Antimalarial multi-drug resistance in Asia: mechanisms and assessment.
The emergence and spread of drug-resistant parasites poses a major problem for management of Plasmodium falciparum malaria in endemic areas. Nowhere is this more apparent than in southeast Asia, where multi-drug resistance to chloroquine and sulfadoxine-pyrimethamine was exacerbated when mefloquine monotherapy began failing in the 1980s. A better understanding of mechanisms of (multi-) drug resistance is urgently warranted to monitor and guide antimalarial chemotherapy regimens more efficiently. Here we review recent advances on identification of molecular markers that can be employed in predicting in vitro and in vivo resistance in southeast Asia. Examples include amplification of PfMDR1 (P. falciparum multi-drug resistant gene 1) and mefloquine, K76T PfCRT and chloroquine, as well as mutations in the dihydroperoate synthase and dihydrofolate reductase genes and the antifolate class of drugs.
Uhlemann
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AC
Division of Cellular and Molecular Medicine, Centre for Infection, St. George's University of London, Cranmer Terrace, London SW17 ORE, UK.
Krishna
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S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001208:Asia; D002738:Chloroquine / Q000494:pharmacology; D016054:DNA, Protozoan / Q000235:genetics; D004094:Dihydropteroate Synthase / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005493:Folic Acid Antagonists / Q000494:pharmacology; D017125:Genes, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D015767:Mefloquine / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D016054:DNA, Protozoan; D005493:Folic Acid Antagonists; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D015767:Mefloquine