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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. Social and environmental risk factors for dengue in Delhi city: A retrospective study

Author

Telle, Olivier, Nikolay, Birgit, Kumar, Vikram, Benkimoun, Samuel, Pal, Rupali, Nagpal, B. N., Paul, Richard, Géographie-cités (GC (UMR_8504)), Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre for Policy Research [New Delhi] (CPR), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Centre de sciences humaines de New Delhi (CSH), Ministère de l'Europe et des Affaires étrangères (MEAE)-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche, France (ANR 10- CEPL-004- AEDESS) to RP ANR: anr.fr/en/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip, and ANR-10-CEPL-0004,AEDESS,Analyse de l'Emergence de la Dengue et Simulation Spatiale(2010)

Subjects
RNA viruses, Viral Diseases, Life Cycles, Mosquito Control, Epidemiology, RC955-962, MESH: Dengue, Pathology and Laboratory Medicine, MESH: Dengue Virus, epidemic, Dengue Fever, [SHS]Humanities and Social Sciences, Medical Conditions, Larvae, Risk Factors, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Arctic medicine. Tropical medicine, Medicine and Health Sciences, MESH: Urbanization, ComputingMilieux_MISCELLANEOUS, MESH: Mosquito Control, Infectious Diseases, Medical Microbiology, Viral Pathogens, Viruses, Pathogens, Public aspects of medicine, RA1-1270, Research Article, Neglected Tropical Diseases, MESH: Socioeconomic Factors, Infectious Disease Control, India, PARIS team, Microbiology, Population Metrics, MESH: Cities, Humans, urban studies, Cities, Microbial Pathogens, Retrospective Studies, Population Density, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Population Biology, Flaviviruses, ACL, Urbanization, Organisms, Biology and Life Sciences, MESH: Retrospective Studies, Dengue Virus, Tropical Diseases, dengue, Socioeconomic Factors, Medical Risk Factors, MESH: India, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Geospatial Analysis, Zoology, Entomology, Developmental Biology
Abstract

Global urbanization is leading to an inexorable spread of several major diseases that need to be stemmed. Dengue is one of these major diseases spreading in cities today, with its principal mosquito vector superbly adapted to the urban environment. Current mosquito control strategies are proving inadequate, especially in the face of such urbanisation and novel, evidence-based targeted approaches are needed. Through combined epidemiological and entomological approaches, we aimed to identify a novel sanitation strategy to alleviate the burden of dengue through how the dengue virus spreads through the community. We combined surveillance case mapping, prospective serological studies, year-round mosquito surveys, socio-economic and Knowledge Attitudes and Practices surveys across Delhi. We identified lack of access to tap water (≤98%) as an important risk factor for dengue virus IgG sero-positivity (adjusted Odds Ratio 4.69, 95% C.I. 2.06–10.67) and not poverty per se. Wealthier districts had a higher dengue burden despite lower mosquito densities than the Intermediary income communities (adjusted Odds Ratio 2.92, 95% C.I. 1.26–6.72). This probably reflects dengue being introduced by people travelling from poorer areas to work in wealthier houses. These poorer, high density areas, where temperatures are also warmer, also had dengue cases during the winter. Control strategies based on improved access to a reliable supply of tap water plus focal intervention in intra-urban heat islands prior to the dengue season could not only lead to a reduction in mosquito abundance but also eliminate the reservoir of dengue virus clearly circulating at low levels in winter in socio-economically disadvantaged areas., Author summary Identifying disease hotspots and individual risk factors for dengue can enable targeted intervention strategies. We conducted combined serological, entomological and socio-economic surveys across 18 areas within Delhi, taken from the total 1280 colonies (i.e. the administrative units of reference in Delhi) for which we classified their socio-economic typology. We additionally performed a Knowledge, Attitudes, Practices survey at a household level within the most socially disadvantaged sub-districts. Finally, we mapped all the winter dengue cases to 250 m x 250 m units along with their winter mean temperatures. We found that access to tap water was an important risk factor for exposure to dengue virus (DENV) and this was confirmed even within the socially disadvantaged sub-districts. The Wealthy colonies had a high burden of DENV infection despite low mosquito densities, likely linked to their connectedness through daily human mobility. The winter burden of dengue occurred majoritarily in the socio-economically disadvantaged colonies, which also have higher mean temperatures and urban heat islands. Improved access to tap water could lead to a reduction in dengue, not only for those directly affected but for the general population. Targeted intervention through mosquito control in winter in the socially disadvantaged areas could offer a rational strategy for optimising control efforts.

