Molecular mechanisms of resistance in antimalarial chemotherapy: the unmet challenge.
The enormous public health problem posed by malaria has been substantially worsened in recent years by the emergence and worldwide spread of drug-resistant parasites. The utility of two major therapies, chloroquine and the synergistic combination of pyrimethamine/sulfadoxine, is now seriously compromised. Although several genetic mechanisms have been described, the major source of drug resistance appears to be point mutations in protein target genes. Clinically significant resistance to these agents requires the accumulation of multiple mutations, which genetic studies of parasite populations suggest arise focally and sweep through the population. Efforts to circumvent resistance range from the use of combination therapy with existing agents to laboratory studies directed toward discovering novel targets and therapies.
Arav-Boger
Ravit
R
Division of Infectious Diseases, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. boger@jhmi.edu
Shapiro
Theresa A
TA
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D000962:Antimalarials