Comprehensive analysis of the potential risk of tick-borne emerging infectious diseases caused by pathogenic Rickettsiales bacteria

• Project/Area Number: 20K07499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: University of Shizuoka
• Principal Investigator: Ohashi Norio 静岡県立大学, 食品栄養科学部, 教授 (10169039)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Rickettsiales / Rickettsia japonica / Japanese spotted fever / Ehrlichia / Tick / マダニ / 感染症 / 日本紅斑熱 / エーリキア症 / リケッチア目細菌 / リケッチア / 新興感染症 / アナプラズマ

Outline of Research at the Start

本研究では、マダニ媒介新興リケッチア目細菌群について、①マダニ内のRickettsia japonica（日本紅斑熱）と非病原性Rickettsiaの定量的識別検出法の確立、②Anaplasma phagocytophilum（アナプラズマ症）とEhrlichia属菌（エーリキア症）の媒介マダニ種の解明、③上記3菌種の媒介マダニ種内の混和性解析、④マダニからの難培養リケッチアの分離の試みなどを実施する。これにより、マダニ媒介新興リケッチア目細菌群の潜在する感染リスクに関する総合的解明を目指す。

Outline of Final Research Achievements

To elucidate the potential risk of tick-borne emerging infectious diseases caused by Rickettsiales bacteria, we analyzed comprehensively pathogenic Rickettsiales bacteria in ticks and blood in febrile patients with Japanese spotted fever by next-generation sequencing and qPCR. As a result, we found that (i) some individual ticks harbor multiple pathogenic Rickettsiales bacteria which may cause the mixed infections in humans, (ii) a candidate of human ehrlichiosis agent in ticks in Japan was successfully indetified, and (iii) the amount of Rickettsia japonica in blood from feburile patients and/or the opportunistic infection by some facultative bacteria may be involved in the risk for severity of Japanese spotted fever. Thus, these results are expected to greatly contribute to the control and treatment of tick-borne infectious diseases caused by pathogenic Rickettsiales bacteria in Japan in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義としては、(i) マダニ1個体において、複数の病原性リケッチア目細菌の混在が明らかになったこと、(ii) 日本国内のマダニには、ヒトに感染性を示すEhrlichia属菌が潜在していること、(iii) 日本紅斑熱の重症化リスクには、血液中のリケッチア量や日和見感染菌との混合感染が係わっている可能性があること、などである。社会的意義としては、公衆衛生学上、啓発活動に役立つ知見が得られたこと、および日本紅斑熱の治療において、重症化を抑えるヒントとなる情報が得られたこと、などである。

Research Products

• [Journal Article] A Case of Human Granulocytic Anaplasmosis Suspected to be Complicated by Cholangitis (2022)
  • Author(s): KAWAKAMI Manri、IKEDA Fusao、FUJIOKA Shinichi、FUJITA Hiromi、KIDA Koji、OHASHI Norio
  • Journal Title: Kansenshogaku Zasshi Volume: 96 Issue: 1 Pages: 29-33
  • DOI: 10.11150/kansenshogakuzasshi.96.29
  • NAID: 130008145404
  • ISSN: 0387-5911, 1884-569X
  • Year and Date: 2022-01-20
  • Peer Reviewed
• [Journal Article] Serologic evidence of human exposure to ehrlichiosis agents in Japan (2022)
  • Author(s): Hongru Su, Kenji Kubo, Shigetoshi Sakabe, Shinsuke Mizuno, Nobuhiro Komiya, Shigehiro Akachi, Hiromi Fujita, Kozue Sato, Hiroki Kawabata, Hiromi Nagaoka, Shuji Ando, Norio Ohashi
  • Journal Title: Emerg Infect Dis. Volume: 28 Issue: 11 Pages: 2355-2357
  • DOI: 10.3201/eid2811.212566
  • Peer Reviewed / Open Access
• [Journal Article] Growth Characteristics of <i>Rickettsia</i> Species LON Strains Closely Related to <i>Rickettsia</i> <i>japonica</i> Isolated from <i>Haemaphysalis longicornis</i> Ticks in Mouse Derived L929 and Human-Derived THP-1 Host Cell Lines (2021)
  • Author(s): Tai H, Su H, Takamoto N, Fujita H, Takano A, Oishi S, Abe F, Ando S, Ohashi N.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 74 Issue: 2 Pages: 102-109
  • DOI: 10.7883/yoken.JJID.2020.444
  • NAID: 130008002351
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2021-03-31
  • Peer Reviewed / Open Access
• [Journal Article] Surveillance of Borrelia miyamotoi-carrying ticks and genomic analysis of isolates in Inner Mongolia, China (2021)
  • Author(s): Gaowa、Wulantuya、Sato Kozue、Liu Dan、Cui Yunhong、Yin Xuhong、Zhang Lihua、Li Hong、Wang Tingfu、Liu Rongxin、Wu Lijing、Lu Saixia、Gao Ting、Zhang Zitong、Cao Minzhi、Wang Guodong、Li Chunpu、Yan Dacheng、Ohashi Norio、Ando Shuji、Kawabata Hiroki
  • Journal Title: Parasites & Vectors Volume: 14 Issue: 1 Pages: 368-368
  • DOI: 10.1186/s13071-021-04809-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diversity unearthed by estimated molecular phylogeny and ecologically quantitative characteristics of uncultured Ehrlichia bacteria in Haemaphysalis ticks, Japan. (2021)
  • Author(s): Su H, Onoda E, Tai H, Fujita H, Sakabe S, Azuma K, Akachi S, Oishi S, Abe F, Ando S, Ohashi N.
  • Journal Title: Sci Rep. Volume: 11 Issue: 1 Pages: 687-687
  • DOI: 10.1038/s41598-020-80690-7
  • Peer Reviewed / Open Access
• [Journal Article] Intracellular proliferation of Anaplasma phagocytophilum is promoted via modulation of endoplasmic reticulum stress signaling in host cells (2020)
  • Author(s): Yoshikawa Y, Sugimoto K, Ochiai Y, Ohashi N.
  • Journal Title: Microbiol Immunol. Volume: 64 Issue: 4 Pages: 70-279
  • DOI: 10.1111/1348-0421.12770
  • Peer Reviewed