Clinical and bacteriological analysis of nontypeable Haemophilus influenzae isolated from invasive diseases

• Project/Area Number: 26461564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Chiba University
• Principal Investigator: ISHIWADA NARUHIKO 千葉大学, 真菌医学研究センター, 准教授 (30344980)
• Research Collaborator: HOSHINO Tadashi ; HISHIKI Haruka ; NAITO Sachiko ; TAKEUCHI Noriko ; OHKUSU Misako ; SEGAWA Shunsuke ; TSUCHIDA Sachio ; SATOH Mamoru ; TAKAHASHI Hiroki ; NISHI Junichiro
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: インフルエンザ菌 / Hibワクチン / 無莢膜株 / 薬剤耐性 / MLST解析 / 侵襲性感染症 / 非b型株 / 血清型解析 / 侵襲性感染症由来インフルエンザ菌 / インフルエンザ菌無莢膜株 / インフルエンザ菌e型 / バイオフィルム産生能 / インフルエンザ菌f型 ST124 / 侵襲性感染症由来インフルエンザ菌無莢膜株 / PFGE解析 / 血清殺菌能 / 細胞通過能

Outline of Final Research Achievements

After the introduction of Haemophilus influenzae type b (Hib) vaccine, invasive H. influenzae infection is now mainly due to nontypeable H. influenzae (NTHi). We investigated the clinical characteristics of invasive NTHi disease in children by clarifying the pathogenicity of NTHi strains isolated from invasive diseases. Most of the strains were biotype II or III. Two β-lactamase positive ampicillin-clavulanate resistant strains were found. Other penicillin non-susceptible strains had multiple amino acid substitutions. The average of biofim formation of hia or pilli positive strains were higher than negative strains. IS1016 was positive in 10.7% of the tested strains. Invasive NTHi strains from our study showed a wide variety of characteristics. Continuous monitoring of the NTHi responsible for invasive diseases in children is important to detect the changes in the epidemiology of invasive H. influenzae infection in the post Hib vaccine era.

