Chemotherapy and drug resistance in malaria.
Over recent years many antimalarial drugs have been rendered useless by the development of resistance by the malaria parasite. New antimalarials are rapidly suffering the same fate as the traditional therapies and yet a biological understanding of the mechanisms of resistance has, until recently, not been described. This review describes recent work which has identified the mechanism of resistance to the dihydrofolate reductase (DHFR) inhibitors as being due to point mutations within the DHFR gene that render the enzyme less susceptible to inhibition by the drugs. The relationship between chloroquine resistance and the recently described multidrug resistance gene is explored and the possibility that this is the main cause of chloroquine resistance by the parasite is discussed. Parasites have developed resistance against many of the quinine-like antimalarials over the past three decades and the possibility that this is linked to the appearance of chloroquine resistance must be considered.
Walter and Eliza Hall Institute of Medical Research. Royal Melbourne Hospital, Victoria, Australia.
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D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D005493:Folic Acid Antagonists; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D010961:Plasmodium / Q000187:drug effects*
D000962:Antimalarials; D005493:Folic Acid Antagonists