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1. Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination

Author

Jordi Landier, Abdullah Abu Sayeed, Seila Suon, Kim-Tuyen Nguyen, Kate Rowlands, Frank Smithuis, Chanon Kunasol, Chanaki Amaratunga, Sasithon Pukrittayakamee, Keobouphaphone Chindavongsa, Jacob Almagro Garcia, Richard D. Pearson, Mozam Ali, Xin Hui S Chan, Katie Love, Naomi Park, Pascal Ringwald, Richard J. Maude, Cristina V. Ariani, Mehul Dhorda, Marie A. Onyamboko, Daniel M. Parker, Tin Maung Hlaing, Scott Goodwin, Namfon Kotanan, Thang Ngo Duc, Gilles Delmas, Huy Rekol, Rick M. Fairhurst, Victoria Simpson, Arjen M. Dondorp, Le Thanh Dong, Bouasy Hongvanthong, Tran Tinh Hien, Rapeephan R. Maude, Thomas J. Peto, Shavanthi Rajatileka, Roberto Amato, Thanat Chookajorn, Ben Jeffery, Anna E. Jeffreys, Nicole Zdrojewski, Caterina I. Fanello, Eleanor Drury, Mihir Kekre, Myo Thant, John Sillitoe, Olivo Miotto, Aung Myint Thu, James J Callery, Subrata Baidya, Paul N. Newton, Ranitha Vongpromek, Prativa K Behera, Borimas Hanboonkunupakarn, Rob W. van der Pluijm, Jim Stalker, Anupkumar R. Anvikar, Sonexay Phalivong, Dawn Muddyman, Nguyen Thuy-Nhien, Christina Hubbart, Rithea Leang, Lorenz von Seidlein, Nicholas P. J. Day, Phrutsamon Wongnak, Jonathan Keatley, Hoa Nguyen, Cinzia Malangone, Parthasarathi Satpathi, Abul Faiz, Dysoley Lek, François Nosten, Christopher G Jacob, Rupam Tripura, Sara E. Canavati, Huynh Hong Quang, Kirk A. Rockett, Neena Valecha, Thuy Nguyen, Kimberly J. Johnson, Tran Minh Nhat, Didar Uddin, Caroline O. Buckee, Akhter ul Islam, Podjanee Jittamala, Mayfong Mayxay, Amir Hossain, Viengxay Vanisaveth, Elizabeth A. Ashley, Dominic P. Kwiatkowski, Sanghamitra Satpathi, Aung Pyae Phyo, Amar Tripura, Nguyen Hoang Chau, Sónia Gonçalves, Khin Lin, Cheah Huch, Wellcome Sanger Institute [Hinxton, Royaume-Uni], Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Mahosot Hospital [Vientiane, Laos], Institute of Research and Education Development [Vientiane, Lao People’s Democratic Republic], University of Health Sciences [Vientiane, Laos] (UHS), University of Oxford [Oxford], Mahidol University [Bangkok], Harvard T.H. Chan School of Public Health, Institute of Malariology, Parasitology, and Entomology [Quy Nhon, Vietnam] (IMPE), Centre of Malariology, Parasitology, and Entomology [Vientiane, Lao People’s Democratic Republic] (CMPE), National Institute of Malariology, Parasitology and Entomology [Hanoi], National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust, Chittagong Medical College Hospital [Chittagong, Bangladesh] (CMCH), World Health Organization [Geneva], Institute of Malariology, Parasitology, and Entomology [Ho Chi Minh City, Vietnam] (IMPE), Vysnova Partners Inc [Hanoi, Vietnam] (VPI), University of Kinshasa (UNIKIN), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [Irvine] (UCI), University of California, Royal Society of Thailand [Bangkok, Thailand], Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], The Department of Medical Research (Upper Myanmar), Defence Services Medical Research Centre [Naypyitaw, Myanmar] (DSMRC), Midnapore Medical College [Midnapur, India] (MMC), ispat general hospital [Rourkela, India] (IGH), Agartala Medical College [Agartala, India] (AMC), National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Ramu Upazila Health Complex [Cox’s Bazar, Bangladesh] (RUHC), The Wellcome Trust Sanger Institute [Cambridge], WorldWide Antimalarial Resistance Network [Bangkok] (WWARN), WorldWide Antimalarial Resistance Network (WWARN), Université de Washington Seattle-Université de Washington Seattle, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of California [Irvine] (UC Irvine), University of California (UC), University of Washington [Seattle]-University of Washington [Seattle], and Malbec, Odile

Subjects
Plasmodium, History, [SDV]Life Sciences [q-bio], Drug Resistance, global health, Drug resistance, Barcode, law.invention, law, Genotype, Biology (General), Aetiology, Microbiology and Infectious Disease, 0303 health sciences, Bangladesh, General Neuroscience, General Medicine, asia, 3. Good health, [SDV] Life Sciences [q-bio], Geography, Infectious Diseases, Democratic Republic of the Congo, Medicine, epidemiology, Genetic Engineering, Malaria control, Infection, Research Article, medicine.medical_specialty, South asia, Asia, QH301-705.5, Science, infectious disease, Plasmodium falciparum, malaria, Library science, Southeastern, India, General Biochemistry, Genetics and Molecular Biology, Antimalarials, 03 medical and health sciences, Rare Diseases, Simple sample, Clinical Research, Environmental health, medicine, Genetics, Humans, Animals, Disease Eradication, 030304 developmental biology, drug resistance, General Immunology and Microbiology, 030306 microbiology, Public health, microbiology, Genetic data, Genetic Therapy, medicine.disease, genetic surveillance, Compendium, Resistance monitoring, Data sharing, Vector-Borne Diseases, Epidemiology and Global Health, Good Health and Well Being, Communicable Disease Control, Antimicrobial Resistance, Biochemistry and Cell Biology, Malaria, 2.6 Resources and infrastructure (aetiology)
Abstract

