Kaposi Sarcoma-associated herpesvirus infection and endemic Burkitt's lymphoma.

BACKGROUND: Endemic Burkitt's lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum (Pf) malaria co-infections. However, the role of Kaposi sarcoma-associated herpesvirus (KSHV), also endemic in Africa, has not been evaluated as a co-factor in eBL pathogenesis. METHODS: Multiplexed seroprofiles for EBV, malaria and KSHV were generated for 266 eBL patients, 78 non-eBL cancers and 202 healthy children; and KSHV and EBV loads were quantified by digital-droplet PCR. RESULTS: KSHV seroprevalence did not differ by study group yet was associated with age. Seropositivity, defined by K8.1/LANA or in combination with 5 other KSHV antigens (ORF59, ORF65, ORF61, ORF38, and K5) was associated with anti-malarial antibody levels to AMA-1 (OR=2.41, p<0.001 and OR=2.07, p<0.001) and MSP-1 (OR=2.41, p=0.0006 and OR=5.78, p<0.001), respectively. KSHV loads did not correlate with antibody levels nor differ across groups, but were significantly lower in children with detectable EBV viremia (p=0.014). CONCLUSIONS: Even though KSHV-EBV dual infection does not increase eBL risk, EBV appears to suppress reactivation of KSHV while malaria exposure is associated with KSHV infection and/or reactivation. Both EBV and malaria should, therefore, be considered as potential effect modifiers for KSHV-associated cancers in sub-Saharan Africa.