Risk factors of herpes simplex type 1 (HSV-1) infection and lifestyle factors associated with HSV-1 manifestations

Abstract

This study investigated risk factors for herpes simplex virus type 1 (HSV-1) infection in a population of university students in Germany and Spain. In addition, factors associated with the occurrence of oral lesions were studied. Serum samples were collected from 596 Spanish students from the Navarra Public University in Pamplona and 174 German students from the University of Bielefeld aged 17-41 years and tested by a HSV-1 type-specific immunoassay using monoclonal antibody-selected gG1 as antigen. Information on clinical manifestations and risk factors were obtained by a standardized questionnaire. The rate of HSV-1 infection was 55.3 and 27.4% of these infected students reported having had oral lesions within the last 12 months. Prevalence of HSV-1 infection did not differ between study sites, and did not vary according to gender or age. Students with coitus experience were more likely to be infected with HSV-1 (Odds ratio (OR), 1.88; 95%CI: 1.31-2.69), while other lifestyle factors were not associated with HSV-1 infection. Risk factors for the occurrence of oral lesions included HSV-1 seropositivity (OR: 6.90; 95%CI: 3.84-12.37) and a higher level of perceived stress, as measured by the Cohen scale of perceived stress (OR: 1.79; 95%CI: 1.15-2.78). Drinking alcohol was found to be a protective factor (OR: 0.59; 95%CI: 0.37-0.93). There was no difference in the clinical pattern and course of infection between the young adults in Germany and Spain. We conclude, that lifestyle factors appear to play an important role in the epidemiology and clinical manifestations of HSV-1.

Full text

Risk factors of herpes simplex type 1 (HSV-1) infection and lifestyle factors
associated with HSV-1 manifestations
Christiane Stock
1
, Francisco Guille
´
n-Grima
2
, Juan Hermoso de Mendoza
2
, Blanca Marin-
Fernandez
2
, Ines Aguinaga-Ontoso
2
& Alexander Kra
¨
mer
1
1
School of Public Health, University of Bielefeld, Bielefeld, Germany;
2
Department of Health Sciences, Navarra Public
University, Pamplona, Spain
Accepted in revised form 14 February 2002
Abstract. This study investigated risk factors for
herpes simplex virus type 1 (HSV-1) infection in a
population of university students in Germany and
Spain. In addition, factors associated with the oc-
currence of oral lesions were studied. Serum samples
were collected from 596 Spanish students from the
Navarra Public University in Pamplona and 174
German students from the University of Bielefeld
aged 17–41 years and tested by a HSV-1 type-specific
immunoassay using monoclonal antibody-selected
gG1 as antigen. Information on clinical manifesta-
tions and risk factors were obtained by a standard-
ized questionnaire. The rate of HSV-1 infection was
55.3 and 27.4% of these infected students reported
having had oral lesions within the last 12 months.
Prevalence of HSV-1 infection did not differ between
study sites, and did not vary according to gender or
age. Students with coitus experience were more likely
to be infected with HSV-1 (Odds ratio (OR), 1.88;
95%CI: 1.31–2.69), while other lifestyle factors were
not associated with HSV-1 infection. Risk factors for
the occurrence of oral lesions included HSV-1 sero-
positivity (OR: 6.90; 95%CI: 3.84–12.37) and a
higher level of perceived stress, as measured by the
Cohen scale of perceived stress (OR: 1.79; 95%CI:
1.15–2.78). Drinking alcohol was found to be a pro-
tective factor (OR: 0.59; 95%CI: 0.37–0.93). There
was no difference in the clinical pattern and course of
infection between the young adults in Germany and
Spain. We conclude, that lifestyle factors appear to
play an important role in the epidemiology and
clinical manifestations of HSV-1.