Author(s): Jacob, Christopher G; Thuy-Nhien, Nguyen; Mayxay, Mayfong; Maude, Richard J; Quang, Huynh Hong; Hongvanthong, Bouasy; Vanisaveth, Viengxay; Ngo Duc, Thang; Rekol, Huy; van der Pluijm, Rob; von Seidlein, Lorenz; Fairhurst, Rick; Nosten, Francois; Hossain, Md Amir; Park, Naomi; Goodwin, Scott; Ringwald, Pascal; Chindavongsa, Keobouphaphone; Newton, Paul; Ashley, Elizabeth; Phalivong, Sonexay; Maude, Rapeephan; Leang, Rithea; Huch, Cheah; Dong, Le Thanh; Nguyen, Kim-Tuyen; Nhat, Tran Minh; Hien, Tran Tinh; Nguyen, Hoa; Zdrojewski, Nicole; Canavati, Sara; Sayeed, Abdullah Abu; Uddin, Didar; Buckee, Caroline; Fanello, Caterina I; Onyamboko, Marie; Peto, Thomas; Tripura, Rupam; Amaratunga, Chanaki; Myint Thu, Aung; Delmas, Gilles; Landier, Jordi; Parker, Daniel M; Chau, Nguyen Hoang; Lek, Dysoley; Suon, Seila; Callery, James; Jittamala, Podjanee; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Phyo, Aung Pyae; Smithuis, Frank; Lin, Khin; Thant, Myo; Hlaing, Tin Maung; Satpathi, Parthasarathi; Satpathi, Sanghamitra; Behera, Prativa K; Tripura, Amar; Baidya, Subrata; Valecha, Neena; Anvikar, Anupkumar R; Ul Islam, Akhter; Faiz, Abul; Kunasol, Chanon; Drury, Eleanor; Kekre, Mihir; Ali, Mozam; Love, Katie; Rajatileka, Shavanthi; Jeffreys, Anna E; Rowlands, Kate; Hubbart, Christina S; Dhorda, Mehul; Vongpromek, Ranitha; Kotanan, Namfon; Wongnak, Phrutsamon; Almagro Garcia, Jacob; Pearson, Richard D; Ariani, Cristina V; Chookajorn, Thanat; Malangone, Cinzia; Nguyen, T; Stalker, Jim; Jeffery, Ben | Abstract: BackgroundNational Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures.MethodsSamples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs.ResultsGenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs.ConclusionsGenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community.FundingThe GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

Published
2021
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2. Towards harmonization of microscopy methods for malaria clinical research studies

Author

Jane Carter, J. Kevin Baird, Ric N. Price, Piero Olliaro, John C. Reeder, Michelle L. Gatton, Peter Obare, Philippe J Guerin, El Hadji Ba, Stephane Proux, Derek Bell, Cheikh Sokhna, Andrew Ramsay, Arjen M. Dondorp, Mehul Dhorda, Ken Lilley, François Nosten, Didier Menard, Kamolrat Silamut, Lenny L Ekawati, Iveth J González, John W. Barnwell, Bernhards Ogutu, Sandra Incardona, WorldWide Antimalarial Resistance Network [Bangkok] (WWARN), WorldWide Antimalarial Resistance Network (WWARN), University of Washington [Seattle]-University of Washington [Seattle], University of Oxford, Mahidol University [Bangkok], 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), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Eijkman Institute for Molecular Biology [Jakarta], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Amref Health Africa [Kenya], African Medical and Research Foundation (AMREF), Queensland University of Technology [Brisbane] (QUT), Terre des hommes [Lausanne], WorldWide Antimalarial Resistance Network, WWARN, Foundation for Innovative New Diagnostics (FIND), Australian Defence Force Malaria and Infectious Disease Institute [Enoggera] (ADFMIDI), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Kenya Medical Research Institute (KEMRI), Menzies School of Health Research [Australia], Charles Darwin University [Australia], University of Saint Andrews, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), UNICEF Headquarters-World Bank Group-United Nations Development Programme (UNDP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université de Washington Seattle-Université de Washington Seattle, University of Oxford [Oxford], Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust, Charles Darwin University, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-UNICEF Headquarters-World Bank Group-United Nations Development Programme (UNDP), and University of St Andrews. School of Medicine

Subjects
Laboratory Proficiency Testing, MESH: Quality Control, Review, MESH: Laboratory Proficiency Testing, Clinical research, 0302 clinical medicine, RA0421, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RA0421 Public health. Hygiene. Preventive Medicine, Microscopy, 030212 general & internal medicine, Reliability (statistics), Standard, 3. Good health, MESH: Reproducibility of Results, MESH: Staining and Labeling, Infectious Diseases, T-DAS, Quality Control, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, MESH: Microscopy, lcsh:RC955-962, 030231 tropical medicine, MESH: Malaria, Harmonization, Sensitivity and Specificity, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, SDG 3 - Good Health and Well-being, parasitic diseases, medicine, Humans, lcsh:RC109-216, Medical physics, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Diagnostic, MESH: Diagnostic Tests, Routine, MESH: Humans, Staining and Labeling, Diagnostic Tests, Routine, business.industry, Reproducibility of Results, medicine.disease, MESH: Sensitivity and Specificity, Malaria, Clinical trial, Quality management system, Parasitology, business, Quality assurance
Abstract

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.

