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Although resistance to chloroquine (CQ) has relegated it from modern chemotherapeutic strategies to treat Plasmodium falciparum malaria, new evidence suggests that higher doses of the drug may exert a different killing mechanism and offers this drug a new lease of life. Whereas the established antimalarial mechanisms of CQ are usually associated with nanomolar levels of the drug, micromolar levels of CQ trigger a distinct cell death pathway involving the permeabilization of the digestive vacuole of the parasite and a release of hydrolytic enzymes. In this paper, we propose that this pathway is a promising antimalarial strategy and suggest that revising the CQ treatment regimen may elevate blood drug levels to trigger this pathway without increasing the incidence of adverse reactions.

Original publication

DOI

10.1016/j.pt.2012.02.005

Type

Journal article

Journal

Trends Parasitol

Publication Date

06/2012

Volume

28

Pages

220 - 224

Keywords

Animals, Antimalarials, Chloroquine, Dose-Response Relationship, Drug, Drug Resistance, Humans, Malaria, Falciparum, Plasmodium falciparum