Understanding the transmission dynamics of norovirus with microbial data in wastewater and machine learning algorithms

• Project/Area Number: 22KJ2358
• Project/Area Number (Other): 20J00793 (2020-2022)
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Multi-year Fund (2023); Single-year Grants (2020-2022)
• Section: 国内
• Review Section: Basic Section 22060:Environmental systems for civil engineering-related
• Research Institution: Ehime University
• Principal Investigator: 三浦 郁修 愛媛大学, 沿岸環境科学研究センター, 特別研究員(CPD)
• Project Period (FY): 2023-03-08 – 2025-03-31
• Project Status: Granted (Fiscal Year 2023)
• Budget Amount: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2024: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2023: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2022: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: 感染症数理モデル / 下水データ / ウイルス動態 / ノロウイルス / SARS-CoV-2 / 下水疫学 / 数理モデル / 感染症疫学 / 理論疫学 / Mpox / 感染症

Outline of Research at the Start

本研究では都市内の微生物情報を大量に含む下水データを活用することで、「観測されない不顕性感染者・非来院患者を含むノロウイルス感染動態の理解」及び「微生物データ等の大規模データと数理モデルを用いた感染者予測・検知」を行うことを目的としている。報告感染者数などの疫学データと下水データを統合し、数理モデルを組み合わせることで、未報告を含む総感染者数の推定や流行トレンドの予測を行う。

Outline of Annual Research Achievements

本研究では都市内の微生物情報を大量に含む水インフラを活用し、「観測されない不顕性感染 者・非来院患者を含むノロウイルス感染動態の理解」及び「微生物データや気象データ等の大 規模データと機械学習モデルを用いた感染者予測・検知」を行うことを目的とした。当初の研究計画ではノロウイルスの下水中濃度の時系列データをモデリングすることを予定していたが、COVID-19パンデミックに伴い、SARS-CoV-2やMpoxなどを適用事例 としながら同様の手法の開発を行った。

本年度の成果として(1)状態空間と拡張カルマンフィルタを用いた下水モデルの提案・論文執筆(2)Mpoxのウイルス排出ダイナミクスの解析・論文執筆、をそれぞれ行った。 (1)については、日本の複数自治体における下水中ウイルス量データに本課題で提案する拡張カルマンフィルタを用いたモデリング手法を適用することで、未報告の感染者を含む総感染者数の推定や、実行再生産数の算出、介入効果を可視化するシナリオ分析などを行った。本成果はEurosurveillance誌に投稿し、追加分析を行った上で、採択された。 (2)については、Mpox患者の個人ごとの排出ウイルス量の経時追跡データを対象として分析を行った。本研究では、数理モデルと機械学習モデルを組合せたアプローチを採用した：第一ステップとして、ウイルスの排出動態を記述する数理モデルを適合し（欠損値などがあっても）統一的に各個人の排出ダイナミクスを推定した。次に、推定されたモデルパラメータ（例えば初期ウイルス量や排出速度などといった機構的な意味付けのあるパラメータ）を機械学習モデルを用いてクラスタリングすることで、個々人の違い・異質性を考慮しながら層別化を行った。ウイルス排出の総量の多い個人・排出期間が長い個人をターゲットとして感染対策や治療を効率化できる可能性を提案した。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

予定していたようなノロウイルスの時系列データを入手することは困難になったが、より詳細なデータがSARS-CoV-2を対象に得られた。また日本の自治体とも連携が進めることができ、実際に複数の都市から詳細な下水データが得られ、新しい研究課題として実際にデータ分析を進めている。また、私企業と連動することで、実際の自治体ニーズをヒアリングしながら産学連携で研究手法を現場で利用してもらえるような形で進展できている。
本年度の成果として(1)の拡張カルマンフィルタを用いた機構モデルについては追加分析を行ったうえで国際誌に受理された。(2)のmpoxのウイルス排出ダイナミクスに関する研究は国際会議での発表や国際誌への投稿までまとめることができた。さらに、複数のフォローアップ研究にも繋がる形で進捗を生むことができた。

