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 fa lciparum in The Gambia in 1995-1996 we measured susceptibility in vivo by quantifying parasitaemia of children with mild malaria on days 4 a nd 8 after treatment, Pretreatment blood samples were used for suscept ibility testing in vitro by the World Health Organization microtest an d the prevalence of the tyrosine (tyr)(86) allele of the Pfmdr1 gene w as 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 antimalaria l treatment. Susceptibility assays Cr vitro were performed an 50 P. fa lciparum isolates obtained rained from eligible children before treatm ent; 36 (72%) were resistant to CQ (greater than or equal to 1.6 mu mo l/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 dihydr oartemisinin 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 i solates. The allele was present in Ii of 22 isolates found to be resis tant to CQ in vitro, but in none of the 9 isolates which mere suscepti ble (Fisher's exact test, P=0.005). All P. falciparum isolates with th e tyr(86) allele were CQ resistant in vitro, but since only half of al l resistant isolates contained the allele, additional explanations for CQ resistance are required.