研究者詳細

顔写真

サイトウ　マユコ
齊藤　繭子
Mayuko Saito
所属
大学院医学系研究科　医科学専攻　病理病態学講座（微生物学分野）
職名
教授
学位

  • 博士（医学）（佐賀大学）

  • 修士（Master of Public Health）（ジョンスホプキンス大学）

e-Rad 研究者番号
20598031

所属学協会 3

  • 米国熱帯医学会

  • 日本細菌学会

  • 日本内科学会

研究キーワード 4

  • 国際保健

  • ウイルス性胃腸炎

  • サポウイルス

  • ノロウイルス

研究分野 2

  • ライフサイエンス / 感染症内科学 / ウイルス性胃腸炎

  • ライフサイエンス / 衛生学、公衆衛生学分野：実験系を含む / 国際保健

論文 120

  1. Norovirus-associated diarrhea and asymptomatic infection in children aged under 4 years: a community-cohort study in the Philippines. 国際誌 査読有り

    Chuyao Yu, Maria Carmen A Corpuz, Joseph M Bonifacio, Makiko Kishi, Takeaki Imamura, Yusuke Sayama, Mariko Saito-Obata, Clyde Dapat, Michiko Okamoto, Hitoshi Oshitani, Mayuko Saito

    IJID regions　14　100549-100549　2025年3月

    DOI： 10.1016/j.ijregi.2024.100549 　

    詳細を見る 詳細を閉じる

    OBJECTIVES: This study aimed to estimate the incidence of norovirus (NoV)-associated diarrhea and asymptomatic infections in children under 4 years of age and identify the genotypes of multiple NoV infections. METHODS: A community-based cohort study was conducted in Tarlac, Philippines. Children aged 0-2 years were followed up for 2 years. The prevalence and incidence rates of NoV-associated diarrhea and asymptomatic infections were calculated. Risk factors were assessed using the Cox proportional hazards model. The genotypes and immunotypes of repeated infections were tabulated. RESULTS: A total of 338 children aged 6208 child-months were analyzed. NoV was detected in 17.4% (84 of 527, 95% confidence interval [CI]: 12.7-19.7%) of diarrheal episodes and 10.8% (219 of 2031, 95% CI: 9.4-12.3%) of asymptomatic stool samples. The highest incidence of NoV-associated diarrhea occurred in children aged 6-11 months (2.31 per 100 child-months, 95% CI: 1.30-3.32) and 18-23 months (2.34 per 100 child-months, 95% CI: 1.57-3.12), whereas the highest incidence of asymptomatic NoV infection was observed in children aged 12-23 months (4.49 per 100 child-months, 95% CI: 3.41-5.56). Repeated NoV infections were detected between different genotypes, except in two children who had repeated NoV GI.3 and two children with GI.9 infections. CONCLUSIONS: Children had the highest risk of NoV-associated diarrhea during their first year of life, whereas asymptomatic NoV infections persisted after the second year. Repeated NoV infections suggest genotype-specific immunity after NoV infection.

  2. Infection by Helicobacter pylori cytotoxin-A-associated antigen-positive strains is associated with iron deficiency anemia in a longitudinal birth cohort in Brazil. 国際誌 査読有り

    Dulciene M M Queiroz, Lucia L C Braga, Gifone A Rocha, Sérgio A Batista, Andreia M C Rocha, Mayuko Saito, William Checkley, Robert H Gilman, Jean E Crabtree

    Haematologica　109　(12)　4112-4115　2024年12月1日

    DOI： 10.3324/haematol.2024.285446 　

  3. Serological analyses against endemic human coronaviruses and SARS-CoV-2 in children and adults using samples collected before the COVID-19 pandemic. 国際誌 査読有り

    Yusuke Sayama, Chuan Lo, Hiroki Tomizawa, Mayuko Saito, Michiko Okamoto, Suguru Ohmiya, Hidekazu Nishimura, Hitoshi Oshitani

