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


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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.
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Risk factors of herpes simplex type 1 (HSV-1) infection and lifestyle factors
associated with HSV-1 manifestations
Christiane Stock
, Francisco Guille
, Juan Hermoso de Mendoza
, Blanca Marin-
, Ines Aguinaga-Ontoso
& Alexander Kra
School of Public Health, University of Bielefeld, Bielefeld, Germany;
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
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.
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
Variables N %
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
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
In calculating proportions missing values were not
Odds ratios were calculated using multivariate logis-
tic regression analysis.
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
Association of HSV-1 antibody prevalence and risk
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
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
Independent variables OR
Sociodemographic variables
High school degree of mother 0.68 0.43–1.09 0.106
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
OR, adjusted for age, gender, place of residence and all
other variables listed in this table.
CI, 95% confidence interval.
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).
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
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
OR, adjusted for age, place of residence and all other
variables listed in this table.
CI, 95% confidence interval.
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.
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
, Ms Inmaculada Serrano Mon-
, Ms Concepcion Brun Sandiumenge
, Dr Lourdes
Sainz Suberviola
, Ms Carmen Garcia Alvero
Carmen Arteta Garcia
, Ms Maria Gon
i Arza
Asier Pinillos Esparza
, Ms Ana Diaz de Rada
Pedro Oviedo de Sola
, Mrs Guadalupe Arribas
Dr Miguel Angel Martinez Gonzalez
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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
... Another major contributor to triggering virus reactivation is the elevated levels of psychosocial stress [69,70]. A meta-analysis covering multiple psychosocial and emotional assessments reported reliable positive correlations between chronic stress and recurrence of HSV-1 infections with clinical symptoms [71]. ...
... In terms of the significance of HSV-1 trigger factors instrumental to herpes symptoms, the patient's age, sex, the environment of residency, or inappropriate lifestyle affecting health such as smoking, consuming alcohol, or taking illicit drugs were less likely to contribute when compared to perceived elevated levels of stress. There were unclear occurrences in multivariate study models and cross-sectional studies, with no conclusive evidence of the apparent association between these putative risk factors and RHL [69]. The commonly reported trigger factors are listed as Table 1. ...
Full-text available
Herpes labialis remains exceedingly prevalent and is one of the most common human viral infections throughout the world. Recurrent herpes labialis evolves from the initial viral infection by herpes simplex virus type 1 (HSV-1) which subsequently presents with or without symptoms. Reactivation of this virus is triggered by psychosocial factors such as stress, febrile environment, ultraviolet light susceptibility, or specific dietary inadequacy. This virus infection is also characterized by uninterrupted transitions between chronic-latent and acute-recurrent phases, allowing the virus to opportunistically avoid immunity and warrant the transmission to other vulnerable hosts simultaneously. This review comprehensively evaluates the current evidence on epidemiology, pathogenesis, transmission modes, clinical manifestations, and current management options of herpes labialis infections.
... Clinically, primary infection occurs as gingivostomatitis with high frequency during childhood and related to socioeconomic status [6]. HSV-1 enters the peripheral nervous system and establishes their latency there; recurrence of symptoms triggered by a proper stimulus as emotional stress, UV radiation, and immune deficiency [7]. Serious infection with HSV-1 can also lead to lethal encephalitis with significant morbidity and mortality and ocular infections that complicated with scarification and corneal blindness [8]. ...
... The represented results indicated that the haemagglutination activity of the lyngabyal lectin was 100% over a wide pH range (4)(5)(6)(7)(8), which revealed that the lyngabyal lectin is stable over wide pH values. However, the agglutination activity of lectin was inhibited at very low pH values (1, 2, 3) with 25% agglutinating activity and very high pH values (10, 11, and 12) with the agglutinating activity of 1.56% detected after neutralization (Fig. 4a). ...
In the present study, a novel lectin was purified from the newly isolated cyanobacterium, Lyngabya confervoides MK012409 and tested for its antiviral and anticancer activity. Out of 30 isolates, Mabroka-s isolate which identified as Lyngabya confervoides MK012409 showed the highest agglutination titer. Lyngabyal lectin showed the greatest haemagglutination activity with pigeon/rabbit erythrocytes with a minimum concentration of 2.4 μg/ml. Physical characterization of Lyngabyal lectin showed ability to keep the activity at a higher temperature up to 80 °C with stability over a wide pH range (4–8) as well as its stability toward chemical denaturants. Carbohydrate specificity test revealed that the sugar alcohols completely inhibited the lectin haemagglutination activity. The electrophoretic analysis revealed that the lyngabyal lectin is a 140 kDa composed of two 70 kDa subunits. Lyngabyal lectin was able to inhibit the proliferation of MCF-7 and Caco-2 cancer cell lines with IC50 values of 246 ± 0.17 and 376.4 ± 0.34 μg/ml, respectively. Lyngabyal lectin also showed virucidal activity against HSV-1 with EC50 of 167 ± 0.52 ng/ml and inhibited plaque formation in the HSV-1 infected Vero cells with EC50 of 84.94 ± 0.34 ng/ml. These findings emphasize the ability of the lyngabyal lectin to fight breast and colon cancer besides it represents a promising antiviral agent.
... 15 This is consistent with the theory that HSV can move from ruptured vesicles to intact mucosa or skin and cause new lesions. 16 If the vesicle fluid hits other areas, autoinoculation will occur. 1 Investigations to confirm the diagnosis of herpes infection are Tzanck smear, serology, viral culture, and polymerase chain reaction (PCR). ...
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Novia Tri Hasanah,1 Wahyu Hidayat2 1Oral Medicine Residency Program, Department of Oral Medicine, Universitas Padjadjaran, Bandung, Indonesia; 2Department of Oral Medicine, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Novia Tri Hasanah, Email This case highlights the role of stress as trigger factor of HSV-1 reactivation causing recurrent intraoral herpes mimicking herpes-associated erythema multiforme (HAEM). A 24-year-old female came with chief complaints of pain in the oral cavity followed by painful swallowing and fever. She admitted under stress due to family problems and also had insomnia for the last three years. Extra-oral examination revealed serosanguineous crusts on lips that were painful and easily bleed. Intra-oral examination showed the white-yellowish multiple and coalescent ulcers, irregular, and painful on the left and right buccal mucosa, upper and lower labial mucosa, dorsum of the tongue, the floor of the mouth, and oropharynx. The results of the Depression Anxiety and Stress Scale (DASS)-21 examination were moderate depression, extremely severe anxiety, and moderate stress. The results of the HSV-1 IgG examination before and after therapy were positive with titer > 200 U/mL. Pharmacological therapy included acyclovir 200 mg tablets, multivitamin, benzydamine HCl lozenges, 0.025% hyaluronic acid mouthwash, 0.9% NaCl, and 100% petroleum jelly. Non-pharmacological therapy included stress management such as self-encouragement and referral to consult with a professional. This therapy generated significant result. In conclusion, stress affects many systems in the body, including the oral cavity. Stress is one of the trigger factors for HSV-1 reactivation which can cause oral manifestation. Early detection of trigger factors is important for better treatment result.Keywords: stress, herpes infection, immunoglobulin, reactivation, case report
... We did not find a significant difference in HSV IgG seroprevalence between males and females or between Saudis and expatriates. On the other hand, the HSV-IgG seropositivity was significantly higher in married individuals, which agrees with Memish et al. and others [13,24,25]. ...
The epidemiology of herpes simplex virus (HSV) infections varies among populations depending on their demographic characteristics and exposure. This study describes the prevalence of HSV 1/2 IgG and IgM antibodies among individuals over a period of 5 years. A retrospective study was conducted to collect data on cases tested for HSV-1 and HSV-2 IgG and IgM antibodies for different medical conditions over five years between January 2014 and December 2018. 620 samples were tested for HSV 1/2 IgG and IgM during the study period. The total HSV seropositivity in the study population was 68% (422/620). The total seropositivity excluding children below 6 months of age was 65.3% (313/479). HSV-IgG seropositivity was significantly higher in married individuals (p<0.001, 95% CI 1.61–3.69). The HSV IgG seropositivity was significantly higher in children under the age of 6 months (N=109, 77.30%) than in children between 7 and 24 months old (27.6%) (Chi-square for linear trend, p<0.001), and it then tends to increase with age more than 24 months (Chi-square for linear trend, p=0.011). Eleven children showed laboratory evidence of recent HSV infection (6.2%) as indicated by HSV IgM antibodies and had diverse clinical conditions. HSV infection is highly prevalent in the Eastern Province of Saudi Arabia. Infection is most probably acquired during early childhood, and the tendency increases with age. However, a significant number of mothers are at risk of infection and transferring the infection to their fetuses.
