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1. Does acute malnutrition in young children increase the risk of treatment failure following artemisinin-based combination therapy? A WWARN individual patient data meta-analysis

Author

Stepniewska, Kasia, Allan, Richard, Anvikar, Anupkumar R, Anyorigiya, Thomas A, Ashley, Elizabeth A, Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bonnet, Maryline, Boulton, Caroline, Bousema, Teun, Carn, Gwenaelle, Carrara, Verena I, D'Alessandro, Umberto, Davis, Timothy ME, Denoeud-Ndam, Lise, Desai, Meghna, Djimde, Abdoulaye A, Dorsey, Grant, Etard, Jean-François, Falade, Catherine, Fanello, Caterina, Gaye, Oumar, Gonzalez, Raquel, Grandesso, Francesco, Grivoyannis, Anastasia D, Grais, Rebecca F, Humphreys, Georgina S, Ishengoma, Deus S, Karema, Corine, Kayentao, Kassoum, Kennon, Kalynn, Kremsner, PeterG, Laman, Moses, Laminou, Ibrahim M, Macete, Eusebio, Martensson, Andreas, Mayxay, Mayfong, Menan, Hervé IB, Menéndez, Clara, Moore, Brioni R, Nabasumba, Carolyn, Ndiaye, Jean-Louis, Nhama, Abel, Nosten, Francois, Onyamboko, Marie, Phyo, Aung Pyae, Ramharter, Michael, Rosenthal, Philip J, Schramm, Birgit, Sharma, Yagya D, Sirima, Sodiomon B, Strub-Wourgaft, Nathalie, Sylla, Khadime, Talisuna, Ambrose O, Temu, Emmanuel A, Thwing, Julie I, Tinto, Halidou, Valentini, Giovanni, White, Nicholas J, Yeka, Adoke, Isanaka, Sheila, Barnes, Karen I, and Guerin, Philippe J

Published
2024
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3. Effect of systematic tuberculosis detection on mortality in young children with severe pneumonia in countries with high incidence of tuberculosis: a stepped-wedge cluster-randomised trial