Key words: Herpes simplex virus type 1 (HSV-1), Oral lesions, Psychosocial stress, Risk factors
Abbreviations: 95%CI ¼ 95% confidence interval; HSV-1 ¼ herpes simplex virus type 1; HSV-2 ¼ herpes
simplex virus type 2; IgG ¼ immunoglobulin G; OR ¼ odds ratio; PSS ¼ perceived stress score
Introduction
Of the two types of herpes simplex viruses (HSV)
HSV-1 is mainly responsible for manifestations above
the waist and HSV-2 for 70–95% of the cases of
genital infection. Direct contact, with transmission
through infected secretions, is the principal mode of
spread. HSV-1 infections are endemic in industrial-
ized and developing countries worldwide and usually
infections occur early in childhood and persist after
that. Studies in adolescents aged 14–17 years in Ger-
many and Spain showed that an estimated proportion
of 40–50% are infected with HSV-1 in this age group
[1, 2]. Seroprevalence increases with age up to levels of
90% by the fifth decade [2]. Although HSV-I is among
the most common infectious agents affecting humans
the epidemiological characteristics have remained
widely unknown so far. The development of new sero-
logical methods for distinguishing between HSV-1
and HSV-2 have provided the opportunity to study
the epidemiology of HSV infection in more detail.
As many as 40% of infected people may develop
recurrent episodes of herpes manifestations [3]. Oral
herpes affects about 75% of the general population at
some time during life. Affected persons may develop
subsequent fever blisters or recurrent herpes labialis
after the primary infection. HSVs are thought to re-
side latently in sensory ganglion neurons and the la-
tent virus is hypothesized to be reactivated under
certain circumstances [4]. The factors believed to
trigger the outbreak of HSV are not completely un-
derstood, but endogenous (e.g. immune deficiency,
emotional stress) and exogenous factors (e.g. UV
radiation) have been implicated. There is evidence
that psychosocial factors can be associated with the
recurrence of herpes labialis symptoms [5–7], and that
psychosocial intervention can reduce the frequency
and severity of recurrences of genital herpes [8].
The purpose of this cross-sectional study was to
examine the role of socioeconomic status, gender,
place of residence, and behavioural variables as po-
tential risk factors for HSV-1 infection in a population
European Journal of Epidemiology 17: 885–890, 2001.
Ó 2002 Kluwer Academic Publishers. Printed in the Netherlands.

of young Spanish and German adults. Another aim of
the study was to identify factors associated with the
recurrence of oral lesions. It was hypothesized that
persons with a higher level of perceived stress were
more likely to report the occurrence of lesions.
Material and methods
Study population
The sample consisted of 770 university students from
two study centres in Pamplona, Spain, and Bielefeld,
Germany. The age of the students was 17–41 years
(mean age: 20.3 [SD 2.8] years). At the Navarra
Public University (Universidad Publica de Navarra,
UPNA), Pamplona, Spain, samples were collected
from 596 students (64% female, 38% male) who were
recruited for a students’ health study. German stu-
dents at the University of Bielefeld (Universita
¨
t Bi-
elefeld, UB) were participants in a longitudinal health
study, who were invited for a follow-up. In this
population (66% females, 34% males) 174 serum
samples were collected. For all data collection par-
ticipants gave their informed consent and all proce-
dures were designed to protect students’ privacy and
allow for anonymous participation.
Questionnaire
The self-administered questionnaire was developed
and pilot-tested in the German language and then
translated into Spanish. The translation was per-
formed twice independently and the results were
checked for inconsistencies. Then, the Spanish ver-
sion was pilot-tested on Spanish students. The ques-
tionnaire addressed demographic information (age,
gender, place of residence, educational status of
parents), self-reported health data and a broad range
of health behaviours including illicit drug use and
sexual behaviour. A higher educational level of
mother/father was defined as at least high school
degree. Smoking was assessed in three categories
(never, occasionally, daily). Since in a previous study
in university students only the category daily smoking
was associated with levels of urinary cotinine above
the cut-off of the enzyme immunoassay [9], daily
smoking vs. occasionally or never smoking was used
for the risk factor analyses. The frequency of alcohol
consumption was measured in three categories (see
Table 1) and the cut-off was set at drinking alcohol
more than one time per week. Students were asked,
whether they had experienced lesions of oral herpes
within the last 12 months. Psychosocial stress was
measured using the Perceived Stress Scale (PSS) in a
four item version evaluating the level of perceived
stress within the last 4 weeks [10]. High levels of
perceived stress were defined as above the median of
the PSS-score. The internal reliability (Cronbach’s a)
of the PSS scale was 0.77.