Published
2020
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3. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data

Author

Ouédraogo J-B., Bertrand Lell, Sanjeev Krishna, Ogobara K. Doumbo, Mbaye Pene, Emiliana Tjitra, Ric N. Price, I Van den Broek, Jennifer A. Flegg, Christian Nsanzabana, Faucher J-F., Jean-René Kiechel, Sue J. Lee, Nicholas J. White, Issaka Zongo, Adoke Yeka, Sodiomon B. Sirima, Halidou Tinto, Michel Vaillant, Etard J-F., K Sylla, Sarah G. Staedke, Andreas Mårtensson, Louis K. Penali, Meghna Desai, Martin M Meremikwu, M A Adjuik, Elizabeth A. Ashley, Peter W. Gething, Sally Hamour, Claude Rwagacondo, Clarissa Moreira, Moses R. Kamya, François Bompart, Julie Thwing, Prabin Dahal, Armedy Ronny Hasugian, Elizabeth Juma, Francesco Grandesso, Hasifa Bukirwa, Loretxu Pinoges, Vincent Jullien, Philip J. Rosenthal, Simon I. Hay, Ndiaye J-L., Raquel González, Bhawna Sharma, D Sow, Anup Anvikar, Neena Valecha, E Espié, Frank Smithuis, Didier Menard, Philippe Deloron, Carol Hopkins Sibley, Peter G. Kremsner, M S Ba, Anders Björkman, Albert Same-Ekobo, Todd D. Swarthout, G Diap, Taylor Wrj., Michael Nambozi, Georgina S Humphreys, Caterina I. Fanello, Tine Rck., Karen I. Barnes, Carolyn Nabasumba, Achille Massougbodji, Hervé Ei Menan, Jeff Smith, A Seck, Patrice Piola, Babacar Faye, Richard Allan, Philippe J Guerin, Corine Karema, Frederic Nikiema, Ambrose O. Talisuna, Véronique Sinou, E A Temu, Lyda Osorio, Gaye O, Piero Olliaro, Francine Ntoumi, Michel Cot, Grant Dorsey, Maryline Bonnet, Hubert Barennes, Birgit Schramm, Umberto D'Alessandro, Kasia Stepniewska, Elisabeth Baudin, Steffen Borrmann, Abdoulaye Djimde, Bernards Ogutu, Guthmann J-P., L M Ibrahim, Francesco Checchi, Fabrice A. Somé, Valerie Lameyre, Clara Menéndez, Quique Bassat, Philippe Brasseur, Cally Roper, Joel Tarning, WorldWide Antimalarial Resistance Network (WWARN), University of Washington [Seattle], National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Epicentre [Paris] [Médecins Sans Frontières], Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Centre Muraz [Bobo-Dioulasso, Burkina Faso], Universitat de Barcelona (UB), Karolinska Institutet [Stockholm], Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Centre Lillois d’Études et de Recherches Sociologiques et Économiques - UMR 8019 (CLERSÉ), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (LSHTM), Institut de Recherche pour le Développement (IRD), University of Oxford-Churchill Hospital Oxford Centre for Haematology, Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Département d'épidémiologie des affections parasitaires (DEAP), Université de Bamako-Malaria Research and Training Center (MRTC)-Facultés de Médecine, de Pharmacie et d'Odonto-Stomatologie-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC), Malaria Research and Training Centre, Université de Bamako-Faculty of Medicine, Pharmacy, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Mahidol Oxford Tropical Medicine Research Unit, University of Oxford-Mahidol University [Bangkok], Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), WorldWide Antimalarial Resistance Network (WWARN) (WWARN), University of Oxford, Università degli Studi di Milano = University of Milan (UNIMI), Institut de Veille Sanitaire (INVS), Institute for Health Metrics and Evaluation [University of Washington], Pharmacologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), University of Tübingen, Division of Cellular and Molecular Medicine, St George's University of London, Sanofi-Aventis R&D, SANOFI Recherche, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Department of Microbiology, Tumour and Cell biology [Stockholm, Sweden] (Malaria Research), Faculté des Sciences de la Santé de Cotonou (Faculté des Sciences de la Santé de Cotonou), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Centre de recherche et de Diagnostic sur le Sida [Abidjan, Côte d'Ivoire] (CeDreS), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), Institut Pasteur du Cambodge, Universidad de la República [Montevideo] (UDELAR), Nuffield Department of Clinical Medicine [Oxford], Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], Tropical Diseases Research Center (TDRC), Université Marien Ngouabi, Kenya Medical Research Institute (KEMRI), WHO-TDR Suisse, WHO-TDR Suisse-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Universidad del Valle [Cali] (Univalle), Institut de Recherche en Sciences de la Santé Bobo Dioulasso (INSSA), Université Polytechnique Nazi Boni Bobo-Dioulasso (UNB), World Wide Antimalarial Resistance Network [West Africa] (WWARN-West Africa Regional Centre), University of Washington [Seattle]-University of Washington [Seattle], Institut Pasteur de Madagascar, Global Health Division, Menzies School of Health Research, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Service de Parasitologie-Mycologie Médicale, Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Université de Bordeaux Ségalen [Bordeaux 2], WWARN is funded by a Bill and Melinda Gates Foundation grant., The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, We thank the patients and all the staff who participated in these clinical trials at all the sites and the WWARN team for technical and administrative support., Université de Washington Seattle, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, University of Oxford [Oxford]-University of Oxford [Oxford], Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), University of California [San Francisco] (UCSF), University of California, University of Oxford [Oxford]-Mahidol University [Bangkok], Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], Università degli Studi di Milano [Milano] (UNIMI), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], University of Abomey Calavi (UAC), Universidad de la República [Montevideo] (UCUR), Université de Washington Seattle-Université de Washington Seattle, and Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Male, Artemether/lumefantrine, Artesunate, Infektionsmedicin, MESH: Africa, Pharmacology, Gastroenterology, MESH: Dose-Response Relationship, Drug, Efficacy, chemistry.chemical_compound, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Recurrence, Risk Factors, Malaria, Falciparum, MESH: Treatment Outcome, MESH: Middle Aged, MESH: Malaria, Falciparum, Artesunate/amodiaquine, Hazard ratio, General Medicine, Middle Aged, Artemisinins, 3. Good health, Drug Combinations, Dosing, Treatment Outcome, Female, medicine.drug, Research Article, medicine.medical_specialty, Infectious Medicine, Fixed-dose combination, Plasmodium falciparum, Amodiaquine, Antimalarials, Internal medicine, MESH: Artemisinins, medicine, Humans, MESH: Amodiaquine, MESH: Drug Combinations, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Antimalarials, MESH: Male, MESH: Recurrence, Malaria, chemistry, Drug resistance, Africa, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Commentary, business, MESH: Female
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

