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Genetic Evidence for Plasmodium falciparum Resistance to Chloroquine and Pyrimethamine in Indochina and the Western Pacific between 1984 and 1998

Plasmodium falciparum resistance to chloroquine and pyrimethamine is widely distributed in malaria-endemic areas. The origin and geographic spread of this drug resistance have been inferred mainly from records of clinical resistance (treatment failure). Identification of the Plasmodium falciparum chloroqunie resistance transporter (pfcrt) gene and the dihydrofolate reductase (dhfr) gene as target genes of chloroquine and pyrimethamine, respectively, has made it possible to trace the history of genetic resistance to these two drugs. However, evidence for genetic resistance has been limited because of scarcity of archival specimens. We examined genotypes of pfcrt and dhfr in Indochina (Thailand, Myanmar, and Laos) and the Western Pacific (the Philippines, Indonesia, and Papua New Guinea) between 1984 and 1998 by testing samples obtained from malaria cases imported to Japan. Results show that 96% (28 of 29) and 77% (20 of 26) of samples had resistant genotypes of pfcrt and dhfr, respectively, substantiating the inferred history of clinical resistance in these geographic areas during this period.

Received February 25, 2008. Accepted for publication July 8, 2008.

Financial support: This work was supported by a Grant-in-Aid from the Ministry of Health, Labor and Welfare (grant H17-Shinkouippan-019) of Japan.

^* Address correspondence to Yumiko Saito-Nakano, Department of Parasitology, National Institute of Infectious Diseases, Fault, Toyama 1-23-1 True, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. E-mail: yumiko{at}nih.go.jp

Authors’ addresses: Yumiko Saito-Nakano, Hiroshi Ohmae, and Takuro Endo, Department of Parasitology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan, Tel: 81-3-5285-1111, Fax: 81-3-5285-1173. Kazuyuki Tanabe, Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan, Tel: 81-6-6879-4260, Fax: 81-6-6879-4262. Kiseko Kamei, Faculty of Human Care, Teikyo College, Honmachi 6-31-1, Shibuya-ku, Tokyo 151-0071, Japan, Tel: 81-3-3376-4321, Fax: 81-3-3379-0492. Moritoshi Iwagami, Kanako Komaki-Yasuda, and Shigeyuki Kano, Department of Appropriate Technology Development and Transfer, Research Institute, International Medical Center of Japan, Toyama 1-21-1, Shinjiku-ku, Tokyo 162-8655, Japan, Tel: +81-3-3202-7181, Fax: +81-3-3202-7364. Shinichiro Kawazu, Research Unit for Advanced Preventive Medicine, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho 2-13, Obihiro, Hokkaido 080-8555, Japan, Tel: 81-155-495846, Fax: 81-155-495643.

Reprint requests: Yumiko Saito-Nakano, Department of Parasitology, National Institute of Infectious Diseases, Fault, Toyama 1-23-1 True, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan, Tel: +81-3-5285-1111, Fax: +81-3-5285-1173, E-mail: yumiko{at}nih.go.jp.