Author

Marcy, Olivier, Serre, Angeline, Badrichani, Anne, Razafimanantsoa, Manoa, Poublan, Julien, Vessière, Aurélia, Roucher, Clémentine, Occelli, Estelle, Beuscart, Aurélie, Charpin, Aurélie, Habiyambere, Gemma, Mesnier, Salomé, Balestre, Eric, Bhatta, Bandana, Maillard, Anne-Laure, Orne-Gliemann, Joanna, Baillet, Emmanuelle, Koskas, Nicolas, D'Elbée, Marc, Gabillard, Delphine, Font, Hélène, Huyen, Minh, Bonnet, Maryline, Lounnas, Manon, Espérou, Hélène, Couffin-Cadiergues, Sandrine, Kuppers, Alexis, Hamze, Benjamin, BORAND, Laurence, de LAUZANNE, Agathe, DIM, Bunnet, Keang, Chanthy, PRING, Long, YIN, Song, SARITH, Channimol, PHAN, Chanvirak, NHEUONG, Sovann, LY, Socheat, KAING, Sanary, SRENG, Vouchleang, LUN, Elen, SAY, Leakhena, SUOM, Sophea, FERHY, Romyka, SO, Dina, BORN, Sorunna, PAL, Sophea, NANG, Boraneath, MAO, Tan Eang, KIM, Ang, Srey, Viso, Kan, Piseth, Hout, leakhena, Ith, Samnang, Oum, Sophany, Sau, Sokunvadhana, Ho, Kim Heang, Kith, Daronic, Nuch, Nathara, Horm, Chhun Leang, Sophon, Cheameas, Roeungdeth, Bosba, MENG, Chhay, RITH, Ravin, PHY, Samnang, SOR, Chanchetra, SAO, Voleak, KHAT, Sophea, MAK, Bunthoeun, UY, Angkeaborin, KHAY, Sreyny, SOM, Kimsan, HACH, rongvirak, SOK, Hay, KUON, Sotheavy, HENG, Synatt, SENG, Amara, NIM, Sopheak, PAN, Reach, KIM, Srean, SREY LEAP, Keo, NET, Bormey, NOUN, Viccheka, LAY, Daven, MANY, Chhaing, Seng, Socheata, Ly, Vuthy, So, Saran, Oun, Sovutthik, CHEY, Sopheap, CHHEA, Rattany, BAONG, Lydeth, THOUNG, Vanna, KHEANG, Chanrithea, BY, Borady, Nguon, Vathanak, MEACH, Eksophea, Tek, Sopheak, Ngeav, Sina, Lun, Tetra, HEM, Deth, CHUT, Nayreang, SARIK, Setha, NANG, Hgekkoung, MEACH, Mengnean, SRENG, Sopal, SAR, Dara, KIN, Rathana, ROS, Phoran, DORN, Chenda, KAK, Chansy, Sambath, Srey Leak, Son, Leakhena, Bin, Linda, Pengong, Eangnay, Pol, Sokha, Khutsorn, Samnang, Seang, Sorsophea, Soun, Virak, Vong, Vuthy, Khoeung, Chandara, Um, Panha, Bou, Sokunthea, Song Pich, Sarin, Nim, Puthy, Khat, Sopheak, Ban Si, Nuon, Ream, Sovannodom, Ing, Sim, Chann, Phanith, Ngeth, Samrith, Sun, Marina, Chhoeung, Sokea, Sean, Soeun, Prak, Ratanak, Taguebue, Jean-Voisin, Kwedi Nolna, Sylvie, Amboua Schouame Onambele, Audrey, Hycenth, Numfor, Melingui, Bernard, Nkembe Medounmga, Angeline, Hougnang Tatmi, Luciole, Etemgoua, Nathalie, Kouesso, Vanessa, Bugin, Jean, Nzedjom, Celestine, Ngoya, Roger, Eyike, Jules, Loudjom, Elyse, Lonsti, Roger, Dang, Ladi, Bintar, Edward, Njayong, Chantal, Ngonsoa O, Cinthia, Ndzeukap, Isabelle, Dzoyem, Pascaline, Dzokou, Clémentine, Dindo, Berthe, Moh, Raoul, Komena, Eric Auguste, Aka Bony, Roger, Kouadio, Christian, Danho, Serge, Goli, Melissa, Folquet, Madeleine, Itchy, Max Valère, Sidibé, Abdel, Cissé, Lancina, Ouattara, Joseph, Konaté, Mamadou, Amon-Tanoh Dick, Flore, Cardena, Melissa, Adonis-Koffi, Laurence, Eugenie, Djabia, Kouamé, Ferdinand, Menan, Hervé, Inwoley, André, Ouassa, Timothée, Nguessan, Marcelle Sandrine, Khosa, Celso, Cumbe, Saniata, Manhiça, Emelva, Zitha, Alcina, Chiúle, Valter, Muxanga, Eva, Gune, Irene, Lima, Yara, Ribeiro, Jorge, Mavale, Sandra, Chilundo, Josina, Maxanguana, Felismina, Morais, Natália, Manhiça, Julieta, Give, Josefina, Atumane, Jafito, Lucas, Gelson, Thai, Arsénio, Chave, Adélio, Rego, Dalila, Guambe, Lúcia, Issa, Faiaz, Carneiro, Rosa, Pene, Neusa, Florindo, Natércia, Machel, Dália, Cumbane, Cecília, Mendes, Helena, Kitungwa, Mule, Muianga, Valdo, Tamele, Humberto, Sulude, Adelino, Mabota, Roda, Comandante, Herquéria, Massangaie, Abelardo, Wobudeya, Eric, Businge, Gerald Bright, Namulinda, Faith, Sserunjogi, Robert, Nassozi, Rashidah, Barungi, Charlotte, Aanyu, Hellen, Muwonge, Doreen, Kagoya, Eva, Aciparu, Serene, Chemutai, Sophia, Ntambi, Samuel, Wasswa, Amir, Nangozi, Juliet, Tagoola, Abner, Mbekeka, Prossy, Kenneth, Sajja, Lubega, John Paul, Nassali, Aidah, Tagobera, Jessica, Agwang, Christine, Kalembe, Florence, Ajambo, Annet, Aguti, Elizabeth, Kasibante, Samuel, Matende, Henry, Odongo, Israel Owen, Mwanga Amumpaire, Juliet, Natukunda, Naome, Ngabirano, Gertrude, Kakwenza, Paul, Nuwamanya, Simpson, Nyangoma, Miria, Nabbuto, Jane, Abok, Florence, Arinaitwe, Rinah, Birungi, Diana, Mwesigwa, Evans, Atwine, Daniel, Mbega, Hassan, Orikiriza, Patrick, Taremwa, Ivan, Turyashemererwa, Esther, Derrick, Hope, Nyehangane, Dan, Kaitano, Rodney, Logoose, Susan, Businge, Steven, Ntambi, Charles, Mugabi, Jerome, Mzee, John, Besigye, Julius, Kanzira, Saul, Turyatemba, Phionah, Twebaze, Florence, Chabala, Chishala, Mulenga, Veronica, Shankalala, Perfect, Hambulo, Chimuka, Kapotwe, Vincent, Ngambi, Marjory, Kasakwa, Kunda, Chirwa, Uzima, Kapula, Chifunda, Zulu, Susan, Nawakwi, Grace, Siasulingana, Teddy, Chilonga, Jessy, Chimbini, Maria, Chilanga, Mutinta, Nduna, Bwendo, Inambao, Muleya, Mwambazi, Mwate, Halende, Barbra, Mumba, Wyclef, Mankunshe, Endreen, Silavwe, Maureen, Chakopo, Moses, Moono, Roy, Mwanga-Amumpaire, Juliet, De Lauzanne, Agathe, Dim, Bunnet, Tiogouo Ngouana, Emeline, Folquet Amorrissani, Madeleine, Cisse, Lassina, Amon Tanoh Dick, Flore, Komena, Eric A, Businge, Gerald, Kim, Ang, Kheang, Chanrithea, Maleche-Obimbo, Elizabeth, Seddon, James A, Mao, Tan Eang, Graham, Stephen M, Delacourt, Christophe, and Borand, Laurence

Published
2023
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4. Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial

Author

Badje, Anani, Moh, Raoul, Gabillard, Delphine, Guéhi, Calixte, Kabran, Mathieu, Ntakpé, Jean-Baptiste, Le Carrou, Jérôme, Kouame, Gérard-Menan, Ouattara, Eric, Messou, Eugène, Anzian, Amani, Minga, Albert, Gnokoro, Joachim, Gouesse, Patrice, Emieme, Arlette, Toni, Thomas-d'Aquin, Rabe, Cyprien, Sidibé, Baba, Nzunetu, Gustave, Dohoun, Lambert, Abo, Yao, Kamagate, Synali, Amon, Solange, Kouame, Amadou-Barenson, Koua, Aboli, Kouamé, Emmanuel, Daligou, Marcelle, Hawerlander, Denise, Ackoundzé, Simplice, Koule, Serge, Séri, Jonas, Ani, Alex, Dembélé, Fassery, Koné, Fatoumata, Oyebi, Mykayila, Mbakop, Nathalie, Makaila, Oyewole, Babatunde, Carolle, Babatunde, Nathaniel, Bleoué, Gisèle, Tchoutedjem, Mireille, Kouadio, Alain-Claude, Sena, Ghislaine, Yededji, Sahinou-Yediga, Karcher, Sophie, Rouzioux, Christine, Kouame, Abo, Assi, Rodrigue, Bakayoko, Alima, Domoua, Serge-K., Deschamps, Nina, Aka, Kakou, N'Dri-Yoman, Thérèse, Salamon, Roger, Journot, Valérie, Ahibo, Hughes, Ouassa, Timothée, Ménan, Hervé, Inwoley, André, Ndja, Ben-Ahoussi, Adou, Blandine, Kanga, Constance, Aoussi, Eba, Bissagnene, Emmanuel, Ba-Gomis, Olivier, Zike, Yves-Alain, Akakpo, Claude, Sassan-Morokro, Madeleine, Mobio, Max, Doféré, Bamba, Mesmin, Koman, Attia, Alain, Mahassadi, Alassane, Horo, Apollinaire, Oussou, Armel, Chaix, Marie-Laure, Peytavin, Gilles, Koné, Mariatou, N'Guessan, Kouamé, Fassassi, Raïmi, Niangoran, Serge, Desgrées-du-Loû, Annabel, Lert, France, Dray Spira, Rosemary, Jean, Kevin, Konan, Romuald, Bohoussou, Franck, Yao-Yapi, Cyril, N'guessan-Koffi, Larissa, Siloué, Bertine, Cissé, Adoulaye, Aboua, Adrienne, Konan, Sylvie, Kouamé, Antoine, N'Chot, Celestin, Amani, Elvis, Clouet, Gwenaëlle, Debono, Bruno, Chêne, Geneviève, Dosso, Mireille, Girard, Pierre-Marie, Jarlier, Vincent, Masumbuko, Jean-Marie, Perronne, Christian, Sow, Papa-Salif, Danel, Christine, Eholié, Serge-Paul, Anglaret, Xavier, Carrou, Jérôme Le, Kouame, Gérard M, Yao, Abo, Domoua, Serge K, Menan, Hervé, and Eholié, Serge P