Published
2015
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4. Episodes of particle ejection from the surface of the active asteroid (101955) Bennu

Author

Christine Hartzell, Guy Libourel, Bashar Rizk, Jian-Yang Li, Daniel J. Scheeres, David Vokrouhlický, C. Drouet d'Aubigny, Derek S. Nelson, Y. Takahashi, Robert A. Jacobson, Michael C. Moreau, Harold C. Connolly, Eric M. Sahr, William F. Bottke, J. A. Seabrook, J. Y. Pelgrift, Leilah K. McCarthy, J. M. Leonard, Ben Rozitis, Kris J. Becker, S. Selznick, J. de León, Josh Emery, Humberto Campins, Javier Licandro, Carl Hergenrother, Erica Jawin, Marina Brozovic, M. Al Asad, A. B. Davis, Florian Thuillet, Jamie Molaro, Pasquale Tricarico, E. J. Lessac-Chenen, Peter G. Antreasian, Jason P. Dworkin, C. K. Maleszewski, Davide Farnocchia, Carina Bennett, Jay W. McMahon, C. Manzoni, C. W. V. Wolner, Steven R. Chesley, P. Michel, Peter Jenniskens, Andrew J. Liounis, J. N. Kidd, Ronald-Louis Ballouz, Dathon Golish, Michael Daly, Daniella DellaGiustina, Daniel P. Glavin, H. L. Roper, William M. Owen, Coralie D. Adam, Brent J. Bos, B. May, Dante S. Lauretta, Laboratoire Kastler Brossel (LKB (Lhomond)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Dept. of Physics, University of Central Florida [Orlando] (UCF), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Universidad Autonoma de Nuevo Leon [Mexique] (UANL), NASA Goddard Space Flight Center (GSFC), Laboratoire de physique de l'état condensé (LPEC), Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM), Dipartimento di Matematica, University of Pisa - Università di Pisa, Université de Washington Seattle, University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Instituto de Astrofisica de Canarias (IAC), Lunar and Planetary Laboratory [Tucson] (LPL), University of Arizona, The Open University [Milton Keynes] (OU), Institute of Astronomy, Charles University [Prague] (CU), ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Central Florida [Orlando], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Le Mans Université (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches Pétrographiques et Géochimiques (CRPG), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Politecnico di Milano [Milan] (POLIMI), Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRe), Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague], and ANR: 15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)

Subjects
Solar System, 010504 meteorology & atmospheric sciences, Origin of water on Earth, Population, [SDU.ASTR.EP]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Astrophysics, 01 natural sciences, 0103 physical sciences, education, 010303 astronomy & astrophysics, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, education.field_of_study, Multidisciplinary, Meteoroid, Spacecraft, [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], business.industry, 13. Climate action, Asteroid, [SDU]Sciences of the Universe [physics], Solar time, Physics::Space Physics, Astrophysics::Earth and Planetary Astrophysics, business, Orbit determination, Geology
Abstract