... Nonetheless, the release of successful virus progeny, also known as virus shedding, continues to take place at this phase. [45,59] activity, hygiene, etc [74,76]. In Navarra Public University, Spain 596 students were observed and from University of Bielefeld, Germany 174 students were selected for the assay. ...
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Purpose: High prevalence of recurrent HSV-1 (Herpes Simplex Virus 1) and its facile mode of transmission requires an elaborated understanding of the virus for mollification. To mitigate its pervasive nature that greatly affects both men and women, a thorough understanding of the viral genome and epidemiology are prerequisites. The review focuses on the existing facts of HSV-1 and acknowledges the prospect of ongoing epidemiological studies. Findings: Recent data indicates a surge of HSV-1 infection in the age ranged 30-50 years along with the emergence of neonatal cases. The newfound receptors indicate the effect and degree of susceptibility of the host and support the statistical data of HSV-1 seropositivity. Recent studies also show that the evolving virus has gained resistance against widely used antiviral drugs such as Acyclovir (ACV). Therefore, trials of several vaccines (eg. GEN-003and HerpV) are garnering attention as a possible prevention method. Summary: As most natural viruses are radically evolving, ensuing rather fatal consequences than previous wild types, every virus requires to be tackled with equal importance. Developing vaccines and potent drugs to eradicate viruses from infected subjects' systems can be the only way to prevent future viral epidemics or pandemics. Therefore, early detection of the virus with accurate assay following immediate treatment can only prevent the cases from future catastrophe.
... Earlier studies showed that HSV seroprevalence was higher among sexual risk behavior groups [6,7] increasing along with the number of sexual partners [10,31]. Early age for first sexual intercourse has been associated with HSV-1 seropositivity among young individuals [32], which was, however, not shown in the present study. The overall small fraction of HSV-2 seropositive individuals in Finland was evident also in our HSV antibody results. ...
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The aim was to evaluate the herpes simplex virus (HSV) seroprevalence and seroconversion among 285 pregnant women and their 120 male spouses in Finland during a six-year follow-up (FU) between 1998–2008. We also studied the effect of sexual habits, pregnancy, and other demographic factors on the acquisition of HSV infection. Combined HSV-1 and HSV-2-IgG antibodies were assessed in the first baseline serum samples with an indirect enzyme immunoassay method. The individuals with seronegative or borderline HSV serology at baseline were additionally tested using their latest FU serum sample available. The overall HSV seroprevalence during the FU was 58.9% (168/285) among the women and 53.3% (64/120) among their spouses. The seroconversion rate was 11.4% (15/132) and 12.5% (8/64) among women and their spouses, respectively. Both spouses were HSV seropositive in 39.2% (47/120). To determine the HSV-2 seroprevalence, we also tested all HSV-seropositive participants using HSV-2-specific antigen. HSV-2 seropositivity was detected in 10.9% (44/405) of the participants. The age (p = 0.006) and history of genital warts (p = 0.006) of the women were associated with combined HSV-1 and/or HSV-2 seropositivity, while a younger age was related to HSV seroconversion (p = 0.023). Among the male spouses, HSV seropositivity was associated with the practice of oral sex (p = 0.033). To conclude, women of childbearing age acquire primary HSV infections and the presence of HSV in oral epithelium is common among HSV-seropositive individuals.
... Viral shedding during reactivation can result in the formation of lesions or might occur in the absence of clinically recognised symptoms (Gupta et al. 2008;Brady und Bernstein 2004). About 20% to 40% of patients, who are HSV-1 seropositive, will develop recurrent clinically recognised infections (Arduino und Porter 2008;Siegel 2002;Stock et al. 2001). The frequency of these recurrent infections varies between individuals, ranging from months to years with most patients suffering 2 or less outbreaks per year (Arduino und Porter 2008;Fatahzadeh und Schwartz 2007b). ...
