Burkitt lymphoma risk shows geographic and temporal associations with <i>Plasmodium falciparum</i> infections in Uganda, Tanzania, and Kenya

Abstract

Endemic Burkitt lymphoma (eBL) is a pediatric cancer coendemic with malaria in sub-Saharan Africa, suggesting an etiological link between them. However, previous cross-sectional studies of limited geographic areas have not found a convincing association. We used spatially detailed data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study to assess this relationship. EMBLEM is a case-control study of eBL from 2010 through 2016 in six regions of Kenya, Uganda, and Tanzania. To measure the intensity of exposure to the malaria parasite, <i>Plasmodium falciparum</i>, among children in these regions, we used high-resolution spatial data from the Malaria Atlas Project to estimate the annual number of <i>P. falciparum</i> infections from 2000 through 2016 for each of 49 districts within the study region. Cumulative <i>P. falciparum</i> exposure, calculated as the sum of annual infections by birth cohort, varied widely, with a median of 47 estimated infections per child by age 10, ranging from 4 to 315 infections. eBL incidence increased 39% for each 100 additional lifetime <i>P. falciparum</i> infections (95% CI: 6.10 to 81.04%) with the risk peaking among children aged 5 to 11 and declining thereafter. Alternative models using estimated annual <i>P. falciparum</i> infections 0 to 10 y before eBL onset were inconclusive, suggesting that eBL risk is a function of cumulative rather than recent cross-sectional exposure. Our findings provide population-level evidence that eBL is a phenotype related to heavy lifetime exposure to <i>P. falciparum</i> malaria and support emphasizing the link between malaria and eBL.