INTRODUCTION Active asteroids are small bodies in the Solar System that show ongoing mass loss, such as the ejection of dust, which may be caused by large impacts, volatile release, or rotational acceleration. Studying them informs our understanding of the evolution and destruction of asteroids and the origin of volatile materials such as water on Earth. The OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer) spacecraft has rendezvoused with the near-Earth asteroid (101955) Bennu. The selection of Bennu as the OSIRIS-REx target was partially based on its spectral similarity to some active asteroids. Observations designed to detect mass loss at Bennu were conducted from Earth and during the spacecraft’s approach, but no signs of asteroid activity were found. However, when the spacecraft entered orbit in January 2019, we serendipitously observed particles in the vicinity of Bennu that had apparently been ejected from its surface. RATIONALE We analyzed the properties and behavior of particles ejected from Bennu to determine the possible mechanisms of ejection and provide understanding of the broader population of active asteroids. Images obtained by the spacecraft indicate multiple discrete ejection events with a range of energies and resultant particle trajectories. We characterized three large ejection events that respectively occurred on 6 January, 19 January, and 11 February 2019. Tracking of individual particles across multiple images by means of optical navigation techniques provided the initial conditions for orbit determination modeling. By combining these approaches, we estimated the locations and times of ejection events and determined initial velocity vectors of particles. We estimated the particle sizes and the minimum energies of the ejection events using a particle albedo and density consistent with observations of Bennu. RESULTS Particles with diameters from 3 m s–1. Estimated energies ranged from 270 mJ for the 6 January event to 8 mJ for the 11 February event. The three events arose from widely separated sites, which do not show any obvious geological distinction from the rest of Bennu’s surface. However, these events all occurred in the late afternoon, between about 15:00 and 18:00 local solar time. In addition to discrete ejection events, we detected a persistent background of particles in the Bennu environment. Some of these background particles have been observed to persist on temporary orbits that last several days—in one case, with a semimajor axis >1 km. The orbital characteristics of these gravitationally bound objects make it possible to determine the ratio of their cross-sectional area to their mass. Combined with their photometric phase functions, this information constrains the parameter space of the particles’ diameters, densities, and albedos. CONCLUSION Plausible mechanisms for the large ejection events include thermal fracturing, volatile release through dehydration of phyllosilicates, and meteoroid impacts. The late-afternoon timing of the events is consistent with any of these mechanisms. Bennu’s boulder geology indicates that thermal fracturing, perhaps enhanced by volatile release, could occur on the asteroid surface. Smaller events, especially those that occur on the night side of Bennu, could be attributable to reimpacting particles. Our observations classify Bennu as an active asteroid. Active asteroids are commonly identified by major mass loss events observable with telescopes, on scales much greater than we observed at Bennu. Our findings indicate that there is a continuum of mass loss event magnitudes among active asteroids.

Published
2019
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5. Tools for surveillance of anti-malarial drug resistance: an assessment of the current landscape

Author

Iveth J. González, Christian Nsanzabana, Philippe J Guerin, Didier Menard, Djibrine Djalle, Foundation for Innovative New Diagnostics (FIND), WorldWide Antimalarial Resistance Network (WWARN), Université de Washington Seattle, Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford]-University of Oxford [Oxford], Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This project has been funded by UK aid from the UK government and by the Australian Government., University of Washington [Seattle], University of Oxford-University of Oxford, and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Drug, lcsh:Arctic medicine. Tropical medicine, Anti malarial, Standardization, lcsh:RC955-962, Emerging technologies, media_common.quotation_subject, 030231 tropical medicine, 030106 microbiology, Plasmodium falciparum, Resistance, Drug Resistance, Antimalarial, Review, Drug resistance, Gene mutation, MESH: Parasitic Sensitivity Tests, lcsh:Infectious and parasitic diseases, Antimalarials, 03 medical and health sciences, 0302 clinical medicine, Parasitic Sensitivity Tests, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, lcsh:RC109-216, Landscape, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Malaria, Falciparum, MESH: Plasmodium falciparum, media_common, Markers, Surveillance, business.industry, MESH: Malaria, Falciparum, Molecular, medicine.disease, MESH: Antimalarials, 3. Good health, Infectious Diseases, Risk analysis (engineering), Parasitology, MESH: Drug Resistance, business, Malaria
Abstract

To limit the spread and impact of anti-malarial drug resistance and react accordingly, surveillance systems able to detect and track in real-time its emergence and spread need to be strengthened or in some places established. Currently, surveillance of anti-malarial drug resistance is done by any of three approaches: (1) in vivo studies to assess the efficacy of drugs in patients; (2) in vitro/ex vivo studies to evaluate parasite susceptibility to the drugs; and/or (3) molecular assays to detect validated gene mutations and/or gene copy number changes that are associated with drug resistance. These methods are complementary, as they evaluate different aspects of resistance; however, standardization of methods, especially for in vitro/ex vivo and molecular techniques, is lacking. The World Health Organization has developed a standard protocol for evaluating the efficacy of anti-malarial drugs, which is used by National Malaria Control Programmes to conduct their therapeutic efficacy studies. Regional networks, such as the East African Network for Monitoring Antimalarial Treatment and the Amazon Network for the Surveillance of Antimalarial Drug Resistance, have been set up to strengthen regional capacities for monitoring anti-malarial drug resistance. The Worldwide Antimalarial Resistance Network has been established to collate and provide global spatial and temporal trends information on the efficacy of anti-malarial drugs and resistance. While exchange of information across endemic countries is essential for monitoring anti-malarial resistance, sustainable funding for the surveillance and networking activities remains challenging. The technology landscape for molecular assays is progressing quite rapidly, and easy-to-use and affordable new techniques are becoming available. They also offer the advantage of high throughput analysis from a simple blood spots obtained from a finger prick. New technologies combined with the strengthening of national reference laboratories in malaria-endemic countries through standardized protocols and training plus the availability of a proficiency testing programme, would contribute to the improvement and sustainability of anti-malarial resistance surveillance networks worldwide. Electronic supplementary material The online version of this article (10.1186/s12936-018-2185-9) contains supplementary material, which is available to authorized users.