Published
2017
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5. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author

Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia

Abstract

Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr

Published
2023
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7. Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author

Mansoor, Rashid, Commons, Robert J, Douglas, Nicholas M, Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O, Adjuik, Martin, Alemayehu, Bereket H, Allan, Richard, Allen, Elizabeth N, Anvikar, Anupkumar R, Arinaitwe, Emmanuel, Ashley, Elizabeth A, Ashurst, Hazel, Asih, Puji BS, Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J, Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy ME, Desai, Meghna, Djimde, Abdoulaye A, Dondorp, Arjen M, Dorsey, Grant, Drakeley, Chris J, Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F, Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S, Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S Patrick, Kager, Piet A, Kamugisha, Erasmus, Kamya, Moses R, Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G, Lalloo, David G, Laman, Moses, Lee, Sue J, Lell, Bertrand, Maiga, Amelia W, Martensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R, Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N, Ngasala, Billy E, Nikiema, Frederic, Nji, Akindeh M, Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R, Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K, Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L, Rombo, Lars, Rosenthal, Philip J, Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B, Smithuis, Frank M, Some, Fabrice A, Staedke, Sarah G, Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D, Syafruddin, Din, Talisuna, Ambrose O, Taylor, Walter R, Temu, Emmanuel A, Thwing, Julie I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A, Tran, T Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A, Were, Vincent, White, Nicholas J, Woodrow, Charles J, Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A, Guerin, Philippe J, Stepniewska, Kasia, Price, Ric N, Roper, Cally, Resistance, WorldWide Antimalarial, WorldWide Antimalarial Resistance Network Falciparum Haematology Study Group, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Epidémiologie des Maladies Chroniques en zone tropicale (EpiMaCT), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Group, WorldWide Antimalarial Resistance Network Falciparum Haematology Study, Mansoor, R, Ashley, EA, Ashurst, H, Burrow, R, Carrara, VI, Das, D, Dondorp, AM, Humphreys, GS, Lee, SJ, Mayxay, M, McGready, R, Newton, PN, Nosten, F, Richmond, CL, Sibley, C, Smithuis, FM, Taylor, WR, Tran, TH, von Seidlein, L, White, NJ, Woodrow, CJ, Guerin, PJ, Stepniewska, K, Price, RN, AII - Infectious diseases, Intensive Care Medicine, Infectious diseases, APH - Global Health, and APH - Quality of Care

Subjects
Infectious Medicine, Plasmodium falciparum, wh_120, Infektionsmedicin, Severe anaemia, Parasitemia, wa_530, Antimalarials, Non-artemisinin-based therapy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, qv_256, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Malaria, Falciparum, Child, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Pooled analysis of individual patient data, Anemia, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Artemisinin-based therapy, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Malaria, wc_750, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Haemoglobin
Abstract

Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.

Published
2022

9. Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis

Author

Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Bassat, Quique, Borrmann, Steffen, Bousema, Teun, Bukirwa, Hasifa, Carrara, Verena, I, Corsi, Marco, D'Alessandro, Umberto, Davis, Timothy M. E., Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Gilayeneh, Julius, Greenwood, Brian, Grivoyannis, Anastasia, Hien, Tran Tinh, Hwang, Jimee, Janssens, Bart, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy, Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Ogutu, Bernhards R., Olliaro, Piero L., Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher, V, Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Vitare, Primum, Rombo, Lars, Rosenthal, Philip J., Sibley, Carol, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala, Thuy-Nhien, Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan D., van Herp, Michel, van Lenthe, Marit, van Vugt, Michele, William, Yavo, Winnips, Cornelis, Zaloumis, Sophie, Zongo, Issaka, White, Nick J., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Arinaitwe, Emmanuel, and Group, WorldWide Antimalarial Resistance Network Methodology Study

Subjects
Infectious Medicine, Efficacy, Follow-up, Recrudescence, Artemether, Lumefantrine Drug Combination, Plasmodium falciparum, Infektionsmedicin, Distribution, Artemisinins, Malaria, Antimalarials, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Recurrence, Child, Preschool, Humans, Parasitology, Artemether, Child
Abstract

Background The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria. Methods Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up. Results Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0–22%] in those treated with ≤ 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution. Conclusions Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.

