Longitudinal evaluation of herpes simplex virus DNA load during episodes of herpes labialis
Introduction
Herpes labialis is mostly caused by herpes simplex virus (HSV) type 1. More than 50% of adults possess HSV-1 antibodies and between 20% and 40% of all adults experience cold sore outbreaks (Spruance et al., 2003). The mean duration of a classical recurrence is 7–8 days although there is a large individual variability (Spruance et al., 1997). Trials of topical and oral antiviral therapy in subjects with recurrent herpes labialis showed best results when rapid, patient-initiated, therapy consisted of administration of high doses of oral antiviral agents (Spruance et al., 2003, Spruance et al., 1999). In most of these trials, the primary endpoint was the time to complete healing of lesions. In contrast to genital herpes where a large number of virological studies have been reported, there are very limited data on the duration and magnitude of viral shedding during episodes of herpes labialis (Corey et al., 2004, Spruance et al., 1997, Wald et al., 2003). The aim of this study was to evaluate viral DNA load kinetics in sequential swabs from immunocompetent subjects with recurrent herpes labialis.
Section snippets
Materials and methods
This virological sub-study included placebo recipients of a randomized trial evaluating a topical antiviral agent in subjects with herpes labialis. Enrolled participants were ≥18 years of age with a clinical history of recurrent herpes simplex labialis (≥4 episodes/year) confirmed by a positive non-type specific HSV serology. Pregnant women and subjects with significant systemic diseases (including HIV seropositivity) were excluded. Within 1 h of onset of prodromal symptoms and/or erythema,
Results
Thirty-six placebo recipients with an episode compatible with herpes labialis were part of this study. Eighteen (50.0%) and 22 (61.1%) subjects had confirmed HSV-1 orolabial infections by culture typing and the melting curve analysis of the PCR, respectively. Four subjects had positive results by PCR only, whereas none had positive cultures only. There were no HSV-2 orolabial infections. Positivity rates for culture and PCR in subjects with confirmed infections at baseline (hs, home swab taken
Discussion
We describe a new real-time PCR assay for sensitive detection and reliable quantification of both HSV-1 and HSV-2 DNA in clinical samples. This assay was used to detect HSV in sequential samples of individuals with herpes labialis and was found to be 10% more sensitive overall than viral culture, with the greatest superiority in sensitivity apparent during the late phase of the episodes. We found that the median duration of viral shedding in lesions of patients was 60 h by PCR, which was 12 h
Acknowledgements
This work was supported by Royalmount-Pharma. The authors would like to thank the principal investigators at each clinical site: Dr. Gregory Grant (Vancouver, BC), Dr. Barbara Romanowski (Edmonton, AB), Dr. Kurt Williams (Saskatoon, SK), Dr. Fred Aoki (Winnipeg, MB), Dr. Mark Miller (Montreal, Quebec), Dr. Sylvie Trottier (Quebec City, Quebec), Dr. Stephen Shafran (Edmonton, AB).
References (13)
- et al.
Simultaneous detection of herpes simplex virus types 1 and 2 by real-time PCR and Pyrosequencing
J Clin Virol
(2005) - et al.
The efficacy of valacyclovir in preventing recurrent herpes simplex virus infections associated with dental procedures
J Am Dent Assoc
(2004) - et al.
Differentiation of herpes simplex virus types 1 and 2 in clinical samples by a real-time taqman PCR assay
J Med Virol
(2005) - et al.
Once-daily valacyclovir to reduce the risk of transmission of genital herpes
N Engl J Med
(2004) - et al.
Duplex real-time polymerase chain reaction assay for detection and quantification of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and cutaneous lesions
Sex Transm Dis
(2004) - et al.
Oral herpes simplex virus type 2 reactivation in HIV-positive and -negative men
J Infect Dis
(2006)