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Pathobiology. Primary herpes simplex virus (HSV) infection occurs through mucosal surfaces, followed by Kaposi’s varicelliform eruption. Immune host responses control this primary infection within 14 to 21 days. What is unique is the retrograde neuronal transport of the virus to the dorsal root ganglia, where a cycle of replication occurs and the virus becomes latent until a provocative stimulus leads to reactivation. At that time, anterior grade transport returns the virus to the mucosal surfaces, where replication ensues.

Incidence and Burden. By adulthood, about 80 percent of the U.S. population has been exposed to nongenital HSV type 1 and is at risk for reactivation, leading to herpes simplex labialis. There are about 750,000 new cases of genital infection per year in the United States, and overall seroprevalence of HSV-2 is about 60 million individuals. Genital herpes generates about 600,000 physician visits and 20,000 unnecessary caesarian sections annually. Two more serious infections are herpes simplex encephalitis and neonatal herpes, each with about 1,500 cases per year. The cost of neonatal herpes is at least $750 million per year, primarily in indirect costs for the long-term management of neurological sequelae from which these babies suffer.

Seroprevalence of HSV type 2 is increasing rapidly. In 1992, seroprevalence for the U.S. population at large was about 31 percent; for persons of color, between 50 and 55 percent. Acquisition is a function of the number of sexual partners to whom an individual is exposed: for heterosexual men with greater than 50 partners, the probability of acquiring HSV-2 is 80 percent or higher; for heterosexual women with more than 50 partners, over 90 percent. Women are more likely to acquire HSV-2 than men. As with other genital ulcerative disease, there is also a four- or fivefold increase in the risk of acquiring HIV infection.

Rationale and Goals of Vaccine. Studies of couples with discordant serostatus suggest that prior HSV-1 infection confers some degree of protection from acquiring HSV-2 infection. When the male is positive for HSV-2 and the female is seronegative, her probability of acquiring HSV-2 is 20 percent during the calendar year. This becomes particularly significant if she becomes pregnant during that year. If the female is seropositive for HSV-1, however, the probability drops to 10 percent. (The reverse also holds: if the male is positive for HSV-1 rather than seronegative, his probability of acquiring HSV-2 drops from 10 percent to 5 percent.) These findings suggest that a vaccine that could seroconvert the mother from at-risk to lower-risk could lower the probability of transmission to the newborn.

The goal of this vaccine would be to prevent or at least reduce the severity of primary infection, and possibly to reduce the frequency and clinical symptoms of reoccurrences. We know that exogenous reinfection is extremely


Based on a presentation by Richard J.Whitley, M.D.

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