BID.  Trifluridine 1% ophthalmic solution causes considerable stinging when instilled in the eye, is expensive, and must be administered > 5 times per day to be effective.  Idoxuridine 0.1% ophthalmic solution does not cause the same degree of stinging when compared to trifluridine, is no longer commercially available, and must be administered q 4 to 6 h to be effective.  Both trifluridine and idoxuridine have low solubility, and as such, their intraocular penetration is low unless the epithelial barrier is altered.  Interferon alpha administered systemically, topically or both appears to exert a virostatic effect on FHV-1 replication.  Interferon alpha at 30 U per os q 24 h may help some cats with suspected chronic FHV-1 infection.  Interferon alpha (600 U/ml or 30 U/gt) at 1 gt in the affected eye(s) q 4 to 6 h may also aid in the management of FHV-1 in some cats.  However, this treatment modality has not been evaluated adequately in clinical trials in order to make definitive claims.  Famciclovir, a prodrug of penciclovir, has been shown in preliminary studies to be safe and effective in cats with primary FHV-1 infection.  Adequate clinical trials have not been performed but 1/4 of a 125 mg tablet per os q 24 h for 21 days appears to be helpful.  Cidofovir 0.5% ophthalmic solution instilled BID has been shown to decrease clinical signs of ocular disease during the acute phase of infection following experimentally induced FHV-1 infection.  Cidofovir is converted to an active metabolite (CDVpp) that inhibits viral synthesis by competitively inhibiting viral DNA polymerase.  Cidofovir has potent antiviral effects in vitro and in vivo against several Herpesviruses of human and veterinary importance.  Cidofovir at concentrations of 0.02 to 0.05 mg/dl has been shown to be extremely effective against FHV-1 infection of feline corneal epithelial cells in vitro.  Cidofovir has not been approved for ophthalmic use and is only available through compounding pharmacies.

Interferon is the only medication currently used for its immunomodulatory effects in the treatment of FHV-1.  Interferon has been reported to be effective in preventing recurrent FHV-1 disease when administered at 30 U per os q 24 h for seven days followed by seven days without treatment in a continuously repeating cycle.

Antibacterial agents can be used topically and/or per os in conjunction with one or more of the treatments discussed above.  Any topical broad spectrum ophthalmic solution should be acceptable (e.g., tobramycin or ofloxacin).  Regarding orally administered antibiotics, I prefer doxycycline at 2.3 mg/lbs per os BID for 21 days or azithromycin at 5 mg/lbs per os q 24 h for 21 days.  Doxycycline has been shown to possess anticollagenase effects and subsequently may help prevent corneal stromal involvement.

Finally, because FHV-1 can cause a permanent reduction in lacrimation, a high-quality artificial tear instilled in the affected eye(s) q 4 to 6 h may help maintain a healthy ocular environment during the convalescent period.

References

  1. Lappin MR. Treating feline upper respiratory tract infections.  Suppl Compend contin Educ Vet 2007; 29: 4-9.
  2. Low HC, Powell CC, Veir JK, Hawley JR, Lappin MR. Prevalence of feline herpesvirus 1, Chlamydophila felis, and Mycoplasma spp DNA in conjunctival cells collected from cats with and without conjunctivitis.  Am J Vet Res 2007; 68: 643-648.
  3. Davidson GS. Compounding for feline herpetic keratitis. Int J of Pharm Compounding 2006; 10: 411-414.
  4. Regnier A. Clinical pharmacology and therapeutics. In: Gelatt KN, ed.  Veterinary Ophthalmology. Ames, Iowa: Blackwell Publishing, 2007: 294-296.
  5. Sandmeyer LS, Keller CB, Bienzle D. Effects of cidofovir on cell death and replication of feline herpesvirus-1 in cultured feline corneal epithelial cells. Am J Vet Res 2005; 66: 217-222.
  6. Fontenelle JP, Powell CC, Gionfriddo JR, Lappin MR. Effect of topical cidofovir on experimentally induced FHV-1 conjunctivitis (abstract). 36th Annual Meeting of the American College of Veterinary Ophthalmologists, 2005: 5.
  7. Thomasy SM, Maggs DJ, Lim CC, Lappin MR, Stanley SD. Safety and efficacy of famciclovir in cats infected with feline herpesvirus 1 (abstract). 37th Annual Meeting of the American College of Veterinary Ophthalmologists, 2006:43.
  8. Stiles J, Townsend WM. Feline ophthalmology. In: Gelatt KN, ed. Veterinary Ophthalmology. Ames, Iowa: Blackwell Publishing, 2007: 1102-1115.