Molecular markers for drug resistance in malaria: use in treatment, diagnosis and epidemiology.
OBJECTIVE
Malaria and the increasing role of drug resistance as an obstacle to its control are global problems. The identification and implications of molecular markers for antimalarial drug resistance - the subject of this review - are key issues in elucidating and eventually controlling resistance.


RESULTS
Recent achievements include the successful expression of the Plasmodium falciparum chloroquine resistance transporter gene, pfcrt, in yeast, the identification of polymorphisms on the gamma-glutamylcysteine synthetase gene, ggcs, as potential determinants of chloroquine and mefloquine resistance, and the usefulness of a combined Plasmodium falciparum dihydrofolate reductase gene, pfdhfr, 59ARG and Plasmodium falciparum dihydropteroate synthase gene, pfdhps, 540GLU marker in reliably representing resistance to antifolates. Moreover, treatment with sulfadoxine-pyrimethamine in the presence of pfdhfr 108ASP alone delayed parasite clearance and increased gametocytogony without an overt loss of the overall therapeutic efficacy of the drug.


CONCLUSIONS
The use of pfdhfr and pfdhps markers in determining antifolate resistance of Plasmodium falciparum has been consolidated. Similar progress has been made with pfcrt markers for chloroquine resistance, auguring well the operational deployment of molecular techniques. Regarding the molecular basis of resistance to arylaminoalcohols, related drugs, and artemisinin and its derivatives, answers remain elusive, but there are promising new leads.
Wernsdorfer
Walther Helmut
WH
Department of Specific Prophylaxis and Tropical Medicine, Institute of Pathophysiology, University of Vienna, Austria. walther.h.wernsdorfer@univie.ac.at
Noedl
Harald
H
D000962:Antimalarials / Q000627:therapeutic use*; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D019450:Genes, MDR; D006801:Humans; D008288:Malaria / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase