Development of practical application of combination therapy against piroplasmosis in animals

• Project/Area Number: 18H02337
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: Igarashi Ikuo 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: Completed (Fiscal Year 2022)
• Budget Amount: ¥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 / 併用薬剤治療 / 動物 / 新規治療 / コンビネーション療法 / 家畜 / 薬剤 / 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 Final Research Achievements

Piroplasmosis is an intra-erythrocytic protozoan disease that causes enormous economic loss to animal industry globally. Current drugs have strong side effect and high relapse possibility. In the current study, drug combination effect was evaluated to develop a new chemotherapy with high efficacy and less low side effect.
New several drug combinations were found to kill parasites by in vitro culture system. These combination drugs showed high chemotherapeutic effect in mouse experimental model. Similar chemotherapeutic effects were observed in dog piroplasmosis and Scid mice that were substituted bovine erythrocytes. There results suggest a high possibility for the combination drug therapy for piroplasmosis.

Academic Significance and Societal Importance of the Research Achievements

ピロプラズマ病は世界的に甚大な被害を与えており、安全性と治療効果が高い新規の治療法の開発が喫緊の課題となっている。本研究では、原虫殺滅効果が高い数種類の薬剤が発見され、これらのの組み合わせにより、従来の治療薬より効果が高く、副作用の少ない安全な治療の開発が可能となる結果が示唆された。現在世界的人口増加に伴う動物性タンパク質の需要の拡大に対して、これらの安定供給が危惧されている現在、本研究の成果は、将来地球規模の食肉、乳製品の生産増加に貢献することが期待される。

