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4. Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Author

Abathina, Amadou, Abubakar, Ismaela, Achidi, Eric, Agbenyega, Tsiri, Aiyegbo, Mohammed, Akoto, Alex, Allen, Angela, Allen, Stephen, Amenga-Etego, Lucas, Amodu, Folakemi, Amodu, Olukemi, Anchang-Kimbi, Judith, Ansah, Nana, Ansah, Patrick, Ansong, Daniel, Antwi, Sampson, Anyorigiya, Thomas, Apinjoh, Tobias, Asafo-Agyei, Emmanuel, Asoala, Victor, Atuguba, Frank, Auburn, Sarah, Bah, Abdou, Bamba, Kariatou, Bancone, Germana, Band, Gavin, Barnwell, David, Barry, Abdoulaye, Bauni, Evasius, Besingi, Richard, Bojang, Kalifa, Bougouma, Edith, Bull, Susan, Busby, George, Camara, Abdoulie, Camara, Landing, Campino, Susana, Carter, Richard, Carucci, Dan, Casals-Pascual, Climent, Ceesay, Ndey, Ceesay, Pa, Chau, Tran, Chuong, Ly, Clark, Taane, Clarke, Geraldine, Cole-Ceesay, Ramou, Conway, David, Cook, Katharine, Cook, Olivia, Cornelius, Victoria, Corran, Patrick, Correa, Simon, Cox, Sharon, Craik, Rachel, Danso, Bakary, Davis, Timothy, Day, Nicholas, Deloukas, Panos, Dembele, Awa, deVries, Jantina, Dewasurendra, Rajika, Diakite, Mahamadou, Diarra, Elizabeth, Dibba, Yaya, Diss, Andrea, Djimdé, Abdoulaye, Dolo, Amagana, Doumbo, Ogobara, Doyle, Alan, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Dunstan, Sarah, Ebonyi, Augustine, Elhassan, Ahmed, Elhassan, Ibrahim, Elzein, Abier, Enimil, Anthony, Esangbedo, Pamela, Evans, Jennifer, Evans, Julie, Farrar, Jeremy, Fernando, Deepika, Fitzpatrick, Kathryn, Fullah, Janet, Garcia, Jacob, Ghansah, Anita, Gottleib, Michael, Green, Angie, Hart, Lee, Hennsman, Meike, Hien, Tran, Hieu, Nguyen, Hilton, Eliza, Hodgson, Abraham, Horstmann, Rolf, Hubbart, Christina, Hughes, Catherine, Hussein, Ayman, Hutton, Robert, Ibrahim, Muntaser, Ishengoma, Deus, Jaiteh, Jula, Jallow, Mariatou, Jallow, Muminatou, Jammeh, Kebba, Jasseh, Momodou, Jeffreys, Anna, Jobarteh, Amie, Johnson, Kimberly, Joseph, Sarah, Jyothi, Dushyanth, Kachala, David, Kamuya, Dorcas, Kanyi, Haddy, Karunajeewa, Harin, Karunaweera, Nadira, Keita, Momodou, Kerasidou, Angeliki, Khan, Aja, Kivinen, Katja, Kokwaro, Gilbert, Konate, Amadou, Konate, Salimata, Koram, Kwadwo, Kwiatkowski, Dominic, Laman, Moses, Le, Si, Leffler, Ellen, Lemnge, Martha, Lin, Enmoore, Ly, Alioune, Macharia, Alexander, MacInnis, Bronwyn, Mai, Nguyen, Makani, Julie, Malangone, Cinzia, Mangano, Valentina, Manjurano, Alphaxard, Manneh, Lamin, Manning, Laurens, Manske, Magnus, Marsh, Kevin, Marsh, Vicki, Maslen, Gareth, Maxwell, Caroline, Mbunwe, Eric, McCreight, Marilyn, Mead, Daniel, Mendy, Alieu, Mendy, Anthony, Mensah, Nathan, Michon, Pascal, Miles, Alistair, Miotto, Olivo, Modiano, David, Mohamed, Hiba, Molloy, Sile, Molyneux, Malcolm, Molyneux, Sassy, Moore, Mike, Moyes, Catherine, Mtei, Frank, Mtove, George, Mueller, Ivo, Mugri, Regina, Munthali, Annie, Mutabingwa, Theonest, Nadjm, Behzad, Ndi, Andre, Ndila, Carolyne, Newton, Charles, Niangaly, Amadou, Njie, Haddy, Njie, Jalimory, Njie, Madi, Njie, Malick, Njie, Sophie, Njiragoma, Labes, Nkrumah, Francis, Ntunthama, Neema, Nyika, Aceme, Nyirongo, Vysaul, O'Brien, John, Obu, Herbert, Oduro, Abraham, Ofori, Alex, Olaniyan, Subulade, Olaosebikan, Rasaq, Oluoch, Tom, Omotade, Olayemi, Oni, Olajumoke, Onykwelu, Emmanuel, Opi, Daniel, Orimadegun, Adebola, O'Riordan, Sean, Ouedraogo, Issa, Oyola, Samuel, Parker, Michael, Pearson, Richard, Pensulo, Paul, Peshu, Norbert, Phiri, Ajib, Phu, Nguyen, Pinder, Margaret, Pirinen, Matti, Plowe, Chris, Potter, Claire, Poudiougou, Belco, Puijalon, Odile, Quyen, Nguyen, Ragoussis, Ioannis, Ragoussis, Jiannis, Rasheed, Oba, Reeder, John, Reyburn, Hugh, Riley, Eleanor, Risley, Paul, Rockett, Kirk, Rodford, Joanne, Rogers, Jane, Rogers, William, Rowlands, Kate, Ruano-Rubio, Valentín, Sabally-Ceesay, Kumba, Sadiq, Abubacar, Saidy-Khan, Momodou, Saine, Horeja, Sakuntabhai, Anavaj, Sall, Abdourahmane, Sambian, David, Sambou, Idrissa, SanJoaquin, Miguel, Sepúlveda, Nuno, Shah, Shivang, Shelton, Jennifer, Siba, Peter, Silva, Nilupa, Simmons, Cameron, Simpore, Jaques, Singhasivanon, Pratap, Sinh, Dinh, Sirima, Sodiomon, Sirugo, Giorgio, Sisay-Joof, Fatoumatta, Sissoko, Sibiry, Small, Kerrin, Somaskantharajah, Elilan, Spencer, Chris, Stalker, Jim, Stevens, Marryat, Suriyaphol, Prapat, Sylverken, Justice, Taal, Bintou, Tall, Adama, Taylor, Terrie, Teo, Yik, Thai, Cao, Thera, Mahamadou, Titanji, Vincent, Toure, Ousmane, Troye-Blomberg, Marita, Usen, Stanley, Uyoga, Sophie, Vanderwal, Aaron, Wangai, Hannah, Watson, Renee, Williams, Thomas, Wilson, Michael, Wrigley, Rebecca, Yafi, Clarisse, Yamoah, Lawrence, Ndila, Carolyne M, Macharia, Alexander W, Nyutu, Gideon, Ojal, John, Shebe, Mohammed, Awuondo, Kennedy O, Mturi, Neema, Tsofa, Benjamin, Clark, Taane G, Kariuki, Silvia, Mackinnon, Margaret, Maitland, Kathryn, Kwiatkowski, Dominic P, Rockett, Kirk A, and Williams, Thomas N

Published
2018
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7. Intertropical Convergence Zone as the Possible Source Mechanism for Southward Propagating Medium-Scale Traveling Ionospheric Disturbances over South American Low-Latitude and Equatorial Region

Author

Essien, Patrick, primary, Figueiredo, Cosme Alexandre Oliveira Barros, additional, Takahashi, Hisao, additional, Klutse, Nana Ama Browne, additional, Wrasse, Cristiano Max, additional, Afonso, João Maria de Sousa, additional, Quispe, David Pareja, additional, Lomotey, Solomon Otoo, additional, Ayorinde, Tunde Toyese, additional, Sobral, José H. A., additional, Eghan, Moses Jojo, additional, Sackey, Samuel Sanko, additional, Barros, Diego, additional, Bilibio, Anderson V., additional, Nkrumah, Francis, additional, and Quagraine, Kwesi Akumenyi, additional

Published
2022
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10. Endemic Burkitt lymphoma is associated with strength and diversity of Plasmodium falciparum malaria stage-specific antigen antibody response

Author

Aka, Peter, Vila, Maria Candida, Jariwala, Amar, Nkrumah, Francis, Emmanuel, Benjamin, Yagi, Masanori, Palacpac, Nirianne Marie Q., Periago, Maria V., Neequaye, Janet, Kiruthu, Christine, Tougan, Takahiro, Levine, Paul H., Biggar, Robert J., Pfeiffer, Ruth M., Bhatia, Kishor, Horii, Toshihiro, Bethony, Jeffrey M., and Mbulaiteye, Sam M.

Published
2013
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17. A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum. (Major Article)

Author

Hale, Braden R., Owusu-Agyei, Seth, Fryauff, David J., Koram, Kwadwo A., Adjuik, Martin, Oduro, Abraham R., Prescott, W. Roy, Baird, J. Kevin, Nkrumah, Francis, Ritchie, Thomas L., Franke, Eileen D., Binka, Fred N., Horton, John, and Hoffman, Stephen L.

Subjects
GlaxoSmithKline PLC -- Product development, Malaria -- Prevention, Plasmodium falciparum -- Physiological aspects, Primaquine -- Usage, Pharmaceutical industry -- Product development, Health, Health care industry
Published
2003

19. Development of an Updated Global Land In Situ‐Based Data Set of Temperature and Precipitation Extremes: HadEX3

Author

Dunn, Robert J. H., primary, Alexander, Lisa V., additional, Donat, Markus G., additional, Zhang, Xuebin, additional, Bador, Margot, additional, Herold, Nicholas, additional, Lippmann, Tanya, additional, Allan, Rob, additional, Aguilar, Enric, additional, Barry, Abdoul Aziz, additional, Brunet, Manola, additional, Caesar, John, additional, Chagnaud, Guillaume, additional, Cheng, Vincent, additional, Cinco, Thelma, additional, Durre, Imke, additional, Guzman, Rosaline, additional, Htay, Tin Mar, additional, Wan Ibadullah, Wan Maisarah, additional, Bin Ibrahim, Muhammad Khairul Izzat, additional, Khoshkam, Mahbobeh, additional, Kruger, Andries, additional, Kubota, Hisayuki, additional, Leng, Tan Wee, additional, Lim, Gerald, additional, Li‐Sha, Lim, additional, Marengo, Jose, additional, Mbatha, Sifiso, additional, McGree, Simon, additional, Menne, Matthew, additional, Milagros Skansi, Maria, additional, Ngwenya, Sandile, additional, Nkrumah, Francis, additional, Oonariya, Chalump, additional, Pabon‐Caicedo, Jose Daniel, additional, Panthou, Gérémy, additional, Pham, Cham, additional, Rahimzadeh, Fatemeh, additional, Ramos, Andrea, additional, Salgado, Ernesto, additional, Salinger, Jim, additional, Sané, Youssouph, additional, Sopaheluwakan, Ardhasena, additional, Srivastava, Arvind, additional, Sun, Ying, additional, Timbal, Bertrand, additional, Trachow, Nichanun, additional, Trewin, Blair, additional, Schrier, Gerard, additional, Vazquez‐Aguirre, Jorge, additional, Vasquez, Ricardo, additional, Villarroel, Claudia, additional, Vincent, Lucie, additional, Vischel, Theo, additional, Vose, Russ, additional, and Bin Hj Yussof, Mohd Noor'Arifin, additional