Background: Viral skin infections are frequently seen in children and adolescents due to their developing immune system, while they are rarely seen in healthy adults Methods: This study investigated 39 adults with severe viral skin infections, including 18 with persistent warts and 21 with recurrent herpes infections. Investigations included, HPV typing and blood value analysis to describe the clinical and immunological features and define any underlying PID. The DLQI was used to understand whether and how viral skin infections impact patients`QoL, and a clinical questionnaire to explore the treatment modalities and responses was deployed. Results: In the wart cohort, nine patients were diagnosed with CVID, one with DOCK8- and one with IL7Ra- deficiency. Warts had effected the patients for a mean of 19 years with 50% having more than 20 warts, with the DOCK8- and the IL17Ra-deficiency patient having the highest number and severity. Patients tried six therapies with cryotherapy used most frequently and imiquimod the most successful. In the HPV DNA type analysis of wart samples, α-HPV was identified in 70% of samples, with 27 (36%), 57 (29%), and 28 (21%) the most common types. β-HPV was identified in all patients with 93 (64%), 8 (50%), and 24 (43%), being the most common types. In the herpes cohort, ten patients were clinically diagnosed with HSV, seven with VZV, four with no definite diagnosis, and none with an underlying PID. Genital herpes was experienced most frequently (52% of patients), followed by herpes orolabialis (48% of patients) and facial herpes (38% of patients). 81 % of the herpes patients were treated with prophylactic antiviral medication while the remaining took symptomatic medication. All patients reported having smaller lesions, a shorter outbreak duration and less severe symptoms since starting medication. Taking prophylactic aciclovir or valaciclovir achieved a significant reduction of outbreaks (70% and 80%). The DLQI scores indicated a large impact on patient’s QoL in the herpes outbreak cohort, and a small impact on patient’s QoL in the wart- and herpes no-outbreak cohort. All patients experienced physical and emotional impacts. Blood value analysis of the CVID patients with warts indicated a reduced or lacking IgA and IgM, low absolute CD4, CD8, CD19, and NK cell counts, a low percentage of CD19+ B cells, NK cells, and IgM memory cells; and in the majority of patients a reduced percentage of switched memory cells and CD4+ naive T cells. Both, the no-PID wart patients and the herpes cohort showed low percentages of NK cells while the herpes cohort, in addition, had a low percentage of CD4+ naive T cells, and a decreased IgM memory. Summary: This study investigated 39 adults with severe viral skin infections, including 18 with persistent warts and 21 with recurrent herpes infections. Warts Patients tried six therapies with cryotherapy used most frequently and imiquimod the most successful, however none was convincingly successful. 81 % of herpes patients were treated with prophylactic antiviral medication. Taking prophylactic aciclovir or valaciclovir achieved a significant reduction of outbreaks. The DLQI scores indicated a large impact on patient’s QoL in the herpes outbreak cohort, and a small impact on patient’s QoL in the wart- and herpes no-outbreak cohort. All patients experienced physical and emotional impacts. When Removing the CVID patients from analysis, laboratory evaluation of the wart and herpes cohort did not raise a suspicion of an underlying PID. However, the Low percentage of CD4+naive and NK cells might have contributed to the increased susceptibility to cutaneous viral infections.
... Terdapat populasi orang yang semakin berisiko pada saat mereka menjadi aktif secara seksual terkait dengan lebih sedikit orang yang terinfeksi di masa kanakkanak, sehingga menghasilkan proporsi yang lebih besar pada transmisi HSV-1 secara seksual. 22,23 Tabel 1 dan 2 menunjukkan prevalensi terendah di instalasi rawat jalan yaitu pasien dengan pendidikan terakhir universitas dan akademi (3,77%), demikian juga pada instalasi rawat inap bahkan tidak ditemukan pasien dengan pendidikan terakhir Universitas dan akademi. Hal ini berkaitan dengan semakin tinggi tingkat pendidikan seseorang maka pengetahuan serta kesadaran terhadap kesehatan juga semakin tinggi. ...
