RECOVERY OF CHLOROQUINE SENSITIVITY AND LOW PREVALENCE OF THE PLASMODIUM FALCIPARUM CHLOROQUINE RESISTANCE TRANSPORTER GENE MUTATION K76T FOLLOWING THE DISCONTINUANCE OF CHLOROQUINE USE IN MALAWI

TOSHIHIRO MITA Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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AKIRA KANEKO Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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J. KOJI LUM Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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BWIJO BWIJO Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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MIHO TAKECHI Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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INNOCENT L. ZUNGU Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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TAKAHIRO TSUKAHARA Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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KAZUYUKI TANABE Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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TAKATOSHI KOBAYAKAWA Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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ANDERS BJÖRKMAN Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi; Laboratory of Biology, Osaka Institute of Technology, Osaka, Japan; Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

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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.

Author Notes

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@research.twmu.ac.jp
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