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1. Factors affecting haemoglobin dynamics in African children with acute uncomplicated Plasmodium falciparum malaria treated with single low-dose primaquine or placebo

Author

Onyamboko, Marie A., Olupot-Olupot, Peter, Were, Winifred, Namayanja, Cate, Onyas, Peter, Titin, Harriet, Baseke, Joy, Muhindo, Rita, Kayembe, Daddy K., Ndjowo, Pauline O., Basara, Benjamin B., Okalebo, Charles B., Williams, Thomas N., Uyoga, Sophie, Taya, Chiraporn, Bamisaiye, Adeola, Fanello, Caterina, Maitland, Kathryn, Day, Nicholas P. J., Taylor, Walter R. J., and Mukaka, Mavuto

Published
2023
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2. Pharmacokinetics of single low dose primaquine in Ugandan and Congolese children with falciparum malaria

Author

Mukaka, Mavuto, Onyamboko, Marie A., Olupot-Olupot, Peter, Peerawaranun, Pimnara, Suwannasin, Kanokon, Pagornrat, Watcharee, Kouhathong, Jindarat, Madmanee, Wanassanan, Were, Winifred, Namayanja, Cate, Onyas, Peter, Titin, Harriet, Baseke, Joy, Muhindo, Rita, Kayembe, Daddy K., Ndjowo, Pauline O., Basara, Benjamin B., Bongo, Georgette S., Okalebo, Charles B., Abongo, Grace, Uyoga, Sophie, Williams, Thomas N., Taya, Chiraporn, Dhorda, Mehul, Dondorp, Arjen M., Waithira, Naomi, Imwong, Mallika, Maitland, Kathryn, Fanello, Caterina, Day, Nicholas P.J., Tarning, Joel, White, Nicholas J., and Taylor, Walter R.J.

Published
2023
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3. Whole blood versus red cell concentrates for children with severe anaemia: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial

Author

Maitland, Kathryn, Walker, Sarah A, George, Elizabeth C, Williams, Thomas N, Gibb, Diana M, Mpoya, Ayub, Frost, Gary, Walsh, Kevin, Olupot-Olupot, Peter, Nteziyaremye, Julius, Namayanja, Cate, Ssenyondo, Tonny, Passi, George, Muhindo, Rita, Masifa, George, Adong, Ruth, Okalebo, Charles B, Atimango, Emmanuela, Thembo, Nobert, Odong, George, Kiluli, Godfrey, Kapsindet, Job, Kiguli, Sarah, Opoka, Robert O, Kayaga, Julianne, Nabawanuka, Eva, Kadama, Eva, Mukisa, Cynthia Williams, Engoru, Charles, Alaroker, Florence, Nakuya, Margaret, Amorut, Denis, Olupot, Moses, Onyas, Pius, Ariimi, Margaret, Itipe, Melda, Atim, Mary G, Abeno, Mary, Okwi, Steven, Kulume, Mary G, Among, Grace, Achipa, Dorreen E, Uyoga, Sophie, Macharia, Alex, Mellewa, Machpherson, Chagaluka, George, Kennedy, Neil, Kumwenda, Felistas, Sochera, Tiferanji Fatch, Malenga, Albert, Chimalizeni, Yamikani FG, Gushu, Benard, Phiri, Tusekile, Chesale, Amisa, Mitole, Ndaona, Chokani, Ellida, Munthali, Annie, Hensbroek, Michael Boele von, South, Annabelle, Thomason, Margaret J, Baptiste, David, Connon, Roisin, MacCabe, Leanne, Ali, Abdul, Khamis, Kibibi, Madoola, Macreen, Abongo, Grace, Bates, Imelda, Urban, Britta, Heydermann, Robert, Kyomuhendo, Flavia, Nakalanzi, Sarah, Chabuka, John, Mkandawire, Nkhafwire, Fitzgerald, Felicity, Evans, Jennifer A, Molyneux, Elizabeth, Lubega, Irene, Crawley, Jane, Kazembe, Peter, Murphy, Mike, Peto, Tim, Todd, Jim, Mirembe, Grace, Musoka, Philipa, Tenu, Filemoni, M'baya, Bridon, Kyeyune Byabazair, Dorothy, Mbanya, Dora, and Walker, A Sarah

Published
2022
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5. Temporal trends of SARS-CoV-2 seroprevalence during the first wave of the COVID-19 epidemic in Kenya

Author

Adetifa, Ifedayo M. O., Uyoga, Sophie, Gitonga, John N., Mugo, Daisy, Otiende, Mark, Nyagwange, James, Karanja, Henry K., Tuju, James, Wanjiku, Perpetual, Aman, Rashid, Mwangangi, Mercy, Amoth, Patrick, Kasera, Kadondi, Ng’ang’a, Wangari, Rombo, Charles, Yegon, Christine, Kithi, Khamisi, Odhiambo, Elizabeth, Rotich, Thomas, Orgut, Irene, Kihara, Sammy, Bottomley, Christian, Kagucia, Eunice W., Gallagher, Katherine E., Etyang, Anthony, Voller, Shirine, Lambe, Teresa, Wright, Daniel, Barasa, Edwine, Tsofa, Benjamin, Bejon, Philip, Ochola-Oyier, Lynette I., Agweyu, Ambrose, Scott, J. Anthony G., and Warimwe, George M.