Strategy for Future Research Activity

申請当初の計画から、データの観点で遂行が困難になった部分については、第二年度の報告書時点で計画の変更を行っている。（COVID-19により構造的な変化が生じ、季節性のあるノロウイルスの流行データを長期時系列として得ることが不可能になったため。）今後の計画としては、得られる疾病データを利用しながら「個人のウイルス排出動態に基づく流行追跡のシミュレーション」や「複数のウイルス変異株が存在するときの感染伝播速度（増加率）の推定」を次の方針として予定している。

Research Products

• [Int'l Joint Research] オランダ公衆衛生環境研究所 (RIVM)/Leiden University Medical Center (LUMC)/UMC Utrecht(オランダ)
• [Int'l Joint Research] ロンドン大学衛生熱帯医学大学院(LSHTM)(英国)
• [Int'l Joint Research] ノースカロライナ大学チャペルヒル校(米国)
• [Int'l Joint Research] Hasselt University/University of Antwerp(ベルギー)
• [Int'l Joint Research] University of Bern(スイス)
• [Int'l Joint Research] オランダ公衆衛生環境研究所(RIVM)/Leiden University Medical Center (LUMC)/UMC Utrecht(オランダ)
• [Int'l Joint Research] ロンドン大学衛生熱帯医学大学院(LSHTM)(英国)
• [Int'l Joint Research] Hasselt Univeristy/University of Antwerp(ベルギー)
• [Int'l Joint Research] University of Bern/EFPL(スイス)
• [Int'l Joint Research] Leiden University Medical Center/RIVM(オランダ)
• [Int'l Joint Research] RIVM/Leiden University Medical Center (LUMC)(オランダ)
• [Journal Article] Wastewater-based reproduction numbers and projections of COVID-19 cases in three areas in Japan, November 2021 to December 2022 (2024)
  • Author(s): Miyazawa Shogo、Wong Ting Sam、Ito Genta、Iwamoto Ryo、Watanabe Kozo、van Boven Michiel、Wallinga Jacco、Miura Fuminari
  • Journal Title: Eurosurveillance Volume: 29 Issue: 8 Pages: 2300277-2300277
  • DOI: 10.2807/1560-7917.es.2024.29.8.2300277
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] No detectable fitness cost of infection by cell-fusing agent virus in <i>Aedes aegypti</i> mosquitoes (2024)
  • Author(s): Suzuki Yasutsugu、Suzuki Takahiro、Miura Fuminari、Reyes Jerica Isabel L.、Asin Irish Coleen A.、Mitsunari Wataru、Uddin Mohammad Mosleh、Sekii Yu、Watanabe Kozo
  • Journal Title: Royal Society Open Science Volume: 11 Issue: 1 Pages: 231373-231373
  • DOI: 10.1098/rsos.231373
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quantifying the Individual Variation in Susceptibility to Endemic Coronavirus and SARS-CoV-2 with Human Challenge Trials (2023)
  • Author(s): Miura Fuminari、Klinkenberg Don、Wallinga Jacco
  • Journal Title: Epidemiology Volume: 35 Issue: 1 Pages: 113-117
  • DOI: 10.1097/ede.0000000000001679
• [Journal Article] Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes (2023)
  • Author(s): Murayama Hiroaki、Pearson Carl A B、Abbott Sam、Miura Fuminari、Jung Sung-mok、Fearon Elizabeth、Funk Sebastian、Endo Akira
  • Journal Title: The Journal of Infectious Diseases Volume: 229 Issue: 1 Pages: 59-63
  • DOI: 10.1093/infdis/jiad254
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Fading of the Mpox Outbreak Among Men Who Have Sex With Men: A Mathematical Modelling Study (2023)
  • Author(s): Xiridou Maria、Miura Fuminari、Adam Philippe、Op de Coul Eline、de Wit John、Wallinga Jacco
  • Journal Title: The Journal of Infectious Diseases Volume: - Issue: 1 Pages: e121-e130
  • DOI: 10.1093/infdis/jiad414
• [Journal Article] Estimated incubation period distributions of mpox using cases from two international European festivals and outbreaks in a club in Berlin, May to June 2022 (2023)