Published
2021
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3. Functional Food for the Stimulation of the Immune System Against Malaria

Author

Pilar Alberdi, Anupkumar R. Anvikar, Helen I Inabo, Timothy Bamgbose, Mohammed Bello, Alejandro Cabezas-Cruz, I.O. Abdullahi, José de la Fuente, National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Ahmadu Bello University, Instituto de Investigación en Recursos Cinegéticos (IREC), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Veterinary Pathobiology, Center of Veterinary Health Sciences, Oklahoma State University [Stillwater], Consejería de Educación, Cultura y Deportes, JCCM, Spain, projects CCM17-PIC-036 (SBPLY/17/180501/000185)., Junta de Comunidades de Castilla-La Mancha, and École nationale vétérinaire d'Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé

Subjects
0301 basic medicine, Plasmodium, 030106 microbiology, Drug resistance, Gut microbiota, Gut flora, Microbiology, digestive system, Article, 03 medical and health sciences, Immune system, Functional food, Malaria transmission, Functional Food, Lactobacillales, parasitic diseases, medicine, Global health, Lactic acid bacteria, Humans, Plasmodium · Probiotics, Molecular Biology, Antibody, 2. Zero hunger, biology, business.industry, Probiotics, digestive, oral, and skin physiology, biology.organism_classification, medicine.disease, Alpha gal, 3. Good health, Gastrointestinal Microbiome, Malaria, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Immune System, Immunology, Molecular Medicine, Malaria control, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Drug resistance has become a threat to global health, and new interventions are needed to control major infectious diseases. The composition of gut microbiota has been linked to human health and has been associated with severity of malaria. Fermented foods contribute to the community of healthy gut bacteria. Despite the studies connecting gut microbiota to the prevention of malaria transmission and severity, research on developing functional foods for the purpose of manipulating the gut microbiota for malaria control is limited. This review summarizes recent knowledge on the role of the gut microbiota in malaria prevention and treatment. This information should encourage the search for lactic acid bacteria expressing α-Gal and those that exhibit the desired immune stimulating properties for the development of functional food and probiotics for malaria control., Research on α-Gal has been supported by the Consejería de Educación, Cultura y Deportes, JCCM, Spain, projects CCM17-PIC-036 (SBPLY/17/180501/000185).

Published
2021
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4. Classification and nomenclature of metacaspases and paracaspases: no more confusion with caspases

Author

Christiane Funk, Vanina E. Alvarez, Heinz D. Osiewacz, Juan José Cazzulo, Simon Stael, Boris Zhivotovsky, Chang Jae Choi, Frank Madeo, Jens Staal, Kailash C. Pandey, Lynn A. Megeney, Yigong Shi, Magali Casanova, Andrei Smertenko, Maurício F.M. Machado, Eric Lam, Renier A. L. van der Hoorn, Juergen Ruland, Ilana Berman-Frank, Panagiotis N. Moschou, Peter V. Bozhkov, Jeremy C. Mottram, Kay D. Bidle, Jerry Ståhlberg, Rudi Beyaert, Christopher M. Overall, Frédéric Bornancin, Kris Gevaert, Margot Thome, Assaf Vardi, Núria S. Coll, Patrick Gallois, Frank Van Breusegem, Thomas Nyström, Vishva M. Dixit, Marko Dolinar, Maria F. Suarez, Stephan Hailfinger, Nicolas Fasel, Emilio Gutierrez-Beltran, John A. Berges, Anna Linusson, Hannele Tuominen, Daniel Krappmann, Guy S. Salvesen, Marina Klemenčič, Elena A. Minina, Eugene V. Koonin, Canaan, Stephane, Swedish University of Agricultural Sciences (SLU), Universiteit Gent = Ghent University (UGENT), Universidad Nacional de San Martin (UNSAM), University of Wisconsin - Milwaukee, University of Haifa [Haifa], Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers), Novartis Institutes for BioMedical Research (NIBR), Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Texas at Austin [Austin], Centre for Research in Agricultural Genomics (CRAG), Genentech, Inc., Genentech, Inc. [San Francisco], University of Ljubljana, Université de Lausanne = University of Lausanne (UNIL), Umeå University, Universidade de Mogi das Cruces = University of Mogi das Cruzes (UMC), Karl-Franzens-Universität Graz, University of Ottawa [Ottawa], Institute of Molecular Biology and Biotechnology (IMBB-FORTH), Foundation for Research and Technology - Hellas (FORTH), University of York [York, UK], University of Gothenburg (GU), Goethe-University Frankfurt am Main, University of British Columbia (UBC), National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Sanford Burnham Prebys Medical Discovery Institute, Westlake University [Zhejiang], Washington State University (WSU), Universidad de Málaga [Málaga] = University of Málaga [Málaga], University of Oxford, Weizmann Institute of Science [Rehovot, Israël], Lomonosov Moscow State University (MSU), Knut and Alice Wallenberg Foundation, Swedish University of Agricultural Sciences and Linnean Center for Plant Biology, Universiteit Gent = Ghent University [Belgium] (UGENT), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), University of Lausanne (UNIL), Karl-Franzens-Universität [Graz, Autriche], University of Oxford [Oxford], University of Graz, and Technical University of Munich (TUM)

