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Establishment of novel in vitro assay for evaluation of killing effect of chloroquine against malaria parasite

Research Project

Project/Area Number 20K16238
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49040:Parasitology-related
Research InstitutionJuntendo University

Principal Investigator

Balikagala Betty  順天堂大学, 大学院医学研究科, 助教 (70805895)

Project Period (FY) 2020-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
KeywordsCytocidal effect / Chloroquine / Plasmodium falciparum / Novel / Cytocidal-assay / Africa / Plasmodium / Cytociday efficacy / Cytocidal-efficacy / In-vitro assay / マラリア / クロロキン
Outline of Research at the Start

クロロキンの殺原虫効果をin vitroで評価できるアッセイを確立し、ウガンダで、クロロキンによる殺原虫効果が回復しているかについて明らかにする。全流行地で第一選択薬として広く用いられているアルテミシニンへの耐性原虫の出現と拡散、さらに同様の効果を示す代替薬の開発が滞っている現状を鑑みると、将来的な熱帯熱マラリア治療への、クロロキンの再導入に直接貢献することができる本研究のインパクトは極めて高い。

Outline of Final Research Achievements

In the research period, 287 additional natural parasite samples were collected (2022=102, 2023=106 and 2024=79) for evaluation. Optimal blood collection and parasite recovery and adaptation protocol was established to determine the chloroquine cytocidal effect. Despite difficulty, at least 20% field parasites adapted in culture for initial assessment. Persistent recovery of chloroquine parasite growth inhibitory effect still exists in Uganda Therefore, there is hope of possible re-introduction of the cheap, safe and potent chloroquine drug for malaria treatment.

Academic Significance and Societal Importance of the Research Achievements

The observed persistent recovery of chloroquine susceptibility in Africa provides hope that classical drugs like chloroquine which are cheap safe and potent can be reintroduced with modifications in the treatment of drug resistant malaria. Leading to reduced malaria morbidity and mortality.

Report

(6 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (25 results)

All 2024 2022 2021 2020 Other

All Int'l Joint Research (6 results) Journal Article (10 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (8 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] Gulu University/St. Mary's Hospital Lacor(ウガンダ)

    • Related Report
      2024 Annual Research Report
  • [Int'l Joint Research] University of Kinshasa/Tropical Medicine and Parasitology(コンゴ民主共和国)

    • Related Report
      2024 Annual Research Report
  • [Int'l Joint Research] National Institute of Research Biology/Department of Parasitology(コンゴ民主共和国)

    • Related Report
      2024 Annual Research Report
  • [Int'l Joint Research] Gulu University/St. Mary's Hospital Lacor(ウガンダ)

    • Related Report
      2023 Research-status Report
  • [Int'l Joint Research] Faculty of Medicine, Gulu University/PO Box 166/Gulu Uganda(ウガンダ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] St. Mary's Hospital Lacor Hospital/PO Box 180/Gulu Uganda(ウガンダ)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Indigenous emergence and spread of kelch13 C469Y artemisinin-resistant Plasmodium falciparum in Uganda2024

    • Author(s)
      Awor P, Coppee R, Khim N, Rondepierre L, Roesch C, Khean C, Kul C, Eam R, Lorn T, Athieno P, Kimera J, Balikagala B, Odongo-Aginya EI, Anywar DA, Mita T, Clain J, Ringwald P, Signorell A, Lengeler C, Burri C, Ariey F, Hetzel MW, Witkowski B
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 68 Issue: 8 Pages: 107340-107340

    • DOI

      10.1128/aac.01659-23

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A longer-chain acylated derivative of Dictyostelium differentiation-inducing factor-1 enhances the antimalarial activity against Plasmodium parasites2024

    • Author(s)
      Yoshida Naoko、Kikuchi Haruhisa、Hirai Makoto、Balikagala Betty、Anywar Denis A.、Taka Hikari、Kaga Naoko、Miura Yoshiki、Fukuda Naoyuki、Odongo-Aginya Emmanuel I.、Kubohara Yuzuru、Mita Toshihiro
    • Journal Title

      Biochemical Pharmacology

      Volume: 225 Pages: 116243-116243

    • DOI

      10.1016/j.bcp.2024.116243

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of drug-resistant malaria in resource-limited settings: efficient and high-throughput surveillance of artemisinin and partner drug resistance2024

    • Author(s)
      Fukuda Naoyuki、Yoshida Naoko、Balikagala Betty、Tsuru Ibuki、Ikeda Mie、Hirai Makoto、Anywar Denis A、Odongo-Aginya Emannuel I、Mita Toshihiro
    • Journal Title

      Journal of Antimicrobial Chemotherapy

      Volume: 79 Issue: 6 Pages: 1418-1422

    • DOI

      10.1093/jac/dkae120

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The impact of sequestration on artemisinin-induced parasite clearance in Plasmodium falciparum malaria in Africa.2022

    • Author(s)
      Fukuda N, Balikagala B, Ueno T, Anywar DA, Kimura E, Palacpac NMQ, Odongo-Aginya EI, Ogwang M, Horii T, Miida T, Mita T.
    • Journal Title

      Clin Infect Dis.