Published
2018
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6. Optimal health and disease management using spatial uncertainty: a geographic characterization of emergent artemisinin-resistant Plasmodium falciparum distributions in Southeast Asia

Author

Arjen M. Dondorp, Shalini Nair, Peter W. Gething, Georgina S Humphreys, Carol Hopkins Sibley, Shannon Takala-Harrison, Mehul Dhorda, Tim J. Anderson, Didier Menard, Mallika Imwong, M. Abul Faiz, Frank Smithuis, Benoit Witkowski, Elizabeth A. Ashley, Charles J. Woodrow, Ric N. Price, Nicholas P. J. Day, Marina McDew-White, François Nosten, Tran Tinh Hien, Jean Marie Kindermans, Paul N. Newton, Eric P. M. Grist, Kyaw Myo Tun, Ignacio Suay Mas, Mayfong Mayxay, Richard J. Maude, Rick M. Fairhurst, Jennifer A. Flegg, Nhien T. Nguyen, Philippe J Guerin, Nicholas J. White, Sasithon Pukrittayakamee, Tin Maung Hlaing, CSIRO Marine and Atmospheric Research (CSIRO-MAR), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), WorldWide Antimalarial Resistance Network (WWARN) (WWARN), WorldWide Antimalarial Resistance Network (WWARN), Territoires, économie, enjeux sociétaux (LARHRA TEES), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 (LARHRA), Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Mahidol Oxford Tropical Medicine Research Unit, University of Oxford [Oxford]-Mahidol University [Bangkok], Strangeways Research Laboratory, University of Oxford [Oxford], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), Centre for Tropical Medicine and Global Health [Oxford, UK] (Nuffield Department of Medicine), Department of Molecular Tropical Medicine and Genetics [Bangkok, Thaïlande], Faculty of Tropical Medicine [Bangkok, Thaïlande], Mahidol University [Bangkok]-Mahidol University [Bangkok], Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Texas Biomedical Research Institute, Institut Pasteur [Paris], Shoklo Malaria Research Unit [Mae Sot, Thailand] (Faculty of Tropical Medicine), Mahidol University [Bangkok]-Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Wellcome Trust, Global Health Division, Menzies School of Health Research, Department of Clinical Tropical Medicine [Bangkok, Thailand] (Faculty of Tropical Medicine), Mahidol University [Bangkok], University of Maryland School of Medicine, University of Maryland System, Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Laboratoire d'épidémiologie moléculaire, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases-National Institutes of Health, Université de Washington Seattle, LECEMO - Les Cultures de l'Europe Méditérranéenne Occidentale - EA 3979 (LECEMO), Université Sorbonne Nouvelle - Paris 3, University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, Centre for Tropical Medicine and Global Health [Oxford, UK], University of Oxford [Oxford]-University of Oxford [Oxford], Monash University [Melbourne], Texas Biomedical Research Institute [San Antonio, TX], Dev Care Foundation [Dhaka, Bangladesh], Spatial Ecology and Epidemiology Group, Hospital for Tropical Diseases, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Defence Services Medical Research Centre [Naypyitaw, Myanmar] (DSMRC), Médecins Sans Frontières Belgique, Harvard T.H. Chan School of Public Health, Réseau International des Instituts Pasteur (RIIP), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Menzies School of Health Research [Australia], Charles Darwin University, Faculty of Tropical Medicine [Bangkok, Thailand], Laboratory of Malaria and Vector Research [Rockville], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], This study was supported by the UK Department for International Development, the Worldwide Antimalarial Resistance Network, the Intramural Research Program of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, and the Bill and Melinda Gates Foundation. The Mahidol-University Oxford Tropical Medicine Research Programme is funded by the Wellcome Trust of Great Britain. KMT was supported by a Li Ka Shing Foundation Scholarship. MI was supported by Mahidol University. EPMG was supported by the ExxonMobile Foundation. Work at Texas Biomedical Research Institute was supported by a National Institutes of Health (NIH) Grant (No. R37AI048071) to TJCA and was done in facilities constructed with support from Research Facilities Improvement Program (Grants C06 RR013556 and RR017515) from the National Center for Research Resources of the NIH., and The authors thank the four anonymous reviewers for critical review of an earlier version of this manuscript. We thank the patients enrolled in the various studies in the Mekong region.

Subjects
MESH: Geography, Health Status, Business, Management and Accounting(all), MESH: Asia, Southeastern, Distribution (economics), Communicable Diseases, Emerging, Southeast asia, 0302 clinical medicine, Anti-Infective Agents, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Communicable Diseases, Emerging, 030212 general & internal medicine, Malaria, Falciparum, Artemisinin, Asia, Southeastern, MESH: Plasmodium falciparum, MESH: Health Status, Surveillance, Geography, biology, MESH: Malaria, Falciparum, Disease Management, Sampling (statistics), Artemisinins, humanities, 3. Good health, Smart surveillance, Population Surveillance, MESH: Drug Resistance, lcsh:R858-859.7, Cartography, Computer Science(all), medicine.drug, General Computer Science, Health geography, Plasmodium falciparum, MESH: Anti-Infective Agents, 030231 tropical medicine, lcsh:Computer applications to medicine. Medical informatics, MESH: Disease Management, MESH: Population Surveillance, 03 medical and health sciences, MESH: Artemisinins, parasitic diseases, medicine, Humans, Greater Mekong Subregion, MESH: Humans, business.industry, Research, Public Health, Environmental and Occupational Health, biology.organism_classification, medicine.disease, General Business, Management and Accounting, Malaria, Drug resistance, business
Abstract

