Search

Your search keyword '"Macharia, Alexander"' showing total 107 results
Start Over Author "Macharia, Alexander"
107 results on '"Macharia, Alexander"'

1. Relation Between the Dantu Blood Group Variant and Bacteremia in Kenyan Children: A Population-Based Case-Control Study.

Author

Kariuki, Silvia N, Gilchrist, James J, Uyoga, Sophie, Macharia, Alexander, Makale, Johnstone, Rayner, Julian C, and Williams, Thomas N

Subjects
BACTERIAL diseases, BACTEREMIA, BLOOD groups, SINGLE nucleotide polymorphisms, KENYANS
Abstract

Background The Dantu blood group variant protects against Plasmodium falciparum infections, but its wider consequences have not been previously explored. Here, we investigate the impact of Dantu on susceptibility to bacteremia. Methods We conducted a case-control study in children presenting with community-acquired bacteremia to Kilifi County Hospital in Kenya between 1998 and 2010. We used logistic regression to test for associations between the Dantu marker single-nucleotide polymorphism rs186873296 A > G and both all-cause and pathogen-specific bacteremia under an additive model. We used date of admission as a proxy measure of malaria transmission intensity, given known differences in malaria prevalence over the course of the study. Results Dantu was associated with protection from all-cause bacteremia (OR, 0.81; P =.014), the association being greatest in homozygotes (OR, 0.30; P =.013). This protection was shared across the major bacterial pathogens but, notably, was only significant during the era of high malaria transmission pre-2003 (OR, 0.79; P =.023). Conclusions Consistent with previous studies showing the indirect impact on bacteremia risk of other malaria-associated red cell variants, our study also shows that Dantu is protective against bacteremia via its effect on malaria risk. Dantu does not appear to be under balancing selection through an increased risk of bacterial infections. [ABSTRACT FROM AUTHOR]

Published
2025
Full Text
View/download PDF

2. Malaria protection due to sickle haemoglobin depends on parasite genotype

Author

Band, Gavin, Leffler, Ellen M., Jallow, Muminatou, Sisay-Joof, Fatoumatta, Ndila, Carolyne M., Macharia, Alexander W., Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Nguyen, Thuy, Gonçalves, Sónia, Ariani, Cristina V., Stalker, Jim, Pearson, Richard D., Amato, Roberto, Drury, Eleanor, Sirugo, Giorgio, d’Alessandro, Umberto, Bojang, Kalifa A., Marsh, Kevin, Peshu, Norbert, Saelens, Joseph W., Diakité, Mahamadou, Taylor, Steve M., Conway, David J., Williams, Thomas N., Rockett, Kirk A., and Kwiatkowski, Dominic P.

Published
2022
Full Text
View/download PDF

3. 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
Full Text
View/download PDF

5. The Dantu blood group prevents parasite growth in vivo: Evidence from a controlled human malaria infection study

Author

Kariuki, Silvia N, Macharia, Alexander W, Makale, Johnstone, Nyamu, Wilfred, Hoffman, Stephen L, Kapulu, Melissa C, Bejon, Philip, Rayner, Julian C, Williams, Thomas N, CHMI-SIKA Study Team, Kariuki, Silvia N [0000-0003-0801-5285], Rayner, Julian C [0000-0002-9835-1014], Williams, Thomas N [0000-0003-4456-2382], and Apollo - University of Cambridge Repository

Subjects
Adult, infectious disease, microbiology, malaria, P. falciparum, Kenya, challenge study, host genetics, genomics, Blood Group Antigens, Animals, Humans, genetics, Parasites, human, Malaria, Falciparum
Abstract