    IJID regions　13　100485-100485　2024年12月

    DOI： 10.1016/j.ijregi.2024.100485 　

    詳細を見る 詳細を閉じる

    OBJECTIVES: Four endemic human coronaviruses (HCoVs), HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43, infect humans during childhood and cause the common cold. COVID-19 caused by SARS-CoV-2 leads to mild symptoms in children, possibly owing to the protection conferred by immunity developed during a previous HCoV infection. This study analyzed the seroreactivity of four endemic HCoVs and SARS-CoV-2 in children and adults. METHODS: A total of 747 serum samples (from individuals aged 6 months to 69 years) were collected from 2015 to 2019 before the COVID-19 pandemic in Japan. The samples were tested for immunoglobulin G antibodies against the four endemic HCoVs and SARS-CoV-2 wild-type spike ectodomain proteins using enzyme-linked immunosorbent assay. RESULTS: The seroprevalence of endemic HCoVs (except HCoV-229E) showed 90% positivity by 3-4 years old, whereas HCoV-229E seroprevalence was observed at 8 years old. Approximately 35% of the samples showed reactivity to SARS-CoV-2 and did not change with age. However, the children's group presented higher antibody levels than the adult group. The sample reactivity against SARS-CoV-2 did not confirm neutralization capability. CONCLUSIONS: The reactive samples against SARS-CoV-2 showed varying antibody levels among different age groups. These findings may contribute to a deeper understanding of the clinical symptoms of COVID-19 and coronavirus diseases.

  4. Quantitative evaluation of water, sanitation, and hygiene measures on COVID-19 pandemic peak reduction in the Philippines. 国際誌 査読有り

    Sewwandi Bandara, Clyde Dapat, Wakana Oishi, Emmanuel Kagning Tsinda, Mayuko Saito, Daisuke Sano

    The Science of the total environment　949　175055-175055　2024年11月1日

    DOI： 10.1016/j.scitotenv.2024.175055 　

    詳細を見る 詳細を閉じる

    New cases of coronavirus disease 2019 (COVID-19) are continually being recorded worldwide, despite global efforts in implementing non-pharmaceutical interventions and establishing vaccination programs. This trend highlights the need to identify the factors associated with the continued spread of COVID-19. The World Health Organization recommends hand washing as a cost-effective intervention for preventing COVID-19, indicating that water, sanitation, and hygiene (WaSH) are central to the prevention of the disease. However, low- and middle-income countries lack adequate access to WaSH, which increases the risk of contracting COVID-19. The aim of this study was to identify the WaSH factors associated with the incidence of COVID-19 and quantitatively estimate the effects of improvements in WaSH on reducing the incidence of COVID-19 during the peak of the pandemic. Lasso regression and extreme gradient boosting models were used to identify the WaSH factors. Distinct estimation models were developed to assess the effect of WaSH in rural regions under two assumptions: increasing regional basic sanitation coverage up to 25 % and 50%. The reduction in the incidence of COVID-19 during the peak of the pandemic was calculated for each rural region. The results of the analyses indicated that basic sanitation is important for reducing the incidence of COVID-19 in rural regions compared to urban regions in the Philippines. In addition, the results suggested that increasing basic sanitation coverage could reduce the incidence of COVID-19 by 2-66 %, alleviating the burden on healthcare facilities. This study indicates that improved basic sanitation infrastructure are needed in rural Philippines. The results of this study emphasise the significance of WaSH as an indicator of COVID-19 incidence, highlighting the need for its enhancement to enable the achievement of sustainable disease prevention and pandemic preparedness goals.

  5. Identification of environmental, socioeconomic, water, sanitation, and hygiene (WaSH) factors associated with COVID-19 incidence in the Philippines: A nationwide modelling study. 国際誌 査読有り

    Sewwandi Bandara, Clyde Dapat, Wakana Oishi, Emmanuel Kagning Tsinda, Lea Necitas G Apostol, Naoko Hirayama, Mayuko Saito, Daisuke Sano

    The Science of the total environment　946　174214-174214　2024年10月10日

    DOI： 10.1016/j.scitotenv.2024.174214 　

    詳細を見る 詳細を閉じる

    Despite the implementation of non-pharmaceutical interventions, the threat of coronavirus disease 2019 (COVID-19) remains significant on a global scale. Identifying external factors contributing to its spread is crucial, especially given the World Health Organization's recommendation emphasizing access to water, sanitation, and hygiene as essential in curbing COVID-19. There is a notable discrepancy in access to sanitation facilities, particularly evident in low- and middle-income countries. However, there is a lack of quantitative assessments regarding these factors. This study examines various environmental, socioeconomic, water, sanitation, and hygiene factors and their associations with COVID-19 incidence. All regions in the Philippines were categorized into clusters based on socioeconomic factors. A conceptual structural equation model (SEM) was developed using domain knowledge. The best-fitting SEM for each cluster was determined, and associations between factors and COVID-19 incidence were estimated. The correlation analysis revealed that rainfall, minimum temperature, and relative humidity were positively correlated with weekly COVID-19 incidence in urban regions. Maximum temperature, mean temperature, wind speed, and wind direction were negatively correlated with weekly COVID-19 incidence in rural regions, with time lags of 0, 3, and 7 weeks. In urban regions (Cluster 1), factors such as urbanization rate (1.00), area (-0.93), and population (0.54) were found to be associated with weekly COVID-19 incidence. Conversely, in rural regions (Cluster 2), factors including area (0.17), basic sanitation (0.84), and wind direction (0.83) showed associations with weekly COVID-19 incidence. These factors were causally associated with a latent variable reflecting the hidden confounders associated with COVID-19 incidence. It is important to note that sanitation factors were associated only in rural regions. Improving access to sanitation facilities in rural regions of the Philippines is imperative to effectively mitigate disease transmission in future pandemics. Identification of the causal effect of unobserved confounders with COVID-19 incidence is recommended for future research.

  6. Characterization of human respiratory syncytial virus in children with severe acute respiratory infection before and during the COVID-19 pandemic. 国際誌 査読有り

    Paul Simusika, Michiko Okamoto, Clyde Dapat, Walter Muleya, Moffat Malisheni, Sikandar Azam, Takeaki Imamura, Mayuko Saito, Innocent Mwape, Evans Mpabalwani, Mwaka Monze, Hitoshi Oshitani

    IJID regions　11　100354-100354　2024年6月

    DOI： 10.1016/j.ijregi.2024.03.009 　

    詳細を見る 詳細を閉じる

    OBJECTIVES: Annual outbreaks of human respiratory syncytial virus (HRSV) are caused by newly introduced and locally persistent strains. During the COVID-19 pandemic, global and local circulation of HRSV significantly decreased. This study was conducted to characterize HRSV in 2018-2022 and to analyze the impact of COVID-19 on the evolution of HRSV. DESIGN/METHODS: Combined oropharyngeal and nasopharyngeal swabs were collected from children hospitalized with severe acute respiratory infection at two hospitals in Zambia. The second hypervariable region of the attachment gene G was targeted for phylogenetic analysis. RESULTS: Of 3113 specimens, 504 (16.2%) were positive for HRSV, of which 131 (26.0%) and 66 (13.1%) were identified as HRSVA and HRSVB, respectively. In early 2021, an increase in HRSV was detected, caused by multiple distinct clades of HRSVA and HRSVB. Some were newly introduced, whereas others resulted from local persistence. CONCLUSIONS: This study provides insights into the evolution of HRSV, driven by global and local circulation. The COVID-19 pandemic had a temporal impact on the evolution pattern of HRSV. Understanding the evolution of HRSV is vital for developing strategies for its control.

  7. Identification of Various Recombinants in a Patient Coinfected With the Different SARS-CoV-2 Variants. 国際誌 査読有り

    Yusuke Sayama, Akie Sakagami, Michiko Okamoto, Masahiro Sakamoto, Hikari Koizumi, Yoko Kimura, Clyde Dapat, Mayuko Saito, Yuko Suzuki, Mie Sasaki, Naoko Sugawara, Hitoshi Oshitani

    Influenza and other respiratory viruses　18　(6)　e13340　2024年6月

    DOI： 10.1111/irv.13340 　

    詳細を見る 詳細を閉じる

    BACKGROUND: Viral recombination that occurs by exchanging genetic materials between two viral genomes coinfecting the same host cells is associated with the emergence of new viruses with different virulence. Herein, we detected a patient coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants and identified various recombinants in the SARS-CoV-2 full-length spike gene using long-read and Sanger sequencing. METHODS: Samples from five patients in Japan with household transmission of coronavirus disease 2019 (COVID-19) were analyzed using molecular assays for detection and identification of SARS-CoV-2. Whole-genome sequencing was conducted using multiplex PCR with short-read sequencing. RESULTS: Among the five SARS-CoV-2-positive patients, the mutation-specific assay identified the Delta variant in three, the Omicron variant in one, and an undetermined in one. The undermined patient was identified as Delta using whole-genome sequencing, but samples showed a mixed population of Delta and Omicron variants. This patient was analyzed for viral quasispecies by long-read and Sanger sequencing using a full-length spike gene amplicon. In addition to the Delta and Omicron sequences, the viral quasispecies analysis identified nine different genetic recombinant sequences with various breakpoints between Delta and Omicron sequences. The nine detected recombinant sequences in the spike gene showed over 99% identity with viruses that were detected during the Delta and Omicron cocirculation period from the United States and Europe. CONCLUSIONS: This study demonstrates that patients coinfected with different SARS-CoV-2 variants can generate various viral recombinants and that various recombinant viruses may be produced during the cocirculation of different variants.

  8. Epidemiology of enterotoxigenic Escherichia coli and impact on the growth of children in the first two years of life in Lima, Peru 査読有り

    Monica J. Pajuelo, Sassan Noazin, Lilia Cabrera, Angie Toledo, Mirza Velagic, Lucero Arias, Mayra Ochoa, Lawrence H. Moulton, Mayuko Saito, Robert H. Gilman, Subhra Chakraborty

    Frontiers in Public Health　12　2024年3月22日

    出版者・発行元： Frontiers Media SA

    DOI： 10.3389/fpubh.2024.1332319 　

    eISSN：2296-2565

    詳細を見る 詳細を閉じる

    Background Enterotoxigenic E. coli (ETEC) is a leading cause of diarrheal morbidity and mortality in children, although the data on disease burden, epidemiology, and impact on health at the community level are limited. Methods In a longitudinal birth cohort study of 345 children followed until 24 months of age in Lima, Peru, we measured ETEC burden in diarrheal and non-diarrheal samples using quantitative PCR (LT, STh, and STp toxin genes), studied epidemiology and measured anthropometry in children. Results About 70% of children suffered from one or more ETEC diarrhea episodes. Overall, the ETEC incidence rate (IR) was 73 per 100 child-years. ETEC infections began early after birth causing 10% (8.9–11.1) ETEC-attributable diarrheal burden at the population level (PAF) in neonates and most of the infections (58%) were attributed to ST-ETEC [PAF 7.9% (1.9–13.5)] and LT + ST-ETEC (29%) of which all the episodes were associated with diarrhea. ETEC infections increased with age, peaking at 17% PAF (4.6–27.7%; p = 0.026) at 21 to 24 months. ST-ETEC was the most prevalent type (IR 32.1) with frequent serial infections in a child. The common colonization factors in ETEC diarrhea cases were CFA/I, CS12, CS21, CS3, and CS6, while in asymptomatic ETEC cases were CS12, CS6 and CS21. Only few (5.7%) children had repeated infections with the same combination of ETEC toxin(s) and CFs, suggested genotype-specific immunity from each infection. For an average ETEC diarrhea episode of 5 days, reductions of 0.060 weight-for-length z-score (0.007 to 0.114; p = 0.027) and 0.061 weight-for-age z-score (0.015 to 0.108; p = 0.009) were noted in the following 30 days. Conclusion This study showed that ETEC is a significant pathogen in Peruvian children who experience serial infections with multiple age-specific pathotypes, resulting in transitory growth impairment.

