@article{fdi:010064693,
  title = {{A} multi-center, open-label trial to compare the efficacy and pharmacokinetics of {A}rtemether-{L}umefantrine in children with severe acute malnutrition versus children without severe acute malnutrition : study protocol for the {MAL}-{NUT} study},
  author = {{D}enoeud {N}dam, {L}. and {D}icko, {A}. and {B}audin, {E}. and {G}uindo, {O}. and {G}randesso, {F}. and {S}agara, {I}. and {L}asry, {E}. and {P}alma, {P}. {P}. and {P}arra, {A}. {M}. {L}. and {S}tepniewska, {K}. and {D}jimde, {A}. {A}. and {B}arnes, {K}. {I}. and {D}oumbo, {O}. {K}. and {E}tard, {J}ean-{F}ran{\c{c}}ois},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {M}alnutrition and malaria frequently coexist in sub-{S}aharan {A}frican countries. {S}tudies on efficacy of antimalarial treatments usually follow the {WHO} standardized protocol in which severely malnourished children are systematically excluded. {F}ew studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. {O}verall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. {H}owever, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies ({ACT}s) and especially artemether-lumefantrine in malnourished children is currently lacking. {T}he main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition ({SAM}) compared to non-{SAM} children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile. {M}ethods/design: {I}n two sites, {O}uelessebougou, {M}ali and {M}aradi, {N}iger, children with uncomplicated microscopically-confirmed {P}. falciparum malaria aged between 6 and 59 months will be enrolled. {T}wo non-{SAM} children will be enrolled after the enrolment of each {SAM} case. {C}hildren with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded. {T}reatment intakes will be supervised and children will be followed-up for 42 days, according to {WHO} guidance for surveillance of antimalarial drug efficacy. {P}olymerase {C}hain {R}eaction genotyping will be used to distinguish recrudescence from re-infection. {SAM} children will also benefit from the national nutritional rehabilitation program. {O}utcomes will be compared between the {SAM} and non-{SAM} populations. {T}he primary outcome will be adequate clinical and parasitological response at day 28 after {PCR} correction, estimated by {K}aplan-{M}eier analysis. {T}o assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). {A} total of 180 {SAM} children and 360 non-{SAM} children will be recruited during the 2013 and 2014 malaria seasons. {D}iscussion: {T}his study will provide important information that is currently lacking on the effect of {SAM} on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. {I}f it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in {SAM} children.},
  keywords = {{M}alaria ; {S}evere acute malnutrition ; {A}rtemether-lumefantrine fixed combination ; {P}harmacokinetics ; {E}fficacy ; {N}iger ; {M}ali ; {MALI} ; {NIGER}},
  booktitle = {},
  journal = {{BMC} {I}nfectious {D}iseases},
  volume = {15},
  numero = {},
  pages = {art. 228 [11 p.]},
  ISSN = {1471-2334},
  year = {2015},
  DOI = {10.1186/s12879-015-0963-3},
  URL = {https://www.documentation.ird.fr/hor/fdi:010064693},
}