Herpes simplex virus type 1 infection: a sexually transmitted infection of adolescence?
ABSTRACT To examine the factors associated with antibodies to herpes simplex virus type 1 (HSV-1).
Cross sectional study with HSV-1 antibody testing performed by University of Washington western blot assay.
Central London STD clinic (1990-1) and central London blood donation centre (1992).
Representative sample of 869 new and rebooked GUM clinic attenders and 1494 consecutive blood donors.
The prevalence of HSV-1 antibody among clinic attenders was 60.4% (95% CI 57.0 to 63.7) and among donors was 46.1% (95% CI 43.5 to 48.7). HSV-1 antibody was independently associated with increasing age in both populations (p<0.001). Among clinic attenders, HSV-1 was less common among heterosexual men than women and homosexual men (p<0.005), and was more common among black people (p=0.001) and those of lower socioeconomic status (p=0.05). Among blood donors, being single rather than married was independently associated with HSV-1 infection (p=0.03). Early age at first intercourse was strongly associated with presence of HSV-1 in both populations. The adjusted odds of HSV-1 among GUM clinic attenders was 0.37 (95% CI 0.21 to 0.65) for someone aged 20 at first intercourse compared with someone aged <or=15. Among blood donors, those aged 20 had an adjusted odds of 0.64 (95% CI 0.39 to 1.05) compared with someone aged 15. HSV-1 was not associated with increasing number of lifetime partners after adjustment for other factors.
Genital herpes due to HSV-1 antibody is increasing in the United Kingdom, particularly among young people. In this study we found that HSV-1 was strongly associated with early age of first sexual intercourse, which may reflect the sexual practices of people initiating sex in this age group.
- International Journal of STD & AIDS 01/1995; 6(2):144. · 1.00 Impact Factor
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ABSTRACT: In the last 3 decades, herpes simplex virus type 2 (HSV-2) infection seroprevalence and neonatal herpes have increased substantially. An effective vaccine for the prevention of genital herpes could help control this epidemic. To evaluate the efficacy of a vaccine for prevention of HSV-2 infection. Two randomized, double-blind, placebo-controlled multicenter trials of a recombinant subunit vaccine containing 30 microg each of 2 major HSV-2 surface glycoproteins (gB2 and gD2) against which neutralizing antibodies are directed, administered at months 0, 1, and 6. Control subjects were given a citrate buffer vehicle. Participants were followed up for 1 year after the third immunization. We enrolled 2393 persons from December 10, 1993, to April 4, 1995, who were HSV-2 and human immunodeficiency virus seronegative. One trial with 18 centers enrolled 531 HSV-2-seronegative partners of HSV-2-infected persons; the other, with 22 centers, enrolled 1862 persons attending sexually transmitted disease clinics. A total of 2268 (94.8%) met inclusion criteria and were included in the analysis with 1135 randomized to placebo and 2012 to vaccine. Time to acquisition of HSV-2 infection, defined by seroconversion or isolation of HSV-2 in culture during the study period by randomization group. Time-to-event curves indicated a 50% lower acquisition rate among vaccine vs placebo recipients during the initial 5 months of the trial; however, overall vaccine efficacy was 9% (95% confidence interval, -29% to 36%). Acquisition rates of HSV-2 were 4.6 and 4.2 per 100 patient-years in the placebo and vaccine recipients, respectively (P =.58). Follow-up of vaccine recipients acquiring HSV-2 infection showed vaccination had no significant influence on duration of clinical first genital HSV-2 episodes (vaccine, median of 7.1 days; placebo, 6.5 days; P>.10) or subsequent frequency of reactivation (median monthly recurrence rate with vaccine, 0.2; with placebo, 0.3; P>.10). The vaccine induced high levels of HSV-2-specific neutralizing antibodies in vaccinated persons who did and did not develop genital herpes. Efficient and sustained protection from sexual acquisition of HSV-2 infection will require more than high titers of specific neutralizing antibodies. Protection against sexually transmitted viruses involving exposure over a prolonged period will require a higher degree of vaccine efficacy than that achieved in this study.JAMA The Journal of the American Medical Association 08/1999; 282(4):331-40. · 29.98 Impact Factor
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ABSTRACT: The acquisition of genital herpes during pregnancy has been associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. The frequency of seroconversion, maternal symptoms of the disease, and the timing of its greatest effect on the outcome of pregnancy have not been systematically studied. We studied 7046 pregnant women whom serologic tests showed to be at risk for herpes simplex virus (HSV) infection. Serum samples obtained at the first prenatal visit, at approximately 16 and 24 weeks, and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV-2) by the Western blot assay, and the results were correlated with the occurrence of antenatal genital infections. Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes infection. Women who were initially seronegative for both HSV-1 and HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent; those who were initially seropositive only for HSV-1 had an estimated chance of HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2-seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among the 60 of the 94 pregnancies for which the time of acquisition of HSV infection was known, 30 percent of the infections occurred in the first trimester, 30 percent in the second, and 40 percent in the third. HSV seroconversion completed by the time of labor was not associated with an increase in neonatal morbidity or with any cases of congenital herpes infection. However, among the infants born to nine women who acquired genital HSV infection shortly before labor, neonatal HSV infection occurred in four infants, of whom one died. Two percent or more of susceptible women acquire HSV infection during pregnancy. Acquisition of infection with seroconversion completed before labor does not appear to affect the outcome of pregnancy, but infection acquired near the time of labor is associated with neonatal herpes and perinatal morbidity.New England Journal of Medicine 09/1997; 337(8):509-15. · 51.66 Impact Factor
ADOLESCENT SEXUAL HEALTH
Herpes simplex virus type 1 infection: a sexually
transmitted infection of adolescence?
