Development of new in vitro phenotypic assay to detect the artemisinin resistant Plasmodium falciparum

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16631
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: Juntendo University
• Principal Investigator: IKEDA Mie 順天堂大学, 大学院医学研究科, 学振特別研究員(RPD) (40734314)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: アルテミシニン耐性 / 熱帯熱マラリア原虫 / pyknotic form / in vitro 検査法 / RSA / qRSA / C469Y / A675V

Outline of Final Research Achievements

Artemisinin is the first-line drug for malaria treatment, and artemisinin resistance Plasmodium falciparum has already appeared in Africa. This study focused on a dead parasite called the pyknotic form, which appeared due to artemisinin. I set out to determine whether this structure is associated with artemisinin resistance. I thought that the existing method could be improved further if the effect of the pyknotic form on the existing method could be clarified.
Contrary to expectations at the beginning of the study, I found no clear relationship between the appearance of the pyknotic form and artemisinin resistance. The new method enables a semi-quantitative assessment of P. falciparum drug resistance by using seven levels of set concentration in the existing method.

Free Research Field

マラリア、薬剤耐性

Academic Significance and Societal Importance of the Research Achievements

Pynotic　formとアルテミシニン耐性の強さには相関が無いこと、pyknotic formの出現にはiマラリア原虫の培養条件が大きく関与することが明らかになった。この事実は、pyknotic formが培養環境の良し悪しを評価する一つの指標となることを示唆している。
また、改良法（qRSA)で行ったウガンダでのアルテミシニン耐性調査によって、ドミナントとなっているC469Yがin vitroレベルでは非常に弱い耐性であることを示した。C469Yが蔓延するウガンダでの今後の薬剤耐性対策には蚊体内やヒト体内でのC469Y原虫の挙動を調べる必要がある。