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NEW HAPLOTYPES OF THE PLASMODIUM FALCIPARUM CHLOROQUINE RESISTANCE TRANSPORTER (PFCRT) GENE AMONG CHLOROQUINE-RESISTANT PARASITE ISOLATES

Mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene were examined to assess their associations with chloroquine resistance in clinical samples from Armopa (Papua) and Papua New Guinea. In Papua, two of the five pfcrt haplotypes found were new: SVIET from Armopa and CVIKT from an isolate in Timika. There was also a strong association (P < 0.0001) between the pfcrt 76T allele and chloroquine resistance in 50 samples. In Papua New Guinea, mutations in the pfcrt gene were observed in 15 isolates with chloroquine minimum inhibitory concentrations (MICs) of 16–64 pmol, while the remaining six isolates, which had a wild-type pfcrt gene at codon 76, had MICs of 2–8 pmol. These observations confirm that mutations at codon 76 in the pfcrt gene are present in both in vivo and in vitro cases of chloroquine resistance, and that detection of the pfcrt 76T allele could predict potential chloroquine treatment failures.

Received September 9, 2002. Accepted for publication December 4, 2002.

Acknowledgments: We thank Alan Cowman for supervision and encouragement during the course of this study; Sangkot Marzuki, Syafruddin, and Graham Brown for their encouragement and support; and Jenny Thompson and Deborah Baldi for providing the D10 parasite. We also thank the Ministry of Health, Republic of Indonesia for assistance in the collection of specimens in Armopa, Papua.

Financial support: This work was supported by the Australian and Indonesian Governments through the Australian Agency for International Development and Bappenas, respectively, and the Global Emerging Infections Surveillance program of the U.S. Department of Defense. Hadya S. Nagesha was supported by a Traveling Fellowship from the Wellcome Research Trust (United Kingdom).

Disclaimer: The views of the authors expressed herein are their own and do not purport or reflect those of the U.S. Navy or the U.S. Department of Defense.

Authors’ addresses: Hadya S. Nagesha and Gerard J. Casey, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, 3050, Australia, Telephone: 62-3-934-52479, Fax: 62-3-934-70852, E-mail: hadya{at}wehi.edu.au and Eijkman Institute for Molecular Biology, Jl Diponegoro 69, Jakarta 10430, Indonesia. Karl H. Rieckmann, Australian Army Malaria Institute, Brisbane, Australia. David J. Fryauff, Budi S. Laksana, Jason D. Maguire, and J. Kevin Baird, United States Naval Medical Research Unit No.2, U.S. Embassy, Jakarta, Indonesia. John C. Reeder, Papua New Guinea Instititute of Medical Research, Goroka, Papua, New Guinea.

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