title: Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens.
abstract: Plasmodium falciparum malaria (Pf-malaria) and Epstein Barr Virus (EBV) infections coexist in children at risk for endemic Burkitt's lymphoma (eBL); yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years) in Kenya from 2002-2004. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic) and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5-9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30-0.99). Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5-9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Snider
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Cole
authors.forename: Kiprotich
authors.initials: K
authors.lastname: Chelimo
authors.forename: Peter Odada
authors.initials: PO
authors.lastname: Sumba
authors.forename: Pia D M
authors.initials: PD
authors.lastname: Macdonald
authors.forename: Chandy C
authors.initials: CC
authors.lastname: John
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: Ann M
authors.initials: AM
authors.lastname: Moormann
mesh_terms: D000293:Adolescent; D002051:Burkitt Lymphoma / Q000453:epidemiology* / Q000276:immunology* / Q000469:parasitology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000276:immunology*; D015995:Prevalence; D012008:Recurrence
chemical_list: D007371:Interferon-gamma