BACKGROUND: The long co-evolution of Homo sapiens and Plasmodium falciparum has resulted in the selection of numerous human genetic variants that confer an advantage against severe malaria and death. One such variant is the Dantu blood group antigen, which is associated with 74% protection against severe and complicated P. falciparum malaria infections in homozygous individuals, similar to that provided by the sickle haemoglobin allele (HbS). Recent in vitro studies suggest that Dantu exerts this protection by increasing the surface tension of red blood cells, thereby impeding the ability of P. falciparum merozoites to invade them and reducing parasite multiplication. However, no studies have yet explored this hypothesis in vivo. METHODS: We investigated the effect of Dantu on early phase P. falciparum (Pf) infections in a controlled human malaria infection (CHMI) study. 141 sickle-negative Kenyan adults were inoculated with 3.2 × 103 aseptic, purified, cryopreserved Pf sporozoites (PfSPZ Challenge) then monitored for blood-stage parasitaemia for 21 days by quantitative polymerase chain reaction (qPCR)analysis of the 18S ribosomal RNA P. falciparum gene. The primary endpoint was blood-stage P. falciparum parasitaemia of ≥500/μl while the secondary endpoint was the receipt of antimalarial treatment in the presence of parasitaemia of any density. On study completion, all participants were genotyped both for Dantu and for four other polymorphisms that are associated with protection against severe falciparum malaria: α+-thalassaemia, blood group O, G6PD deficiency, and the rs4951074 allele in the red cell calcium transporter ATP2B4. RESULTS: The primary endpoint was reached in 25/111 (22.5%) non-Dantu subjects in comparison to 0/27 (0%) Dantu heterozygotes and 0/3 (0.0%) Dantu homozygotes (p=0.01). Similarly, 49/111 (44.1%) non-Dantu subjects reached the secondary endpoint in comparison to only 7/27 (25.9%) and 0/3 (0.0%) Dantu heterozygotes and homozygotes, respectively (p=0.021). No significant impacts on either outcome were seen for any of the other genetic variants under study. CONCLUSIONS: This study reveals, for the first time, that the Dantu blood group is associated with high-level protection against early, non-clinical, P. falciparum malaria infections in vivo. Learning more about the mechanisms involved could potentially lead to new approaches to the prevention or treatment of the disease. Our study illustrates the power of CHMI with PfSPZ Challenge for directly testing the protective impact of genotypes previously identified using other methods. FUNDING: The Kenya CHMI study was supported by an award from Wellcome (grant number 107499). SK was supported by a Training Fellowship (216444/Z/19/Z), TNW by a Senior Research Fellowship (202800/Z/16/Z), JCR by an Investigator Award (220266/Z/20/Z), and core support to the KEMRI-Wellcome Trust Research Programme in Kilifi, Kenya (203077), all from Wellcome. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. CLINICAL TRIAL NUMBER: NCT02739763.

Published
2023

6. Sickle cell anaemia and severe Plasmodium falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT)

Author

Uyoga, Sophie, primary, Olupot-Olupot, Peter, additional, Connon, Roisin, additional, Kiguli, Sarah, additional, Opoka, Robert O, additional, Alaroker, Florence, additional, Muhindo, Rita, additional, Macharia, Alexander W, additional, Dondorp, Arjen M, additional, Gibb, Diana M, additional, Walker, A Sarah, additional, George, Elizabeth C, additional, Maitland, Kathryn, additional, and Williams, Thomas N, additional

Published
2022
Full Text
View/download PDF

7. Case Report: β-thalassemia major on the East African coast

Author

Macharia, Alexander W., primary, Mochamah, George, additional, Makale, Johnstone, additional, Howard, Thad, additional, Mturi, Neema, additional, Olupot-Olupot, Peter, additional, Färnert, Anna, additional, Ware, Russell E., additional, and Williams, Thomas N., additional

Published
2022
Full Text
View/download PDF

9. The Dantu blood group prevents parasite growth in vivo: Evidence from a controlled human malaria infection study.

Author

Kariuki, Silvia N., Macharia, Alexander W., Makale, Johnstone, Nyamu, Wilfred, Hoffman, Stephen L., Kapulu, Melissa C., Bejon, Philip, Rayner, Julian C., and Williams, Thomas N.

Subjects
*BLOOD groups, *MALARIA, *BLOOD group antigens, *GENETIC variation, *ERYTHROCYTES, *GLUCOSE-6-phosphate dehydrogenase deficiency
Abstract

Background: The long co- evolution of Homo sapiens and Plasmodium falciparum has resulted in the selection of numerous human genetic variants that confer an advantage against severe malaria and death. One such variant is the Dantu blood group antigen, which is associated with 74% protection against severe and complicated P. falciparum malaria infections in homozygous individuals, similar to that provided by the sickle haemoglobin allele (HbS). Recent in vitro studies suggest that Dantu exerts this protection by increasing the surface tension of red blood cells, thereby impeding the ability of P. falciparum merozoites to invade them and reducing parasite multiplication. However, no studies have yet explored this hypothesis in vivo. Methods: We investigated the effect of Dantu on early phase P. falciparum (Pf) infections in a controlled human malaria infection (CHMI) study. 141 sickle- negative Kenyan adults were inoculated with 3.2 103 aseptic, purified, cryopreserved Pf sporozoites (PfSPZ Challenge) then monitored for blood- stage parasitaemia for 21 days by quantitative polymerase chain reaction (qPCR)analysis of the 18S ribosomal RNA P. falciparum gene. The primary endpoint was blood- stage P. falciparum parasitaemia of ≥500/μl while the secondary endpoint was the receipt of antimalarial treatment in the presence of parasitaemia of any density. On study completion, all participants were genotyped both for Dantu and for four other polymorphisms that are associated with protection against severe falciparum malaria: α+- thalassaemia, blood group O, G6PD deficiency, and the rs4951074 allele in the red cell calcium transporter ATP2B4. Results: The primary endpoint was reached in 25/111 (22.5%) non- Dantu subjects in comparison to 0/27 (0%) Dantu heterozygotes and 0/3 (0.0%) Dantu homozygotes (p=0.01). Similarly, 49/111 (44.1%) non- Dantu subjects reached the secondary endpoint in comparison to only 7/27 (25.9%) and 0/3 (0.0%) Dantu heterozygotes and homozygotes, respectively (p=0.021). No significant impacts on either outcome were seen for any of the other genetic variants under study. Conclusions: This study reveals, for the first time, that the Dantu blood group is associated with high- level protection against early, non- clinical, P. falciparum malaria infections in vivo. Learning more about the mechanisms involved could potentially lead to new approaches to the prevention or treatment of the disease. Our study illustrates the power of CHMI with PfSPZ Challenge for directly testing the protective impact of genotypes previously identified using other methods. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

