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Population genetic analysis of the negative selection of chloroquine resistant Plasmodium falciparum parasites in the absence of antimalarial pressure

Research Project

Project/Area Number 15590375
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including Sanitary zoology)
Research InstitutionTokyo Women's Medical University

Principal Investigator

MITA Toshihiro  Tokyo Women's Medical University, the Medical Department, Assistant, 医学部, 助手 (80318013)

Co-Investigator(Kenkyū-buntansha) TSUKAHARA Takahiro  Tokyo Women's Medical University, the Medical Department, Assistant, 医学部, 助手 (90328378)
金子 明  東京女子医科大学, 医学部, 助教授 (60169563)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsPlasmodium falciparum / chloroquine / resistance / selection / fitness / pfcrt / pfmdr1 / 薬剤圧 / cost / 淘汰
Research Abstract

In Malawi, the first line drug for treatment of P.falciparum was officially changed from chloroquine to sulfadoxine/pyrimethamine in 1993 because of increasing treatment failure rates that eventually reached 80 %. We previously conducted two drug efficacy surveys in 1998 and 2000 in Salima district in Malawi and found a significant recovery of chloroquine sensitivity both in vitro (3 %) and in vivo (9 %). Concomitant with the recovery of chloroquine sensitivity, the prevalence of the K76T mutation was observed to be substantially lower (9%) than in other African countries where chloroquine use has continued (41-81%). We evidenced that an increased prevalence of the wild type pfcrt haplotype is implicated in the recent recovery of chloroquine sensitivity in Malawi since chloroquine withdrawal. In contrast, we did not see any haplotypes consistent with a K76T→K76 back mutation. Reintroduction of chloroquine as a component drug of combination regimes may be a possible option in places where the complete disappearance of resistant parasites is confirmed.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (4 results)

All 2004 Other

All Journal Article (1 results) Publications (3 results)

  • [Journal Article] Expansion of wild type allele rather than back mutation in pfcrt explains the recent recovery of chloroquine sensitivity of Plasmodium falciparum in Malawi.2004

    • Author(s)
      Mita T, Kaneko A et al.
    • Journal Title

      Mol Biochem Parasitol 135

      Pages: 159-163

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Publications] Mita T, et al.: "Recovery of chlo+roquine sensitivity and low prevalence of pfcrt K76T in Plasmodium falciparum following withdrawal of chlorocguine use in Malawi"Am J Trop Med Hyg. 68(4). 413-415 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mita T, et al.: "Expansion of wild type allele rather than back mutation in Pfcrt explains the recent recovery of chloroquine sensitivity of Plasmodium falciparum in Malawi"Mol Biochem Parasitol. (In print). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bwijo B, Mita T, et al.: "High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi"Acta Trop. 85(3). 363-373 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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