Subjects
Consensus, METACASPASES, Protein Conformation, [SDV]Life Sciences [q-bio], Computational biology, Article, purl.org/becyt/ford/1 [https], Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, Terminology as Topic, medicine, Animals, Humans, CRYSTAL-STRUCTURE, purl.org/becyt/ford/1.6 [https], SPECIFICITY, Molecular Biology, Nomenclature, Caspase, PARACASPASES, ComputingMilieux_MISCELLANEOUS, Plant Proteins, 030304 developmental biology, Confusion, 0303 health sciences, biology, MALT1, Biology and Life Sciences, Cell Biology, 3. Good health, PROTEASES, [SDV] Life Sciences [q-bio], KEY, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein, Caspases, biology.protein, CLAN CD, medicine.symptom, 030217 neurology & neurosurgery
Abstract

Metacaspases and paracaspases are proteases that were first identified as containing a caspase-like structural fold (Uren et al., 2000). Like caspases, metacaspases and paracaspases are multifunctional proteins regulating diverse biological phenomena, such as aging, immunity, proteostasis, and programmed cell death. The broad phylogenetic distribution of metacaspases and paracaspases across all kingdoms of life and large variation of their biochemical and structural features complicate classification and annotation of the rapidly growing number of identified homologs. Establishment of an adequate classification and unified nomenclature of metacaspases and paracaspases is especially important to avoid frequent confusion of these proteases with caspases—a tenacious misnomer that unfortunately does not appear to decline with time. This Letter represents a consensus opinion of researchers studying different aspects of caspases, metacaspases, and paracaspases in various organisms, ranging from microbes to plants and animals., This work was supported by the Knut and Alice Wallenberg Foundation.

Published
2020
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5. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

Author

Catherine L. Moyes, Lee Ching Ng, Sin Ying Koou, Isabelle Dusfour, Ademir Jesus Martins, João Pinto, Kamaraju Raghavendra, John Vontas, David Weetman, Jean-Philippe David, Vincent Corbel, Big Data Institute, University of Oxford, Institute of Molecular Biology and Biotechnology (IMBB-FORTH), Foundation for Research and Technology - Hellas (FORTH), Agricultural University of Athens, Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Environment Health Institute [Singapore], National Environment Agency [Singapore] (NEA), Entomologie médicale, Laboratoire de Parasitologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Liverpool School of Tropical Medicine (LSTM), The preparation of this review was funded by an award from the World Health Organization's Special Programme for Research and Training in Tropical Diseases (http://www.who.int/tdr/) to VC, JPD, and the WIN network. The bioassay data extraction was funded by Wellcome Trust (https://wellcome.ac.uk/) grant 108440/Z/15/Z awarded to CLM., We thank Hilary Ranson for providing the complete datasets from her 2010 review. We also thank Maria de Lourdes Macoris, Laboratório de Entomologia Aplicada, Sucen, São Paulo, for compiling an extensive dataset for Brazil, and Poonam Sharma Velamuri and Elamathi Natarajan for their work on the data for India. We thank the following groups and individuals for contributing unpublished datasets: Gonçalo Seixas and Carla Alexandra Sousa, Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Beniamino Caputo and Alessandra della Torre, Istituto Pasteur-Fondazione Cenci-Bolognetti, Dipartimento di Sanità Pubblica e Malattie Infettive, Università 'Sapienza', Rome, Italy, Sébastien Marcombe and Paul Brey, Institut Pasteur du Laos, Vientiane, Lao People’s Democratic Republic Waraporn Juntarajumnong, Kasetsart University, Bangkok, Thailand, Ferdinand V. Salazar, Department of Medical Entomology, Research Institute of Tropical Medicine, Department of Health, Philippines, Laboratório de Entomologia Aplicada (LEnA), Sucen, Marília, SP/ Brazil., University of Oxford [Oxford], and Fundação Oswaldo Cruz (FIOCRUZ)