Published
2021
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6. Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial

Author

Maitland, Kathryn, Olupot-Olupot, Peter, Kiguli, Sarah, Chagaluka, George, Alaroker, Florence, Opoka, Robert O, Mpoya, Ayub, Walsh, Kevin, Engoru, Charles, Nteziyaremye, Julius, Mallewa, Machpherson, Kennedy, Neil, Nakuya, Margaret, Namayanja, Cate, Kayaga, Julianne, Nabawanuka, Eva, Sennyondo, Tonny, Aromut, Denis, Kumwenda, Felistas, Musika, Cynthia Williams, Thomason, Margaret J, Bates, Imelda, von Hensbroek, Michael Boele, Evans, Jennifer A, Uyoga, Sophie, Williams, Thomas N, Frost, Gary, George, Elizabeth C, Gibb, Diana M, and Walker, A Sarah

Published
2019
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8. Non-O ABO blood group genotypes differ in their associations with Plasmodium falciparum rosetting and severe malaria

Author

Opi, D. Herbert, primary, Ndila, Carolyne M., additional, Uyoga, Sophie, additional, Macharia, Alex W., additional, Fennell, Clare, additional, Ochola, Lucy B., additional, Nyutu, Gideon, additional, Siddondo, Bethseba R., additional, Ojal, John, additional, Shebe, Mohammed, additional, Awuondo, Kennedy O., additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Band, Gavin, additional, Maitland, Kathryn, additional, Kwiatkowski, Dominic P., additional, Rockett, Kirk A., additional, Williams, Thomas N., additional, and Rowe, J. Alexandra, additional

Published
2023
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9. SARS‐CoV‐2 seroprevalence and implications for population immunity: Evidence from two Health and Demographic Surveillance System sites in Kenya, February–December 2022

Author

Kagucia, E. Wangeci, primary, Ziraba, Abdhala K., additional, Nyagwange, James, additional, Kutima, Bernadette, additional, Kimani, Makobu, additional, Akech, Donald, additional, Ng'oda, Maurine, additional, Sigilai, Antipa, additional, Mugo, Daisy, additional, Karanja, Henry, additional, Gitonga, John, additional, Karani, Angela, additional, Toroitich, Monica, additional, Karia, Boniface, additional, Otiende, Mark, additional, Njeri, Anne, additional, Aman, Rashid, additional, Amoth, Patrick, additional, Mwangangi, Mercy, additional, Kasera, Kadondi, additional, Ng'ang'a, Wangari, additional, Voller, Shirine, additional, Ochola‐Oyier, Lynette I., additional, Bottomley, Christian, additional, Nyaguara, Amek, additional, Munywoki, Patrick K., additional, Bigogo, Godfrey, additional, Maitha, Eric, additional, Uyoga, Sophie, additional, Gallagher, Katherine E., additional, Etyang, Anthony O., additional, Barasa, Edwine, additional, Mwangangi, Joseph, additional, Bejon, Philip, additional, Adetifa, Ifedayo M. O., additional, Warimwe, George M., additional, Scott, J. Anthony G., additional, and Agweyu, Ambrose, additional

Published
2023
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14. Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial

Author

Olupot-Olupot, Peter, primary, Okiror, William, additional, Mnjalla, Hellen, additional, Muhindo, Rita, additional, Uyoga, Sophie, additional, Mpoya, Ayub, additional, Williams, Thomas N, additional, terHeine, Rob, additional, Burger, David M, additional, Urban, Britta, additional, Connon, Roisin, additional, George, Elizabeth C, additional, Gibb, Diana M, additional, Walker, A Sarah, additional, and Maitland, Kathryn, additional

Published
2023
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15. Sero-surveillance for IgG to SARS-CoV-2 at antenatal care clinics in three Kenyan referral hospitals: Repeated cross-sectional surveys 2020–21

Author

Lucinde, Ruth K., primary, Mugo, Daisy, additional, Bottomley, Christian, additional, Karani, Angela, additional, Gardiner, Elizabeth, additional, Aziza, Rabia, additional, Gitonga, John N., additional, Karanja, Henry, additional, Nyagwange, James, additional, Tuju, James, additional, Wanjiku, Perpetual, additional, Nzomo, Edward, additional, Kamuri, Evans, additional, Thuranira, Kaugiria, additional, Agunda, Sarah, additional, Nyutu, Gideon, additional, Etyang, Anthony O., additional, Adetifa, Ifedayo M. O., additional, Kagucia, Eunice, additional, Uyoga, Sophie, additional, Otiende, Mark, additional, Otieno, Edward, additional, Ndwiga, Leonard, additional, Agoti, Charles N., additional, Aman, Rashid A., additional, Mwangangi, Mercy, additional, Amoth, Patrick, additional, Kasera, Kadondi, additional, Nyaguara, Amek, additional, Ng’ang’a, Wangari, additional, Ochola, Lucy B., additional, Namdala, Emukule, additional, Gaunya, Oscar, additional, Okuku, Rosemary, additional, Barasa, Edwine, additional, Bejon, Philip, additional, Tsofa, Benjamin, additional, Ochola-Oyier, L. Isabella, additional, Warimwe, George M., additional, Agweyu, Ambrose, additional, Scott, J. Anthony G., additional, and Gallagher, Katherine E., additional

