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- Title
Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations.
- Authors
Sidhu, Amar Bir Singh; Verdier-Pinard, Dominik; Fidock, David A
- Abstract
Plasmodium falciparum chloroquine resistance is a major cause of worldwide increases in malaria mortality and morbidity. Recent laboratory and clinical studies have associated chloroquine resistance with point mutations in the gene pfcrt. However, direct proof of a causal relationship has remained elusive and most models have posited a multigenic basis of resistance. Here, we provide conclusive evidence that mutant haplotypes of the pfcrt gene product of Asian, African, or South American origin confer chloroquine resistance with characteristic verapamil reversibility and reduced chloroquine accumulation. pfcrt mutations increased susceptibility to artemisinin and quinine and minimally affected amodiaquine activity; hence, these antimalarials warrant further investigation as agents to control chloroquine-resistant falciparum malaria.
- Publication
Science (New York, N.Y.), 2002, Vol 298, Issue 5591, p210
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1074045