@article{fdi:010068244,
  title = {{E}fficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition : an open comparative intervention study in {M}ali and {N}iger},
  author = {{D}enoeud {N}dam, {L}ise and {D}icko, {A}. and {B}audin, {E}. and {G}uindo, {O}. and {G}randesso, {F}. and {D}iawara, {H}. and {S}issoko, {S}. and {S}anogo, {K}. and {T}raore, {S}. and {K}eita, {S}. and {B}arry, {A}. and de {S}met, {M}. and {L}asry, {E}. and {S}mit, {M}. and {W}iesner, {L}. and {B}arnes, {K}. {I}. and {D}jimde, {A}. {A}. and {G}uerin, {P}. {J}. and {G}rais, {R}. {F}. and {D}oumbo, {O}. {K}. and {E}tard, {J}ean-{F}ran{\c{c}}ois},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {S}evere acute malnutrition ({SAM}) affects almost all organs and has been associated with reduced intestinal absorption of medicines. {H}owever, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. {W}e assessed artemether-lumefantrine ({AL}) clinical efficacy in children with {SAM} compared to those without. {M}ethods: {C}hildren under 5 years of age with uncomplicated {P}. falciparum malaria were enrolled between {N}ovember 2013 and {J}anuary 2015 in {M}ali and {N}iger, one third with uncomplicated {SAM} and two thirds without. {AL} was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food ({RUTF} - {P}lumpy'{N}ut ({R})) in {SAM} children, twice daily during 3 days. {C}hildren were followed for 42 days, with {PCR}-corrected adequate clinical and parasitological response ({ACPR}) at day 28 as the primary outcome. {L}umefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7. {R}esults: {A} total of 399 children (360 in {M}ali and 39 in {N}iger) were enrolled. {C}hildren with {SAM} were younger than their non-{SAM} counterparts (mean 17 vs. 28 months, {P} < 0.0001). {PCR}-corrected {ACPR} was 100 % (95 % {CI}, 96.8-100 %) in {SAM} at both day 28 and 42, versus 98.8 % (96.4-99.7 %) at day 28 and 98.3 % (95.6-99.4 %) at day 42 in non-{SAM} ({P} = 0.236 and 0.168, respectively). {C}ompared to younger children, children older than 21 months experienced more reinfections and {SAM} was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio = 2.10 (1.04-4.22), {P} = 0.038). {D}ay 7 lumefantrine concentrations were significantly lower in {SAM} than non-{SAM} (median 251 vs. 365 ng/m{L}, {P} = 0.049). {C}onclusions: {T}his study shows comparable therapeutic efficacy of {AL} in children without {SAM} and in those with {SAM} when given in combination with {RUTF}, but a higher risk of reinfection in older children suffering from {SAM}. {T}his could be associated with poorer exposure to the antimalarials as documented by a lower lumefantrine concentration on day 7.},
  keywords = {{P}lasmodium falciparum malaria ; {S}evere acute malnutrition ; {A}rtemether-lumefantrine ; {T}reatment outcome ; {P}harmacokinetics ; {N}iger ; {M}ali ; {MALI} ; {NIGER}},
  booktitle = {},
  journal = {{BMC} {M}edicine},
  volume = {14},
  numero = {},
  pages = {art. 167 [14 p.]},
  ISSN = {1741-7015},
  year = {2016},
  DOI = {10.1186/s12916-016-0716-1},
  URL = {https://www.documentation.ird.fr/hor/fdi:010068244},
}