Laboratory methods
Blood was drawn by venipuncture and after centri-
fugation serum samples were immediately frozen at
)20 °C for later determination. IgG antibodies
against HSV-1 were measured by a commercially
available quantitative enzyme immunoassay (DRG
Instruments, Marburg, Germany) using monoclonal
antibody-selected gG1 as antigen. The sensitivity and
specificity of the test reported by the manufacturer
was 98 and 99% respectively. The coefficient of test
variance has been obtained below 10%. Seventeen
(22.1% of the total) indeterminate samples (cut-
off  10%) were excluded from further analysis. In
a subsample of sexually active students (n ¼ 352)
antibodies against HSV-2 were measured using an
enzyme-immunoassay from the same manufacturer.
Twelve samples (3.4%) were found seropositive for
HSV-2 (2.1% in males, 4.4% in females). Since only
five samples were positive for HSV-1 and HSV-2 the
cross-reactivity of the tests was considered as low.
The HSV-1 and HSV-2 specific enzyme immunoas-
says used gG-1 and gG-2 as antigens. All laboratory
tests were done in the laboratory at UB using a
standardized protocol. Serum samples from UPNA
were shipped for analysis on dry ice.
Data analysis
Statistical analyses were carried out using the SPSS
statistical package version 10.0. The prevalence esti-
mates were completed by 95% confidence intervals.
Table 1. Characteristics of students evaluated for HSV-1
serostatus
Variables N %
a
Sociodemographic variables
Age (years)
17–19 400 52.4
20–24 320 41.8
>24 44 5.8
Male gender 284 37.0
High school degree of mother 248 32.4
High school degree of father 432 57.2
Students from University of Bielefeld 174 23.3
Behaviours
Drinking alcohol
Never 116 15.5
Once a week 236 31.6
More than once a week 394 52.9
Daily smoking 212 28.5
Having ever had sexual intercourse 342 49.3
HSV-1 seropositive 421 55.3
Oral lesions within
the last 12 months
138 17.9
a
In calculating proportions missing values were not
included.
886

Odds ratios were calculated using multivariate logis-
tic regression analysis.
Results
Prevalence of HSV-1 and occurrence of oral herpes
The rate of positive antibody tests against HSV-1 was
55.3% (95%CI: 51.6–58.6) in all students tested
(Table 1), 56.9% (95%CI: 52.8–60.8) in Spanish
students, and 48.9% (95%CI: 41.5–56.3) in German
students. Oral lesions within the last 12 months were
reported from 17.9% (95%CI: 15.2–20.6) in all stu-
dents, and from 17.1% (95%CI: 14.1–20.1) in Span-
ish and 20.5% (95%CI: 14.5–26.6) in German
students. Among HSV-1 infected individuals (n ¼
421) oral lesions within the last 12 months were re-
ported by 27.4% (95%CI: 23.2–31.7) of all respon-
dents, while only 7.8% (95%CI: 4.3–11.3) of HSV-1
negative individuals reported manifestations of oral
herpes.
Association of HSV-1 antibody prevalence and risk
factors
In the unadjusted, bivariate analyses having had
sexual intercourse ever (p ¼ 0:0007), drinking alcohol
more than one time per week (p ¼ 0:016), and
smoking (p ¼ 0:006) were positively associated with
HSV-I infection (Table 2). The higher education of
the mother, defined as at least a high school degree,
was a protective factor of HSV-I infection (p ¼
0:018). Place of residence, age, gender, educational
level of father, and level of perceived stress were not
significantly associated with HSV-1 infection.
Predictors of HSV-1 infection in students with
defined HSV-1 serostatus were analysed using a
multivariate logistic regression model. The model
included all variables determined significant (p <
0:05) in the bivariate analysis (education of mother,
alcohol consumption, smoking, sexual experience),
and the variables age, gender and place of residence.
The only risk factor independently associated with
HSV-1 infection was having ever had sexual inter-
course (p ¼ 0:001) (Table 3).
Risk factors of oral lesions
In the bivariate analyses HSV-1 infection was highly
associated with the occurrence of oral lesions in the
last 12 months (p < 0:0001) (Table 2). Besides this
factor, female gender (p ¼ 0:023), having had sexual
intercourse ever (p ¼ 0:011), and a high level of per-
ceived stress (p ¼ 0:020) were significantly associated
with symptoms of oral herpes (Table 2). Drinking
alcohol more than once a week was a protective
factor (p ¼ 0:019). Place of residence, age, educa-
tional level of parents, and smoking were not signif-
icantly associated with symptoms of oral herpes.
The results of a multivariate logistic regression
model estimating predictors for the occurrence of
oral lesions are shown in Table 4. The model in-
cluded all variables determined significant (p < 0:05)
Table 2. Predictors of HSV-1 infection and of oral lesions in students with defined HSV-1 serostatus (n = 753) by bivariate
analysis
HSV-1 infection Oral lesions
Variables OR 95%CI p-Value OR 95%CI p-Value
HSV-1 seropositive 5.77 3.54–9.43 <0.0001
Age (per year) 1.02 0.97–1.07 0.481 1.06 0.99–1.12 0.064
Male gender 0.82 0.61–1.10 0.173 0.63 0.42–0.94 0.023
High school degree of mother 0.60 0.39–0.92 0.018 0.64 0.35–1.18 0.156
High school degree of father 0.88 0.66–1.19 0.408 0.95 0.65–1.39 0.783
Living in Germany 0.75 0.53–1.05 0.096 1.25 0.81–1.31 0.314
Drinking alcohol >once a week 1.43 1.07–1.91 0.016 0.64 0.43–0.93 0.019
Daily smoking 1.59 1.14–2.20 0.006 1.06 0.69–1.60 0.790
Having ever had sexual intercourse 1.69 1.25–2.29 0.0007 1.68 1.13–2.49 0.011
High level of perceived stress 1.09 0.81–1.46 0.565 1.57 1.07–2.30 0.020
Table 3. Multivariate logistic regression analysis of char-
acteristics associated with HSV-1 infection in university
students
Independent variables OR
a
CI
b
p-Value
Sociodemographic variables
High school degree of mother 0.68 0.43–1.09 0.106
Behaviours
Daily smoking 1.07 0.74–1.56 0.710
Drinking alcohol > once
a week 1.36 0.97–1.91 0.077
Having ever had sexual
intercourse 1.88 1.31–2.69 0.001
a
OR, adjusted for age, gender, place of residence and all
other variables listed in this table.
b
CI, 95% confidence interval.
887

in the bivariate analysis (HSV-1 status, gender, al-
cohol consumption, sexual experience, psychosocial
stress) and the variables age and place of residence. In
this model HSV-1 infection was highly associated
with the occurrence of oral lesions (p < 0:001). A
higher level of perceived stress was independently
associated with symptoms of oral herpes (p ¼ 0:009)
and drinking alcohol more than one time per week
was found to be a protective factor (p ¼ 0:024).
Discussion
The aim of this study was to highlight the epidemi-
ology of the latent virus infection HSV-1 in a popu-
lation of young adults in Germany and Spain. The
use of type-specific antibody assays distinguishing
between HSV-1 and HSV-2, which detect subclinical
as well as clinical infections, enabled us to estimate
HSV-1 seroprevalence in the student population. The
accuracy of these specific immunoassays have been
shown to be as accurate and sensitive as immunoblot
techniques for the detection of herpes antibodies [2,
11]. The HSV-1 prevalence rate found was 55.3% and
did not differ significantly between the German and
the Spanish study sites. The rate of HSV-1 seroposi-
tivity in the student populations was slightly lower
than that found in other populations of similar age in
Germany and Spain [1, 2]. However, it was in the
same range as reported from blood donors in London
[12], and from pregnant women in Tokyo [13].