Published
2020
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20. The Association between the Comprehensive Epstein–Barr Virus Serologic Profile and Endemic Burkitt Lymphoma

Author

Coghill, Anna E., primary, Proietti, Carla, additional, Liu, Zhiwei, additional, Krause, Lutz, additional, Bethony, Jeff, additional, Prokunina-Olsson, Ludmila, additional, Obajemu, Adeola, additional, Nkrumah, Francis, additional, Biggar, Robert J., additional, Bhatia, Kishor, additional, Hildesheim, Allan, additional, Doolan, Denise L., additional, and Mbulaiteye, Sam M., additional

Published
2020
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26. Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Author

Ndila, Carolyne M, Uyoga, Sophie, Macharia, Alexander W, Nyutu, Gideon, Peshu, Norbert, Ojal, John, Shebe, Mohammed, Awuondo, Kennedy O, Mturi, Neema, Tsofa, Benjamin, Sepúlveda, Nuno, Clark, Taane G, Band, Gavin, Clarke, Geraldine, Rowlands, Kate, Hubbart, Christina, Jeffreys, Anna, Kariuki, Silvia, Marsh, Kevin, Mackinnon, Margaret, Maitland, Kathryn, Kwiatkowski, Dominic P, Rockett, Kirk A, Williams, Thomas N, Abathina, Amadou, Abubakar, Ismaela, Achidi, Eric, Agbenyega, Tsiri, Aiyegbo, Mohammed, Akoto, Alex, Allen, Angela, Allen, Stephen, Amenga-Etego, Lucas, Amodu, Folakemi, Amodu, Olukemi, Anchang-Kimbi, Judith, Ansah, Nana, Ansah, Patrick, Ansong, Daniel, Antwi, Sampson, Anyorigiya, Thomas, Apinjoh, Tobias, Asafo-Agyei, Emmanuel, Asoala, Victor, Atuguba, Frank, Auburn, Sarah, Bah, Abdou, Bamba, Kariatou, Bancone, Germana, Barnwell, David, Barry, Abdoulaye, Bauni, Evasius, Besingi, Richard, Bojang, Kalifa, Bougouma, Edith, Bull, Susan, Busby, George, Camara, Abdoulie, Camara, Landing, Campino, Susana, Carter, Richard, Carucci, Dan, Casals-Pascual, Climent, Ceesay, Ndey, Ceesay, Pa, Chau, Tran, Chuong, Ly, Clark, Taane, Cole-Ceesay, Ramou, Conway, David, Cook, Katharine, Cook, Olivia, Cornelius, Victoria, Corran, Patrick, Correa, Simon, Cox, Sharon, Craik, Rachel, Danso, Bakary, Davis, Timothy, Day, Nicholas, Deloukas, Panos, Dembele, Awa, Devries, Jantina, Dewasurendra, Rajika, Diakite, Mahamadou, Diarra, Elizabeth, Dibba, Yaya, Diss, Andrea, Djimdé, Abdoulaye, Dolo, Amagana, Doumbo, Ogobara, Doyle, Alan, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Dunstan, Sarah, Ebonyi, Augustine, Elhassan, Ahmed, Elhassan, Ibrahim, Elzein, Abier, Enimil, Anthony, Esangbedo, Pamela, Evans, Jennifer, Evans, Julie, Farrar, Jeremy, Fernando, Deepika, Fitzpatrick, Kathryn, Fullah, Janet, Garcia, Jacob, Ghansah, Anita, Gottleib, Michael, Green, Angie, Hart, Lee, Hennsman, Meike, Hien, Tran, Hieu, Nguyen, Hilton, Eliza, Hodgson, Abraham, Horstmann, Rolf, Hughes, Catherine, Hussein, Ayman, Hutton, Robert, Ibrahim, Muntaser, Ishengoma, Deus, Jaiteh, Jula, Jallow, Mariatou, Jallow, Muminatou, Jammeh, Kebba, Jasseh, Momodou, Jobarteh, Amie, Johnson, Kimberly, Joseph, Sarah, Jyothi, Dushyanth, Kachala, David, Kamuya, Dorcas, Kanyi, Haddy, Karunajeewa, Harin, Karunaweera, Nadira, Keita, Momodou, Kerasidou, Angeliki, Khan, Aja, Kivinen, Katja, Kokwaro, Gilbert, Konate, Amadou, Konate, Salimata, Koram, Kwadwo, Kwiatkowski, Dominic, Laman, Moses, Si, Le, Leffler, Ellen, Lemnge, Martha, Lin, Enmoore, Alioune, Ly, Macharia, Alexander, Macinnis, Bronwyn, Mai, Nguyen, Makani, Julie, Malangone, Cinzia, Mangano, Valentina, Manjurano, Alphaxard, Manneh, Lamin, Manning, Laurens, Manske, Magnus, Marsh, Vicki, Maslen, Gareth, Maxwell, Caroline, Mbunwe, Eric, Mccreight, Marilyn, Mead, Daniel, Mendy, Alieu, Mendy, Anthony, Mensah, Nathan, Michon, Pascal, Miles, Alistair, Miotto, Olivo, Modiano, David, Mohamed, Hiba, Molloy, Sile, Molyneux, Malcolm, Molyneux, Sassy, Moore, Mike, Moyes, Catherine, Mtei, Frank, Mtove, George, Mueller, Ivo, Mugri, Regina, Munthali, Annie, Mutabingwa, Theonest, Nadjm, Behzad, Ndi, Andre, Ndila, Carolyne, Newton, Charles, Niangaly, Amadou, Njie, Haddy, Njie, Jalimory, Njie, Madi, Njie, Malick, Njie, Sophie, Njiragoma, Labes, Nkrumah, Francis, Ntunthama, Neema, Nyika, Aceme, Nyirongo, Vysaul, O'Brien, John, Obu, Herbert, Oduro, Abraham, Ofori, Alex, Olaniyan, Subulade, Olaosebikan, Rasaq, Oluoch, Tom, Omotade, Olayemi, Oni, Olajumoke, Onykwelu, Emmanuel, Opi, Daniel, Orimadegun, Adebola, O'Riordan, Sean, Ouedraogo, Issa, Oyola, Samuel, Parker, Michael, Pearson, Richard, Pensulo, Paul, Phiri, Ajib, Phu, Nguyen, Pinder, Margaret, Pirinen, Matti, Plowe, Chris, Potter, Claire, Poudiougou, Belco, Puijalon, Odile, Quyen, Nguyen, Ragoussis, Ioannis, Ragoussis, Jiannis, Rasheed, Oba, Reeder, John, Reyburn, Hugh, Riley, Eleanor, Risley, Paul, Rockett, Kirk, Rodford, Joanne, Rogers, Jane, Rogers, William, Ruano-Rubio, Valentín, Sabally-Ceesay, Kumba, Sadiq, Abubacar, Saidy-Khan, Momodou, Saine, Horeja, Sakuntabhai, Anavaj, Sall, Abdourahmane, Sambian, David, Sambou, Idrissa, Sanjoaquin, Miguel, Shah, Shivang, Shelton, Jennifer, Siba, Peter, Silva, Nilupa, Simmons, Cameron, Simpore, Jaques, Singhasivanon, Pratap, Sinh, Dinh, Sirima, Sodiomon, Sirugo, Giorgio, Sisay-Joof, Fatoumatta, Sissoko, Sibiry, Small, Kerrin, Somaskantharajah, Elilan, Spencer, Chris, Stalker, Jim, Stevens, Marryat, Suriyaphol, Prapat, Sylverken, Justice, Taal, Bintou, Tall, Adama, Taylor, Terrie, Teo, Yik, Thai, Cao, Thera, Mahamadou, Titanji, Vincent, Toure, Ousmane, Troye-Blomberg, Marita, Usen, Stanley, Vanderwal, Aaron, Wangai, Hannah, Watson, Renee, Williams, Thomas, Wilson, Michael, Wrigley, Rebecca, Yafi, Clarisse, Yamoah, Lawrence, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, London School of Hygiene and Tropical Medicine (LSHTM), The Wellcome Trust Sanger Institute [Cambridge], St Mary's Hospital, Imperial College, TNW and MM are funded through awards from the Wellcome Trust (grants 091758 and 202800 [to TNW] and grant 088634 [to MM]) and DPK and TGC receive support from the Medical Research Council (grant G19/9 [to DPK] and grants MR/K000551/1, MR/M01360X/1, MR/N010469/1, and MC_PC_15103 [to TGC]). The research leading to these results received funding from the European Community's Seventh Framework Programme (FP7/2007-2013, under grant agreement 242095) and from the Medical Research Council (grant G0600718). MalariaGEN is supported by the Wellcome Trust (WT077383/Z/05/Z) and by the Foundation for the National Institutes of Health (grant 566) as part of the Bill & Melinda Gates' Grand Challenges in Global Health Initiative. The Resource Centre for Genomic Epidemiology of Malaria is supported by the Wellcome Trust (grant 090770/Z/09/Z). Support was also provided by the Medical Research Council (grant G0600718). The Wellcome Trust also provides core awards to the Wellcome Trust Centre for Human Genetics (grant 090532/Z/09/Z) and to the Wellcome Trust Sanger Institute (grant 098051). This work forms part of a larger collaboration with the MalariaGEN Consortium, whose members are listed at http://www.malariagen.net/projects/host/consortium-members. This paper is published with permission from the Director of the Kenya Medical Research Institute (KEMRI)., MalariaGEN Consortium (Anavaj Sakuntabhai), and European Project: 242095,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,EVIMALAR(2009)

