The overall prevalence of KSHV (seropositive to lytic KSHV K8.1 or latent KSHV Orf73) was 47.5% (Table 1). Although the prevalence of KSHV was highest in sex workers (50.5%), in contrast to the prevalence of HIV and other STI, this was not significantly different to that in mineworkers (48.4%), male township residents (47.5%) and female township residents (46.0%) (chi-square 3 df 1.3; P > 0.73).
In contrast to HIV and syphilis the prevalence of KSHV did not follow the pattern expected of an STI (Table 2). The age group most at risk was over 46 years (OR 1.4, 95% CI 1.0–1.8) and the area of residence had no impact on the prevalence of KSHV. Sexual intercourse and the number of sexual partners were not risk factors for KSHV. In contrast to HIV, positive serology for another STI had no impact on the risk of KSHV infection (Table 3). KSHV prevalence was similar between HIV-positive (48.5%) and HIV-negative (46.8%) subjects (P = 0.44). The prevalence of KSHV was also similar in those with no STI (46.1%) compared with those with STI (47.9%; P > 0.48).
The mean antibody titre (± SD) for K8.1 was similar among all non-township and township community groups [mean antibody titre (± SD) 0.61 (0.52) versus 0.44 (0.49), respectively; P > 0.05]. For Orf73 the mean antibody titre (± SD) was significantly higher in sex workers than in any other community group (P < 0.05), but was similar among mineworkers, female township residents and male township residents (P > 0.05).
Seropositivity to K8.1 antibodies (43.0%) was significantly higher than seropositivity to Orf73 antibodies (28.5%; P < 0.0001). Seropositivity to K8.1 antibodies was similar among all the community groups, ranging from 41.6% in female township residents to 47.4% in sex workers (P = 0.22; chi-square 3 df 1.2; P = 0.75). No increased risks for K8.1 antibodies were noted in any of the community groups compared with male township residents (P > 0.25). The prevalence of K8.1 antibodies was similar between those with or without evidence of an STI, HSV-2 and HIV (P > 0.5). No increased risks for K8.1 antibodies were observed for HIV or any STI (P > 0.16).
Seropositivity to Orf73 was highest in sex workers (40.0%) compared with male township residents (27.7%), female township residents (27.4%), and mineworkers (28.7%; chi-square 3 df 6.7; P = 0.08). The risk of seropositivity to Orf73 was 1.7-fold higher in sex workers compared with male township residents (OR 1.7, 95% CI 1.1–2.8), and similar in mineworkers (OR 1.0, 95% CI 0.8–1.3) and female township residents (OR 1.0, 95% CI 0.7–1.3), compared with male township residents (OR 1). No differences in the prevalences of latent KSHV seropositivity were noted when subjects where divided by HIV status and other STI (P > 0.3).
A total of 506 subjects(24.1%) tested seropositive to both lytic K8.1 and latent KSHV Orf73 antibodies, 398 (18.9%) and 94 (4.5%) were seropositive to only lytic KSHV K8.1 or latent KSHV Orf73, respectively (κ = 0.50). A significant correlation between the optical density of the lytic K8.1 and latent KSHV Orf73 assays was noted (r = 0.53; P < 0.0001). Risk factors for being positive on both assays were similar to being positive on either assay. Being positive on both assays was not associated with STI or other measures of sexual behavior. Sex workers and those residing in hotspots were, however, more likely to be positive for both assays (OR 1.7, 95% CI 1.1–2.9 and OR 2.0, 95% CI 1.2–3.4).
In contrast, KSHV seropositivity in this population was not associated with the presence of chlamydia, gonococcal, syphilitic or HSV-2 infection (Table 3). This is in agreement with a study in Uganda that showed no association between STI and KSHV . In our study, KSHV infection did not differ significantly by HIV status. This was in contrast to a recent study in South African children, in which HIV co-infection was associated with KSHV seropositivity . KSHV infection was not associated with any measures of sexual activity, including the number of lifetime sexual partners. Most significantly, being a sex worker carried no greater risk of KSHV infection than other township residents, a finding supported by work in Djibouti . This lack of association between KSHV, STI and measures of sexual behavior in this population indicates that sexual transmission is not an important transmission route in the Carletonville population. This may be attributed to the existing high background of KSHV exposure in the population before sexual activity, thus masking the role of sexual transmission. KSHV is, however, prevalent to a similar degree in MSM in the United States and United Kingdom, where a clear role for sexual risk factors has been reported [6,7].
Evidently, in this population and other African and Mediterranean populations, non-sexual modes of transmission play an important role in KSHV infection [38,41,42]. In this study, a number of interesting associations have emerged. Whereas the reduced risk of HIV infection conferred by circumcision shown in this study (OR 0.8, 95% CI 0.6–1.0) is well recognized [43,44], circumcision appeared to carry a significant risk of KSHV infection (OR 1.3, 95% CI 1.0–1.6). This is contrary to a previous report from Kenya . In our study, circumcision was related to the home language, with most of the circumcised subjects speaking isiXhosa (70%) or Sesotho (50%) and only approximately 20% of those speaking isiZulu, Setswana and other languages. In South Africa, these languages are indicative of different social practices and geographical origins. Unexpectedly, the risk of KSHV infection was significant if the home language was isiZulu compared with Setswana, and no association was noted with other languages (Table 2). It follows that the association with circumcision found in this study may have more to do with geographical and cultural factors than with the absence of a foreskin. Other associations are difficult to explain. Drinking alcohol was a risk factor for both HIV and KSHV, and although this may be linked to sexual behavior it could also be related to the common practice of sharing drinking vessels and KSHV transmission via saliva, which is thought to be an important route of KSHV infection [13,23,46,47].
The highest prevalence of latent KSHV Orf73 antibody was seen in sex workers who also had a very high prevalence of HIV infection, an association not seen for lytic KSHV K8.1. Sex workers also had the highest latent Orf73 KSHV antibody titres compared with any other community group and were also more likely to express both lytic and latent antibodies together. The biological significance of this finding is unclear.
The risk factors relating to the transmission of KSHV in African populations require considerable further study. Having an infected family member, especially an infected mother, is clearly an important risk factor [22–24,47,48]. A role for environmental risk factors, such as the source of household water and insect vectors, has been proposed [49–51]. The role of HIV infection in facilitating the transmission of KSHV needs careful study because changes in the prevalence of KSHV as a result of the HIV epidemic will have important public health implications. Further longitudinal epidemiological studies specifically designed to identify risk factors for KSHV are required in African populations.
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