Longitudinal trends in Japan indicate a decrease
in HSV-1 prevalence in the last decades [14], but
comparable data is lacking in Europe. As HSV-1
prevalence is associated with markers of low socio-
economic status such as crowding [15] and insufficient
sanitary conditions, prevalence rates below 60% up
to the age of 30 may indicate a higher socioeconomic
status [13].
In addition to the seroprevalence of HSV-1, this
study revealed insights into risk factors associated
with HSV-1 infection. It is well documented that
HSV-1 seroprevalence steadily increases at a young
age with not much further increase beyond the age of
40 years [2, 13]. In our sample age was not a signifi-
cant risk factor for infection, which may be explained
by the narrow age range of the study population. In
the multivariate model only sexual activity remained
a significant risk factor for infection. Since students
ever having had sexual intercourse were twice as
likely to be infected with HSV-1, sexual transmission
seemed to contribute to HSV-1 transmission in this
population. A higher HSV-1 prevalence in females
with coitus experience were also reported from a
study in teenage girls in Sweden [16]. Recently, sev-
eral studies have described a relatively high frequency
of genital manifestation of HSV-1 infection in sexu-
ally active adults [13, 17]. Oral–genital contact was
shown to be a risk factor for genital HSV-1 infection
[18]. We therefore conclude, that sexual activity is
playing a significant role in HSV-1 transmission, and
oral–oral contact during sexual interplay may also
contribute to sexual transmission of HSV-1. How-
ever, genital manifestations were only reported from
1.8% of HSV-1 positive/HSV-2 negative individuals
in our sample.
A proportion of 27% of HSV-1 seropositive stu-
dents reported clinical symptoms of herpes labialis
within the last 12 months. A prospective study of the
Chiron HSV vaccine study group [17] showed that
nearly two-thirds of incident cases of HSV-1 infection
were symptomatic indicating that the lifetime preva-
lence of symptomatic persons in our study was likely
to be higher than 27% of infected persons. Since the
annual seroconversion rate can be estimated at about
5% [19] only a small proportion of seropositive stu-
dents were likely to be primarily infected during the
last 12 months. This indicates that the majority of
symptomatic individuals developed recurrent symp-
toms related to lifelong persistent infection.
In the multivariate model, which controlled for
HSV-1 status, age, gender, place of residence, alcohol
consumption, and sexual experience, a higher level of
perceived stress remained a significant risk factor for
herpes symptoms. In addition, students who used to
drink alcohol more frequently were significantly less
likely to develop clinical symptoms. Due to the cross-
sectional design of the study the causal relationship
between the identified risk factors and the occurrence
of oral lesions remains unclear. However, in psy-
choneuroimmunological studies psychosocial stress
was often cited as the most significant factor in the
recurrence of lesions [6, 20]. Prospective studies have
shown an association between changes in stress,
mood states and immune and neuroendocrine
markers with the recurrence of oral herpes lesions [5,
7], indicating stress induced changes in immune
function as the underlying mechanism of virus reac-
tivation. Therefore, these psychophysiological studies
led to the assumption that chronic stress, as indicated
by a higher PSS-score, may have contributed to virus
reactivation via neuroimmune pathways.
Table 4. Multivariate logistic regression analysis of char-
acteristics associated with oral lesions
Independent variables OR
a
CI
b
p-Value
HSV-1 seropositive 6.90 3.84–12.37 <0.0001
Male gender 0.78 0.49–1.24 0.289
Drinking alcohol > once
a week 0.59 0.37–0.93 0.024
High level of perceived stress 1.79 1.15–2.78 0.009
Having ever had
sexual intercourse 1.26 0.77–2.06 0.350
a
OR, adjusted for age, place of residence and all other
variables listed in this table.
b
CI, 95% confidence interval.
888

To our knowledge this is the first study showing an
association between oral herpes and alcohol con-
sumption. The pathway through which the potential
protective effect of alcohol consumption on herpes
lesions could possibly be mediated is currently un-
known and prospective studies are needed to clarify
the relationship between alcohol consumption and
oral herpes lesions. In addition to alcohol consump-
tion and smoking, data about the use of illicit drugs
(cannabis, cocaine, heroine, and amphetamines/ec-
stacy) were also collected. However, the use of these
drugs (vs. never use) showed no effect in the multi-
variate models with respect to HSV-1 infection or to
oral lesions and did not evidently change the other
odds ratios.
There are several limitations to this study. First of
all, the student population cannot be compared to the
general population of that age, because it is selected
towards a higher socioeconomic status. A potential
source of bias that was likely to exist at both study
sites was that students who are more interested in
health issues were more likely to participate in the
survey study. However, we do not think that this type
of selection bias has markedly influenced the ob-
served prevalence rates, since HSV-1 infection pre-
dominantly takes place in early childhood. Another
limitation is due to the fact that the self reports of
students were not independently verified. Therefore
misclassification cannot be ruled out. From a vali-
dation study measuring the accuracy of self-reported
smoking in university students at the University of
Bielefeld, we know that self-reports were quite reli-
able (sensitivity 88%, specificity 97%) [9], but this
result cannot be generalized to all self-reported data.
In conclusion, this study gave some new insight
into factors associated with HSV-1 infection and
symptoms of oral herpes. It was shown that the
pattern and course of infection was not different be-
tween young adults in Germany and Spain. While
sexual activity was associated with HSV-1 infection,
psychosocial stress and alcohol consumption were
associated with the occurrence of oral lesions.
Therefore, lifestyle factors appear to play an impor-
tant role in the epidemiology and clinical sequelae of
HSV-1 infection.
Acknowledgements
This study was supported by an educational grant
from Merck & Co., Inc, Whitehouse Station, NJ,
USA and by a grant from Departmento de la Salud
del Gobierno de Navarra, Spain. The authors thank
Mrs Sonja Wolff-Franke for conducting the labora-
tory work and all other members of the Navarra’s
Universities Cohort Study Group namely Dr Jose
Javier Vines Rueda
1
, Ms Inmaculada Serrano Mon-
zo
2
, Ms Concepcion Brun Sandiumenge
1
, Dr Lourdes
Sainz Suberviola
1
, Ms Carmen Garcia Alvero
1
,Ms
Carmen Arteta Garcia
1
, Ms Maria Gon
˜
i Arza
1
,Mr
Asier Pinillos Esparza
1
, Ms Ana Diaz de Rada
1
,Dr
Pedro Oviedo de Sola
4
, Mrs Guadalupe Arribas
2
,and
Dr Miguel Angel Martinez Gonzalez
3
.
References
1. Gil A, Gonzalez A, Dal-Re R, Ortega P, Dominguez V.
Prevalence of antibodies against varicella zoster, herpes
simplex (types 1 and 2), hepatitis B and A among
Spanish adolescents. J Infect 1998; 36: 53–56.
2. Wutzler P, Doerr HW, Fa
¨
rber I, et al. Seroprevalence
of herpes simplex virus type 1 and type 2 in selected
German populations – relevance for the incidence of
genital herpes. J Med Virol 2000; 61: 201–207.
3. Embil JA, Stephens RG, Manuel FR. Prevalence of
recurrent herpes labialis and aphthous ulcers among
young adults on six continents. Can Med Assoc J 1975;
113: 627–630.
4. Miller CS, Danaher RJ, Jacob RJ. Molecular aspects of
herpes simplex virus I latency, reactivation, and re-
currence. Crit Rev Oral Biol Med 1998; 9: 541–562.
5. Dalkvist J, Robins Wahlin T-B, Bartsch E, Forsbeck
M. Herpes simplex and mood: A prospective study.
Psychosom Med 1995; 57: 127–137.