  9. Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection. 国際誌 査読有り

    Sudhasini Panda, Jeffrey Morgan, Catherine Cheng, Mayuko Saito, Robert H Gilman, Nelly Ciobanu, Valeriu Crudu, Donald G Catanzaro, Antonino Catanzaro, Timothy Rodwell, Judy S B Perera, Teshan Chathuranga, Bandu Gunasena, Aruna D DeSilva, Bjoern Peters, Alessandro Sette, Cecilia S Lindestam Arlehamn

    Nature communications　15　(1)　765-765　2024年1月26日

    DOI： 10.1038/s41467-024-45058-9 　

    詳細を見る 詳細を閉じる

    There is still incomplete knowledge of which Mycobacterium tuberculosis (Mtb) antigens can trigger distinct T cell responses at different stages of infection. Here, a proteome-wide screen of 20,610 Mtb-derived peptides in 21 patients mid-treatment for active tuberculosis (ATB) reveals IFNγ-specific T cell responses against 137 unique epitopes. Of these, 16% are recognized by two or more participants and predominantly derived from cell wall and cell processes antigens. There is differential recognition of antigens, including TB vaccine candidate antigens, between ATB participants and interferon-gamma release assay (IGRA + /-) individuals. We developed an ATB-specific peptide pool (ATB116) consisting of epitopes exclusively recognized by ATB participants. This pool can distinguish patients with pulmonary ATB from IGRA + /- individuals from various geographical locations, with a sensitivity of over 60% and a specificity exceeding 80%. This proteome-wide screen of T cell reactivity identified infection stage-specific epitopes and antigens for potential use in diagnostics and measuring Mtb-specific immune responses.

  10. Effects of breastfeeding on children's gut colonization with multidrug-resistant Enterobacterales in peri-urban Lima, Peru. 国際誌 査読有り

    Maya L Nadimpalli, Luismarcelo Rojas Salvatierra, Subhra Chakraborty, Jenna M Swarthout, Lilia Z Cabrera, Amy J Pickering, Maritza Calderon, Mayuko Saito, Robert H Gilman, Monica J Pajuelo

    Gut microbes　16　(1)　2309681-2309681　2024年

    DOI： 10.1080/19490976.2024.2309681 　

    詳細を見る 詳細を閉じる

    Children living in low-resource settings are frequently gut-colonized with multidrug-resistant bacteria. We explored whether breastfeeding may protect against children's incident gut colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella, Enterobacter, or Citrobacter spp. (ESBL-KEC). We screened 937 monthly stool samples collected from 112 children aged 1-16 months during a 2016-19 prospective cohort study of enteric infections in peri-urban Lima. We used 52,816 daily surveys to examine how exposures to breastfeeding in the 30 days prior to a stool sample were associated with children's risks of incident gut-colonization, controlling for antibiotic use and other covariates. We sequenced 78 ESBL-Ec from 47 children to explore their diversity. Gut-colonization with ESBL-Ec was increasingly prevalent as children aged, approaching 75% by 16 months, while ESBL-KEC prevalence fluctuated between 18% and 36%. Through 6 months of age, exclusively providing human milk in the 30 days prior to a stool sample did not reduce children's risk of incident gut-colonization with ESBL-Ec or ESBL-KEC. From 6 to 16 months of age, every 3 additional days of breastfeeding in the prior 30 days was associated with 6% lower risk of incident ESBL-Ec gut-colonization (95% CI: 0.90, 0.98, p = .003). No effects were observed on incident ESBL-KEC colonization. We detected highly diverse ESBL-Ec among children and few differences between children who were predominantly breastfed (mean age: 4.1 months) versus older children (10.8 months). Continued breastfeeding after 6 months conferred protection against children's incident gut colonization with ESBL-Ec in this setting. Policies supporting continued breastfeeding should be considered in efforts to combat antibiotic resistance.

  11. Time-varying overdispersion of SARS-CoV-2 transmission during the periods when different variants of concern were circulating in Japan. 国際誌 査読有り

    Yura K Ko, Yuki Furuse, Kanako Otani, Masato Yamauchi, Kota Ninomiya, Mayuko Saito, Takeaki Imamura, Alex R Cook, Tadayuki Ahiko, Shunji Fujii, Yoshiharu Mori, Emiko Suzuki, Keiko Yamada, Yoshikazu Ashino, Hidetoshi Yamashita, Yuichi Kato, Katsumi Mizuta, Motoi Suzuki, Hitoshi Oshitani

    Scientific reports　13　(1)　13230-13230　2023年8月14日

    DOI： 10.1038/s41598-023-38007-x 　

    詳細を見る 詳細を閉じる

    Japan has implemented a cluster-based approach for coronavirus disease 2019 (COVID-19) from the pandemic's beginning based on the transmission heterogeneity (overdispersion) of severe acute respiratory coronavirus 2 (SARS-CoV-2). However, studies analyzing overdispersion of transmission among new variants of concerns (VOCs), especially for Omicron, were limited. Thus, we aimed to clarify how the transmission heterogeneity has changed with the emergence of VOCs (Alpha, Delta, and Omicron) using detailed contact tracing data in Yamagata Prefecture, Japan. We estimated the time-varying dispersion parameter ([Formula: see text]) by fitting a negative binomial distribution for each transmission generation. Our results showed that even after the emergence of VOCs, there was transmission heterogeneity of SARS-CoV-2, with changes in [Formula: see text] during each wave. Continuous monitoring of transmission dynamics is vital for implementing appropriate measures. However, a feasible and sustainable epidemiological analysis system should be established to make this possible.

  12. Lack of zoonotic coronavirus species detected among children hospitalized with pneumonia in the Philippines. 国際誌 査読有り

    Yusuke Sayama, Michiko Okamoto, Mayuko Saito, Raita Tamaki, Mariko Saito-Obata, Reynaldo Frederick Negosa Quicho, Christina Dahlia Joboco, Socorro Lupisan, Hitoshi Oshitani

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America　2023年7月20日

    DOI： 10.1093/cid/ciad430 　

  13. Rapid Detection of SARS-CoV-2 RNA Using Reverse Transcription Recombinase Polymerase Amplification (RT-RPA) with Lateral Flow for N-Protein Gene and Variant-Specific Deletion-Insertion Mutation in S-Protein Gene. 国際誌 査読有り

    Jose L Malaga, Monica J Pajuelo, Michiko Okamoto, Emmanuel Kagning Tsinda, Kanako Otani, Pablo Tsukayama, Lucero Mascaro, Diego Cuicapuza, Masamichi Katsumi, Kazuhisa Kawamura, Hidekazu Nishimura, Akie Sakagami, Yo Ueki, Suguru Omiya, Satoshi Okamoto, Asami Nakayama, Shin-Ichi Fujimaki, Chuyao Yu, Sikandar Azam, Eiichi Kodama, Clyde Dapat, Hitoshi Oshitani, Mayuko Saito

    Viruses　15　(6)　2023年5月26日

    DOI： 10.3390/v15061254 　

    詳細を見る 詳細を閉じる

    Rapid molecular testing for severe acute respiratory coronavirus 2 (SARS-CoV-2) variants may contribute to the development of public health measures, particularly in resource-limited areas. Reverse transcription recombinase polymerase amplification using a lateral flow assay (RT-RPA-LF) allows rapid RNA detection without thermal cyclers. In this study, we developed two assays to detect SARS-CoV-2 nucleocapsid (N) gene and Omicron BA.1 spike (S) gene-specific deletion-insertion mutations (del211/ins214). Both tests had a detection limit of 10 copies/µL in vitro and the detection time was approximately 35 min from incubation to detection. The sensitivities of SARS-CoV-2 (N) RT-RPA-LF by viral load categories were 100% for clinical samples with high (>9015.7 copies/µL, cycle quantification (Cq): < 25) and moderate (385.5-9015.7 copies/µL, Cq: 25-29.9) viral load, 83.3% for low (16.5-385.5 copies/µL, Cq: 30-34.9), and 14.3% for very low (<16.5 copies/µL, Cq: 35-40). The sensitivities of the Omicron BA.1 (S) RT-RPA-LF were 94.9%, 78%, 23.8%, and 0%, respectively, and the specificity against non-BA.1 SARS-CoV-2-positive samples was 96%. The assays seemed more sensitive than rapid antigen detection in moderate viral load samples. Although implementation in resource-limited settings requires additional improvements, deletion-insertion mutations were successfully detected by the RT-RPA-LF technique.

  14. Transmission of COVID-19 in Nightlife, Household, and Health Care Settings in Tokyo, Japan, in 2020 査読有り

    Takeaki Imamura, Aika Watanabe, Yusuke Serizawa, Manami Nakashita, Mayuko Saito, Mayu Okada, Asamoe Ogawa, Yukiko Tabei, Yoshiko Soumura, Yoko Nadaoka, Naoki Nakatsubo, Takashi Chiba, Kenji Sadamasu, Kazuhisa Yoshimura, Yoshihiro Noda, Yuko Iwashita, Yuji Ishimaru, Naomi Seki, Kanako Otani, Tadatsugu Imamura, Matthew Myers Griffith, Kelly DeToy, Motoi Suzuki, Michihiko Yoshida, Atsuko Tanaka, Mariko Yauchi, Tomoe Shimada, Hitoshi Oshitani

    JAMA Network Open　6　(2)　e230589-e230589　2023年2月24日

    出版者・発行元： American Medical Association (AMA)

    DOI： 10.1001/jamanetworkopen.2023.0589 　

    eISSN：2574-3805

    詳細を見る 詳細を閉じる

    Importance There have been few studies on the heterogeneous interconnection of COVID-19 outbreaks occurring in different social settings using robust, surveillance epidemiological data. Objectives To describe the characteristics of COVID-19 transmission within different social settings and to evaluate settings associated with onward transmission to other settings. Design, Setting, and Participants This is a case series study of laboratory-confirmed COVID-19 cases in Tokyo between January 23 and December 5, 2020, when vaccination was not yet implemented. Using epidemiological investigation data collected by public health centers, epidemiological links were identified and classified into 7 transmission settings: imported, nightlife, dining, workplace, household, health care, and other. Main Outcomes and Measures The number of cases per setting and the likelihood of generating onward transmissions were compared between different transmission settings. Results Of the 44 054 confirmed COVID-19 cases in this study, 25 241 (57.3%) were among male patients, and the median (IQR) age of patients was 36 (26-52) years. Transmission settings were identified in 13 122 cases, including 6768 household, 2733 health care, and 1174 nightlife cases. More than 6600 transmission settings were detected, and nightlife (72 of 380 [18.9%]; P &amp;amp;lt; .001) and health care (119 [36.2%]; P &amp;amp;lt; .001) settings were more likely to involve 5 or more cases than dining, workplace, household, and other settings. Nightlife cases appeared in the earlier phase of the epidemic, while household and health care cases appeared later. After adjustment for transmission setting, sex, age group, presence of symptoms, and wave, household and health care cases were less likely to generate onward transmission compared with nightlife cases (household: adjusted odds ratio, 0.03; 95% CI, 0.02-0.05; health care: adjusted odds ratio, 0.57; 95% CI, 0.41-0.79). Household settings were associated with intergenerational transmission, while nonhousehold settings mainly comprised transmission between the same age group. Among 30 932 cases without identified transmission settings, cases with a history of visiting nightlife establishments were more likely to generate onward transmission to nonhousehold settings (adjusted odds ratio, 5.30 [95% CI, 4.64-6.05]; P &amp;amp;lt; .001) than those without such history. Conclusions and Relevance In this case series study, COVID-19 cases identified in nightlife settings were associated with a higher likelihood of spreading COVID-19 than household and health care cases. Surveillance and interventions targeting nightlife settings should be prioritized to disrupt COVID-19 transmission, especially in the early stage of an epidemic.

  15. Seroprevalence of four endemic human coronaviruses and, reactivity and neutralization capability against SARS-CoV-2 among children in the Philippines. 国際誌 査読有り

    Yusuke Sayama, Michiko Okamoto, Mayuko Saito, Mariko Saito-Obata, Raita Tamaki, Christine Dahlia Joboco, Socorro Lupisan, Hitoshi Oshitani