Subjects
Enzyme Metabolism, Gene Identification and Analysis, MESH: Insect Vectors/genetics, Review, MESH: Africa, Dengue virus, Biochemistry, Zika virus, 0302 clinical medicine, MESH: Insecticides/classification, MESH: Animals, Chikungunya, Enzyme Chemistry, MESH: Larva/drug effects, MESH: Aedes/genetics, Organic Compounds, MESH: Asia, Yellow fever, MESH: Arboviruses/pathogenicity, 3. Good health, Physical Sciences, Inactivation, Metabolic, Biological Assay, Agrochemicals, Ethers, lcsh:RC955-962, MESH: Insect Control/methods, Aedes Aegypti, MESH: Biological Assay, 03 medical and health sciences, qx_600, Genetics, MESH: Aedes/drug effects, Humans, Mutation Detection, MESH: Humans, Organisms, Chemical Compounds, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Correction, lcsh:RA1-1270, MESH: Insecticide Resistance/genetics, medicine.disease, Invertebrates, Virology, Geographic Distribution, Insect Vectors, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Species Interactions, 030104 developmental biology, MESH: Arboviruses/classification, Infectious disease (medical specialty), Africa, MESH: Inactivation, Metabolic, Americas, 0301 basic medicine, Insecticides, MESH: Insect Vectors/virology, viruses, Population Dynamics, Disease Vectors, medicine.disease_cause, Mosquitoes, Insecticide Resistance, Aedes, Genotype, Medicine and Health Sciences, MESH: Insecticides/pharmacology, lcsh:Public aspects of medicine, Agriculture, Organophosphates, MESH: Insect Vectors/drug effects, Insects, Chemistry, Infectious Diseases, Larva, lcsh:Arctic medicine. Tropical medicine, Asia, Arthropoda, 030231 tropical medicine, wc_524, Aedes aegypti, Biology, Insect Control, Virus, medicine, qx_525, MESH: Americas, Animals, Population Biology, MESH: Aedes/virology, Organic Chemistry, biology.organism_classification, qx_650, Enzymology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Arboviruses
Abstract

International audience; Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

Published
2017
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6. An epidemiological study of dengue in Delhi, India

Author

B N Nagpal, Aparup Das, Anushrita, Rekha Saxena, Olivier Telle, Neena Valecha, Richard Paul, Himmat Singh, Veena Pande, N R Tuli, Kumar Vikram, N K Yadav, Aruna Srivastava, Sanjeev Kumar Gupta, Anup Anvikar, National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Department of Biotechnology, Kumaon University, Municipal Corporation of Delhi, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Authors are thankful to Paster Institut, Paris, France for the funding support ANR. We are also thankful to MCD for helping us in selection of study sites in Delhi. We thank the entire field staff for their careful performance in serological testing and data collection., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Pediatrics, MESH: Dengue/epidemiology, Dengue virus, medicine.disease_cause, Dengue fever, Dengue, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Child, Epidemiology, Mass Screening, 030212 general & internal medicine, MESH: Incidence, Child, Aged, 80 and over, education.field_of_study, Rapid diagnostic test, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, MESH: Epidemiologic Studies, Incidence, Incidence (epidemiology), Asymptomatic infection, Middle Aged, 3. Good health, MESH: India/epidemiology, Infectious Diseases, Child, Preschool, Female, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, Veterinary (miscellaneous), 030231 tropical medicine, Population, MESH: Mass Screening/statistics & numerical data, India, Asymptomatic, Young Adult, 03 medical and health sciences, medicine, Humans, education, Mass screening, Aged, MESH: Adolescent, MESH: Humans, business.industry, Secondary dengue infection, MESH: Child, Preschool, Infant, Primary dengue infection, MESH: Adult, Dengue Virus, medicine.disease, Epidemiologic Studies, Index case, MESH: Dengue Virus/isolation & purification, Insect Science, Immunology, Parasitology, business, MESH: Female
Abstract

International audience; Delhi, the capital of India, is an important metropolitan hub for major financial and sociocultural exchanges, offering challenging threats to current public health infrastructure. In recent past, an upsurge of dengue cases in Delhi posed a significant menace to the existing dengue control policies. To reform the control strategies and take timely intervention to prevent future epidemics, an epidemiological study on the proportion of both asymptomatic and symptomatic dengue infections in selected population was conducted. The aim of the study was to investigate and assess the epidemiology of dengue infection and to estimate the proportion of asymptomatic and symptomatic dengue infections in Delhi. In this study, around 50 confirmed dengue cases, a total of 2125 individuals as household and neighbourhood contacts, with or without dengue febrile illness, were finger pricked and serologically detected as dengue positive or negative using SD Duo Bioline Rapid Diagnostic Test (SD Inc, Korea) with NS1, IgM & IgG combo test, which detected dengue virus antigen and antibodies to dengue virus in human blood. Out of 2125 individuals , 768 (36.1%) individuals showed positive dengue test with past (25.5%), primary (1.88%) or secondary (8.8%) dengue infections. Higher percentage of IgG was found in age groups 15–24 years and 25–50 years (36% each). Infants (