6. Glaser R. Kiecolt-Glaser JK. Chonic stress modulates
the virus-specific immune response to latent herpes
simplex virus type 1. Ann Behav Med 1997; 19: 78–82.
7. Logan HL, Lutgendorf S, Hartwig A, Lilly J, Berberich
SL. Immune, stress, and mood markers related to re-
current oral herpes outbreaks. Surg Oral Med Oral
Pathol Oral Radiol Endod 1998; 86: 48–54.
8. Longo DJ, Clum GA, Yaeger NJ. Psychosocial treat-
ment for recurrent genital herpes. J Consult Clin Psy-
chol 1988; 56: 61–66.
9. Cohen S, Kamarck T, Mermelstein R. A global mea-
sure of perceived stress. J Health Soc Behav 1983; 24:
385–396.
10. Stock C, Wille L, Kra
¨
mer A. Gender-specific health
behaviors of German university students predict the
interest in campus health promotion. Health Prom Int
2001; 16(2): 145–154.
11. Ashley RL, Militoni J, Lee FK, Nahmias A, Corey L.
Comparison of Western blot (immunoblot) and glyco-
protein G-specific immunodot enzyme assay for de-
tecting antibodies to herpes simplex types 1 and 2.
J Clin Microbiol 1988; 26: 662–667.
12. Cowan FM, Johnson AM, Ashley R, Corey L, Mindel
A. Antibody to herpes simplex type 2 as serological
marker of sexual lifestyle in populations. Br Med J
1994; 309: 1325–1329.
13. Hashido M, Lee FK, Nahmias AJ, Tsudami H, Isom-
ura S, Nagata Y, Sonoda S, Kawana T. An epidemi-
ologic study of herpes simplex virus type 1 and 2
1
Department of Health Sciences, Navarra Public Univer-
sity.
2
School of Nursing, University of Navarra.
3
Department of Epidemiology, University of Navarra,
Medical School.
4
Department of Health, City of Pamplona.
889

infection in Japan based on type-specific serological
assays. Epidemiol Infect 1998; 120: 179–186.
14. Toba K. Seroepidemiology of herpes simplex virus in-
fections. In: Mori R, Kawana T (eds.) Infections with
herpes simplex virus. Tokyo: Medical Tribune, 1986,
161–172.
15. Conde-Glez CJ, Juarez-Figueroa L, Uribe-Salas F,
et al. Analysis of Herpes simplex virus 1 and 2 infection
in women with high risk sexual behaviour in Mexico.
Int J Epidemiology 1999; 28: 571–576.
16. Andersson-Ellstrom A, Svennerholm B, Forssman L.
Seropositivity to herpes virus type 1 and 2, cytomega-
lovirus and Epstein-Barr virus in teenage girls. Scand J
Infect Dis 1995; 27: 315–318.
17. Andria GM, Langenberg A, Corey L, Ashley RL,
Leong WP, Straus SE. A prospective study of new in-
fections with herpes simplex virus type 1 and type 2.
New Eng J Med 1999; 19: 1432–1438.
18. Lafferty WE, Downey L, Celum C, Wald A. Herpes
simplex virus type 1 as a cause of genital herpes: Impact
on surveillance and prevention. J Infect Dis 2000; 181:
1454–1457.
19. Laubereau B, Zwahlen M, Neuenschwander B, Heini-
ger U, Schaad UB, Desgrandchamps D. Herpes sim-
plex virus type 1 and 2 in Switzerland. Schweiz Med
Wochenschr 2000; 130: 143–150.
20. Glaser R, Kiecolt-Glaser JK, Speicher CE, Holliday
JE. Stress, loneliness, and changes in herpes virus la-
tency. J Behav Med 1985; 8: 249–260.
Address for correspondence: Christiane Stock, School of
Public Health, Public Health Medicine, University of Biele-
feld, P.O. Box 100 131, D-33501 Bielefeld, Germany
Phone: +49-521-1064257; Fax: +49-521-1062968
E-mail: cstock@uni-bielefeld.de
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