  • Author(s): McFarland Sarah E、Marcus Ulrich、Hemmers Lukas、Miura Fuminari、....、Coyer Liza、Boberg Ronja、Jurke Annette、Werber Dirk、Bartel Alexander
  • Journal Title: Eurosurveillance Volume: 28 Issue: 27
  • DOI: 10.2807/1560-7917.es.2023.28.27.2200806
• [Journal Article] Mpox emergence in Japan: ongoing risk of establishment in Asia (2023)
  • Author(s): Endo Akira、Jung Sung-mok、Miura Fuminari
  • Journal Title: The Lancet Volume: 401 Issue: 10392 Pages: 1923-1924
  • DOI: 10.1016/s0140-6736(23)00766-3
  • Open Access / Int'l Joint Research
• [Journal Article] Time Scales of Human Mpox Transmission in The Netherlands (2023)
  • Author(s): Miura Fuminari、Backer Jantien A、...、the Dutch Mpox Response Team
  • Journal Title: The Journal of Infectious Diseases Volume: - Issue: 3 Pages: 800-804
  • DOI: 10.1093/infdis/jiad091
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Modelling patterns of SARS-CoV-2 circulation in the Netherlands, August 2020-February 2022, revealed by a nationwide sewage surveillance program (2023)
  • Author(s): van Boven Michiel、Hetebrij Wouter A.、Swart Arno M.、Nagelkerke Erwin、van der Beek Rudolf F.H.J.、Stouten Sjors、Hoogeveen Rudolf T.、Miura Fuminari、Kloosterman Astrid、van der Drift Anne-Merel R.、Welling Anne、Lodder Willemijn J.、de Roda Husman Ana M.
  • Journal Title: Eurosurveillance Volume: -
  • DOI: 10.1101/2022.05.25.22275569
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mpox outbreak in the Netherlands, 2022: public health response, characteristics of the first 1,000 cases and protection of the first-generation smallpox vaccine (2023)
  • Author(s): van Ewijk Catharina E、Miura Fuminari、...、the Dutch Mpox Response Team
  • Journal Title: Eurosurveillance Volume: 28 Issue: 12
  • DOI: 10.2807/1560-7917.es.2023.28.12.2200772
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A scenario modelling analysis to anticipate the impact of COVID-19 vaccination in adolescents and children on disease outcomes in the Netherlands, summer 2021 (2022)
  • Author(s): Ainslie Kylie E C、Backer Jantien A、de Boer Pieter T、van Hoek Albert Jan、Klinkenberg Don、Korthals Altes Hester、Leung Ka Yin、de Melker Hester、Miura Fuminari、Wallinga Jacco
  • Journal Title: Eurosurveillance Volume: 27 Issue: 44
  • DOI: 10.2807/1560-7917.es.2022.27.44.2101090
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Estimated incubation period for monkeypox cases confirmed in the Netherlands, May 2022 (2022)
  • Author(s): Miura Fuminari、van Ewijk Catharina E、Backer Jantien A、Xiridou Maria、Franz Eelco、Op de Coul Eline、Brandwagt Diederik、van Cleef Brigitte、van Rijckevorsel Gini、Swaan Corien、van den Hof Susan、Wallinga Jacco
  • Journal Title: Eurosurveillance Volume: 27 Issue: 24
  • DOI: 10.2807/1560-7917.es.2022.27.24.2200448
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genotype-dependent kinetics of enterovirus inactivation by free chlorine and ultraviolet (UV) irradiation (2022)
  • Author(s): Torii Shotaro、Corre Marie-Helene、Miura Fuminari、Itamochi Masae、Haga Kei、Katayama Kazuhiko、Katayama Hiroyuki、Kohn Tamar
