Human Herpesvirus 8 Seropositivity in Rural Uganda: Maturation of Sero-epidemiological Studies

Abstract

Human herpesvirus 8 (HHV8, also called Kaposi sarcoma [KS]–associated herpesvirus) is a necessary but insufficient cause of KS [1]. KS is a major public health problem in Africa, where it was endemic before the human immunodeficiency virus (HIV) infection epidemic [2], accounting for up to 18% of cancers in adults in some regions, including parts of Uganda, the Congo, and Rwanda [3]. The disease was known to occur in children [4], intuitively suggesting that HHV8 could be transmitted during childhood. Currently, KS is the most common cancer in men and the second most common cancer in women and children in Uganda, highlighting the dramatic impact of the HIV infection epidemic on KS incidence [5]. The discovery of HHV8 in 1994 [1] and subsequent development of antibody assays with reasonable sensitivity and specificity paved the way for seroepidemiological studies to characterize the distribution of HHV8, the risk factors for infection, and the risk for KS after HHV8 infection. The geographic distribution of HHV8 seropositivity generally parallels that of KS [6, 7]. In sub-Saharan Africa, HHV8 seropositivity is higher (50%–80% in adults) in the eastern and central regions and lower (10%–40% in adults) in western and southern regions [7]. HHV8 infection seroprevalence increases with age in children [8] and is associated with having an HHV8-seropositive mother or family member [9]. HHV8 can be transmitted by transfusion, but the risk is relatively small (2%–3% per transfusion), compared with the risk of community-acquired HHV8 (3% per year) [10, 11]. HHV8 DNA is detected frequently and at high levels in saliva of asymptomatic individuals [12, 13], consistent with the theory that saliva is the dominant conduit of HHV8 spread [14]. Among adults, some studies [15], but not all [16], have shown a modest association of HHV8 seropositivity with age. The association of HHV8 seropositivity with sexual risk factors has been inconsistent [16–20]. The article by Butler et al [21] in this issue of the Journal is the largest population-based study to evaluate epidemiological risk factors of HHV8 infection among children and adults in a country where KS is a major public health problem. Thus far, our knowledge of HHV8 sero-epidemiology in Africa has been derived from studies that suffered from many limitations, including relatively small size and especially the reliance on selected populations, such as children attending hospital clinics [10], commercial sex workers[18, 20], patients attending sexually transmitted disease clinics, or selected occupational groups [17, 19]. These limitations may explain, in part, some of the conflicting associations and/or lingering doubts that even consistent findings can be generalized. Butler et al [21] avoided many of the limitations of prior studies. They studied 1383 children (age. 18 months–13 years) and 1477 adults enrolled from their homes in a rural parish in Uganda. They meticulously documented socioeconomic and behavioral risk factors, including saliva sharing practices, which have not been evaluated before, using questionnaires. In addition, they tested for serologic evidence of other infections (cytomegalovirus [CMV], herpes simplex virus-1 [HSV1], hepatitis B virus [HBV]), and HIV) that have established modes of transmission. They detected HHV8 antibodies using an in-house K8.1 immunoassay with which they have accumulated substantial experience in other studies conducted in Uganda [11]. Among the children, they found that HHV8 infection seroprevalence increased with age, doubling from 15.5% Received 21 October 2010; accepted 19 November 2010. The content is the responsibility of the authors alone and does not necessarily reflect the views or the policies of the United States Department of Health and Human Services or participating entities. Potential conflicts of interest: none reported. Reprints or correspondence: James J. Goedert, MD, 6120 Executive Blvd, Executive Plaza South, Rm 7068, MSC 7248, Rockville, MD 20852 (goedertj@mail.nih.gov). The Journal of Infectious Diseases 2011;203:575–577 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011. 1537-6613/2011/2035-0001$15.00 DOI: 10.1093/infdis/jiq094