The epidemiology of Kaposi’s sarcoma associated-herpesvirus in Uganda

Over the past two decades there has been an explosion in the number of cases of Kaposi’s sarcoma (KS) in parts of sub-Saharan Africa, where Kaposi’s sarcoma associated-herpesvirus (KSHV) and HIV are relatively prevalent. Currently KS is the most commonly reported cancer in Uganda causing significant morbidity and mortality. Limiting KSHV transmission or halting disease progression could prevent KS. Here, I describe an investigation of factors that might impact on transmission of KSHV and report the first prospective study of antibody titre to KSHV to determine risk of KS from Africa. Stored samples from Medical Research Council, Uganda cohorts were tested using an ELISA to KSHV antigens. Results from a birth cohort found that among both mothers and children malaria parasitaemia was identified as a novel association with KSHV seropositivity. Among children HIV exposure and HIV infection was associated with antibodies to KSHV. A random effects meta-analysis conducted to clarify wider evidence of an association between KSHV and HIV found that HIV was associated with an increased prevalence of antibodies to KSHV in mothers and children. A case-control study nested within a longitudinal HIV cohort found among individuals who develop KS, antibody titres to KSHV are higher and increased over time compared to adults who did not. It is plausible that control of malaria may also reduce the spread of KSHV. How malaria may interact with KSHV and if malaria control will reduce transmission are key future questions. Prevention and treatment of HIV with anti-retroviral therapy may lower KSHV transmission between mothers and children. For individuals with HIV-KSHV co-infection, increasing antibody titre to KSHV precedes development of KS. Research is required to elucidate co-factors driving progression to cancer. A clinically valid tool to screen for risk of HIV-associated KS is urgently needed.