@article{fdi:010094359, title = {{A}ssessment of ex vivo antimalarial drug efficacy in {A}frican {P}lasmodium falciparum parasite isolates, 2016-2023 : a genotype-phenotype association study}, author = {{R}osado, {J}. and {F}ola, {A}. {A}. and {C}ojean, {S}. and {S}arrasin, {V}. and {C}opp{\'e}e, {R}. and {B}ailly, {J}ustine and {Z}affaroulah, {R}. and {B}ouzayene, {A}. and {C}ic{\'e}ron, {L}. and {H}ouz{\'e}, {L}. and {C}rudale, {R}. and {M}usset, {L}. and {T}hellier, {M}. and {P}radines, {B}. and {C}lain, {J}. and {B}ailey, {J}. {A}. and {H}ouz{\'e}, {S}.}, editor = {}, language = {{ENG}}, abstract = {{B}ackground {G}iven the altered responses to both artemisinins and lumefantrine in {E}astern {A}frica, monitoring antimalarial drug resistance in all {A}frican countries is paramount. {M}ethods {W}e measured the susceptibility to six antimalarials using ex vivo growth inhibition assays ({IC}50) for a total of 805 {P}lasmodium falciparum isolates obtained from travellers returning to {F}rance (2016-2023), mainly from {W}est and {C}entral {A}frica. {I}solates were sequenced using molecular inversion probes ({MIP}s) targeting forty-three genes across the parasite genome, of which nineteen are drug resistance genes. {F}indings {E}x vivo susceptibility of all assessed antimalarial compounds was consistent with their potent activity. {T}he median {IC}50 values for the six drugs were 1.1 n{M} [{IQR}: 0.8-1.7] for {DHA}, 16.7 n{M} [9.9-27.4] for {LMF}, 29.5 n{M} [19.1-45.5] for {MFQ}, 23.4 n{M} [17.1-39.0] for {MDAQ}, 26.7 n{M} [18.0-41.2] for {CQ}, and 18.5 n{M} [15.1-24.3] for {PPQ}. {O}nly four isolates carried a validated pfkelch13 mutation. {M}ultiple mutations in pfcrt and one in pfmdr1 ({A}sn86{T}yr) were significantly associated with altered susceptibility to multiple drugs, and their frequencies decreased over time. {P}fcrt and pfmdr1 mutations altered susceptibility to lumefantrine and mefloquine in an additive manner, with the wild-type haplotype (pfcrt {K}76-pfmdr1 {N}86) exhibiting the lowest susceptibility. {I}nterpretation {O}ur study on {P}. falciparum isolates from {W}est and {C}entral {A}frica indicates a low frequency of molecular markers associated with artemisinin resistance and a modest but significant decrease (1.6-2.3{X}) in the frequency of multidrug resistance markers. {T}hese genotypic changes likely mark parasite adaptation to sustained drug pressure and call for intensifying the monitoring of antimalarial drug resistance in {A}frica.}, keywords = {{A}ntimalarial drug resistance ; {E}x-vivo susceptibility ; {G}rowth inhibition assay ; {G}enotype ; {AFRIQUE} {DE} {L}'{EST}}, booktitle = {}, journal = {{E}biomedicine}, volume = {118}, numero = {}, pages = {105835 [12 p.]}, ISSN = {2352-3964}, year = {2025}, DOI = {10.1016/j.ebiom.2025.105835}, URL = {https://www.documentation.ird.fr/hor/fdi:010094359}, }