Publications

@article{Adjuik2015,

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

author = {Martin A. Adjuik and Richard Allan and Anupkumar R. Anvikar and Elizabeth A. Ashley and Mamadou S. Ba and Hubert Barennes and Karen I. Barnes and Quique Bassat and Elisabeth Baudin and Anders Bj\"{o}rkman and Fran\c{c}ois Bompart and Maryline Bonnet and Steffen Borrmann and Philippe Brasseur and Hasifa Bukirwa and Francesco Checchi and Michel Cot and Prabin Dahal and Umberto D'Alessandro and Philippe Deloron and Meghna Desai and Graciela Diap and Abdoulaye A. Djimde and Grant Dorsey and Ogobara K. Doumbo and Emmanuelle Espi\'{e} and Jean Francois Etard and Caterina I. Fanello and Jean Fran\c{c}ois Faucher and Babacar Faye and Jennifer A. Flegg and Oumar Gaye and Peter W. Gething and Raquel Gonz\'{a}lez and Francesco Grandesso and Philippe J. Guerin and Jean Paul Guthmann and Sally Hamour and Armedy Ronny Hasugian and Simon I. Hay and Georgina S. Humphreys and Vincent Jullien and Elizabeth Juma and Moses R. Kamya and Corine Karema and Jean R. Kiechel and Peter G. Kremsner and Sanjeev Krishna and Val\'{e}rie Lameyre and Laminou M. Ibrahim and Sue J. Lee and Bertrand Lell and Andreas Martensson and Achille Massougbodji and Herv\'{e} Menan and Didier M\'{e}nard and Clara Men\'{e}ndez and Martin Meremikwu and Clarissa Moreira and Carolyn Nabasumba and Michael Nambozi and Jean Louis Ndiaye and Frederic Nikiema and Christian Nsanzabana and Francine Ntoumi and Bernhards R. Ogutu and Piero Olliaro and Lyda Osorio and Jean Bosco Ou\'{e}draogo and Louis K. Penali and Mbaye Pene and Loretxu Pinoges and Patrice Piola and Ric N. Price and Cally Roper and Philip J. Rosenthal and Claude Emile Rwagacondo and Albert Same-Ekobo and Birgit Schramm and Amadou Seck and Bhawna Sharma and Carol Hopkins Sibley and V\'{e}ronique Sinou and Sodiomon B. Sirima and Jeffery J. Smith and Frank Smithuis and Fabrice A. Som\'{e} and Doudou Sow and Sarah G. Staedke and Kasia Stepniewska and Todd D. Swarthout and Khadime Sylla and Ambrose O. Talisuna and Joel Tarning and Walter R. J. Taylor and Emmanuel A. Temu and Julie I. Thwing and Emiliana Tjitra and Roger C. K. Tine and Halidou Tinto and Michel T. Vaillant and Neena Valecha and Ingrid Van Broek and Nicholas J. White and Adoke Yeka and Issaka Zongo},

doi = {10.1186/s12916-015-0301-z},

issn = {17417015},

year  = {2015},

date = {2015-01-01},

journal = {BMC Medicine},

volume = {13},

issue = {1},

publisher = {BioMed Central Ltd.},

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 \< 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},

keywords = {Amodiaquine, Artesunate, Dosing, Drug Resistance, Efficacy, Malaria, Plasmodium falciparum},

pubstate = {published},

tppubtype = {article}

}