Background Artemisinin-resistant Plasmodium falciparum malaria parasites are now present across much of mainland Southeast Asia, where ongoing surveys are measuring and mapping their spatial distribution. These efforts require substantial resources. Here we propose a generic ‘smart surveillance’ methodology to identify optimal candidate sites for future sampling and thus map the distribution of artemisinin resistance most efficiently. Methods The approach uses the ‘uncertainty’ map generated iteratively by a geostatistical model to determine optimal locations for subsequent sampling. Results The methodology is illustrated using recent data on the prevalence of the K13-propeller polymorphism (a genetic marker of artemisinin resistance) in the Greater Mekong Subregion. Conclusion This methodology, which has broader application to geostatistical mapping in general, could improve the quality and efficiency of drug resistance mapping and thereby guide practical operations to eliminate malaria in affected areas. Electronic supplementary material The online version of this article (doi:10.1186/s12942-016-0064-6) contains supplementary material, which is available to authorized users.

Published
2016
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7. Discovery of new thienopyrimidinone derivatives displaying antimalarial properties toward both erythrocytic and hepatic stages of Plasmodium

Author

Audrey Lorthiois, Sylvain Rault, Anita Cohen, Pascal Rathelot, Carol Hopkins Sibley, Lucie Paloque, Maxime D. Crozet, Aurélien Lesnard, Pierre Verhaeghe, Peggy Suzanne, Eric Deharo, Nadine Azas, Patrice Vanelle, Louise Basmaciyan, Jean-Charles Lancelot, Patrick Dallemagne, Sébastien Hutter, Aurélien Dumètre, Michèle Laget, Dominique Mazier, Alexis Valentin, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), WorldWide Antimalarial Resistance Network (WWARN), Université de Washington Seattle, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Activity against Plasmodium liver stages, Erythrocytes, In vitro antiplasmodial profile, Parasitemia, Pharmacology, 01 natural sciences, Mice, Chloroquine, Cricetinae, Drug Discovery, Antiplasmodial mechanism of action, 0303 health sciences, biology, Chemistry, antiplasmodial profile, Hep G2 Cells, General Medicine, 3. Good health, Liver, Biochemistry, Thieno[3,2-dlpyrimidin-4(3H)-one, Plasmodium yoelii, medicine.drug, Plasmodium falciparum, CHO Cells, Antimalarials, Structure-Activity Relationship, 03 medical and health sciences, Cricetulus, In vitro, In vivo, parasitic diseases, medicine, Animals, Humans, [CHIM]Chemical Sciences, Trophozoites, IC50, Cell Proliferation, 030304 developmental biology, 2-d]pyrimidin-4(3H)-one, 010405 organic chemistry, Organic Chemistry, biology.organism_classification, medicine.disease, Malaria, 0104 chemical sciences, Pyrimidines, Specific activity, Pharmacomodulation, Thieno[3, Genotoxicity
Abstract

International audience; A preliminary in vitro screening of compounds belonging to various chemical families from our library revealed the thieno[3,2-d]pyrimidin-4(3H)-one scaffold displayed a promising profile against Plasmodium falciparum. Then, 120 new derivatives were synthesized and evaluated in vitro; compared to drug references, 40 showed good activity toward chloroquine sensitive (IC50 35-344 nM) and resistant (IC50 45-800 nM) P. falciparum strains. They were neither cytotoxic (CC50 15-50 mu M) toward HepG2 and CHO cells, nor mutagenic. Structure activity relationships were defined. The lead-compound also appeared active against the Plasmodium liver stages (Plasmodium yoelii IC50 = 35 nM) and a preliminary in vivo evaluation indicated the in vitro activity was preserved (45% reduction in parasitemia compared to untreated infected mice). A mechanistic study demonstrated these molecules do not involve any of the pathways described for commercial drugs and exert a specific activity on the ring and trophozoite stages. 2015 Elsevier Masson SAS. All rights reserved.

Published
2015
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8. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine

Author

Nahla B Gadalla, Badria B. El-Sayed, Mary C. Oguike, Mehul Dhorda, Ahmed Zeynudin, Sally Hamour, Jean-René Kiechel, A. Fabrice Some, Colin J. Sutherland, Erasmus Kamugisha, Philippe J Guerin, Didier Menard, Anders Björkman, Bernhards Ogutu, Alexis Nzila, Johan Ursing, Ric N. Price, Julie Thwing, Abdoulaye Djimde, Kasia Stepniewska, Francesco Checchi, Issaka Zongo, Nicole Berens-Riha, Frederick N. Baliraine, George O. Ademowo, Grant Dorsey, Fred Kironde, Gabrielle Fröberg, Catherine O. Falade, Lars Rombo, Christian Nsanzabana, Prabin Dahal, Teferi Eshetu, Samuel L. Nsobya, Simon Kariuki, Meghna Desai, Jacob D. Johnson, Frederick Eyase, Jean-Bosco Ouédraogo, Meera Venkatesan, Ishag Adam, Christopher V. Plowe, Cesar Arze, Birgit Schramm, Steffen Borrmann, Timothy M. E. Davis, Poul-Erik Kofoed, Billy Ngasala, Jean-François Faucher, Sandrine Houzé, Andreas Mårtensson, Philip J. Rosenthal, François Nosten, Maja Malmberg, Carol Hopkins Sibley, Patrice Piola, Anastasia Grivoyannis, Sabina Dahlström Otienoburu, Rina P. M. Wong, Clarissa Moriera, Leah Mwai, Jacques Lebras, Centre for Tropical Medicine and Global Health, University of Oxford, WorldWide Antimalarial Resistance Network (WWARN), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, Global Health Division, Menzies School of Health Research, Department of Microbiology, Tumour and Cell biology [Stockholm, Sweden] (Malaria Research), Karolinska Institutet [Stockholm], University of California [San Francisco] (UCSF), University of California, London School of Hygiene and Tropical Medicine (LSHTM), LECEMO - Les Cultures de l'Europe Méditérranéenne Occidentale - EA 3979 (LECEMO), Université Sorbonne Nouvelle - Paris 3, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), University of Maryland School of Medicine, University of Maryland System, German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Department of Infectious and Tropical Diseases, University of Oxford [Oxford], Département d'épidémiologie des affections parasitaires (DEAP), Université de Bamako-Malaria Research and Training Center (MRTC)-Facultés de Médecine, de Pharmacie et d'Odonto-Stomatologie-Centre National de la Recherche Scientifique (CNRS), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Drugs for Neglected Diseases Initiative, Kenya Medical Research Institute (KEMRI), Muhimbili University of Health and Allied Sciences, Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Makerere University [Kampala, Ouganda] (MAK), King Fahd University of Petroleum and Minerals (KFUPM), Institut de Recherche en Sciences de la Santé Bobo Dioulasso (INSSA), Université Polytechnique Nazi Boni Bobo-Dioulasso (UNB), Université de Washington Seattle, Epicentre [Paris] [Médecins Sans Frontières], The WorldWide Antimalarial Resistance Network is supported by the Bill and Melinda Gates Foundation., and The ASAQ Molecular Marker Study Group

Subjects
Artemether/lumefantrine, MESH: Lumefantrine, Drug Resistance, Protozoan Proteins, Datasets as Topic, Drug resistance, Kaplan-Meier Estimate, MESH: Genetic Markers, Pharmacology, MESH: Membrane Transport Proteins, MESH: Genotype, chemistry.chemical_compound, 0302 clinical medicine, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, MESH: Child, MESH: Datasets as Topic, Artemether, Artemisinin, Malaria, Falciparum, Child, MESH: Protozoan Proteins, MESH: Plasmodium falciparum, 0303 health sciences, MESH: Artemether, biology, MESH: Malaria, Falciparum, Artesunate/amodiaquine, Chloroquine, Articles, MESH: Chloroquine, MESH: Amino Acid Substitution, MESH: Infant, Artemisinins, 3. Good health, Drug Combinations, Infectious Diseases, Ethanolamines, Child, Preschool, MESH: Drug Resistance, Drug Therapy, Combination, Multidrug Resistance-Associated Proteins, Erratum, MESH: Multidrug Resistance-Associated Proteins, medicine.drug, Genetic Markers, Genotype, 030231 tropical medicine, Plasmodium falciparum, Amodiaquine, Lumefantrine, MESH: Ethanolamines, 03 medical and health sciences, Antimalarials, Virology, MESH: Polymorphism, Genetic, MESH: Artemisinins, parasitic diseases, medicine, MESH: Fluorenes, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Amodiaquine, MESH: Kaplan-Meier Estimate, MESH: Drug Combinations, Fluorenes, MESH: Humans, Polymorphism, Genetic, 030306 microbiology, MESH: Child, Preschool, Infant, Membrane Transport Proteins, biology.organism_classification, MESH: Antimalarials, MESH: Drug Therapy, Combination, chemistry, Amino Acid Substitution, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Parasitology
Abstract

Erratum in :- Errata. [Am J Trop Med Hyg. 2015]- Erratum. [Am J Trop Med Hyg. 2019]; International audience; Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

Published
2014
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9. Le rôle stratégique de la qualité du produit

Author

David A. Aaker, Robert Jacobson, Bouladi, Emna, and Université de Washington Seattle

Subjects
General Computer Science, [SHS.GESTION]Humanities and Social Sciences/Business administration, [SHS.GESTION] Humanities and Social Sciences/Business administration
Abstract

International audience; Les auteurs étudient le rôle de la qualité du produit comme moyen d'acquérir un avantage comparatif. Ils démontrent que l'on ne peut évaluer le rôle de la qualité et les hypothèses principales qui s'y rapportent i / si l'on ne prend pas en compte une rétroaction entre la qualité et les autres facteurs stratégiques, et 2 / si l'on ne contrôle pas les effets spécifiques à la firme. En utilisant la base de données PIMS, les auteurs déterminent les effets de rétroaction entre la qualité du produit et d'autres variables stratégiques. Les résultats mettent en valeur l'importance de la qualité du produit et suggèrent qu'une mise en œuvre d'une stratégie fondée sur la qualité peut favoriser un accroissement de la rentabilité à la fois dans une stratégie de niche ou de gain de part de marché.

Published
1988

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