MALARIA CHEMOTHERAPY - RESISTANCE TO QUINOLINE CONTAINING DRUGS IN PLASMODIUM-FALCIPARUM

Resistance to quinoline containing drugs, particularly chloroquine (CQ ), is a major impediment to the successful chemotherapy and prophylaxi s of malaria. CQ-resistant parasites fail to accumulate as much drug a s their sensitive counterparts and two major hypotheses have been prop osed to account for this phenemenon. CQ-resistant parasites are though t to maintain lower intracellular drug levels by means of an active ef flux system, similar to that found in multi-drug resistant cancer cell s, despite major differences in both the genetic and biochemical manif estations of drug resistance in the two cell types. Alternatively, CQ- resistance could be linked to a defective CQ uptake mechanism, possibl y an impaired acidification process in the food vacuole of the resista nt parasite. These two theories are discussed in detail in the followi ng review. The potential of pharmacological intervention to override t hese resistance mechanisms is also discussed.