title: Selection of pfmdr1 and pfcrt alleles in amodiaquine treatment failure in north-western Burkina Faso.
abstract: In 111 children under five years of age and with uncomplicated malaria in Nouna, north-western Burkina Faso, amodiaquine treatment failed in 75% (after PCR-based exclusion of new infections, 32%). In these, we assessed the role of Plasmodium falciparum pfmdr1 and pfcrt polymorphisms in amodiaquine resistance. Except for pfmdr1 1246Y (prevalence, 5%), no P. falciparum allele predicted treatment outcome. Pfcrt 76T as well as pfmdr1 86Y, 86Y-184F-1246D, and 86Y-184Y-1246Y were positively selected in treatment failures, and pfmdr1 86N-184F-1246D negatively. The weak association of pfmdr1/pfcrt alleles with amodiaquine treatment outcome suggests further factors to be involved in the unsatisfactory low efficacy of the drug and limits the usefulness of these markers in this area.
authors.affiliation: Institute of Tropical Medicine and International Health, Charité - University Medical School Berlin, Spandauer Damm 130, 14050 Berlin, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Danquah
authors.forename: Boubacar
authors.initials: B
authors.lastname: Coulibaly
authors.forename: Peter
authors.initials: P
authors.lastname: Meissner
authors.forename: Inga
authors.initials: I
authors.lastname: Petruschke
authors.forename: Olaf
authors.initials: O
authors.lastname: Müller
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D000655:Amodiaquine / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002050:Burkina Faso; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy*; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins / Q000235:genetics*; D012641:Selection, Genetic; D017211:Treatment Failure
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D016054:DNA, Protozoan; 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