  • Journal Title: Water Research Volume: 220 Pages: 118712-118712
  • DOI: 10.1016/j.watres.2022.118712
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Public Health Risks of Waterborne Pathogen Exposure Under a Climate Change Scenario in Indonesia (2022)
  • Author(s): Setiawati Martiwi Diah、Jarzebski Marcin Pawel、Miura Fuminari、Mishra Binaya Kumar、Fukushi Kensuke
  • Journal Title: - Volume: - Pages: 607-624
  • DOI: 10.1007/978-3-031-15501-7_24
  • ISBN: 9783031155000, 9783031155017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Optimal vaccine allocation for COVID-19 in the Netherlands: A data-driven prioritization (2021)
  • Author(s): Miura Fuminari、Leung Ka Yin、Klinkenberg Don、Ainslie Kylie E. C.、Wallinga Jacco
  • Journal Title: PLOS Computational Biology Volume: 17 Issue: 12 Pages: e1009697-e1009697
  • DOI: 10.1371/journal.pcbi.1009697
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Estimating the asymptomatic proportion of SARS-CoV-2 infection in the general population: Analysis of nationwide serosurvey data in the Netherlands (2021)
  • Author(s): McDonald Scott A.、Miura Fuminari、Vos Eric R. A.、van Boven Michiel、de Melker Hester E.、van der Klis Fiona R. M.、van Binnendijk Rob S.、den Hartog Gerco、Wallinga Jacco
  • Journal Title: European Journal of Epidemiology Volume: 36 Issue: 7 Pages: 735-739
  • DOI: 10.1007/s10654-021-00768-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Age-dependent association between SARS-CoV-2 cases reported by passive surveillance and viral load in wastewater (2021)
  • Author(s): Omori Ryosuke、Miura Fuminari、Kitajima Masaaki
  • Journal Title: Science of The Total Environment Volume: 792 Pages: 148442-148442
  • DOI: 10.1016/j.scitotenv.2021.148442
  • Peer Reviewed / Open Access
• [Journal Article] The impact of vaccinating adolescents and children on COVID-19 disease outcomes (2021)
  • Author(s): Ainslie Kylie E. C.、Backer Jantien、de Boer Pieter、van Hoek Albert Jan、Klinkenberg Don、Altes Hester Korthals、Leung Ka Yin、de Melker Hester、Miura Fuminari、Wallinga Jacco
  • Journal Title: medRxiv Volume: -
  • DOI: 10.1101/2021.10.21.21265318
  • Open Access
• [Journal Article] Duration of SARS-CoV-2 viral shedding in faeces as a parameter for wastewater-based epidemiology: Re-analysis of patient data using a shedding dynamics model (2021)
  • Author(s): Miura Fuminari、Kitajima Masaaki、Omori Ryosuke
  • Journal Title: Science of The Total Environment Volume: 769 Pages: 144549-144549
  • DOI: 10.1016/j.scitotenv.2020.144549
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Estimating the asymptomatic proportion of SARS-CoV-2 infection in the general population: Analysis of a nationwide serosurvey in the Netherlands (2021)
  • Author(s): McDonald SA、Miura F、Vos ERA、Boven M van、de Melker H、van der Klis F、van Binnendijk R、Hartog G den、Wallinga J
  • Journal Title: medRxiv Volume: -
  • DOI: 10.1101/2021.03.29.21254334
  • Open Access / Int'l Joint Research
• [Journal Article] COVID-19 risk assessment at the opening ceremony of the Tokyo 2020 Olympic Games (2021)
