Drug resistance in Plasmodium falciparum malaria.
Four classes of drugs are reviewed: blood schizontocides acting only on the hemoglobin-digesting blood stages, the antifolates which attack tetrahydrofolate synthesis in all the growing stages, antimitochondrials affecting synthesis and electron transport, and 8-aminoquinolines which interfere with redox processes. Drug efflux via a multidrug resistance membrane protein, and the production of a protein competing with the drug for the target hemin are thought to be responsible for resistance to blood schizontocides. Structural changes in target enzymes are responsible for easily-developed resistance to antifolates and antimitochondrials. The judicious use of drug combinations can help to avoid development of resistance and combat resistant infections, but new drugs are urgently needed.
Warhurst
D C
DC
London School of Hygiene and Tropical Medicine, UK.
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000502:physiology*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D012680:Sensitivity and Specificity
D000962:Antimalarials