M A J O R A R T I C L E
Seroprevalence of Herpes Simplex Virus Types 1
and 2—United States, 1999–2010
Heather Bradley,1Lauri E. Markowitz,1Theda Gibson,2and Geraldine M. McQuillan3
1Centers for Disease Control and Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of STD Prevention,
2Department of Pediatrics, Emory University School of Medicine, and3Division of Health and Nutrition Examination Surveys, Centers for Disease Control
and Prevention, National Center for Health Statistics, Atlanta, Georgia
(See the editorial commentary by Kimberlin on pages 315–7.)
quelae. HSV-1 is an increasingly important cause of genital herpes in industrialized countries.
Methods. Using nationally representative data from the National Health and Nutrition Examination Survey
(NHANES), we examined HSV-1 and HSV-2 seroprevalence among 14- to 49-year-olds in the United States. We
estimated seroprevalence in 1999–2004 and 2005–2010, stratified by sociodemographic characteristics and sexual
behaviors. We also reviewed HSV-1 and HSV-2 seroprevalence from 1976–1980 to 2005–2010.
Results.In 2005–2010, the seroprevalence of HSV-1 was 53.9%, and the seroprevalence of HSV-2 was 15.7%.
From 1999–2004 to 2005–2010, HSV-1 seroprevalence declined by nearly 7% (P<.01), but HSV-2 seroprevalence
did not change significantly. The largest decline in HSV-1 seroprevalence from 1999–2004 to 2005–2010 was ob-
served among adolescents aged 14–19 years, among whom seroprevalence declined by nearly 23%, from 39.0% to
30.1% (P<.01). In this age group, HSV-1 seroprevalence declined >29% from 1976–1980 to 2005–2010 (P<.01).
Conclusions.An increasing number of adolescents lack HSV-1 antibodies at sexual debut. In the absence of de-
clines in HSV-2 infections, the prevalence of genital herpes may increase.
Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are common infections with serious se-
Keywords.HSV-1; HSV-2; herpes simplex virus; genital herpes; adolescents; NHANES.
Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2)
are lifelong infections. In 1999–2004, HSV-1 seropreva-
lence in the United States was 57.7% and HSV-2 sero-
prevalence was 17.0% . HSV-2 is almost always
transmitted sexually, whereas HSV-1 has typically been
transmitted nonsexually during childhood. Because
most HSV-1 and HSV-2 infections are subclinical,
many people with these viruses do not know they are
infected. When symptoms do occur, they consist
primarily of episodic ulcerative lesions at the site of in-
fection. HSV-1 infection typically causes orolabial
lesions, and HSV-2 infection typically causes genital
lesions. Although either HSV-1 or HSV-2 can cause
genital herpes, HSV-1 infection is characterized by
fewer recurrences of lesions and less viral shedding
than HSV-2 infection. .
Although rare, HSV-1 and HSV-2 have several
serious sequelae. Both can be transmitted perinatally
from mother to child, and in some cases, cause fatal
infection in infants. Other serious complications in
adults include blindness, encephalitis, and aseptic men-
ingitis .Of major public health importance is the in-
teraction of HSV-2 with human immunodeficiency
virus (HIV). HSV-2 infection increases the risk of ac-
quiring HIV infection 2- to 3-fold  and of transmit-
ting HIV infection 4-fold .
Largely due to the synergy between HSV-2 and HIV
more frequently described than patterns of HSV-1 in-
fection. However, HSV-1 seroprevalence is increasingly
Received 14 May 2013; accepted 11 June 2013; electronically published 16
Presented in part: Society for Adolescent Health and Medicine Meeting,
Atlanta, Georgia, March 2013; and International Society for Sexually Transmitted
Diseases Research Meeting, Vienna, Austria, July 2013.
Correspondence: Heather Bradley, PhD, Epidemiology and Surveillance Branch,
Division of STD Prevention, CDC, 1600 Clifton Rd NE, MS E-02, Atlanta, GA 30333
The Journal of Infectious Diseases2014;209:325–33
Published by Oxford University Press on behalf of the Infectious Diseases Society of
America 2013. This work is written by (a) US Government employee(s) and is in the
public domain inthe US.
HSV-1 and HSV-2 Seroprevalence in the US • JID 2014:209 (1 February) • 325
by guest on November 14, 2015
important to monitor. Two HSV vaccine trials found efficacy
against symptomatic disease for HSV-2 among HSV-1–nega-
tive women only ,although a follow-up trial did not find effi-
cacy among this group . HSV-1 seroprevalence data can be
helpful for ongoing HSV vaccine development efforts, including
for characterization of efficacy trial target populations and for
vaccine policy considerations.
HSV-1 is a significant cause of genital herpes in industrial-
ized countries . In a study of US college students, the per-
centage of genital herpes specimens that were attributable to
HSV-1 increased from 31% in 1993 to 78% in 2001 . More
recently, results from an HSV vaccine trial in the United States
indicated that nearly 60% of incident genital herpes infections
were attributable to HSV-1 [6, 9]. Similar trends have been ob-
served in other industrialized countries [10–12]. One possible
explanation for increasing genital HSV-1 infection is that HSV-
1 acquisition may be declining prior to sexual debut, rendering
young people without HSV-1 antibodies susceptible to genital
HSV-1 acquisition if exposed.
In this study, we estimated the seroprevalence of HSV-1 and
HSV-2 infection using the National Health and Nutrition Ex-
amination Survey (NHANES) data. We examined change in
the seroprevalence of HSV-1 and HSV-2 across surveys. HSV-1
and HSV-2 are lifelong infections, and seroprevalence increases
with age. Emergent change in population-level risk for HSV in-
fections is most effectively detected in the youngest age groups.
