Herpes simplex virus (HSV) belongs to subfamily alpha of herpesvirinae and has two types: HSV-1 and HSV-2. Both infect epithelial cells and establish latent infections in neurons, causing an infection that persists for life. Although HSV-1 and HSV-2 infections are generally asymptomatic, both viruses can cause a wide spectrum of clinical manifestations. HSV-1 is classically associated with oropharyngeal lesions transmitted horizontally in childhood, causes recurrent attacks of "fever blisters", and has been shown to account for an increasing proportion of primary genital herpes, especially in women [1]. It is also the leading cause of sporadic encephalitis in the United States and several other countries [2]. HSV-2 primarily infects the genital mucosa and is the main cause of genital herpes. HSV-2 infection is acquired primarily through contact with infected genital secretions and this strong association, provides a useful marker for sexual behavior [3]. Further, it is widely implicated as an important cofactor for HIV acquisition [4, 5]. HSV-2 is one of the most common causes of neonatal herpes and also can cause encephalitis in the immunocompromised host [6]. Meanwhile, clinical manifestations of a chronic HSV infection (HSV-1 or HSV-2) among HIV/AIDS patients have been regarded by the World Health Organization (WHO) as an important presentation defining the disease progression of HIV/AIDS [7].

Both HSV-1 and HSV-2 infections are known to be common throughout the world [8]. However, China currently has no estimates of the prevalence of HSV-1 infection and only limited estimates of HSV-2 infection among selected subpopulations [9–16]. Additionally there have been no studies that have ascertained age- and gender-specific seroprevalence of HSV-1 and HSV-2 in the general population in China. Such information is valuable for understanding HSV transmission dynamics and designing type-specific, population-based prevention and intervention programs for HSV. To provide these estimates, we conducted a seroepidemiologic survey of HSV among rural community residents in Zhejiang province, Eastern China. Given the association of HSV-2 infection with sexual behavior and HIV acquisition, we also tested for HIV infection in this study. Furthermore, since Hepatitis B virus (HBV) infection is endemic in China and is also associated with sexual contact and classified by WHO as a sexually transmitted disease, we also reported the seroprevalence of HBV infection among the study participants.

To our knowledge, this is the first study to document age- and gender-specific seroprevalence of both types of HSV in a general population sample in China. We observed a very high level of HSV-1 infection (92.0%) and a relatively low level of HSV-2 infection (13.2%). These observations are consistent with those in other countries [8], but are significant, as HSV-1 prevalence has never been reported in China. Limited studies conducted in China have demonstrated HSV-2 prevalence as high as 70% among female sex workers and as low as 5% among general male rural migrants [10, 13–15], with rates typically higher in women than men. Our gender-specific HSV-2 prevalence was 10.5% for males and 15.3% for females and was found to be higher than that among market vendors (6.4% for males and 12.0% for females) in Fuzhou, the capital city of Fujian province and among male migrants in Shanghai (5.5%) [9, 10, 15]. Such differences might be due to differences in the characteristics of the study subjects. For instance, the participants in the present study were local permanent residents while those in the referred two studies were rural-to-urban migrants, with possible greater opportunity for infection.

Differences in the age distributions between HSV-1 and HSV-2 infections in the present study provide evidence to the supposition that HSV-1 and HSV-2 have different transmission modes and dynamics [17, 18]. While HSV-1 is highly epidemic and ubiquitous for all age groups, HSV-2 infection is most likely to occur among sexually active people. Our findings suggest that future HSV prevention and intervention programs should be type-specific. Meanwhile, we found that a substantially higher proportion of couple participants were seroconcordant HSV-1 positive (90.7%) versus HSV-1 serodiscordant (8.6%) than seroconcordant HSV-2 positive (8.0%) versus HSV-2 serodiscordant (11.6%). These findings have two possible explanations. First, HSV-1 prevalence was found to be very high among the general adult population. Therefore, the low proportion of HSV-1 serodiscordance among couples might be due to the low prevalence of HSV-1 negative; Second, HSV-1 can be transmitted by both sexual and nonsexual contacts whereas HSV-2 is almost always transmitted by sexual contacts. Therefore, HSV-1 transmission between couples is more likely to occur than HSV-2. Given that HSV-2 is predominantly sexually transmitted and most couples in China do not use condoms for marital sex [19], marital HSV-2 transmission could be a concern for future STI prevention and control programs in Eastern China.

The limitations of the serological tests for HSV-1 and HSV-2 should be noted. In this study, Focus Diagnostics ELISAs were used for HSV-1 and HSV-2 serum antibody detection in order to determine cumulative lifetime exposure to infection. Previous validation studies have shown high sensitivity but relatively poorer specificity for HSV-1 and HSV-2 Focus Diagnostics ELISAs using index values of 1.10 when compared to the golden standard HSV western blot [20, 21]. This relatively poor specificity could yield false positives, which might have leaded to an overestimation of the prevalence of HSV-1 and HSV-2 [20, 21]. However, this study was based on a large sample size, thus the age- and gender-specific prevalence patterns for HSV-1 and for HSV-2 should be negligibly affected.

In addition, no one in the present study was positive for HIV, suggesting a low HIV epidemic at the population level. On the other hand, HBV infection was still prevalent in this population especially among those aged over 15 years. As HBV infection could be sexually transmitted and because both HIV and HBV have severe health outcomes, they are not ignorable for any successful STI prevention and intervention programs in these communities.

HSV-1 infection is highly prevalent among all age groups whereas HSV-2 infection is most likely to occur among sexually active people in Eastern China. HSV-1 and HSV-2 have different transmission modes and dynamics in the population, and need type specific prevention and control programs.