{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:57:20Z","timestamp":1793505440201,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100011541","name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute","doi-asserted-by":"publisher","award":["HHSN261201100063C"],"award-info":[{"award-number":["HHSN261201100063C"]}],"id":[{"id":"10.13039\/100011541","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011541","name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute","doi-asserted-by":"publisher","award":["HHSN261201100007I"],"award-info":[{"award-number":["HHSN261201100007I"]}],"id":[{"id":"10.13039\/100011541","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["SJR"],"award-info":[{"award-number":["SJR"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Endemic Burkitt lymphoma (eBL) is an aggressive B cell non-Hodgkin lymphoma associated with antigenic stimulation from <jats:italic>Plasmodium falciparum<\/jats:italic> malaria. Whether eBL risk is related to malaria parasite density is unknown. To address this issue, children with eBL, asymptomatic and clinical malaria, as a surrogate of malaria parasite density, were assessed.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Malaria-related laboratory results (parasite density, haemoglobin, platelet count, and white cell count [WBC]) count) were compiled for 4019 eBL cases and 80,532 subjects evaluated for asymptomatic malaria or clinical malaria (severe malaria anaemia, hyperparasitaemia, cerebral malaria, malaria prostration, moderate malaria, and mild malaria) in 21 representative studies published in Africa (mostly East Africa) and 850 eBL cases and 2878 controls with primary data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) case\u2013control study in Uganda, Tanzania, and Kenya. The average values of malaria-related laboratory results were computed by condition and trends across single-year age groups were assessed using regression and spline models.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Overall, malaria infection or malaria was diagnosed in 37,089 of children compiled from the literature. Children with eBL and asymptomatic parasitaemia\/antigenaemia, but not those with clinical malaria, were closest in their mean age (age 7.1\u20137.2 vs. 7.4\u20139.8\u00a0years), haemoglobin level (10.0\u201310.4 vs. 11.7\u201312.3\u00a0g\/dL), malaria parasite density (2800 vs. 1827\u20137780 parasites\/\u00b5L), platelet count (347,000\u2013353,000 vs. 244,000\u2013306,000 platelets\/\u00b5L), and WBC count (8180\u20138890 vs. 7100\u20137410 cells\/\u00b5L). Parasite density in these two groups peaked between four to five years, then decreased steadily thereafter; conversely, haemoglobin showed a corresponding increase with age. Children with clinical malaria were markedly different: all had an average age below 5\u00a0years, had dramatically elevated parasite density (13,905\u2013869,000 parasites\/\u00b5L) and dramatically decreased platelet count (&lt;\u2009159,000 platelets\/\u00b5L) and haemoglobin (&lt;\u20097\u00a0g\/dL).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>eBL and asymptomatic parasitaemia\/antigenaemia, but not clinical malaria, were the most similar conditions with respect to mean age and malaria-related laboratory results. These results suggest that children with asymptomatic parasitaemia\/antigenaemia may be the population at risk of eBL.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12936-020-03312-7","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T23:04:59Z","timestamp":1595891099000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"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"],"prefix":"10.1186","volume":"19","author":[{"given":"Lawrence S.","family":"Redmond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin D.","family":"Ogwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Kerchan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance N.","family":"Tenge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Were","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Kuremu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nestory","family":"Masalu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Kawira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Otim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail D.","family":"Legason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herry","family":"Dhudha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leona W.","family":"Ayers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishor","family":"Bhatia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Goedert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8273-9831","authenticated-orcid":false,"given":"Sam M.","family":"Mbulaiteye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"3312_CR1","first-page":"19","volume":"42","author":"DP Burkitt","year":"1969","unstructured":"Burkitt DP. Etiology of Burkitt\u2019s lymphoma\u2014an alternative hypothesis to a vectored virus. J Natl Cancer Inst. 1969;42:19\u201328.","journal-title":"J Natl Cancer Inst"},{"key":"3312_CR2","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/ijc.22179","volume":"120","author":"JJ Rainey","year":"2007","unstructured":"Rainey JJ, Omenah D, Sumba PO, Moormann AM, Rochford R, Wilson ML. Spatial clustering of endemic Burkitt\u2019s lymphoma in high-risk regions of Kenya. Int J Cancer. 2007;120:121\u20137.","journal-title":"Int J Cancer"},{"key":"3312_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ijc.2910060102","volume":"6","author":"GW Kafuko","year":"1970","unstructured":"Kafuko GW, Burkitt DP. Burkitt\u2019s lymphoma and malaria. Int J Cancer. 1970;6:1\u20139.","journal-title":"Int J Cancer"},{"key":"3312_CR4","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/S1470-2045(08)70175-X","volume":"9","author":"DM Parkin","year":"2008","unstructured":"Parkin DM, Sitas F, Chirenje M, Stein L, Abratt R, Wabinga H. Part I: cancer in indigenous Africans\u2014burden, distribution, and trends. Lancet Oncol. 2008;9:683\u201392.","journal-title":"Lancet Oncol."},{"key":"3312_CR5","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13027-019-0236-7","volume":"14","author":"L Hammerl","year":"2019","unstructured":"Hammerl L, Colombet M, Rochford R, Ogwang DM, Parkin DM. The burden of Burkitt lymphoma in Africa. Infect Agent Cancer. 2019;14:17.","journal-title":"Infect Agent Cancer."},{"key":"3312_CR6","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1182\/blood-2012-12-475665","volume":"122","author":"P Aka","year":"2013","unstructured":"Aka P, Vila MC, Jariwala A, Nkrumah F, Emmanuel B, Yagi M, et al. Endemic Burkitt lymphoma is associated with strength and diversity of Plasmodium falciparum malaria stage-specific antigen antibody response. Blood. 2013;122:629\u201335.","journal-title":"Blood"},{"key":"3312_CR7","doi-asserted-by":"publisher","first-page":"e2505","DOI":"10.1371\/journal.pone.0002505","volume":"3","author":"N Mutalima","year":"2008","unstructured":"Mutalima N, Molyneux E, Jaffe H, Kamiza S, Borgstein E, Mkandawire N, et al. Associations between Burkitt lymphoma among children in Malawi and infection with HIV, EBV and malaria: results from a case-control study. PLoS ONE. 2008;3:e2505.","journal-title":"PLoS ONE"},{"key":"3312_CR8","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1002\/ijc.23254","volume":"122","author":"LM Carpenter","year":"2008","unstructured":"Carpenter LM, Newton R, Casabonne D, Ziegler J, Mbulaiteye S, Mbidde E, et al. Antibodies against malaria and Epstein-Barr virus in childhood Burkitt lymphoma: a case-control study in Uganda. Int J Cancer. 2008;122:1319\u201323.","journal-title":"Int J Cancer"},{"key":"3312_CR9","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1002\/ijc.26203","volume":"130","author":"M Guech-Ongey","year":"2012","unstructured":"Guech-Ongey M, Yagi M, Palacpac NM, Emmanuel B, Talisuna AO, Bhatia K, et al. Antibodies reactive to Plasmodium falciparum serine repeat antigen in children with Burkitt lymphoma from Ghana. Int J Cancer. 2012;130:1908\u201314.","journal-title":"Int J Cancer"},{"key":"3312_CR10","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1136\/jmg.3.3.177","volume":"3","author":"AO Williams","year":"1966","unstructured":"Williams AO. Haemoglobin genotypes, ABO blood groups, and Burkitt\u2019s tumour. J Med Genet. 