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Expression of concern regarding paper by Park et al, published on 25 June 2015: “Epidemiological investigation of MERS-CoV spread in a single hospital in South Korea, May to June 2015”, Euro Surveill. It has been brought to our attention that some of the authors may not have been informed about the content of the above paper. Citation style for this article: Sauerbrei A, Schmitt S, Scheper T, Brandstadt A, Saschenbrecker S, Motz M, Soutschek E, Wutzler P. The prevalence of herpes simplex virus (HSV) type-specific IgG was determined in sera taken in 1999 to 2006 from 1,100 children aged 0–18 years, 800 blood donors and 200 pregnant women in Thuringia, Germany, using tests based on the HSV glycoproteins (g) gG. Herpes simplex virus (HSV) is one of the most common pathogens affecting humans: it can remain latent lifelong in sensory ganglia and can be reactivated periodically. Excretion of the virus from herpetic lesions (mainly lips and genitals) in symptomatic people with recurrent infections and excretion of the virus in the saliva and genitals of asymptomatic people are regarded as the most important source of the virus [2]. Unlike HSV-1, HSV-2 is predominantly acquired through sexual activity [3] and causes the great majority of genital herpes [4]. HSV type-specific seroprevalence has been extensively studied in many countries all over the world.
The envelope glycoproteins (g) G of HSV-1 (gG-1) and HSV-2 (gG-2) are known to be type-specific antigens [14] and have been used in nearly all conclusive HSV-1 and HSV-2 seroprevalence studies [3].
As there are few data on the prevalence of HSV antibodies in Germany, we carried out a seroepidemiological study to determine the HSV-1 and HSV-2 antibody prevalence in children, adults and pregnant women in the German federal state of Thuringia. In this study, 1,100 sera from infants, children and adolescents aged 0 to 18 years, (hereafter referred to as children aged 0 to 18 years), 800 sera from blood donors aged 19 to 30 years and 200 pregnant women aged between 17 and 40 years were included. For the blood donors and pregnant women, informed oral consent for use of their sera was obtained. Samples from those aged 18 years or under lived in Erfurt, the capital of Thuringia, and its rural surroundings. Serum samples from the pregnant women were taken from those who delivered at their local district hospital (in Thuringia) between January 1999 and January 2000. Sera were stored in aliquots at –20 °C without interruption until tested for antibodies to HSV-1 and HSV-2. All samples with discordant results in the gG-1 and gC-1 ELISAs were retested twice and the most frequent result (including the original test result) was accepted. A sample size of about 150 subjects per pre-specified age group was planned to assure that a two-sided 95% confidence interval (CI) for the prevalence of HSV antibodies would extend at most 8% from the observed value for a prevalence range of 5–95%. Antibody prevalence was calculated using the number of seropositive cases divided by the number of all subjects tested. The amount of agreement between gG-1 and gC-1 ELISAs was computed using the number of sera with concordant results divided by the number of sera tested.
Data on the prevalence of IgG antibodies against HSV-1 in the samples tested are shown in Table 1. The Figure shows the age- and sex-specific prevalence of HSV-1 IgG in the children and adults (blood donors) tested. Of the 2,100 sera tested in this study, 71 showed equivocal results in either of the HSV-1 ELISAs after having been repeated twice and were excluded from the comparison of both ELISAs. Of the 32 sera that gave equivocal results in the HSV-2 gG ELISA, after having been repeated twice, 28 were negative by immunoblot assay (Table 3). After retesting of sera that were positive in the HSV-2 gG-2 ELISA (n=201), 191 (95%) were also positive in the HSV-2 immunoblot.
Seroprevalence studies of HSV-1 and HSV-2 are vital for a better understanding of the public health importance of disease due to HSV. As expected, the prevalence of antibodies against HSV-1 and HSV-2 was significantly lower in children and adolescents than in adults; however, for HSV-1, this concerned children only up to the age of 15 years. A considerable delay of HSV-1 infection during childhood has been reported from Finland, where only 17% of children at the age of eight years had antibodies to HSV-1 [21].
In our study, adults (blood donors) aged between 19 and 30 years had an HSV-2 seroprevalence of 13.6%. Our finding of a higher seroprevalence of HSV-2 among women than among men is in agreement with several other studies [10,30,31]. Disclaimer: The opinions expressed by authors contributing to Eurosurveillance do not necessarily reflect the opinions of the European Centre for Disease Prevention and Control (ECDC) or the editorial team or the institutions with which the authors are affiliated. Seroprevalence of herpes simplex virus type 1 and type 2 in Thuringia, Germany, 1999 to 2006. In persons with past primary HSV-1 infection, the risk of acquiring HSV-2 is probably reduced since most antibodies cross-react between HSV-1 and HSV-2 [5]. Seroprevalence rates of HSV-1 of between 50% and 85% or more have been shown in adults from developed countries, such as Germany, Spain and Norway, in the last two decades [3,10].
