Exposure to Holoendemic Malaria Results in Suppression of Epstein‐Barr Virus–Specific T Cell Immunosurveillance in Kenyan Children

Abstract

Background. Malaria and Epstein-Barr virus (EBV) infection are cofactors in the pathogenesis of endemic Burkitt lymphoma (eBL). The mechanisms by which these pathogens predispose to eBL are not known. Methods. Healthy Kenyan children with divergent malaria exposure were measured for responses to EBV latent and lytic antigens by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay and interleukin (IL)-10 ELISA. Phytohemagglutinin (PHA), purified protein derivative (PPD), and T cell epitope peptides derived from merozoite surface protein (MSP)-1, a malaria blood-stage antigen, were also evaluated. Results. Children 5–9 years old living in an area holoendemic for malaria had significantly fewer EBV-specific IFN-γ responses than did children of the same age living in an area with unstable malaria transmission. This effect was not observed for children 9 years old. In contrast, IFN-γ responses to PHA, PPD, and Plasmodium falciparum MSP-1 peptides did not significantly differ by age. IL-10 responses to EBV lytic antigens, PPD, and PHA correlated inversely with malaria exposure regardless of age. Conclusions. Children living in malaria-holoendemic areas have diminished EBV-specific T cell immunosurveillance between the ages of 5 and 9 years, which coincides with the peak age incidence of eBL.