Research Products

• [Int'l Joint Research] Yale University/Tufts University(米国)
• [Int'l Joint Research] Universidad Autonoma de Queretaro(メキシコ)
• [Int'l Joint Research] IPB University/Balai Veteriner Subang (DIC Subang)(インドネシア)
• [Int'l Joint Research] 東北医科薬科大学(日本)
• [Int'l Joint Research] Mongolian Veterinary In sistute/National University of Mongolia,/Khovd University(モンゴル)
• [Int'l Joint Research] Mansoura University/Damanhour University(エジプト)
• [Int'l Joint Research] Makerere University(ウガンダ)
• [Journal Article] Animal models of the immunology and pathogenesis of human babesiosis (2023)
  • Author(s): Kumar Abhinav、Kabra Aditya、Igarashi Ikuo、Krause Peter J.
  • Journal Title: Trends in Parasitology Volume: 39 Issue: 1 Pages: 38-52
  • DOI: 10.1016/j.pt.2022.11.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Imidazo[1,2-a]pyridine: a Highly Potent Therapeutic Agent Clears Piroplasm Infection In Vitro (2023)
  • Author(s): Rizk Mohamed Abdo、El-Sayed Shimaa Abd El-Salam、El-Alfy El-Sayed、Igarashi Ikuo
  • Journal Title: Acta Parasitologica Volume: 68 Issue: 1 Pages: 249-256
  • DOI: 10.1007/s11686-022-00655-w
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of a promising antigenic cocktail for the global detection of Babesia caballi in horse by ELISA (2023)
  • Author(s): El-Sayed Shimaa Abd El-Salam、Rizk Mohamed Abdo、Baghdadi Hanadi B.、Ringo Aaron Edmond、Sambuu Gantuya、Nugraha Arifin Budiman、Igarashi Ikuo
  • Journal Title: PLOS ONE Volume: 18 Issue: 4 Pages: e0284535-e0284535
  • DOI: 10.1371/journal.pone.0284535
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Babesia gibsoni (2022)
  • Author(s): Liu Mingming、Igarashi Ikuo、Xuan Xuenan
  • Journal Title: Trends in Parasitology Volume: 38 Issue: 9 Pages: 815-816
  • DOI: 10.1016/j.pt.2022.03.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ascorbic acid co-administration with a low dose of diminazene aceturate inhibits the in vitro growth of Theileria equi, and the in vivo growth of Babesia microti (2022)
  • Author(s): Rizk Mohamed Abdo、El-Sayed Shimaa Abd El-Salam、Igarashi Ikuo
  • Journal Title: Parasitology International Volume: 90 Pages: 102596-102596
  • DOI: 10.1016/j.parint.2022.102596
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of the in vitro and in vivo inhibitory effects of Artemisia herba-alba against the growth of piroplasm parasites (2022)
  • Author(s): Eltaysh Rasha、Rizk Mohamed、Sayed Shimaa、Abouelnasr Khaled、Abdallah Abdelnaser、Igarashi Ikuo
  • Journal Title: Journal of Advanced Veterinary and Animal Research Volume: 9 Issue: 2 Pages: 267-267
  • DOI: 10.5455/javar.2022.i592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pomegranate (Punica granatum) Peel Inhibits the In Vitro and In Vivo Growth of Piroplasm Parasites (2022)
  • Author(s): Eltaysh Rasha、Rizk Mohamed Abdo、Elmishmishy Bassem、El-Sayed Shimaa Abd El-Salam、Abouelnasr Khaled、Igarashi Ikuo
  • Journal Title: Journal of Parasitology Research Volume: 2022 Pages: 1-9
  • DOI: 10.1155/2022/8574541
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Repurposing of the Malaria Box for Babesia microti in mice identifies novel active scaffolds against piroplasmosis (2022)
  • Author(s): Rizk Mohamed Abdo、Baghdadi Hanadi B.、El-Sayed Shimaa Abd El-Salam、Eltaysh Rasha、Igarashi Ikuo
  • Journal Title: Parasites & Vectors Volume: 15 Issue: 1 Pages: 329-329
  • DOI: 10.1186/s13071-022-05430-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] <i>In vivo</i> activity and atom pair fingerprint analysis of MMV665941 against the apicomplexan parasite Babesia microti, the causative agent of babesiosis in humans and rodents (2022)
  • Author(s): Rizk Mohamed Abdo、El-Sayed Shimaa Abd El-Salam、Igarashi Ikuo
  • Journal Title: Pathogens and Global Health Volume: 117 Issue: 3 Pages: 315-321
  • DOI: 10.1080/20477724.2022.2128571
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] In Vitro Inhibitory Effects and Bioinformatic Analysis of Norfloxacin and Ofloxacin on Piroplasm (2022)
  • Author(s): Rizk Mohamed Abdo、El-Sayed Shimaa Abd El-Salam、Igarashi Ikuo
  • Journal Title: Acta Parasitologica Volume: 68 Issue: 1 Pages: 213-222
  • DOI: 10.1007/s11686-022-00648-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The GP-45 Protein, a Highly Variable Antigen from Babesia bigemina, Contains Conserved B-Cell Epitopes in Geographically Distant Isolates (2022)
  • Author(s): Mercado-Uriostegui Miguel Angel、Castro-S?nchez Luis Alberto、Batiha Gaber El-Saber、Valdez-Espinoza Uriel Mauricio、Falc?n-Neri Alfonso、Ramos-Aragon Juan Alberto、Hern?ndez-Ortiz Ruben、Kawazu Shin-Ichiro、Igarashi Ikuo、Mosqueda Juan
  • Journal Title: Pathogens Volume: 11 Issue: 5 Pages: 591-591
  • DOI: 10.3390/pathogens11050591
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Assay methods for in vitro and in vivo anti-Babesia drug efficacy testing: Current progress, outlook, and challenges (2020)
  • Author(s): Rizk et al.
  • Journal Title: Vet Parasitol Volume: 279 Pages: 109013-109013
