Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria

Chloroquine (CQ)-resistant Plasmodium vivax malaria was first reported 12 y ears ago, nearly 30 years after the recognition of CQ-resistant P. falcipar um. Loss of CQ efficacy now poses a severe problem for the prevention and t reatment of both diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene, pfcrt, were shown recently to have a central role in th e CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt ortholog ues of other Plasmodium species are involved in CQR remains an open questio n. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. be rghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and m onkey-adapted lines has shown no association between in vivo CQR and codon mutations in the P. vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum.