title: West Africa International Centers of Excellence for Malaria Research: Drug Resistance Patterns to Artemether-Lumefantrine in Senegal, Mali, and The Gambia.
abstract: In 2006, artemether-lumefantrine (AL) became the first-line treatment of uncomplicated malaria in Senegal, Mali, and the Gambia. To monitor its efficacy, between August 2011 and November 2014, children with uncomplicated Plasmodium falciparum malaria were treated with AL and followed up for 42 days. A total of 463 subjects were enrolled in three sites (246 in Senegal, 97 in Mali, and 120 in Gambia). No early treatment failure was observed and malaria infection cleared in all patients by day 3. Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) was 100% in Mali, and the Gambia, and 98.8% in Senegal. However, without PCR adjustment, ACPR was 89.4% overall; 91.5% in Mali, 98.8% in Senegal, and 64.3% in the Gambia (the lower value in the Gambia attributed to poor compliance of the full antimalarial course). However, pfmdr1 mutations were prevalent in Senegal and a decrease in parasite sensitivity to artesunate and lumefantrine (as measured by ex vivo drug assay) was observed at all sites. Recrudescent parasites did not show Kelch 13 (K13) mutations and AL remains highly efficacious in these west African sites.
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Baba
authors.initials: B
authors.lastname: Dieye
authors.affiliation: Medical Research Council, The Gambia.
authors.forename: Muna
authors.initials: M
authors.lastname: Affara
authors.affiliation: University of Bamako, Mali.
authors.forename: Lassana
authors.initials: L
authors.lastname: Sangare
authors.affiliation: Medical Research Council, The Gambia.
authors.forename: Fatou
authors.initials: F
authors.lastname: Joof
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Yaye D
authors.initials: YD
authors.lastname: Ndiaye
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Jules F
authors.initials: JF
authors.lastname: Gomis
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Mouhamadou
authors.initials: M
authors.lastname: Ndiaye
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Aminata
authors.initials: A
authors.lastname: Mbaye
authors.affiliation: University of Bamako, Mali.
authors.forename: Mouhamadou
authors.initials: M
authors.lastname: Diakite
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Ngayo
authors.initials: N
authors.lastname: Sy
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Babacar
authors.initials: B
authors.lastname: Mbengue
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Awa B
authors.initials: AB
authors.lastname: Deme
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Rachel
authors.initials: R
authors.lastname: Daniels
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Ambroise D
authors.initials: AD
authors.lastname: Ahouidi
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Tandakha
authors.initials: T
authors.lastname: Dieye
authors.affiliation: Medical Research Council, The Gambia.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Abdullahi
authors.affiliation: University of Bamako, Mali.
authors.forename: Seydou
authors.initials: S
authors.lastname: Doumbia
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Ndiaye
authors.affiliation: University of Bamako, Mali.
authors.forename: Ayouba
authors.initials: A
authors.lastname: Diarra
authors.affiliation: Medical Research Council, The Gambia.
authors.forename: Abubakar
authors.initials: A
authors.lastname: Ismaela
authors.affiliation: University of Bamako, Mali.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Coulibaly
authors.affiliation: Tulane University, New Orleans, Louisiana.
authors.forename: Clint
authors.initials: C
authors.lastname: Welty
authors.affiliation: Medical Research Council, The Gambia.
authors.forename: Alfred Amambua
authors.initials: AA
authors.lastname: Ngwa
authors.affiliation: Tulane University, New Orleans, Louisiana.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shaffer
authors.affiliation: Medical Research Council, The Gambia.|London School of Hygiene and Tropical Medicine, London, United Kingdom.|Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|The Broad Institute of MIT and Harvard, Cambridge, Massachusetts.|Simmons College School of Nursing and Health Sciences, Boston, Massachusetts.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Volkman
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|The Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Dyann F
authors.initials: DF
authors.lastname: Wirth
authors.affiliation: Tulane University, New Orleans, Louisiana.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Krogstad
authors.affiliation: University of Bamako, Mali.
authors.forename: Ousmane
authors.initials: O
authors.lastname: Koita
authors.affiliation: Medical Research Council, The Gambia.
authors.forename: Davis
authors.initials: D
authors.lastname: Nwakanma
authors.affiliation: Cheikh Anta Diop University, Dakar, Senegal. dndiaye@hsph.harvard.edu.
authors.forename: Daouda
authors.initials: D
authors.lastname: Ndiaye
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000962:Antimalarials / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D004983:Ethanolamines / Q000627:therapeutic use*; D005449:Fluorenes / Q000627:therapeutic use*; D005500:Follow-Up Studies; D005714:Gambia; D056426:Genetic Loci; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008302:Mali; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D012675:Senegal; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077549:Artemether; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum