Skip to Main content Skip to Navigation
Journal articles

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

Martin Adjuik 1 Richard Allan 1 Anupkumar Anvikar 2 Elizabeth Ashley 3 Mamadou Ba 4 Hubert Barennes 5 Karen Barnes 1 Quique Bassat 6 Elisabeth Baudin 3 Anders Bjorkman 7 François Bompart Maryline Bonnet 8 Steffen Borrmann 9 Philippe Brasseur 10 Hasifa Bukirwa Francesco Checchi 11 Michel Cot 12 Prabin Dahal 13, 14 Umberto d'Alessandro Philippe Deloron 15, 16 Meghna Desai Graciela Diap Abdoulaye Djimde 17 Grant Dorsey 18 Ogobara Doumbo 19 Emmanuelle Espié 20 Jean-François Etard 3 Caterina Fanello 21 Jean-François Faucher 22 Babacar Faye 23 Jennifer Flegg 24 Oumar Gaye 4 Peter Gething 25 Raquel Gonzalez 26 Francesco Grandesso Philippe Guerin 13, 14, * Jean-Paul Guthmann 27 Sally Hamour Armedy Ronny Hasugian Simon Hay 28 Georgina Humphreys Vincent Jullien 29, 30 Elizabeth Juma Moses Kamya Corine Karema Jean Kiechel Peter Kremsner 31 Sanjeev Krishna 32 Valerie Lameyre 33 Laminou Ibrahim Sue Lee 34 Bertrand Lell Andreas Martensson 35 Achille Massougbodji 36 Hervé Menan 37 Didier Ménard 38 Clara Menéndez 39 Martin Meremikwu Clarissa Moreira 40 Carolyn Nabasumba 41 Michael Nambozi 42 Jean-Louis Ndiaye Frederic Nikiema Christian Nsanzabana 14, 13, * Francine Ntoumi 43 Bernhards Ogutu 44 Piero Olliaro 45 Lyda Osorio 46 Jean-Bosco Ouédraogo 47 Louis Penali 48 Mbaye Pene Loretxu Pinoges 3 Patrice Piola 49 Ric Price 50 Cally Roper Philip Rosenthal Claude Emile Rwagacondo Albert Same-Ekobo Birgit Schramm 3 Amadou Seck 1 Bhawna Sharma Carol Hopkins Sibley 1 Veronique Sinou 51 Sodiomon Sirima 52 Jeffery Smith Frank Smithuis 53 Fabrice Somé Doudou Sow 4 Sarah Staedke Kasia Stepniewska Todd Swarthout Khadime Sylla 54 Ambrose Talisuna Joel Tarning 21 Walter Taylor Emmanuel Temu Julie Thwing Emiliana Tjitra Roger Tine 4 Halidou Tinto 55 Michel Vaillant 56 Neena Valecha 2 Ingrid van den Broek Nicholas White 21 Adoke Yeka Issaka Zongo
* Corresponding author
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, 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.
Complete list of metadatas

Cited literature [83 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02560653
Contributor : Didier Menard <>
Submitted on : Thursday, May 7, 2020 - 3:13:56 PM
Last modification on : Tuesday, June 2, 2020 - 4:34:37 PM

File

effect of dosing strategies on...
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Martin Adjuik, Richard Allan, Anupkumar Anvikar, Elizabeth Ashley, Mamadou Ba, et al.. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data. BMC Medicine, BioMed Central, 2015, 13 (1), pp.66. ⟨10.1186/s12916-015-0301-z⟩. ⟨hal-02560653⟩

Share

Metrics

Record views

71

Files downloads

38