Predicting the emergence of drug-resistant malaria: Development of a comprehensive laboratory evolution system with accelerated evolution system

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H04074
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Juntendo University
• Principal Investigator: Mita Toshihiro 順天堂大学, 医学(系)研究科(研究院), 教授 (80318013)
• Co-Investigator(Kenkyū-buntansha): 平井 誠 順天堂大学, 医学部, 准教授 (50326849)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: マラリア / 薬剤耐性 / 進化

Outline of Final Research Achievements

We successfully produced protozoa in a few weeks that could survive and proliferate at the piperaquine concentration 6 times higher than that of susceptible strains. There were eight common mutations in these, including the N351I mutation in the chloroquine-resistant gene, crt. When this mutation was introduced into a susceptible strain, a slight decrease in susceptibility to piperaquine and a marked decrease in growth rate were observed. These indicate that the remaining mutation(s) may be involved in the decreased susceptibility and/or compensation of fitness. Further analysis is underway on the significance of these mutations to piperaquine resistance. In a validation study on real malaria samples, we has evidenced the emergence of artemisinin-resistant falciparum malaria in Uganda, which was the first report of the artemisinin resistance in Africa. We have also revealed that there was nearly half the resistance to mefloquine in Uganda.

Free Research Field

熱帯医学、疫学

Academic Significance and Societal Importance of the Research Achievements

本研究によってマラリア原虫が薬剤耐性を獲得するまでのプロセスをラボで迅速に解明する道が開けた。自然界に薬剤耐性マラリアが出現する前に起こる遺伝的な変化を解明することによって、流行地域における耐性が出現する前にアラートを出すことを可能とする。この段階で迅速に治療政策を変更することによって耐性が実際に出現することを防止できる。これによって新薬開発→耐性出現→新薬開発、という終わりないレースに終止符を打つ。2050年には抗生物質耐性病原体の蔓延による世界の死亡数はがん死亡数を上回るとされており、本研究構想が対策の実際面や開発に与える社会的波及面でのインパクトは高い。