Risk factors for kaposi sarcoma-associated herpesvirus (KSHV) and kaposi sarcoma (KS) mortality in sub-Saharan Africa, The

The largest worldwide burden of Kaposi sarcoma (KS), 85% of all cases, is found in sub-Saharan Africa. Kaposi sarcoma-associated herpesvirus (KSHV) is the etiological agent for KS. KSHV seroprevalence is inconsistent across and within countries which suggests environmental factors contribute to KSHV susceptibility and infection. Sub-Saharan Africa has up to 95% seropositive rates in some populations and is also malaria endemic, principally caused by Plasmodium falciparum (Pf). The geographic concordance of these two infections, together with malaria's ability to depress the immune system led to the hypothesis that malaria may be driving the high rates of KSHV and KS in sub-Saharan Africa. Whether malaria is a precipitous factor of KSHV seroconversion or a trigger for viral reactivation and/or KS disease is unknown and requires further inspection. Chapter IV of this dissertation describes a cohort of pregnant Kenyan women followed through delivery to elucidate whether Pf exposure during pregnancy reduces transplacental transfer of KSHV antibodies. Using the Luminex® assay we found that Pf during pregnancy did not appear to have an impact on KSHV antibody transfer across the placenta. The mechanism between malaria and KSHV must lie elsewhere. Chapter V of this dissertation explores whether Pf infection during childhood led to earlier ages of KSHV seroconversion among a cohort of Kenyan children followed through 24 months of age. This study demonstrated that KSHV seroconversion, as measured by Luminex®, occurred at higher frequencies and earlier ages than previously identified. It also showed that children with Pf had earlier KSHV seroconversion, supporting the theory that malaria increases KSHV susceptibility. Among people living with acquired immunodeficiency syndrome-associated KS (PLWA-KS), mortality rates are highest in sub-Saharan Africa. In chapter VI, a case series of Zimbabwean PLWA-KS was employed to determine factors associated with mortality. Findings revealed a high burden of all-cause mortality in Zimbabwean PLWA-KS and showed that distance to a facility with adequate treatment, other than antiretroviral therapy, is crucial for survival. The barriers to PLWA-KS seeking and receiving care requires better understanding. This work describes different facets of KSHV/KS, beginning with factors that determine infection susceptibility and finishing with those affecting mortality.