pfmdr1 mutations in imported African Plasmodium falciparum isolates.
Amodiaquine/artesunate and artemether/lumefantrine are currently implemented as antimalarial drugs in Africa. In this study, we assessed Plasmodium falciparum pfmdr1 alleles suggesting reduced sensitivity to amodiaquine/artesunate (86Y-184Y-1246Y) and artemether/lumefantrine (184F and 86N-184F-1246D) in 111 African isolates imported to Germany between 1997 and 2005. pfmdr1 86Y-184Y-1246Y occurred less frequently in West African isolates (2.5%) than in East African parasites (45.8%) (P<0.001) and less frequently in infections contracted in countries currently implementing amodiaquine/artesunate (5.7%) compared with countries with an artemether/lumefantrine policy (20.8%) (P=0.03). pfmdr1 184F showed an opposite pattern. pfmdr1 alleles reveal significant differences between West and East Africa, supporting the current implementation of first-line antimalarials.
Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Spandauer Damm 130, 14050 Berlin, Germany.
Anja K
AK
Dippmann
Ulrich
U
Bienzle
Gundel
G
Harms
Frank P
FP
Mockenhaupt
D000349:Africa; D000483:Alleles; D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D004983:Ethanolamines / Q000627:therapeutic use; D005449:Fluorenes / Q000627:therapeutic use; D019450:Genes, MDR / Q000235:genetics; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*
D000655:Amodiaquine; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513498:Mdr1 protein, Plasmodium falciparum