scholarly journals Comparison of effects of famciclovir and valaciclovir on pathogenesis of herpes simplex virus type 2 in a murine infection model.

1996 ◽  
Vol 40 (4) ◽  
pp. 846-851 ◽  
Author(s):  
A M Thackray ◽  
H J Field

The effects of famciclovir (FCV) and valaciclovir (VACV) were compared in a cutaneous infection model for herpes simplex virus type 2 (HSV-2). The compounds were administered orally from day 1 to day 5 postinfection. Both compounds reduced local inflammation and virus replication in the skin. FCV markedly reduced mortality and virus replication in the nervous system. On the cessation of therapy after 5 days, when the levels of infectious virus in the tissues were reduced to below the level of detection, there followed a rebound of virus replication in the ganglia and brain stems of mice that had been treated with VACV. The recurrence of infection in the brain stem occurred on three separate occasions. No such recurrences were observed following FCV treatment. When ganglia were explanted from survivors 6 weeks later, latent virus was shown to be reactivated in all 10 of 10 control, untreated mice. The number of mice whose ganglia yielded virus was reduced to 60% in mice that had been treated with VACV, whereas no mice that had been treated with FCV had evidence of latent infection by this test.

1997 ◽  
Vol 8 (4) ◽  
pp. 317-326 ◽  
Author(s):  
AM Thackray ◽  
HJ Field

Mice with or without immunosuppression by cyclosporin (Cy) were inoculated with herpes simplex virus type 1 in the ear pinna. Without immunosuppression, 20% of the mice died; clinical signs resolved in survivors and infectious virus was cleared by 7 to 10 days post-inoculation (p.i.). With Cy, mortality was 50%, clinical signs increased and infectious virus persisted. Mice were treated with either valaciclovir (VACV) or famciclovir (FCV) from days 1–5 or 5–10 p.i. and both compounds moderated the disease, but only FCV led to rapid restoration of body weight and complete protection from mortality. Resolution of clinical signs was more marked with immunosuppression. On cessation of VACV therapy, infectious virus recurred on individual days. Without immunosuppression, recurrence was detected in neural tissues only, but with Cy, infectious virus also recurred in skin. No recurrences of infectious virus were observed in any FCV-treated mice.


2000 ◽  
Vol 44 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Alana M. Thackray ◽  
Hugh J. Field

ABSTRACT Young adult mice were inoculated with herpes simplex virus type 2 (HSV-2) in the ear pinna. A relatively severe infection resulted, and 45% of the mice died by 11 days postinfection. Therapy at 1 mg/ml by means of the drinking water with either famciclovir for periods of 5 or 10 days or valaciclovir for 5, 10, 15, or 20 days decreased clinical signs and reduced mortality to 15% or less. Throughout a period of 27 days, mice were tested daily for the presence of infectious virus in the ear pinna, brain stem, and ipsilateral trigeminal ganglia. Virus was cleared from these tissues in surviving, untreated animals by 12 days postinfection, and no infectious virus was detected subsequently in any tissue. Furthermore, no infectious virus was detected after day 9 in mice that had been treated with famciclovir. In mice that had received valaciclovir therapy, however, infectious virus was repeatedly detected in the trigeminal ganglia and brain stem tissue samples up to 7 days after treatment was discontinued. To date, no specific mechanism to account for these results has been discovered; however, possible mechanisms for the persistence of potentially infectious virus in neural tissue of treated mice are discussed.


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