Published
2022

10. AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4 Cell Counts in HIV-Infected Adults Before Starting Antiretroviral Therapy in Côte d'Ivoire

Author

The ANRS 12222 Morbidity/Mortality Study Group, Anglaret, Xavier, Minga, Albert, Gabillard, Delphine, Ouassa, Timothée, Messou, Eugene, Morris, Brandon, Traore, Moussa, Coulibaly, Ali, Freedberg, Kenneth A., Lewden, Charlotte, Ménan, Hervé, Abo, Yao, Dakoury-Dogbo, Nicole, Toure, Siaka, and Seyler, Catherine

Published
2012
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11. Low Risk of Nevirapine Resistance Mutations in the Prevention of Mother-to-Child Transmission of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus, Abidjan, Côte d'Ivoire

Author

Agence Nationale de Recherches sur le SIDA Ditrame Plus Study Group, Chaix, Marie-Laure, Ekouevi, Didier Koumavi, Rouet, François, Tonwe-Gold, Besigin, Viho, Ida, Bequet, Laurence, Peytavin, Gilles, Toure, Hassane, Menan, Hervé, Leroy, Valériana, Dabis, Francois, and Rouzioux, Christine

Published
2006

12. Virological failure and drug resistance in West African HIV-infected adults who started ART immediately or deferred ART initiation

Author

Gabillard, Delphine, N'Takpe, Jean-Baptiste, Chaix, Marie Laure, KOUAME, Menan Gerard, Moh, Raoul, Toni, Thomas D'Aquin, LE CARROU, Jerome, Karcher, Sophie, BADJE, Anani, Emieme, Arlette, MENAN, Herve, Danel, Christine, Anglaret, Xavier, Eholie, Serge Paul, TEMPRANO, Anrs Study Group, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

BACKGROUND: Asymptomatic HIV-infected people who start ART early may feel less motivated and neglect compliance. This might promote the emergence of resistance. METHODS: In the Temprano trial, ART-naive HIV-infected adults with high CD4 counts were randomly assigned to start ART immediately (immediate group) or defer ART until the WHO criteria were met (deferred group). All participants were monitored for 30 months. Those in the deferred group who started ART were monitored for longer, until they had completed 30 months on ART. We compared the rate of virological failure and drug resistance between the immediate and deferred groups 30 months after ART initiation. RESULTS: Of the 2056 participants in Temprano, 1033 were assigned to start ART immediately and 1023 to defer ART. Of the latter, 488 started ART during trial follow-up. Patients in the deferred group who started ART had a lower median CD4 count (280 versus 465 cells/mm3) and a higher median plasma HIV-1 RNA (5.1 versus 4.7 log10 copies/mL) at baseline. During follow-up, participants in both groups had similar antiretroviral drug exposure. Thirty months after ART initiation, patients in the deferred group had a higher rate of virological failure (35.3% versus 29.9%, P = 0.04) and a lower genotypic susceptibility score (P = 0.04). CONCLUSIONS: Starting ART early decreases the risk of virological failure and drug resistance in the medium term. This benefit is of particular importance in countries where access to viral load monitoring and the number of antiretroviral drug lines is limited.

Published
2021

14. High prevalence of Schistosoma haematobium x Schistosoma bovis hybrids in schoolchildren in Cote d'Ivoire

Author

Angora, Etienne K., Allienne, Jean-francois, Rey, Olivier, Menan, Herve, Toure, Andre O., Coulibaly, Jean T., Raso, Giovanna, Yavo, William, N'Goran, Eliezer K., Utzinger, Jurg, Balmer, Oliver, Boissier, Jerome, Angora, Etienne K., Allienne, Jean-francois, Rey, Olivier, Menan, Herve, Toure, Andre O., Coulibaly, Jean T., Raso, Giovanna, Yavo, William, N'Goran, Eliezer K., Utzinger, Jurg, Balmer, Oliver, and Boissier, Jerome

