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In 1993, Malawi stopped treating patients with chloroquine for Plasmodium falciparum malaria because of a high treatment failure rate (58%). In 1998, the in vitro resistance rate to chloroquine was 3% in the Salima District of Malawi; in 2000, the in vivo resistance rate was 9%. We assayed two genetic mutations implicated in chloroquine resistance (N86Y in the P. falciparum multiple drug resistance gene 1 and K76T in the P. falciparum chloroquine resistance transporter gene) in 82 P. falciparum isolates collected during studies in 1998 and 2000. The prevalence of N86Y remained similar to that in neighboring African countries that continued to use chloroquine. In contrast, the prevalence of K76T was substantially lower than in neighboring countries, decreasing significantly from 17% in 1998 to 2% in 2000 (P < 0.02). However, neither mutation was significantly associated with in vivo or in vitro resistance (P > 0.29). Withdrawal of the use of chloroquine appears to have resulted in the recovery of chloroquine efficacy and a reduction in the prevalence of K76T. However, other polymorphisms are also expected to contribute to resistance.
Received August 7, 2002. Accepted for publication January 3, 2003.
Acknowledgments: We thank the people in the Salima District of Malawi for their kind cooperation, which made the study possible, the staff of the Community Health Sciences Unit (Lilongue, Malawi) and Dr. Yoshinari Moriyama for assistance in the field, and Dr. Takashi Nomura for technical advice.
Financial support: This study was supported in part by a grant-in-aid for research on international medical cooperation from the Ministry of Health, Labor, and Welfare of Japan (Tokyo, Japan), and by grants-in-aid for scientific research (11670254, 13576030, 13770127, and 14021125) from Ministry of Education, Culture, Sports, Science, and Technology of Japan (Tokyo, Japan).
Authors’ addresses: Toshihiro Mita, Akira Kaneko, J. Koji Lum, Bwijo Bwijo, Takahiro Tsukahara, and Takatoshi Kobayakawa, Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Miho Takechi and Innocent L. Zungu, Community Health Sciences Unit, Ministry of Health and Population, Private Bag 65, Lilongwe, Malawi, Telephone: 265-742-035, Fax: 265-742-103. Kazuyuki Tanabe, Laboratory of Biology, Osaka Institute of Technology, 5-16-1, Ohmiya, Asahi-ku, Osaka 535-8585, Japan, Telephone and Fax: 81-6-6954-4385. Anders Björk-man, Department of Medicine, Karolinska Hospital, Karolinska Institutet, 171 76 Stockholm, Sweden. Telephone: 46-8-517-718-77, Fax: 46-8-517-718-06.
Reprint requests: Toshihiro Mita, Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan, Telephone and Fax: 81-3-5269-7422, E-mail: hiro-tm{at}research.twmu.ac.jp
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