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Requests for Reprints: Lawrence Corey, MD, University of Washington, Virology Division, Room 9301, 1200 12th Avenue South, Seattle, WA 98144. Acknowledgments: The authors thank Michael Remington, PA, Carol Winter, RN, Cathy Critchlow, PhD, Stacy Selke, MA, Joan Dragavon, Colleen Olson, Michele Crist, Judy Zeh, PhD, Paul Van Veldheisen, MS, Carolyn Lapinsky, WHCS, Anita Fahnlander, RN, and others whose collaborative efforts over a 14-year period made possible the establishment of our genital herpes database. Anyone can submit a comment any time after publication, but only those submitted within 4 weeks of an article’s publication will be considered for print publication. Approximately two-thirds of all people under age 50 across the globe are infected with herpes simplex virus type 1 (HSV-1), the virus most commonly associated with cold sores, according to a World Health Organization (WHO) report released today in the journal PLOS One. The burden of infection varies in different parts of the world and between men and women, according to the report. HSV-1 is the same virus most commonly responsible for causing skin lesions, or “cold sores,” around the mouth, a disease than can be transmitted via skin-to-skin contact, such as kissing. The research suggests that HSV-1 may be increasingly responsible for genital herpes as well, and it’s also been known to cause infections leading to blindness and, albeit rarely, encephalitis.
In 2012, the WHO released a report on HSV-2 estimating that its global prevalence in people between the ages of 15 and 49 is around 11.3% — low in comparison to the HSV-1 estimates released in the new paper. This is likely because of the differing methods of transmission between the two viruses, says Anna Wald, a professor at the University of Washington’s School of Medicine whose research specialties include the herpes simplex virus.
Since HSV-2 most commonly affects the genitals, it typically isn’t transmitted until people become sexually active.
However, in recent years research has increasingly shown that both HSV types can be responsible for either oral or genital infections, and either type may be transmitted via oral sex. It’s thought that genital HSV-1 infections are becoming particularly prevalent in developed nations. So if fewer people are infected with the virus as children, they’re susceptible to genital infection as they become sexually active later in life, the WHO paper says. The authors conclude that genital HSV-1 infections are becoming a public health concern in certain parts of the developed world.
In other parts of the world, such as in Africa and Southeast Asia, the authors note that oral transmission in childhood is still high and has a tendency to protect people from genital infection later on. In addition to better tracking of a sexually-transmitted infection, such data collection can help scientists gain a better understanding of the ways the virus could influence other serious health conditions, Wald says.
It’s unclear whether infection with HSV-1 has a similar effect as HSV-2 in raising the risk of HIV, according to Wald. And HSV-1 is a leading cause of a condition known as HSV keratitis, which is an infection of the cornea that can lead to blindness. Both types of HSV can also cause encephalitis, which is rare but can lead to severe brain damage or death. Both types of HSV are usually responsible for skin lesions only, which can be painful but are not typically seen as a serious health risk. This behavior is part of what makes the virus so difficult to track, as many people are unaware that they are infected.
In the absence of symptoms, many medical providers also typically do not test for either type of the virus during routine sexually transmitted diseases (STD) screenings for a variety of reasons, some of them practical and others ethical. The Centers for Disease Control and Prevention (CDC) does not recommend testing for people who do not present with symptoms, stating, “STD screening tests are usually done for infections that can have serious outcomes if they are left untreated. That said, as HSV infection can be the cause of serious complications in some cases, it’s worth tracking on both a regional and global scale, Wald says. Cullen said it is perplexing that there's not more of an effort to cure both types of the Herpes virus. While there are medications that can help prevent outbreaks, there is currently neither a cure nor a vaccine for either HSV-1 or HSV-2.
In the new paper, the WHO concludes that continued global monitoring of the virus might help make a difference on that front. Persons using assistive technology might not be able to fully access information in this file. Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted infections worldwide and the primary cause of genital and neonatal herpes and genital ulcer disease (1).
NHANES surveys are cross-sectional surveys designed to compile nationally representative statistics on the health of the U.S.


HSV-2 infection is an important public health concern because of the morbidity associated with symptomatic infection, the potential for high rates of clinical and subclinical recurrences, and the strong association between HSV-2 and HIV infections; genital HSV-2 infection in pregnant women can lead to serious infection in neonates through vertical transmission. Persons infected with HSV-2 are at greater risk for HIV acquisition, even in the absence of HSV-2 symptoms (2). CDC recommends that persons with genital herpes avoid sexual activity with uninfected partners when lesions or prodromal symptoms are present because the greater viral shedding that accompanies these symptoms likely increases risk for HSV-2 transmission (5). Persons with known HSV-2 infection should be tested for HIV and adopt HIV risk-reduction strategies, such as limiting the number of sex partners and using condoms consistently and correctly. Routine serologic testing might identify numerous unrecognized HSV-2 infections; however, the role of routine serologic screening in population-based prevention efforts has been controversial (10). Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted infection in the United States and is associated with an increased risk for human immunodeficiency virus (HIV) infection. Health-care providers should consider HSV-2 infection in the differential diagnosis of genital complaints consistent with HSV-2 infection; patients with known HSV-2 infection should be tested for HIV. Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S.
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Thirty-eight percent had at least 6 recurrences during the first year and 20% had more than 10 recurrences. One month after publication, editors review all posted comments and select some for publication in the Letters section of the print version of Annals. Above this age, the burden of infection would probably “trend toward 100%” in many places, says Bryan Cullen, director of the Duke University Center for Virology, although the WHO study doesn’t include these statistics. But while cold sores are a mostly cosmetic issue, there’s good reason to collect data on the virus, argue some experts. The other, HSV-2, has historically been associated with genital herpes and is almost exclusively sexually transmitted. HSV-1, on the other hand, has historically been commonly transmitted in early childhood, for instance if an infected adult kisses an uninfected child. The new paper notes that, worldwide, about half a billion people between the ages of 15 and 49 have a genital herpes infection caused by either HSV-1 or HSV-2.
Once infected with the virus in one part of the body, the immune system generally protects against infection in another area.
In fact, it’s the “biggest cause of infectious blindness in the United States,” says Cullen.
And infection of either HSV type in newborns can sometimes cause severe reactions, including high fever, seizures or even death. And while the lesions may recur repeatedly in some infected people, others become asymptomatic after the first outbreak — or they may never have an outbreak at all.
And while it’s possible to perform a blood test that will show whether the virus is present, “those kinds of studies are expensive and take up a lot of resources,” Wald says. Back when i was doing herpes vaccine research in college there was a lot of data out there that at some point in their life 70 to 90% percent of people will be infected.
Multiple studies have shown that HSV-2 infection increases the risk for human immunodeficiency virus (HIV) infection by at least twofold (2).
Increased susceptibility to HIV infection likely occurs because even HSV-2 ulcerations that are microscopic can provide a portal of entry for HIV, and HSV-2 reactivation recruits potential target cells for HIV to the genital skin and mucosa. Viral shedding and transmission to sex partners can occur in the absence of symptoms or a noticeable lesion (5).
Infected persons also should be counseled regarding the HSV-2 transmission risk associated with viral shedding in the absence of symptoms. Serologic HSV-2 testing is not recommended currently for the general population because of concerns related to test performance in low-prevalence settings and a lack of data regarding the benefits of screening (10). Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.
Effect of acyclovir on HIV-1 acquisition in herpes simplex virus type 2 seropositive women and men who have sex with men: a randomized, double blind, placebo-controlled trial.


Seroprevalence of human immunodeficiency virus in the US household population aged 18--49 years: the National Health and Nutrition Examination Surveys, 1999--2006.
Development of clinically recognizable genital lesions among women previously identified as having "asymptomatic" herpes simplex virus type 2 infection. Clinicians, health departments, health-care organizations, and community groups should promote measures that prevent HSV-2 transmission, including minimizing the number of sex partners, avoiding concurrent sexual partnerships, and using condoms consistently and correctly. In the Eastern Mediterranean, 75% of both men and women are infected and 87% of both men and women are infected in Africa. Infection with HSV-2 can have more serious consequences, too, since it has been shown to increase a person’s risk of becoming infected with HIV. HSV-2 infection is lifelong, and serologic testing provides the best method to estimate HSV-2 prevalence. Two large randomized controlled trials among persons who were HSV-2-infected and HIV negative found that daily antiviral (acyclovir) therapy to suppress HSV-2 infection did not decrease the risk for HIV acquisition (4).
Multiple prevention strategies used alone or in combination are potentially useful in limiting acquisition and transmission of HSV-2. Nonetheless, HSV serologic screening might be useful in selected populations at high risk, such as persons with multiple sex partners or HIV infection, and men who have sex with men (5).
Twenty-six percent of women and 8% of men had no or 1 recurrence in year 1 of follow-up, whereas 14% of women and 26% of men had more than 10 recurrences. Since 1976, CDC has monitored HSV-2 seroprevalence in the United States through the National Health and Nutrition Examination Survey (NHANES). Most notably, HSV-2 seroprevalence among non-Hispanic blacks was approximately three times that of non-Hispanic whites and nearly four times that of Mexican Americans. Thus, primary prevention of HSV-2 infection might be the only available strategy to reduce the increased risk for HIV infection associated with HSV-2. For persons with symptomatic HSV-2 infection, daily antiviral therapy has been shown to reduce clinical and subclinical reactivation rates of HSV-2 and to reduce the risk for HSV-2 transmission to uninfected partners by 50% (6). A recent meta-analysis found that persons who reported always using condoms had a 30% decreased risk for acquiring HSV-2 infection compared with persons who reported no condom use (7). Second, no information was collected regarding genital symptoms to assess the extent of symptomatic but undiagnosed HSV-2 infection.
Therefore, health-care providers should consider testing for HSV-2 infection in those patients with either typical or atypical genital complaints, especially when the symptoms are recurrent (5). Additional research is needed to determine the benefits, feasibility, and cost effectiveness of serologic testing, alone or in combination with antiviral treatment, to prevent HSV-2 acquisition and transmission (10).
Increasing awareness of the high HSV-2 prevalence in the United States and the link between HSV-2 and HIV infections are important first steps in addressing the increased risk for HIV infection, especially among persons at greatest risk for HSV-2 and HIV infections. Additionally, persons with HSV-2 infection should be encouraged to inform partners of their infection status before initiating a sexual relationship. Finally, because of insufficient sample size, coinfection with HSV-2 and HIV could not be assessed. Finally, research into development of an HSV-2 vaccine should continue and might result in a more effective preventive measure in the future. Participants also were asked, "Has a doctor or other health-care professional ever told you that you had genital herpes?" Statistical software was used to generate seroprevalence estimates and 95% confidence intervals.
However, a previous report using data from multiyear NHANES found a strong association between HSV-2 seropositivity and HIV infection in the general population (8).
Recurrence rates are especially high in persons with an extended first episode of infection, regardless of whether they receive antiviral chemotherapy with acyclovir. All seroprevalence estimates were weighted using medical examination weights of the survey to represent the U.S. Men with genital HSV-2 infection have about 20% more recurrences than do women, a factor that may contribute to the higher rate of HSV-2 transmission from men to women than from women to men and to the continuing epidemic of genital herpes in the United States.



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