학술논문

The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data.
Document Type
article
Author
WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study GroupAdjuik, Martin AAllan, RichardAnvikar, Anupkumar RAshley, Elizabeth ABa, Mamadou SBarennes, HubertBarnes, Karen IBassat, QuiqueBaudin, ElisabethBjörkman, AndersBompart, FrançoisBonnet, MarylineBorrmann, SteffenBrasseur, PhilippeBukirwa, HasifaChecchi, FrancescoCot, MichelDahal, PrabinD'Alessandro, UmbertoDeloron, PhilippeDesai, MeghnaDiap, GracielaDjimde, Abdoulaye ADorsey, GrantDoumbo, Ogobara KEspié, EmmanuelleEtard, Jean-FrancoisFanello, Caterina IFaucher, Jean-FrançoisFaye, BabacarFlegg, Jennifer AGaye, OumarGething, Peter WGonzález, RaquelGrandesso, FrancescoGuerin, Philippe JGuthmann, Jean-PaulHamour, SallyHasugian, Armedy RonnyHay, Simon IHumphreys, Georgina SJullien, VincentJuma, ElizabethKamya, Moses RKarema, CorineKiechel, Jean RKremsner, Peter GKrishna, SanjeevLameyre, ValérieIbrahim, Laminou MLee, Sue JLell, BertrandMårtensson, AndreasMassougbodji, AchilleMenan, HervéMénard, DidierMenéndez, ClaraMeremikwu, MartinMoreira, ClarissaNabasumba, CarolynNambozi, MichaelNdiaye, Jean-LouisNikiema, FredericNsanzabana, ChristianNtoumi, FrancineOgutu, Bernhards ROlliaro, PieroOsorio, LydaOuédraogo, Jean-BoscoPenali, Louis KPene, MbayePinoges, LoretxuPiola, PatricePrice, Ric NRoper, CallyRosenthal, Philip JRwagacondo, Claude EmileSame-Ekobo, AlbertSchramm, BirgitSeck, AmadouSharma, BhawnaSibley, Carol HopkinsSinou, VéroniqueSirima, Sodiomon BSmith, Jeffery JSmithuis, FrankSomé, Fabrice ASow, DoudouStaedke, Sarah GStepniewska, KasiaSwarthout, Todd DSylla, KhadimeTalisuna, Ambrose OTarning, JoelTaylor, Walter RJTemu, Emmanuel AThwing, Julie ITjitra, EmilianaTine, Roger CK
Source
BMC medicine. 13(1)
Subject
WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group
Humans
Malaria
Falciparum
Recurrence
Artemisinins
Amodiaquine
Drug Combinations
Antimalarials
Treatment Outcome
Risk Factors
Dose-Response Relationship
Drug
Middle Aged
Africa
Female
Male
Malaria
Plasmodium falciparum
Drug resistance
Artesunate
Dosing
Efficacy
Falciparum
Dose-Response Relationship
Drug
Medical and Health Sciences
General & Internal Medicine
Language
Abstract
BackgroundArtesunate-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.MethodsIndividual 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.ResultsForty-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