Research Products

• [Journal Article] ワクチンのメリットとデメリット インフルエンザ菌b型ワクチン (2017)
  • Author(s): 石和田稔彦
  • Journal Title: 化学療法の領域 Volume: 33
• [Journal Article] 小児科領域における肺炎球菌ワクチンとインフルエンザ菌b型ワクチンの効果と今後の問題 (2016)
  • Author(s): 石和田稔彦
  • Journal Title: 感染症 Volume: 46 Pages: 9-15
• [Journal Article] 話題の感染症 インフルエンザ菌b型ワクチンは日本の小児感染症に変化をもたらしたか？ (2016)
  • Author(s): 石和田稔彦
  • Journal Title: モダンメディア Volume: 62 Pages: 191-195
• [Journal Article] The impact of heptavalent pneumococcal conjugate vaccine on the incidence of childhood community-acquired pneumonia and bacteriologically confirmed pneumococcal pneumonia in Japan (2016)
  • Author(s): Naito S, Tanaka J, Nagashima K, Chang B, Hishiki H, Takahashi Y, Oikawa J, Nagasawa K, Shimojo N, Ishiwada N.
  • Journal Title: Epidemiol Infect. Volume: 144 Issue: 3 Pages: 494
  • DOI: 10.1017/s0950268815001272
  • Peer Reviewed
• [Journal Article] Analysis of Haemophilus influenzae serotype f isolated from three Japanese children with invasive H. influenzae infection. (2015)
  • Author(s): Hoshino T, Hachisu Y, Kikuchi T, Tokutake S, Okui H, Kutsuna S, Fukasawa C, Murayama K, Oohara A, Shimizu H, Ito M, Takahashi Y, Ishiwada N.
  • Journal Title: J Med Microbiol Volume: E-pub ahead of print Issue: 4 Pages: 355-358
  • DOI: 10.1099/jmm.0.000031
  • Peer Reviewed
• [Journal Article] Nationwide population-based surveillance of invasive pneumococcal disease in Japanese children: Effects of the seven-valent pneumococcal conjugate vaccine. (2015)
  • Author(s): Suga S, Chang B, Asada K, Akeda H, Nishi J, Okada K, Wakiguchi H, Maeda A, Oda M, Ishiwada N, Saitoh A, Oishi T, Hosoya M, Togashi T, Oishi K, Ihara T.
  • Journal Title: Vaccine Volume: 33 Issue: 45 Pages: 6054-6060
  • DOI: 10.1016/j.vaccine.2015.07.069
  • Peer Reviewed
• [Journal Article] 小児臨床検体由来インフルエンザ菌非b型莢膜株に関する検討 (2015)
  • Author(s): 朽名悟，星野直，深沢千絵，徳武翔子，奥井秀由起，澤田恭子，佐藤洋子，高橋喜子，石和田稔彦
  • Journal Title: 感染症学会雑誌 Volume: 89 Pages: 237-243
  • NAID: 130005868547
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hibワクチン、肺炎球菌結合型ワクチンの普及と効果 (2015)
  • Author(s): 石和田稔彦
  • Journal Title: 日本小児科医会会報 Volume: 49 Pages: 11-16
• [Journal Article] 小児臨床検体由来インフルエンザ菌非b型莢膜株に関する検討 (2015)
  • Author(s): 朽名悟，星野直，深沢千絵，徳武翔子，奥井秀由起，澤田恭子，佐藤洋子，高橋喜子，石和田稔彦
  • Journal Title: 感染症誌 Volume: 89 Pages: 237-243
  • NAID: 130005868547
  • Peer Reviewed / Open Access
• [Journal Article] The incidence of pediatric invasive Haemophilus influenzae and pneumococcal disease in Chiba prefecture, Japan before and after the introduction of conjugate vaccines (2014)
  • Author(s): Ishiwada N, Hishiki H, Nagasawa K, Naito S, Sato Y, Chang B, Sasaki Y, Kimura K, Ohnishi M, Shibayama K.
  • Journal Title: Vaccine Volume: 32 Issue: 42 Pages: 5425
  • DOI: 10.1016/j.vaccine.2014.07.100
  • Peer Reviewed
• [Journal Article] Haemophilus influenzae BLNAR無莢膜株による細菌性髄膜炎を発症した1歳女児例 (2014)
  • Author(s): 阿部克昭，星野直，藺牟田直子，西順一郎，石和田稔彦
  • Journal Title: 感染症誌 Volume: 88 Pages: 291-296
  • NAID: 130005868599
  • Peer Reviewed / Open Access
• [Journal Article] Hibワクチン3回接種後に発症したインフルエンザ菌f型髄膜炎の1例 (2014)
  • Author(s): 大原亜沙実，清水博之，原良紀，福島亮介，佐近琢磨，船曳哲典，高橋幸子，菱木はるか，石和田稔彦
  • Journal Title: 日児誌 Volume: 118 Pages: 1079-1084
  • Peer Reviewed
• [Presentation] 質量分析計（MALDI-TOF-MS)を用いたHaemophilus influenzaeの莢膜型決定法の検討 (2017)
  • Author(s): 竹内典子、石和田稔彦、大楠美佐子、瀬川俊介、村田正太、土田祥央、佐藤守、野村文夫
  • Organizer: 第28回日本臨床微生物学会総会・学術集会
  • Place of Presentation: 長崎ブリックホール（長崎県 長崎市）
  • Year and Date: 2017-01-20
• [Presentation] ワクチン普及により変化する感染症と求められる臨床微生物検査 (2017)
  • Author(s): 石和田稔彦
  • Organizer: 第28回日本臨床微生物学会総会・学術集会
  • Place of Presentation: 長崎ブリックホール（長崎県 長崎市）
  • Year and Date: 2017-01-20
  • Invited
• [Presentation] Epidemiologic and Microbiologic analysis of invasive pneumococcal disease and pneumococcal pneumonia among children in Chiba prefecture, Japan after introduction of the 13-valent pneumococcal conjugate vaccine (2016)
  • Author(s): Ishiwada N, Naito S, Takeuchi N, Ohkusu M, Hishiki H, Chang B
  • Organizer: 10th ISPPD
  • Place of Presentation: Glasgow, UK
  • Year and Date: 2016-06-26
  • Int'l Joint Research
• [Presentation] 小児臨床検体由来インフルエンザ菌非b型莢膜株のMultilocus Sequence Typing(MLST)法による分子疫学的検討 (2016)
  • Author(s): 徳武 翔子, 星野 直, 澤田 恭子, 佐藤 万里, 佐藤 洋子, 石和田 稔彦
  • Organizer: 第27回日本臨床微生物学会総会・学術集会
  • Place of Presentation: 仙台国際センター（宮城県 仙台市）
  • Year and Date: 2016-01-29
• [Presentation] Clinical and bacteriological analysis of non-typeable Haemophilus influenzae isolated from blood in pediatric patients (2016)
  • Author(s): Naruhiko Ishiwada
  • Organizer: US-Japan ARI panel meeting
  • Place of Presentation: Washington DC USA
  • Year and Date: 2016-01-13
  • Int'l Joint Research
• [Presentation] ワクチン普及により変化する細菌感染症 (2015)
  • Author(s): 石和田稔彦
  • Organizer: 第26回日本臨床微生物学会総会学術集会
  • Place of Presentation: 京王プラザホテル （東京都 新宿区）
  • Year and Date: 2015-01-31 – 2015-02-01
  • Invited
• [Presentation] 小児臨床検体由来インフルエンザ菌非b型莢膜株のMultilocus Sequence Typing（MLST)法による分子疫学的検討 (2014)
  • Author(s): 徳武翔子，星野直，蜂巣友嗣，奥井秀由起，朽名悟，深沢千絵，高橋喜子，澤田恭子，佐藤洋子，石和田稔彦
  • Organizer: 第63回日本感染症学会東日本地方会総会学術集会
  • Place of Presentation: 東京ドームホテル (東京都 文京区）
  • Year and Date: 2014-10-29 – 2014-10-31
• [Book] 小児用ワクチンUPDATE2017 (2017)
  • Author(s): 石和田稔彦（編集 五十嵐隆）
  • Total Pages: 150
  • Publisher: 医歯薬出版株式会社
• [Book] 小児の予防接種ハンドブックⅡワクチンの最新情報 インフルエンザ菌b型（Hib）ワクチン (2016)
  • Author(s): 石和田稔彦 （編集 渡辺博）
  • Total Pages: 271
  • Publisher: 総合医学社