Publication:
The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data

Issued Date

2015-03-31

Resource Type

Article

ISSN

17417015

DOI

10.1186/s12916-015-0301-z

Other identifier(s)

2-s2.0-84928776445

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

BMC Medicine. Vol.13, No.1 (2015)

Suggested Citation

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. BMC Medicine. Vol.13, No.1 (2015). doi:10.1186/s12916-015-0301-z Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/36484

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Title

The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data

Author(s)

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

Other Contributor(s)

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

Abstract

© 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.

Keyword(s)

Medicine

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URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/36484

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