Journal
SCIENCE
Volume 298, Issue 5591, Pages 210-213Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1074045
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Funding
- NIAID NIH HHS [R01 AI050234-03, R01 AI050234, R01 AI50234, R37 AI050234] Funding Source: Medline
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Plasmodium falciparum chloroquine resistance is 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 causal relationship has remained elusive and most models have posited 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.
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