In vitro antimalarial susceptibility profile and prcrt/pfmdr-1 genotypes of Plasmodium falciparum field isolates from Malawi.
We measured in vitro antimalarial drug susceptibility of 84 Plasmodium falciparum field isolates from Blantyre, Southern Malawi, using the WHO microtest and the lactate dehydrogenase assay. We also genotyped these isolates to investigate whether variation in their absolute drug sensitivity is associated with specific sets of pfcrt and pfmdr-1 mutations harbored by parasites. Our results show that nearly a decade after the withdrawal of chloroquine (CQ) as a first-line antimalarial in Malawi, most isolates are now sensitive to CQ and none is CQ-resistant as predicted by their drug sensitivity phenotype and pfcrt genotype. We also found that these isolates are uniformly sensitive to a range of quinoline-based antimalarials and artemisinin derivatives. These findings reinforce previous reports about a reduction in the proportion of CQ-resistant parasites after the withdrawal of CQ in 1993 and pave the way for reassessing the clinical usefulness of CQ, artemisinins and other quinoline-based antimalarials in Malawi.
Nkhoma
Standwell
S
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Malawi. snkhoma@mlw.medcol.mw
Molyneux
Malcolm
M
Ward
Stephen
S
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D020128:Inhibitory Concentration 50; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D008295:Malawi / Q000453:epidemiology; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics*; D018709:Statistics, Nonparametric
D000962:Antimalarials; D016054:DNA, Protozoan; D007770:L-Lactate Dehydrogenase; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum