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Genital Herpes
Symptom |
Genital
Herpes Information
Genital
Herpes
Seroepidemiology of Genital Herpes / Herpes Simplex virus type 1
and 2 in Western and Southern Switzerland in
adults aged 25–74 in 1992–93 : a population-based
study
Dominique Bünzli1 , Vincent
Wietlisbach3 , Fabrizio Barazzoni4 , Roland Sahli1 and Pascal RA
Meylan1 ,2,
1Institut de Microbiologie, CHUV,
Lausanne, Switzerland,
2Service des Maladies Infectieuses, CHUV,
Lausanne, Switzerland,
3Institut Universitaire de Médecine
Sociale et Préventive, Lausanne, Switzerland,
4Ente Ospedaliero Cantonale, Bellinzona,
Switzerland,
BMC Infectious Diseases 2004, 4:10 doi:10.1186/1471-2334-4-10 © 2004 Bünzli et al; licensee
BioMed Central Ltd. This is an Open Access article:
verbatim copying and redistribution of this article
are permitted in all media for any purpose, provided
this notice is preserved along with the article's
original URL.
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Genital
Herpes Information part 3 |
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Discussion
In the present study,
data regarding the prevalence of HSV-1 (Herpes
Simplex Virus type 1) and, more importantly
HSV-2, have been obtained for the first time
from a multistage probability sample of the general
population in two regions of Switzerland. Generating
a population-based repository is a complex and
costly task; however only such a repository provides
information on the prevalence and allows to analyze
predictors for infection in the general population.
Indeed, few studies of Herpes Simplex Virus seroprevalence
have used such repositories [16,25,26].
Most of the published seroprevalence data have been
from selected groups of populations [2].
The
present serum repository was harvested in the
framework of a population-based study of
cardiovascular risk
factors: as such, our study has several limitations.
First, the low participation rate (53%) of the
population survey in the Vaud-Fribourg region
challenges the representativeness of the data. While
lower than participation in a similar major study,
the availability of the majority of the sera led to
51% of the sample having a serostatus determined,
versus 60.2% in the NHANES III study [16].
In addition, the results have been weighted by sex
and age to adjust for participation bias. Second,
because of its limited age range (25 to 74), the
study does not provide information about the HSV
prevalence rates among children and adolescents.
Third, the serum repository was harvested during a
single cross-sectional survey in the early nineties
and time trends in Herpes Simplex Viruses seroprevalence in
Switzerland cannot be monitored using these data.
Fourth, sampling occurred in only two (French and
Italian-speaking) regions. Recent data from the
Zurich area using selected samples of population
however seem to indicate a similar high HSV-2
seroprevalence in the German-speaking area (S.
Lautenschlager, personal communication). Finally,
the questionnaire did not include questions
regarding sexual behaviour, precluding HSV
prevalence analysis for these variables.
Nevertheless, our study provides data interesting to
compare in particular with HSV-1 (Herpes
Simplex Virus type 1) and -2 seroprevalence data
gathered at about the same time in the US [16,31].
The figures obtained indicate that HSV-1
seroprevalence is very similar in Switzerland and in
the US, and varies similarly according to age, and
socio-economic variables. HSV-2
seroprevalence was somewhat lower in Switzerland,
with a very similar effect of age on prevalence. In
particular, in both populations, HSV-2
seroprevalence plateaus among middle age subjects
from the third to the sixth decade of life.
Interestingly, we observed
a
significant peak HSV-2 seroprevalence among
elderly men (65–74 year old). These are
subjects who were 15 to 24 year old during second
world war (in 1942–43). Although we are unaware of
any report of epidemics of
sexually
transmitted diseases in Switzerland at that
time, it is well know that social disruption related
to the war led to epidemics of STD elsewhere
in the world, even in areas not directly involved in
the conflict [32]. We therefore
wonder whether this observation is a sero-archeological
testimony of past changes in STD
epidemiology, i.e. increased STD transmission
in Swiss males fifty years before the survey was
conducted. Why this would not be paralleled by a
higher HSV-2 seroprevalence in females is
unknown. However, this epidemic might have been
preferentially transmitted to young males by a small
core group of promiscuous females (e.g.
prostitutes), which would be in number negligible
compared to the general population. These females
might also have been older than their sexual mates.
While
HSV-2 seroprevalence was similar in the US in
metropolitan and non urban counties [16],
our study allowed to analyse the relationship
between the size of the community (commune) of
residence and HSV-2 seropositivity probably
with a better resolution, and indeed demonstrates
that at the time of the survey, individuals, and
particularly women, living in rural areas and
villages had a significantly reduced risk of
HSV-2 infection.
