The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data
© The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group; licensee BioMed Central. 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...
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Medicine Martin A. Adjuik Richard Allan Anupkumar R. Anvikar Elizabeth A. Ashley Mamadou S. Ba Hubert Barennes Karen I. Barnes Quique Bassat Elisabeth Baudin Anders Björkman François Bompart Maryline Bonnet Steffen Borrmann Philippe Brasseur Hasifa Bukirwa Francesco Checchi Michel Cot Prabin Dahal Umberto D'Alessandro Philippe Deloron Meghna Desai Graciela Diap Abdoulaye A. Djimde Grant Dorsey Ogobara K. Doumbo Emmanuelle Espié Jean Francois Etard Caterina I. Fanello Jean François Faucher Babacar Faye Jennifer A. Flegg Oumar Gaye Peter W. Gething Raquel González Francesco Grandesso Philippe J. Guerin Jean Paul Guthmann Sally Hamour Armedy Ronny Hasugian Simon I. Hay Georgina S. Humphreys Vincent Jullien Elizabeth Juma Moses R. Kamya Corine Karema Jean R. Kiechel Peter G. Kremsner Sanjeev Krishna Valérie Lameyre Laminou M. Ibrahim Sue J. Lee Bertrand Lell Andreas Martensson Achille Massougbodji Hervé Menan Didier Ménard Clara Menéndez Martin Meremikwu Clarissa Moreira Carolyn Nabasumba Michael Nambozi Jean Louis Ndiaye Frederic Nikiema Christian Nsanzabana Francine Ntoumi Bernhards R. Ogutu Piero Olliaro Lyda Osorio Jean Bosco Ouédraogo Louis K. Penali Mbaye Pene The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data |
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© The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group; licensee BioMed Central. Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. Conclusions: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories. |
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INDEPTH Network Martin A. Adjuik Richard Allan Anupkumar R. Anvikar Elizabeth A. Ashley Mamadou S. Ba Hubert Barennes Karen I. Barnes Quique Bassat Elisabeth Baudin Anders Björkman François Bompart Maryline Bonnet Steffen Borrmann Philippe Brasseur Hasifa Bukirwa Francesco Checchi Michel Cot Prabin Dahal Umberto D'Alessandro Philippe Deloron Meghna Desai Graciela Diap Abdoulaye A. Djimde Grant Dorsey Ogobara K. Doumbo Emmanuelle Espié Jean Francois Etard Caterina I. Fanello Jean François Faucher Babacar Faye Jennifer A. Flegg Oumar Gaye Peter W. Gething Raquel González Francesco Grandesso Philippe J. Guerin Jean Paul Guthmann Sally Hamour Armedy Ronny Hasugian Simon I. Hay Georgina S. Humphreys Vincent Jullien Elizabeth Juma Moses R. Kamya Corine Karema Jean R. Kiechel Peter G. Kremsner Sanjeev Krishna Valérie Lameyre Laminou M. Ibrahim Sue J. Lee Bertrand Lell Andreas Martensson Achille Massougbodji Hervé Menan Didier Ménard Clara Menéndez Martin Meremikwu Clarissa Moreira Carolyn Nabasumba Michael Nambozi Jean Louis Ndiaye Frederic Nikiema Christian Nsanzabana Francine Ntoumi Bernhards R. Ogutu Piero Olliaro Lyda Osorio Jean Bosco Ouédraogo Louis K. Penali Mbaye Pene |
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Martin A. Adjuik Richard Allan Anupkumar R. Anvikar Elizabeth A. Ashley Mamadou S. Ba Hubert Barennes Karen I. Barnes Quique Bassat Elisabeth Baudin Anders Björkman François Bompart Maryline Bonnet Steffen Borrmann Philippe Brasseur Hasifa Bukirwa Francesco Checchi Michel Cot Prabin Dahal Umberto D'Alessandro Philippe Deloron Meghna Desai Graciela Diap Abdoulaye A. Djimde Grant Dorsey Ogobara K. Doumbo Emmanuelle Espié Jean Francois Etard Caterina I. Fanello Jean François Faucher Babacar Faye Jennifer A. Flegg Oumar Gaye Peter W. Gething Raquel González Francesco Grandesso Philippe J. Guerin Jean Paul Guthmann Sally Hamour Armedy Ronny Hasugian Simon I. Hay Georgina S. Humphreys Vincent Jullien Elizabeth Juma Moses R. Kamya Corine Karema Jean R. Kiechel Peter G. Kremsner Sanjeev Krishna Valérie Lameyre Laminou M. Ibrahim Sue J. Lee Bertrand Lell Andreas Martensson Achille Massougbodji Hervé Menan Didier Ménard Clara Menéndez Martin Meremikwu Clarissa Moreira Carolyn Nabasumba Michael Nambozi Jean Louis Ndiaye Frederic Nikiema Christian Nsanzabana Francine Ntoumi Bernhards R. Ogutu Piero Olliaro Lyda Osorio Jean Bosco Ouédraogo Louis K. Penali Mbaye Pene |
author_sort |
Martin A. Adjuik |
title |
The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data |
title_short |
The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data |
title_full |
The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data |
title_fullStr |
The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data |
title_full_unstemmed |
The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data |
title_sort |
effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/36484 |
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1763495639507795968 |
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th-mahidol.364842018-11-23T17:48:04Z The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data Martin A. Adjuik Richard Allan Anupkumar R. Anvikar Elizabeth A. Ashley Mamadou S. Ba Hubert Barennes Karen I. Barnes Quique Bassat Elisabeth Baudin Anders Björkman François Bompart Maryline Bonnet Steffen Borrmann Philippe Brasseur Hasifa Bukirwa Francesco Checchi Michel Cot Prabin Dahal Umberto D'Alessandro Philippe Deloron Meghna Desai Graciela Diap Abdoulaye A. Djimde Grant Dorsey Ogobara K. Doumbo Emmanuelle Espié Jean Francois Etard Caterina I. Fanello Jean François Faucher Babacar Faye Jennifer A. Flegg Oumar Gaye Peter W. Gething Raquel González Francesco Grandesso Philippe J. Guerin Jean Paul Guthmann Sally Hamour Armedy Ronny Hasugian Simon I. Hay Georgina S. Humphreys Vincent Jullien Elizabeth Juma Moses R. Kamya Corine Karema Jean R. Kiechel Peter G. Kremsner Sanjeev Krishna Valérie Lameyre Laminou M. Ibrahim Sue J. Lee Bertrand Lell Andreas Martensson Achille Massougbodji Hervé Menan Didier Ménard Clara Menéndez Martin Meremikwu Clarissa Moreira Carolyn Nabasumba Michael Nambozi Jean Louis Ndiaye Frederic Nikiema Christian Nsanzabana Francine Ntoumi Bernhards R. Ogutu Piero Olliaro Lyda Osorio Jean Bosco Ouédraogo Louis K. Penali Mbaye Pene INDEPTH Network MENTOR Initiative National Institute of Malaria Research India Epicentre Universite Cheikh Anta Diop Centre MURAZ French Foreign Affairs WorldWide Antimalarial Resistance Network University of Cape Town Centro de Investigação em Saúde de Manhiça Instituto de Salud Global de Barcelona Karolinska Institutet Sanofi S.A. Universitat Tubingen German Centre for Infection Research Institut de Recherche pour le Developpement Dakar Uganda Malaria Surveillance Project IRD Institut de Recherche pour le Developpement Universite Paris Descartes WorldWide Antimalarial Resistance Network (WWARN) Nuffield Department of Clinical Medicine Prins Leopold Instituut voor Tropische Geneeskunde Medical Research Council Unit Centers for Disease Control and Prevention Drugs for Neglected Diseases Initiative University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology University of California, San Francisco Institut Pasteur de Dakar IRD Centre de Montpellier Mahidol University Besançon University Medical Center Monash University University of Oxford UCL Badan Penelitian Dan Pengembangan Kesehatan, Kementerian Kesehatan Republik Indonesia Kenya Medical Research Institute Makerere University Ministry of Health Centre de Recherches Médicales de Lambaréné University of London Centre de Recherche Médicale et Sanitaire Uppsala Universitet University of Abomey-Calavi University of Cocody Institut Pasteur du Cambodge University of Calabar Mbarara University of Science and Technology Tropical Diseases Research Centre Institut de Recherche en Sciences de la Santé Universite Marien Ngouabi United States Army Organisation Mondiale de la Sante Centro Internacional de Entrenamiento e Investigaciones Medicas WorldWide Antimalarial Resistance Network (WWARN)-West Africa Regional Centre Institut Pasteur de Madagascar Menzies School of Health Research London School of Hygiene & Tropical Medicine UNICEF Centre Hospitalier et Universitaire de Yaounde Drugs for Neglected Diseases initiative University of Washington, Seattle Universite de la Mediterranee Aix-Marseille II Centre National de Recherche et de Formation sur le Paludisme (CNRFP) World Wide Antimalarial Resistance Network (WWARN)-Asia Regional Centre University of Maryland School of Medicine Médecins sans Frontières/Holland Medical Action Myanmar Infectious Diseases Research Collaboration Médecins Sans Frontières East Africa Regional Office Hopitaux universitaires de Geneve Swiss Tropical and Public Health Institute (Swiss TPH) Universitat Basel Medicine © The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group; licensee BioMed Central. Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. Conclusions: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories. 2018-11-23T10:48:04Z 2018-11-23T10:48:04Z 2015-03-31 Article BMC Medicine. Vol.13, No.1 (2015) 10.1186/s12916-015-0301-z 17417015 2-s2.0-84928776445 https://repository.li.mahidol.ac.th/handle/123456789/36484 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84928776445&origin=inward |