@article{fdi:010088829, title = {{E}volution and spread of {P}lasmodium falciparum mutations associated with resistance to sulfadoxine-pyrimethamine in central {A}frica : a cross-sectional study}, author = {{G}u{\'e}mas, {E}. and {C}opp{\'e}e, {R}. and {M}{\'e}nard, {S}. and du {M}anoir, {M}. and {N}sango, {S}. and {M}vumbi, {D}. {M}. and {N}akoune, {E}. and {M}oukoko, {C}. {E}. {E}. and {A}kotet, {M}. {K}. {B}. and {M}irabeau, {T}. {Y}. and {M}anguin, {S}ylvie and {Y}obi, {D}. {M}. and {A}kiana, {J}. and {K}ouna, {L}. {C}. and {M}boumba, {D}. {P}. {M}. and {V}oumbo-{M}atoumona, {D}. {F}. and {O}tam, {A}. {L}. and {R}ubbo, {P}. {A}. and {L}ombart, {J}. {P}. and {K}wanai, {E}. and {C}ohen, {O}. and {I}riart, {X}. and {A}yong, {L}. and {L}ekana-{D}ouki, {J}. {B}. and {A}riey, {F}. and {B}erry, {A}.}, editor = {}, language = {{ENG}}, abstract = {{B}ackground {E}fficacy of sulfadoxine-pyrimethamine, the malaria chemoprophylaxis used in pregnant women, and in children when combined with amodiaquine, is threatened by the accumulation of mutations in the {P}lasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes. {D}ata on the prevalence of resistant alleles in central {A}frica and the new pfdhps {I}431{V} mutation, particularly associated with other mutations to form the pfdhps vag{K}gs allele, are scarce. {W}e explored the frequency and geographical distribution of pfdhps and pfdhfr mutations in central {A}frica in 2014-18, and assessed the evolutionary origin of the vag{K}gs allele.{M}ethods {S}amples were collected at 18 health-care centres in seven countries ({A}ngola, {C}ameroon, {C}entral {A}frican {R}epublic, {D}emocratic {R}epublic of the {C}ongo, {G}abon, {N}igeria, and {R}epublic of the {C}ongo) from patients who showed possible symptoms of malaria between {M}arch 1, 2014, and {O}ct 31, 2018. {S}amples that were positive for {P} falciparum were transported to a laboratory in {T}oulouse, {F}rance, and genotyped. {T}he frequency of pfdhfr and pfdhps mutations was studied in 1749 samples. {M}icrosatellites in pfdhps flanking regions and whole-genome analysis compared with parasite genomes from the data-sharing network {M}alaria{GEN} were performed on samples carrying the vag{K}gs allele.{F}indings {M}apping of the prevalence of single nucleotide polymorphisms and corresponding alleles of pfdhfr and pfdhps showed a substantial spread of alleles associated with sulfadoxine-pyrimethamine resistance in central {A}frica during the 2014-18 period, especially an increase going west to east in pfdhps alleles carrying the {K}540{E} and {A}581{G} mutations. {A} high prevalence of the pfdhps {I}431{V} mutation was observed in {C}ameroon (exceeding 50% in the northern region) and {N}igeria. {G}enomic analysis showed a recent {A}frican emergence and a clonal expansion of the most frequent pfdhps vag{K}gs allele.{I}nterpretation {R}educed sulfadoxine-pyrimethamine efficacy due to increased resistance is a worrying situation, especially because the malaria transmission level is high in central {A}frica. {A}lthough the resistance phenotype remains to be confirmed, the emergence and spread of the vag{K}gs allele in west and central {A}frica could challenge the use of sulfadoxine-pyrimethamine.{F}unding {T}oulouse {I}nstitute for {I}nfectious and {I}nflammatory {D}iseases.{C}opyright (c) 2023 {T}he {A}uthor(s). {P}ublished by {E}lsevier {L}td. {T}his is an {O}pen {A}ccess article under the {CC} {BY}-{NC}-{ND} 4.0 license.}, keywords = {{CAMEROUN} ; {CONGO} ; {GABON} ; {ANGOLA} ; {REPUBLIQUE} {DEMOCRATIQUE} {DU} {CONGO} ; {CENTRAFRICAINE} {REPUBLIQUE}}, booktitle = {}, journal = {{L}ancet {M}icrobe}, volume = {4}, numero = {12}, pages = {{E}983--{E}993 [11 p.]}, year = {2023}, DOI = {10.1016/s2666-5247(23)00211-2}, URL = {https://www.documentation.ird.fr/hor/fdi:010088829}, }