The
marital status had a similar influence on HSV-2
seroprevalence in the US and in Switzerland,
suggesting that being separated/divorced or widowed
is associated with a higher risk of infection. In
contrast,
the relationship between the socio-economic status,
as expressed here by the education level, and
HSV-2 seropositivity was opposite particularly
in women in the Switzerland compared to the
US, [16,33] and
indeed to other countries [26,34].
This contrasts also with the inverse correlation
between HSV-1 seroprevalence and
socio-economic level in our study, a well known
worldwide observation [2]. In the
absence of information regarding determinants of
exposure to
sexually transmitted diseases in our
database, we attempted to explain this paradoxical
relationship, by resorting to data in an unrelated
study performed in 1992–94 and assessing sexual
behaviour in relation with sociodemographic
variables in the same area (Western Switzerland)
where our study was performed [35].
By re-analysing these data, we could evidence a
positive correlation between education level and the
life time number of sex partners which almost
reached significance in female subjects. However, no
such correlation was observed in males. In fact
HSV-2 seroprevalence in our study is the result
of transmission events that occurred over several
decades before the serum collection. We interpret
this observation as consistent with the hypothesis
that in Switzerland, the liberal changes in the
sexual behaviour that occurred during these decades
have had more of an impact on the higher social
strata. Interestingly, a similar trend, though not
statistically significant, was recently described in
a similar population-based study in France [25].
There
is a continuum in the extent to which the spread of
various STDs require very high rates of
partner change and unprotected exposure to new
partners [36]. Those that appear
not to require high rates of partner change include
HSV and HPV, are less concentrated in core
groups, compared to bacterial STDs and more
widely spread across a variety of socio-economic
categories in populations [36].
Our data demonstrate that HSV-2 transmission
is not only spread across a large variety of
socio-economic categories, but, under given
conditions, can concentrate among strata of
populations usually at lower risk for STDs.
The potential impact of our observation for the
design of future prevention campaigns against STDs
remains to be evaluated.
Among
women who had been pregnant within twelve months
before participating to the study, a little more
than 9% were seropositive for HSV-2. They
were thus at risk for genital herpes reactivation
which carries a moderate risk for neonatal herpes
[37]. On the other hand, close to
30% were seronegative for HSV-1, (the cause
for about 50% of primary genital infections
in Switzerland [6] and in Europe [7,38])
and 90% were seronegative for HSV-2. These
were thus at risk for a primary infection with the
corresponding virus, a condition associated with a
very high risk of neonatal herpes [37].
Our data thus provide an estimate of the population
at risk for transmitting herpes to neonates.
The actual incidence of neonatal herpes,
which obviously varies with the rate for acquiring
genital herpes
during the third trimester of the pregnancy, a rate
unknown in Switzerland, is currently determined in a
countrywide prospective surveillance for neonatal
herpes in the framework of the Swiss Pediatric
Surveillance Unit.
Interaction between HSV-1 and HSV-2
remains a contentious issue. While it is generally
admitted that patients with antibodies against
HSV-1 and -2 are less likely to report a
symptomatic genital herpes compared to
patients with antibodies against HSV-2 only [4,31,39],
it is less clear whether antecedent HSV-1
infection can protect against subsequent HSV-2
acquisition. On one hand, cross-sectional studies
using type-specific immunoassays have suggested that
HSV-1 afford such a protection against
subsequent HSV-2 infection, with an odd ratio
of 0.7 among women attending family planning clinics
[33], 0.78 in STD clinic
attendees in California [40] and
of 0.37 among Mexican prostitutes [41].
On the other hand, Xu et al. recently did not detect
any significant protection neither in males nor in
females in the general US population [31].
Similar data were reported recently in a population
of Dutch STD clinic attendees, but the effect
of HSV-1 on HSV-2 seropositivity rate
was not analyzed by sex [42]. This
question has also been examined in the framework of
prospective studies measuring the rate of HSV-2
transmission among serodiscordant couples. For
instance, Mertz et al. [13] and
Bryson et al. [43] evidenced
a reduced
rate of acquisition of HSV-2 infection in
partners with previous HSV-1 infection
as compared to HSV-1-uninfected partners. In
contrast, no such protective effect of HSV-1
infection was observed in pregnant women followed up
prospectively [44] nor in HSV-2
seronegative sexually active participants to vaccine
trials followed up prospectively [4].
