@article{fdi:010064473,
  title = {{T}he effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data},
  author = {{B}rasseur, {P}hilippe and {C}ot, {M}ichel and {D}eloron, {P}hilippe and {E}tard, {J}ean-{F}ran{\c{c}}ois and et al.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {A}rtesunate-amodiaquine ({AS}-{AQ}) is one of the most widely used artemisinin-based combination therapies ({ACT}s) to treat uncomplicated {P}lasmodium falciparum malaria in {A}frica. {W}e investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. {M}ethods: {I}ndividual patient data from {AS}-{AQ} clinical trials were pooled using the {W}orld{W}ide {A}ntimalarial {R}esistance {N}etwork ({WWARN}) standardised methodology. {R}isk factors for treatment failure were identified using a {C}ox regression model with shared frailty across study sites. {R}esults: {F}orty-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}). {T}he 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]). {P}atients treated with {FDC} received a median dose of 32.4 mg/kg [{IQR}: 27-39.0]. {A}fter 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). {A}fter 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. {C}onclusions: {T}here was substantial variation in the total dose of amodiaquine administered in different {AS}-{AQ} combination regimens. {F}ixed dose {AS}-{AQ} combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.},
  keywords = {{PALUDISME} ; {TRAITEMENT} {MEDICAL} ; {MEDICAMENT} ; {DOSAGE} ; {EFFICACITE} ; {RESISTANCE} ; {AMODIAQUINE} ; {ARTESUNATE} ; {MONDE}},
  booktitle = {},
  journal = {{BMC} {M}edicine},
  volume = {13},
  numero = {},
  pages = {art. no 66 [19 ]},
  ISSN = {1741-7015},
  year = {2015},
  DOI = {10.1186/s12916-015-0301-z},
  URL = {https://www.documentation.ird.fr/hor/fdi:010064473},
}