Use of the designation “shedder” in mucosal detection of herpes simplex virus DNA involving repeated sampling
- 1Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
- 2Programs in Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- 3Department of Medicine, University of Washington, Seattle, Washington, USA
- 4Department of Epidemiology, University of Washington, Seattle, Washington, USA
- 5Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Dr Amalia S Magaret, University of Washington, Virology Research Clinic, Box 359928, Seattle, WA 98195, USA;
- Accepted 26 January 2009
- Published Online First 11 February 2009
Objectives: We evaluated two methods to describe detection of herpes simplex virus (HSV) from the genital mucosa.
Methods: We assessed genital swabs from HSV-2 seropositive people participating in longitudinal studies of HSV DNA detection at the University of Washington Virology Research Clinic. We determined the length of observation period necessary to ensure some HSV detection for most individuals. We compared two measures to assess differences in shedding according to HIV status, the shedding rate ratio, defined as the proportion of total samples with detectable HSV in HIV-1 seropositive versus HIV-1 seronegative participant, and the ratio of “shedders”, defined as the proportion of people with any shedding over the interval in HIV-1 seropositive versus HIV-1 seronegative people.
Results: While only 17% (51/308) of HSV-2 seropositive people shed on their first day on study, 77% (238/308) had some genital shedding over 30 days (any HSV DNA detected on genital swabs). Shedding rate ratios (SRR) for HIV-seropositive versus HIV-seronegative people varied from SRR = 1.42 using 10 samples to SRR = 1.35 using 50 samples. The ratio of “shedders” (RS) approached 1 as the observation period increased (RS = 1.13 using 10 samples to RS = 1.01 using 50 samples). In a hypothetical case, the ratio of “shedders” was shown to exceed 1 when shedding rates were equal.
Conclusions: Most HSV-2 seropositive people shed HSV from the genital mucosa. Dichotomisation of people into “shedders” and “non-shedders” or “high” and “low” shedders yields inferences that depend upon sampling interval length. Overall shedding rates provide consistent measures regardless of the number of swabs collected.
Funding: This work was funded primarily through NIH grants P01 AI-30731-13 and K24 071113-01.
Competing interests: AM and CJ have received grant support from the National Institutes of Health. AW has received grant support from the National Institutes of Health, GlaxoSmithKline, Antigenics and Astellas. She has been a consultant for Medigene, Aicuris and a speaker for Merck Vaccines.
Contributors: AM performed the analyses and wrote the initial draft of the manuscript. CJ and AW contributed the clinical relevance of the paper and critical edits to the manuscript.