Published
2016
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7. The Spread of Dengue in an Endemic Urban Milieu–The Case of Delhi, India

Author

N K Yadav, Alain Vaguet, Richard Paul, B N Nagpal, Bertrand Lefebvre, Alexandre Cebeillac, Olivier Telle, Eric Daudé, Institut Pasteur [Paris] (IP), Géographie-cités (GC (UMR_8504)), Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Identité et Différenciation de l’Espace, de l’Environnement et des Sociétés (IDEES), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Municipal Corporation of Delhi, National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), ANR-10-CEPL-0004,AEDESS,Analyse de l'Emergence de la Dengue et Simulation Spatiale(2010), European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Institut Pasteur [Paris], Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Géographie-cités (GC), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la recherche (grant CEPL 10-04)., Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Identités et Différenciation de l'Environnement des Espaces et des Sociétés (IDEES), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Geographic mobility, Mosquito Control, Urban Environment, Epidemiology, Population Dynamics, lcsh:Medicine, Dengue virus, Disease Vectors, medicine.disease_cause, Mosquitoes, Dengue fever, Disease Outbreaks, Urban Environments, Geographical Locations, Dengue, 0302 clinical medicine, Aedes aegypti, Environmental protection, Risk Factors, Geoinformatics, Medicine and Health Sciences, 030212 general & internal medicine, lcsh:Science, Socioeconomics, Multidisciplinary, Geography, [SHS.GEO]Humanities and Social Sciences/Geography, Terrestrial Environments, 3. Good health, Insects, Mosquito control, Infectious Diseases, Research Design, Physical Sciences, Statistics (Mathematics), Research Article, Computer and Information Sciences, Census, Asia, Arthropoda, Infectious Disease Control, 030231 tropical medicine, India, Context (language use), Disease cluster, Research and Analysis Methods, 03 medical and health sciences, Urbanization, medicine, Confidence Intervals, Population growth, Delhi, Animals, Humans, Survey Research, Population Biology, lcsh:R, Ecology and Environmental Sciences, Organisms, Biology and Life Sciences, Correction, Dengue Virus, medicine.disease, Invertebrates, Geographic Distribution, Insect Vectors, Socioeconomic Factors, People and Places, Geographic Information Systems, Earth Sciences, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mathematics
Abstract

International audience; Background: Dengue is a major international public health concern, one of the most important arthropod-borne diseases. More than 3.5 billion people are at risk of dengue infection and there are an estimated 390 million dengue infections annually. This prolific increase has been connected to societal changes such as population growth and increasing urbanization generating intense agglomeration leading to proliferation of synanthropic mosquito species. Quantifying the spatio-temporal epidemiology of dengue in large cities within the context of a Geographic Information System is a first step in the identification of socio-economic risk factors.Methodology/Principal Findings: This Project has been approved by the ethical committee of Institut Pasteur. Data has been anonymized and de-identified prior to geolocalisation and analysis. A GIS was developed for Delhi, enabling typological characterization of the urban environment. Dengue cases identified in the Delhi surveillance system from 2008 to 2010 were collated, localised and embedded within this GIS. The spatio-temporal distribution of dengue cases and extent of clustering were analyzed. Increasing distance from the forest in Delhi reduced the risk of occurrence of a dengue case. Proximity to a hospital did not increase risk of a notified dengue case. Overall, there was high heterogeneity in incidence rate within areas with the same socio-economical profiles and substantial inter-annual variability. Dengue affected the poorest areas with high density of humans, but rich areas were also found to be infected, potentially because of their central location with respect to the daily mobility network of Delhi. Dengue cases were highly clustered in space and there was a strong relationship between the time of introduction of the virus and subsequent cluster size. At a larger scale, earlier introduction predicted the total number of cases.Conclusions/Significance: DENV epidemiology within Delhi has a forest fire signature. The stochastic nature of this invasion process likely smothers any detectable socio-economic risk factors. However, the significant finding that the size of the dengue case cluster depends on the timing of its emergence emphasizes the need for early case detection and implementation of effective mosquito control. A better understanding of the role of population mobility in contributing to dengue risk could also help focus control on areas at particular risk of dengue virus importation.

Published
2015
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8. 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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