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Population genetic analysis of dynamism of malaria drug resistance in Papua New Guinea

Research Project

Project/Area Number 22406012
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Parasitology (including Sanitary zoology)
Research InstitutionJuntendo University (2012-2013)
Tokyo Women's Medical University (2010-2011)

Principal Investigator

MITA Toshihiro  順天堂大学, 医学(系)研究科(研究院), 教授 (80318013)

Co-Investigator(Kenkyū-buntansha) TANABE Kazuyuki  大阪大学微生物学研究所, 招聘教授 (40047410)
TSUKAHARA Takahiro  東京女子医科大学, 医学部, 講師 (90328378)
HAYAKAWA Toshiyuki  九州大学, 基幹教育院, 准教授 (80418681)
Project Period (FY) 2010-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords薬剤耐性 / 熱帯熱マラリア原虫 / クロロキン / ピリメサミン / ファンシダール / アルテミシニン / 集団遺伝 / パプアニューギニア / 薬剤使用量 / マラリア / 熱帯熱マラリア / pfcrt / dhfr / dhps / Papua New Guinea / 集団構造 / serca
Research Abstract

This study aimed to elucidate the dynamism of drug-resistant Plasmodium falciparum in Papua New Guinea where pyrimethamine and sulfadoxine were added to the first-treatment policy of malaria in 2000. We found significant selection of resistant-parasites to both antimalarial drugs. Emergence of resistance to pyrimethamine preceded sulfadoxine. Until 2011, all parasites harbored the resistant-related multi-locus mutations for chloroquine and pyrimethamine. Nearly 80% of parasites harbored resistant-related mutations for sulfadoxine, which migrated from Southeast Asia. Parasites showing resistance to artemisinin was not identified in the study period. This may be partly explained the fact that artemisinin combination therapy has been implemented in our study area around 2012 despite it was officially introduced in 2010.

Report

(5 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (50 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (24 results) (of which Peer Reviewed: 17 results) Presentation (23 results) (of which Invited: 5 results) Book (3 results)

  • [Journal Article] Ordered accumulation of mutations conferring resistance to sulfadoxine-pyrimethamine in the Plasmodium falciparum parasite2014

    • Author(s)
      Mita, T., Ohashi, J., Venkatesan, M., Marma, A. S., Nakamura, M., Plowe, C. V., & Tanabe, K
    • Journal Title

      J Infect Dis

      Volume: 209 Pages: 130-139

    • Related Report
      2013 Final Research Report
  • [Journal Article] Ordered accumulation of mutations conferring resistance to sulfadoxine-pyrimethamine in the Plasmodium falciparum parasite.2014

    • Author(s)
      Mita T*, Ohashi J, Venkatesan M, Marma AS., Plowe, CV, Tanabe, K.
    • Journal Title

      J Infect Dis

      Volume: 209 Issue: 1 Pages: 130-139

    • DOI

      10.1093/infdis/jit415

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasmodium falciparum: Genetic diversity and complexity of infections in an isolated village in western Thailand.2014

    • Author(s)
      Tanabe K, Zollnerc G, Vaughanc JA, Sattabongkotc J, Khuntiratc B, Honma H, Mita T, Tsuboi T, Coleman R.
    • Journal Title

      Parasitol Int.

      Volume: 未定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Rodent Malaria Parasites with a High Mutation Rate by destructing Proofreading activity of DNA Polymerase.2014

    • Author(s)
      Honma H, Hirai M, Nakamura S, Hakimi H, Kawazu S, Palacpac N, Hisaeda H, Matsuoka H, Kawai S, Endo H, Yssunaga T, Ohashi J, Mita T, Horii T, Furusawa M, Tanabe K.
    • Journal Title

      DNA Res

      Volume: 未定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasmodium falciparum mitochondrial genetic diversity exhibits isolation-by-distance patterns supporting a sub-Saharan African origin2013

    • Author(s)
      Tanabe K, Jombart T, Horibe S, Palacpac N, Honma H, Tachibana S, Nakamura M, Horii T, Kishinod H, Mita T
    • Journal Title

      Mitochondrion

      Volume: 13 Pages: 630-636

    • Related Report
      2013 Final Research Report
  • [Journal Article] Plasmodium falciparum mitochondrial genetic diversity exhibits isolation-by-distance patterns supporting a sub-Saharan African origin.2013

    • Author(s)
      Tanabe K, Jombart T, Horibe S, Palacpac N, Honma H, Tachibana S, Nakamura M, Horii T, Kishinod H, Mita T*.
    • Journal Title

      Mitochondrion

      Volume: 13 Issue: 6 Pages: 630-636

    • DOI

      10.1016/j.mito.2013.08.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Travellers as Sentinels: Assaying the worldwide distribution of polymorphisms associated with ACT resistance in P. falciparum using malaria cases imported into Scotland.2013

    • Author(s)
      Hunja CW, Unger H, Ferreira P, Lumsden R, Morris R, Aman R, Alexander C, Mita T* & Culleton R.
    • Journal Title

      Int J Parasitol

      Volume: 43 Issue: 11 Pages: 885-889

    • DOI

      10.1016/j.ijpara.2013.07.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A comprehensive survey of polymorphisms conferring anti-malarial resistance in Plasmodium falciparum across Pakistan.2013

    • Author(s)
      Khattak A, Vankatesan M, Jacob C, Artimovich E, Nadeem M, Nighat F, Hombhanje F, Mita T, Malik S, Plowe C.
    • Journal Title

      Malaria J

      Volume: 12 Issue: 1 Pages: 300-300

    • DOI

      10.1186/1475-2875-12-300

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Within-population genetic diversity of Plasmodium falciparum vaccine candidate antigens reveals geographic distance from a Central sub-Saharan African origin.2013

    • Author(s)
      Tanabe K., Mita T., Palacpac N., Arisue N., Tougan T., Kawai S.,Jombart T., Kobayashi F., Horii T.
    • Journal Title

      Vaccine

      Volume: 31 Issue: 9 Pages: 1334-9

    • DOI

      10.1016/j.vaccine.2012.12.039

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evolution of Plasmodium falciparum drug resistance : implications for the development and containment of artemisinin resistance2012

    • Author(s)
      Mita, T., Tanabe,K
    • Journal Title

      Jpn J Infect Dis

      Volume: 65 Pages: 465-445

    • NAID

      130002588753

    • Related Report
      2013 Final Research Report
  • [Journal Article] A large scale survey for novel genotypes of the Plasmodium falciparum chloroquine-resistant p fcrt gene2012

    • Author(s)
      Takahashi, N., Tanabe, K., Tsukahara, T., Dzodzomenyo, M.,Dysoley, L., Khamlome, B., Sattabongkot, J., Nakamura, M., Sakurai, M., Kobayashi, J., Endo, H., Hombhanje, F., Tsuboi, T., Mita, T
    • Journal Title

      Malaria J

      Volume: 11 Pages: 92-92

    • Related Report
      2013 Final Research Report
  • [Journal Article] Large-scale survey for novel genotypes of Plasmodium falciparum chloroquine-resistance gene pfcrt2012

    • Author(s)
      Takahashi N, Tanabe K, Tsukahara T, Dzodzomenyo M, Dysoley L, Khamlome B, Sattabongkot J, Nakamura M, Sakurai M, Kobayashi J, Kaneko A, Endo H, Hombhanje F, Tsuboi T, Mita T
    • Journal Title

      Malaria Journal

      Volume: 11 Issue: 1 Pages: 92-92

    • DOI

      10.1186/1475-2875-11-92

    • NAID

      120006985384

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA52012

    • Author(s)
      Tanabe K, Arisue N, 他12名
    • Journal Title

      Vaccine

      Volume: 30 Issue: 9 Pages: 1583-1593

    • DOI

      10.1016/j.vaccine.2011.12.124

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.2012

    • Author(s)
      Tachibana S, Mita T.
    • Journal Title

      Nature Genet

      Volume: 44 Issue: 9 Pages: 1051-5

    • DOI

      10.1038/ng.2375

    • NAID

      120006985529

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evolution of <i>Plasmodium falciparum</i> drug resistance: implications for the development and containment of artemisinin resistance2012

    • Author(s)
      Mita, T. Tanabe K
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 65 Issue: 6 Pages: 465-475

    • DOI

      10.7883/yoken.65.465

    • NAID

      130002588753

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations2011

    • Author(s)
      Mita, T, Venkatesan, M, Ohashi, J, Culleton, R, Takahashi, N, Tsukahara, T, Ndounga, M, Dysoley, L, Endo, H, Hombhanje, F, Ferreira, M, Plowe, CV, Tanabe, K
    • Journal Title

      J Infect Dis

      Volume: 204 Pages: 1980-1988

    • Related Report
      2013 Final Research Report
  • [Journal Article] Spontaneous mutations in the Plasmodium falciparum sarco/endoplasmic reticulum Ca2+-ATPase (PfATP6) gene among wide geographical parasite populations unexposed to artemisinin-based combination therapies2011

    • Author(s)
      Tanabe, K, Zakeri, S, Palacpac M, Afsharpad, M, Randrianarivelojosia M, Kaneko, A, Marma, AS, Horii, T, Mita, T
    • Journal Title

      Antimicrob Agents Chemother

      Volume: 55 Pages: 94-100

    • Related Report
      2013 Final Research Report
  • [Journal Article] Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations2011

    • Author(s)
      Mita, T, Tanabe K
    • Journal Title

      J Infect Dis

      Volume: 204 Issue: 12 Pages: 1980-8

    • DOI

      10.1093/infdis/jir664

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of pyrimethamine- and chloroquine-resistant Plasmodium falciparum in Africa between 1984 and 1998 : genotyping of archive blood samples2011

    • Author(s)
      Saito-Nakano, Y., Mita, T.
    • Journal Title

      Malaria J

      Volume: 10 Issue: 1 Pages: 388-388

    • DOI

      10.1186/1475-2875-10-388

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent increase of genetic diversity in Plasmodium vivax population in the Republic of K2011

    • Author(s)
      Honma H., Mita T.
    • Journal Title

      Malaria J

      Volume: 10 Issue: 1 Pages: 257-257

    • DOI

      10.1186/1475-2875-10-257

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Worldwide sequence conservation of transmission-blocking vaccine candidate Pvs230 in Plasmodium vivax2011

    • Author(s)
      Doi, M, Mita, T
    • Journal Title

      Vaccine

      Volume: 29 Issue: 26 Pages: 4308-15

    • DOI

      10.1016/j.vaccine.2011.04.028

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spontaneous mutations in the Plasmodium falciparum sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (PfATP6) gene among geographically widespread parasite populations unexposed to artemisinin-based combination therapies.2011

    • Author(s)
      Tanabe K, Zakeri S, Palacpac NM, Afsharpad M, Randrianarivelojosia M, Kaneko A, Marma AS, Horii T, Mita T.
    • Journal Title

      Antimicrob Agents Chemother

      Volume: 55 Pages: 94-100

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Rodent Malaria Parasites with a High Mutation Rate by destructing Proofreading activity of DNA Polymerase

    • Author(s)
      Honma H, Hirai M, Nakamura S, Hakimi H, Kawazu S, Palacpac N, Hisaeda H, Matsuoka H, Kawai S, Endo H, Yssunaga T, Ohashi J, Mita T, Horii T, Furusawa M, Tanabe K
    • Journal Title

      DNA Res

      Volume: (In press)

    • Related Report
      2013 Final Research Report
  • [Journal Article] A large scale survey for novel genotypes of the Plasmodium falciparum chloroquine-resistant pfcrt gene

    • Author(s)
      Takahashi, N., Mita, T.
    • Journal Title

      Malaria J

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Interrelated paths for accumulation of mutations in the two malaria parasite genes for antifolate resistance : inference from population-genetics based approach2013

    • Author(s)
      Mita T
    • Organizer
      Biochemistry toward malaria control (Symposium), 第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Interrelated paths for accumulation of mutations in the two malaria parasite genes for antifolate resistance: inference from population-genetics based approach.2013

    • Author(s)
      Mita T.
    • Organizer
      Biochemistry toward malaria control (Symposium), 第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Evolution of Plasmodium falciparum Pyrimethamine/Sufadoxine Resistance.2013

    • Author(s)
      Mita T, Ohashi J, Tanabe K.
    • Organizer
      Forum Cheju 16
    • Place of Presentation
      Seoul, Korea, Yeongon Campus Seoul National University.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] アーカイブ血液スメア標本による熱帯熱マラリア原虫sulfadoxine/pyrimethamine耐性遺伝子型の同定2013

    • Author(s)
      中野由美子、中曽根英子、美田敏宏
    • Organizer
      第82回日本寄生虫学会大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Spirometra erinaceieuropaeiミトコンドリア呼吸鎖の生化学的解析.2013

    • Author(s)
      高宮信三郎、中村謙、福田孝一、美田敏宏
    • Organizer
      第82回日本寄生虫学会大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Independence from glucose-based intermediary and energy metabolisms in Diplonema papillatum, a close relative o f trypanosomatids.2013

    • Author(s)
      Jorge Morales、Mita Toshihiro,
    • Organizer
      第82回日本寄生虫学会大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Sulfadoxine/Pyrimethamine耐性をもたらす熱帯熱マラリア原虫dhfr/dhps遺伝子型はどのように進化していくのか2012

    • Author(s)
      美田敏宏
    • Organizer
      第81回日本寄生虫学会大会
    • Place of Presentation
      兵庫医科大学
    • Year and Date
      2012-03-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 高頻度突然変異発生マラリア原虫(マラリアミューテーター)のゲノムワイド解析と薬剤耐性研究への応用2012

    • Author(s)
      本間一、美田敏宏
    • Organizer
      第81回日本寄生虫学会大会
    • Place of Presentation
      兵庫医科大学
    • Year and Date
      2012-03-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 超加速変異型ネズミマラリア原虫の創出と、その順遺伝学への応用2012

    • Author(s)
      平井誠、美田敏宏
    • Organizer
      第81回日本寄生虫学会大会
    • Place of Presentation
      兵庫医科大学
    • Year and Date
      2012-03-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prescribers? use of malaria rapid diagnostic tests and adherence to test results in high and low malaria transmission areas in Madagascar2012

    • Author(s)
      塚原高広、美田敏宏
    • Organizer
      第81回日本寄生虫学会大会
    • Place of Presentation
      兵庫医科大学
    • Year and Date
      2012-03-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 薬剤耐性熱帯熱マラリア原虫の急速な選択は原虫集団の遺伝的多様性を低下させうるのか-パプアニューギニアにおける検討2012

    • Author(s)
      美田敏宏
    • Organizer
      第53回日本熱帯医学会大会
    • Place of Presentation
      帯広
    • Related Report
      2012 Annual Research Report
  • [Presentation] 薬剤耐性熱帯熱マラリア原虫の急速な選択は原虫集団の遺伝的多様性を低下させうるのか.2012

    • Author(s)
      美田敏宏
    • Organizer
      第72回日本寄生虫学会東日本支部大会, 第10回分子寄生虫マラリア研究フォーラム合同大会
    • Place of Presentation
      群馬
    • Related Report
      2012 Annual Research Report
  • [Presentation] Impact of an introduction of antimalarials combination therapy on the Plasmodium falciparum population in Papua New Guinea2011

    • Author(s)
      Mita T
    • Organizer
      Nagasaki Symposium on Malaria Biology 2011
    • Place of Presentation
      長崎大学(招待講演)
    • Year and Date
      2011-11-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] パプアニューギニアにおける抗マラリア薬の併用療法による熱帯熱マラリア原虫薬剤耐性遺伝子頻度の上昇2011

    • Author(s)
      美田敏宏
    • Organizer
      第52回日本熱帯医学会大会第26回日本国際保健医療学会学術大会合同大会
    • Place of Presentation
      東京大学
    • Year and Date
      2011-11-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] パプアニューギニア村落におけるマラリア早期治療を阻む因子2011

    • Author(s)
      塚原高広, 美田敏宏
    • Organizer
      第52回日本熱帯医学会大会第26回日本国際保健医療学会学術大会合同大会
    • Place of Presentation
      東京大学
    • Year and Date
      2011-11-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] 進化する薬剤耐性マラリア原虫:研究と対策の最前線2011

    • Author(s)
      美田敏宏
    • Organizer
      第71回日本寄生虫学会東日本支部大会
    • Place of Presentation
      杏林大学(招待講演)
    • Year and Date
      2011-10-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] アジア、太平洋、アフリカ地域におけるクロロキン耐性熱帯熱マラリア原虫の起源および拡散様式の検討2011

    • Author(s)
      高橋延之, 美田敏宏
    • Organizer
      第71回日本寄生虫学会東日本支部大会
    • Place of Presentation
      杏林大学
    • Year and Date
      2011-10-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] 一次医療が普及したパプアニューギニア村落部におけるマラリア適正治療の現状2011

    • Author(s)
      塚原高広, 美田敏宏
    • Organizer
      第71回日本寄生虫学会東日本支部大会
    • Place of Presentation
      杏林大学
    • Year and Date
      2011-10-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations2011

    • Author(s)
      Mita T
    • Organizer
      International Union of Microbiological Societies 2011 Congress
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2011-09-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] 熱帯マラリア原虫の進化と地理的拡散,「病原体と薬剤耐性-現状をどう捉え、どう向き合うか-」2011

    • Author(s)
      美田敏宏
    • Organizer
      第21回感染研シンポジウム
    • Place of Presentation
      国立感染症研究所(招待講演)
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] 熱帯マラリア原虫の進化と地理的拡散2011

    • Author(s)
      美田敏宏
    • Organizer
      第21回感染研シンポジウム「病原体と薬剤耐性-現状をどう捉え、どう向き合うか-」
    • Place of Presentation
      国立感染症研究所,東京
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 熱帯熱マラリア原虫はどのような順番でdhps遺伝子に変異を蓄積していくか2010

    • Author(s)
      美田敏宏, 塚原高広, 高橋延之, 遠藤弘良, 田邉和桁
    • Organizer
      第79回日本寄生虫学会総会
    • Place of Presentation
      旭川
    • Related Report
      2010 Annual Research Report
  • [Presentation] Evolution of Plasmodium falciparum Pyrimethamine/Sufadoxine Resistance

    • Author(s)
      Mita T, Ohashi J, Tanabe K
    • Organizer
      Forum Cheju 16
    • Place of Presentation
      Seoul, Korea, Yeongon Campus Seoul National University
    • Related Report
      2013 Final Research Report
    • Invited
  • [Book] マラリア/バベシア.今日の治療指針20142014

    • Author(s)
      美田敏宏
    • Related Report
      2013 Final Research Report
  • [Book] 今日の治療指針2014 マラリア/バベシア256-72014

    • Author(s)
      美田敏宏
    • Total Pages
      2014
    • Publisher
      医学書院
    • Related Report
      2013 Annual Research Report
  • [Book] 熱帯性脾腫.症候群ハンドブック2011

    • Author(s)
      遠藤弘良、美田敏宏
    • Total Pages
      274
    • Related Report
      2013 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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