Published
2022
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16. Revealing the extent of the first wave of the COVID-19 pandemic in Kenya based on serological and PCR-test data

Author

Ojal, John, primary, Brand, Samuel P. C., additional, Were, Vincent, additional, Okiro, Emelda A., additional, Kombe, Ivy K., additional, Mburu, Caroline, additional, Aziza, Rabia, additional, Ogero, Morris, additional, Agweyu, Ambrose, additional, Warimwe, George M., additional, Uyoga, Sophie, additional, Adetifa, Ifedayo M. O., additional, Scott, J. Anthony G., additional, Otieno, Edward, additional, Ochola-Oyier, Lynette I., additional, Agoti, Charles N., additional, Kasera, Kadondi, additional, Amoth, Patrick, additional, Mwangangi, Mercy, additional, Aman, Rashid, additional, Ng’ang’a, Wangari, additional, Tsofa, Benjamin, additional, Bejon, Philip, additional, Barasa, Edwine, additional, Keeling, Matt J., additional, and Nokes, D. James, additional

Published
2022
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17. SARS-CoV-2 seroprevalence in three Kenyan health and demographic surveillance sites, December 2020-May 2021

Author

Etyang, Anthony O., primary, Adetifa, Ifedayo, additional, Omore, Richard, additional, Misore, Thomas, additional, Ziraba, Abdhalah K., additional, Ng’oda, Maurine A., additional, Gitau, Evelyn, additional, Gitonga, John, additional, Mugo, Daisy, additional, Kutima, Bernadette, additional, Karanja, Henry, additional, Toroitich, Monica, additional, Nyagwange, James, additional, Tuju, James, additional, Wanjiku, Perpetual, additional, Aman, Rashid, additional, Amoth, Patrick, additional, Mwangangi, Mercy, additional, Kasera, Kadondi, additional, Ng’ang’a, Wangari, additional, Akech, Donald, additional, Sigilai, Antipa, additional, Karia, Boniface, additional, Karani, Angela, additional, Voller, Shirine, additional, Agoti, Charles N., additional, Ochola-Oyier, Lynette I., additional, Otiende, Mark, additional, Bottomley, Christian, additional, Nyaguara, Amek, additional, Uyoga, Sophie, additional, Gallagher, Katherine, additional, Kagucia, Eunice W., additional, Onyango, Dickens, additional, Tsofa, Benjamin, additional, Mwangangi, Joseph, additional, Maitha, Eric, additional, Barasa, Edwine, additional, Bejon, Philip, additional, Warimwe, George M., additional, Scott, J. Anthony G., additional, and Agweyu, Ambrose, additional

Published
2022
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18. Epidemiological impact and cost-effectiveness analysis of COVID-19 vaccination in Kenya

Author

Orangi, Stacey, primary, Ojal, John, additional, Brand, Samuel PC, additional, Orlendo, Cameline, additional, Kairu, Angela, additional, Aziza, Rabia, additional, Ogero, Morris, additional, Agweyu, Ambrose, additional, Warimwe, George M, additional, Uyoga, Sophie, additional, Otieno, Edward, additional, Ochola-Oyier, Lynette I, additional, Agoti, Charles N, additional, Kasera, Kadondi, additional, Amoth, Patrick, additional, Mwangangi, Mercy, additional, Aman, Rashid, additional, Ng'ang'a, Wangari, additional, Adetifa, Ifedayo MO, additional, Scott, J Anthony G, additional, Bejon, Philip, additional, Keeling, Matt J, additional, Flasche, Stefan, additional, Nokes, D James, additional, and Barasa, Edwine, additional

Published
2022
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20. The clinical epidemiology of sickle cell anemia In Africa

Author

Macharia, Alex W., Mochamah, George, Uyoga, Sophie, Ndila, Carolyne M., Nyutu, Gideon, Makale, Johnstone, Tendwa, Metrine, Nyatichi, Emily, Ojal, John, Shebe, Mohammed, Awuondo, Kennedy O., Mturi, Neema, Peshu, Norbert, Tsofa, Benjamin, Scott, J. Anthony G., Maitland, Kathryn, and Williams, Thomas N.

Published
2018
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21. BIRC6 modifies risk of invasive bacterial infection in Kenyan children

Author

Gilchrist, James J, primary, Kariuki, Silvia N, additional, Watson, James A, additional, Band, Gavin, additional, Uyoga, Sophie, additional, Ndila, Carolyne M, additional, Mturi, Neema, additional, Mwarumba, Salim, additional, Mohammed, Shebe, additional, Mosobo, Moses, additional, Alasoo, Kaur, additional, Rockett, Kirk A, additional, Mentzer, Alexander J, additional, Kwiatkowski, Dominic P, additional, Hill, Adrian VS, additional, Maitland, Kathryn, additional, Scott, J Anthony G, additional, and Williams, Thomas N, additional

Published
2022
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22. Whole blood versus red cell concentrates for children with severe anaemia: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial

Author

George, Elizabeth C, primary, Uyoga, Sophie, additional, M'baya, Bridon, additional, Kyeyune Byabazair, Dorothy, additional, Kiguli, Sarah, additional, Olupot-Olupot, Peter, additional, Opoka, Robert O, additional, Chagaluka, George, additional, Alaroker, Florence, additional, Williams, Thomas N, additional, Bates, Imelda, additional, Mbanya, Dora, additional, Gibb, Diana M, additional, Walker, A Sarah, additional, Maitland, Kathryn, additional, Walker, Sarah A, additional, George, Elizabeth C, additional, Mpoya, Ayub, additional, Frost, Gary, additional, Walsh, Kevin, additional, Nteziyaremye, Julius, additional, Namayanja, Cate, additional, Ssenyondo, Tonny, additional, Passi, George, additional, Muhindo, Rita, additional, Masifa, George, additional, Adong, Ruth, additional, Okalebo, Charles B, additional, Atimango, Emmanuela, additional, Thembo, Nobert, additional, Odong, George, additional, Kiluli, Godfrey, additional, Kapsindet, Job, additional, Kayaga, Julianne, additional, Nabawanuka, Eva, additional, Kadama, Eva, additional, Mukisa, Cynthia Williams, additional, Engoru, Charles, additional, Nakuya, Margaret, additional, Amorut, Denis, additional, Olupot, Moses, additional, Onyas, Pius, additional, Ariimi, Margaret, additional, Itipe, Melda, additional, Atim, Mary G, additional, Abeno, Mary, additional, Okwi, Steven, additional, Kulume, Mary G, additional, Among, Grace, additional, Achipa, Dorreen E, additional, Macharia, Alex, additional, Mellewa, Machpherson, additional, Kennedy, Neil, additional, Kumwenda, Felistas, additional, Sochera, Tiferanji Fatch, additional, Malenga, Albert, additional, Chimalizeni, Yamikani FG, additional, Gushu, Benard, additional, Phiri, Tusekile, additional, Chesale, Amisa, additional, Mitole, Ndaona, additional, Chokani, Ellida, additional, Munthali, Annie, additional, Hensbroek, Michael Boele von, additional, South, Annabelle, additional, Thomason, Margaret J, additional, Baptiste, David, additional, Connon, Roisin, additional, MacCabe, Leanne, additional, Ali, Abdul, additional, Khamis, Kibibi, additional, Madoola, Macreen, additional, Abongo, Grace, additional, Urban, Britta, additional, Heydermann, Robert, additional, Kyomuhendo, Flavia, additional, Nakalanzi, Sarah, additional, Chabuka, John, additional, Mkandawire, Nkhafwire, additional, Fitzgerald, Felicity, additional, Evans, Jennifer A, additional, Molyneux, Elizabeth, additional, Lubega, Irene, additional, Crawley, Jane, additional, Kazembe, Peter, additional, Murphy, Mike, additional, Peto, Tim, additional, Todd, Jim, additional, Mirembe, Grace, additional, Musoka, Philipa, additional, and Tenu, Filemoni, additional

Published
2022
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23. 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
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25. Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data