      Volume: 10 Issue: 9 Pages: 1585-1593

    • DOI

      10.1093/cid/ciac944

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circulation of an Artemisinin-Resistant Malaria Lineage in a Traveler Returning from East Africa to France.2022

    • Author(s)
      Coppee R, Bailly J, Sarrasin V, Vianou B, Zinsou BE, Mazars E, Georges H, Hamane S, Lavergne RA, Dannaoui E, Balikagala B, Fukuda N, Odongo-Aginya EI, Mita T, Houze S, Clain J.
    • Journal Title

      Clin Infect Dis.

      Volume: 75 Issue: 7 Pages: 1242-4

    • DOI

      10.1093/cid/ciac162

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] African-specific polymorphisms in Plasmodium falciparum serine repeat antigen 5 in Uganda and Burkina Faso clinical samples do not interfere with antibody response to BK-SE36 vaccination2022

    • Author(s)
      Arisue Nobuko、Palacpac Nirianne Marie Q.、Ntege Edward H.、Yeka Adoke、Balikagala Betty、Kanoi Bernard N.、Bougouma Edith Christiane、Tiono Alfred B.、Nebie Issa、Diarra Amidou、Houard Sophie、D’Alessio Flavia、Leroy Odile、Sirima Sodiomon B.、Egwang Thomas G.、Horii Toshihiro
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 12 Pages: 1058081-1058081

    • DOI

      10.3389/fcimb.2022.1058081

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evidence of Artemisinin-Resistant Malaria in Africa.2021

    • Author(s)
      Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana SI, Yamauchi M, Opio W, Emoto S, Anywar DA, Kimura E, Palacpac NMQ, Odongo-Aginya EI, Ogwang M, Horii T, Mita T.
    • Journal Title

      N Engl J Med.

      Volume: 385 Issue: 13 Pages: 1163-71

    • DOI

      10.1056/nejmoa2101746

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in Northern Uganda2021

    • Author(s)
      Fukuda N, Tachibana S-I、Ikeda M、Sakurai-Yatsushiro M、Balikagala B、Katuro O、Yamauchi M、Emoto S、Hashimoto M、Yatsushiro S、Sekihara Makoto、et al
    • Journal Title

      Parasitology International

      Volume: 81 Pages: 102277-102277

    • DOI

      10.1016/j.parint.2020.102277

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda2020

    • Author(s)
      Balikagala Betty、Sakurai-Yatsushiro Miki、Hirai Makoto  et al
    • Journal Title

      Malaria Journal

      Volume: 19 Issue: 1 Pages: 1-12

    • DOI

      10.1186/s12936-020-03157-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Global repertoire of human antibodies against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a malaria exposed population2020

    • Author(s)
      Kanoi Bernard N.、Nagaoka Hikaru、Morita Masayuki、White Michael T.、Palacpac Nirianne M.Q.、Ntege Edward H.、Balikagala Betty、Yeka Adoke、Egwang Thomas G.、Horii Toshihiro、Tsuboi Takafumi、Takashima Eizo
    • Journal Title

      Frontiers in Immunology

      Volume: "" Pages: 1-12

    • DOI

      10.3389/fimmu.2020.00893

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Elucidating the mechanism of spread of artemisinin resistant Plasmodium falciparum parasites in northern Uganda:A communitybased2024

    • Author(s)
      Makoto Kubo, Balikagala Betty
    • Organizer
      The 93rd Annual meeting of Japanese Society of Parasitology
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular evidence of PfK13 A675V and C469Y mutations in North-eastern Democratic Republic of Congo (DRC)2024

    • Author(s)
      Patrick Mamona, Balikagala Betty
    • Organizer
      The 93rd Annual meeting of Japanese Society of Parasitology
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evidence for artemisinin artemisinin resistance in Gulu, Northern Uganda2022

    • Author(s)
      Balikagala Betty
    • Organizer
      Presented in the American Society of Tropical Medicine and Hygiene Symposium 91
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Evidence of artemisinin resistance in Africa.2022

    • Author(s)
      Betty Balikagala
    • Organizer
      Presented in a meeting titled Malaria: Research for impact in the COVID-19 era, in Madrid Spain
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Evidence of artemisinin resistantce in Uganda2022

    • Author(s)
      Betty Balikagala
    • Organizer
      PMI-supported Antimalarial Resistance Monitoring in Africa (PARMA) Webinar: Artemisinin Resistance.
    • Related Report
      2022 Research-status Report
  • [Presentation] Efficacy of piperaquine drug in Northern Uganda,a region where artemisinin resistance has emerged2022

    • Author(s)
      Betty Balikagala
    • Organizer
      Japanese society of parasitology
    • Related Report
      2022 Research-status Report
  • [Presentation] Emergence of artemisinin resistance in Africa2021

    • Author(s)
      Balikagala Betty
    • Organizer
      The 90th Annual meeting of the Japanese Society of Parasitology
    • Related Report
      2021 Research-status Report
  • [Presentation] In vivo artemisinin resistance has emerged in Uganda (Africa)2020

    • Author(s)
      Balikagala Betty
    • Organizer
      The United States-Japan Cooperative Medical Science Program
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Remarks] Department of Tropical Medicine and Parasitology

    • URL

      https://www.juntendo.ac.jp/graduate/laboratory/labo/kiseityu/en-index.html

    • Related Report
      2024 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2026-01-16  

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