Abstract

Schistosomiasis is a neglected tropical disease, though it is highly prevalent in many parts of sub-Saharan Africa. While Schistosoma haematobium-bovis hybrids have been reported in West Africa, no data about Schistosoma hybrids in humans are available from Cote d'Ivoire. This study aimed to identify and quantify S. haematobium-bovis hybrids among schoolchildren in four localities of Cote d'Ivoire. Urine samples were collected and examined by filtration to detect Schistosoma eggs. Eggs were hatched and 503 miracidia were individually collected and stored on Whatman(R) FTA cards for molecular analysis. Individual miracidia were molecularly characterized by analysis of mitochondrial cox1 and nuclear internal transcribed spacer 2 (ITS 2) DNA regions. A mitochondrial cox1-based diagnostic polymerase chain reaction was performed on 459 miracidia, with 239 (52.1%) exhibiting the typical band for S. haematobium and 220 (47.9%) the S. bovis band. The cox1 and ITS 2 amplicons were Sanger sequenced from 40 randomly selected miracidia to confirm species and hybrids status. Among the 33 cox1 sequences analysed, we identified 15 S. haematobium sequences (45.5%) belonging to seven haplotypes and 18 S. bovis sequences (54.5%) belonging to 12 haplotypes. Of 40 ITS 2 sequences analysed, 31 (77.5%) were assigned to pure S. haematobium, four (10.0%) to pure S. bovis and five (12.5%) to S. haematobium-bovis hybrids. Our findings suggest that S. haematobium-bovis hybrids are common in Cote d'Ivoire. Hence, intense prospection of domestic and wild animals is warranted to determine whether zoonotic transmission occurs.

Published
2020
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15. Antiplasmodial activity and acute oral toxicity of Rauvolfia vomitoria leaves extracts

Author

Cynthia Nkoua-Badzi, Tano Konan Dominique, Dable Marius Tresor, Nsonde-Ntandou Gelase Fredy, Kigbafori D Silue, Kouakou-Siransy Gisele, Parra Henri-Joseph, Menan Herve, Abena Ange Antoine, and Yavo William

Subjects
lcsh:Therapeutics. Pharmacology, Sybr Green assay, lcsh:RM1-950, acute oral toxicity, Antiplasmodial activity, field isolates, reference strain
Abstract

Background: Malaria is one of the most important diseases in Republic of Congo with 47.9% of outpatients visit for 64.8% admissions. The rise of antimalarial resistant strains requires the active search of new active compounds and medicinal plants can be an alternative. From an ethnobotanical survey a list of plants with antimalarial reputations was drawn up, including Rauvolfia vomitoria. Aim: The objective of this study is to see if we can validate the supposed activity of Rauvolfia vomitoria and its toxicity. Material and Methods: Rauvolfia vomitoria’s leaves have been collected, dried and sprayed. Leaves powder were macerated in distilled water for 24 hours. Another part of leaves powder were macerated for 24 hours successively in hexane, dichloromethane, mix of diclhoromethane: methanol (v:v) and methanol. The crude extracts were prepared and tested for antiplasmodial activity on NF54 strains and field isolates with the SYBR Green I-based in vitro assay technique. The extracts with the best antiplasmodial activities were used on rats for acute toxicity. Results: All Rauvolfia vomitoria’s leaves extracts have shown a very good antiplasmodial activity (0.63 ≤ CI50 ≤ 20.19µg/ml) and no toxicity up to 2000mg/kg. Conclusion: Rauvolfia vomitoria’s leaves have an antiplasmodial activity. This study confirms the use of the plant by the traditional healers. We will pursue the work to find the active compounds of the plant.

Published
2018

16. CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): a randomised trial

Author

Danel, Christine, Moh, Raoul, Minga, Albert, Anzian, Amani, Ba-Gomis, Olivier, Kanga, Constance, Nzunetu, Gustave, Gabillard, Delphine, Rouet, Francois, Sorho, Souleymane, Chaix, Marie-Laure, Eholie, Serge, Menan, Herve, Sauvageot, Delphine, Bissagnene, Emmanuel, Salamon, Roger, and Anglaret, Xavier

Subjects
HIV infection -- Drug therapy, Highly active antiretroviral therapy -- Health aspects
Published
2006

18. HIV-1-related morbidity in adults, Abidjan, Cote d'Ivoire: a nidus for bacterial diseases

Author

Attia, Alain, Huet, Charlotte, Anglaret, Xavier, Toure, Siaka, Ouassa, Timothee, Gourvellec, Gwenola, Menan, Herve, Dakoury-Dogbo, Nicole, Combe, Patrice, Chene, Genevieve, N'Dri-Yoman, Therese, and Salamon, Roger

