201

SHORT REPORT

Seroprevalence of HSV-1 and HSV-2 infection in the

general French population
J-E Malkin, P Morand, D Malvy, T D Ly, B Chanzy, C de Labareyre, A El Hasnaoui,
S Hercberg
.............................................................................................................................

Sex Transm Infect 2002;78:201–203

ogy of HSV infection and recent improvements in available

Background: In spite of the large prevalence and tests allow discrimination between HSV-1 and HSV-2.
growing incidence of herpes simplex infection (HSV-1 and Here, we report the results of the HERPIMAX survey, which
HSV-2), relatively few large serological surveys are was the first epidemiological assessment of HSV prevalence
available worldwide and it is still difficult compare carried out in France in the general population.
frequencies of HSV contaminations in various countries.
We present the results of HERPIMAX, the first epidemiologi- METHODS
cal inquiry on HSV prevalence in the general French popu- Study population
lation. The survey population was a random sample of the
Methods: Of a cohort of 12 735 presumed healthy adult SU.VI.MAX programme, which was primarily a French
volunteers included in the prospective study SU.VI.MAX, prospective, randomised, double blind study designed to
designed to assess the relation between nutritional supple- assess the impact of a daily supplementation in minerals and
mentations and degenerative diseases, HERPIMAX ran- vitamins to reduce the frequency of degenerative diseases
domly selected 4412 subjects (females 66.5%, males such as cancers or cardiovascular diseases.5 SU.VI.MAX
33.5%). All serum samples were assessed for HSV-1 and included 12 735 presumed healthy volunteers of each sex,
HSV-2 IgG antibodies with a HSV type specific, enzyme aged between 35 and 60 years (females) or 45 and 60 years
immunosorbent assay (EIA). Equivocal result were retested (males), representative of the geographical and socioeconomic
with another HSV type specific immunoblot assay status of the French population.
combined with a type common HSV IgG EIA in order to Of the SU.VI.MAX population, 4412 people were randomly
give a definitive interpretation. selected and included into the HERPIMAX survey; 33.5% of
Results: The mean seroprevalence was 67% for HSV-1 them were male and 66.5% were women, this imbalance being
and 17.2% for HSV-2. For HSV-2 the seroprevalence was ascribable to the difference in age groups included according
higher in females (17.9%) compared with males (13.7%) to sex. The serum samples used in this survey were collected
(p <0.001). For both HSV types, there was no significant during the year 1996 and stored at −20°C until use at inclusion
difference in prevalence as regards age distribution in in SU.VI.MAX. Informed consent was obtained from all indi-
males and females, whereas prevalence increased signifi- viduals.
cantly with age in females for HSV-1. Univariate analysis
showed a significant association between HSV-1 preva- Serological testing
lence and education level in males and females (p Serum testing was performed in two different laboratories
<0.001) and between HSV-2 prevalence and marital according to the same procedures (Institut A Fournier, Paris;
status in both sexes (p <0.001). There were geographical Laboratoire de virologie, CHU, Grenoble, France) and the sam-
disparities, with a higher HSV-2 prevalence in the south of ples were randomly distributed between both of them. Serum
France as well as in Paris. samples were first screened with a commercial HSV type spe-
Conclusion: These results confirm a high prevalence of cific enzyme immunosorbent assay (EIA) (Gull HSV gG-EIA,
HSV infection in France. They are also in agreement with Gull Laboratories Salt Lake City, UT, USA). Equivocal serum
previous results of other survey carried out in other devel- samples (with absorbance values between 0.91 and 0.99 times
oped countries as regards higher prevalence of HSV-2 the value for the reference) were then tested with the type
infection in women, the stability of seroprevalence for both common HSV IgG EIA Enzygnost (Dade Behring). A negative
HSV types after 35 years of age in females and 45 years result to this latter test was interpreted as reflecting lack of
of age in males. HSV infection. A positive or equivocal result led to a confirma-
tory test using an HSV type specific immunoblot (RIBA HSV
type 1/2 Strip Immunoblot Assay, Chiron Corporation, Emery-
ville, CA, USA). Those samples remaining untyped by this test
were definitely considered as negative.

H
erpes simplex virus (HSV) infections are quite common
throughout the world.1 Apart from the morbidity due to The sensibility and sensitivity of the two HSV type specific
symptomatic episodes, HSV infections may have severe tests have been demonstrated in previous studies.6 7
consequences in immunosuppressed hosts or neonates.2 Statistical analysis
Furthermore, genital ulcer disease due to HSV is a risk factor The χ2 test was used to compare the distribution of infected
for sexual acquisition and transmission of HIV infection.3 subjects according to their demographic characteristics. Single
Assessing the extent of HSV infections is notoriously difficult linear regression was used to identify predictors of HSV infec-
for a variety of reasons: in most countries, they are not notified tion related to socioeconomical status or geographical location
diseases, the majority of infected subjects are asymptomatic4 in France. Statistical analyses were performed with SAS
or unaware of their infection. However, since the 1980s, sero- software (SAS Institute, Cary, NC, USA). All reported values
logical methods have made it possible to study the epidemiol- are two sided.

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202 Malkin, Morand, Malvy, et al

Table 1 HSV-1 and HSV-2 seroprevalence in HERPIMAX by age group and sex (%)
35–40 years 40–45 years 45–50 years 50–55 years >55 years

HSV-1
Male – – 64.5 64.6 70.9
Female 58.8* 59.2* 66.4* 68.5* 74.7*
HSV-2
Male – – 12.5 14.2 15.0
Female 15.7 18.8 18.1 17.0 19.5

*p<0.01.