NHANES is a program of cross-sectional surveys that are de-
signed to be representative of the noninstitutionalized US pop-
ulation. Surveys have been conducted by the National Center
for Health Statistics (NCHS) since the 1960s to describe the
health and nutritional status of adults and children. In addition
to interviews, the NHANES survey methodology includes a
physical examination, during which blood and urine specimens
are collected for further testing. Previously, NHANES was a
series of surveys conducted at predetermined time intervals. In
1999, the methodology was modified such that surveys are now
administered continuously. Since NHANES’ inception, the
surveys have utilized a multistage, complex sampling scheme to
produce nationally representative estimates. NHANES is ap-
proved by the NCHS/Centers for Disease Control and Preven-
tion Research Ethics Review board. Informed consent was
obtained from all participants. Permission from parents or
legal guardians was obtained for participants aged <18 years.
Serologic testing for HSV-1 and HSV-2 has been conducted
as part of NHANES since the 1988–1994 survey; stored serum
samples from the 1976–1980 survey were previously tested. The
same glycoprotein G–based assays have been used to detect type-
specific HSV antibodies in all NHANES surveys. These assays
have been previously described in detail; they are highly sensitive
and specific, and discriminate well between HSV-1 and HSV-2
[13–15].Demographic information was collected via face-to-face
interview, and information about income and sexual behavior
was collected via audio computer assisted self-interview.
For the main analyses, we used NHANES data from the
period 1999–2010. To examine change in seroprevalence of
HSV-1 and HSV-2 over time, we categorized these data into 2
groups including 6 years each: 1999–2004 and 2005–2010. We
included respondents aged 14–49 years who were tested for
HSV-1 and HSV-2. During 1999–2004, 82% of screened partic-
ipants were interviewed, 78% were examined, and 72% were
tested for HSV-1 and HSV-2. During 2005–2010, 80% of
screened participants were interviewed, 78% were examined,
and 71% were tested for HSV-1 and HSV-2. From 1999 to
2010, 0.2% of respondents had an indeterminate HSV-1 result,
and 0.3% had an indeterminate HSV-2 result. These results
were recoded as negative for analytic purposes.
To make the estimates nationally representative of the US
noninstitutionalized population, we used NHANES participants’
medical examination sample weights for all analyses. These
weights are provided by NCHS and account for the differential
probabilities of selection, nonresponse, and noncoverage. We
used SAS version 9.3 software, which uses Taylor linearization to
incorporate the survey’s complex sample design and the weights
[16,17]. First, we calculated the percent change and correspond-
ing 95% confidence intervals in age-specific seroprevalence of
HSV-1 and HSV-2, from one time period to the next. The χ2test
for independence was used to assess statistical differences in age-
specific seroprevalence by time period. We used 2 criteria to
evaluate potential statistical unreliability of prevalence estimates:
having a relative standard error of >30% or having <10 cases in
the numerator. None of ourestimates met eitherof these criteria.
To better understand emerging change in HSV-1 seropreva-
lence, we examined seroprevalence among individuals aged
14–19 and 20–29 years in both time periods, stratified by re-
spondents’ sociodemographic characteristics and sexual behav-
iors. We calculated the percent change (and corresponding 95%
confidence intervals) in the seroprevalence of HSV-1 and HSV-
2 in each stratum and performed χ2tests to detect statistically
significant change from one time period to the next. To assess
potential confounding of the relationship between time period
and HSV-1 prevalence, we examined associations between re-
spondent characteristics and HSV-1 using prevalence ratios and
χ2tests. We also tested potential differences between respondent
characteristics in the 2 time periods (not shown).
Last, we examined HSV-1 and HSV-2 seroprevalence in every
survey period for which NHANES conducted serosurveys. We
estimated and compared overall and age-specific seroprevalence
of HSV-1 and HSV-2 in 1976–1980, 1988–1994, 1999–2004,
and 2005–2010. The 95% confidence intervals were calculated
for each seroprevalence estimate, and tests for trend were con-
ducted for overall samples and separately for each age group.
326 • JID 2014:209 (1 February) • Bradley et al
by guest on November 14, 2015
22. Vyse AJ, Gay NJ, Slomka MJ, et al. The burden of infection with
HSV-1 and HSV-2 in England and Wales: implications for the
changing epidemiology of genital herpes. Sex Transm Infect 2000; 76:
23. Schillinger JA, Xu F, Sternberg MJ, et al. National seroprevalence and
trends in herpes simplex virus type 1 in the United States, 1976–1994.
Sex Transm Dis 2004; 31:753–60.
24. Pouget ER, Kershaw TS, Blankenship KM, Ickovics JR, Niccolai LM.
Racial/ethnic disparities in undiagnosed infection with herpes simplex
virus type 2. Sex Transm Dis 2010; 37:538–43.
25. Centers for Disease Control and Prevention. Teenagers in the United
States: Sexual activity, contraceptive use, and childbearing, 2006–2010
National Survey of Family Growth. Vital Health Stat 2011; 23:1–35.
26. Copen CE, Chandra A, Martinez G. Prevalence and timing of oral sex
with opposite-sex partners among females and males aged 15–24 years:
United States, 2007–2010. National Health Statistics Reports; 2012; No.
56. Hyattsville, MD: National Center for Health Statistics.
27. Langenberg AG, Corey L, Ashley RL, Leong WP, Straus SE; Chiron HSV
Vaccine Study Group. A prospective study of new infections with herpes
simplex virustype 1 and type 2. New Engl J Med 1999; 341:1432–8.
HSV-1 and HSV-2 Seroprevalence in the US • JID 2014:209 (1 February) • 333
by guest on November 14, 2015