Recently, gC-1 was shown to be an equivalent antigenic target for type-specific diagnosis of HSV-1 infections [15].
For detection of HSV-1-specific antibodies, results from two enzyme-linked immunosorbent assays (ELISAs) based on the detection of gG-1 or gC-1 were compared for 2,100 serum samples collected during 1999 to 2006. These samples had been taken for routine serological tests, for example, medical check-ups or determination of immune status, during 1999 to 2006.


Those that still gave equivocal results after retesting were analysed using immunoblot recomLine HSV-1 & HSV-2 IgG, as were all sera that were positive, to avoid false-positive results, as results from other studies suggests that HSV-2 ELISAs may results in false-positive results [17].
Adjusted for age, the prevalence of HSV-1 antibodies among girls aged between 0 and 18 years was significantly lower than among boys of the same age (p=0.039).
Adjusted for age, a significantly higher prevalence of HSV-2 IgG in women than in men was detected (p=0.021).
In this study, we were particularly interested in determining the HSV seroprevalence of children up to the age of 18 years, since there is little known about this. After the disappearance of maternal antibodies in the first year of life, there was an increase in HSV-1 IgG prevalence to 20% by the age of 2–3 years, to 40% by 4–6 years, to almost 60% by 10–12 years, to 70% by 16–18 years and to about 80% by the age of 28–30 years. Surprisingly, the prevalence of HSV-1 antibodies among girls was lower than among boys in our study. In those aged 16–18 years, the prevalence increased to 7.3%, indicating a rising incidence of primary HSV-2 infections, probably due to the start of sexual activity. There was a significantly higher prevalence of HSV-2-specific antibodies among women (16%) than among men (11%) and in pregnant women, the prevalence was 18%.
This may result from the differential role of sex on clinical presentation since men appear to have a higher tendency of asymptomatic HSV-2 infection [30]. A recent study revealed that gC-1 and gG-1 may be comparable antigenic targets for the serodiagnosis of HSV-1 infections [15].
Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. Genital herpes simplex virus type 1 in women: detection in cervicovaginal specimens from gynecological practices in the United States. Common use of inaccurate antibody assays to identify infection status with herpes simplex virus type 2. Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection.
Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Herpes simplex virus: incidence of neonatal herpes simplex virus, maternal screening, management during pregnancy, and HIV.
Seroprevalence of herpes simplex virus type 1 and type 2 in selected German populations-relevance for the incidence of genital herpes. Early acquisition of herpes simplex virus type 1 antibodies in children–a longitudinal serological study.
Antigenic differences between HSV-1 and HSV-2 glycoproteins and their importance for type-specific serology. The glycoproteins C and G are equivalent target antigens for the determination of herpes simplex virus type 1-specific antibodies.
Die (Weiter-) Verwendung von menschlichen Korpermaterialien fur Zwecke der medizinischen Forschung (2003) [The (further) use of human body samples for the purpose of medical research (2003) English translation of the title].
Prevalence of herpes simplex virus types 1 and 2 among children and adolescents attending a sexual abuse clinic.
Development of antibodies against cytomegalovirus, varicella-zoster virus and herpes simplex virus in Finland during the first eight years of life: a prospective study. National seroprevalence and trends in herpes simplex virus type 1 in the United States, 1976-1994.
Prevalence of antibodies against herpes simplex virus types 1 and 2 in children and young people in an urban region in Tanzania.
Herpes simplex virus infection in pregnancy and in neonate: status of art of epidemiology, diagnosis, therapy and prevention.
Seroprevalence study of herpes simplex virus type 2 among pregnant women in Germany using a type-specific enzyme immunoassay. The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes. Premarket evaluation of a commercial glycoprotein G-based enzyme immunoassay for herpes simplex virus type-specific antibodies. Comparison of four enzyme immunoassays with a western blot assay for the determination of type-specific antibodies to herpes simplex virus. Novel recombinant ELISA assays for determination of type-specific IgG antibodies against HSV-1 and HSV-2.
Neither ECDC nor any person acting on behalf of ECDC is responsible for the use that might be made of the information in this journal. There are two types, HSV-1 and HSV-2, which differ not only genetically but also in the principal route of transmission, the body site predominantly affected, seroprevalence and rate of reactivation [1].
Although no clinical signs can be recognised in many people with HSV-2 infections, as is also the case for HSV-1 infections, asymptomatic people can shed the virus, and thus there is a substantial risk of viral transmission to their sexual partners [6]. For HSV-2, seroprevalence varied as a function of age, sex, number of lifetime sexual partners and socio-economic status [3,10]. For all people whose samples were included, the clinical or laboratory data did not indicate the presence of infectious diseases.


