@article{fdi:010065266,
  title = {{C}linical determinants of early parasitological response to {ACT}s in {A}frican patients with uncomplicated falciparum malaria : a literature review and meta-analysis of individual patient data},
  author = {{A}bdulla, {S}. and {A}dam, {I}. and {A}djei, {G}. {O}. and {A}djuik, {M}. {A}. and {A}lemayehu, {B}. and {A}llan, {R}. and {A}rinaitwe, {E}. and {A}shley, {E}. {A}. and {B}a, {M}. {S}. and {B}arennes, {H}. and {B}arnes, {K}. {I}. and {B}assat, {Q}. and {B}audin, {E}. and {B}erens-{R}iha, {N}. and {B}jorkman, {A}. and {B}ompart, {F}. and {B}onnet, {M}. and {B}orrmann, {S}. and {B}ousema, {T}. and {B}rasseur, {P}hilippe and {B}ukirwa, {H}. and {C}hecchi, {F}. and {D}ahal, {P}. and {D}'{A}lessandro, {U}. and {D}esai, {M}. and {D}icko, {A}. and {D}jimde, {A}. {A}. and {D}orsey, {G}. and {D}oumbo, {O}. {K}. and {D}rakeley, {C}. {J}. and {D}uparc, {S}. and {E}shetu, {T}. and {E}spie, {E}. and {E}tard, {J}ean-{F}ran{\c{c}}ois and et al.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {A}rtemisinin-resistant {P}lasmodium falciparum has emerged in the {G}reater {M}ekong sub-region and poses a major global public health threat. {S}low parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. {T}his study was designed to establish the baseline values for clearance in patients from {S}ub-{S}aharan {A}frican countries with uncomplicated malaria treated with artemisinin-based combination therapies ({ACT}s). {M}ethods: {A} literature review in {P}ub{M}ed was conducted in {M}arch 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including {ACT}s conducted in {S}ub-{S}aharan {A}frica, between 1960 and 2012. {I}ndividual patient data from these studies were shared with the {W}orld{W}ide {A}ntimalarial {R}esistance {N}etwork ({WWARN}) and pooled using an a priori statistical analytical plan. {F}actors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. {T}he risk of bias in included studies was evaluated based on study design, methodology and missing data. {R}esults: {I}n total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). {T}he overall parasite clearance rate was rapid. {T}he parasite positivity rate ({PPR}) decreased from 59.7 % (95 % {CI}: 54.5-64.9) on day 1 to 6.7 % (95 % {CI}: 4.8-8.7) on day 2 and 0.9 % (95 % {CI}: 0.5-1.2) on day 3. {T}he 95th percentile of observed day 3 {PPR} was 5.3 %. {I}ndependent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio ({AOR}) = 1.16 (95 % {CI}: 1.08-1.25); per 2-fold increase in parasite density, {P} <0.001); fever (>37.5 degrees {C}) ({AOR} = 1.50 (95 % {CI}: 1.06-2.13), {P} = 0.022); severe anaemia ({AOR} = 2.04 (95 % {CI}: 1.21-3.44), {P} = 0.008); areas of low/moderate transmission setting ({AOR} = 2.71 (95 % {CI}: 1.38-5.36), {P} = 0.004); and treatment with the loose formulation of artesunate-amodiaquine ({AOR} = 2.27 (95 % {CI}: 1.14-4.51), {P} = 0.020, compared to dihydroartemisinin-piperaquine). {C}onclusions: {T}he three {ACT}s assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in {S}ub-{S}aharan {A}frica. {A} threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in {S}ub-{S}aharan {A}frica compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.},
  keywords = {{AFRIQUE} {SUBSAHARIENNE}},
  booktitle = {},
  journal = {{B}mc {M}edicine},
  volume = {13},
  numero = {},
  pages = {art. 212 [16 p.]},
  ISSN = {1741-7015},
  year = {2015},
  DOI = {10.1186/s12916-015-0445-x},
  URL = {https://www.documentation.ird.fr/hor/fdi:010065266},
}