11. A predictive algorithm for identifying children with sickle cell anemia among children admitted to hospital with severe anemia in Africa

Author

Olupot‐Olupot, Peter, primary, Connon, Roisin, additional, Kiguli, Sarah, additional, Opoka, Robert O., additional, Alaroker, Florence, additional, Uyoga, Sophie, additional, Nakuya, Margret, additional, Okiror, William, additional, Nteziyaremye, Julius, additional, Ssenyondo, Tonny, additional, Nabawanuka, Eva, additional, Kayaga, Juliana, additional, Williams Mukisa, Cynthia, additional, Amorut, Denis, additional, Muhindo, Rita, additional, Frost, Gary, additional, Walsh, Kevin, additional, Macharia, Alexander W., additional, Gibb, Diana M., additional, Walker, A. Sarah, additional, George, Elizabeth C., additional, Maitland, Kathryn, additional, and Williams, Thomas N., additional

Published
2022
Full Text
View/download PDF

12. A novel locus of resistance to severe malaria in a region of ancient balancing selection

Author

Band, Gavin, Rockett, Kirk A., Spencer, Chris C.A., Kwiatkowski, Dominic P., Le, Quang Si, Clarke, Geraldine M., Kivinen, Katja, Leffler, Ellen M., Cornelius, Victoria, Conway, David J., Williams, Thomas N., Taylor, Terrie, Bojang, Kalifa A., Doumbo, Ogobara, Thera, Mahamadou A., Modiano, David, Sirima, Sodiomon B., Wilson, Michael D., Koram, Kwadwo A., Agbenyega, Tsiri, Achidi, Eric, Marsh, Kevin, Reyburn, Hugh, Drakeley, Chris, Riley, Eleanor, Molyneux, Malcolm, Jallow, Muminatou, Pinder, Margaret, Toure, Ousmane B., Konate, Salimata, Sissoko, Sibiri, Bougouma, Edith C., Mangano, Valentina D., Amenga-Etego, Lucas N., Ghansah, Anita K., Hodgson, Abraham V.O., Ansong, Daniel, Enimil, Anthony, Evans, Jennifer, Apinjoh, Tobias O., Macharia, Alexander, Ndila, Carolyne M., Newton, Charles, Peshu, Norbert, Uyoga, Sophie, Manjurano, Alphaxard, Kachala, David, Nyirongo, Vysaul, Mead, Daniel, Drury, Eleanor, Auburn, Sarah, Campino, Susana G., MacInnis, Bronwyn, Stalker, Jim, Gray, Emma, Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Mendy, Alieu, Craik, Rachel, Fitzpatrick, Kathryn, Molloy, Sile, Hart, Lee, Hutton, Robert, Kerasidou, Angeliki, and Johnson, Kimberly J.

Published
2015
Full Text
View/download PDF

13. Malaria protection due to sickle haemoglobin depends on parasite genotype

Author

Band, Gavin, primary, Leffler, Ellen M., additional, Jallow, Muminatou, additional, Sisay-Joof, Fatoumatta, additional, Ndila, Carolyne M., additional, Macharia, Alexander W., additional, Hubbart, Christina, additional, Jeffreys, Anna E., additional, Rowlands, Kate, additional, Nguyen, Thuy, additional, Gonçalves, Sónia, additional, Ariani, Cristina V., additional, Stalker, Jim, additional, Pearson, Richard D., additional, Amato, Roberto, additional, Drury, Eleanor, additional, Sirugo, Giorgio, additional, d’Alessandro, Umberto, additional, Bojang, Kalifa A., additional, Marsh, Kevin, additional, Peshu, Norbert, additional, Saelens, Joseph W., additional, Diakité, Mahamadou, additional, Taylor, Steve M., additional, Conway, David J., additional, Williams, Thomas N., additional, Rockett, Kirk A., additional, and Kwiatkowski, Dominic P., additional

Published
2021
Full Text
View/download PDF

14. Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision

Author

Watson, James A, primary, Ndila, Carolyne M, primary, Uyoga, Sophie, additional, Macharia, Alexander, additional, Nyutu, Gideon, additional, Mohammed, Shebe, additional, Ngetsa, Caroline, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Rockett, Kirk, additional, Leopold, Stije, additional, Kingston, Hugh, additional, George, Elizabeth C, additional, Maitland, Kathryn, additional, Day, Nicholas PJ, additional, Dondorp, Arjen M, additional, Bejon, Philip, additional, Williams, Thomas N, additional, Holmes, Chris C, additional, and White, Nicholas J, additional

Published
2021
Full Text
View/download PDF

15. Author response: Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision

Author

Watson, James A, primary, Ndila, Carolyne M, additional, Uyoga, Sophie, additional, Macharia, Alexander, additional, Nyutu, Gideon, additional, Mohammed, Shebe, additional, Ngetsa, Caroline, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Rockett, Kirk, additional, Leopold, Stije, additional, Kingston, Hugh, additional, George, Elizabeth C, additional, Maitland, Kathryn, additional, Day, Nicholas PJ, additional, Dondorp, Arjen M, additional, Bejon, Philip, additional, Williams, Thomas, additional, Holmes, Chris C, additional, and White, Nicholas J, additional

Published
2021
Full Text
View/download PDF

16. The protective effect of sickle cell haemoglobin against severe malaria depends on parasite genotype

Author

Band, Gavin, primary, Leffler, Ellen M., additional, Jallow, Muminatou, additional, Sisay-Joof, Fatoumatta, additional, Ndila, Carolyne M., additional, Macharia, Alexander W., additional, Hubbart, Christina, additional, Jeffreys, Anna E., additional, Rowlands, Kate, additional, Nguyen, Thuy, additional, Goncalves, Sonia M., additional, Ariani, Cristina V., additional, Stalker, Jim, additional, Pearson, Richard D., additional, Amato, Roberto, additional, Drury, Eleanor, additional, Sirugo, Giorgio, additional, D’Alessandro, Umberto, additional, Bojang, Kalifa A., additional, Marsh, Kevin, additional, Peshu, Norbert, additional, Conway, David J., additional, Williams, Thomas N., additional, Rockett, Kirk A., additional, and Kwiatkowski, Dominic P., additional

Published
2021
Full Text
View/download PDF

17. Plasma Plasmodium falciparum Histidine-rich Protein 2 Concentrations in Children With Malaria Infections of Differing Severity in Kilifi, Kenya

Author

Uyoga, Sophie, primary, Wanjiku, Perpetual, additional, Rop, Jesse C, additional, Makale, Johnstone, additional, Macharia, Alexander W, additional, Nyutu, Gideon M, additional, Shebe, Mohammed, additional, Awuondo, Kennedy A, additional, Mturi, Neema, additional, Woodrow, Charles J, additional, Dondorp, Arjen M, additional, Maitland, Kathryn, additional, and Williams, Thomas N, additional

Published
2020
Full Text
View/download PDF

19. 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
Full Text
View/download PDF

21. Sickle cell anaemia and severe Plasmodium falciparummalaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT)

Author

Uyoga, Sophie, Olupot-Olupot, Peter, Connon, Roisin, Kiguli, Sarah, Opoka, Robert O, Alaroker, Florence, Muhindo, Rita, Macharia, Alexander W, Dondorp, Arjen M, Gibb, Diana M, Walker, A Sarah, George, Elizabeth C, Maitland, Kathryn, and Williams, Thomas N

Abstract

Sickle cell anaemia (SCA) has historically been associated with high levels of childhood mortality in Africa. Although malaria has a major contribution to this mortality, to date, the clinical pathology of malaria among children with SCA has been poorly described. We aimed to explore the relationship between SCA and Plasmodium falciparummalaria in further detail by investigating the burden and severity of malaria infections among children recruited with severe anaemia to the TRACT trial of blood transfusion in Africa.

Published
2022
Full Text
View/download PDF

22. Plasma Plasmodium falciparum Histidine-rich Protein 2 Concentrations in Children With Malaria Infections of Differing Severity in Kilifi, Kenya.

Author

Uyoga, Sophie, Wanjiku, Perpetual, Rop, Jesse C, Makale, Johnstone, Macharia, Alexander W, Nyutu, Gideon M, Shebe, Mohammed, Awuondo, Kennedy A, Mturi, Neema, Woodrow, Charles J, Dondorp, Arjen M, Maitland, Kathryn, and Williams, Thomas N

Subjects
PROTOZOA, PROTEINS, HISTIDINE, PARASITEMIA, CONFIDENCE intervals, BLOOD plasma, MALARIA, SEVERITY of illness index, RISK assessment, MIXED infections, DESCRIPTIVE statistics, BACTERIAL diseases, ANTIGENS, CHILDREN
Abstract

Background Most previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections. Methods We estimated P. falciparum parasite loads in 3 groups of children with malaria infections of differing severity: (1) children with World Health Organization–defined severe malaria (n = 1544), (2) children admitted with malaria but without features of severity (n = 200), and (3) children in the community with asymptomatic parasitemia (n = 33). Results Peripheral parasitemias were highest in those with uncomplicated malaria (geometric mean [GM] parasite count, 111 064/μL; 95% confidence interval, CI, 86 798–141 819/μL), almost 3 times higher than in those with severe malaria (39 588/μL; 34 990–44 791/μL) and >100 times higher than in those with asymptomatic malaria (1092/μL; 523–2280/μL). However, the GM P. falciparum histidine-rich protein 2 (Pf HRP2) values (95% CI) increased with severity, being 7 (4–12) ng/mL in asymptomatic malaria, 843 (655–1084) ng/mL in uncomplicated malaria, and 1369 (1244–1506) ng/mL in severe malaria. Pf HRP2 concentrations were markedly lower in the subgroup of patients with severe malaria and concomitant invasive bacterial infections of blood or cerebrospinal fluid (GM concentration, 312 ng/mL; 95% CI, 175–557 ng/mL; P <.001) than in those without such infections (1439 ng/mL; 1307–1584; P <.001). Conclusions The clinical severity of malaria infections related strongly to the total burden of P. falciparum parasites. A quantitative test for plasma concentrations of Pf HRP2 could be useful in identifying children at the greatest clinical risk and identifying critically ill children in whom malaria is not the primary cause. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

23. Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia

Author

Opi, D Herbert, primary, Swann, Olivia, additional, Macharia, Alexander, additional, Uyoga, Sophie, additional, Band, Gavin, additional, Ndila, Carolyne M, additional, Harrison, Ewen M, additional, Thera, Mahamadou A, additional, Kone, Abdoulaye K, additional, Diallo, Dapa A, additional, Doumbo, Ogobara K, additional, Lyke, Kirsten E, additional, Plowe, Christopher V, additional, Moulds, Joann M, additional, Shebbe, Mohammed, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Maitland, Kathryn, additional, Raza, Ahmed, additional, Kwiatkowski, Dominic P, additional, Rockett, Kirk A, additional, Williams, Thomas N, additional, and Rowe, J Alexandra, additional

Published
2018
Full Text
View/download PDF

24. Author response: Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia

Author

Opi, D Herbert, primary, Swann, Olivia, additional, Macharia, Alexander, additional, Uyoga, Sophie, additional, Band, Gavin, additional, Ndila, Carolyne M, additional, Harrison, Ewen M, additional, Thera, Mahamadou A, additional, Kone, Abdoulaye K, additional, Diallo, Dapa A, additional, Doumbo, Ogobara K, additional, Lyke, Kirsten E, additional, Plowe, Christopher V, additional, Moulds, Joann M, additional, Shebbe, Mohammed, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Maitland, Kathryn, additional, Raza, Ahmed, additional, Kwiatkowski, Dominic P, additional, Rockett, Kirk A, additional, Williams, Thomas N, additional, and Rowe, J Alexandra, additional

Published
2018
Full Text
View/download PDF

25. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer MG, Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G, Band, Gavin, Clarke, Geraldine M, Spencer, Christopher CA, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimdé, Abdoulaye, Maiga, Boubacar, Touré, Ousmane, Doumbo, Ogobara K, Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D, Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B, Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J, Riley, Eleanor M, Kwiatkowski, Dominic P, Rockett, Kirk A, MalariaGEN Consortium, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], London School of Hygiene and Tropical Medicine (LSHTM), National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare Products Regulatory Agency (MHRA), Nuffield Department of Population Health [Oxford], The Wellcome Trust Sanger Institute [Cambridge], Unité d'Epidémiologie des Maladies Infectieuses, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Immunologie Moléculaire des Parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Stockholm University, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), University of Khartoum, KEMRI-Wellcome Trust Research Programme (KWTRP), Tumaini University Makumira, National Institute for Medical Research [Tanzania] (NIMR), University of Edinburgh, University of Colombo [Sri Lanka], MalariaGEN is supported by the Wellcome Trust (077383/Z/05/Z) and by the Foundation for the National Institutes of Health (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 (090770/Z/09/Z). Support was also provided by the Medical Research Council (G0600718). DPK receives support from the Medical Research Council (G19/9). CCAS was supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). The Wellcome Trust also provides core awards to The Wellcome Trust Centre for Human Genetics (075491/Z/04, 090532/Z/09/Z) and the Wellcome Trust Sanger Institute (077012/Z/05/Z). MTB and BM received funding through the EU Network of Excellence EviMalar. VDM was funded by a Biomalpar (European Community’s Sixth Framework Programme) PhD fellowship. FV was funded by the Italian Malaria Network, sponsored by Compagnia di San Paolo, Turin, Italy. TNW is supported by a Senior Research Fellowship from the Wellcome Trust (091758/Z/10/Z). This study was conducted as part of the Joint Malaria Programme, a collaboration between the National Institute for Medical Research (NIMR), Kilimanjaro Christian Medical College (KCMC), the London School of Hygiene and Tropical Medicine (LSHTM) and the Centre for Medical Parasitology, University of Copenhagen (CMP) with funding from the UK Medical Research Council (GG9901439) and the Danish International Development Agency. CJD is supported by the Wellcome Trust (091924). RD is supported by the University of Colombo Research Grants 2011 (AP/3/2011/PG/15)., European Project: 26843,BIOMALPAR, University of Oxford, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)

