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MOLECULAR ANALYSIS OF PLASMODIUM FALCIPARUM FROM DRUG TREATMENT FAILURE PATIENTS IN PAPUA NEW GUINEA

A study was conducted in Papua New Guinea to analyze Plasmodium falciparum drug resistance polymorphisms in patients presenting with resistant malaria. One hundred ninety-nine P. falciparum-positive patients were recruited at two sites, Madang and Maprik. Exposure to the 4-aminoquinolines chloroquine and amodiaquine was uniformly high, at 84% overall. However, 59% of these were taken in various combinations of sulfadoxine/pyrimethamine and/or primaquine and/or quinine. Two markers for 4-aminoquinoline resistance, P. falciparum chloroquine resistance transporter 76T and P. falciparum multidrug resistance 1, were fixed in the population and two markers for pyrimethamine resistance, dihydrofolate reductase (dhps) 59R and 108N, were found at moderate to high levels, overall 60% and 75%, respectively. No polymorphisms in dhps associated with sulfadoxine resistance were present. Differences between the two sites are analyzed. The study period encompasses a change in standard malaria treatment policy. These findings stress the need for regular monitoring of the effects of standard drug treatment of uncomplicated malaria in Papua New Guinea.

Received May 27, 2003. Accepted for publication November 4, 2003.

Acknowledgments: We thank the people of East Sepik and Madang who made themselves available for this study. Thanks are also given to Inoni Betuela for assistance in setting up the comparative drug trial from which this data was taken, Eric Kum, Jacob Dago, and Roslyn Kilungen for assistance with patient recruitment, and the many Papua New Guinea Institute of Medical Research staff in Madang and Maprik who provided invaluable assistance with this project.

Financial support: This investigation was supported by the Broken Hill Proprietary Community Trust of Australia. The Papua New Guinea Institute of Medical Research Maprik site receives general support from the Australian Agency for International Development.

Authors’ addresses: Gerard J. Casey, Papua New Guinea Institute of Medical Research, PO Box 378, Madang 511, Papua New Guinea and The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. Meza Ginny, Papua New Guinea Institute of Medical Research, PO Box 378, Madang 511, Papua New Guinea. Merolyn Uranoli, Papua New Guinea Institute of Medical Research, PO Box 400, Maprik, Papua New Guinea. Ivo Mueller and John C. Reeder, Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, Papua New Guinea. Blaise Genton, Swiss Tropical Institute, Socinstrasse 57, 4002 Basel Switzerland. Alan F. Cowman, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.

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