Acknowledgments
We thank the patients and all the staff who participated in these clinical trials at all the sites and the WorldWide Antimalarial Resistance Network (WWARN) team for technical and administrative support. We would also like to thank Sigma-Tau for sharing data and Hasifa Bukirwa, Marco Corsi, Oumar Faye, Bouasy Hongvanthong, Anand Joshi, Maniphone Khanthavong Moussa Kone, Elfaith Malik, Ushma Mehta, Albert Same-Ekobo, Bhwana Sharma, and Roger CK Tine for their contributions to the studies used in the pooled analysis. WWARN is funded by a Bill and Melinda Gates Foundation grant. The funder did not participate in developing the protocol or writing the paper. Teun Bousema is supported by a fellowship from the European Research Council (ERC-2014-StG 639776).
The members of the WWARN Gametocytes Study Group are the authors of this paper:
Salim Abdulla, Ifakara Health Institute, Dar es Salaam, Tanzania; Jane Achan, Uganda Malaria Surveillance Project, Kampala, Uganda and Medical Research Council Unit, Fajara, The Gambia; Ishag Adam, Faculty of Medicine, University of Khartoum, Khartoum, Sudan; Bereket H Alemayehu, ICAP at Mailman School of Public Health, Columbia University, New York, USA; Richard Allan, The MENTOR Initiative, Crawley, UK; Elizabeth N Allen, Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Anupkumar R Anvikar, National Institute of Malaria Research, New Delhi, India; Emmanuel Arinaitwe, Infectious Diseases Research Collaboration, Kampala, Uganda; Elizabeth A Ashley, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand and Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Puji Budi Setia Asih, Eijkman Institute for Molecular Biology; Ghulam Rahim Awab, The Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand and Ministry of Public Health, Islamic Republic of Afghanistan, Kabul, Afghanistan; Karen I Barnes, WWARN, Oxford, UK and Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Quique Bassat, Centro de Investigação em Saude de Manhiça, Manhiça, Mozambique and ISGlobal, Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Elisabeth Baudin, Epicentre, Paris, France; Anders Björkman, Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Francois Bompart, Sanofi, Access to Medicines, Paris, France; Maryline Bonnet, Epicentre, Mbarara, Uganda and Institute de Recherche pour le Developpement UMI233, INSERM U1175, Université de Montpellier, Montelier, France; Steffen Borrmann, Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya and Institute for Tropical Medicine, University of Tübingen, Germany; Teun Bousema, Department of Infection and Immunity, London School of Hygiene & Tropical Medicine (LSHTM), London, UK and Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Njimegen, The Netherlands; Verena I Carrara, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand and the Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand; Fabio Cenci, Sigma Tau, Rome, Italy; Francesco Checchi, Epicentre, Paris, France; Michel Cot, IRD, Mother and Child Health in the Tropics Research Unit, Université Paris Descartes, Paris, France; Prabin Dahal, WWARN, Oxford, UK and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Umberto D’Alessandro, Medical Research Council Unit, Fajara, The Gambia, LSHTM, London, UK and Institute of Tropical Medicine, Antwerp, Belgium; Philippe Deloron, Institut de Recherche pour le Développement, Mother and Child Faced with Tropical Infections Research Unit, Paris, France and PRES Paris Sorbonne Cité, Université Paris Descartes, Paris, France; Abdoulaye Djimde, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, University of Bamako, Bamako, Mali; Arjen Dondorp, The Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Grant Dorsey, Department of Medicine, University of California San Francisco, San Francisco, USA; Ogobara K Doumbo, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, University of Bamako, Bamako, Mali; Chris J Drakeley, Department of Infection and Immunity, LSHTM, London, UK; Stephan Duparc, Medicines for Malaria Venture, Geneva, Switzerland; Emmanuelle Espie, Epicentre, Paris, France; Abul Faiz, Dev Care Foundation, Bangladesh; Catherine O Falade, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria; Caterina Fanello, The Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand; Jean‐François Faucher, Institut