The pfmdr1 gene encodes the drug transporter MDR1, which is responsible for drug efflux from the parasite digestive vacuole. Chloroquine (CQ) resistance in Plasmodium falciparum has been associated with mutations at codons 86, 1042 and 1246 of the pfmdr1 gene (Foote et al., 1990). Recently, a mutation at codon 76 of the pfcrt gene was also implicated (Fidock et al., 2000). The world health organisation (WHO) have recommended the use of CoArtem®, a fixed combination of artemether and lumefantrine, as an alternative to CQ. Evidence suggests this may prolong the therapeutic life of existing treatments by limiting the spread of multidrug resistant P. falciparum. We have investigated the expression of pfmdr 1 in the context of response to chloroquine (CQ), artemether (ARM), its primary metabolite, dihydroartemisinin (DHA), and lumefantrine (LUM). A chloroquine sensitive (CQS) strain (D10/D10) and its chloroquine resistant (CQR) mutant (D10/7G8) were used in these analyses. The results obtained are shown in Table1.

*P- values for Mann-Whitney test for D10/D10 are not equal to D10/7G8. P< 0.05. Results are expressed as median with range.

Table 1. Median IC₅₀ values for D10/D10 and D10/7G8 P. falciparum malaria parasite strains using chloroquine, artemether, dihydroartemisinin and lumefantrine

These data illustrate that replacement of the 'D10 allele' in the pfmdr1 with the mutant '7G8 allele' (Tyr184Phe; Ser1034Cys; Asn1042Asp, and Asp1246Tyr) in the CQS had no significant effect on drug sensitivity for CQ, ARM, and DHA, respectively. However, LUM showed a significant decrease in its median IC₅₀, indicating that allelic change in pfmdr1 contributes to the increased susceptibility of this strain to the drug.

Fidock et al., Mol Cell. 2000 6, 861-71.
Foote et al., Nature.1990 345, 255-8.