Subjects
Case-Control Studies, Child, Child, Preschool, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Kenya, Malaria, Male, Polymorphism, Genetic, Hematology, macromolecular substances, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Article, Genetic, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, parasitic diseases, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Polymorphism, Preschool
Abstract

Summary Background Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative.

Published
2018

28. 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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33. Severe falciparum malaria in young children of the Kassena-Nankana district of northern Ghana

Author

Anto Francis, Ansah Akosua, Anyorigiya Thomas, Ansah Patrick, Atuguba Frank, Rogers William, Koram Kwadwo A, Oduro Abraham R, Mensah Nathan, Hodgson Abraham, and Nkrumah Francis

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Study design Severe falciparum malaria in children was studied as part of the characterization of the Kassena-Nankana District Ghana for future malaria vaccine trials. Children aged 6–59 months with diagnosis suggestive of acute disease were characterized using the standard WHO definition for severe malaria. Results Of the total children screened, 45.2% (868/1921) satisfied the criteria for severe malaria. Estimated incidence of severe malaria was 3.4% (range: 0.4–8.3%) cases per year. The disease incidence was seasonal: 560 cases per year, of which 70.4% occurred during the wet season (June-October). The main manifestations were severe anaemia (36.5%); prolonged or multiple convulsions (21.6%); respiratory distress (24.4%) and cerebral malaria (5.4%). Others were hyperpyrexia (11.1%); hyperparasitaemia (18.5%); hyperlactaemia (33.4%); and hypoglycaemia (3.2%). The frequency of severe anaemia was 39.8% in children of six to 24 months of age and 25.9% in children of 25–60 months of age. More children (8.7%) in the 25–60 months age group had cerebral malaria compared with 4.4% in the 6–24 months age group. The overall case fatality ratio was 3.5%. Cerebral malaria and hyperlactataemia were the significant risk factors associated with death. Severe anaemia, though a major presentation, was not significantly associated with risk of death. Conclusion Severe malaria is a frequent and seasonal childhood disease in northern Ghana and maybe an adequate endpoint for future malaria vaccine trials.

