Efficiency of ACT on malaria treatments and analysis of polymorphisms in drug resistance genes of Plasmodium falciparum

• Project/Area Number: 16H05817
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Nagasaki University
• Principal Investigator: UEMURA Haruki 長崎大学, 熱帯医学研究所, 客員准教授 (60184975)
• Co-Investigator(Kenkyū-buntansha): 五十棲 理恵 大阪市立大学, 大学院医学研究科, 講師 (30550355)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 熱帯熱マラリア / 薬剤耐性 / アルテミシニン / pfdhps遺伝子 / インドネシア / リアルタイムPCR / 薬剤耐性遺伝子 / 熱帯熱マラリア原虫

Outline of Final Research Achievements

No artemisinin-resistant malaria parasites have been reported in Indonesia and we also have confirmed it in this research project. Study on efficacy of artemisinin combination therapy (ACT) was conducted with malaria patients in Flores Island and its efficacy was confirmed; no detectable malaria parasites remained in the patient peripheral blood on day 3 of ACT.In addition, no mutation were observed in the Kelch13 propeller region of Plasmodium falciparum isolates from several area of Indonesia.
We then developed a simple and reliable real-time PCR procedure for malaria parasite detection and quantitation with this Flores Island field samples.
Further analysis of polymorphisms in several drug resistant genes of Plasmodium falciparum revealed origins and spread of two unique K540T and I588F pfdhps genetic variants in Indonesia and alteration of pfcrt genotype polymorphism in an East Kalimantan district after ACT introduction.

Academic Significance and Societal Importance of the Research Achievements

アルテミシニン併用療法（ACT）の導入によってインドネシアでも多くの地域でマラリア感染数が減少しており、今回の研究では治療にACTが有効であることを示すことが出来た。このような中でマラリア感染が残っているのは診療所から距離のある地区が大部分であり、そのような場所でも使用することの出来る、簡便で感度の高い方法として、リアルタイムPCRを用いたマラリア原虫の検出、定量、原虫種の同定の有用性を示した。持ち運びのできるリアルタイムPCRで薬剤耐性遺伝子の同定も可能であり、今後のマラリア対策に寄与することが出来ると考えている。

Research Products

• [Int'l Joint Research] アイルランガ大学(インドネシア)
• [Int'l Joint Research] アイルランガ大学(インドネシア)
• [Journal Article] Origins and spread of novel genetic variants of sulfadoxine?pyrimethamine resistance in Plasmodium falciparum isolates in Indonesia (2018)
  • Author(s): Basuki Sukmawati, Fitriah, Risamasu Petronella M., Kasmijati, Ariami Pancawati, Riyanto Sugeng, Hidayat Ari, Susilowati Dewi, Iskandar, Armika Budi, Budiono, Dachlan Yoes P. , Kanbara Hiroji, Uemura Haruki
  • Journal Title: Malaria Journal Volume: 17 Issue: 1 Pages: 475-475
  • DOI: 10.1186/s12936-018-2597-6
  • NAID: 120006987866
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Polymorphisms of Plasmodium falciparum drug resistant genes in Indonesia (2019)
  • Author(s): Basuki S, Fitriah, Budiono, Risamasu PM, Rossyanti R, Pusarawati S, Habibi M, Arnoldina DDW, Merrylin, Surya A, Uemura H
  • Organizer: 第88回日本寄生虫学会大会
• [Presentation] Polymorphism in Drug Resistant genes of Plasmodium falciparum After Introduction of Artemisin Combination Therapy in East Kalimantan, Indonesia (2018)
  • Author(s): Basuki S, Fitriah, Habibi M, Budiono, Uemura H
  • Organizer: 14th International Congress of Parasitology
  • Int'l Joint Research
• [Presentation] Genetic Variants of Sulfadoxine-Pyrimethamine-resistance in Plasmodium falciparum isolates in Indonesia (2018)
  • Author(s): Uemura H, Basuki S, Fitriah, Risamasu PM, Kasmijati, Ariami P, Riyanto S, Hidayat A, Susilowati D, Iskandar, Armika B, Budiono, Dachlan YP, Kanbara H
  • Organizer: 14th International Congress of Parasitology
  • Int'l Joint Research
• [Presentation] Reduced Polymorphism in Drug Resistant Genes of Plasmodium falciparum after Introduction of Artemisinin Combination Therapy in Indonesia (2018)
  • Author(s): Basuki S, Fitriah, Budiono, Kasmijati, Ariami P, Armika B, Risamasu PM, Rossyanti R, Aspriyanto W, Pusarawati S, Habibi M, Arnoldina DDW, Merrylin, Surya A, Isozumi R, Uemura H
  • Organizer: 第59回日本熱帯医学会大会
• [Presentation] Sulphadoxine-Pyrimethamine Efficiency and Plasmodium falciparum dhfr and dhps Genotypes in Indonesia Parasites (2017)
  • Author(s): Basuki S, Fitriah, Risamasu PM, Kasmijati, Ariami P, Riyanto S, Hidayat A, Susilowati D, Iskandar, Armika B, Budiono, Dachlan YP, Kanbara H, Uemura H
  • Organizer: 2nd Molecular and Cellular Life Sciences International Conference
  • Int'l Joint Research
• [Presentation] インドネシアの熱帯熱マラリア原虫の薬剤感受性と遺伝子解析 (2017)
  • Author(s): Basuki S, Fitriah, Risamasu PM, Kasmijati, Ariami P, Riyanto S, Hidayat A, Susilowati D, Iskandar, Armika B, Budiono, Dchlan YP, kanbara H, Uemura H
  • Organizer: 第86回日本寄生虫学会大会
• [Presentation] Analysis of Plasmodium falciparum of Kelch 13 and other drug resistant genes after introduction of Artemisinin Combination Therapy in East Kalimantan, Indonesia (2017)
  • Author(s): Basuki S, Fitriah, Habibi M, Budiono, Surya A, Uemura H
  • Organizer: グローバルヘルス合同大会2017
• [Presentation] Drug Resistance of Malaria Parasite; Local Concern for Global Problem (2016)
  • Author(s): Sukmawati Basuki, Rie Isozumi, and Haruki Uemura
  • Organizer: the International Seminar on Global Strategy to Combat Emerging Infectious Diseases in Borderless Era (GSEID2016)
  • Int'l Joint Research / Invited
• [Presentation] Efikasi Sulfadoksin-Pirimetamin dan Variasi genetik Pfdhfr/Pfdhps di Indonesia (2016)
  • Author(s): Basuki S, Fitriah, Risamasu PM, Kasmijati, Ariami P, Riyanto S, Hidayat A, Susilowati D, Iskandar, Armika B, Budiono, Dachlan YP, Kanbara H, Uemura H
  • Organizer: Annual Malaria Research in Indonesia
• [Presentation] Malaria Asimtomatik di Daerah Eliminasi Malaria di Barito Utara, Kalimantan Tengah, Indonesia (2016)
  • Author(s): Aspriyanto W, Rossyanti L, Sulistyawati SW, Pusarawati S, Fitriah, Budiono, Dachlan YP, Uemura H, Hadi U, Basuki S
  • Organizer: Annual Malaria Research in Indonesia