Mechanistic interactions between Plasmodium falciparum and Epstein-Barr virus in endemic Burkitt Lymphoma pathogenesis: a narrative review (2010-2026).

Abstract

Endemic Burkitt Lymphoma, characterized by an MYC translocation during B-cell activation, is an aggressive, fast-proliferating cancer that predominantly accounts for more than half of all childhood cancers in sub-Saharan Africa. Although a well-established epidemiologic association exists between Epstein-Barr virus infection and Plasmodium falciparum malaria, disentangling their mechanistic interactions in the pathogenesis of endemic Burkitt Lymphoma remains difficult. To address this challenge, a comprehensive narrative review of studies published between 2010 and 2026, was conducted. Evidence from mouse models, in vitro and ex vivo studies was synthesized to identify potential key effector cells, cytokine groups, and molecular pathways likely involved in fostering an immune environment that supports lymphomagenesis. The synthesized evidence informed the development of a speculative multi-hit model of endemic Burkitt Lymphoma, in which chronic Plasmodium falciparum exposure reconfigures the immune landscape through sustained inflammation, altered effector cell function, and impaired immune surveillance. Within this framework, these changes may subsequently facilitate Epstein-Barr virus persistence, intermittent B-cell reactivation, and cumulative genomic instability, ultimately increasing the likelihood of MYC translocations and the development of endemic Burkitt Lymphoma. The review also proposes incorporating emerging immune effector populations into this conceptual multi-hit model. Although several of the mechanistic relationships explored remain inferential, the framework identifies potential therapeutic and preventive immune targets that warrant further investigation in experimental and longitudinal human studies in high-burden regions.