African Burkitt Lymphoma: Age-Specific Risk and Correlations with Malaria Biomarkers

Benjamin Emmanuel Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Benjamin Emmanuel in
Current site
Google Scholar
PubMed Close
,
Esther Kawira Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Esther Kawira in
Current site
Google Scholar
PubMed Close
,
Martin D. Ogwang Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Martin D. Ogwang in
Current site
Google Scholar
PubMed Close
,
Henry Wabinga Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Henry Wabinga in
Current site
Google Scholar
PubMed Close
,
Josiah Magatti Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Josiah Magatti in
Current site
Google Scholar
PubMed Close
,
Francis Nkrumah Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Francis Nkrumah in
Current site
Google Scholar
PubMed Close
,
Janet Neequaye Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Janet Neequaye in
Current site
Google Scholar
PubMed Close
,
Kishor Bhatia Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Kishor Bhatia in
Current site
Google Scholar
PubMed Close
,
Glen Brubaker Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Glen Brubaker in
Current site
Google Scholar
PubMed Close
,
Robert J. Biggar Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Robert J. Biggar in
Current site
Google Scholar
PubMed Close
, and
Sam M. Mbulaiteye Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Shirati Health, Education, and Development Foundation, Shirati, Tanzania; Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda; Kampala Cancer Registry, Makerere College of Health Sciences, Kampala, Uganda; Shirati Hospital, Shirati, North Mara, Tanzania; Emeritus Prof. Noguchi Memorial Institute, Accra, Ghana; Department of Child Health, Korle Bu University Teaching Hospital, Accra, Ghana; Shirati Hospital, Shirati, North Mara, Tanzania/Interchurch Medical Assistance, New Windsor, Maryland; Department of Epidemiology Research, Staten Serum Institute, Copenhagen, Denmark

Search for other papers by Sam M. Mbulaiteye in
Current site
Google Scholar
PubMed Close
DOI:
https://doi.org/10.4269/ajtmh.2011.10-0450
Volume/Issue:
Volume 84: Issue 3
Page(s):
397–401
Restricted access
Get Permissions

African Burkitt lymphoma is an aggressive B-cell, non-Hodgkin lymphoma linked to Plasmodium falciparum malaria. Malaria biomarkers related to onset of African Burkitt lymphoma are unknown. We correlated age-specific patterns of 2,602 cases of African Burkitt lymphoma (60% male, mean ± SD age = 7.1 ± 2.9 years) from Uganda, Ghana, and Tanzania with malaria biomarkers published from these countries. Age-specific patterns of this disease and mean multiplicity of P. falciparum malaria parasites, defined as the average number of distinct genotypes per positive blood sample based on the merozoite surface protein-2 assessed by polymerase chain reaction, were correlated and both peaked between 5 and 9 years. This pattern, which was strong and consistent across regions, contrasted parasite prevalence, which peaked at 2 years and decreased slightly, and geometric mean parasite density, which peaked between 2 and 3 years and decreased sharply. Our findings suggest that concurrent infection with multiple malaria genotypes may be related to onset of African Burkitt lymphoma.

Author Notes

*Address correspondence to Benjamin Emmanuel, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Executive Plaza South, Room 7080, Rockville, MD 20852-7248. E-mail: emmanuelb@mail.nih.gov

Financial support: The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services (grants HHSN26120090068P, HHSN261200555004C, N02-CP-31003, and N01-CO-12400).

Authors' addresses: Benjamin Emmanuel, Kishor Bhatia, and Sam M. Mbulaiteye, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, E-mails: emmanuelb@mail.nih.gov, bhatiak@mail.nih.gov, and mbulaits@mail.nih.gov. Esther Kawira, Shirati Health, Education, and Development Foundation, Shirati, Tanzania, E-mail: elkawira@gmail.com. Martin D. Ogwang, Department of Surgery, St. Mary's Hospital, Lacor, Gulu, Uganda, E-mail: ogwang.martin@lacorhospital.org. Henry Wabinga, Kampala Cancer Registry, Department of Pathology, Makerere University, Kampala, Uganda, E-mail: hwabinga@med.mak.ac.ug. Josiah Magatti and Glen Brubaker, Interchurch Medical Assistance, New Windsor, MD, E-mails: jomagati2000@yahoo.com and grb176@comcast.net. Francis Nkrumah, Noguchi Memorial Institute, University of Ghana, Legon, Legon, Ghana, E-mail: fnkrumah@noguchi.mimcom.org. Janet Neequaye, Department of Child Health, Korle Bu University Teaching Hospital, Korle-Bu, Accra, Ghana, E-mail: janet.neequaye@yahoo.com. Robert J. Biggar, Department of Epidemiology Research, Staten Serum Institute, Copenhagen S, Denmark, E-mail: rjbiggar@gmail.com.

Reprint requests: Sam M. Mbulaiteye, 6120 Executive Boulevard, Executive Plaza South, Room 7080, Rockville, MD 20852-7248, E-mail: mbulaits@mail.nih.gov.

Copyright:
©The American Society of Tropical Medicine and Hygiene 2011
Received:
12 Aug 2010
|
Accepted:
26 Oct 2010
|
Published Online:
04 Mar 2011
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
  • 1.

    Burkitt D, 1958. A sarcoma involving the jaws in African children. Br J Surg 46: 218–223.

  • 2.

    Leoncini L, Raphael M, Stein H, Harris NL, Jaffe ES, Kluin PM, 2008. Burkitt Lymphoma. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, eds. WHO Classification of Tumors of Hematopoetic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer, 262–264.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Epstein MA, Achong BG, Barr YM, 1964. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet 1: 702–703.

  • 4.

    Henle G, Henle W, Clifford P, Diehl V, Kafuko GW, Kirya BG, Klein G, Morrow RH, Munube GM, Pike P, Tukei PM, Ziegler JL, 1969. Antibodies to Epstein-Barr virus in Burkitt's lymphoma and control groups. J Natl Cancer Inst 43: 1147–1157.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Klein G, 2009. Burkitt lymphoma–a stalking horse for cancer research? Semin Cancer Biol 19: 347–350.

  • 6.

    de-The G, Geser A, Day NE, Tukei PM, Williams EH, Beri DP, Smith PG, Dean AG, Bronkamm GW, Feorino P, Henle W, 1978. Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt's lymphoma from Ugandan prospective study. Nature 274: 756–761.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Biggar RJ, Henle G, Bocker J, Lennette ET, Fleisher G, Henle W, 1978. Primary Epstein-Barr virus infections in African infants. II. Clinical and serological observations during seroconversion. Int J Cancer 22: 244–250.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Bornkamm GW, 2009. Epstein-Barr virus and the pathogenesis of Burkitt's lymphoma: more questions than answers. Int J Cancer 124: 1745–1755.

  • 9.

    Burkitt D, 1962. A children's cancer dependent on climatic factors. Nature 194: 232–234.

  • 10.

    Rainey JJ, Omenah D, Sumba PO, Moormann AM, Rochford R, Wilson ML, 2007. Spatial clustering of endemic Burkitt's lymphoma in high-risk regions of Kenya. Int J Cancer 120: 121–127.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Morrow RH Jr, 1985. Epidemiological evidence for the role of falciparum malaria in the pathogenesis of Burkitt's lymphoma. IARC Sci Publ 60: 177–186.

  • 12.

    Hill AV, 1999. The immunogenetics of resistance to malaria. Proc Assoc Am Physicians 111: 272–277.

  • 13.

    Pike MC, 1970. Burkitt's lymphoma and sickle-cell trait in Uganda. Br J Prev Soc Med 24: 63.

  • 14.

    Williams AO, 1966. Haemoglobin genotypes, ABO blood groups, and Burkitt's tumour. J Med Genet 3: 177–179.

  • 15.

    Nkrumah FK, Perkins IV, 1976. Sickle cell trait, hemoglobin C trait, and Burkitt's lymphoma. Am J Trop Med Hyg 25: 633–636.

  • 16.

    Carpenter LM, Newton R, Casabonne D, Ziegler J, Mbulaiteye S, Mbidde E, Wabinga H, Jaffe H, Beral V, 2008. Antibodies against malaria and Epstein-Barr virus in childhood Burkitt lymphoma: a case-control study in Uganda. Int J Cancer 122: 1319–1323.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Mutalima N, Molyneux E, Jaffe H, Kamiza S, Borgstein E, Mkandawire N, Liomba G, Batumba M, Lagos D, Gratrix F, Boshoff C, Casabonne D, Carpenter LM, Newton R, 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: e2505.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Lam KM, Syed N, Whittle H, Crawford DH, 1991. Circulating Epstein-Barr virus-carrying B cells in acute malaria. Lancet 337: 876–878.

  • 19.

    Chene A, Donati D, Guerreiro-Cacais AO, Levitsky V, Chen Q, Falk KI, Orem J, Kironde F, Wahlgren M, Bejarano MT, 2007. A molecular link between malaria and Epstein-Barr virus reactivation. PLoS Pathog 3: e80.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Ogwang MD, Bhatia K, Biggar RJ, Mbulaiteye SM, 2008. Incidence and geographic distribution of endemic Burkitt lymphoma in northern Uganda revisited. Int J Cancer 123: 2658–2663.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Parkin DM, Nambooze S, Wabwire-Mangen F, Wabinga HR, 2010. Changing cancer incidence in Kampala, Uganda, 1991–2006. Int J Cancer 126: 1187–1195.