1966;3:177\u20139.","journal-title":"J Med Genet"},{"key":"3312_CR11","doi-asserted-by":"publisher","first-page":"10693","DOI":"10.7196\/SAMJ.2016.v106i7.10693","volume":"106","author":"PB Hesseling","year":"2016","unstructured":"Hesseling PB, Jam DT, Palmer DD, Wharin P, Tuh GS, Bardin R, et al. Burkitt\u2019s lymphoma patients in Northwest Cameroon have a lower incidence of sickle cell trait (Hb AS) than healthy controls. S Afr Med J. 2016;106:10693.","journal-title":"S Afr Med J"},{"key":"3312_CR12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ebiom.2017.09.037","volume":"25","author":"ID Legason","year":"2017","unstructured":"Legason ID, Pfeiffer RM, Udquim KI, Bergen AW, Gouveia MH, Kirimunda S, et al. Evaluating the causal link between malaria infection and endemic Burkitt Lymphoma in Northern Uganda: a Mendelian randomization study. EBioMedicine. 2017;25:58\u201365.","journal-title":"EBioMedicine."},{"key":"3312_CR13","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/ng.388","volume":"41","author":"M Jallow","year":"2009","unstructured":"Jallow M, Teo YY, Small KS, Rockett KA, Deloukas P, Clark TG, et al. Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat Genet. 2009;41:657\u201365.","journal-title":"Nat Genet"},{"key":"3312_CR14","first-page":"63","volume":"24","author":"MC Pike","year":"1970","unstructured":"Pike MC. Burkitt\u2019s lymphoma and sickle-cell trait in Uganda. Br J Prev Soc Med. 1970;24:63.","journal-title":"Br J Prev Soc Med."},{"key":"3312_CR15","doi-asserted-by":"publisher","first-page":"633","DOI":"10.4269\/ajtmh.1976.25.633","volume":"25","author":"FK Nkrumah","year":"1976","unstructured":"Nkrumah FK, Perkins IV. Sickle cell trait, hemoglobin C trait, and Burkitt\u2019s lymphoma. Am J Trop Med Hyg. 1976;25:633\u20136.","journal-title":"Am J Trop Med Hyg"},{"key":"3312_CR16","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1002\/ijc.28378","volume":"134","author":"DH Mulama","year":"2014","unstructured":"Mulama DH, Bailey JA, Foley J, Chelimo K, Ouma C, Jura WG, et al. Sickle cell trait is not associated with endemic Burkitt lymphoma: an ethnicity and malaria endemicity-matched case-control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer. Int J Cancer. 2014;134:645\u201353.","journal-title":"Int J Cancer"},{"key":"3312_CR17","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1098\/rstb.1997.0124","volume":"352","author":"K Marsh","year":"1997","unstructured":"Marsh K, Snow RW. Host-parasite interaction and morbidity in malaria endemic areas. Philos Trans R Soc Lond B Biol Sci. 1997;352:1385\u201394.","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"3312_CR18","volume-title":"Guidelines for the treatment of malaria","author":"WHO","year":"2010","unstructured":"WHO. Guidelines for the treatment of malaria. 2nd ed. Geneva: World Health Organization; 2010.","edition":"2"},{"key":"3312_CR19","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1002\/ijc.32390","volume":"146","author":"S Peprah","year":"2020","unstructured":"Peprah S, Ogwang MD, Kerchan P, Reynolds SJ, Tenge CN, Were PA, et al. Risk factors for Burkitt lymphoma in East African children and minors: a case\u2013control study in malaria-endemic regions in Uganda, Tanzania and Kenya. Int J Cancer. 2020;146:953\u201369.","journal-title":"Int J Cancer"},{"key":"3312_CR20","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12936-017-1778-z","volume":"16","author":"M Maziarz","year":"2017","unstructured":"Maziarz M, Kinyera T, Otim I, Kagwa P, Nabalende H, Legason ID, et al. Age and geographic patterns of Plasmodium falciparum malaria infection in a representative sample of children living in Burkitt lymphoma-endemic areas of northern Uganda. Malar J. 2017;16:124.","journal-title":"Malar J."},{"key":"3312_CR21","doi-asserted-by":"publisher","first-page":"54","DOI":"10.4269\/ajtmh.18-0481","volume":"100","author":"S Peprah","year":"2019","unstructured":"Peprah S, Tenge C, Genga IO, Mumia M, Were PA, Kuremu RT, et al. A cross-sectional population study of geographic, age-specific, and household risk factors for asymptomatic Plasmodium falciparum malaria infection in Western Kenya. Am J Trop Med Hyg. 2019;100:54\u201365.","journal-title":"Am J Trop Med Hyg"},{"key":"3312_CR22","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1186\/s12936-016-1529-6","volume":"15","author":"F Grandesso","year":"2016","unstructured":"Grandesso F, Nabasumba C, Nyehangane D, Page AL, Bastard M, De Smet M, et al. Performance and time to become negative after treatment of three malaria rapid diagnostic tests in low and high malaria transmission settings. Malar J. 2016;15:496.","journal-title":"Malar J."