Evidence for Different Mechanisms of Chloroquine Resistance in 2 Plasmodium Species That Cause Human Malaria

Authors

Takashi Nomura, Kyoto University
Jane M-R. Carlton, National Institutes of Health
J. Kevin Baird, U.S. Naval Medical Research Unit # 2Follow
Hernando A. del Portillo, Universidade de Sao Paulo
David J. Fryauff, U.S. Naval Medical Research CenterFollow
Dharmendar Rathore, National Institutes of Health
David A. Fidock, Albert Einstein College of Medicine
Xin-zhuan Su, National Institutes of Health
William E. Collins, Centers for Disease Control and Prevention
Thomas F. McCutchan, National Institutes of Health
John C. Wootton, National Institutes of Health
Thomas E. Wellems, National Institutes of HealthFollow

Date of this Version

2001

Citation

Published in The Journal of Infectious Diseases (2001)183: 1653–61

Abstract

Chloroquine (CQ)–resistant Plasmodium vivax malaria was first reported 12 years ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of CQ efficacy now poses a severe problem for the prevention and treatment 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 the CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species are involved in CQR remains an open question. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and monkey-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.