Human herpesvirus-8 in northwestern China: epidemiology and characterization among blood donors

Human herpes virus 8 (HHV-8) is the etiologic agent associated with the development of classical, AIDS-related, iatrogenic, and endemic Kaposi's sarcoma (KS) [1, 2]. HHV-8 is also associated with lymphoproliferative diseases, including primary effusion lymphomas and multicentric Castleman's disease [3, 4]. Emerging evidence suggests that HHV-8 may be transmitted through sexual contact [5, 6], saliva [7], and blood transfusion [8‐10]. In the USA, where HHV-8 seroprevalence is low (<10%), HHV-8 is spread by the sexual route, at least among homosexual men [5, 6]. In regions or countries with high HHV-8 seroprevalence (>25%), HHV-8 infection increases throughout childhood, suggesting that transmission occurs through saliva or other horizontal routes [11‐13]. Of note, HHV-8 infection has been observed in patients who received non-leukocyte-reduced blood [8]. Infectious viruses or viral DNA have been identified from blood donors in the USA and Africa [14, 15]. HHV-8 infection has been observed in patients receiving blood transfusions in Uganda, thereby indicating blood-borne transmission of HHV-8 [9, 10].

HHV-8 seroprevalence among blood donors varies between different regions. HHV-8 prevalence ranges from 0.2% in Japan, 0-15% in the USA and the UK, up to >50% in some African countries [16, 17]. There is a wide range of variations in HHV-8 infection in South America [18]. A few studies focusing on small study populations have been carried out in China. In the inland areas of China, HHV-8 seroprevalence in general population was <8% [19, 20]. In Xinjiang, in the northwest of China, HHV-8 seroprevalence ranged from 12.5% to 48% depending on different populations [21‐24]. The mode of HHV-8 transmission remains undefined, but the unique pattern of HHV-8 infection in this geographic region correlated well with an increased incidence of KS [21, 22, 24].

The present study was the first large-scale survey of HHV-8 seroprevalence in blood donors in China. Recent reports showed that HHV-8 seroprevalence was 7.3% in Liaonin province and 5.7% in Shandong province among healthy blood donors [19, 25]. These studies focused on the Han ethnic group, and the study population was small. A study in the Han ethnic group in Hubei province revealed that HHV-8 seroprevalence was 5.2% [20]. The prevalence of HHV-8 infection reported in these studies was similar to those among the adult population in North America [6, 14, 26]. These observations suggest that HHV-8 seroprevalence in China was, in general, low. The Xinjiang area, located in the northwest of China, exhibited a distinct pattern. We noted that HHV-8 seroprevalence was relatively high in the Han ethnic group living in Xinjiang: 18.6% of blood donors were HHV-8 positive. Moreover, HHV-8 seroprevalence was 17.7% among the 1140 non-residential Han ethnic group who migrated to Xinjiang from inland areas. Thus, an elevated HHV-8 seroprevalence in the Han ethnic group in Xinjiang province implies an association of HHV-8 infection with the living environment. These potential factors which contribute to the differences within the same ethnic group suggest an increased opportunity for members of the Han ethnic group to have close contact with highly infected populations. And the relatively low level of public health in Xinjiang province due to the economic situation in this region may benefit the spread or transmission of HHV-8, but this hypothesis needs conformation. The precise impact of being resident in Xinjiang on HHV-8 infection could not be ascertained because of the cross-sectional nature of the present study.

The present study suggested that HHV-8 seroprevalence was associated with ethnicity but not with sex, age, marital status, occupation, educational level, blood type, and time of donation of blood components. Among blood donors, HHV-8 seroprevalence was 18.6% in the Han group, 25.9% in the Uygur group, 29.2% in the Kazak group, and 36.8% in the Mongolian group. When combined, the mean prevalence of HHV-8 infection in local minorities was 30.6%. Compared with Han subjects living in Xinjiang, the elevated HHV-8 seroprevalence in local minorities was significant. Hence, what was the basis for the observed differences? It is known that local minorities have resided in Xinjiang for generations, and that they have unique cultural practices. An intriguing possibility is that different cultural practices or social behaviors may play a part in HHV-8 infection. Alternatively, genetic factors may affect the susceptibility to HHV-8 infection. Additional studies are required to address these issues.

Several studies have demonstrated that HHV-8 seroprevalence is correlated with the occurrence of KS in Europe and Africa [27‐30]. In Ghana and Egypt, a high prevalence of HHV-8 does not correlate well with KS onset [11, 31]. HHV-8 seroprevalence is high among Amerindians in Brazil, French Guiana and Ecuador [32‐34]. Nonetheless, KS has not been reported for these populations. The present study revealed that HHV-8 seroprevalence was higher in Han subjects residing in Xinjiang than in the inland areas of China. Furthermore, it was higher in local minority groups than in Han subjects. HHV-8 prevalence remained high in blood donors residing in Xinjiang, but classical KS and AIDS-related KS were observed only among local minority groups [21, 22]. Taken together, these data support the hypothesis that additional factors other than HHV-8 may be involved in KS development.

Several researchers reported blood-borne transmission of HHV-8 among a large cohort of drug users, or prospective studies on blood-transfusion recipients [8, 10]. The present study was in accordance with these studies because it established a positive relationship between an increasing prevalence of infection with the corresponding frequency of donation of whole blood. To a certain extent, the time of donation represents the opportunity of blood exposure. In China, laws pertaining to donation of whole blood were passed in 1992. Before 1992, non-standard protocols for blood collection, and absence of instruments and materials were common. These conditions could increase the prevalence of HHV-8 infection by blood exposure. A possible explanation for the contradictory results in the univariate analysis with respect to the time of donation of blood components may be due to the small number of samples in each group or undetermined factors.

There was a difference in HHV-8 antibody titers among HHV-8-seropositive individuals in the present study. Specifically, a larger fraction of local minorities had high HHV-8 antibody titers than Han subjects. This was evident in the Uygur and Kazak ethnic groups. Whether this reflects enhanced replication of HHV-8 or enhanced immune responses is not clear. Notably, KS patients are seen in Uygur and Kazak ethnic groups in Xinjiang hospitals [21, 22]. The patients are typically elderly men who have multiple nodular lesions in the lower or upper extremities. Intriguingly, KS patients tend to be younger among those who are also infected with HIV. Hence, high HHV-8 antibody titers in Uygur and Kazak groups appeared to correlate with the development of KS in these ethnic groups.