Subjects
Male, Hemoglobin, Sickle, Antibodies, Protozoan, Sickle, MESH: Linear Models, MESH: Child, Child, HbAS, MESH: Infant, Newborn, Antibody, CD36, Genotype, Malaria, Sickle cell trait, Adolescent, Adult, Africa South of the Sahara, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Linear Models, Sri Lanka, Young Adult, Infectious Diseases, Parasitology, MESH: Infant, MESH: Young Adult, Protozoan, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Malaria, Antibodies, parasitic diseases, MESH: Antibodies, Protozoan, Hemoglobin, MESH: Africa South of the Sahara, Preschool, MESH: Sri Lanka, MESH: Adolescent, MESH: Humans, Research, MESH: Child, Preschool, MESH: Adult, Newborn, MESH: Hemoglobin, Sickle, MESH: Male, antibody, cd36, genotype, hbas, malaria, sickle cell trait, infectious diseases, parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract

Background Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0833-x) contains supplementary material, which is available to authorized users.

Published
2015
Full Text
View/download PDF

26. Additional file 3: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Abstract

Additional File LFST1A: Details of gene regions selected for genotyping and the SNP assay design details. This file contains a list of the genes from which SNPs were selected and typed for this study. Information is provided on the gene and its genomic location with respect to the Human Reference genome build GRCh37. Also provided is a table containing the assay design details for each SNP used in this study for the Agena Biosciences iPLEX genotyping platform. SNPs are grouped into multiplexes as assigned by the assay design software.

Published
2015
Full Text
View/download PDF

27. Additional file 17: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Abstract

Additional Figure SF5: Plot for 178 SNPs with logged anti-malarial antibody levels. Plot for the P-values of the analyses of 178 SNPs with logged anti-malarial antibody levels Adjusted for age, gender, parasite density, village (>20), ethnicity (>20), sample month (>20) and study. This is an extension to that shown in the main text and is a reduced dataset as not all sites provided parasitaemia data.

Published
2015
Full Text
View/download PDF

28. A novel locus of resistance to severe malaria in a region of ancient balancing selection

Author

Band, Gavin, Rockett, Kirk A., Spencer, Chris C. A., Kwiatkowski, Dominic P., Si Le, Quang, Clarke, Geraldine M., Kivinen, Katja, Leffler, Ellen M., Cornelius, Victoria, Conway, David J., Williams, Thomas N., Taylor, Terrie, Bojang, Kalifa A., Doumbo, Ogobara, Thera, Mahamadou A., Modiano, David, Sirima, Sodiomon B., Wilson, Michael D, Koram, Kwadwo A., Agbenyega, Tsiri, Achidi, Eric, Marsh, Kevin, Reyburn, Hugh, Drakeley, Chris, Riley, Eleanor, Molyneux, Malcolm, Jallow, Muminatou, Pinder, Margaret, Toure, Ousmane B., Konate, Salimata, Sissoko, Sibiri, Bougouma, Edith C., Mangano, Valentina D., Amenga Etego, Lucas N., Ghansah, Anita K., Hodgson, Abraham V. O., Wilson, Michael D., Ansong, Daniel, Enimil, Anthony, Evans, Jennifer, Apinjoh, Tobias O., Macharia, Alexander, Ndila, Carolyne M., Newton, Charles, Peshu, Norbert, Uyoga, Sophie, Manjurano, Alphaxard, Kachala, David, Nyirongo, Vysaul, Mead, Daniel, Drury, Eleanor, Auburn, Sarah, Campino, Susana G., Macinnis, Bronwyn, Stalker, Jim, Gray, Emma, Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Mendy, Alieu, Craik, Rachel, Fitzpatrick, Kathryn, Molloy, Sile, Hart, Lee, Hutton, Robert, Kerasidou, Angeliki, and Johnson, Kimberly J.

Subjects
Male, Erythrocytes, Genome-wide association study, Balancing selection, 0302 clinical medicine, Glycophorins, Malaria, Falciparum, malaria, genetic, resistance, Child, Conserved Sequence, Genetics, 0303 health sciences, Extracellular Matrix Proteins, Multidisciplinary, Natural selection, Single Nucleotide, 3. Good health, Female, Glycophorin, Falciparum, Pan troglodytes, Evolution, Plasmodium falciparum, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Article, ABO Blood-Group System, Host-Parasite Interactions, Evolution, Molecular, 03 medical and health sciences, Genetic, parasitic diseases, medicine, Animals, Humans, Genetic Predisposition to Disease, Polymorphism, Selection, Genetic, Selection, Gene, 030304 developmental biology, Haplotype, Erythrocyte Membrane, Molecular, medicine.disease, biology.organism_classification, Malaria, Haplotypes, Africa, Genome-Wide Association Study, 030217 neurology & neurosurgery
Abstract

Malaria Genomic Epidemiology Network The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. Here we report a novel malaria resistance locus close to a cluster of genes encoding glycophorins that are receptors for erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that provides 33% protection against severe malaria (odds ratio= 0.67, 95% confidence interval= 0.60-0.76, P value= 9.5× 10-11) and is linked to polymorphisms that have previously been shown to have features of ancient balancing selection, on the basis of haplotype sharing between humans and chimpanzees. Taken together with previous observations on the malaria-protective role of blood group O, these data reveal that two of the strongest GWAS signals for severe malaria lie in or close to genes encoding the glycosylated surface coat of the erythrocyte cell membrane, both within regions of the genome where it appears that evolution has maintained diversity for millions of years. These findings provide new insights into the host-parasite interactions that are critical in determining the outcome of malaria infection.