  • DOI: 10.1016/j.vetpar.2019.109013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Myrrh Oil in Vitro Inhibitory Growth on Bovine and Equine Piroplasm Parasites and Babesia microti of Mice (2020)
  • 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 Issue: 3 Pages: 173-173
  • DOI: 10.3390/pathogens9030173
  • 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 Vivo (2020)
  • 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 Issue: 4 Pages: 996-996
  • DOI: 10.3390/molecules25040996
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Therapeutic Effects of Atranorin towards the Proliferation of Babesia and Theileria Parasites (2020)
  • 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 Issue: 2 Pages: 127-127
  • DOI: 10.3390/pathogens9020127
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria (2020)
  • 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 Issue: 2 Pages: e0228996-e0228996
  • DOI: 10.1371/journal.pone.0228996
  • 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 Issue: 13 Pages: 1646-1654
  • DOI: 10.1017/s0031182019001161
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of the in vitro and in vivo inhibitory effect of thymoquinone on piroplasm parasites (2019)
  • Author(s): El-Sayed Shimaa Abd El-Salam、Rizk Mohamed Abdo、Yokoyama Naoaki、Igarashi Ikuo
  • Journal Title: Parasites & Vectors Volume: 12 Issue: 1 Pages: 37-46
  • DOI: 10.1186/s13071-019-3296-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of unstable resistance to diminazene aceturate in Babesia bovis (2019)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Flavonoids isolated from the flowers of Pulsatilla flavescens and their anti-piroplasm activity (2019)
  • 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 Issue: 3 Pages: 1-8
  • DOI: 10.1007/s11418-019-01294-8
  • NAID: 40021912748
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The effects of nitidine chloride and camptothecin on the growth of Babesia and Theileria parasites (2018)
  • 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 Issue: 5 Pages: 1192-1201
  • DOI: 10.1016/j.ttbdis.2018.04.019
  • 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 importance (2018)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Expressing of Green Fluorescent Protein in intraerythrocytic stage of Theileria equi (2019)
  • 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
• [Presentation] Development of unstable resistance to diminazene aceturate in Babesia bovis (2019)
  • Author(s): Bumduuren Tuvshintulga，Thillaiampalam Sivakumar，Naoaki Yokoyama，Ikuo Igarashi
  • Organizer: 第６０回日本熱帯医学会大会
• [Presentation] The in vitro and in vivo inhibitory effect of Moringa olivera leaves on Babesia and Theileria parasites (2019)
  • Author(s): Mohamed A. Rizk, Shimaa El-Sayed, Noakia Yokoyama, Ikuo Igarashi
  • Organizer: The 88th Annual Meeting of Japanese Society of Parasitology
• [Presentation] An immunochromatographic test for serodiagnosis of human babesiosi (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Developmentof novel diagnostic methods and drugs for babesiosis (2018)
  • Author(s): Ikuo Igarashi
  • Organizer: The 14th International Congress of Parasitology
  • Int'l Joint Research / Invited
• [Presentation] An immunochromatographic test for human babesiosis caused by Babesia microti (2018)
  • Author(s): Ikuo Igarashi
  • Organizer: The 14th International Congress of Parasitology
  • Int'l Joint Research
• [Presentation] Clofazimine as a potential agent for treating human babesiosis caused by Babesia microti (2018)
  • Author(s): B. Tuvshintulga, T. Sivakumar, N. Yokoyama, I. Igarashi
  • Organizer: The 14th International Congress of Parasitology
  • Int'l Joint Research
• [Presentation] Evaluation of the in vitro and in vivo inhibitory effect of thymoquinone on Babesia and Theileria parasite (2018)
  • Author(s): Mohamed Abdo Rizk, Shimaa Abd El-Salam El-Sayed, Naoaki Yokoyama, and Ikuo Igarash
  • Organizer: The 14th International Congress of Parasitology
  • Int'l Joint Research
• [Presentation] Cryptolepine and ellagic acid inhibit Babesia and Theileria in vitro (2018)
  • Author(s): Amani Magdi Beshbishy, Gaber El-Saber Batiha, Naoaki Yokoyama, Ikuo Igarashi
  • Organizer: The 14th International Congress of Parasitology
  • Int'l Joint Research
• [Presentation] Serological and molecular prevalence of equine piroplasmosis in Western Java, Indonesia (2018)
  • 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
• [Presentation] Inhibitory effects of chalcone and trans-chalcone on the growth of Babesia and Theileria (2018)
  • 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
• [Presentation] Evaluation of the Chemotherapeutic Potential of Nitidine chloride and Camptothecin Against Babesia and Theileria (2018)
  • 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
• [Presentation] Screening the Medicines for Malaria Venture Pathogen Box against piroplasm parasites (2018)
  • 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
• [Presentation] Inhibitory effects of ivermectin on the growth Babesia and Theileria (2018)
  • 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