Table 2 HSV-1 and HSV-2 seroprevalence in HERPIMAX according to education

level and to marital status (%)
HSV-1 HSV-2

Male Female Male Female

No diploma or undergraduate 72.2 73.5 14.0 16.7

Graduate or postgraduate 62.5 61.1 13.5 19.0
p Value <0.001 <0.001 ns ns
Married 66.0 66.8 12.7 15.8
Single 64.8 54.0 20.4 24.9
Widowed/separated/divorced 68.4 62.9 23.7 25.6
p Value ns ns 0.001 0.001

RESULTS with the finding of the same studies showing a lower

Among the 4412 selected subjects the mean seroprevalence seroprevalence in single individuals than in married people.
was 67% for HSV-1 and 17.2% for HSV-2. According to sex the This discrepancy could be explained by the fact that the
seroprevalence was comparable in males (66.4%) and in HERPIMAX population does not include young age groups
females (65.0%) for HSV-1 but it was significantly higher in and therefore single individuals included in our study should
females (17.9%) than in males (13.7%) for HSV-2 (p < 0.001). have a greater lifetime sexual activity than single people
Although there was a slight increase with age in prevalence included in other studies. Likewise, the higher prevalence of
of both HSV-1 and HSV-2 infections, the differences between HSV-1 infection founded in people of low education level was
age groups did not reach statistical significance for males; for not an unexpected result either.12 Whereas the NHANES III
females, there was a significant increase for HSV-1 but not for survey showed that a less formal education was a predictor of
HSV-2. Within each age group, no significant sex effect was HSV-2 infection,8 our study did not found the same correlation
observed for HSV-1, whereas HSV-2 seroprevalence remained in France.
consistently higher in females compared to males (table 1). Finally, HERPIMAX suggests significant geographical dis-
Univariate analysis suggested inverse correlation between parities in HSV prevalence, with highest rates of HSV-2
HSV-1 seroprevalence and education level, the relation reaching infections being found in the south of France as well as in the
statistical significance (p <0.001) for both males and females. city of Paris.
Likewise, there was a marked association in both genders These geographical differences could be due to variations in
between marital status and HSV-2 prevalence (table 2), with a sexual behaviour: a previous study has shown that the presence
significantly higher prevalence in people living alone (single, of antibody to HSV-2 is a marker of sexual lifestyle.11 These vari-
widowed, separated, or divorced) (>20% in both sexes) ations in sexual behaviour could be related to cultural diversity
compared to people living in couples (<15%; p <0.001). and/or to the level of urbanisation (Paris area and south of
France are two of the most inhabited regions in France).
DISCUSSION Further analysis of these data will focus on correlations
The primary result of this survey is a demonstration of a high between serological status and the clinical expression of the
prevalence of HSV infections in French adults, with more than disease. Epidemiological research should also focus on the
two thirds of the population infected with HSV-1 and almost identification of additional predictors and the design of
one fifth with HSV-2. Nevertheless our study shows a preventive measures.
prevalence of HSV-2 infection lower in France (17.2 %) than in
United States (21.9 %) where a population based survey ACKNOWLEDGEMENT
(NHANES III) was performed during a period from 1988 to Gull and Chiron Laboratories provided kits for serological testing.
1994.8 This work was supported by a grant from GlaxoWellcome France.
HSV-2 prevalence appears significantly higher in women
than in men.This finding could be explained in part by a CONTRIBUTORS
transmission of HSV-2 much more efficient from men to CdL and AEH were responsible for raising the design of the study; PM,
women compared with from women to men and possibly by BC, and TDL did the serological analysis; DM and SHg conducted the
study and were responsible for statistical analysis; JEM coordinated
differences between women and men in sexual behaviour.9 the study and wrote the paper.
The stability of this prevalence after 35–45 years was also an
expected result which suggests that the first contamination .....................
mainly occurs within the first two decades of sexual life.10
Authors’ affiliations
Comparing with previous studies8 11 our results confirm a J-E Malkin, Centre Médical de l’Institut Pasteur, Paris, France
higher HSV-2 seroprevalence in widowed, separated, and P Morand, B Chanzy, Virology, Grenoble, France
divorced people than in married people, but are inconsistent D Malvy, Institut de Santé Publique, Bordeaux, France

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Seroprevalence of HSV infection in the French population 203

T Duong Ly, Institut Alfred Fournier, Paris, France 6 Eis-Hubinger AM, Daumer M, Matz B, et al. Evaluation of three
C de Labareyre, A El Hasnaoui, GlaxoWellcome, Marly-le Roi, France glycoprotein G2- based enzyme immunoassays for detection of
S Hercberg, ISTNA CNAM, Paris, France antibodies to herpes simplex virus type 2 in human sera. J Clin Microbiol
1999;37:1242–6.
Correspondence to: Dr Jean-Elie Malkin, Service de Pathologie Infectieuse 7 Groen J, Van Dijk G, Niesters HG, et al. Comparison of two
et Tropicale, Centre médical de l’Institut Pasteur, 211 rue de Vaugirard, enzyme-linked immunosorbent assays and one rapid immunoblot assay
75724, Paris cedex 15, France; [email protected] for detection of herpes simplex virus type 2-specific antibodies in serum. J
Clin Microbiol 1998;36:845–7.
Accepted for publication 7 March 2002
8 Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus
type 2 in the United States, 1976 to 1994. N Engl J Med
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