Published
2014

29. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer M. G., Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G., Band, Gavin, Clarke, Geraldine M., Spencer, Christopher C. A., Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimde, Abdoulaye, Maiga, Boubacar, Toure, Ousmane, Doumbo, Ogobara K., Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D., Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B., Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N., Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J., Riley, Eleanor M., Kwiatkowski, Dominic P., Rockett, Kirk A., Shelton, Jennifer M. G., Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G., Band, Gavin, Clarke, Geraldine M., Spencer, Christopher C. A., Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimde, Abdoulaye, Maiga, Boubacar, Toure, Ousmane, Doumbo, Ogobara K., Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D., Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B., Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N., Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J., Riley, Eleanor M., Kwiatkowski, Dominic P., and Rockett, Kirk A.

Abstract

Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP) 4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)(4) epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demons

Published
2015
Full Text
View/download PDF

32. An assessment of the impact of host polymorphisms on Plasmodium falciparum var gene expression patterns among Kenyan children.

Author

Warimwe, George M., Fegan, Gregory, Kiragu, Esther W., Musyoki, Jennifer N., Macharia, Alexander W., Marsh, Kevin, Williams, Thomas N., and Bull, Peter C.

Abstract

Background: Host genotype accounts for a component of the variability in susceptibility to childhood Plasmodium falciparum malaria. However, despite numerous examples of host polymorphisms associated with tolerance or resistance to infection, direct evidence for an impact of host genetic polymorphisms on the in vivo parasite population is difficult to obtain. Parasite molecules whose expression is most likely to be associated with such adaptation are those that are directly involved in the host-parasite interaction. A prime candidate is the family of parasite var gene-encoded molecules on P. falciparum-infected erythrocytes, PfEMP1, which binds various host molecules and facilitates parasite sequestration in host tissues to avoid clearance by the spleen. Methods: To assess the impact of host genotype on the infecting parasite population we used a published parasite var gene sequence dataset to compare var gene expression patterns between parasites from children with polymorphisms in molecules thought to interact with or modulate display of PfEMP1 on the infected erythrocyte surface: ABO blood group, haemoglobin S, alpha-thalassaemia, the T188G polymorphism of CD36 and the K29M polymorphism of ICAM1. Results: Expression levels of ‘group A-like’ var genes, which encode a specific group of PfEMP1 variants previously associated with low host immunity and severe malaria, showed signs of elevation among children of blood group AB. No other host factor tested showed evidence for an association with var expression. Conclusions: Our preliminary findings suggest that host ABO blood group may have a measurable impact on the infecting parasite population. This needs to be verified in larger studies. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

33. Co-inheritance of α+-thalassaemia and sickle trait results in specific effects on haematological parameters.

Author

Wambua, Sammy, Mwacharo, Jedidah, Uyoga, Sophie, Macharia, Alexander, and Williams, Thomas N.

Subjects
SICKLE cell anemia, HEMOLYTIC anemia, GENETIC polymorphisms, HEMOGLOBINOPATHY, HEMATOLOGY, HEMOGLOBINS
Abstract

Both the sickle cell trait (HbAS) and α+-thalassaemia are common in many tropical areas. While their individual haematological effects are well described, few studies describe their effects when inherited together. We present data from the Kenyan coast, which suggest that HbAS and α+-thalassaemia may interact to produce specific effects on haematological parameters. Overall, the difference in Hb concentrations between non-thalassaemics ( α α/ α α) and α+-thalassaemia homozygotes (− α/− α) was greater in non-HbAS (HbAA) (0·63 g/dl) than in HbAS children (0·25 g/dl). HbAS also ameliorated both the reduced mean cell volume and mean cell haemoglobin normally associated with the − α/− α genotype. Potential mechanisms and implications are discussed. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
View/download PDF

34. High mortality from Plasmodium falciparummalaria in children living with sickle cell anemia on the coast of Kenya

Author

McAuley, Charlotte F., Webb, Clare, Makani, Julie, Macharia, Alexander, Uyoga, Sophie, Opi, Daniel H., Ndila, Carolyne, Ngatia, Antony, Scott, John Anthony G., Marsh, Kevin, and Williams, Thomas N.