F M Cowan, A Copas, A M Johnson, R Ashley, L Corey, A Mindel
Sex Transm Infect 2002;78:346–348
Objectives: To examine the factors associated with
antibodies to herpes simplex virus type 1 (HSV-1).
Design: Cross sectional study with HSV-1 antibody testing
performed by University of Washington western blot
Setting: Central London STD clinic (1990–1) and central
London blood donation centre (1992).
Participants: Representative sample of 869 new and
rebooked GUM clinic attenders and 1494 consecutive
Results: The prevalence of HSV-1 antibody among clinic
attenders was 60.4% (95% CI 57.0 to 63.7) and among
donors was 46.1% (95% CI 43.5 to 48.7). HSV-1
antibody was independently associated with increasing
attenders, HSV-1 was less common among heterosexual
men than women and homosexual men (p<0.005), and
was more common among black people (p=0.001) and
those of lower socioeconomic status (p=0.05). Among
blood donors, being single rather than married was inde-
pendently associated with HSV-1 infection (p=0.03). Early
age at first intercourse was strongly associated with
presence of HSV-1 in both populations. The adjusted odds
of HSV-1 among GUM clinic attenders was 0.37 (95% CI
0.21 to 0.65) for someone aged 20 at first intercourse
compared with someone aged <15. Among blood
donors, those aged 20 had an adjusted odds of 0.64
(95% CI 0.39 to 1.05) compared with someone aged 15.
HSV-1 was not associated with increasing number of
lifetime partners after adjustment for other factors.
Conclusions: Genital herpes due to HSV-1 antibody is
increasing in the United Kingdom, particularly among
young people. In this study we found that HSV-1 was
strongly associatedwith early
intercourse, which may reflect the sexual practices of
people initiating sex in this age group.
indicate that infection with HSV was almost universal in
adulthood.1However by the 1970s only 50% of adults were
infected.1This decrease has been attributed to the improve-
ment in socioeconomic circumstances that occurred over that
time. When type specific HSV serological tests first became
available, Nahmias conducted a global survey of HSV-1 and
HSV-2 infection and concluded that HSV-1 may be a useful
marker of temporal change in sociological patterns within
communities.2A recent serological survey of over 5000
samples collected as part of the UK PHLS serosurveillance
programme showed that the rate of infection among 10–14
year olds had dropped from 34% in 1986–7 to 24% in 1994–5.3
The majority of young people are therefore HSV-1 naive at the
erpes simplex virus type 1 (HSV-1) infection is a
common viral illness,which classically causes oro-labial
herpes (cold sores). Serological studies from the 1940s
onset of sexual activity. In addition, descriptive studies of
genital herpes from the United Kingdom have noted that the
proportion of infection due to HSV-1 rather than HSV-2 is
increasing,particularly in young people4–6;however,the extent
of sexual acquisition of HSV-1 at a population level is
We report the results of a serological survey of antibodies to
HSV performed among attenders at a department of
genitourinary medicine (GUM) and donors attending a blood
donation centre in central London, which examines the
demographic and behavioural factors associated with HSV-1
Between November 1990 and December 1991,869 consecutive
GUM clinic patients attending a representative sample of clin-
ics were invited to participate in the study, as were 1494 con-
secutive blood donors between February and April 1992. All
participants had a blood sample taken for antibodies to HSV
and self completed a questionnaire, which collected infor-
mation on demographic and behavioural characteristics as
well as on symptoms/history of herpes infection. Results on
HSV-2 seroprevalence and symptoms of herpes infection have
been published elsewhere.7 8
Blood samples were tested for herpes simplex virus
antibody at University of Washington by western blot
is sensitive and specific for identifying patients with past
herpes simplex virus type 1 and herpes simplex virus type 2
or co-infected with both agents.
