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Cancer Control Research

Abstract

DESCRIPTION (provided by applicant): Human herpesvirus type 8 (HHV-8) or Kaposi's sarcoma associated herpesvirus (KSHV) is the etiologic agent associated with Kaposi's sarcoma (KS). Since the onset of the AIDS epidemic, KS has become the most frequently diagnosed }ediatdc tumor in sub-Saharan Africa. Vertical and horizontal transmission of HHV-8 has been reported, but the mechanisms of both routes remain poody understood. The first phase of our program to understand HHV-8 transmission focused on the possibility of vertical transmission in a high seroprevalence country, Zambia. By following a mother/infant cohort for more than three years, cases of perinatal transmission of HHV-8 in children were documented, but the rate is too low to account for the childhood seroprevalence observed. Moreover, we identified infants who seroconverted to HHV-8 when their mothers were not HHV-8 infected. Therefore, our findings suggest that a major mode of HHV-8 transmission in infants is horizontal. We have found that HHV-8 can be detected frequently in seroposiUve mothers' saliva, but not in breast milk between 2-6 months postpartum. The proposed study will focus on determining the incidence of and mechanisms by which horizontal HHV-8 transmission to children occurs in Lusaka, Zambia. A number of questions concerning the routes and factors that may affect this process will be addressed; one is the effect of HIV-1 infection in the donor or recipient, a second is the effect of high HHV-8 viral load, and another will be ethnographic behaviors or risk factors that may result in exposure of infants to HHV-8 contaminated saliva. Other questions of significant interest are: who is the most significant source of the virus (mother, father or other), and whether the presence of multiple HHV-8 infected individuals has direct impact on incidence or time to seroconversion. The overall objective is to establish the rates at which horizontal transmission of HHV-8 occurs and to identify virologic, immunologic and ethnographic risk factors that predispose children to infection by HHV-8. The proposed project will utilize relevant participants in the existing cohort and recruit additional subjects to substantiate analyses of the hypotheses within three defined and inter-related specific aims. It is anticipated that the proposed studies will define horizontal transmission rates in children, identify primary sources for horizontal virus transmission, and elucidate the potential risk factors involved. Moreover, it is anticipated that the information generated will be useful in the development of future intervention strategies.