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1. Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa

Author

Zhou, Weiyin, Fischer, Anja, Ogwang, Martin D., Luo, Wen, Kerchan, Patrick, Reynolds, Steven J., Tenge, Constance N., Were, Pamela A., Kuremu, Robert T., Wekesa, Walter N., Masalu, Nestory, Kawira, Esther, Kinyera, Tobias, Otim, Isaac, Legason, Ismail D., Nabalende, Hadijah, Ayers, Leona W., Bhatia, Kishor, Goedert, James J., Gouveia, Mateus H., Cole, Nathan, Hicks, Belynda, Jones, Kristine, Hummel, Michael, Schlesner, Mathias, Chagaluka, George, Mutalima, Nora, Borgstein, Eric, Liomba, George N., Kamiza, Steve, Mkandawire, Nyengo, Mitambo, Collins, Molyneux, Elizabeth M., Newton, Robert, Glaser, Selina, Kretzmer, Helene, Manning, Michelle, Hutchinson, Amy, Hsing, Ann W., Tettey, Yao, Adjei, Andrew A., Chanock, Stephen J., Siebert, Reiner, Yeager, Meredith, Prokunina-Olsson, Ludmila, Machiela, Mitchell J., and Mbulaiteye, Sam M.

Published
2023
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2. Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma

Author

Thomas, Nicole, Dreval, Kostiantyn, Gerhard, Daniela S., Hilton, Laura K., Abramson, Jeremy S., Ambinder, Richard F., Barta, Stefan, Bartlett, Nancy L., Bethony, Jeffrey, Bhatia, Kishor, Bowen, Jay, Bryan, Anthony C., Cesarman, Ethel, Casper, Corey, Chadburn, Amy, Cruz, Manuela, Dittmer, Dirk P., Dyer, Maureen A., Farinha, Pedro, Gastier-Foster, Julie M., Gerrie, Alina S., Grande, Bruno M., Greiner, Timothy, Griner, Nicholas B., Gross, Thomas G., Harris, Nancy L., Irvin, John D., Jaffe, Elaine S., Henry, David, Huppi, Rebecca, Leal, Fabio E., Lee, Michael S., Martin, Jean Paul, Martin, Marie-Reine, Mbulaiteye, Sam M., Mitsuyasu, Ronald, Morris, Vivian, Mullighan, Charles G., Mungall, Andrew J., Mungall, Karen, Mutyaba, Innocent, Nokta, Mostafa, Namirembe, Constance, Noy, Ariela, Ogwang, Martin D., Omoding, Abraham, Orem, Jackson, Ott, German, Petrello, Hilary, Pittaluga, Stefania, Phelan, James D., Ramos, Juan Carlos, Ratner, Lee, Reynolds, Steven J., Rubinstein, Paul G., Sissolak, Gerhard, Slack, Graham, Soudi, Shaghayegh, Swerdlow, Steven H., Traverse-Glehen, Alexandra, Wilson, Wyndham H., Wong, Jasper, Yarchoan, Robert, ZenKlusen, Jean C., Marra, Marco A., Staudt, Louis M., Scott, David W., and Morin, Ryan D.

Published
2023
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6. Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma

Author

Liu, Zhiwei, primary, Luo, Yang, additional, Kirimunda, Samuel, additional, Verboom, Murielle, additional, Onabajo, Olusegun O., additional, Gouveia, Mateus H., additional, Ogwang, Martin D., additional, Kerchan, Patrick, additional, Reynolds, Steven J., additional, Tenge, Constance N., additional, Were, Pamela A., additional, Kuremu, Robert T., additional, Wekesa, Walter N., additional, Masalu, Nestory, additional, Kawira, Esther, additional, Kinyera, Tobias, additional, Otim, Isaac, additional, Legason, Ismail D., additional, Nabalende, Hadijah, additional, Dhudha, Herry, additional, Ayers, Leona W., additional, Bhatia, Kishor, additional, Goedert, James J., additional, Cole, Nathan, additional, Luo, Wen, additional, Liu, Jia, additional, Manning, Michelle, additional, Hicks, Belynda, additional, Prokunina-Olsson, Ludmila, additional, Chagaluka, George, additional, Johnston, W. Thomas, additional, Mutalima, Nora, additional, Borgstein, Eric, additional, Liomba, George N., additional, Kamiza, Steve, additional, Mkandawire, Nyengo, additional, Mitambo, Collins, additional, Molyneux, Elizabeth M., additional, Newton, Robert, additional, Hsing, Ann W., additional, Mensah, James E., additional, Adjei, Anthony A., additional, Hutchinson, Amy, additional, Carrington, Mary, additional, Yeager, Meredith, additional, Blasczyk, Rainer, additional, Chanock, Stephen J., additional, Raychaudhuri, Soumya, additional, and Mbulaiteye, Sam M., additional

Published
2024
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7. Inverse association of falciparum positivity with endemic Burkitt lymphoma is robust in analyses adjusting for pre-enrollment malaria in the EMBLEM case-control study

Author

Peprah, Sally, Ogwang, Martin D., Kerchan, Patrick, Reynolds, Steven J., Tenge, Constance N., Were, Pamela A., Kuremu, Robert T., Wekesa, Walter N., Masalu, Nestory, Kawira, Esther, Otim, Isaac, Legason, Ismail D., Ayers, Leona W., Bhatia, Kishor, Goedert, James J., Pfeiffer, Ruth M., and Mbulaiteye, Sam M.