Statistical analysis was undertaken using STATA 6.0. The
unadjusted odds of HSV-1 were calculated for socio-
demographic and behavioural factors.The adjusted odds were
calculated adjusting for all other factors. This complete case
analysis was based on 759 (STI clinic attenders), and 1144
(blood donors) participants respectively. In order to examine
the extent to which sexual behaviour is associated with HSV-1
acquisition, the calculation of adjusted odds of HSV-1 only
included individuals who had ever had sex. In order to
separate the effects of age and age at first sexual intercourse,a
subset of the data was reanalysed (individuals >25 years who
had had sex before age 25). These results are not presented
here,but this analysis did not substantially change the results.
The response rate was 98% among eligible participants at both
sites. The demographic and behavioural characteristics of the
populations are shown in table 1. Sixty four per cent of clinic
attenders were single, 84.6% were white and 76.9% were in
social class I, II, or III. Thirty five per cent of male and 51% of
female donors were single and overall 94% were white. Infor-
mation on occupation was not collected from blood donors.
The prevalence of antibody to HSV-1 among clinic attenders
was 60.4% (95% CI 57.0 to 63.7) and among donors was 46.1%
(95% CI 43.5 to 48.7). The demographic and behavioural fac-
tors associated with presence of antibody to HSV-1 are shown
in table 2. On univariate analysis, the prevalence of antibodies
to HSV-1 increased with age in both populations, HSV-1 was
more common in black GUM clinic attenders than white and
was less common among GUM attenders of higher socioeco-
nomic status. Married blood donors were more likely to be
infected than single.
In GUM clinic attenders, the adjusted odds of HSV-1
indicated that HSV-1 was less common among heterosexual
men than women and homosexual men, became more
common with increasing age and was more common among
black people and those of lower socioeconomic status. Among
blood donors,only increasing age and being single rather than
married were independently associated with HSV-1 infection.
In relation to the behavioural factors,it is striking that early
age at first intercourse is much more strongly associated with
presence of HSV-1, than lifetime partners in both groups.
Among GUM clinic attenders someone who was aged 20 was
over 60% less likely to have HSV-1 than someone who had sex
for the first time aged 15. Although the association was less
marked in blood donors, those aged 20 at first intercourse
were 36% less likely to have HSV-1 than those who had sex for
the first time aged <15.
Population based studies of sexual behaviour confirm that the
age of first sexual intercourse in Britain has decreased over the
past 30 years, although this has likely stabilised over the past
acquisition of HSV-1 (presumably non-sexual) is declining
and that a majority of young people are HSV-1 naive when
they start to become sexually active.3Several centres in the
United Kingdom report that primary genital HSV-1 is now the
most common cause of genital herpes in young women.4
In this study we demonstrate that in the United Kingdom
HSV-1 behaves similarly to some of the viral STIs, such as
HSV-2 and HIV.It is more common among women and homo-
sexual men than heterosexual men and among GUM clinic
attenders than blood donors. Age of first intercourse is the
strongest predictor of infection. However, serological evidence
of HSV-1 antibody provides no information about likely site of
sexually acquired HSV-1.Study participants were asked about
past diagnosis and symptoms of both oro-labial and genital
indicate that around 16% of GUM attenders with HSV-1 anti-
body alone had symptoms suggestive of genital herpes but
that this rate was much lower in blood donors (3%). Sexual
transmission of HSV-1 can result in oro-labial herpes (through
kissing) or genital herpes (through either oro-genital or possi-
bly genital-genital contact). However, the fact that more than
60% of genital infections in young women in some centres are
due to HSV-1 means that at least some of these infections are
likely to be genitally acquired.4
These data have two implications for young people. It
appears that people who start having sex at an early age are
particularly vulnerable to infection with HSV-1, more likely as
a result of their sexual behaviour than because of any biologi-
cal predisposition. Of note, because HSV-1 is transmitted
through both social and sexual contact, individuals who have
never had sex but are infected with HSV-1 can potentially
transmit genital herpes to their sexual partners. Secondly,
because transmission studies have not shown that HSV-1
infection is protective of acquisition of infection with HSV-
2,11 12an individual who acquires genital herpes due to HSV-1
early in life could potentially acquire infection with HSV-2
subsequently, which is more likely to become recurrent.
10Data from other studies confirm that childhood
F M Cowan, A Copas, A M Johnson, Department of Sexually
Transmitted Diseases, Royal Free and University College Medical School,
University College London, UK
R Ashley, L Corey, University of Washington, Seattle, USA
A Mindel, University of Sydney and Westmead Hospital, Sydney,
Correspondence to: Dr Frances Cowan, Department of Sexually
Transmitted Diseases, Royal Free and University College Medical School,
Mortimer Market Centre, off Capper Street, London WC1E 6AU, UK;
Accepted for publication 12 August 2002
characteristics of the two study samples
Demographic and behavioural
% (No) % (No)
Lifetime sexual partners
Age at first sexual intercourse
• HSV-1 is a common infection in adults in the UK (46% in
blood donors and 60% of GUM clinic attenders are
• This study shows that HSV-1 infection is related to sexual
behaviour in that prevalence is strongly related to age at
first intercourse (and to sexual orientation and sex in
GUM clinic attenders)
• The association with early age at first intercourse is
striking and may reflect the particular sexual practices of
people initiating sex in this age group.
1 Corey L, Wald A. Genital herpes. In Holmes KK, Sparling PF, Mardh
P-A, Lemon SM, Stamm WE, Piot P, et al, eds. Sexually transmitted
diseases. New York: McGraw Hill, 1999:285–312.
2 Nahmias AJ, Lee FK, Beckman-Nahmias S. Sero-epidemiological and
-sociological patterns of herpes simplex virus infection in the world.
Scand J Infect Dis 1990.
3 Vyse A, Gay N, 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;76:183–7.
4 Ross JDC, Smith IW, Elton RA. The epidemiology of herpes simplex
types 1 and 2 infection of the genital tract in Edinburgh 1978–1991.
Genitourin Med 1993;69:381–3.
5 Scoular A, Leask BGS, Carrington D. Changing trends in genital herpes
due to Herpes simplex virus type 1 in Glasgow, 1985–88. Genitourin
6 Rodgers CA,.O’Mahony C. High prevalence of herpes simplex virus
type 1 in female anogenital herpes simplex. Int J STD AIDS 1995;6:144.
7 Cowan FM, Johnson AM, Ashley R, et al. Antibody to herpes simplex
virus type 2 as a serological marker of sexual lifestyle in populations.
8 Cowan FM, Johnson AM, Ashley R, et al. Relationship between
antibodies to herpes simplex virus (HSV) and symptoms of HSV infection.
J Infect Dis 1996;174:470–5.
9 Ashley RL, Militoni J, Lee F, et al. Comparison of western blot
(immunoblot) and glycoprotein G-specific immunodot enzyme assay for
detecting antibodies to herpes simplex virus types 1 and 2 in human
sera. J Clin Microbiol 1988;26:662–7.
10 Wellings K, Nanchahal K, Macdowall W, et al. Sexual behaviour
in Britain: early heterosexual experience. Lancet 2001;358:
11 Corey L, Langenberg A, Ashley RL, et al. Recombinant glycoprotein
vaccine for the prevention of genital HSV-2 infections—2 randomised
controlled trials. JAMA 1999;282:331–40.
12 Brown ZA, Selke S, Zeh J, et al. The acquisition of herpes simplex virus
during pregnancy. N Engl J Med 1997;337:509–15.
(ORs) based in all participants and adjusted ORs based on sexually active participants only
Demographic and behavioural associations with HSV-1 antibody prevalence, with unadjusted odds ratios
GUM attendersBlood donors
(No HSV-1 +ve)
(No HSV-1 +ve)
Lifetime sexual partners*
Age at first sexual intercourse*
*For these ordinal factors, statistical tests are based on the raw figures, not the grouped data. The Mann-Whitney test is used for the unadjusted testing,
and the adjusted is based on the inclusion of the linear term in the logistic regression model.
348Cowan, Copas, Johnson, et al