Author

Connon, Roisin, George, Elizabeth C., Olupot-Olupot, Peter, Kiguli, Sarah, Chagaluka, George, Alaroker, Florence, Opoka, Robert O., Mpoya, Ayub, Walsh, Kevin, Engoru, Charles, Nteziyaremye, Julius, Mallewa, Macpherson, Kennedy, Neil, Nakuya, Margaret, Namayanja, Cate, Nabawanuka, Eva, Sennyondo, Tonny, Amorut, Denis, Williams Musika, C., Bates, Imelda, Boele van Hensbroek, M., Evans, Jennifer A., Uyoga, Sophie, Williams, Thomas N., Frost, Gary, Gibb, Diana M., Maitland, Kathryn, Walker, A. Sarah, Kiguli, S., Opoka, R. O., Nabawanuka, E., Kayaga, J., Kadama, E., Mbwali, I., Nuwabaine, L., Nakikwaku, R., Nsubuga, J., Mpande, K., Adoo, R., Ouma, O., Adia, N. K., Olupot-Olupot, P., Nteziyaremye, J., Namanyanga, C., Passi, G., Sennyondo, T., Adong, R., Okalebo, C. B., Atimango, E., Mwamula, S., Kapsindet, J., Muhindo, G. Kiluli R., Thembo, G. Masifa N., Odong, G., Engoru, C., Aloroker, F., Nakuya, M., Amorut, D., Ariima, M., Itipe, M., Atim, M. G., Abeno, M., Amede, B., Olupot, M., Okwi, S., Kulume, M. G., Among, G., Onyas, P., Achipa, E. D., Maitland, K., Mpoya, A., Maitha, P., Uyoga, S., Williams, T. N., Macharia, A., Mallewa, M., Chagaluka, G., Chimalizeni, Y., Kennedy, N., Kumwenda, F., Nkosi, E., Sochera, T., Malenga, A., Gushu, B., Phiri, T., Chisale, A., Mitole, N., Chokani, E., Munthali, A., Frost, G., Walsheto, K., Gibb, D. M., George, E. C., Thomason, M., Baptiste, D., McCabe, L., Walker, A. S., Ali, A., Khamis, K., Madula, M., Abongo, G., Heydermann, R., Bates, I., Urban, B., Kyomuhendo, F., Nakalanzi, S., Chabuka, J., Mkandawire, N., Evans, J. A., Fitzgerald, F., Molyneux, E., Murphy, I. Lubega M., Kazembe, P., Crawley, J., Peto, T., Musoke, P., Todd, J., Mirembe, G., and Tenu, F.

Subjects
wh_155, ws_300, wa_395, wa_320
Abstract

Background: Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions.\ud Methods: Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering.\ud Results: Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48\ud (95% CI 1.63–3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19–1.74), p < 0.001); history of transfusion (1.48(1.13–1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21–1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features),\ud who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47–0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47–0.76), p < 0.001); younger-age (1.07 (1.03–1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46–0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23–2.44) and 1.46(1.18–1.82) respectively compared to no splenomegaly.\ud Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severe\ud malaria.\ud Conclusions: Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important.\ud Trial registration: ISRCTN ISRCTN84086586.\ud Keywords: Severe anaemia, Readmission

Published
2021

26. Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immunoglobulin G Antibody Seroprevalence Among Truck Drivers and Assistants in Kenya

Author

Kagucia, E Wangeci, Gitonga, John N, Kalu, Catherine, Ochomo, Eric, Ochieng, Benard, Kuya, Nickline, Karani, Angela, Nyagwange, James, Karia, Boniface, Mugo, Daisy, Karanja, Henry K, Tuju, James, Mutiso, Agnes, Maroko, Hosea, Okubi, Lucy, Maitha, Eric, Ajuck, Hossan, Mukabi, David, Moracha, Wycliffe, Bulimu, David, Andanje, Nelson, Aman, Rashid, Mwangangi, Mercy, Amoth, Patrick, Kasera, Kadondi, Ng'ang'a, Wangari, Nyaguara, Amek, Voller, Shirine, Otiende, Mark, Bottomley, Christian, Agoti, Charles N, Ochola-Oyier, Lynette I, Adetifa, Ifedayo MO, Etyang, Anthony O, Gallagher, Katherine E, Uyoga, Sophie, Barasa, Edwine, Bejon, Philip, Tsofa, Benjamin, Agweyu, Ambrose, Warimwe, George M, Scott, J Anthony G, and Magarini Sub-County TDA SARS-CoV-2 Serosurveillance Team, The Bu

Subjects
viruses, virus diseases, human activities
Abstract

In October 2020, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G seroprevalence among truck drivers and their assistants (TDA) in Kenya was 42.3%, higher than among healthcare workers and blood donors. Truck drivers and their assistants transport essential supplies during the coronavirus disease 2019 pandemic, placing them at increased risk of being infected and of transmitting SARS-CoV-2 over a wide geographical area.

Published
2021

27. Point‐of‐care haemoglobin testing in African hospitals: a neglected essential diagnostic test

Author

Uyoga, Sophie, George, Elizabeth C., Bates, Imelda, Olupot‐Olupot, Peter, Chimalizeni, Yami, Molyneux, Elizabeth M., and Maitland, Kathryn

Subjects
wh_100, wh_155, ws_300, wa_395, wh_190
Abstract

Summary: Owing to the rapid turnaround time in the assessment of haemoglobin level by point‐of‐care tests (POC Hb), these have grown in popularity and scope in large parts of the world. However, whilst POC testing for malaria and HIV remains has been integrated into patient management in Africa, the use of POC haemoglobin testing remains neglected by health services. The main users of transfusions (paediatric, maternity and trauma services) present largely as emergencies. Ward‐based POC Hb could result in more rapid and accurate diagnosis of anaemia, contributing to saving of lives and at the same time reduce unnecessary transfusions which deplete the limited supplies of donated blood in Africa. Severe anaemia requiring transfusion is a major cause of paediatric admission in Africa. At a dissemination meeting to discuss the results of a large phase III paediatric transfusion trial and steps to implementation of the findings participants strongly recommended that one of the most pressing actions required was to prioritise the use of POC haemoglobin testing. This would facilitate implementation of the new transfusion algorithm, developed at the meeting, which refines patient management including blood transfusions. We present the rationale for the strongly recommended prioritisation of POC Hb, using paediatric transfusion as an exemplar.

