| Project/Area Number |
17590380
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
MITA Toshihiro Tokyo Women's Medical University, School of Medicine, Senior Lecturer (80318013)
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Kazuyuki Osaka University, Research Institute for Microbial Diseases, Professor (40047410)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Plasmodium falciparum / drug resistance / pyrimethamine / sulfadoxine / dhfr / microsatellite / polymorphism / evolution / spatial spread |
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| Research Abstract |
Objectives: Resistance to pyrimethamine in Plasmodium falciparum is conferred by mutations in the gene encoding dihydrofolate reductase (dhfr). It is known that dhfr double mutants have evolved independently in multiple geographic areas, whereas the triple mutant prevalent in Africa appears to have originated in Southeast Asia. We investigated the spatio-temporal spread of drug-resistant P. falciparum parasites using samples from various endemic regions.
Results:
1. dhfrtriple mutant parasites (high resistant type) have been prevalent in all studied endemic regions except Melanesia.
2. Indigenous evolution of the triple mutant from the double mutant appears to have occurred in a step-wise manner in Kenya and Ghana or in nearby countries in East and West Africa.
3. The generation of indigenous resistant parasites in Africa (about 1960s) would be earlier than the invasion of resistant parasites into Africa (about ate of the 1970s).
4. dhfr double mutants (medium resistant type) are multiple origins in Africa, whereas single origin in Southeast Asia and Melanesia.
5. In Melanesia, both the Southeast origin and indigenous origin resistant-parasites have been prevalent, both of which coincidently appeared.
6. dhfrsingle mutants (low resistant type) are multiple origins in all studied endemic regions.
7. The addition of chloroquine to pyrimethamine/sulfadoxine could not delay the activity of pyrimethamine/sulfadoxine resistance in Papua New Guinea.
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