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Pendahuluan: Salah satu virus yang menginfeksi rongga mulut adalah Herpes Simpleks Virus-1 (HSV-1). Virus ini menjadi patogen utama pada berbagai macam inang dan dapat menyebabkan berbagai macam penyakit orofasial. Tatalaksana infeksi HSV-1 memiliki pola terapi yang beragam bergantung pada kondisi klinis pasien. Tujuan penelitian ini adalah memperoleh data mengenai pola dan terapi penyakit mulut karena infeksi HSV-1. Metode: Data yang dikumpulkan merupakan data sekunder berasal dari logbook dan rekam medik pasien di Poliklinik Gigi dan Mulut RSUP Dr. Hasan Sadikin Bandung periode 2013-2017. Sampel penelitian ditentukan menggunakan metode purposive sampling, yaitu rekam medik pasien dengan diagnosis penyakit mulut karena infeksi HSV-1. Hasil: Pola penyakit mulut pada instalasi rawat jalan yaitu Recurrent Intraoral Herpes (RIH) sebanyak 84,91%, Herpes Associated Erythema Multiforme (HAEM) 9,43%, Herpes labialis 3,77%, dan Primary Herpetic Gingivo Stomatitis (PHGS) 1,89%. Pola penyakit mulut pada rawat inap yaitu Recurrent Intraoral Herpes (RIH) sebanyak 85,71% dan Herpes labialis sebanyak 14,29%. Pemberian terapi sangat bervariatif yaitu kombinasi asiklovir, antiseptik, multivitamin, antiinflamasi steroid, NSAID, pelembab bibir, antibiotik, antihistamin, dan antifungal. Simpulan: Penyakit mulut karena infeksi HSV-1 yang paling sering ditemukan baik pada instalasi rawat jalan maupun rawat inap adalah recurrent intraoral herpes. Pemberian terapi yang paling sering digunakan pada instalasi rawat jalan yaitu kombinasi obat antiinflamasi steroid dan multivitamin, sedangkan pada instalasi rawat inap yaitu multivitamin dan kombinasi asiklovir, antiseptik, dan multivitamin.Kata kunci: Pola penyakit mulut, pola terapi, infeksi Herpes Simpleks Virus-1 ABSTRACTIntroduction: One of the viruses that infect the oral cavity is Herpes Simplex Virus-1 (HSV-1). This virus becomes the primary pathogen in various types of hosts and can cause various kinds of orofacial diseases. Management of HSV-1 infection has a diverse pattern of therapy depending on the clinical condition of the patient. The purpose of this study was to obtain data on the patterns and treatment of oral diseases due to HSV-1 infection. Methods: Data collected was secondary data from the logbook and medical records of patients at the Dental Polyclinic of Dr Hasan Sadikin Hospital Bandung in 2013-2017. The study sample was determined using a purposive sampling method, namely medical records of patients with a diagnosis of oral disease due to HSV-1 infection. Results: The pattern of oral disease in outpatient installations, namely Recurrent Intraoral Herpes (RIH) 84.91%, Associated Erythema Multiforme (HAEM) Herpes 9.43%, Herpes labialis 3.77%, and Primary Herpetic Gingivo Stomatitis (PHGS) 1.89%. The pattern of oral disease in inpatient installations, namely Recurrent Intraoral Herpes (RIH) as much as 85.71% and Herpes labialis 14.29%. Given therapy was very varied, namely a combination of acyclovir, antiseptic, multivitamin, anti-inflammatory steroid, NSAIDs, lip moisturisers, antibiotics, antihistamines, and antifungal. Conclusion: Oral disease due to HSV-1 infection that is most often found both in outpatient and inpatient installations is recurrent intraoral herpes. The most commonly used therapy in outpatient installations is a combination of steroid anti-inflammatory drugs and multivitamins, while in inpatient installations are multivitamins and a combination of acyclovir, antiseptic, and multivitamins.Keywords: Oral disease patterns, therapy patterns, Herpes Simplex Virus-1 infection
Objectives To identify factors which influence the intraoral prevalence of human herpes viruses using mucosal swabs, saliva samples and qPCR analysis. Methodology In this cross‐sectional observational study, matched saliva and oral swabs were collected from a total of 115 subjects: 70 immunocompetent subjects with no mucosal abnormalities, 22 with mucosal abnormalities and 23 therapeutically immunocompromised individuals. Extracted DNA was analysed by multiplex qPCR for detection and quantification of human herpes viruses 1‐6. Results At least one human herpes virus was detected in 77.1% of immunocompetent individuals with no mucosal abnormalities, with EBV the most commonly detected at 61.4%. HHV‐6 was detected in 17.1%, HSV‐1 in 4.3% and CMV in 1.1%. Detection was higher in saliva than in oral swabs. There was no detection of HSV‐2 or VZV. Neither presence of oral mucosal abnormality nor therapeutic immunocompromise was related to increased detection of human herpes virus. Conclusion Commensal detection rates of EBV are high and caution in clinical correlation of positive detection is warranted. Commensal CMV rates are low and detection is likely to be clinically relevant. This study presents a comprehensive commensal detection rate of human herpes viruses 1‐6 by qPCR in saliva and swabs.