Published
2007
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34. Burkitt lymphoma express oncofetal Chondroitin Sulfate without being a reservoir for placental malaria sequestration

Author

Agerbæk, Mette Ø., Pereira, Marina A., Clausen, Thomas M., Pehrson, Caroline, Oo, Htoo Zarni, Spliid, Charlotte, Rich, Jamie R., Fung, Vincent, Nkrumah, Francis, Neequaye, Janet, Biggar, Robert J., Reynolds, Steven J., Tosato, Giovanna, Pullarkat, Sheeja T., Ayers, Leona W., Theander, Thor G., Daugaard, Mads, Bhatia, Kishor, Nielsen, Morten A., Mbulaiteye, Sam M., and Salanti, Ali

Subjects
Male, Erythrocytes, Adolescent, Placenta, Chondroitin Sulfates, Plasmodium falciparum, Antibodies, Protozoan, Antigens, Protozoan, Burkitt Lymphoma, Article, Recombinant Proteins, Antigens, Neoplasm, Pregnancy, Cell Line, Tumor, Child, Preschool, Immunoglobulin G, embryonic structures, parasitic diseases, Humans, Female, Proteoglycans, Malaria, Falciparum, Child
Abstract

Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. OfCS is absent from other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor-site for VAR2CSA-expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non-malignant tissue, encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL-derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL-derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy.

Published
2017

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

Published
2018
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36. Potential impact of 1.5 °C and 2 °C global warming on consecutive dry and wet days over West Africa

Author

Klutse, Nana Ama Browne, primary, Ajayi, Vincent O, additional, Gbobaniyi, Emiola Olabode, additional, Egbebiyi, Temitope S, additional, Kouadio, Kouakou, additional, Nkrumah, Francis, additional, Quagraine, Kwesi Akumenyi, additional, Olusegun, Christiana, additional, Diasso, Ulrich, additional, Abiodun, Babatunde J, additional, Lawal, Kamoru, additional, Nikulin, Grigory, additional, Lennard, Christopher, additional, and Dosio, Alessandro, additional

Published
2018
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40. High-throughput sequencing reveals novel features of immunoglobulin gene rearrangements in Burkitt lymphoma

Author

Lombardo, Katharine A., primary, Coffey, David G., additional, Morales, Alicia J., additional, Carlson, Christopher S., additional, Towlerton, Andrea M. H., additional, Gerdts, Sarah E., additional, Nkrumah, Francis K., additional, Neequaye, Janet, additional, Biggar, Robert J., additional, Orem, Jackson, additional, Casper, Corey, additional, Mbulaiteye, Sam M., additional, Bhatia, Kishor G., additional, and Warren, Edus H., additional

Published
2017
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41. High-throughput sequencing of the B-cell receptor in African Burkitt lymphoma reveals clues to pathogenesis

Author

Lombardo, Katharine A., primary, Coffey, David G., additional, Morales, Alicia J., additional, Carlson, Christopher S., additional, Towlerton, Andrea M. H., additional, Gerdts, Sarah E., additional, Nkrumah, Francis K., additional, Neequaye, Janet, additional, Biggar, Robert J., additional, Orem, Jackson, additional, Casper, Corey, additional, Mbulaiteye, Sam M., additional, Bhatia, Kishor G., additional, and Warren, Edus H., additional

Published
2017
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42. Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration

Author

Agerbaek, Mette Ø., primary, Pereira, Marina A., additional, Clausen, Thomas M., additional, Pehrson, Caroline, additional, Oo, Htoo Zarni, additional, Spliid, Charlotte, additional, Rich, Jamie R., additional, Fung, Vincent, additional, Nkrumah, Francis, additional, Neequaye, Janet, additional, Biggar, Robert J., additional, Reynolds, Steven J., additional, Tosato, Giovanna, additional, Pullarkat, Sheeja T., additional, Ayers, Leona W., additional, Theander, Thor G., additional, Daugaard, Mads, additional, Bhatia, Kishor, additional, Nielsen, Morten A., additional, Mbulaiteye, Sam M., additional, and Salanti, Ali, additional