  • Author(s): Murakami Michio、Miura Fuminari、Kitajima Masaaki、Fujii Kenkichi、Yasutaka Tetsuo、Iwasaki Yuichi、Ono Kyoko、Shimazu Yuzo、Sorano Sumire、Okuda Tomoaki、Ozaki Akihiko、Katayama Kotoe、Nishikawa Yoshitaka、Kobashi Yurie、Sawano Toyoaki、Abe Toshiki、Saito Masaya M.、Tsubokura Masaharu、Naito Wataru、Imoto Seiya
  • Journal Title: Microbial Risk Analysis Volume: - Pages: 100162-100162
  • DOI: 10.1016/j.mran.2021.100162
  • Peer Reviewed / Open Access
• [Journal Article] Impact of the Heterogeneity in Free Chlorine, UV254, and Ozone Susceptibilities Among Coxsackievirus B5 on the Prediction of the Overall Inactivation Efficiency (2021)
  • Author(s): Torii Shotaro、Miura Fuminari、Itamochi Masae、Haga Kei、Katayama Kazuhiko、Katayama Hiroyuki
  • Journal Title: Environmental Science & Technology Volume: 55 Issue: 5 Pages: 3156-3164
  • DOI: 10.1021/acs.est.0c07796
  • Peer Reviewed / Open Access
• [Presentation] Quantifying vaccine effect and heterogeneity in susceptibility using human challenge studies. (2023)
  • Author(s): Miura, F.*, Klinkenberg, D., & Wallinga, J.
  • Organizer: 34th Annual Scientific Meeting of the Japan Epidemiological Association
  • Int'l Joint Research
• [Presentation] Inferring properties of next-generation matrices and contact patterns from observations in real time. (2023)
  • Author(s): Miura, F.*, Hens, N., & Wallinga, J.
  • Organizer: 9th International Conference on Infectious Disease Dynamics
  • Int'l Joint Research
• [Presentation] The fading of the mpox outbreak among MSM in the Netherlands. (2023)
  • Author(s): Xiridou, M., Miura, F.*, Adam P., Op de Coul, E., de Wit, J., & Wallinga, J.
  • Organizer: 9th International Conference on Infectious Disease Dynamics
  • Int'l Joint Research
• [Presentation] Dynamic landscape of mpox importation risks driven by heavy-tailed sexual contact networks among men who have sex with men: A mathematical modeling study. (2023)
  • Author(s): Jung, S-M.*, Miura, F., Murayama, H., Funk, S., Wallinga, J., Lessler, J., & Endo, A.
  • Organizer: 9th International Conference on Infectious Disease Dynamics
  • Int'l Joint Research
• [Presentation] Quantitative analysis of viral dynamics in mpox patients: Application to isolation guidelines. (2023)
  • Author(s): Jeong, Y-D*., Miura, F., & Iwami, S.;
  • Organizer: 9th International Conference on Infectious Disease Dynamics
  • Int'l Joint Research
• [Presentation] How human challenge studies reveal vaccine efficacy and mode of action. (2022)
  • Author(s): Miura, F., Klinkenberg, D., Ainslie, K. E. C., Backer, J. A., Leung, K. Y., McDonald, S. A., de Boer, P., & Wallinga, J
  • Organizer: 1th Congress (OPTIONS XI) for the control of influenza, Belfast, September 2022
  • Int'l Joint Research
• [Presentation] Time course of SARS-CoV-2 viral shedding in feces: a modelling study. (2022)
  • Author(s): Miura, F., Omori, R., & Kitajima, M.
  • Organizer: 7th Food and Environmental Virology Conference, Santiago de Compostela, May 2022
  • Int'l Joint Research