As
discussed recently [31], our study
is admittedly not ideally suited for the study of
the interaction between HSV-1 and HSV-2
because the data are cross-sectional. However, the
difference in transmission mode between these two
viruses results in HSV-1 preceding HSV-2
infection in a vast majority of cases [1],
raising the possibility that antecedent HSV-1
infection may affect the susceptibility to, or the
clinical expression of, HSV-2 infection.
In the
present study, HSV-1 seropositivity, when
introduced in the multivariate logistic model, was
associated with protection against HSV-2
infection, significantly so in women.
However, for a protection against an infection to
appear in a given population, this population has to
be exposed. Using a decision analysis procedure, our
study population was stratified by sex in five
strata from the lowest to highest risk of acquiring
HSV-2 infection, based on identified
predictors other than HSV-1 seropositivity.
The HSV-2 seropositivity rate was most
strikingly reduced by HSV-1 seropositivity
among women at the highest risk for HSV-2
infection.
Our
results are thus consistent with the hypothesis that
HSV-1 can prevent the acquisition of
subsequent HSV-2 infection, and that this
effect can be observed primarily among heavily
exposed individuals, i.e. women highly exposed to
HSV-2. Our observations may therefore explain
why this protective effect is not universally
observed in studies, depending on the study
population exposure to HSV-2 infection. It is
interesting to speculate why protection was observed
only in women, reminiscent of the recent observation
that a gD2-based vaccine demonstrated efficacy
against infection limited to women).)[45].
First, the risk of transmission is higher from males
to females than from females to males [46],
making it easier to demonstrate protection in
females than in males. Second, if protection is
afforded by locally produced antibodies, then a
mucous membrane covered by fluid containing
antibodies such as the female genital mucosa is more
likely to be protected than dry skin.
In addition, it is
interesting to note the recent epidemiological trend
for a reduced acquisition of HSV-1 during
childhood, leading to an increasing sexual
transmission of HSV-1 [5,42].
Therefore, assuming that HSV-1 precedes
HSV-2 infection may become less valid an
assumption in the future.
Conclusions
The present study
provides a snapshot view of the epidemiology of
Herpes simplex viruses in the Western and
Southern Swiss population in the early nineties.
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Assuming that the Herpes Simplex
Viruses type 2 (HSV-2) seroprevalence is similar
throughout Switzerland as supported by recent
studies in the Zurich area (S. Lautenschlager,
personal communication), a projection suggests that
countrywide, about 500'000 out of 2'633'000 people
aged 35 to 64 in 1992 were infected by HSV-2.
Risk factors for HSV-2 infections were
identified as age, marital status (separated,
divorced or widowed), residence in towns of middle
to large size, and paradoxically, higher education
in women. Herpes Simples Viruses type 1 infection was associated with
a lower HSV-2 seroprevalence particularly in
HSV-2 exposed women. These data are important
for the design of public health interventions aimed
at preventing
genital herpes spread. As sexual behavior
surveillance studies have shown increased condom use
without changes in other indicators, predicting the
course of HSV-2 epidemic beyond 1992–3 is
difficult. Hence, follow up studies in Switzerland
should include, in addition to surveillance for
neonatal herpes, a repeated population-based
study to assess any temporal trend in HSV
seroprevalence. |
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List of abbreviations
HSV: Herpes Simplex
virus, HPV: human papilloma virus, MONICA:
Monitoring trends and determinants in Cardiovascular
disease, ELISA: enzyme linked immuno sorbent assay,
STD: sexually-transmitted disease
Competing interests
Pascal Meylan is
consultant for GlaxoSmithKline, which commercialises
drugs for the prevention and treatment of herpes
viruses infection. He has received fees and
funding. Attracting attention to this problem may
boost drug sales.
Authors' contributions
DB performed the
serological testing, VW is responsible for the
MONICA database and did the statistical analysis of
the main study, FB organized the MONICA study in
Ticino, RS supervised the serological testing and
PRAM designed and coordinated the study and wrote
the manuscript. All authors read and approved the
final manuscript.
Acknowledgements
We thank the staff of
the serology laboratory for invaluable help and
Martin Rickenbach for help in providing access to
the serum repository.
This work was supported
by a grant from the Swiss Federal Office for Public
Health #01.000428, by GlaxoSmithKline Switzerland,
Novartis Switzerland, Focus Technologies, Cypress,
CA 90630 USA and by Pharma Consulting Marion Senn
GMBH, Burgdorf, Switzerland
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Transfer Factor
can
strengthen your immune cells (NK cells) by educating them to
recognise harmful invasion to your body, remember
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