@article{fdi:010061733,
  title = {{P}lasmodium falciparum polymorphisms associated with ex vivo drug susceptibility and clinical effectiveness of artemisinin-based combination therapies in {B}enin},
  author = {{D}ahlstrom, {S}. and {A}ubouy, {A}gn{\`e}s and {M}aiga-{A}scofare, {O}. and {F}aucher, {J}. {F}. and {W}akpo, {A}. and {E}zinmegnon, {S}. and {M}assougbodji, {A}. and {H}ouze, {P}. and {K}endjo, {E}. and {D}eloron, {P}hilippe and {L}e {B}ras, {J}. and {H}ouze, {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{A}rtemisinin-based combination therapies ({ACT}s) are the main option to treat malaria, and their efficacy and susceptibility must be closely monitored to avoid resistance. {W}e assessed the association of {P}lasmodium falciparum polymorphisms and ex vivo drug susceptibility with clinical effectiveness. {P}atients enrolled in an effectiveness trial comparing artemether-lumefantrine (n = 96), fixed-dose artesunate-amodiaquine (n = 96), and sulfadoxine-pyrimethamine (n = 48) for the treatment of uncomplicated malaria 2007 in {B}enin were assessed. pfcrt, pfmdr1, pfmrp1, pfdhfr, and pfdhps polymorphisms were analyzed pretreatment and in recurrent infections. {D}rug susceptibility was determined in fresh baseline isolates by {P}lasmodium lactate dehydrogenase enzyme-linked immunosorbent assay ({ELISA}). {A} majority had 50% inhibitory concentration ({IC}50) estimates (the concentration required for 50% growth inhibition) lower than those of the 3{D}7 reference clone for desethylamodiaquine, lumefantrine, mefloquine, and quinine and was considered to be susceptible, while dihydroartemisinin and pyrimethamine {IC}(50)s were higher. {N}o association was found between susceptibility to the {ACT} compounds and treatment outcome. {S}election was observed for the pfmdr1 {N}86 allele in artemether-lumefantrine recrudescences (recurring infections) (4/7 [57.1%] versus 36/195 [18.5%]), and of the opposite allele, 86{Y}, in artesunate-amodiaquine reinfections (new infections) (20/22 [90.9%] versus 137/195 [70.3%]) compared to baseline infections. {T}he importance of pfmdr1 {N}86 in lumefantrine tolerance was emphasized by its association with elevated lumefantrine {IC}(50)s. {G}enetic linkage between {N}86 and {Y}184 was observed, which together with the low frequency of 1246{Y} may explain regional differences in selection of pfmdr1 loci. {S}election of opposite alleles in artemether-lumefantrine and artesunate-amodiaquine recurrent infections supports the strategy of multiple first-line treatment. {S}urveillance based on clinical, ex vivo, molecular, and pharmacological data is warranted.},
  keywords = {{BENIN}},
  booktitle = {},
  journal = {{A}ntimicrobial {A}gents and {C}hemotherapy},
  volume = {58},
  numero = {1},
  pages = {1--10},
  ISSN = {0066-4804},
  year = {2014},
  DOI = {10.1128/aac.01790-12},
  URL = {https://www.documentation.ird.fr/hor/fdi:010061733},
}