de Recherche pour le Développement (IRD), Mother and Child Health in the Tropics Research Unit, Paris, France and Faculté de Pharmacie, Université Paris Descartes, Paris, France and Department of Infectious Diseases, Besançon University Medical Center, Besançon, France; Babacar Faye, Department of Medical Parasitology, Medical Faculty, Université Cheikh Anta Diop, Dakar, Senegal; Scott Filler, The Global Fund to Fight AIDS, Tuberculosis and Malaria, Geneva, Switzerland; Bakary Fofana, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, University of Bamako, Bamako, Mali; Carole Fogg, University of Portsmouth, Portsmouth, UK; Adama Gansane, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso; Oumar Gaye, Department of Medical Parasitology, Medical Faculty, Université Cheikh Anta Diop, Dakar, Senegal; Blaise Genton, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland and Division of Infectious Diseases and Department of Ambulatory Care and Community Medicine, University Hospital, Lausanne, Switzerland; Peter W Gething, Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, UK; Raquel Gonzalez, Centro de Investigação em Saude de Manhiça, Manhiça, Mozambique and ISGlobal, Barcelona Ctr. Int Health Res. (CRESIB), Hospital Clínic, Universitat de Barcelona, Spain; Francesco Grandesso, Epicentre, Paris, France; Brian Greenwood, Department of Diseases Control, LSHTM, London, UK; Anastasia Grivoyannis, University of Washington, USA; Philippe J Guerin, WWARN, Oxford, UK and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Kamal Hamed, Novartis Pharmaceuticals Corporation, East Hanover, USA; Christoph Hatz, Medical Department, Swiss Tropical Institute, Basel, Switzerland; Simon I Hay, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK and Institute for Health Metrics and Evaluation, University of Washington, Seattle, USA; Eva Maria Hodel, Swiss Tropical Institute and Public Health Institute, Basel, Switzerland and Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK; Georgina S Humphreys, WWARN, Oxford, UK and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Jimee Hwang, U.S. Centers for Disease Control and Prevention, Atlanta, USA and Global Health Group, University of California San Francisco, San Francisco, USA; Bart Janssens, Médecins Sans Frontières, Operational Centre Brussels, Brussels, Belgium; Daddi Jima, Federal Ministry of Health, Addis Ababa, Ethiopia; Elizabeth Juma, Kenya Medical Research Institute, Nairobi, Kenya; S Patrick Kachur, U.S. Centers for Disease Control and Prevention, Atlanta, USA; Piet Kager, Academic Medical Centre, Amsterdam, Netherlands; Moses R Kamya, Makerere University College of Health Sciences, Kampala, Uganda; Melissa Kapulu, Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Corine Karema, Malaria & Other Parasitic Diseases Division, RBC, Ministry of Health, Kigali, Rwanda; Kassoum Kayentao, Malaria Research and Training Centre, Department of Epidemiology of Parasitologic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Mali; Jean R Kiechel, Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland; Poul-Erik Kofoed, Projecto de Saúde de Bandim, Bissau, Guinea-Bissau and Health Services Research Unit, Lillebaelt Hospital/IRS University of Southern Denmark, Vejle, Denmark and Department of Paediatrics, Kolding Hospital, Kolding, Denmark; Valerie Lameyre, Sanofi, Access to Medicines, Paris, France; Sue J Lee, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Bertrand Lell, Institute for Tropical Medicine, University of Tubingen, Tubingen, Germany and Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; Nines Lima, Médecins Sans Frontières – Operational Centre Barcelona Athens, Barcelona, Spain; Kevin Marsh, Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK and Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya; Andreas Mårtensson, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden and Department of Women’s and Children’s Health, International Maternal and Child Health (IMCH), Upssala University, Uppsala, Sweden; Achille Massougbodji, Centre d’Etudes et de Recherche sur le Paludisme Associé à la Grossesse et à l’Enfant (CERPAGE), Faculté des Sciences de la Santé (FSS), Université d’Abomey-Calavi, Cotonou, Bénin; Mayfong Mayxay, Lao-Oxford-Mahosot Hospital, Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR and Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Lao PDR and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Rose McGready, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Hervé Menan, Department of Parasitology, Faculty of Pharmacy, University of Cocody, Abidjan, Côte d'Ivoire; Clara Menendez, Barcelona Institute for Global Health (ISGlobal) Hospital Clinic, University of Barcelona, Spain and CISM, Manhiça Health Research Center, Manhiça, Mozambique; Petra Mens, Royal Tropical Institute, KIT Biomedical Research, Amsterdam, The Netherlands and Division of Infectious Diseases, Center for Tropical Medicine & Travel Medicine, Academic Medical Center, University of Amsterdam, The Netherlands; Martin Meremikwu, Department of Paediatrics, University of Calabar and Nigeria Institute of Tropical Diseases Research & Prevention, Calabar, Nigeria; Frank P Mockenhaupt, Institute of Tropical Medicine and International Health, Charite-Universitatsmedizin Berlin, Germany; Clarissa Moreira, WWARN, Oxford, UK and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Carolyn Nabasumba, Epicentre, Paris, France and Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; Michael Nambozi, Tropical Diseases Research Centre, Ndola, Zambia; Jean-Louis Ndiaye, Parasitology and Mycology Laboratory, Medical Faculty, Université Cheikh Anta Diop, Dakar, Senegal; Paul N Newton, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Mahosot Hospital, Vientiane, Lao PDR and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Billy E Ngasala, Department of Parasitology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania and Malaria Research, Infectious Disease Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Francois Nosten, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Christian Nsanzabana, WWARN, Oxford, UK and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Andre Toure Offianan, Malariology Department, Institut Pasteur, Abidjan, Côte d'Ivoire; Mary Oguike, Department of Immunology & Infection, LSHTM, London, UK; Bernhards R Ogutu, Kenya Medical Research Institute/United States Army Medical Research Unit, Kisumu, Kenya; Piero Olliaro, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland; Sabah A Omar, International Centre for Insect Physiology and Ecology (ICIPE), Mbita Point, Kenya; Lyda Osorio, Facultad de Salud, Universidad del Valle, Cali, Colombia; Seth Owusu-Agyei, Kintampo Health Research Centre, Kintampo, Ghana; Louis K Penali, WWARN, Dakar, Senegal; Mbaye Pene, Department of Medical Parasitology, Medical Faculty, Université Cheikh Anta Diop, Dakar, Senegal; Judy Peshu, Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya; Patrice Piola, Institut Pasteur de Madagascar, Antananarivo, Madagascar; Zul Premji, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Ric N Price, Menzies School of Health Research and Charles Darwin University, Darwin, Australia and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK and WWARN, Oxford, UK; Michael Ramharter, Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University Vienna, Austria and Institut für Tropenmedizin, Universität Tübingen, Germany and Centre de Recherches Medicales de Lambaréné, Gabon; Lars Rombo, Infectious Diseases Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Cally Roper, LSHTM, London, UK; Philip J Rosenthal, Department of Medicine, University of California San Francisco, San Francisco, USA; Issaka Sagara, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, University of Bamako, Bamako, Mali; Patrick Sawa, Human Health Division, International Centre for Insect Physiology and Ecology, Mbita, Kenya; Henk DFH Schallig, Royal Tropical Institute, KIT Biomedical Research, Amsterdam, The Netherlands; Birgit Schramm, Epicentre, Paris, France; Seif A Shekalaghe, Ifakara Health Institute, Bagamoyo, Tanzania; Carol H Sibley, WWARN, Oxford, UK and Department of Genome Sciences, University of Washington, Seattle, USA; Sodiomon Sirima, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso; Frank Smithuis, Myanmar Oxford Clinical Research Unit (MOCRU), Yangon, Myanmar and Medical Action Myanmar, Yangon, Myanmar; Doudou Sow, Service de Parasitologie, Medical Faculty, Université Cheikh Anta Diop, Dakar, Sénégal; Sarah G Staedke, Department of Clinical Research, LSHTM, London, UK and Infectious Disease