Short report: polymorphisms in the pfcrt and pfmdr1 genes of Plasmodium falciparum and in vitro susceptibility to amodiaquine and desethylamodiaquine. Am J Trop Med Hyg 77

Abstract. The potential role of polymorphisms in the pfcrt and pfmdr1 genes and in vitro susceptibility to amodi-aquine and desethylamodiaquine were explored in 15 chloroquine-resistant Colombian Plasmodium falciparum isolates. Single nucleotide polymorphisms in the pfcrt gene, including a newly reported mutation (S334N), were seen in isolates with decreased susceptibility to amodiaquine and desethylamodiaquine. The lowest susceptibility found to amodiaquine was observed in an isolate carrying a pfcrt and pfmdr1 Dd2-like haplotype, whereas a pfcrt haplotype related to the 7G8 Brazilian strain was found in a Colombian isolate with the lowest susceptibility to desethylamodiaquine. This exploratory study suggests that polymorphisms in the pfcrt and pfmdr1 genes play a role in amodiaquine and desethylamodiaquine resistance and warrants further study. The development and expansion of resistance to the main-stay antimalarials chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) are the major causes for the increased morbidity and mortality of P. falciparum. In response to the increasing resistance, combination therapy, and especially ar-temisinin-based combination therapy (ACT), is now increas-ingly advocated as first-line therapy.1 The hypothesis is that