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.
Highlights
Plasmodium falciparum (Pf) malaria and Epstein Barr Virus (EBV) have been identified as co-factors in the pathogenesis of endemic Burkitt’s lymphoma [1] which is estimated to account for 70% of cancers among children in equatorial Africa [2,3]
Our study demonstrates that the prevalence of positive EBV lyticbut not latent-antigen CD8+ T-cell IFN-c responses decreases in a malaria holoendemic area and not a hypoendemic area
In an effort to control viral replication induced by recurrent Pf-malaria infections [14], we hypothesize that EBV lytic antigen CD8+ T-cells have become exhausted and unable to produce IFN-c or alternatively these cells were culled through apoptosis
Summary
Plasmodium falciparum (Pf) malaria and Epstein Barr Virus (EBV) have been identified as co-factors in the pathogenesis of endemic Burkitt’s lymphoma (eBL) [1] which is estimated to account for 70% of cancers among children in equatorial Africa [2,3]. Most children experience primary EBV infection by 3 years of age, followed by life-long infection in memory B-lymphocytes [12,13]. P. falciparum induces polyclonal B-cell expansion and lytic EBV reactivation [14], increasing the number of latently-infected B-cells. Repeated Pf-malaria infections could lead to exhaustion or hypo-responsiveness of EBV latent or lytic antigen CD8+ T-cells, increasing the chance for this EBV-associated malignancy to arise
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