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Development of practical application of combination therapy against piroplasmosis in animals

Research Project

Project/Area Number 18H02337
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionObihiro University of Agriculture and Veterinary Medicine

Principal Investigator

五十嵐 郁男  帯広畜産大学, 原虫病研究センター, 名誉教授 (80159582)

Co-Investigator(Kenkyū-buntansha) 横山 直明  帯広畜産大学, 原虫病研究センター, 教授 (80301802)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Granted (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywordsピロプラズマ病 / 家畜 / 薬剤 / コンビネーション療法 / 新規治療 / 新規治療法 / コンビネーション / バベシア / タイレリア / コンビネーション治療
Outline of Annual Research Achievements

(1)牛赤血球置換SCID(SCID-Bo)マウスによるコンビネーション療法による治療効果の評価 1)Diminazene aceturate (DMA) 、Clofazimine (CFZ)、 Pyronaridine tetraphosphate (PYR)を用いて、培養B. bovisに対する増殖抑制効果を検討した結果、DMAとCFZを1:2の割合での組み合わせが高い効果を示した。 2)97%以上の牛赤血球に置換されたSCID-Boマウスに、B. bovisを1x107個腹腔内接種し、赤血球寄生率が1% に達した時点で、ら、DMA、CFZ、PYRおよびDMAとCFZのコンビネーションで1回投与し、その後の赤血球寄生率を検討した。その結果、DMAとCFZのコンビネーション治療群で感染後7日で原虫が認められなくなり非治療群に比較して高い治療効果を示した。また、コンビネーション治療群で体重の減少も軽減されていた。

(2)犬を用いたコンビネーション療法による治療効果の評価
1) MMV396693 とImidocarb dipropionateおよびPyronaridine tetraphosphateの組み合わせを用いて培養B. gibsoniに対する増殖抑制効果を検討した結果、MMV396693 とImidocarb dipropionateを1:1の割合での組み合わせが高い効果を示した。2)脾臓を摘出したビーグル犬にB. gibsoniを感染させ、赤血球寄生率が1%に達した時点で、MMV396693 とPyronaridine tetraphosphateを、翌日にImidocarb dipropionateを投与した。その結果、非治療群に比較して80%の高い治療効果が得られた。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

犬の培養原虫で得られた結果を基に、犬の感染治療実験を行い、増殖抑制効果が得られた。また、SCID-Boto
牛のバベシア原虫を用いた実験でも、ジミナゼンとクロファジミンの併用効果が認められた。

Strategy for Future Research Activity

今後はSCID-Boを用いて牛バベシア原虫に対する投与量、期間を再検討し、コンビネーション治療効果を確認する。
また、これらの結果を基に、モンゴルにおいて、馬および牛を用いて感染・治療実験を行う。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(32 results)

All 2020 2019 2018 Other

All Int'l Joint Research (7 results) Journal Article (11 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 11 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Int'l Joint Research] Yale University/Tufts University(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Universidad Autonoma de Queretaro(メキシコ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] IPB University/Balai Veteriner Subang (DIC Subang)(インドネシア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] 東北医科薬科大学(日本)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Mongolian Veterinary In sistute/National University of Mongolia,/Khovd University(モンゴル)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Mansoura University/Damanhour University(エジプト)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Makerere University(ウガンダ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Assay methods for in vitro and in vivo anti-Babesia drug efficacy testing: Current progress, outlook, and challenges2020

    • Author(s)
      Rizk et al.
    • Journal Title

      Veterinary Parasitology

      Volume: 279 Pages: 109013-109013

    • DOI

      10.1016/j.vetpar.2019.109013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Myrrh Oil in Vitro Inhibitory Growth on Bovine and Equine Piroplasm Parasites and Babesia microti of Mice2020

    • Author(s)
      AbouLaila Mahmoud、El-Sayed Shimaa Abd El-Salam、Omar Mosaab A.、Al-Aboody Mohammad Saleh、Abdel Aziz Amer R.、Abdel-Daim Mohamed M.、Rizk Mohamed Abdo、Igarashi Ikuo
    • Journal Title

      Pathogens

      Volume: 9 Pages: 173-173

    • DOI

      10.3390/pathogens9030173

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phytochemical Characterization and Chemotherapeutic Potential of Cinnamomum verum Extracts on the Multiplication of Protozoan Parasites In Vitro and In Vivo2020

    • Author(s)
      Batiha Gaber El-Saber、Beshbishy Amany Magdy、Guswanto Azirwan、Nugraha Arifin、Munkhjargal Tserendorj、M. Abdel-Daim Mohamed、Mosqueda Juan、Igarashi Ikuo
    • Journal Title

