Apr 13, 2011

Persons With Asymptomatic Genital Herpes Still Shed Virus

Persons with herpes simplex virus 2 (HSV-2) infection but without symptoms shed virus in the genital tract less often than symptomatic individuals, but even in asymptomatic individuals, genital HSV shedding was often not associated with a lesion, suggesting a high risk for transmission from persons with unrecognized HSV-2 infection.

Anna Wald, MD, MPH, senior author from the University of Washington and the Fred Hutchinson Cancer Research Center, in Seattle, and colleagues reported the findings in the April 13 issue of JAMA.

“These findings extend earlier observations that genital HSV shedding in persons who are seropositive for this virus is likely universal but that the clinical manifestations of disease differ widely,” the authors suggest.

“Most HSV-2 infections are acquired from persons without a clinical history of genital herpes,” they note. Thus, the risk for sexual transmission does not correlate with the recognition of clinical signs and symptoms of HSV-2, but most likely correlates with viral shedding.

Dr. Wald and colleagues sought to assess the virologic and clinical course of HSV genital shedding among individuals with symptomatic and asymptomatic HSV-2 infection in a cohort of 498 people who were seropositive for HSV-2. Participants collected swabs of the genital area for at least 30 days. HSV DNA was measured by quantitative real-time fluorescence polymerase chain reaction.

Virus Detected Even When Lesions Not Present

In 410 people with HSV-2 symptoms, the virus was detected in 20.1% of days (95% confidence interval [CI], 18.3% – 22.0%). In contrast, in asymptomatic individuals, HSV-2 was detected on 10.2% of days (95% CI, 7.7% – 13.6%; P < .001).

Subclinical shedding rates were higher in persons with symptomatic infection compared with asymptomatic infection (13.1% vs 8.8%; P < .001), although the amount of HSV detected during subclinical shedding episodes was similar, with a median of just more than 4 log10 copies.

Days with lesions accounted for 43.0% of the days with genital viral shedding among persons with symptomatic genital HSV-2 infection compared with 16.4% among persons with asymptomatic infection (P < .001).

Higher Genital Shedding in Some

The researchers also found in an adjusted analysis that both a higher number of recurrences per year and white race also remained predictive of higher genital shedding rate.

“Even among persons with a history of genital HSV-2 infection, the spectrum of clinical disease is large, and our findings show that the virologic spectrum is also broad, with substantial overlap across the 2 groups,” the authors conclude.

They add that the findings suggest that best practices management of HSV-2-infected persons who learn that they are infected from serologic testing should include anticipatory guidance with regard to genital symptoms, as well as counseling about the potential for transmission.

“The issue of infectivity is both a patient management and a public health concern. The primary concern of many HSV-2-seropositive persons is the risk of transmission to sexual partners; in our experience this is the main source of angst in patients with genital herpes,” they write.

Several Questions Remain Unanswered

“We don’t really understand what determines the differences in the severity,” noted Dr. Wald during a JAMA Theme Issue Media Briefing.

According to Dr. Wald, condom use, daily valacyclovir therapy, and disclosure of HSV-2 serostatus each approximately halve the risk for HSV-2 transmission, although these approaches have not decreased the seroprevalence of HSV-2 in recent years.

The first author of the study, Beth Tronstein, MPH, also from the University of Washington, said that previously they have shown that people who are infected with HSV-2 but do not have symptoms can shed virus or develop symptoms, but that the frequency of viral shedding was not clearly defined.

The findings indicate that people “who are sexually active, who are concerned about sexually transmitted infections, may want to be tested for HSV-2,” she told Medscape Medical News.

According to Ms. Tronstein, remaining questions include finding out why some people remain asymptomatic, while others exhibit symptoms, and also understanding why the shedding rate varies so widely. Another unanswered question is how much virus is necessary for sexual or perinatal transmission.

Study Implications

“Hopefully, this study will get clinicians to understand that virtually all individuals with genital HSV-2 infection will shed virus, and do so asymptomatically, whether or not that individual provides a history of genital herpes disease, whether they were diagnosed by serologic screening, whether they are male or female, or they are years away from their initial diagnosis,” Peter Leone, MD, from the University of North Carolina in Chapel Hill, told Medscape Medical News.

According to Dr. Leone, the study underscores the need for a broader offering of serologic screening for HSV-2 infection for sexually active adults and highlights the need for a national strategy for control and management of HSV-2 in the United States.

“This is a continuation of outstanding studies that have been done by Anna Wald and Larry Corey,” Rich Whitley, MD, from the University of Alabama in Birmingham, toldMedscape Medical News. “The data reinforce that [those who are] asymptomatic shed virus, albeit less than those who are symptomatic. Regardless, it reinforces the knowledge that individuals can transmit infection when totally asymptomatic. Indeed, most transmission occurs under these circumstances.”

According to Dr. Whitley, the real issue is whether we can develop a vaccine. “Right now, the answer is no,” he said.

The study was supported by a grant from the National Institutes of Health. Several study authors, including Dr. Wald, report receiving financial support from GlaxoSmithKline and from AiCuris. Other authors report receiving financial support from Immune Design. Dr. Whitley has disclosed no relevant financial relationships. Dr. Leone reports that he has the following financial associations: Abbott Diagnostics: research, speaker; GlaxoSmithKline: research, speaker; Trinity Diagnostics: consultant; Genocea: research; Norvartis: research, speaker.

JAMA. 2011;305:1441-1449. Abstract

— Emma Hitt, PhD

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