  • 22.

    Nkrumah FK, Olweny CL, 1985. Clinical features of Burkitt's lymphoma: the African experience. IARC Sci Publ 60: 87–95.

  • 23.

    Geser A, Brubaker G, Draper CC, 1989. Effect of a malaria suppression program on the incidence of African Burkitt's lymphoma. Am J Epidemiol 129: 740–752.

  • 24.

    Wabinga HR, Parkin DM, Wabwire-Mangen F, Nambooze S, 2000. Trends in cancer incidence in Kyadondo County, Uganda, 1960–1997. Br J Cancer 82: 1585–1592.

  • 25.

    Parkin DM, Wabinga H, Nambooze S, 2001. Completeness in an African cancer registry. Cancer Causes Control 12: 147–152.

  • 26.

    Smith T, Beck HP, Kitua A, Mwankusye S, Felger I, Fraser-Hurt N, Irion A, Alonso P, Teuscher T, Tanner M, 1999. Age dependence of the multiplicity of Plasmodium falciparum infections and of other malariological indices in an area of high endemicity. Trans R Soc Trop Med Hyg 93 (Suppl 1): 15–20.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Owusu-Agyei S, Smith T, Beck HP, Amenga-Etego L, Felger I, 2002. Molecular epidemiology of Plasmodium falciparum infections among asymptomatic inhabitants of a holoendemic malarious area in northern Ghana. Trop Med Int Health 7: 421–428.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Peyerl-Hoffmann G, Jelinek T, Kilian A, Kabagambe G, Metzger WG, von Sonnenburg F, 2001. Genetic diversity of Plasmodium falciparum and its relationship to parasite density in an area with different malaria endemicities in West Uganda. Trop Med Int Health 6: 607–613.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Uganda Bureau of Statistics, 2009. 2009 Statistical Abstract. Available at: http://www.ubos.org/onlinefiles/uploads/ubos/pdf%20documents/2009Statistical_%20Abstract.pdf. Accessed March 29, 2010.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Acheampong PK, 1982. Rainfall anomaly along the coast of Ghana. Its nature and causes. Geogr Ann, Ser A 64: 199–211.

  • 31.

    Mackinnon MJ, Marsh K, 2010. The selection landscape of malaria parasites. Science 328: 866–871.

  • 32.

    Ofosu-Okyere A, Mackinnon MJ, Sowa MP, Koram KA, Nkrumah F, Osei YD, Hill WG, Wilson MD, Arnot DE, 2001. Novel Plasmodium falciparum clones and rising clone multiplicities are associated with the increase in malaria morbidity in Ghanaian children during the transition into the high transmission season. Parasitology 123: 113–123.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Farnert A, Rooth I, Svensson , Snounou G, Bjorkman A, 1999. Complexity of Plasmodium falciparum infections is consistent over time and protects against clinical disease in Tanzanian children. J Infect Dis 179: 989–995.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Gupta S, Trenholme K, Anderson RM, Day KP, 1994. Antigenic diversity and the transmission dynamics of Plasmodium falciparum. Science 263: 961–963.

  • 35.

    Mbulaiteye SM, Anderson WF, Bhatia K, Rosenberg PS, Linet MS, Devesa SS, 2010. Trimodal age-specific incidence patterns for Burkitt lymphoma in the United States, 1973–2005. Int J Cancer 126: 1732–1739.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Biggar RJ, Nkrumah FK, 1979. Burkitt's lymphoma in Ghana: urban-rural distribution, time-space clustering and seasonality. Int J Cancer 23: 330–336.

  • 37.

    Morrow RH, Pike MC, Smith PG, 1977. Further studies of space-time clustering of Burkitt's lymphoma in Uganda. Br J Cancer 35: 668–673.

  • 38.

    Williams EH, Day NE, Geser AG, 1974. Seasonal variation in onset of Burkitt's lymphoma in the West Nile District of Uganda. Lancet 2: 19–22.

  • 39.

    Smith T, Charlwood JD, Kihonda J, Mwankusye S, Billingsley P, Meuwissen J, Lyimo E, Takken W, Teuscher T, Tanner M, 1993. Absence of seasonal variation in malaria parasitaemia in an area of intense seasonal transmission. Acta Trop 54: 55–72.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 614 579 185
Full Text Views 473 13 0
PDF Downloads 125 11 0
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save