Polymorphism of the Pfmdr1 gene and chloroquine resistance in Plasmodium falciparum in The Gambia

To assess the level of resistance to chloroquine (CQ) of Plasmodium falciparum in The Gambia in 1995-1996 we measured susceptibility in vivo by quantifying parasitaemia of children with mild malaria on days 4 and 8 after treatment, Pretreatment blood samples were used for susceptibility testing in vitro by the World Health Organization microtest and the prevalence of the tyrosine (tyr)(86) allele of the Pfmdr1 gene was assessed by the polymerase chain reaction and restriction fragment length polymorphism analysis. Seven of 42 children (17%) treated with CQ remained parasitaemic on day 4 and required a change of antimalarial treatment. Susceptibility assays Cr vitro were performed an 50 P. falciparum isolates obtained rained from eligible children before treatment; 36 (72%) were resistant to CQ (greater than or equal to 1.6 mu mol/L). The median minimum inhibitory concentration (MIC) of artemether was 3.38 nmol/L (range 0.42-13.51 nmol/L) and the median MIC of dihydroartemisinin was 0.88 nmol/L (range 0.22-14.04 nmol/L). Susceptibility in vitro to CQ and the Pfmdr1 genotype were determined for 31 fresh isolates. The allele was present in Ii of 22 isolates found to be resistant to CQ in vitro, but in none of the 9 isolates which mere susceptible (Fisher's exact test, P=0.005). All P. falciparum isolates with the tyr(86) allele were CQ resistant in vitro, but since only half of all resistant isolates contained the allele, additional explanations for CQ resistance are required.