Published
2021
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8. Sickle cell allele HBB‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa

Author

Hong, Hyokyoung G., primary, Gouveia, Mateus H., additional, Ogwang, Martin D., additional, Kerchan, Patrick, additional, Reynolds, Steven J., additional, Tenge, Constance N., additional, Were, Pamela A., additional, Kuremu, Robert T., additional, Wekesa, Walter N., additional, Masalu, Nestory, additional, Kawira, Esther, additional, Kinyera, Tobias, additional, Wang, Xunde, additional, Zhou, Jiefu, additional, Leal, Thiago Peixoto, additional, Otim, Isaac, additional, Legason, Ismail D., additional, Nabalende, Hadijah, additional, Dhudha, Herry, additional, Mumia, Mediatrix, additional, Baker, Francine S., additional, Okusolubo, Temiloluwa, additional, Ayers, Leona W., additional, Bhatia, Kishor, additional, Goedert, James J., additional, Woo, Joshua, additional, Manning, Michelle, additional, Cole, Nathan, additional, Luo, Wen, additional, Hicks, Belynda, additional, Chagaluka, George, additional, Johnston, W. Thomas, additional, Mutalima, Nora, additional, Borgstein, Eric, additional, Liomba, George N., additional, Kamiza, Steve, additional, Mkandawire, Nyengo, additional, Mitambo, Collins, additional, Molyneux, Elizabeth M., additional, Newton, Robert, additional, Hutchinson, Amy, additional, Yeager, Meredith, additional, Adeyemo, Adebowale A., additional, Thein, Swee Lay, additional, Rotimi, Charles N., additional, Chanock, Stephen J., additional, Prokunina‐Olsson, Ludmila, additional, and Mbulaiteye, Sam M., additional

Published
2023
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9. A case-control study of Burkitt lymphoma in East Africa: are local health facilities an appropriate source of representative controls?

Author

Baik, Sonya, Mbaziira, Mike, Williams, Makeda, Ogwang, Martin D, Kinyera, Tobias, Emmanuel, Benjamin, Ziegler, John L, Reynolds, Steven J, and Mbulaiteye, Sam M

Abstract

Abstract Background We investigated the feasibility and appropriateness of enrolling controls for Burkitt lymphoma (BL) from local health facilities in two regions in Uganda. Methods BL case data were compiled from two local hospitals with capacity to diagnose and treat BL in North-west and North-central regions of Uganda during 1997 to 2009. Local health facility data were compiled from children attending four representative local health facilities in the two regions over a two week period in May/June 2010. Age and sex patterns of BL cases and children at local facilities were compared and contrasted using frequency tables. Results There were 999 BL cases diagnosed in the study area (92% of all BL cases treated at the hospitals): 64% were from North-central and 36% from North-west region. The mean age of BL cases was 7.0 years (standard deviation [SD] 3.0). Boys were younger than girls (6.6 years versus 7.2 years, P = 0.004) and cases from North-central region were younger than cases from North-west region (6.8 years versus 7.3 years, P = 0.014). There were 1012 children recorded at the four local health facilities: 91% at facilities in North-central region and 9% from facilities in North-west region. Daily attendance varied between 1 to 75 children per day. The mean age of children at health facilities was 2.2 years (SD 2.8); it did not differ by sex. Children at North-central region facilities were younger than children at North-west region facilities (1.8 years versus 6.6 years, P < 0.001). Conclusions While many children attend local health facilities, confirming feasibility of obtaining controls, their mean age is much lower than BL cases. Health facilities may be suitable for obtaining young, but not older, controls.

Published
2012

10. Endemic Burkitt lymphoma: a complication of asymptomatic malaria in sub-Saharan Africa based on published literature and primary data from Uganda, Tanzania, and Kenya

Author

Redmond, Lawrence S., Ogwang, Martin D., Kerchan, Patrick, Reynolds, Steven J., Tenge, Constance N., Were, Pamela A., Kuremu, Robert T., Masalu, Nestory, Kawira, Esther, Otim, Isaac, Legason, Ismail D., Dhudha, Herry, Ayers, Leona W., Bhatia, Kishor, Goedert, James J., and Mbulaiteye, Sam M.

Published
2020
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11. Sickle cell allele HBB‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.

Author

Hong, Hyokyoung G., Gouveia, Mateus H., Ogwang, Martin D., Kerchan, Patrick, Reynolds, Steven J., Tenge, Constance N., Were, Pamela A., Kuremu, Robert T., Wekesa, Walter N., Masalu, Nestory, Kawira, Esther, Kinyera, Tobias, Wang, Xunde, Zhou, Jiefu, Leal, Thiago Peixoto, Otim, Isaac, Legason, Ismail D., Nabalende, Hadijah, Dhudha, Herry, and Mumia, Mediatrix

Published
2024
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13. Burkitt lymphoma risk shows geographic and temporal associations with Plasmodium falciparum infections in Uganda, Tanzania, and Kenya

Author

Broen, Kelly, primary, Dickens, Joey, additional, Trangucci, Rob, additional, Ogwang, Martin D., additional, Tenge, Constance N., additional, Masalu, Nestory, additional, Reynolds, Steven J., additional, Kawira, Esther, additional, Kerchan, Patrick, additional, Were, Pamela A., additional, Kuremu, Robert T., additional, Wekesa, Walter N., additional, Kinyera, Tobias, additional, Otim, Isaac, additional, Legason, Ismail D., additional, Nabalende, Hadija, additional, Buller, Ian D., additional, Ayers, Leona W., additional, Bhatia, Kishor, additional, Biggar, Robert J., additional, Goedert, James J., additional, Wilson, Mark L., additional, Mbulaiteye, Sam M., additional, and Zelner, Jon, additional

Published
2023
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14. DNA Methylation-Based Burkitt Lymphoma Epitypes Have Distinct Molecular and Clinical Features

Author

Thomas, Nicole, primary, Dreval, Kostiantyn, additional, Gerhard, Daniela S., additional, Hilton, Laura K, additional, Abramson, Jeremy S., additional, Bartlett, Nancy L., additional, Bethony, Jeffrey, additional, Bowen, Jay, additional, Bryan, Anthony, additional, Casper, Corey, additional, Dyer, Maureen, additional, Esteller, Manel, additional, Garcia-Prieto, Carlos, additional, Gastier-Foster, Julie M, additional, Gerrie, Alina S., additional, Grande, Bruno M., additional, Greiner, Timothy C., additional, Griner, Nicholas B., additional, Gross, Thomas G., additional, Harris, Nancy Lee, additional, Irvin, John D., additional, Jaffe, Elaine S., additional, Leal, Fabio, additional, Martin, Jean Paul, additional, Martin, Marie-Reine, additional, Mbulaiteye, Sam M., additional, Mullighan, Charles G., additional, Mungall, Andrew J., additional, Mungall, Karen, additional, Namirembe, Constance, additional, Noy, Ariela, additional, Ogwang, Martin D, additional, Orem, Jackson, additional, Ott, German, additional, Petrello, Hilary, additional, Reynolds, Steven J, additional, Swerdlow, Steven H., additional, Traverse-Glehen, Alexandra, additional, Wilson, Wyndham H., additional, Marra, Marco A., additional, Staudt, Louis M., additional, Scott, David W., additional, and Morin, Ryan D., additional

Published
2022
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16. Epstein-Barr Virus in Burkitt Lymphoma in Africa Reveals a Limited Set of Whole Genome and LMP-1 Sequence Patterns: Analysis of Archival Datasets and Field Samples From Uganda, Tanzania, and Kenya

Author

Liao, Hsiao-Mei, primary, Liu, Hebing, additional, Chin, Pei-Ju, additional, Li, Bingjie, additional, Hung, Guo-Chiuan, additional, Tsai, Shien, additional, Otim, Isaac, additional, Legason, Ismail D., additional, Ogwang, Martin D., additional, Reynolds, Steven J., additional, Kerchan, Patrick, additional, Tenge, Constance N., additional, Were, Pamela A., additional, Kuremu, Robert T., additional, Wekesa, Walter N., additional, Masalu, Nestory, additional, Kawira, Esther, additional, Ayers, Leona W., additional, Pfeiffer, Ruth M., additional, Bhatia, Kishor, additional, Goedert, James J., additional, Lo, Shyh-Ching, additional, and Mbulaiteye, Sam M., additional

Published
2022
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17. Plasma EBV DNA: A Promising Diagnostic Marker for Endemic Burkitt Lymphoma

Author

Xian, Rena R., primary, Kinyera, Tobias, additional, Otim, Isaac, additional, Sampson, Joshua N., additional, Nabalende, Hadijah, additional, Legason, Ismail D., additional, Stone, Jennifer, additional, Ogwang, Martin D., additional, Reynolds, Steven J., additional, Kerchan, Patrick, additional, Bhatia, Kishor, additional, Goedert, James J., additional, Mbulaiteye, Sam M., additional, and Ambinder, Richard F., additional

Published
2021
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18. Additional file 1 of Inverse association of falciparum positivity with endemic Burkitt lymphoma is robust in analyses adjusting for pre-enrollment malaria in the EMBLEM case-control study

Author

Peprah, Sally, Ogwang, Martin D., Kerchan, Patrick, Reynolds, Steven J., Tenge, Constance N., Were, Pamela A., Kuremu, Robert T., Wekesa, Walter N., Masalu, Nestory, Kawira, Esther, Otim, Isaac, Legason, Ismail D., Ayers, Leona W., Bhatia, Kishor, Goedert, James J., Pfeiffer, Ruth M., and Mbulaiteye, Sam M.

Abstract

Additional file 1: Supplementary Table 1. Questionnaire variables/data elements and how they were coded for exploratory factor analysis. Supplementary Table 2. Eigenvalue and variance explained by extracted factors shown for each imputed dataset and by study country. Supplementary Table 3. Odds ratios and 95% confidence intervals (CIs) of the association of factors with falciparum infection risk in controls, by country. Supplementary Table 4. Odds ratios and 95% confidence intervals (CIs) of the association of factors with eBL risk, by country.

Published
2021
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19. Genomic Landscape of Epstein-Barr Virus in Endemic Burkitt Lymphoma

Author

Legason, Ismail D, Burns, Adam, Ridout, Kate, Jennings, Daisy, Ogwang, Martin D, Otim, Isaac, Nabalende, Hadijah, Achola, Caroline, Ayitewala, Alisen, Sseruyange, Julius, Chamba, Clara C, Josephat, Emmanuel, Christopher, Heavenlight, Mawalla, William F, Mkwizu, Elifurah, Mremi, Alex, Mwamtemi, Hadija, Dreau, Helene, El Mouden, Claire, Vavoulis, Dimitris, Leung, Carol Sze, and Schuh, Anna

Published
2023
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20. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics

Author

Schmitz, Roland, Young, Ryan M., Ceribelli, Michele, Jhavar, Sameer, Xiao, Wenming, Zhang, Meili, Wright, George, Shaffer, Arthur L., Hodson, Daniel J., Buras, Eric, Liu, Xuelu, Powell, John, Yang, Yandan, Xu, Weihong, Zhao, Hong, Kohlhammer, Holger, Rosenwald, Andreas, Kluin, Philip, Müller-Hermelink, Hans Konrad, Ott, German, Gascoyne, Randy D., Connors, Joseph M., Rimsza, Lisa M., Campo, Elias, Jaffe, Elaine S., Delabie, Jan, Smeland, Erlend B., Ogwang, Martin D., Reynolds, Steven J., Fisher, Richard I., Braziel, Rita M., Tubbs, Raymond R., Cook, James R., Weisenburger, Dennis D., Chan, Wing C., Pittaluga, Stefania, Wilson, Wyndham, Waldmann, Thomas A., Rowe, Martin, Mbulaiteye, Sam M., Rickinson, Alan B., and Staudt, Louis M.

Published
2012
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21. Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studies

Author

Derkach, Andriy, Otim, Isaac, Pfeiffer, Ruth M., Onabajo, Olusegun O., Legason, Ismail D., Nabalende, Hadijah, Ogwang, Martin D., Kerchan, Patrick, Talisuna, Ambrose O., Ayers, Leona W., Reynolds, Steven J., Nkrumah, Francis, Neequaye, Janet, Bhatia, Kishor, Theander, Thor G., Prokunina-Olsson, Ludmila, Turner, Louise, Goedert, James J., Lavstsen, Thomas, Mbulaiteye, Sam M., Derkach, Andriy, Otim, Isaac, Pfeiffer, Ruth M., Onabajo, Olusegun O., Legason, Ismail D., Nabalende, Hadijah, Ogwang, Martin D., Kerchan, Patrick, Talisuna, Ambrose O., Ayers, Leona W., Reynolds, Steven J., Nkrumah, Francis, Neequaye, Janet, Bhatia, Kishor, Theander, Thor G., Prokunina-Olsson, Ludmila, Turner, Louise, Goedert, James J., Lavstsen, Thomas, and Mbulaiteye, Sam M.

Abstract

Background: Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma linked to Plasmodium falciparum (Pf) malaria in sub-Saharan Africa. We investigated antibody reactivity to several human receptor-binding domains of the Pf erythrocyte membrane protein 1 (PfEMP1) that play a key role in malaria pathogenesis and are targets of acquired immunity to malaria. Methods: Serum/plasma IgG antibody reactivity was measured to 22 Pf antigens, including 18 to PfEMP1 CIDR domains between cases and controls from two populations (149 eBL cases and 150 controls from Ghana and 194 eBL cases and 600 controls from Uganda). Adjusted odds ratios (aORs) for case-control associations were estimated by logistic regression. Findings: There was stronger reactivity to the severe malaria associated CIDRα1 domains than other CIDR domains both in cases and controls. eBL cases reacted to fewer antigens than controls (Ghana: p = 0·001; Uganda: p = 0·03), with statistically significant lower ORs associated with reactivity to 13+ antigens in Ghana (aOR 0·39, 95% CI 0·24–0·63; pheterogeneity = 0·00011) and Uganda (aOR 0·60, 95% CI 0.41–0·88; pheterogeneity = 0·008). eBL was inversely associated with reactivity, coded as quartiles, to group A variant CIDRδ1 (ptrend = 0·035) in Ghana and group B CD36-binding variants CIDRα2·2 (ptrend = 0·006) and CIDRα2·4 (ptrend = 0·033) in Uganda, and positively associated with reactivity to SERA5 in Ghana (ptrend = 0·017) and Uganda (ptrend = 0·007) and group A CIDRα1·5 variant in Uganda only (ptrend = 0·034). Interpretation: eBL cases reacted to fewer antigens than controls using samples from two populations, Ghana and Uganda. Attenuated humoral immunity to Pf EMP1 may contribute to susceptibility to low-grade malaria and eBL risk. Funding: Intramural Research Program, National Cancer Institute and National Institute of Allergy and Infectious Diseases, Natio

Published
2019

22. Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma

Author

Grande, Bruno M., primary, Gerhard, Daniela S., additional, Jiang, Aixiang, additional, Griner, Nicholas B., additional, Abramson, Jeremy S., additional, Alexander, Thomas B., additional, Allen, Hilary, additional, Ayers, Leona W., additional, Bethony, Jeffrey M., additional, Bhatia, Kishor, additional, Bowen, Jay, additional, Casper, Corey, additional, Choi, John Kim, additional, Culibrk, Luka, additional, Davidsen, Tanja M., additional, Dyer, Maureen A., additional, Gastier-Foster, Julie M., additional, Gesuwan, Patee, additional, Greiner, Timothy C., additional, Gross, Thomas G., additional, Hanf, Benjamin, additional, Harris, Nancy Lee, additional, He, Yiwen, additional, Irvin, John D., additional, Jaffe, Elaine S., additional, Jones, Steven J. M., additional, Kerchan, Patrick, additional, Knoetze, Nicole, additional, Leal, Fabio E., additional, Lichtenberg, Tara M., additional, Ma, Yussanne, additional, Martin, Jean Paul, additional, Martin, Marie-Reine, additional, Mbulaiteye, Sam M., additional, Mullighan, Charles G., additional, Mungall, Andrew J., additional, Namirembe, Constance, additional, Novik, Karen, additional, Noy, Ariela, additional, Ogwang, Martin D., additional, Omoding, Abraham, additional, Orem, Jackson, additional, Reynolds, Steven J., additional, Rushton, Christopher K., additional, Sandlund, John T., additional, Schmitz, Roland, additional, Taylor, Cynthia, additional, Wilson, Wyndham H., additional, Wright, George W., additional, Zhao, Eric Y., additional, Marra, Marco A., additional, Morin, Ryan D., additional, and Staudt, Louis M., additional

Published
2019
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23. Genetic signatures of gene flow and malaria-driven natural selection in sub-Saharan populations of the "endemic Burkitt Lymphoma belt"

Author

Gouveia, Mateus H., primary, Bergen, Andrew W., additional, Borda, Victor, additional, Nunes, Kelly, additional, Leal, Thiago P., additional, Ogwang, Martin D., additional, Yeboah, Edward D., additional, Mensah, James E., additional, Kinyera, Tobias, additional, Otim, Isaac, additional, Nabalende, Hadijah, additional, Legason, Ismail D., additional, Mpoloka, Sununguko Wata, additional, Mokone, Gaonyadiwe George, additional, Kerchan, Patrick, additional, Bhatia, Kishor, additional, Reynolds, Steven J., additional, Birtwum, Richard B., additional, Adjei, Andrew A., additional, Tettey, Yao, additional, Tay, Evelyn, additional, Hoover, Robert, additional, Pfeiffer, Ruth M., additional, Biggar, Robert J., additional, Goedert, James J., additional, Prokunina-Olsson, Ludmila, additional, Dean, Michael, additional, Yeager, Meredith, additional, Lima-Costa, M. Fernanda, additional, Hsing, Ann W., additional, Tishkoff, Sarah A., additional, Chanock, Stephen J., additional, Tarazona-Santos, Eduardo, additional, and Mbulaiteye, Sam M., additional

Published
2019
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24. Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studies

Author

Derkach, Andriy, primary, Otim, Isaac, additional, Pfeiffer, Ruth M., additional, Onabajo, Olusegun O., additional, Legason, Ismail D., additional, Nabalende, Hadijah, additional, Ogwang, Martin D., additional, Kerchan, Patrick, additional, Talisuna, Ambrose O., additional, Ayers, Leona W., additional, Reynolds, Steven J., additional, Nkrumah, Francis, additional, Neequaye, Janet, additional, Bhatia, Kishor, additional, Theander, Thor G., additional, Prokunina-Olsson, Ludmila, additional, Turner, Louise, additional, Goedert, James J., additional, Lavstsen, Thomas, additional, and Mbulaiteye, Sam M., additional

Published
2019
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25. Cango Lyec (Healing the Elephant): Gender Differences in HIV Infection in Post-conflict Northern Uganda

Author

Spittal, Patricia M., primary, Malamba, Samuel S., additional, Ogwang, Martin D., additional, Musisi, Seggane, additional, Ekwaru, J. Paul, additional, Sewankambo, Nelson K., additional, Pearce, Margo E., additional, Jongbloed, Kate, additional, Patel, Sheetal H., additional, Katamba, Achilles, additional, Blair, Alden H., additional, Muyinda, Herbert, additional, and Schechter, Martin T., additional

Published
2018
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26. Accuracy of burkitt lymphoma diagnosis in constrained pathology settings: importance to epidemiology

Author

Ogwang, Martin D., Zhao, Weiqiang, Ayers, Leona W., and Mbulaiteye, Sam M.

Subjects
Immunohistochemistry, Non-Hodgkin's lymphomas, Formaldehyde, Epidemiology, Burkitt's lymphoma, Health
Abstract

Context.--Burkitt lymphoma (BL) is endemic in Uganda and because of the high incidence, diagnosis is often presumed during clinical care and epidemiologic studies. Objectives.--To assess the accuracy of the clinical and the local pathology diagnosis of BL as assessed by an outside pathology review diagnosis and to understand the limitations on histopathology practice in a resource-constrained setting at 1 hospital in Uganda. Design.--Clinically presumed pediatric ( Results.--Local pathology laboratory procedures were inconsistent and suboptimal, especially for tissue fixation. There were 88 clinically presumed BL cases. Sixty-three could be reviewed by outside pathology (25 cases of lost blocks or no remaining tumor) and showed a clinical diagnostic accuracy of 75% (47 confirmed of 63), with a possible range of 62% to 85%, depending on the actual diagnosis of the 25 nonevaluable cases. There were 64 BL cases diagnosed by local pathology. Forty-five could be reviewed by outside pathology (19 cases of lost blocks or no remaining tumor) and showed a local pathology diagnostic accuracy of 82% (37 confirmed of 45), with a possible range of 58% to 88%, depending on the actual diagnosis of the 19 nonevaluable cases. Non-BL diagnoses included other non-Hodgkin lymphomas, Hodgkin lymphoma, and benign infectious lymphadenopathy. Conclusions.--Accuracy of clinical diagnosis of BL was reduced by inclusion of other diseases with similar clinical presentations. Local pathology, using morphology alone, only marginally improved clinical accuracy and often could not support outside pathology review due to inadequate laboratory procedures. There is an urgent need to improve pathology services in Uganda before conducting high-quality clinical and epidemiologic studies., Accurate and reliable histopathology diagnosis is critical for confirmation of significant diseases, disease classification, disease registration, and clinical and epidemiologic studies, especially of cancer. Fewer than 50% of cancers in [...]

Published
2011

27. Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study

Author

Legason, Ismail D., primary, Pfeiffer, Ruth M., additional, Udquim, Krizia-Ivana, additional, Bergen, Andrew W., additional, Gouveia, Mateus H., additional, Kirimunda, Samuel, additional, Otim, Isaac, additional, Karlins, Eric, additional, Kerchan, Patrick, additional, Nabalende, Hadijah, additional, Bayanjargal, Ariunaa, additional, Emmanuel, Benjamin, additional, Kagwa, Paul, additional, Talisuna, Ambrose O., additional, Bhatia, Kishor, additional, Yeager, Meredith, additional, Biggar, Robert J., additional, Ayers, Leona W., additional, Reynolds, Steven J., additional, Goedert, James J., additional, Ogwang, Martin D., additional, Fraumeni, Joseph F., additional, Prokunina-Olsson, Ludmila, additional, and Mbulaiteye, Sam M., additional

Published
2017
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28. Age and geographic patterns of Plasmodium falciparum malaria infection in a representative sample of children living in Burkitt lymphoma-endemic areas of northern Uganda

Author

Maziarz, Marlena, primary, Kinyera, Tobias, additional, Otim, Isaac, additional, Kagwa, Paul, additional, Nabalende, Hadijah, additional, Legason, Ismail D., additional, Ogwang, Martin D., additional, Kirimunda, Samuel, additional, Emmanuel, Benjamin, additional, Reynolds, Steven J., additional, Kerchan, Patrick, additional, Joloba, Moses M., additional, Bergen, Andrew W., additional, Bhatia, Kishor, additional, Talisuna, Ambrose O., additional, Biggar, Robert J., additional, Goedert, James J., additional, Pfeiffer, Ruth M., additional, and Mbulaiteye, Sam M., additional

Published
2017
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29. Burkitt Lymphoma Genome Sequencing Project (BLGSP): Introduction

Author

Gerhard, Daniela S, primary, Grande, Bruno, additional, Griner, Nicholas, additional, Casper, Corey, additional, Gerdts, Sarah E., additional, Omoding, Abraham, additional, Orem, Jackson, additional, Mbulaiteye, Sam M, additional, Ogwang, Martin D., additional, Reynolds, Steven J., additional, Bhatia, Kishor, additional, Ayers, Leona, additional, Choi, John K, additional, Mullighan, Charles G., additional, Sandlund, John T., additional, Alexander, Thomas B., additional, Abramson, Jeremy S., additional, Gross, Thomas G., additional, Noy, Ariela, additional, Bethony, Jeffrey, additional, Leal, Fabio, additional, Greiner, Timothy C, additional, Jaffe, Elaine S., additional, Harris, Nancy Lee, additional, Gastier-Foster, Julie M., additional, Bowen, Jay, additional, Hanf, Benjamin, additional, Schmitz, Roland, additional, Martin, Jean-Paul, additional, Martin, Marie-Reine, additional, Irvin, John D., additional, Miller, Ellen, additional, Gesuwan, Patee, additional, Hermida, Leandro C., additional, Davidsen, Tanja M., additional, Mungall, Andrew J., additional, Ma, Yussanne, additional, Marra, Marco A., additional, Morin, Ryan D., additional, and Staudt, Louis M., additional

Published
2016
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30. “The Cango Lyec Project - Healing the Elephant”: HIV related vulnerabilities of post-conflict affected populations aged 13–49 years living in three Mid-Northern Uganda districts

Author

Malamba, Samuel S., primary, Muyinda, Herbert, additional, Spittal, Patricia M., additional, Ekwaru, John P., additional, Kiwanuka, Noah, additional, Ogwang, Martin D., additional, Odong, Patrick, additional, Kitandwe, Paul K., additional, Katamba, Achilles, additional, Jongbloed, Kate, additional, Sewankambo, Nelson K., additional, Kinyanda, Eugene, additional, Blair, Alden, additional, and Schechter, Martin T., additional

Published
2016
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32. Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma

Author

Thomas, Nicole, Dreval, Kostiantyn, Gerhard, Daniela S., Hilton, Laura K., Abramson, Jeremy S., Ambinder, Richard F., Barta, Stefan, Bartlett, Nancy L., Bethony, Jeffrey, Bhatia, Kishor, Bowen, Jay, Bryan, Anthony C., Cesarman, Ethel, Casper, Corey, Chadburn, Amy, Cruz, Manuela, Dittmer, Dirk P., Dyer, Maureen A., Farinha, Pedro, Gastier-Foster, Julie M., Gerrie, Alina S., Grande, Bruno M., Greiner, Timothy, Griner, Nicholas B., Gross, Thomas G., Harris, Nancy L., Irvin, John D., Jaffe, Elaine S., Henry, David, Huppi, Rebecca, Leal, Fabio E., Lee, Michael, Martin, Jean Paul, Martin, Marie-Reine, Mbulaiteye, Sam M., Mitsuyasu, Ronald, Morris, Vivian, Mullighan, Charles G., Mungall, Andrew J., Mungall, Karen, Mutyaba, Innocent, Nokta, Mostafa, Namirembe, Constance, Noy, Ariela, Ogwang, Martin D., Omoding, Abraham, Orem, Jackson, Ott, German, Petrello, Hilary, Pittaluga, Stefania, Phelan, James D., Ramos, Juan Carlos, Ratner, Lee, Reynolds, Steven J., Rubinstein, Paul, Sissolak, Gerhard, Slack, Graham, Soudi, Shaghayegh, Swerdlow, Steven H., Traverse-Glehen, Alexandra, Wilson, Wyndham H., Wong, Jasper, Yarchoan, Robert, ZenKlusen, Jean C., Marra, Marco A., Staudt, Louis M., Scott, David W., and Morin, Ryan D.

Abstract

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

Published
2022
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33. A cross-sectional study of asymptomatic <italic>Plasmodium falciparum</italic> infection burden and risk factors in general population children in 12 villages in northern Uganda.

Author

Maziarz, Marlena, Nabalende, Hadijah, Otim, Isaac, Legason, Ismail D., Kinyera, Tobias, Ogwang, Martin D., Talisuna, Ambrose O., Reynolds, Steven J., Kerchan, Patrick, Bhatia, Kishor, Biggar, Robert J., Goedert, James J., Pfeiffer, Ruth M., and Mbulaiteye, Sam M.

Subjects
PLASMODIUM falciparum, EPIDEMIOLOGY, MALARIA, LYMPHOMAS, MICROSCOPY
Abstract

Background: Plasmodium falciparum malaria is an important cause of morbidity in northern Uganda. This study was undertaken to assess village-, household-, and individual-level risk factors of asymptomatic falciparum malaria in children in 12 villages in northern Uganda. Methods: Between 10/2011 and 02/2014, 1006 apparently healthy children under 16 years old were enrolled in 12 villages using a stratified, multi-stage, cluster survey design and assessed for P. falciparum malaria infection using the rapid diagnostic test (RDT) and thick film microscopy (TFM), and structured interviewer-administered questionnaires. Associations between weighted P. falciparum malaria prevalence (pfPR), based on RDT, and covariates were estimated as odds ratios and 95% confidence intervals (ORs, 95% CIs) using logistic models accounting for the survey design. Results: Among 942 (93.5%) children successfully tested, pfPR was 52.4% by RDT and 32.7% by TFM. Overall pfPR was lower in villages where indoor residual insecticide spray (IRS) was, versus not, implemented (18.4% versus 75.2%, P < 0.0001). However, pfPR was heterogeneous both within IRS (10.6–34.8%) and non-IRS villages (63.6–86.2%). Elevated pfPR was associated with having a sibling who was RDT positive (OR 5.39, 95% CI 2.94–9.90, P = 0.0006) and reporting a fever at enrollment (aOR 4.80, 95% CI 1.94–11.9, P = 0.0094). Decreased pfPR was associated with living in an IRS village (adjusted OR 0.06, 95% CI 0.04–0.07, P < 0.0001), in a household with one (aOR 0.48, 95% CI 0.30–0.76) or more than one child below 5 years (aOR 0.23, 95% CI 0.12–0.44, Ptrend = 0.014), and reporting keeping a goat inside or near the house (aOR 0.42, 95% CI 0.29–0.62, P = 0.0021). Conclusions: The results show high but heterogeneous pfPR in villages in northern Uganda, confirm significantly decreased pfPR associated with IRS implementation, and suggest significant associations with some household characteristics. Further research is needed to elucidate the factors influencing malaria heterogeneity in villages in Uganda. [ABSTRACT FROM AUTHOR]

Published
2018
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34. Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda.

Author

Liao, Hsiao-Mei, Liu, Hebing, Lei, Heiyan, Li, Bingjie, Chin, Pei-Ju, Tsai, Shien, Bhatia, Kishor, Gutierrez, Marina, Epelman, Sidnei, Biggar, Robert J., Nkrumah, Francis, Neequaye, Janet, Ogwang, Martin D., Reynolds, Steven J., Lo, Shyh-Ching, and Mbulaiteye, Sam M.

Subjects
B cell lymphoma, BIOPSY, CONFIDENCE intervals, EPIDEMIOLOGICAL research, EPSTEIN-Barr virus, EPSTEIN-Barr virus diseases, MICROBIAL genetics, POLYMERASE chain reaction, SEQUENCE analysis, ODDS ratio
Abstract

Epstein-Barr virus (EBV) is linked to several cancers, including endemic Burkitt lymphoma (eBL), but causal variants are unknown. We recently reported novel sequence variants in the LMP-1 gene and promoter in EBV genomes sequenced from 13 of 14 BL biopsies. Alignments of the novel sequence variants for 114 published EBV genomes, including 27 from BL cases, revealed four LMP-1 variant patterns, designated A to D. Pattern A variant was found in 48% of BL EBV genomes. Here, we used PCR-Sanger sequencing to evaluate 50 additional BL biopsies from Ghana, Brazil, and Argentina, and peripheral blood samples from 113 eBL cases and 115 controls in Uganda. Pattern A was found in 60.9% of 64 BL biopsies evaluated. Compared to PCR-negative subjects in Uganda, detection of Pattern A in peripheral blood was associated with eBL case status (odds ratio [OR] 31.7, 95% confidence interval: 6.8–149), controlling for relevant confounders. Variant Pattern A and Pattern D were associated with eBL case status, but with lower ORs (9.7 and 13.6, respectively). Our results support the hypothesis that EBV LMP-1 Pattern A may be associated with eBL, but it is not the sole associated variant. Further research is needed to replicate and elucidate our findings. [ABSTRACT FROM AUTHOR]

Published
2018
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35. Cango Lyec (Healing the Elephant): HIV Prevalence and Vulnerabilities Among Adolescent Girls and Young Women in Postconflict Northern Uganda.

Author

Muyinda H, Jongbloed K, Zamar DS, Malamba SS, Ogwang MD, Katamba A, Oneka A, Atim S, Odongpiny TO, Sewankambo NK, Schechter MT, and Spittal PM

Subjects
Adolescent, Female, Humans, Prevalence, Sexual Behavior, Uganda epidemiology, Young Adult, HIV Infections prevention & control, Syphilis
Abstract

Objectives: Adolescent girls and young women younger than 25 years (AGYW) account for disproportionate HIV infections in sub-Saharan Africa. Impacts of war in Northern Uganda continue to affect HIV-related health and wellbeing of young people postconflict. Prevalence and incidence of HIV infection were estimated, and factors associated with HIV prevalence among sexually active AGYW in Northern Uganda were investigated., Methods: Cango Lyec is a cohort involving conflict-affected populations in Northern Uganda. Nine randomly selected communities in Gulu, Nwoya, and Amuru districts were mapped. House-to-house census was conducted. Consenting participants aged 13-49 years were enrolled over 3 study rounds (2011-2015), of whom 533 were AGYW and had ever had sex. Data were collected on trauma, depression, and sociodemographic-behavioral characteristics. Venous blood was taken for HIV and syphilis serology. Multivariable logistic regression determined baseline factors associated with HIV prevalence., Results: HIV prevalence among AGYW was 9.7% (95% CI: 7.3 to 12.6). AGYW living in Gulu (adjusted risk ratio, aRR: 2.48; 95% CI: 1.12 to 5.51) or Nwoya (aRR: 2.65; 95% CI: 1.03 to 6.83) were more likely than in Amuru to be living with HIV. Having self-reported genital ulcers (aRR: 1.93; 95% CI: 0.97 to 3.85) or active syphilis (aRR: 3.79; 95% CI: 2.35 to 6.12) was associated with increased risk of HIV infection. The likelihood of HIV was higher for those who experienced sexual violence in the context of war (aRR: 2.37; 95% CI: 1.21 to 4.62) and/or probable depression (aRR: 1.95; 95% CI: 1.08 to 3.54). HIV incidence was 8.9 per 1000 person-years., Conclusion: Ongoing legacies of war, especially gender violence and trauma, contribute to HIV vulnerability among sexually active AGYW. Wholistic approaches integrating HIV prevention with culturally safe initiatives promoting sexual and mental health in Northern Uganda are essential., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Published
2023
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36. Cango Lyec (Healing the Elephant): Gender Differences in HIV Infection in Post-conflict Northern Uganda.

Author

Spittal PM, Malamba SS, Ogwang MD, Musisi S, Ekwaru JP, Sewankambo NK, Pearce ME, Jongbloed K, Patel SH, Katamba A, Blair AH, Muyinda H, and Schechter MT

Subjects
Adolescent, Adult, Depression psychology, Female, HIV Infections psychology, HIV Seroprevalence, Humans, Male, Middle Aged, Rape, Stress Disorders, Post-Traumatic psychology, Surveys and Questionnaires, Uganda epidemiology, Young Adult, Armed Conflicts, HIV Infections epidemiology, Sex Factors
Abstract

Background: As previously encamped resettle, potential for rapid HIV transmission in post-conflict Northern Uganda is concerning. Women in particular may be experiencing heightened vulnerability resulting from war-related sexual violence., Setting: Cango Lyec (Healing the Elephant) Project is a cohort involving conflict-affected people in 3 districts in Northern Uganda., Methods: Eight randomly selected communities were mapped, and a census was conducted. Participants aged 13-49 years completed questionnaires in Luo on war-related experiences, mental health, sexual vulnerabilities, and sociodemographics. Blood samples were tested for HIV and syphilis. Baseline data from all sexually active participants was used to determine gender differences in HIV prevalence. Multivariate modeling determined correlates of HIV by gender., Results: Among 2008 participants, HIV prevalence was higher among women [17.2; 95% confidence interval (CI): 14.7 to 19.7] compared to men (10.6; 95% CI: 8.0 to 13.2, <0.001). Among women, correlates of HIV included: war-related sexual assault [adjusted odds ratio (AOR): 1.95; 95% CI: 1.16 to 3.26]; probable depression (AOR: 2.22; 95% CI: 1.46 to 3.37); probable post-traumatic stress disorder (AOR: 2.03; 95% CI: 1.45 to 2.84); experiencing ≥12 traumatic events (AOR: 2.04; 95% CI: 1.31 to 3.18); suicide ideation (AOR: 1.67; 95% CI: 1.22 to 2.28); living in a female-headed household (AOR: 2.76; 95% CI: 1.70 to 4.49); first sexual partner ≥10 years older (AOR: 1.69; 95% CI: 1.07 to 2.67); sex for exchange (AOR: 5.51; 95% CI: 1.76 to 17.31); having 2 (AOR: 2.54; 95% CI: 1.23 to 5.23) or 3+ (AOR: 4.65; 95% CI: 2.65 to 8.18) sexual partners; inconsistent condom use (AOR: 0.40; 95% CI: 0.29 to 0.57); genital ulcers (AOR: 3.08; 95% CI: 2.16 to 4.38); active syphilis (AOR: 4.33; 95% CI: 1.22 to 15.40); and ill health without medical care (AOR: 2.02; 95% CI: 1.22 to 3.34). Among men, correlates of HIV included no condom at sexual debut (AOR: 1.92; 95% CI: 1.30 to 2.83) and genital ulcers (AOR: 4.40; 95% CI: 1.35 to 14.40)., Conclusion: Women are disproportionately impacted by HIV, trauma, and depression in this conflict-affected population. Trauma-informed HIV prevention and culturally safe mental health initiatives are urgently required.

Published
2018
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