A Wald, J Zeh, S Selke et al. N Engl J Med 2000;342:844-850

Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection. We conducted a prospective study to investigate genital shedding of HSV among 53 subjects who had antibodies to HSV-2 but who reported having no history of genital herpes, and we compared their patterns of viral shedding with those in a similar cohort of 90 subjects with symptomatic HSV-2 infection. Genital secretions of the subjects in both groups were sampled daily and cultured for HSV for a median of 94 days. HSV was isolated from the genital mucosa in 38 of the 53 HSV-2-seropositive subjects (72%) who reported no history of genital herpes, and HSV DNA was detected by the polymerase chain reaction assay in cultures prepared from genital mucosal swabs in six additional subjects. The rate of subclinical shedding of HSV in the subjects with no reported history of genital herpes was similar to that in the subjects with such a history (3.0% versus 2.7%). Of the 53 subjects who had no reported history of genital herpes, 33 (62%) subsequently reported having typical herpetic lesions; the duration of their recurrences in these subjects was shorter (median, three days versus five days; P<0.001) and the frequency lower (median, 3.0 per year versus 8.2 per year; P<0.001) than in the 90 subjects with previously diagnosed symptomatic infection. Only one of these 53 subjects had no clinical or virologic evidence of HSV infection. Seropositivity for HSV-2 is associated with viral shedding in the genital tract, even in subjects with no reported history of genital herpes.