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

Authors

• Takashi Nomura, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
• Jane M-R Carlton, Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda
• J. Kevin Baird, US Naval Medical Research Unit No. 2, Jakarta, IndonesiaFollow
• Hernando A. del Portillo, Departamento de Parasitologia, Universidade de São Paulo, São Paulo, Brazil
• David J. Fryauff, Malaria Program, Naval Medical Research Center, Silver Spring, MarylandFollow
• Dharmendar Rathore, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
• David A. Fidock, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
• Xin-zhuan Su, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
• William E. Collins, Centers for Disease Control and Prevention, Chamblee, Georgia
• Thomas F. McCutchan, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
• John C. Wootton, Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda
• Thomas E. Wellems, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases

Date of this Version

2001

Citation

The Journal of Infectious Diseases 2001;183:1653–61

Comments

U.S. Government Works

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.