      Molecules

      Volume: 25 Pages: 996-996

    • DOI

      10.3390/molecules25040996

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic Effects of Atranorin towards the Proliferation of Babesia and Theileria Parasites2020

    • Author(s)
      Beshbishy Amany Magdy、Batiha Gaber El-Saber、Alkazmi Luay、Nadwa Eman、Rashwan Eman、Abdeen Ahmed、Yokoyama Naoaki、Igarashi Ikuo
    • Journal Title

      Pathogens

      Volume: 9 Pages: 127-127

    • DOI

      10.3390/pathogens9020127

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria2020

    • Author(s)
      El-Saber Batiha Gaber、Magdy Beshbishy Amany、Stephen Adeyemi Oluyomi、Nadwa Eman、Rashwan Eman、Yokoyama Naoaki、Igarashi Ikuo
    • Journal Title

      PLOS ONE

      Volume: 15

    • DOI

      10.1371/journal.pone.0228996

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RON2, a novel gene in Babesia bigemina, contains conserved, immunodominant B-cell epitopes that induce antibodies that block merozoite invasion.2019

    • Author(s)
      Mosqueda, J., Hidalgo-Ruiz, M., Calvo-Olvera, DA., Hernandez-Silva, DJ., Ueti, MW., Mercado-Uriostegui, MA., Rodriguez, A., Ramos-Aragon, JA., Hernandez-Ortiz, R., Kawazu, SI., and garashi, I.
    • Journal Title

      Parasitology

      Volume: 146(13 Pages: 1646-1654

    • DOI

      10.1017/s0031182019001161

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evaluation of the in vitro and in vivo inhibitory effect of thymoquinone on piroplasm parasites2019

    • Author(s)
      El-Sayed Shimaa Abd El-Salam、Rizk Mohamed Abdo、Yokoyama Naoaki、Igarashi Ikuo
    • Journal Title

      Parasites & Vectors

      Volume: 12 Pages: 37-46

    • DOI

      10.1186/s13071-019-3296-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of unstable resistance to diminazene aceturate in Babesia bovis2019

    • Author(s)
      Tuvshintulga Bumduuren、Sivakumar Thillaiampalam、Yokoyama Naoaki、Igarashi Ikuo
    • Journal Title

      International Journal for Parasitology: Drugs and Drug Resistance

      Volume: 9 Pages: 87-92

    • DOI

      10.1016/j.ijpddr.2019.02.001

    • NAID

      120006603076

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Flavonoids isolated from the flowers of Pulsatilla flavescens and their anti-piroplasm activity2019

    • Author(s)
      Ganchimeg Dorj、Batbold Badarch、Murata Toshihiro、Davaapurev Bekh-Ochir、Munkhjargal Tserendorj、Tuvshintulga Bumduuren、Suganuma Keisuke、Igarashi Ikuo、Buyankhishig Buyanmandakh、Sasaki Kenroh、Batsuren Dulamjav、Batkhuu Javzan
    • Journal Title

      Journal of natural medicines

      Volume: 07 Pages: 633-640

    • DOI

      10.1007/s11418-019-01294-8

    • NAID

      40021912748

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The effects of nitidine chloride and camptothecin on the growth of Babesia and Theileria parasites2018

    • Author(s)
      Tayebwa Dickson Stuart、Tuvshintulga Bumduuren、Guswanto Azirwan、Nugraha Arifin Budiman、Batiha Gaber El-Saber、Gantuya Sambuu、Rizk Mohamed Abdo、Vudriko Patrick、Sivakumar Thillaiampalam、Yokoyama Naoaki、Igarashi Ikuo
    • Journal Title

      Ticks and Tick-borne Diseases

      Volume: 9 Pages: 1192-1201

    • DOI

      10.1016/j.ttbdis.2018.04.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inhibitory effects of fluoroquinolone antibiotics on <em>Babesia divergens</em> and <em>Babesia microti</em>, blood parasites of veterinary and zoonotic importance2018

    • Author(s)
      Rizk Mohamed Abdo、AbouLaila Mahmoud、El-Sayed Shimaa Abd、Guswanto Azirwan、Yokoyama Naoaki、Igarashi Ikuo
    • Journal Title

      Infection and Drug Resistance

      Volume: Volume 11 Pages: 1605-1615

    • DOI

      10.2147/idr.s159519

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Expressing of Green Fluorescent Protein in intraerythrocytic stage of Theileria equi2019

    • Author(s)
      Arifin Nugraha,Bumduuren Tuvshintulga,Ming Ming Liu,Xuenan Xuan,Naoaki Yokoyama, Ikuo Igarashi
    • Organizer
      第60回日本熱帯医学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of unstable resistance to diminazene aceturate in Babesia bovis2019

