Despite consistent increasing understanding of KSHV biology and its clinical manifestations, progress has not been significantly made in its epidemiology which in turn hampered the management of KSHV-associated diseases and public health. In this study, we based on a large general population to explore the epidemiologic feature of KSHV infection. The seropositivity of KSHV was 2.05%, higher than previous study [17]. And the results supported that KSHV appears to be sexually transmitted in MSM in this low-risk, heterosexual population.
In the present study, we explored the potential correlates of sexual behaviors with KSHV and HSV-2 infection, and found that KSHV transmission may be related to sexual activity in men, especially in male homosexuals. Our results showed MSM had an approximately fivefold increased risk of KSHV infection (OR = 4.98), which was generally consistent with previous studies [21–23]. Thus, the transmission of KSHV in MSM is clearly associated with sexual risk factors, whereas evidence of heterosexual transmission of KSHV is less consistent. Homosexual individuals were more likely to have oral sex and with multiple sexual partners [24]. While KSHV can be detected common in the saliva of infected subjects, indicating that saliva is the most likely source of KSHV during transmission between MSM [25]. Our results did not show a clear between the number of sexual partners and KSHV seropositivity (P = 0.574). This may be affected by the methods of data acquisition. The data on sexual behaviors are obtained through interview with gerneral population, which may cause some selection biases.
As expected, there was an increased HSV-2 prevalence with earlier initial sexual age and number of sexual partners in life. Meanwhile, HSV-2 infection risk increased about threefold (OR = 2.85) among MSM. High prevalence of the two viral among MSM suggests that the two viral may facilitate the acquisition of each other through sexual contacts with this population and further supported KSHV transmission may be related to male homosexuals. HSV-2 infection can contribute to the sexual transmission of KSHV and may also be associated with reactivation of KSHV latent infection. Previous studies in Northern Cameroon showed similar results [7]. HSV-2 infection is known to recruit at the site of replication white blood cells including B and CD8 lymphocyte that can be infected by KSHV. In addition, reactivation of HSV-2 might increase the load at mucosal and systemic levels of other viruses including KSHV, HIV [26], and HCV [27]. Viral shedding and transmission to sex partners can occur in the absence of symptoms or a noticeable lesion [28]. Noticeably, our study revealed that 95.12% of HSV-2 infections were asymptomatic or unrecognized, and this could exacerbate the transmission of KSHV. We also found that HSV-2 positive subjects were more likely to be infected with KSHV (OR = 1.58), this association implies that HSV-2 and KSHV may share similar transmission routes.
Furthermore, we have also confirmed KSHV infection was associated with increasing age, compared with subjects between 18–29 years old, the risk among 50–59 years old was increased about twofold (OR = 2.27) and among 60–80 years old was increased about threefold (OR = 3.43). Unlike the relatively stable age pattern of HSV-2 seroprevalence, the prevalence of KSHV increases steadily with age, suggesting that KSHV may be not sexually transmitted. The role of education level and economic status against KSHV have been explored by other investigators, however, the results are controversial [29]. Our study suggests that higher education level and higher economic status are protective factors for KSHV infection. Participants with higher education and economic level may pay more attention to self-protection [30]. Regarding the household size, we did not found correlation with KSHV seroprevalence, however, we did not know people who living together whether sharing public utensils. Thus, we cannot infer the possible transmission route through saliva from the household size.
Defining modes of transmission of KSHV remains a challenge, especially in non-endemic areas. In this study, we were able to compare the well-known pattern of sexually related risk factors for HSV-2, with that seen for KSHV in a community at risk of both. The implication of our findings is that KSHV appears to be sexually transmitted in MSM, although transmission among heterosexuals is less likely.
Some limitation should be noted here. First, there is a lack of standard KSHV serological assay. We are based on the results from the EIAs, which may different with other methods. Second, NHANES III lacks data on specific sexual practices are unavailable, which prevented us from exploring potential routes of sexual transmission in more details.