According to the Central Ethical Committee of Germany [16], when residual samples are used for research studies, patient consent is not required in exceptional cases and the effort needed to obtain the consent is not justifiable. A standard curve based on the extinction values of three calibration sera containing 2, 20 or 200 relative units (RU) per mL was used to the calculate results. However, a limitation of the study is that the collection of sera over a seven-year period may mask changes in seroepidemiology.
These data add to previous findings from the German population, using a relatively small number of sera from infants, children and adolescents [10]. However, the difference in prevalence between pregnant women and female blood donors was statistically not significant. To our knowledge, the study presented here is the first comprehensive serosurvey that includes both gG-1- and gC-1-based ELISAs. The prevalence of HSV-1 antibodies among girls was significantly lower than among boys and a significantly higher prevalence of HSV-2 IgG in women than in men was detected.
Even though the risk of vertical viral transmission is lower than that for acquiring primary infection, recurrent genital herpes must be regarded as the most common cause of neonatal infections [7]: up to 85% of neonatal herpes infections are caused by HSV-2 [8], which are associated with a poor prognosis [9].
In Germany, the prevalence of HSV-1 IgG antibodies reached levels of more than 90% in adults during 1996 to 1998, whereas about 15% of adults possessed IgG antibodies to HSV-2 [10].
Our findings are in contrast to the study from Davidovici et al., which demonstrated significantly higher HSV-1 seroprevalence in females aged 10–19 years in Israel [22].
The seroprevalence data of HSV-2 in blood donors in this study are comparable with findings from other parts of Germany [10].
Saschenbrecker are employed by the Institute of Experimental Immunology (affiliated to Euroimmun AG), and M. The reduced incidence of HSV-1 infections during childhood, especially in girls, has to be followed up since a higher number of primary HSV-2 infections may result. In HSV-1 infection, the body above the waist is predominantly affected; in HSV-2, it is mainly below the waist. Further studies revealed that the prevalence of antibodies to both HSV types has not changed over the last two to three decades in Germany [11]. In keeping with the findings from Israel, our study suggests that HSV-1 infection is being acquired later in life.
It should not be forgotten, however, that the low HSV-2 IgG prevalence might also be caused, at least partially, by false-positive test results because of the limited specificity of HSV-2 antibody tests [17].
The considerably lower seroprevalence rate of 8.9% among pregnant women from Stuttgart (Germany) [28] can only be interpreted in the context of the different serological methods used and differences between the populations tested. Except where otherwise stated, all manuscripts published after 1 January 2016 will be published under the Creative Commons Attribution (CC BY) licence.
For HSV-1, primary infections occur mostly during infancy and childhood, after maternal antibodies have disappeared in the first year of life. However, only a few studies have analysed the time of HSV seroconversion during infancy, childhood and adolescence. Seroprevalence was calculated only on the basis of the ELISAs using gG-1 and gG-2 and the retest results using an immunoblot assay, where appropriate.
The age- and sex-specific prevalence of HSV-2 IgG in the children and adults (blood donors) tested is shown in the Figure.
This is in contrast to data from the data from the United States, where 68% of the population aged over 12 years had HSV-1 antibodies [23], The overall age-specific HSV seroprevalence rates in childhood obtained from Brazil are 1.5 times higher [24] and the figures from Tanzania are two to three times higher [25] than in this study, from one part of Germany.
A review of the literature suggests that the incidence of neonatal diseases caused by both types of HSV ranges widely, from 5 to 31 per 100,000 live births [27]. These factors have also to be considered for the interpretation of data from several countries, where HSV-2 seroprevalence ranged from 4% (in England and Wales) to 24% (in Bulgaria) [29]. You are free to share and adapt the material, but you must give appropriate credit, provide a link to the licence, and indicate if changes were made. In particular, little is known about the seroprevalence of HSV-2 in children: seroprevalence in childhood is often used to estimate the incidence of intrauterine and neonatal HSV-2 infections. Relatively high prevalence rates of HSV-2 infection in Tanzanian children suggest that non-sexual transmission of HSV-2 (e.g. Recent studies have shown that nearly one third of children in Sweden [12] have been infected with HSV-1 and there is a gradual development of antibodies throughout childhood [3,12]. Since previous infection with HSV-1 may protect against HSV-2 infection or attenuate the severity of disease, lower antibody prevalence among girls may result in a higher number of primary HSV-2 infections that are mostly localised in the genital tract in sexually active individuals. In contrast, HSV-2 antibodies have been reported to appear generally after sexual debut [3,13]. Hence, a reduced incidence of HSV-1 infections during childhood and adolescence, especially in girls, has to be followed up in further HSV-1 seroprevalence studies.



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