    • Author(s)
      Bumduuren Tuvshintulga,Thillaiampalam Sivakumar,Naoaki Yokoyama,Ikuo Igarashi
    • Organizer
      第60回日本熱帯医学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The in vitro and in vivo inhibitory effect of Moringa olivera leaves on Babesia and Theileria parasites2019

    • Author(s)
      Mohamed A. Rizk, Shimaa El-Sayed, Noakia Yokoyama, Ikuo Igarashi
    • Organizer
      The 88th Annual Meeting of Japanese Society of Parasitology
    • Related Report
      2018 Annual Research Report
  • [Presentation] An immunochromatographic test for serodiagnosis of human babesiosi2018

    • Author(s)
      Hiroshi Isek, Azirwan Guswanto, Chul-min Kim, Atsuko Saito-Ito, Yuka Minoda, Hisashi Inokuma, Naoaki Yokoyama, Peter J Krause, and Ikuo Igarashi
    • Organizer
      The first human babesiosis conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Developmentof novel diagnostic methods and drugs for babesiosis2018

    • Author(s)
      Ikuo Igarashi
    • Organizer
      The 14th International Congress of Parasitology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] An immunochromatographic test for human babesiosis caused by Babesia microti2018

    • Author(s)
      Ikuo Igarashi
    • Organizer
      The 14th International Congress of Parasitology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clofazimine as a potential agent for treating human babesiosis caused by Babesia microti2018

    • Author(s)
      B. Tuvshintulga, T. Sivakumar, N. Yokoyama, I. Igarashi
    • Organizer
      The 14th International Congress of Parasitology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of the in vitro and in vivo inhibitory effect of thymoquinone on Babesia and Theileria parasite2018

    • Author(s)
      Mohamed Abdo Rizk, Shimaa Abd El-Salam El-Sayed, Naoaki Yokoyama, and Ikuo Igarash
    • Organizer
      The 14th International Congress of Parasitology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cryptolepine and ellagic acid inhibit Babesia and Theileria in vitro2018

    • Author(s)
      Amani Magdi Beshbishy, Gaber El-Saber Batiha, Naoaki Yokoyama, Ikuo Igarashi
    • Organizer
      The 14th International Congress of Parasitology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Serological and molecular prevalence of equine piroplasmosis in Western Java, Indonesia2018

    • Author(s)
      Arifin Budiman Nugraha, Umi Cahyaningsih, Amrozi, Azirwan Guswanto, Sambuu Gantuya, Bumduuren Tuvshintulga, Thillaiampalam Sivakumar, Naoaki Yokoyama, Ikuo Igarashi
    • Organizer
      The 116th Annual Meeting of the Japanese Society of Veterinary Medicine
    • Related Report
      2018 Annual Research Report
  • [Presentation] Inhibitory effects of chalcone and trans-chalcone on the growth of Babesia and Theileria2018

    • Author(s)
      Gaber El-Saber Batiha, Amany Magdy Beshbishy, Naoaki Yokoyama and Ikuo Igarashi
    • Organizer
      The 116th Annual Meeting of the Japanese Society of Veterinary Medicine
    • Related Report
      2018 Annual Research Report
  • [Presentation] Evaluation of the Chemotherapeutic Potential of Nitidine chloride and Camptothecin Against Babesia and Theileria2018

    • Author(s)
      Ikuo Igarashi, Dickson S. Tayebwa, Bumduuren Tuvshintulga, Azirwan Guswanto, Thillaiampalam Sivakumar, Naoaki Yokoyama
    • Organizer
      The 67th Annual Meeting of American Society of Tropical Medine
    • Related Report
      2018 Annual Research Report
  • [Presentation] Screening the Medicines for Malaria Venture Pathogen Box against piroplasm parasites2018

    • Author(s)
      Arifin Budiman Nugraha, Bumdureen Tuvshintulga, Mohamed Abdo Rizk, Sambuu Gantuya, Gaber El-Saber Batiha, Thillaiampalam Sivakumar, Naoaki Yokoyama, Ikuo Igarashi.
    • Organizer
      The 59th Annual Meeting of Japanese Society of Tropical Medine
    • Related Report
      2018 Annual Research Report
  • [Presentation] Inhibitory effects of ivermectin on the growth Babesia and Theileria2018

    • Author(s)
      Gaber El-Saber Batiha, Amany Magdy Beshbishy, Naoaki Yokoyama and Ikuo Igarashi
    • Organizer
      The 59th Annual Meeting of Japanese Society of Tropical Medine
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2021-01-27  

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