Abstract

Although malaria is widely considered a major cause of death in young children born with sickle cell anemia (SCA) in sub-Saharan Africa, this is poorly quantified. We attempted to investigate this question through 4 large case-control analyses involving 7164 children living on the coast of Kenya. SCA was associated with an increased risk of admission to hospital both with nonmalaria diseases in general (odds ratio [OR] = 4.17; 95% confidence interval [CI], 1.95-8.92; P< .001) and with invasive bacterial diseases in particular (OR = 8.73; 95% CI, 4.51-16.89; P< .001). We found no evidence for a strongly increased risk of either uncomplicated malaria (OR = 0.43; 95% CI, 0.09-2.10; P= .30) or malaria complicated by a range of well-described clinical features of severity (OR = 0.80; 95% CI, 0.25-2.51; P= .70) overall; nevertheless, mortality was considerably higher among SCA than non-SCA children hospitalized with malaria. Our findings highlight both the central role that malaria plays in the high early mortality seen in African children with SCA and the urgent need for better quantitative data. Meanwhile, our study confirms the importance of providing all children living with SCA in malaria-endemic areas with effective prophylaxis.

Published
2010
Full Text
View/download PDF

35. Additional file 13: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST7Aâ E: Results of site-specific linear regression analysis investigating the effect of age, gender and malaria status as determined by microscopy on antibody levels to the different antibodies measured in the study. This data shows the site-specific analyses of the various epidemiological parameters and antibody measurements.

36. Additional file 16: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST10: Meta-analysis p-values obtained for 178 SNPs passing QC criteria detailed in materials and methods. Details of the analyses for each SNP and antibody across all sites for different genetic inheritance models.

37. Additional file 10: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF4: Scatter plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site and age-group. This plot shows the pairwise correlations (as r2) for each malariaâ malaria antibody pair as a function of each study site. The sites are ordered according to malaria microscopically-positive-prevalence recorded at sample collection (low to high). Several panels are shown according to age-group.

38. Additional file 4: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

MalariaGEN Supplementary Sample Handling Procedures. This file includes more detail on sample handling procedures including extracting DNA, genotyping methodology, ELISA protocols with ELISA data processing.

39. Additional file 9: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF3: Heatmap matrix plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site. Matrix plot of the pairwise correlations as r2 between antibody titres using data from all sites.

40. Additional file 14: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Table ST8: Results of linear regression analysis investigating the effect of age, gender, malaria status as determined by microscopy and bednet use* on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. This table shows the results of the analysis of antibody levels with bednet use. Results shown as betas indicating the direction of effect of the clinical covariates on antibody levels.

41. Additional file 10: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF4: Scatter plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site and age-group. This plot shows the pairwise correlations (as r2) for each malariaâ malaria antibody pair as a function of each study site. The sites are ordered according to malaria microscopically-positive-prevalence recorded at sample collection (low to high). Several panels are shown according to age-group.

42. Additional file 7: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
Statistics::Machine Learning, Statistics::Theory, Statistics::Methodology, Statistics::Computation, 3. Good health
Abstract

Additional Table ST3A-D: Details of the linear regression models used in this study. Model formulae for the various linear regression analyses showing how the different co-variates were used.

43. Additional file 6: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF2: Histograms of residuals from antibody linear regression models with non-genetic factors. Histograms of the residuals from the antibody linear regression model analysis with non-genetic factors.

44. Additional file 13: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST7Aâ E: Results of site-specific linear regression analysis investigating the effect of age, gender and malaria status as determined by microscopy on antibody levels to the different antibodies measured in the study. This data shows the site-specific analyses of the various epidemiological parameters and antibody measurements.

45. Additional file 2: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST2: Details of covariates adjusted for in linear regression analysis of non-genetic factors with logged antibody levels, their relevance to the study and their previous association(s) with malaria or anti-malarial antibodies. Information on the covariates used in this study as con-variates in the various analyses.

46. Additional file 5: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, endocrine system, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF1: Histograms of logged antibody levels before further manipulations were made. Histograms of the logged antibody titres across all samples for each antibody measured in this study.

47. Additional file 15: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST9: Details of 196 genotyped SNPs and their derived allele frequencies at each site. This table shows allele frequencies for each SNP analysed in this study according to each study site.

48. Additional file 16: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST10: Meta-analysis p-values obtained for 178 SNPs passing QC criteria detailed in materials and methods. Details of the analyses for each SNP and antibody across all sites for different genetic inheritance models.

49. Additional file 11: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional table ST5: Linear regression analysis of the correlations between residuals from the malaria antibody pairs. This data shows the results of the analysis of the correlations between antibodies.

50. Additional file 8: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Table ST4: Results of linear regression analysis investigating the effect of age, gender and HbS genotype on parasite density in malaria-positive individuals using combined site data. Results of linear regression analysis investigating the effect of age, gender and HbS genotype on parasite density in malaria-positive individuals using combined data. This is an extension to that shown in the main text and is a reduced dataset as not all sites provided parasitaemia data.

Catalog

Books, media, physical & digital resources
See catalog results