Published
2021

28. Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia

Author

Abuga, Kelvin M., primary, Muriuki, John Muthii, additional, Uyoga, Sophie M., additional, Mwai, Kennedy, additional, Makale, Johnstone, additional, Mogire, Reagan M., additional, Macharia, Alex W., additional, Mohammed, Shebe, additional, Muthumbi, Esther, additional, Mwarumba, Salim, additional, Mturi, Neema, additional, Bejon, Philip, additional, Scott, J. Anthony G., additional, Nairz, Manfred, additional, Williams, Thomas N., additional, and Atkinson, Sarah H., additional

Published
2021
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29. 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
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30. 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
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31. Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial

Author

Olupot-Olupot, Peter, primary, Okiror, William, additional, Mnjalla, Hellen, additional, Muhindo, Rita, additional, Uyoga, Sophie, additional, Mpoya, Ayub, additional, Williams, Thomas N, additional, terHeine, Rob, additional, Burger, David M, additional, Urban, Britta, additional, Connon, Roisin, additional, George, Elizabeth C, additional, Gibb, Diana M, additional, Walker, A Sarah, additional, and Maitland, Kathryn, additional

Published
2021
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32. Revealing the extent of the first wave of the COVID-19 pandemic in Kenya based on serological and PCR-test data

Author

Ojal, John, primary, Brand, Samuel P. C., additional, Were, Vincent, additional, Okiro, Emelda A., additional, Kombe, Ivy K., additional, Mburu, Caroline, additional, Aziza, Rabia, additional, Ogero, Morris, additional, Agweyu, Ambrose, additional, Warimwe, George M., additional, Uyoga, Sophie, additional, Adetifa, Ifedayo M. O., additional, Scott, J. Anthony G., additional, Otieno, Edward, additional, Ochola-Oyier, Lynette I., additional, Agoti, Charles N., additional, Kasera, Kadondi, additional, Amoth, Patrick, additional, Mwangangi, Mercy, additional, Aman, Rashid, additional, Ng’ang’a, Wangari, additional, Tsofa, Benjamin, additional, Bejon, Philip, additional, Barasa, Edwine, additional, Keeling, Matt J., additional, and Nokes, D. James, additional

Published
2021
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33. Additional file 1 of Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data

Author

Connon, Roisin, George, Elizabeth C., Olupot-Olupot, Peter, Kiguli, Sarah, Chagaluka, George, Alaroker, Florence, Opoka, Robert O., Mpoya, Ayub, Walsh, Kevin, Engoru, Charles, Nteziyaremye, Julius, Mallewa, Macpherson, Kennedy, Neil, Nakuya, Margaret, Namayanja, Cate, Nabawanuka, Eva, Sennyondo, Tonny, Amorut, Denis, Williams Musika, C., Bates, Imelda, Boele van Hensbroek, M., Evans, Jennifer A., Uyoga, Sophie, Williams, Thomas N., Frost, Gary, Gibb, Diana M., Maitland, Kathryn, and Walker, A. Sarah

Abstract

Additional file 1: Supplementary Table 1. Univariable summary statistics of all factors considered. Supplementary Table 2. Risk score calculation. Supplementary Table 3. Description of clusters.

Published
2021
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34. Revealing the extent of the COVID-19 pandemic in Kenya based on serological and PCR-test data

Author

Ojal, John, Brand, Samuel PC, Were, Vincent, Okiro, Emelda A, Kombe, Ivy K, Mburu, Caroline, Aziza, Rabia, Ogero, Morris, Agweyu, Ambrose, Warimwe, George M, Uyoga, Sophie, Adetifa, Ifedayo MO, Scott, J Anthony G, Otieno, Edward, Ochola-Oyier, Lynette I, Agoti, Charles N, Kasera, Kadondi, Amoth, Patrick, Mwangangi, Mercy, Aman, Rashid, Ng’ang’a, Wangari, Tsofa, Benjamin, Bejon, Philip, Barasa, Edwine, Keeling, Matt J, and Nokes, D James

Abstract

Policy makers in Africa need robust estimates of the current and future spread of SARS-CoV-2. Data suitable for this purpose are scant. We used national surveillance PCR test, serological survey and mobility data to develop and fit a county-specific transmission model for Kenya. We estimate that the SARS-CoV-2 pandemic peaked before the end of July 2020 in the major urban counties, with 34 - 41% of residents infected, and will peak elsewhere in the country within 2-3 months. Despite this penetration, reported severe cases and deaths are low. Our analysis suggests the COVID-19 disease burden in Kenya may be far less than initially feared. A similar scenario across sub-Saharan Africa would have implications for balancing the consequences of restrictions with those of COVID-19.