},{"key":"3312_CR23","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/1471-2288-14-135","volume":"14","author":"X Wan","year":"2014","unstructured":"Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range. BMC Med Res Methodol. 2014;14:135.","journal-title":"BMC Med Res Methodol"},{"key":"3312_CR24","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/apm.13018","volume":"128","author":"MDP Quintana","year":"2020","unstructured":"Quintana MDP, Smith-Togobo C, Moormann A, Hviid L. Endemic Burkitt lymphoma\u2014an aggressive childhood cancer linked to Plasmodium falciparum exposure, but not to exposure to other malaria parasites. APMIS. 2020;128:129\u201335.","journal-title":"APMIS."},{"key":"3312_CR25","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1093\/infdis\/jiw301","volume":"214","author":"I Rodriguez-Barraquer","year":"2016","unstructured":"Rodriguez-Barraquer I, Arinaitwe E, Jagannathan P, Boyle MJ, Tappero J, Muhindo M, et al. Quantifying heterogeneous malaria exposure and clinical protection in a cohort of Ugandan children. J Infect Dis. 2016;214:1072\u201380.","journal-title":"J Infect Dis"},{"key":"3312_CR26","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/nrmicro1089","volume":"3","author":"R Rochford","year":"2005","unstructured":"Rochford R, Cannon MJ, Moormann AM. Endemic Burkitt\u2019s lymphoma: a polymicrobial disease? Nat Rev Microbiol. 2005;3:182\u20137.","journal-title":"Nat Rev Microbiol"},{"key":"3312_CR27","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1128\/CMR.00025-08","volume":"22","author":"DL Doolan","year":"2009","unstructured":"Doolan DL, Dobano C, Baird JK. Acquired immunity to malaria. Clin Microbiol Rev. 2009;22:13\u201336.","journal-title":"Clin Microbiol Rev"},{"key":"3312_CR28","doi-asserted-by":"publisher","first-page":"397","DOI":"10.4269\/ajtmh.2011.10-0450","volume":"84","author":"B Emmanuel","year":"2011","unstructured":"Emmanuel B, Kawira E, Ogwang MD, Wabinga H, Magatti J, Nkrumah F, et al. African Burkitt lymphoma: age-specific risk and correlations with malaria biomarkers. Am J Trop Med Hyg. 2011;84:397\u2013401.","journal-title":"Am J Trop Med Hyg"},{"key":"3312_CR29","doi-asserted-by":"publisher","first-page":"3741","DOI":"10.1038\/srep03741","volume":"4","author":"WT Johnston","year":"2014","unstructured":"Johnston WT, Mutalima N, Sun D, Emmanuel B, Bhatia K, Aka P, et al. Relationship between Plasmodium falciparum malaria prevalence, genetic diversity and endemic Burkitt lymphoma in Malawi. Sci Rep. 2014;4:3741.","journal-title":"Sci Rep."},{"key":"3312_CR30","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1093\/infdis\/jiz510","volume":"221","author":"M Eldh","year":"2020","unstructured":"Eldh M, Hammar U, Arnot D, Beck HP, Garcia A, Liljander A, et al. Multiplicity of asymptomatic Plasmodium falciparum infections and risk of clinical malaria: a systematic review and pooled analysis of individual participant data. J Infect Dis. 2020;221:775\u201385.","journal-title":"J Infect Dis"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-020-03312-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12936-020-03312-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-020-03312-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T23:27:34Z","timestamp":1627428454000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-020-03312-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,28]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["3312"],"URL":"https:\/\/doi.org\/10.1186\/s12936-020-03312-7","relation":{},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,28]]},"assertion":[{"value":"21 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethical approval to conduct the EMBLEM study was given by the Uganda Virus Research Institute Research and Ethics Committee, the Uganda National Council of Science and Technology (HS-816), and the National Cancer Institute Special Studies Institutional Review Board (10-C-N133).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the parents or guardians of children in EMBLEM and written informed assent was obtained from children in EMBLEM aged 7\u00a0years or older prior to enrolment.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The manuscript does not include details, images, or videos relating to an individual person. All data are presented in aggregate and are not identifiable at the individual level.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"239"}}