Overlapping reactivations of herpes simplex virus type 2 in the genital and perianal mucosa

Abstract

Background: Genital shedding of herpes simplex virus (HSV) type 2 occurs frequently. Anatomic patterns of genital HSV-2 reactivation have not been intensively studied.

Methods: Four HSV-2-seropositive women with symptomatic genital herpes attended a clinic daily during a 30-day period. Daily samples were collected from 7 separate genital sites. Swab samples were assayed for HSV DNA by quantitative polymerase chain reaction. Anatomic sites of clinical HSV-2 recurrences were recorded.

Results: HSV was detected on 44 (37%) of 120 days and from 136 (16%) of 840 swab samples. Lesions were documented on 35 (29%) of 120 days. HSV was detected at >1 anatomic site on 25 (57%) of 44 days with HSV shedding (median, 2 sites; range, 1-7), with HSV detected bilaterally on 20 (80%) of the 25 days. The presence of a lesion was significantly associated with detectable HSV from any genital site (incident rate ratio [IRR], 5.41; 95% confidence interval [CI], 1.24-23.50; P= .02) and with the number of positive sites (IRR, 1.19; 95% CI, 1. 01-1.40; P=.03). The maximum HSV copy number detected was associated with the number of positive sites (IRR, 1.62; 95% CI, 1.44-1.82; P<.001).

Conclusions: HSV-2 reactivation occurs frequently at widely spaced regions throughout the genital tract. To prevent HSV-2 reactivation, suppressive HSV-2 therapy must control simultaneous viral reactivations from multiple sacral ganglia.

Figure 1

Distribution of number of genital sites with HSV detected

Figure 2. Appearance and progression of HSV-2 lesion and genital shedding over a 4 day period

On the day before the appearance of lesion (Day 0), HSV shedding was present at 10⁷ copies/ml in the perianal area, and also on the right labia majora and left labia minora at 10² copies/ml. On Day 1, the lesion appeared, shedding was detected at all of the sampled sites, with highest level of shedding at the site of lesion. In the following days, shedding from the lesion persisted, at decreasing copy number each day. HSV shedding continued after the perianal lesion healed for an additional 2 days (data not shown). no HSV DNA detected 2-3 log₁₀copies/ml HSV DNA detected, 3-4 log₁₀copies/ml HSV DNA detected, site of lesion, with log₁₀copies/ml HSV DNA detected. L=left, R=right. MJ=Labia majora, MN=labia minora, PA=perianal, URE=urethra. Numbers represent log₁₀ copy number/ml detected.

Figure 3

Clinical and subclinical HSV-2 shedding at site-specific locations in 2 participants NOTE: R=Right, L =Left *indicates the presence of a lesion Log ₁₀ copies/ml indicated in color: No HSV-2 detected, =10², =10³, =10⁴, =10⁵, =10⁶