The origins and spread of antimalarial drug resistance: lessons for policy makers.
Understanding the frequency with which new resistance alleles arise and their subsequent patterns of spread is critical to our attempts to manage drug resistance in parasite populations. We review recent molecular evolutionary studies utilizing marker loci situated close to resistance loci on the Plasmodium falciparum genome that have given surprising insights into the origins and spread of drug resistance loci. We discuss possible reasons for the patterns observed, and highlight the implications of these results for resistance management. In particular, we show that many resistance mutations have rather few independent origins. De novo mutation appears to be less important than migration for introducing resistance alleles into parasite populations. Attempts to manage drug resistance will be of limited effectiveness unless this is taken into account.
Anderson
Tim J C
TJ
Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245-0549, USA. tanderso@darwin.sfbr.org
Roper
Cally
C
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000429:Alcohol Oxidoreductases / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D004094:Dihydropteroate Synthase / Q000235:genetics; D018432:Drug Resistance, Multiple; D019450:Genes, MDR / Q000235:genetics; D018503:Genome, Protozoan; D006291:Health Policy; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology / Q000635:transmission; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D000429:Alcohol Oxidoreductases; C056570:dihydroflavanol 4-reductase; D004094:Dihydropteroate Synthase