Published
2020

35. Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency

Author

Gilchrist, James J, Uyoga, Sophie, Pirinen, Matti, Rautanen, Anna, Mwarumba, Salim, Njuguna, Patricia, Mturi, Neema, Kenyan Bacteraemia Study Group, Hill, Adrian VS, Scott, J Anthony G, and Williams, Thomas N

Subjects
hemic and lymphatic diseases, parasitic diseases
Abstract

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency state in humans. The clinical phenotype is variable and includes asymptomatic individuals, episodic hemolysis induced by oxidative stress, and chronic hemolysis. G6PD deficiency is common in malaria-endemic regions, an observation hypothesized to be due to balancing selection at the G6PD locus driven by malaria. G6PD deficiency increases risk of severe malarial anemia, a key determinant of invasive bacterial disease in malaria-endemic settings. The pneumococcus is a leading cause of invasive bacterial infection and death in African children. The effect of G6PD deficiency on risk of pneumococcal disease is undefined. We hypothesized that G6PD deficiency increases pneumococcal disease risk and that this effect is dependent upon malaria. METHODS: We performed a genetic case-control study of pneumococcal bacteremia in Kenyan children stratified across a period of falling malaria transmission between 1998 and 2010. RESULTS: Four hundred twenty-nine Kenyan children with pneumococcal bacteremia and 2677 control children were included in the study. Among control children, G6PD deficiency, secondary to the rs1050828 G>A mutation, was common, with 11.2% (n = 301 of 2677) being hemi- or homozygotes and 33.3% (n = 442 of 1329) of girls being heterozygotes. We found that G6PD deficiency increased the risk of pneumococcal bacteremia, but only during a period of high malaria transmission (P = 0.014; OR 2.33, 95% CI 1.19-4.57). We estimate that the population attributable fraction of G6PD deficiency on risk of pneumococcal bacteremia in areas under high malaria transmission is 0.129. CONCLUSIONS: Our data demonstrate that G6PD deficiency increases risk of pneumococcal bacteremia in a manner dependent on malaria. At the population level, the impact of G6PD deficiency on invasive pneumococcal disease risk in malaria-endemic regions is substantial. Our study highlights the infection-associated morbidity and mortality conferred by G6PD deficiency in malaria-endemic settings and adds to our understanding of the potential indirect health benefits of improved malaria control.

Published
2020

36. The effect of [[alpha].sup.+]-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya

Author

Wambua, Sammy, Mwangi, Tabitha W., Kortok, Moses, Uyoga, Sophie M., Macharia, Alex W., Mwacharo, Jedidah K., Weatherall, David J., Snow, Robert W., Marsh, Kevin, and Williams, Thomas N.

Subjects
Thalassemia -- Case studies, Thalassemia -- Physiological aspects, Malaria -- Physiological aspects, Malaria -- Genetic aspects, Children -- Diseases
Abstract

ABSTRACT Background The [alpha]-thalassaemias are the commonest genetic disorders of humans. It is generally believed that this high frequency reflects selection through a survival advantage against death from malaria; nevertheless, [...]

Published
2006

39. 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

42. 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
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43. The clinical epidemiology of sickle cell anemia In Africa

Author

Macharia, Alex W., primary, Mochamah, George, additional, Uyoga, Sophie, additional, Ndila, Carolyne M., additional, Nyutu, Gideon, additional, Makale, Johnstone, additional, Tendwa, Metrine, additional, Nyatichi, Emily, additional, Ojal, John, additional, Shebe, Mohammed, additional, Awuondo, Kennedy O., additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Scott, J. Anthony G., additional, Maitland, Kathryn, additional, and Williams, Thomas N., additional

Published
2017
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44. Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children

Author

Kenyan Bacteraemia Study Group, Wellcome Trust Case Control Consortium 2 (WTCCC2), Rautanen, Anna, Pirinen, Matti, Mills, Tara C, Rockett, Kirk A, Strange, Amy, Ndungu, Anne W, Naranbhai, Vivek, Gilchrist, James J, Bellenguez, Céline, Freeman, Colin, Band, Gavin, Bumpstead, Suzannah J, Edkins, Sarah, Giannoulatou, Eleni, Gray, Emma, Dronov, Serge, Hunt, Sarah E, Langford, Cordelia, Pearson, Richard D, Su, Zhan, Vukcevic, Damjan, Macharia, Alex W, Uyoga, Sophie, Ndila, Carolyne, Mturi, Neema, Njuguna, Patricia, Mohammed, Shebe, Berkley, James A, Mwangi, Isaiah, Mwarumba, Salim, Kitsao, Barnes S, Lowe, Brett S, Morpeth, Susan C, Khandwalla, Iqbal, Kilifi Bacteraemia Surveillance Group, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin NA, Plomin, Robert, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas W, Deloukas, Panos, Peltonen, Leena, Williams, Thomas N, Scott, J Anthony G, Chapman, Stephen J, Donnelly, Peter, Hill, Adrian VS, Spencer, Chris CA, Markus, Hugh [0000-0002-9794-5996], Sawcer, Stephen [0000-0001-7685-0974], and Apollo - University of Cambridge Repository

Subjects
Polymorphism, Genetic, Adolescent, Infant, Newborn, Infant, Bacteremia, Pneumonia, Pneumococcal, Kenya, Streptococcus pneumoniae, Risk Factors, Case-Control Studies, Child, Preschool, parasitic diseases, Humans, RNA, Long Noncoding, Child, Genome-Wide Association Study
Abstract

Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease.

Published
2016

45. Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial

Author

Mpoya, Ayub, Kiguli, Sarah, Olupot-Olupot, Peter, Opoka, Robert O., Engoru, Charles, Mallewa, Macpherson, Chimalizeni, Yami, Kennedy, Neil, Kyeyune, Dorothy, Wabwire, Benjamin, M’baya, Bridon, Bates, Imelda, Urban, Britta, von Hensbroek, Michael Boele, Heyderman, Robert, Thomason, Margaret J., Uyoga, Sophie, Williams, Thomas N., Gibb, Diana M., George, Elizabeth C., Walker, A. Sarah, Maitland, Kathryn, Global Health, and Paediatric Infectious Diseases / Rheumatology / Immunology

Subjects
Malawi, Time Factors, Health Status, Medicine (miscellaneous), Nutritional Status, Anaemia, Severity of Illness Index, Drug Administration Schedule, wb_356, Study Protocol, Hemoglobins, Patient Admission, SDG 3 - Good Health and Well-being, Clinical Protocols, Recurrence, Risk Factors, Sepsis, Infant Mortality, Trimethoprim, Sulfamethoxazole Drug Combination, Humans, Pharmacology (medical), Blood Transfusion, Uganda, Micronutrients, Hospital Mortality, Child, Children, Antibiotic prophylaxis, Anthelmintics, wh_155, Transfusion, Age Factors, Infant, Transfusion Reaction, Anemia, Vitamins, Haemoglobinopathies, Malaria, ws_300, ws_366, Treatment Outcome, Research Design, Child, Preschool, Africa, Child Mortality, Dietary Supplements, Emergency medicine, Biomarkers
Abstract

Background\ud In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9–10 %), 6-month mortality and relapse (6 %). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted.\ud \ud Methods/Design\ud TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin

Published
2015

46. 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

47. Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children

Author

Rautanen, Anna, primary, Pirinen, Matti, additional, Mills, Tara C., additional, Rockett, Kirk A., additional, Strange, Amy, additional, Ndungu, Anne W., additional, Naranbhai, Vivek, additional, Gilchrist, James J., additional, Bellenguez, Céline, additional, Freeman, Colin, additional, Band, Gavin, additional, Bumpstead, Suzannah J., additional, Edkins, Sarah, additional, Giannoulatou, Eleni, additional, Gray, Emma, additional, Dronov, Serge, additional, Hunt, Sarah E., additional, Langford, Cordelia, additional, Pearson, Richard D., additional, Su, Zhan, additional, Vukcevic, Damjan, additional, Macharia, Alex W., additional, Uyoga, Sophie, additional, Ndila, Carolyne, additional, Mturi, Neema, additional, Njuguna, Patricia, additional, Mohammed, Shebe, additional, Berkley, James A., additional, Mwangi, Isaiah, additional, Mwarumba, Salim, additional, Kitsao, Barnes S., additional, Lowe, Brett S., additional, Morpeth, Susan C., additional, Khandwalla, Iqbal, additional, Blackwell, Jenefer M., additional, Bramon, Elvira, additional, Brown, Matthew A., additional, Casas, Juan P., additional, Corvin, Aiden, additional, Duncanson, Audrey, additional, Jankowski, Janusz, additional, Markus, Hugh S., additional, Mathew, Christopher G., additional, Palmer, Colin N.A., additional, Plomin, Robert, additional, Sawcer, Stephen J., additional, Trembath, Richard C., additional, Viswanathan, Ananth C., additional, Wood, Nicholas W., additional, Deloukas, Panos, additional, Peltonen, Leena, additional, Williams, Thomas N., additional, Scott, J. Anthony G., additional, Chapman, Stephen J., additional, Donnelly, Peter, additional, Hill, Adrian V.S., additional, and Spencer, Chris C.A., additional

Published
2016
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50. Identifying children with excess malaria episodes after adjusting for variation in exposure: identification from a longitudinal study using statistical count models

Author

Ndungu, Francis Maina, primary, Marsh, Kevin, additional, Fegan, Gregory, additional, Wambua, Juliana, additional, Nyangweso, George, additional, Ogada, Edna, additional, Mwangi, Tabitha, additional, Nyundo, Chris, additional, Macharia, Alex, additional, Uyoga, Sophie, additional, Williams, Thomas N, additional, and Bejon, Philip, additional

Published
2015
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