• [Presentation] Determining optimal vaccine allocation with approximation of next generation matrices (2022)
  • Author(s): Miura, F.
  • Organizer: UMC Utrecht seminar series
  • Invited
• [Presentation] Incubation period for monkeypox cases confirmed in the Netherlands, May 2022 (2022)
  • Author(s): Miura, F.
  • Organizer: WHO calls for the monkeypox data analytics, Online (Geneva), July 2022
  • Invited
• [Presentation] Incubation period for monkeypox cases confirmed in the Netherlands, May 2022 (2022)
  • Author(s): Miura, F.
  • Organizer: 6th ECDC/EACS webinar on the monkeypox outbreak, Online (Stockholm), July 2022
  • Invited
• [Presentation] Time scales of human mpox transmission in the Netherlands (2022)
  • Author(s): Wallinga, J. and Miura, F.
  • Organizer: WHO MPX analytics call, Online (Geneva), December 2022
  • Invited
• [Presentation] 国内主要都市における定量的下水疫学情報に基づくCOVID-19流行動向の把握 (2022)
  • Author(s): 荒川千智，岩本遼，三浦郁修，左近直美，橋本温，原本英司，岡部聡，北島正章．
  • Organizer: 第56回日本水環境学会年会
• [Presentation] Inferring vaccine efficacy and mode of action from human challenge studies. (2021)
  • Author(s): Miura, F., Klinkenberg, D., & Wallinga, J.
  • Organizer: 8th International Conference on Infectious Disease Dynamics
  • Int'l Joint Research
• [Presentation] The impact of vaccinating adolescents on SARS-CoV-2 transmission: a modelling study. (2021)
  • Author(s): Ainslie, K. E., Backer, J., de Boer, P., van Hoek A. J., Klinkenberg, D., Lagerwij, G., McDonald, S., Miura, F., & Wallinga, J
  • Organizer: 8th International Conference on Infectious Disease Dynamics
  • Int'l Joint Research
• [Presentation] 国内主要都市における長期間の定量的COVID-19下水疫学調査 (2021)
  • Author(s): 荒川千智，三浦郁修，岩本遼，左近直美，橋本温，原本英司，岡部聡，北島正章．
  • Organizer: 土木学会第58回環境工学研究フォーラム
• [Presentation] 国内主要都市における長期間の定量的下水疫学調査から推定するCOVID-19流行実態 (2021)
  • Author(s): 荒川千智，三浦郁修，岩本遼，左近直美，橋本温，原本英司，岡部聡，北島正章．
  • Organizer: 第24 回日本水環境学会シンポジウム
• [Presentation] Wastewater as an alternative surveillance: how can we translate environmental data into public health implications via mathematical modelling? (2021)
  • Author(s): 三浦郁修
  • Organizer: Tsukuba conference
  • Int'l Joint Research / Invited
• [Presentation] Wastewater as an interface between environmental engineering and epidemiology (2021)
  • Author(s): 三浦郁修
  • Organizer: 応用生態工学会・国際シンポジウム
  • Int'l Joint Research / Invited
• [Presentation] 下水中ウイルス情報と数理モデルによる隠れた感染動態の把握 (2021)
  • Author(s): 三浦郁修
  • Organizer: ネオMEセミナー（名古屋大学）
  • Invited
• [Presentation] 新型コロナウイルスの下水中モニタリングと疾病制御：数理疫学からみた現状と展望 (2021)
  • Author(s): 三浦郁修，大森亮介，北島正章，渡辺幸三
  • Organizer: 第55回日本水環境学会年会
• [Presentation] 国内のCOVID-19感染流行期における都市下水中のSARS-CoV-2 RNAの検出 (2021)
  • Author(s): 荒川千智，三浦郁修，岡部聡，北島正章
  • Organizer: 第55回日本水環境学会年会
• [Presentation] 疫学調査および微生物データに基づく潜在的な感染症拡大の統計的推定 (2020)
  • Author(s): 三浦郁修
  • Organizer: 第23回日本水環境学会シンポジウム
• [Presentation] 下水中 SARS-CoV-2 RNA 濃度に基づくCOVID-19 感染者数推定モデルの構築と適用 (2020)
  • Author(s): 三浦郁修，荒川千智，原本英司，北島正章
  • Organizer: 第23回日本水環境学会シンポジウム
• [Book] 地球の危機図鑑（第８章：パンデミックを担当） (2022)
  • Author(s): 福士謙介
  • Total Pages: 112
  • Publisher: 学研プラス
  • ISBN: 4055013698