Background: To investigate how intense Plasmodium falciparum infection predisposes to Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL), we analyzed the effect of acute malaria on existing EBV-host balance.
Methods: EBV genome loads in peripheral blood mononuclear cells were assayed by quantitative polymerase chain reaction, and EBV-specific CD8(+) T cell responses were assayed by interferon-gamma enzyme-linked immunospot assay.
Results: Gambian children, from whom samples were obtained during an acute malaria attack and again up to 6 weeks later, had extremely high viral loads, reaching levels that in the United Kingdom are seen only in patients with infectious mononucleosis. Gambian control subjects (children and adults with no recent history of malaria) had lower median viral loads, although they were still >10-fold above the median for healthy UK adults. Limited experiments with EBV epitope peptides (restricted through the HLA-B 3501 and HLA-B 5301 alleles) also suggested an impairment of virus-specific CD8(+) T cell function in children with malaria, but only during acute disease.
Conclusions: Acute malaria is associated with sustained increase in EBV load and, possibly, a transient decrease in EBV-specific T cell surveillance. We infer that the unusually high set point of virus carriage in P. falciparum-challenged populations, allied with the parasite's capacity to act as a chronic B cell stimulus, probably contributes to the pathogenesis of endemic BL.