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Sera from patients with culture-proven genital herpes infections were tested for herpes simplex virus type 1 (HSV-1)- and HSV-2-specific antibodies by both a Western blot (immunoblot) technique (WBA) and immunodot enzyme assays (IEAs) specific for HSV-1 or HSV-2 glycoprotein G (gG). Of 137 serum samples tested, none was mistyped by either WBA or IEA. Both tests were most sensitive with sera obtained at least 21 days after onset of primary HSV-2 infections or sera drawn during recurrent HSV-2 genital episodes: 75 of 76 (99%) such serum samples were positive for HSV-2 antibody by WBA and 73 of 76 (96%) were positive by IEA. Of sera drawn earlier than 21 days from onset of primary genital HSV-2, antibodies to HSV-2 were detected in 25% by WBA and 8% by IEA. In patients with culture-proven primary genital HSV-1 infection, WBA detected antibodies to HSV-1 proteins in 16 of 17 (94%) serum samples drawn at least 21 days after onset of primary genital HSV-1 infection, compared with 9 of 17 (53%) serum samples tested for gG-1 by IEA. Both WBA and IEA are accurate and sensitive tests for HSV-2 antibody in patients convalescing from a first episode or having symptomatic or asymptomatic recurrent genital herpes. WBA was more sensitive than IEA in detecting seroconversion following primary HSV-1 genital herpes, although both assays may miss persons undergoing early seroconversion to HSV-2.
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To examine the epidemiology of antibody to herpes simplex virus type 2 and to assess its suitability as a serological marker of sexual behaviour in populations with high and low prevalences. Cross sectional survey. Department of genitourinary medicine and blood donation centre in central London. Representative sample of 869 patients attending department between November 1990 and December 1991, and 1494 consecutive blood donors attending for donation between February and April 1992. Participants had a blood sample taken for antibody testing with a novel type specific assay and completed a questionnaire. Prevalence of antibody differed significantly between the two groups (188/833 (22.7%) clinic attenders; 102/1347 (7.6%) blood donors). In both populations antibody was strongly associated with sex, sexual orientation, years of sexual activity, number of lifetime sexual partners, and past infection with sexually transmitted diseases after other factors were controlled for. Only 130 (45%) of all those with antibody had symptoms suggestive of genital herpes, and 79 (27.4%) had had genital herpes diagnosed. Of those without antibody to herpes simplex viruses type 1 and 2, 8.0% reported genital blisters or sores and 1.1% had had genital herpes diagnosed by a doctor. The strong relation between herpes simplex virus type 2 and sexual lifestyle suggests that the presence of antibody to the virus may be suitable for use as an objective, serological marker of patterns of sexual behaviour in different populations. These data show that only a minority of those infected with herpes simplex virus type 2 have a diagnosis of genital herpes or express clinical symptoms, making serological determinants of infection essential for epidemiological studies.
The aim of this cross-sectional study was to assess the seroprevalence of antibodies against varicella zoster (VZV), herpes simplex type 1 (HSV-1) and type 2 (HSV-2), hepatitis B (HBV) and hepatitis A (HAV) viruses in adolescents (14-17 years of age) in Madrid, Spain. At the study visit, demographic data and blood samples were obtained. The enzyme linked immunosorbent assay (ELISA) method was used to assess the presence of anti-VZV, anti-HSV-1, anti-HSV-2, anti-HBc and anti-HAV antibodies. A total of 1191 serum samples were collected. Mean age (SD) and male/female ratio of the study population were 15.3 (1.1) years and 0.9, respectively. Seroprevalences obtained were as follows: anti-VZV (94%), anti-HSV-1 (46%), anti-HSV-2 (5%), anti-HBc (3%) and anti-HAV (5%). These data show that Spanish adolescents should be considered a target group for prevention programmes against HSV-2, HBV and HAV infections.
