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Am. J. Trop. Med. Hyg., 72(2), 2005, pp. 174-181
Copyright © 2005 by The American Society of Tropical Medicine and Hygiene

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MOLECULAR EPIDEMIOLOGY OF PLASMODIUM FALCIPARUM RESISTANCE TO ANTIMALARIAL DRUGS IN INDONESIA

DIN SYAFRUDDIN, PUJI B. S. ASIH, GERARD J. CASEY, JASON MAGUIRE, J. KEVIN BAIRD, HADYA S. NAGESHA, ALAN F. COWMAN, AND JOHN C. REEDER
Eijkman Institute for Molecular Biology, Jakarta, Indonesia; Department of Parasitology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia; United States Naval Medical Research Unit No. 2, Jakarta, Indonesia; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea

The extent of gene polymorphisms associated with resistance to chloroquine and sulfadoxine-pyrimethamine was examined in field isolates of Plasmodium falciparum from Indonesia. Eight malaria-endemic areas, representing a broad region of the western and eastern Indonesian Archipelago were surveyed. Blood from 20–50 patients was collected at each site, DNA was isolated, and the sequences of four different genes (dihydrofolate reductase [dhfr], dihydropteroate synthase [dhps], P. falciparum multidrug resistance 1 [pfmdr1], and P. falciparum chloroquine resistance transporter [pfcrt]) were analyzed using polymerase chain reaction and restriction fragment length polymorphisms to detect polymorphisms previously shown to be associated with resistance. This analysis identified polymorphisms in dhfr at 108-Asn/Thr, 16-Val, and 59-Arg. Polymorphisms in dhps were found less frequently, either 437-Gly alone or paired with 540-Glu. The pfcrt 76-Thr polymorphism was fixed in all parasite populations and pfmdr1 86-Tyr polymorphisms in all populations except in the most eastern regions. The pfmdr1 1042-Asp polymorphism occurred less frequently. These findings indicate that polymorphisms in genes associated with drug resistance in P. falciparum are found across a broad region of Indonesia.

Received January 6, 2004. Accepted for publication July 26, 2004.

Acknowledgments: We thank the officials of the Ministry of Health at the selected areas for providing us with technical support during the malariometric surveys in a the given areas, and Dr. Supargiyono (Gajah Mada University, Yogyakarta, Indonesia) and Dr. P. Hariyanto (Sam Ratulangi University, Manado, Indonesia) for helping us with sample collection. We also thank Professor Sangkot Marzuki (Director of the Eijkman Institute, Jakarta, Indonesia) for his input.

Financial support: This work was supported by the Indonesian and Australian Governments through Bappenas and the Australian Agency for International Development through the Australia Indonesia Medical Research Initiative program. Hadya S. Nagesha was supported by the Wellcome Trust (United Kingdom).

Authors’ addresses: Din Syafruddin, Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia and Department of Parasitology, Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan Km 10, Makassar 90245, Indonesia. Puji B. S. Asih, Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia. Gerard J. Casey, Hadya S. Nagesha, and Alan F. Cowman, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. Jason Maguire and J. Kevin Baird, United States Naval Medical Research Unit No. 2, Jakarta, Indonesia. John C. Reeder, Papua New Guinea Institute of Medical Research, Goroka EHP441, PO Box 60, Papua New Guinea.

Reprint requests: Din Syafruddin, Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta 10430, Indonesia, Telephone: 62-21-3917131, Fax: +62-21-3147982, E-mail: din{at}eijkman.go.id.




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