Published
2017
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44. Dynamic analysis of the West African Monsoon and its variability over Ghana

Author

Nkrumah, Francis

Subjects
Dynamic analysis, West African Monsoon, Variability, Ghana, Climatology Project
Abstract

ii,116p.:ill, In this study, the International Center for Theoretical Physics’ Regiona l Climate Model Version 4 (RegCM4) is used over the period 1998-2010, to study the dynamics of rainfall over West Africa. The study also attempts to understand the West African Monsoon (WAM) circulation and its characteristics. Global Precipitation Climatology Project precipitation (GPCP), Tropical Rainfa ll Measuring Mission (TRMM), global atmospheric reanalysis (ERA-Inter im, ERAINT), RegCM4 winds and National Centers for Environmental Prediction (NCEP) reanalysis were used to aid in the understanding of the WAM circulat ion dynamics. The main WAM circulation features and the general pattern of rainfa ll in the model simulation compare well with observations. The model simulates the mean rainfall at the peak of the West African summer rainy season (June-July- August), and it captures well the rainbelt associated with the ITCZ. Examination of the intraseasonal variability of rainfall shows that the model captures the three distinct phases of the West African monsoon circulation: onset, intensification and cessation phases. The simulation, for the monthly variability, well depicts the bimodal and unimodal nature of rainfall over southern and northern Ghana respectively. The association between Sea Surface Temperatures (SSTs) and rainfall showed a high positive correlation in most part of the Guinean Coast over the June-July-August (JJA) rainfall season. This depict that a rise in temperatures over the ocean is associated with high rainfall over the coast of West Africa including Ghana.

Published
2014

45. Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study

Author

Koram, Kwadwo A., primary, Adu, Bright, additional, Ocran, Josephine, additional, Karikari, Yaa S., additional, Adu-Amankwah, Susan, additional, Ntiri, Michael, additional, Abuaku, Benjamin, additional, Dodoo, Daniel, additional, Gyan, Ben, additional, Kronmann, Karl C., additional, and Nkrumah, Francis, additional

Published
2016
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46. Epstein-Barr virus from Burkitt Lymphoma biopsies from Africa and South America share novel LMP-1 promoter and gene variations

Author

Lei, Haiyan, primary, Li, Tianwei, additional, Li, Bingjie, additional, Tsai, Shien, additional, Biggar, Robert J., additional, Nkrumah, Francis, additional, Neequaye, Janet, additional, Gutierrez, Marina, additional, Epelman, Sidnei, additional, Mbulaiteye, Sam M., additional, Bhatia, Kishor, additional, and Lo, Shyh-Ching, additional

Published
2015
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47. Polymorphisms in the Haem Oxygenase-1 promoter are not associated with severity of Plasmodium falciparum malaria in Ghanaian children

Author

Hansson, Helle H, primary, Maretty, Lasse, additional, Balle, Christina, additional, Goka, Bamenla Q, additional, Luzon, Elisa, additional, Nkrumah, Francis N, additional, Schousboe, Mette L, additional, Rodrigues, Onike P, additional, Bygbjerg, Ib Christian, additional, Kurtzhals, Jørgen AL, additional, Alifrangis, Michael, additional, and Hempel, Casper, additional

Published
2015
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49. Elevated serum levels of interleukin-6 in endemic Burkitt lymphoma in Ghana

Author

Aka, Peter, primary, Emmanuel, Benjamin, additional, Vila, Maria Candida, additional, Jariwala, Amar, additional, Nkrumah, Francis, additional, Periago, Maria V., additional, Neequaye, Janet, additional, Kiruthu, Christine, additional, Levine, Paul H., additional, Biggar, Robert J., additional, Bhatia, Kishor, additional, Bethony, Jeffrey M., additional, and Mbulaiteye, Sam M., additional

Published
2014
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