{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T19:35:30Z","timestamp":1789328130279,"version":"build-2803163510"},"reference-count":136,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) National Institutes of Health, Department of Health and Human Services"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Burkitt lymphoma (BL) is an aggressive B-cell lymphoma endemic in children in regions of sub-Saharan Africa, where its incidence geographically overlaps holoendemic Plasmodium falciparum malaria and poorly controlled childhood Epstein\u2013Barr virus (EBV) infection. Despite decades of research, the precise mechanistic synergy between these two pathogens remains incompletely defined. This review synthesizes current epidemiological, immunological, and molecular evidence to propose an integrated model for the etiology of endemic BL. We outline a paradoxical, dual-edged relationship wherein EBV infection during infancy may provide a short-term child survival advantage against severe malaria while simultaneously increasing the long-term oncogenic risk in B-cells infected by EBV. P. falciparum infection triggers polyclonal B-cell activation, increasing the probability of an activation-induced cytidine deaminase (AID)-mediated c-MYC translocation in proportion to the recurrent parasite burden. Concurrently, EBV expands within this B-cell pool and modulates the host immune response, potentially through viral interleukin-10 (vIL-10), to prevent lethal malarial inflammation. At the cellular level, EBV provides a critical \u201csecond hit\u201d when it establishes latency I infection that rescues c-MYC-translocated B-cells from apoptosis. This framework explains why BL manifests as a \u201ctumor of malaria survivors,\u201d peaking in incidence years after the highest-risk period for malaria mortality. Ultimately, this model underscores that malaria control is a critical form of cancer control and highlights key future directions for validating these pathways in prospective clinical studies.<\/jats:p>","DOI":"10.3390\/cancers18132146","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:59:47Z","timestamp":1783065587000},"page":"2146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Complex Interplay of Malaria and EBV in Burkitt Lymphoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0001-5152","authenticated-orcid":false,"given":"Rosemary","family":"Rochford","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8273-9831","authenticated-orcid":false,"given":"Sam M.","family":"Mbulaiteye","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/bjs.18004619704","article-title":"A sarcoma involving the jaws in African children","volume":"46","author":"Burkitt","year":"1958","journal-title":"Br. J. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41572-022-00404-3","article-title":"Burkitt lymphoma","volume":"8","author":"Burkhardt","year":"2022","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/ijc.70468","article-title":"Attributable Fraction of Epstein-Barr Virus in Subtypes of Lymphoma: A Systematic Review and Global Meta-Analysis","volume":"159","author":"Hirabayashi","year":"2026","journal-title":"Int. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/ijc.22179","article-title":"Spatial clustering of endemic Burkitt\u2019s lymphoma in high-risk regions of Kenya","volume":"120","author":"Rainey","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ijc.2910060102","article-title":"Burkitt\u2019s lymphoma and malaria","volume":"6","author":"Kafuko","year":"1970","journal-title":"Int. J. Cancer"},{"key":"ref_6","first-page":"429","article-title":"An Improved Map for the Study of Burkitt\u2019s Lymphoma Syndrome in Africa","volume":"40","author":"Haddow","year":"1963","journal-title":"East Afr. Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.cell.2015.07.019","article-title":"Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma","volume":"162","author":"Robbiani","year":"2015","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Torgbor, C., Awuah, P., Deitsch, K., Kalantari, P., Duca, K.A., and Thorley-Lawson, D.A. (2014). A multifactorial role for P. falciparum malaria in endemic Burkitt\u2019s lymphoma pathogenesis. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004170"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/jimmun\/vkaf005","article-title":"Sustained activation induced cytidine deaminase (AID) expression in B cells following Plasmodium falciparum malaria infection in Kenyan children","volume":"214","author":"Ariera","year":"2025","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1086\/594373","article-title":"The effects of acute malaria on Epstein-Barr virus (EBV) load and EBV-specific T cell immunity in Gambian children","volume":"199","author":"Njie","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jayasooriya, S., de Silva, T.I., Njie-Jobe, J., Sanyang, C., Leese, A.M., Bell, A.I., McAulay, K.A., Yanchun, P., Long, H.M., and Dong, T. (2015). Early virological and immunological events in asymptomatic epstein-barr virus infection in african children. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004746"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/0140-6736(91)90203-2","article-title":"Circulating Epstein-Barr virus-carrying B cells in acute malaria","volume":"337","author":"Lam","year":"1991","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3390\/hemato3030030","article-title":"Burkitt Lymphoma Incidence in Five Continents","volume":"3","author":"Mbulaiteye","year":"2022","journal-title":"Hemato"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1111\/j.1365-3156.2007.01875.x","article-title":"Spatial distribution of Burkitt\u2019s lymphoma in Kenya and association with malaria risk","volume":"12","author":"Rainey","year":"2007","journal-title":"Trop. Med. Int. Health"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1136\/bmj.2.5760.491","article-title":"Burkitt\u2019s lymphoma: A time-space cluster of cases in Bwamba County of Uganda","volume":"2","author":"Morrow","year":"1971","journal-title":"Br. Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/S1470-2045(04)01650-X","article-title":"Is endemic Burkitt\u2019s lymphoma an alliance between three infections and a tumour promoter?","volume":"5","year":"2004","journal-title":"Lancet Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"149780","DOI":"10.1155\/2012\/149780","article-title":"EBV Reactivation and Chromosomal Polysomies: Euphorbia tirucalli as a Possible Cofactor in Endemic Burkitt Lymphoma","volume":"2012","author":"Mannucci","year":"2012","journal-title":"Adv. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/0277-5379(93)90009-T","article-title":"Epstein-Barr virus markers in a series of Burkitt\u2019s lymphomas from the West Nile District, Uganda","volume":"19","author":"Geser","year":"1983","journal-title":"Eur. J. Cancer Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/227245a0","article-title":"Presence of EB virus nucleic acid homology in a \u201cvirus-free\u201d line of Burkitt tumour cells","volume":"227","year":"1970","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/2281056a0","article-title":"EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx","volume":"228","author":"Klein","year":"1970","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/ijc.33840","article-title":"Epstein-Barr virus prevalence among subtypes of malignant lymphoma in Rwanda, 2012 to 2018","volume":"150","author":"Mpunga","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_22","first-page":"Ec14","article-title":"Lymphomas in Ile-Ife, Nigeria: Immunohistochemical Characterization and Detection of Epstein-Barr virus Encoded RNA","volume":"9","author":"Onwubuya","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1182\/blood.V93.2.758","article-title":"What is Burkitt\u2019s lymphoma and when is it endemic?","volume":"93","author":"Wright","year":"1999","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1002\/ijc.23800","article-title":"Incidence and geographic distribution of endemic Burkitt lymphoma in northern Uganda revisited","volume":"123","author":"Ogwang","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/pbc.22047","article-title":"Sporadic childhood Burkitt lymphoma incidence in the United States during 1992-2005","volume":"53","author":"Mbulaiteye","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/1097-0142(19820301)49:5<1016::AID-CNCR2820490527>3.0.CO;2-H","article-title":"The American Burkitt\u2019s Lymphoma Registry: Eight years\u2019 experience","volume":"49","author":"Levine","year":"1982","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0047-6374(00)00137-8","article-title":"Age-related changes of human bone marrow: A histometric estimation of proliferative cells, apoptotic cells, T cells, B cells and macrophages","volume":"117","author":"Ogawa","year":"2000","journal-title":"Mech. Ageing Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1182\/bloodadvances.2018029199","article-title":"Prospective study of Burkitt lymphoma treatment in adolescents and adults in Malawi","volume":"3","author":"Painschab","year":"2019","journal-title":"Blood Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/S0140-6736(11)61177-X","article-title":"Burkitt\u2019s lymphoma","volume":"379","author":"Molyneux","year":"2012","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e594","DOI":"10.1016\/S2352-3026(20)30126-5","article-title":"HIV-associated Burkitt lymphoma","volume":"7","author":"Murphy","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Korir, A., Mauti, N., Moats, P., Gurka, M.J., Mutuma, G., Metheny, C., Mwamba, P.M., Oyiro, P.O., Fisher, M., and Ayers, L.W. (2014). Developing clinical strength-of-evidence approach to define HIV-associated malignancies for cancer registration in Kenya. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085881"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101265","DOI":"10.1016\/j.lanmic.2025.101265","article-title":"Sex-based differences in Plasmodium infection in the control groups of controlled human malaria infection trials in malaria-naive populations in the USA and the Netherlands: A pooled analysis","volume":"7","author":"Duncombe","year":"2026","journal-title":"Lancet Microbe"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e59872","DOI":"10.7554\/eLife.59872","article-title":"Sex-based differences in clearance of chronic Plasmodium falciparum infection","volume":"9","author":"Briggs","year":"2020","journal-title":"eLife"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/S0140-6736(97)02038-2","article-title":"Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa","volume":"349","author":"Snow","year":"1997","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0020-2452(98)80025-0","article-title":"The epidemiology of clinical malaria among African children","volume":"96","author":"Snow","year":"1998","journal-title":"Bull. Inst. Pasteur"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0169-4758(91)90096-7","article-title":"Why do some African children develop severe malaria?","volume":"7","author":"Greenwood","year":"1991","journal-title":"Parasitol. Today"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nri1311","article-title":"Innate immunity to malaria","volume":"4","author":"Stevenson","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.ijpara.2004.10.006","article-title":"Natural killer cells and innate immunity to protozoan pathogens","volume":"34","author":"Korbel","year":"2004","journal-title":"Int. J. Parasitol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/6560","article-title":"Immunity to non-cerebral severe malaria is acquired after one or two infections","volume":"5","author":"Gupta","year":"1999","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1086\/517818","article-title":"Risk of severe malaria among African infants: Direct evidence of clinical protection during early infancy","volume":"177","author":"Snow","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ly, A., and Hansen, D.S. (2019). Development of B Cell Memory in Malaria. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00559"},{"key":"ref_43","first-page":"20142657","article-title":"Gradual acquisition of immunity to severe malaria with increasing exposure","volume":"282","author":"Griffin","year":"2015","journal-title":"Proc. Biol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/cid\/cit174","article-title":"An intensive longitudinal cohort study of Malian children and adults reveals no evidence of acquired immunity to Plasmodium falciparum infection","volume":"57","author":"Tran","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/aje\/kwy213","article-title":"Association Between Age and Plasmodium falciparum Infection Dynamics","volume":"188","author":"Buchwald","year":"2019","journal-title":"Am. J. Epidemiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12936-017-1778-z","article-title":"Age and geographic patterns of Plasmodium falciparum malaria infection in a representative sample of children living in Burkitt lymphoma-endemic areas of northern Uganda","volume":"16","author":"Maziarz","year":"2017","journal-title":"Malar. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/infdis\/jiz510","article-title":"Multiplicity of Asymptomatic Plasmodium falciparum Infections and Risk of Clinical Malaria: A Systematic Review and Pooled Analysis of Individual Participant Data","volume":"221","author":"Eldh","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1086\/644781","article-title":"Submicroscopic infection in Plasmodium falciparum-endemic populations: A systematic review and meta-analysis","volume":"200","author":"Okell","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"99","DOI":"10.4269\/ajtmh.15-0004","article-title":"Malaria Diagnosis Across the International Centers of Excellence for Malaria Research: Platforms, Performance, and Standardization","volume":"93","author":"Kobayashi","year":"2015","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s12936-020-03312-7","article-title":"Endemic Burkitt lymphoma: A complication of asymptomatic malaria in sub-Saharan Africa based on published literature and primary data from Uganda, Tanzania, and Kenya","volume":"19","author":"Redmond","year":"2020","journal-title":"Malar. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1098\/rstb.1997.0124","article-title":"Host-parasite interaction and morbidity in malaria endemic areas","volume":"352","author":"Marsh","year":"1997","journal-title":"Philos. Trans. R Soc. Lond. B Biol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0950-3536(11)80022-3","article-title":"Anaemia of Plasmodium falciparum malaria","volume":"5","author":"Phillips","year":"1992","journal-title":"Baillieres Clin. Haematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1186\/s12936-015-1028-1","article-title":"Dysregulation of the haem-haemopexin axis is associated with severe malaria in a case-control study of Ugandan children","volume":"14","author":"Elphinstone","year":"2015","journal-title":"Malar. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1586\/eri.13.45","article-title":"The silent threat: Asymptomatic parasitemia and malaria transmission","volume":"11","author":"Lindblade","year":"2013","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1475-2875-4-56","article-title":"Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia","volume":"4","author":"Helleberg","year":"2005","journal-title":"Malar. J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Chaves, A.R., Dossou, Y., Dj\u00e8nontin, A., Adimi, E., Akoho, R., Bailly, J., Boura\u00efma, A., Matondo, D., Sissinto, Y., and Houinato, D. (2025). Association between asymptomatic submicroscopic and microscopic malaria infections and anemia: A study in southern Benin. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0317345"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chen, I., Clarke, S.E., Gosling, R., Hamainza, B., Killeen, G., Magill, A., O\u2019Meara, W., Price, R.N., and Riley, E.M. (2016). Asymptomatic\u201d Malaria: A Chronic and Debilitating Infection That Should Be Treated. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1001942"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e2211055120","DOI":"10.1073\/pnas.2211055120","article-title":"Burkitt lymphoma risk shows geographic and temporal associations with Plasmodium falciparum infections in Uganda, Tanzania, and Kenya","volume":"120","author":"Broen","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.pt.2013.03.002","article-title":"How malaria modulates memory: Activation and dysregulation of B cells in Plasmodium infection","volume":"29","author":"Scholzen","year":"2013","journal-title":"Trends Parasitol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1073\/pnas.0608745104","article-title":"Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9","volume":"104","author":"Parroche","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12967-017-1152-5","article-title":"Heterogeneity of Toll-like receptor 9 signaling in B cell malignancies and its potential therapeutic application","volume":"15","author":"Bai","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.coi.2005.03.003","article-title":"Signaling in B cells via Toll-like receptors","volume":"17","author":"Peng","year":"2005","journal-title":"Curr. Opin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4479","DOI":"10.4049\/jimmunol.173.7.4479","article-title":"CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10","volume":"173","author":"He","year":"2004","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1353\/pbm.1964.0023","article-title":"An Epidemiologic Approach to the Lymphomas of African Children and Burkitt\u2019s Sacroma of the Jaws","volume":"7","author":"Dalldorf","year":"1964","journal-title":"Perspect. Biol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0035-9203(72)90159-9","article-title":"Burkitt\u2019s lymphoma and malaria","volume":"66","author":"Ziegler","year":"1972","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_66","unstructured":"Morrow, R.H. (1985). Epidemiological evidence for the role of falciparum malaria in the pathogenesis of Burkitt\u2019s lymphoma. IARC Sci. Publ., 177\u2013186."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/ijc.23254","article-title":"Antibodies against malaria and Epstein-Barr virus in childhood Burkitt lymphoma: A case-control study in Uganda","volume":"122","author":"Carpenter","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mutalima, N., Molyneux, E., Jaffe, H., Kamiza, S., Borgstein, E., Mkandawire, N., Liomba, G., Batumba, M., Lagos, D., and Gratrix, F. (2008). Associations between Burkitt lymphoma among children in Malawi and infection with HIV, EBV and malaria: Results from a case-control study. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002505"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1182\/blood-2012-12-475665","article-title":"Endemic Burkitt lymphoma is associated with strength and diversity of Plasmodium falciparum malaria stage-specific antigen antibody response","volume":"122","author":"Aka","year":"2013","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ebiom.2018.12.020","article-title":"Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studies","volume":"39","author":"Derkach","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_71","first-page":"671","article-title":"CD4 T-cell subsets in malaria: TH1\/TH2 revisited","volume":"5","author":"Langhorne","year":"2014","journal-title":"Front Immunol."},{"key":"ref_72","first-page":"jiaf588","article-title":"Selective Immune Tolerance: A Unifying Mechanism Linking Heavy Malaria Exposure, Waning Vaccine Antibodies, and Burkitt Lymphoma","volume":"234","author":"Mbulaiteye","year":"2026","journal-title":"J. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1093\/oxfordjournals.aje.a115189","article-title":"Effect of a malaria suppression program on the incidence of African Burkitt\u2019s lymphoma","volume":"129","author":"Geser","year":"1989","journal-title":"Am. J. Epidemiol."},{"key":"ref_74","unstructured":"World Health Organization (2020). World Malaria Report 2020: 20 Years of Global Progress and Challenges, World Health Organization."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/S0140-6736(25)00038-8","article-title":"Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum and Plasmodium vivax malaria, 2000-22: A spatial and temporal modelling study","volume":"405","author":"Weiss","year":"2025","journal-title":"Lancet"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Mwaniki, M.K., Mohammed, S., Kariuki, N., Wamalwa, D.C., Mutisya, F., and Newton, C.R. (2025). A \u201cFamiliar Foe Revisited\u201d: Examining the relationship between endemic Burkitt\u2019s lymphoma and changing malaria admissions in the coastal region of Kenya. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-15450-9"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e247351","DOI":"10.1001\/jamanetworkopen.2024.7351","article-title":"Mosquito Bed Net Use and Burkitt Lymphoma Incidence in Sub-Saharan Africa: A Systematic Review and Meta-Analysis","volume":"7","author":"Schmit","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1056\/NEJM197606172942501","article-title":"Infectious mononucleosis. Epstein-Barr-virus shedding in saliva and the oropharynx","volume":"294","author":"Niederman","year":"1976","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1093\/infdis\/jiv290","article-title":"Breast Milk as a Potential Source of Epstein-Barr Virus Transmission Among Infants Living in a Malaria-Endemic Region of Kenya","volume":"212","author":"Daud","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_80","first-page":"211","article-title":"Infectious Mononucleosis","volume":"390","author":"Dunmire","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1093\/infdis\/jir872","article-title":"Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from Western Kenya: Clues to the etiology of endemic Burkitt lymphoma","volume":"205","author":"Piriou","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/ijc.2910220304","article-title":"Primary Epstein-Barr virus infections in African infants. I. Decline of maternal antibodies and time of infection","volume":"22","author":"Biggar","year":"1978","journal-title":"Int. J. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1093\/infdis\/jiv525","article-title":"Impact of Plasmodium falciparum Coinfection on Longitudinal Epstein-Barr Virus Kinetics in Kenyan Children","volume":"213","author":"Reynaldi","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1002\/jmv.21485","article-title":"Serological evidence for long-term Epstein-Barr virus reactivation in children living in a holoendemic malaria region of Kenya","volume":"81","author":"Piriou","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1086\/500839","article-title":"Clearance of circulating Epstein-Barr virus DNA in children with acute malaria after antimalaria treatment","volume":"193","author":"Donati","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1365-3083.2005.01589.x","article-title":"Circulating epstein-barr virus in children living in malaria-endemic areas","volume":"61","author":"Rasti","year":"2005","journal-title":"Scand. J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/infdis\/jiad264","article-title":"Effect of Malaria Infection on Epstein-Barr Virus Persistence in Kenyan Children","volume":"229","author":"Weigel","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.trstmh.2005.08.009","article-title":"Persistent Epstein-Barr viral reactivation in young African children with a history of severe Plasmodium falciparum malaria","volume":"100","author":"Yone","year":"2006","journal-title":"Trans. R Soc. Trop. Med. Hyg."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Jayasooriya, S., Hislop, A., Peng, Y., Croom-Carter, D., Jankey, Y., Bell, A., Dong, T., Rowland-Jones, S., Rickinson, A., and Walther, M. (2012). Revisiting the effect of acute P. falciparum malaria on Epstein-Barr virus: Host balance in the setting of reduced malaria endemicity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031142"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1084\/jem.190.4.567","article-title":"Epstein-barr virus-infected resting memory B cells, not proliferating lymphoblasts, accumulate in the peripheral blood of immunosuppressed patients","volume":"190","author":"Babcock","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_91","first-page":"151","article-title":"EBV Persistence--Introducing the Virus","volume":"390","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.4269\/ajtmh.16-0554","article-title":"A Malaria-Resistant Phenotype with Immunological Correlates in a Tanzanian Birth Cohort Exposed to Intense Malaria Transmission","volume":"96","author":"Nash","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"S68","DOI":"10.4314\/eamj.v81i8.9210","article-title":"Burkitt\u2019s lymphoma in Kenya: Geographical, age, gender and ethnic distribution","volume":"81","author":"Mwanda","year":"2004","journal-title":"East Afr. Med. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1086\/428910","article-title":"Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children","volume":"191","author":"Moormann","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1186\/s12936-018-2402-6","article-title":"Haemolysis and haem oxygenase-1 induction during persistent \u201casymptomatic\u201d malaria infection in Burkinab\u00e9 children","volume":"17","author":"Mooney","year":"2018","journal-title":"Malar. J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5438","DOI":"10.1182\/blood-2010-07-296483","article-title":"Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2","volume":"117","author":"Muto","year":"2011","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/imr.12201","article-title":"Orchestration of plasma cell differentiation by Bach2 and its gene regulatory network","volume":"261","author":"Igarashi","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1128\/JVI.79.2.1296-1307.2005","article-title":"Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo","volume":"79","author":"Laichalk","year":"2005","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Burnet, A.M., Brunetti, T., and Rochford, R. (2023). Hemin treatment drives viral reactivation and plasma cell differentiation of EBV latently infected B cells. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011561"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Chene, A., Donati, D., Guerreiro-Cacais, A.O., Levitsky, V., Chen, Q., Falk, K.I., Orem, J., Kironde, F., Wahlgren, M., and Bejarano, M.T. (2007). A molecular link between malaria and Epstein-Barr virus reactivation. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030080"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.semcancer.2009.10.002","article-title":"Endemic Burkitt\u2019s lymphoma as a polymicrobial disease: New insights on the interaction between Plasmodium falciparum and Epstein-Barr virus","volume":"19","author":"Chene","year":"2009","journal-title":"Semin. Cancer Biol."},{"key":"ref_102","first-page":"47","article-title":"Burkitt Lymphoma","volume":"475","author":"Moormann","year":"2025","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1093\/immhor\/vlaf045","article-title":"CD4 and CD8 T-cell response is dominated by IL-10-secreting cells in children with uncomplicated Plasmodium falciparum malaria","volume":"9","author":"Ariera","year":"2025","journal-title":"Immunohorizons"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.it.2020.04.009","article-title":"AID in Antibody Diversification: There and Back Again","volume":"41","author":"Feng","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.cell.2008.09.062","article-title":"AID is required for the chromosomal breaks in c-myc that lead to c-myc\/IgH translocations","volume":"135","author":"Robbiani","year":"2008","journal-title":"Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/iid3.134","article-title":"Plasmodium chabaudi infection induces AID expression in transitional and marginal zone B cells","volume":"4","author":"Wilmore","year":"2016","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Vecchio, E., Fiume, G., Correnti, S., Romano, S., Iaccino, E., Mimmi, S., Maisano, D., Nistic\u00f2, N., and Quinto, I. (2020). Insights about MYC and Apoptosis in B-Lymphomagenesis: An Update from Murine Models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124265"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1093\/infdis\/jir438","article-title":"The plasma concentration of the B cell activating factor is increased in children with acute malaria","volume":"204","author":"Nduati","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.4049\/jimmunol.1302960","article-title":"BAFF and BAFF receptor levels correlate with B cell subset activation and redistribution in controlled human malaria infection","volume":"192","author":"Scholzen","year":"2014","journal-title":"J. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.coph.2004.02.009","article-title":"The role of the BAFF\/APRIL system in B cell homeostasis and lymphoid cancers","volume":"4","author":"Mackay","year":"2004","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1128\/CMR.00046-17","article-title":"The Role of BAFF System Molecules in Host Response to Pathogens","volume":"30","author":"Sakai","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Paschos, K., Smith, P., Anderton, E., Middeldorp, J.M., White, R.E., and Allday, M.J. (2009). Epstein-barr virus latency in B cells leads to epigenetic repression and CpG methylation of the tumour suppressor gene Bim. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000492"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1182\/blood-2018-09-871418","article-title":"Genome-wide discovery of somatic coding and non-coding mutations in pediatric endemic and sporadic Burkitt lymphoma","volume":"133","author":"Grande","year":"2019","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.4049\/jimmunol.171.10.5215","article-title":"EBV-encoded latent membrane protein 1 cooperates with BAFF\/BLyS and APRIL to induce T cell-independent Ig heavy chain class switching","volume":"171","author":"He","year":"2003","journal-title":"J. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1084\/jem.20160120","article-title":"Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells","volume":"213","author":"Kalchschmidt","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/ijc.29127","article-title":"AID expression in peripheral blood of children living in a malaria holoendemic region is associated with changes in B cell subsets and Epstein-Barr virus","volume":"136","author":"Wilmore","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e70042","DOI":"10.1002\/gcc.70042","article-title":"Subtyping Burkitt Lymphoma by DNA Methylation","volume":"64","author":"Glaser","year":"2025","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.semcancer.2009.10.001","article-title":"To the genesis of Burkitt lymphoma: Regulation of apoptosis by EBNA-1 and SAP may determine the fate of Ig-myc translocation carrying B lymphocytes","volume":"19","author":"Nagy","year":"2009","journal-title":"Semin. Cancer Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e214","DOI":"10.1016\/S2666-5247(24)00016-8","article-title":"The 2023 WHO World malaria report","volume":"5","author":"Venkatesan","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1126\/science.2161559","article-title":"Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI","volume":"248","author":"Moore","year":"1990","journal-title":"Science"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/0140-6736(93)90364-M","article-title":"Does Epstein-Barr virus infection confer selective advantage to malaria-infected children?","volume":"341","author":"Watier","year":"1993","journal-title":"Lancet"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1126\/science.2173142","article-title":"Expression of Interleukin-10 Activity by Epstein-Barr Virus Protein BCRF1","volume":"250","author":"Hsu","year":"1990","journal-title":"Science"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1016\/S0140-6736(97)09439-7","article-title":"Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria","volume":"351","author":"Kurtzhals","year":"1998","journal-title":"Lancet"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/ijc.10372","article-title":"Promiscuous expression of Epstein-Barr virus genes in Burkitt\u2019s lymphoma from the central African country Malawi","volume":"99","author":"Xue","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4413","DOI":"10.1007\/s00253-022-12029-3","article-title":"The roles of DNA methylation on the promotor of the Epstein-Barr virus (EBV) gene and the genome in patients with EBV-associated diseases","volume":"106","author":"Zhang","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Burton, E.M., Mitra, B., Guo, R., Asara, J.M., and Gewurz, B.E. (2026). Epstein-Barr Virus Latent Membrane Protein 1 Suppresses Ferroptosis via Pentose Phosphate Pathway and Glutathione Metabolism. bioRxiv.","DOI":"10.64898\/2026.03.09.710628"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.1038\/s41388-023-02846-9","article-title":"MYC directly transactivates CR2\/CD21, the receptor of the Epstein\u2013Barr virus, enhancing the viral infection of Burkitt lymphoma cells","volume":"42","author":"Molina","year":"2023","journal-title":"Oncogene"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Navari, M., Etebari, M., De Falco, G., Ambrosio, M.R., Gibellini, D., Leoncini, L., and Piccaluga, P.P. (2015). The presence of Epstein-Barr virus significantly impacts the transcriptional profile in immunodeficiency-associated Burkitt lymphoma. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00556"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"10989","DOI":"10.1073\/pnas.1832776100","article-title":"The EBV nuclear antigen 1 (EBNA1) enhances B cell immortalization several thousandfold","volume":"100","author":"Humme","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1056\/NEJMra032015","article-title":"Persistence of the Epstein-Barr virus and the origins of associated lymphomas","volume":"350","author":"Gross","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Matar, C.G., Anthony, N.R., O\u2019Flaherty, B.M., Jacobs, N.T., Priyamvada, L., Engwerda, C.R., Speck, S.H., and Lamb, T.J. (2015). Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004858"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrmicro2491","article-title":"The good viruses: Viral mutualistic symbioses","volume":"9","author":"Roossinck","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.1073\/pnas.91.9.3715","article-title":"Parasite virulence and disease patterns in Plasmodium falciparum malaria","volume":"91","author":"Gupta","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.4269\/ajtmh.25-0695","article-title":"Natural History and the Burden of Malaria During the First Year of Life in the High-Transmission Setting of Uganda","volume":"114","author":"Aguti","year":"2026","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"6512","DOI":"10.1038\/s41467-025-61462-1","article-title":"Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort","volume":"16","author":"LaVerriere","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1128\/IAI.00593-10","article-title":"Hierarchical, domain type-specific acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 in Tanzanian children","volume":"78","author":"Cham","year":"2010","journal-title":"Infect. Immun."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/13\/2146\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:48:28Z","timestamp":1783068508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/13\/2146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":136,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cancers18132146"],"URL":"https:\/\/doi.org\/10.3390\/cancers18132146","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]}}}