The prevalence of recurrent herpes labialis (RHL) and recurrent aphthous ulcers (RAU) in young adults - - 635 armed-forces recruits and 9897 health-profession students - - in 48 institutions in 21 countries was determined by a questionnaire survey. Two or more occurrences (lifetime prevalence) of RHL were reported by 33.2% of men and 28.0% of women; the corresponding figures for RAU were 38.7% and 49.7%. North American respondents, mainly from Canada, had a significantly higher prevalence of both lesions. There were some differences in relation to profession. Approximately 15% of all the people surveyed had had herpes labialis and 25% had had aphthous ulcers at least once during the previous year. Persons with a history of recurrence of one lesion were more likely to have a history of recurrence of the other.
This study used a prospective design to examine the influence of examination stress and loneliness on herpesvirus latency as measured by changes in antibody levels to three herpesviruses, Epstein-Barr virus (EBV), Herpes simplex type I (HSV-1), and cytomegalovirus (CMV). Three blood samples were obtained from 49 first-year medical students, with the first sample drawn 1 month before final examinations, the second on the first day of final examinations, and the third during the first week after their return from summer vacation. A median split on the UCLA Loneliness Scale divided subjects into high- and low-scoring loneliness groups. There were significant changes in the antibody titers to all three herpesviruses across the sample points, with the lowest levels found in the third (low stress) sample. High-loneliness subjects had significantly higher EBV antibody titers than low-loneliness subjects. These data suggest that stress-related immunosuppression can significantly modulate herpesvirus latency.
Thirty-one individuals with recurrent genital herpes were randomly assigned to one of three conditions: psychosocial intervention, social support, or waiting-list control. Each treatment condition contained two 5-member groups, and the waiting-list condition contained 11 members. Six consecutive weekly 90-min group treatment sessions were conducted for subjects in the first two conditions, whereas those in the waiting-list control condition were offered treatment at follow-up. Subjects in psychosocial intervention were provided with herpes simplex virus (HSV) information, relaxation training, stress management instructions, and an imagery technique. The social support groups shared feelings and experiences about the disease and served as placebo control subjects. Individuals receiving psychosocial intervention reported significantly greater reductions in herpes activity and significant improvements on emotional distress, social support, and cognitive measures when compared with the other individuals. It was concluded that psychosocial intervention effectively reduced the chronicity of recurrent HSV infections and facilitated adjustment to the disease. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
This paper presents evidence from three samples, two of college students and one of participants in a community smoking-cessation program, for the reliability and validity of a 14-item instrument, the Perceived Stress Scale (PSS), designed to measure the degree to which situations in one's life are appraised as stressful. The PSS showed adequate reliability and, as predicted, was correlated with life-event scores, depressive and physical symptomatology, utilization of health services, social anxiety, and smoking-reduction maintenance. In all comparisons, the PSS was a better predictor of the outcome in question than were life-event scores. When compared to a depressive symptomatology scale, the PSS was found to measure a different and independently predictive construct. Additional data indicate adequate reliability and validity of a four-item version of the PSS for telephone interviews. The PSS is suggested for examining the role of nonspecific appraised stress in the etiology of disease and behavioral disorders and as an outcome measure of experienced levels of stress.
The effect of mood, the common cold, amount of sleep, and sunshine on recurring herpes simplex virus (HSV) infection was investigated using daily self-reports over a 3-month period from 23 female and 15 male patients with genital herpes and 26 female and two male patients with oral herpes. Results showed recurring genital HSV infection to be preceded by reduced and decreasing overall emotional well being over a period of 10 days, with a temporary improvement in the middle of the period. This pattern was significantly represented by rated nervousness and rated alertness. Females showed more marked trends for reported mood than did the males, which could not be attributed to the menstrual cycle. Conversely, males showed a more marked, strongly significant fourth-order trend for reported amount of sleep, with nadirs on the 8th and the 3rd day before the recurrence. Neither exposure to sunshine nor the common cold showed any relation to recurrence of genital HSV infection. The common cold appeared as the major precipitating factor in oral herpes. Except for a significant fourth-order trend for rated alertness, no relationship between mood and subsequent onset was found. This negative finding was interpreted as a masking effect of the common cold. Two alternative physiological theories, the ganglion trigger theory and the skin trigger theory, were discussed in relation to present findings. It was suggested that various possible mediators between mood states and recurring herpes should be investigated using the present approach, with structured diaries as complement to the rating scales.