Subjects
AIDS (Disease) -- Patient outcomes, HIV infection -- Research, Bacterial infections -- Natural history, Opportunistic infections -- Research, Mycoses -- Research, Health
Abstract

HIV-1-related morbidity was studied in adults in Abidjan, Cote d'Ivoire, with emphasis on baseline CD4(super.+) cell count. Among symptomatic, ambulatory HIV-infected adults seen at urban community health centers , the overall probability of death at 1 year was 20%, and almost entirely restricted to patients in whom the CD4(super.+) cell count was less than 200/mm(super.3) at baseline. The probability of remaining free from an episode of HIV-related morbidity was 61% for patients with baseline CD4(super.+) cell counts greater than or equal to 200/mm(super.3). Those in the study had access to free, early access to care. Other data are included.

Published
2001

19. Low risk of nevirapine resistance mutations in the prevention of mother-to-child transmission of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus, Abidjan, Cote d'Ivoire

Author

Chaix, Marie-Laure, Ekouevi, Didier Koumavi, Rouet, Francois, Tonwe-Gold, Besigin, Viho, Ida, Bequet, Laurence, Peytavin, Gilles, Toure, Hassane, Menan, Herve, Leroy, Valeriane, Dabis, Francois, and Rouzioux, Christine

Subjects
HIV infection in children -- Prevention, HIV infection in children -- Analysis, HIV infection -- Diagnosis, HIV infection -- Care and treatment, HIV infection -- Prevention, Health
Published
2006

20. Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis

Author

Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Awab, Ghulam Rahim, Bassat, Quique, Bjorkman, Anders, Bompart, Francois, Borrmann, Steffen, Bousema, Teun, Broek, Ingrid, Bukirwa, Hasifa, Carrara, Verena I., Corsi, Marco, Cot, Michel, D'Alessandro, Umberto, Davis, Timothy M. E., de Wit, Marit, Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Greenwood, Brian, Grivoyannis, Anastasia, Hamed, Kamal, Hien, Tran Tinh, Hughes, David, Humphreys, Georgina, Hwang, Jimee, Ibrahim, Maman Laminou, Janssens, Bart, Jullien, Vincent, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lameyre, Valerie, Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy E., Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher V., Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Rombo, Lars, Rosenthal, Philip J., Sawa, Patrick, Schramm, Birgit, Sibley, Carol, Sinou, Veronique, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala L., Thuy, Nhien Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan, van Herp, Michel, van Vugt, Michele, Whitty, Christopher, William, Yavo, Winnips, Cornelis, Zongo, Issaka, Guerin, Philippe, Price, Ric N., Stepniewska, Kasia, Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Awab, Ghulam Rahim, Bassat, Quique, Bjorkman, Anders, Bompart, Francois, Borrmann, Steffen, Bousema, Teun, Broek, Ingrid, Bukirwa, Hasifa, Carrara, Verena I., Corsi, Marco, Cot, Michel, D'Alessandro, Umberto, Davis, Timothy M. E., de Wit, Marit, Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Greenwood, Brian, Grivoyannis, Anastasia, Hamed, Kamal, Hien, Tran Tinh, Hughes, David, Humphreys, Georgina, Hwang, Jimee, Ibrahim, Maman Laminou, Janssens, Bart, Jullien, Vincent, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lameyre, Valerie, Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy E., Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher V., Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Rombo, Lars, Rosenthal, Philip J., Sawa, Patrick, Schramm, Birgit, Sibley, Carol, Sinou, Veronique, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala L., Thuy, Nhien Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan, van Herp, Michel, van Vugt, Michele, Whitty, Christopher, William, Yavo, Winnips, Cornelis, Zongo, Issaka, Guerin, Philippe, Price, Ric N., and Stepniewska, Kasia

Abstract

Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model. Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold

Published
2019
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22. Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data

Author

Abdulla, Salim, Adam, Ishag, Adjei, George O., Adjuik, Martin A., Alemayehu, Bereket, Allan, Richard, Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Berens-Riha, Nicole, Bjoerkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Dahal, Prabin, D'Alessandro, Umberto, Desai, Meghna, Dicko, Alassane, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Drakeley, Chris J., Duparc, Stephan, Eshetu, Teferi, Espie, Emmanuelle, Etard, Jean-Francois, Faiz, Abul M., Falade, Catherine O., Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Faye, Oumar, Filler, Scott, Flegg, Jennifer A., Fofana, Bakary, Fogg, Carole, Gadalla, Nahla B., Gaye, Oumar, Genton, Blaise, Gething, Peter W., Gil, Jose P., Gonzalez, Raquel, Grandesso, Francesco, Greenhouse, Bryan, Greenwood, Brian, Grivoyannis, Anastasia, Guerin, Philippe J., Guthmann, Jean-Paul, Hamed, Kamal, Hamour, Sally, Hay, Simon I., Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ibrahim, Maman L., Jima, Daddi, Jones, Joel J., Jullien, Vincent, Juma, Elizabeth, Kachur, Patrick S., Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kiechel, Jean-Rene, Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Lell, Bertrand, Lima, Angeles, Makanga, Michael, Malik, ElFatih M., Marsh, Kevin, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Mens, Petra F., Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Ngasala, Billy E., Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Oguike, Mary, Ogutu, Bernhards R., Olliaro, Piero, Omar, Sabah A., Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Penali, Louis K., Pene, Mbaye, Peshu, Judy, Piola, Patrice, Plowe, Christopher V., Premji, Zul, Price, Ric N., Randrianarivelojosia, Milijaona, Rombo, Lars, Roper, Cally, Rosenthal, Philip J., Sagara, Issaka, Same-Ekobo, Albert, Sawa, Patrick, Schallig, Henk D. F. H., Schramm, Birgit, Seck, Amadou, Shekalaghe, Seif A., Sibley, Carol H., Sinou, Vronique, Sirima, Sodiomon B., Som, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Sutherland, Colin J., Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tine, Roger C. K., Tinto, Halidou, Tommasini, Silva, Toure, Offianan A., Ursing, Johan, Vaillant, Michel T., Valentini, Giovanni, Van den Broek, Ingrid, Van Vugt, Michele, Ward, Stephen A., Winstanley, Peter A., Yavo, William, Yeka, Adoke, Zolia, Yah M., Zongo, Issaka, and WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group

Subjects
parasitic diseases
Abstract

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P 37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Published
2015

23. HIV-1 infection and malaria parasitaemia

Author

Verhoef, Hans, Veenemans, Jacobien, West, Clive E, Whitworth, J, Morgan, D, Quigley, M, Menan, Herve, Dakoury-Dogbo, Nicole, Rouet, Francois, Huet, Charlotte, Anglaret, Xavier, Wabwire-Mangen, Fred, Gray, Ronald H, Wawer, Maria J, Sewankambo, Nelson, and Serwadda, David

Subjects
HIV infection -- Complications, Malaria -- Risk factors
Published
2001

24. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data

Author

Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, Zongo, Issaka, Adjuik, Martin A., Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Ba, Mamadou S., Barennes, Hubert, Barnes, Karen I., Bassat, Quique, Baudin, Elisabeth, Bjorkman, Anders, Bompart, Francois, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A., Dorsey, Grant, Doumbo, Ogobara K., Espie, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I., Faucher, Jean-Francois, Faye, Babacar, Flegg, Jennifer A., Gaye, Oumar, Gething, Peter W., Gonzalez, Raquel, Grandesso, Francesco, Guerin, Philippe J., Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I., Humphreys, Georgina S., Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R., Karema, Corine, Kiechel, Jean R., Kremsner, Peter G., Krishna, Sanjeev, Lameyre, Valerie, Ibrahim, Laminou M., Lee, Sue J., Lell, Bertrand, Martensson, Andreas, Massougbodji, Achille, Menan, Herve, Menard, Didier, Menendez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R., Olliaro, Piero, Osorio, Lyda, Ouedraogo, Jean-Bosco, Penali, Louis K., Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N., Roper, Cally, Rosenthal, Philip J., Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Veronique, Sirima, Sodiomon B., Smith, Jeffery J., Smithuis, Frank, Some, Fabrice A., Sow, Doudou, Staedke, Sarah G., Stepniewska, Kasia, Swarthout, Todd D., Sylla, Khadime, Talisuna, Ambrose O., Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel A., Thwing, Julie I., Tjitra, Emiliana, Tine, Roger C. K., Tinto, Halidou, Vaillant, Michel T., Valecha, Neena, Van den Broek, Ingrid, White, Nicholas J., Yeka, Adoke, and Zongo, Issaka

Abstract

Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated

Published
2015
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