To kill or not to kill, that is the question: cytocidal antimalarial drug resistance

• Cytostatic versus cytocidal drug resistance.
• IC50 versus LD50 drug susceptibility assays.
• Genetics of static versus cidal chloroquine resistance.

Elucidating mechanisms of antimalarial drug resistance accelerates development of improved diagnostics and the design of new, effective malaria therapy. Recently, several studies have emphasized that chloroquine (CQ) resistance (CQR) can be quantified in two very distinct ways, depending on whether sensitivity to the growth inhibitory effects or parasite-kill effects of the drug are being measured. It is now clear that these cytostatic and cytocidal CQR phenotypes are not equivalent, and recent genetic, cell biological, and biophysical evidence suggests how the molecular mechanisms may overlap. These conclusions have important implications for elucidating other drug resistance phenomena and emphasize new concepts that are essential for the development of new drug therapy.