Research Collaboration, Kampala, Uganda; Kasia Stepniewska, WWARN, Oxford, UK and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Inge Sutanto, Department of Parasitology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; Colin J Sutherland , Department of Immunology & Infection, LSHTM, London, UK; Todd D Swarthout, Médecins Sans Frontières, London, UK; Din Syafruddin, Eijkman Institute for Molecular Biology, Jakarta, Indonesia; Khadime Sylla, Service de Parasitologie-Mycologie Médicale, Université Cheikh Anta Diop, Dakar, Senegal; Ambrose O Talisuna, University of Oxford/KEMRI/Wellcome Trust Research Programme, Nairobi, Kenya; Walter R Taylor, Institute for Biomechanics, Department of Health Science and Technology, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland; Emmanuel A Temu, The MENTOR Initiative, Crawley, UK and Swiss Tropical and Public Health Institute, Basel, Switzerland and University of Basel, Basel, Switzerland; Feiko Ter Kuile, Liverpool School of Tropical Medicine, Liverpool, UK and Kenya Medical Research Institute (KEMRI), Centre for Global Health Research, Kisumu, Kenya; Halidou Tinto, Institut de Recherce en Sciences de la Sante, Bobo Dioulasso, Burkina Faso and Centre Muraz, Bobo Dioulasso, Burkina Faso; Emiliana Tjitra, National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia; Johan Ursing, Projecto de Saúde de Bandim, Indepth Network, Bissau, Guinea-Bissau and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Neena Valecha, National Institute of Malaria Research, New Delhi, India; Ingrid van den Broek, Médecins Sans Frontières, London, UK and Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Michel van Herp, Médecins Sans Frontières, Operational Centre Brussels, Brussels, Belgium; Michele van Vugt, Division of Infectious Diseases, Center for Tropical Medicine & Travel Medicine, Academic Medical Center, University of Amsterdam, The Netherlands; Stephen A Ward, Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, UK; Nicholas J White, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Peter A Winstanley, School of Clinical Sciences, University of Liverpool, Liverpool, UK; Charles J Woodrow, The Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand and Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Adoke Yeka, Uganda Malaria Surveillance Project, Kampala, Uganda; Julien Zwang, Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
Authors’ contributions
TB, KSt, GSH, CJD, CHS, PJG and RNP conceived and designed the experiments. KSt and GSH analyzed the pooled individual patient data. GSH, CNs and PDa performed literature search. GSH, PDa and CMo data management. SA, JA, IA, BHA, RA, ENA, ARA, EA, EAA, PBSA, GRA, KIB, QB, EB, AB, FB, MB, SB, TB, VIC, FC, FCh, MC, UdA, PDe, ADj, ADo, GD, OKD, CJD, SD, EE, AF, COF, CFa, JFF, BFa, SF, BFo, CFo, AGa, OG, BGe, PWG, RG, FG, BGr, AGr, PJG, KH, CH, SIH, EMH, JH, BJ, DJ, EJ, SPK, PK, MRK, MK, CK, KK, JRK, PEK, VL, SJL, BL, NL, KM, AMar, AMas, MMa, RM, HM, CMe, PM, MMe, FPM, CNa, MN, JLN, PNN, BEN, FN, CNs, ATO, MO, BRO, PO, SAO, LO, SOA, LKP, MP, JP, PP, ZP, RNP, MR, LR, CR, PJR, ISa, PS, HDFHS, BS, SAS, SS, FS, DSo, SGS, KSt, ISu, CJS, TDS, DSy, KSy, AOT, WRT, EAT, FTK, HT, ET, JU, NV, IvdB, MvH, MvV, SAW, NJW, PAW, CJW, AY and JZ performed the original experiments. PWG and SIH provided transmission intensity estimates. TB, KSt, GSH, CJD, CHS, PJG and RNP wrote the first draft of the manuscript. SA, JA, IA, BHA, RA, ENA, ARA, EA, EAA, PBSA, GRA, KIB, QB, EB, AB, FB, MB, SB, TB, VIC, FC, FCh, MC, PDa, UdA, PDe, ADj, ADo, GD, OKD, CJD, SD, EE, AF, COF, CFa, JFF, BFa, SF, BFo, CFo, AGa, OG, BGe, PWG, RG, FG, BGr, AGr, PJG, KH, CH, SIH, EMH, GSH, JH, BJ, DJ, EJ, SPK, PK, MRK, MK, CK, KK, JRK, PEK, VL, SJL, BL, NL, KM, AMar, AMas, MMa, RM, HM, CMe, PM, MMe, FPM, CMo, CNa, MN, JLN, PNN, BEN, FN, CNs, ATO, MO, BRO, PO, SAO, LO, SOA, LKP, MP, JP, PP, ZP, RNP, MR, LR, CR, PJR, ISa, PS, HDFHS, BS, SAS, CHS, SS, FS, Dso, SGS, KSt, ISu, CJS, TDS, Dsy, KSy, AOT, WRT, EAT, FTK, HT, ET, JU, NV, IvdB, MvH, MvV, SAW, NJW, PAW, CJW, AY and JZ International Committee of Medical Journal Editors (ICMJE) criteria for authorship read and met. All authors contributed to the writing of the manuscript and agree with manuscript results and conclusions. All authors read and approved the final manuscript.