Development of predictive model for future prevalence of antimalarial-resistant gene using microsatellite polymorphism

• Project/Area Number: 23590498
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including Sanitary zoology)
• Research Institution: Juntendo University (2012-2014); Tokyo Women's Medical University (2011)
• Principal Investigator: Mita Toshihiro 順天堂大学, 医学(系)研究科(研究院), 教授 (80318013)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: マラリア / 薬剤耐性 / 耐性遺伝子 / 予測モデル / シミュレーション / 数理モデル / 熱帯熱マラリア / 数理解析 / 耐性遺伝子頻度予測

Outline of Final Research Achievements

Malaria is one of the three major infectious disease including tuberculosis and HIV/AIDS. The biggest barrier for the global achievement of malaria control is emergence and spread of drug resistant malaria. This study successfully created a model that can estimate a level of selective advantage in drug-resistant parasite by one-point sampling and by using this estimate, predict the trajectory of drug resistant allele prevalence. This model will be able to be applicable to various malaria endemic regions and provide future estimation of drug-resistance without frequent sampling.

Research Products

• [Journal Article] Patterns and dynamics of genetic diversity in Plasmodium falciparum: what past Human migrations tell us about malaria. (2015)
  • Author(s): Mita T*, Jombart, T.
  • Journal Title: Parasitol Int. Volume: 64(3) Issue: 3 Pages: 238-243
  • DOI: 10.1016/j.parint.2014.09.007
  • Peer Reviewed
• [Journal Article] Global distribution of polymorphisms associated with delayed Plasmodium falciparum parasite clearance following artemisinin treatment: genotyping of archive blood samples. (2014)
  • Author(s): Murai K, Culleton R, Hisaoka T, Endo H, Mita T*.
  • Journal Title: Parasitol Int. Volume: 64(3) Issue: 3 Pages: 267-273
  • DOI: 10.1016/j.parint.2014.11.002
  • Peer Reviewed / Open Access
• [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
  • 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
  • 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
  • Peer Reviewed
• [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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Large-scale survey for novel genotypes of Plasmodium falciparum chloroquine-resistance gene pfcrt (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Evolution of <i>Plasmodium falciparum</i> drug resistance: implications for the development and containment of artemisinin resistance (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA5 (2012)
  • 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
  • Peer Reviewed
• [Journal Article] A large scale survey for novel genotypes of the Plasmodium falciparum chloroquine-resistant pfcrt gene. (2012)
  • Author(s): Takahashi, N.Mita, T.
  • Journal Title: Malaria J Volume: 11
• [Journal Article] Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations (2011)
  • Author(s): Mita, T, Tanabe K
  • Journal Title: J Infect Dis Volume: 204 Issue: 12 Pages: 1980-8
  • DOI: 10.1093/infdis/jir664
  • Peer Reviewed
• [Journal Article] Identification of pyrimethamine- and chloroquine-resistant Plasmodium falciparum in Africa between 1984 and 1998 : genotyping of archive blood samples (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Recent increase of genetic diversity in Plasmodium vivax population in the Republic of K (2011)
  • Author(s): Honma H., Mita T.
  • Journal Title: Malaria J Volume: 10 Issue: 1 Pages: 257-257
  • DOI: 10.1186/1475-2875-10-257
  • Peer Reviewed
• [Journal Article] Worldwide sequence conservation of transmission-blocking vaccine candidate Pvs230 in Plasmodium vivax (2011)
  • Author(s): Doi, M, Mita, T
  • Journal Title: Vaccine Volume: 29 Issue: 26 Pages: 4308-15
  • DOI: 10.1016/j.vaccine.2011.04.028
  • Peer Reviewed
• [Presentation] マラリアミューテーターを用いたピペラキン耐性原虫の迅速単離と耐性機構の解明 (2015)
  • Author(s): 池田美恵、平井誠、美田敏宏
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学 三鷹キャンパス
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] ウガンダにおけるex vivo薬剤感受性試験を用いた熱帯熱マラリア原虫のクロロキン感受性の回復 (2015)
  • Author(s): 櫻井美樹、Mawagali Betty Balikagala、矢代聖基、池田美恵、Ntege Edward、佐伯亜美、本間一、Palacpac Nirianne M.Q.、片岡正俊、坪井敬文、木村英作、遠藤弘良、堀井俊宏、美田敏宏
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学 三鷹キャンパス
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Temporal patterns of molecular marker associated with artemisinin resistance before and after the implementation of artemisinin derivatives in Myanmar (2015)
  • Author(s): Win Zin Zayar、上村春樹、Wah Win Htike、Khin San San、北潔、美田敏宏
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学 三鷹キャンパス
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] アルテミシニン耐性熱帯熱マラリア原虫出現以前の大規模検体を用いた耐性候補遺伝子Ｋ１３-propellerのベースライン多型解析 (2015)
  • Author(s): 美田敏宏、高橋延之、遠藤弘良、大橋順
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学 三鷹キャンパス
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] ウガンダにおけるRing Stage Survival Assayを用いたアルテミシニン感受性低下熱帯熱マラリア原虫のスクリーニング (2015)
  • Author(s): 金子恵、池田美恵、Mawagali Betty Balikagala、櫻井美樹、矢代聖基、加納永将、佐伯亜美、Palacpac Nirianne M.Q.、片岡正俊、坪井敬文、木村英作、堀井俊宏、美田敏宏
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学 三鷹キャンパス
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] ミューテーターマラリア原虫を用いた突然変異蓄積パターンの解析 (2015)
  • Author(s): 本間一、平井誠、新倉保、美田敏宏、小林富美恵、堀井俊宏、遠藤弘良
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学 三鷹キャンパス
  • Year and Date: 2015-03-21 – 2015-03-22
• [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: 第86回日本生化学会大会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] Evolution of Plasmodium falciparum Pyrimethamine/Sufadoxine Resistance. (2013)
  • Author(s): Mita T.
  • Organizer: Forum Cheju 16
  • Place of Presentation: Seoul, Korea, Yeongon Campus Seoul National University.
  • Invited
• [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
• [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
• [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
• [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
• [Presentation] Impact of an introduction of antimalarials combination therapy on the Plasmodium falciparum population in Papua New Guinea. (2011)
  • Author(s): Mita T.
  • Organizer: Nagasaki Symposium on Malaria Biology 2011.(招待講演)
  • Place of Presentation: 長崎大学
• [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(招待講演)
  • Place of Presentation: 国立感染症研究所
• [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(招待講演)
  • Place of Presentation: 杏林大学
• [Presentation] Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations. (2011)
  • 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
• [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
• [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
• [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: 東京大学
• [Book] 今日の治療指針2014 マラリア/バベシア 256-7 (2014)
  • Author(s): 美田敏宏
  • Total Pages: 2014
  • Publisher: 医学書院
• [Book] 検査値を読む2013：寄生虫卵・虫体検査．内科 111: 1049 (2013)
  • Author(s): 美田敏宏、北潔
  • Total Pages: 1621
  • Publisher: 南江堂