The effects of acute malaria on Epstein-Barr virus (EBV) load and EBV-specific T cell immunity in Gambian children.
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.
Njie
Ramou
R
Cancer Research UK Institute for Cancer Studies, The Medical School, University of Birmingham, Birmingham, United Kingdom.
Bell
Andrew I
AI
Jia
Hui
H
Croom-Carter
Debbie
D
Chaganti
Sridhar
S
Hislop
Andrew D
AD
Whittle
Hilton
H
Rickinson
Alan B
AB
D000208:Acute Disease; D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology; D005714:Gambia / Q000453:epidemiology; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008288:Malaria / Q000150:complications*; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load