Search

Your search keyword '"Georgina S. Humphreys"' showing total 2 results
Start Over Author "Georgina S. Humphreys" Journal bmc medicine
2 results on '"Georgina S. Humphreys"'

1. Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data

Author

Kasia Stepniewska, Elizabeth N. Allen, Georgina S. Humphreys, Eugenie Poirot, Elaine Craig, Kalynn Kennon, Daniel Yilma, Teun Bousema, Philippe J. Guerin, Nicholas J. White, Ric N. Price, Jaishree Raman, Andreas Martensson, Richard O. Mwaiswelo, Germana Bancone, Guido J. H. Bastiaens, Anders Bjorkman, Joelle M. Brown, Umberto D’Alessandro, Alassane A. Dicko, Badria El-Sayed, Salah-Eldin Elzaki, Alice C. Eziefula, Bronner P. Gonçalves, Muzamil Mahdi Abdel Hamid, Akira Kaneko, Simon Kariuki, Wasif Khan, Titus K. Kwambai, Benedikt Ley, Billy E. Ngasala, Francois Nosten, Joseph Okebe, Aaron M. Samuels, Menno R. Smit, Will J. R. Stone, Inge Sutanto, Feiko Ter Kuile, Roger C. Tine, Alfred B. Tiono, Chris J. Drakeley, Roly Gosling, Andy Stergachis, Karen I. Barnes, and Ingrid Chen

Subjects
Malaria, Primaquine, Clinical trial, Safety, Haemoglobin, Haemoglobinuria adverse events, Medicine
Abstract

Abstract Background In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. Methods A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. Results Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17–0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19–0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. Conclusions Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. Trial registration PROSPERO, CRD42019128185

Published
2022
Full Text
View/download PDF

2. 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

Catalog

Books, media, physical & digital resources
See catalog results