    Scientific reports　13　(1)　2310-2310　2023年2月9日

    DOI： 10.1038/s41598-023-29072-3 　

    詳細を見る 詳細を閉じる

    Four endemic human coronaviruses (HCoV), HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43, are closely related to SARS-CoV-2. These coronaviruses are known to infect humans living in temperate areas, including children under 5 years old; however, the seroprevalence of four HCoVs among children in tropical areas, including the Philippines, remains unclear. This study aimed to assess the prevalence of antibodies against four HCoVs and to determine the reactivity and neutralization of these antibodies against SARS-CoV-2 among children in the Philippines. A total of 315 serum samples collected from 2015 to 2018, before the emergence of SARS-CoV-2, in Biliran island, Philippines, were tested for the presence of antibodies against four HCoVs and SARS-CoV-2 using recombinant spike ectodomain proteins by IgG-enzyme-linked immunosorbent assay (ELISA). Reactivity to and neutralization of SARS-CoV-2 were also investigated. The seroprevalence of the four HCoVs was 63.8% for HCoV-229E, 71.4% for HCoV-NL63, 76.5% for HCoV-HKU1, and 83.5% for HCoV-OC43 by ELISA. Age group analysis indicated that seropositivity to all HCoVs reached 80% by 2-3 years of age. While 69/315 (21.9%) of the samples showed reactive to SARS-CoV-2, almost no neutralization against SARS-CoV-2 was detected using neutralization assay. Reactivity of antibodies against SARS-CoV-2 spike protein obtained by ELISA may not correlate with neutralization capability.

  16. Comparison of Rhinovirus A-, B-, and C-Associated Respiratory Tract Illness Severity Based on the 5'-Untranslated Region Among Children Younger Than 5 Years. 国際誌 査読有り

    Akiko Sayama, Michiko Okamoto, Raita Tamaki, Mariko Saito-Obata, Mayuko Saito, Taro Kamigaki, Yusuke Sayama, Irene Lirio, Joanna Ina G Manalo, Veronica L Tallo, Socorro P Lupisan, Hitoshi Oshitani

    Open forum infectious diseases　9　(10)　ofac387　2022年10月

    DOI： 10.1093/ofid/ofac387 　

    詳細を見る 詳細を閉じる

    BACKGROUND: Rhinoviruses (RVs) are among the most frequently detected viruses from hospitalized children with severe acute respiratory infections, being classified into RV-A, RV-B, and RV-C (4 clades: C, GAC1, GAC2, and A2). This study aimed to compare the clinical characteristics and respiratory tract illness severity between the RV species and RV-C clades in children in primary care and hospital settings in rural communities in the Philippines. METHODS: Clinical samples and information of children <5 years old in the Philippines were collected from 2014 to 2016. The samples were tested by reverse-transcription polymerase chain reaction (RT-PCR) targeting the 5'-untranslated region. PCR-positive samples were sequenced, and RV species were identified by phylogenetic analysis. RESULTS: Overall, 3680 respiratory tract illness episodes in 1688 cohort children were documented; 713 of those were RV positive and identified as RV-A (n = 271), RV-B (n = 47), and RV-C (n = 395: C [n = 76], GAG1 [n = 172], GAG2 [n = 8], A2 [n = 138], and unidentified [n = 1]). Severe illnesses, low oxygen saturation, cough, and wheezing were more common in patients with RV-C, especially with GAC1, than in those with RV-A or RV-B. Furthermore, severe illness was significantly more common in RV-C (GAC1)-positive cases than in RV-A-positive cases (odds ratio, 2.61 [95% CI, 1.17-4.13]). CONCLUSIONS: Children infected with RV-C had more severe illnesses than children infected with RV-A and RV-B. Moreover, emerging clades of RV-C were associated with increased severity.

  17. Incidence of lower respiratory tract infection and associated viruses in a birth cohort in the Philippines. 国際誌 査読有り

    Kanako Otani, Mayuko Saito, Michiko Okamoto, Raita Tamaki, Mariko Saito-Obata, Taro Kamigaki, Irene C Lirio, Edelwisa Segubre-Mercado, Veronica Tallo, Socorro Lupisan, Hitoshi Oshitani

    BMC infectious diseases　22　(1)　313-313　2022年3月30日

    DOI： 10.1186/s12879-022-07289-3 　

    詳細を見る 詳細を閉じる

    BACKGROUND: Lower respiratory tract infection (LRTI) is an important cause of morbidity and mortality in infants and young children. However, the etiological role of viruses and the timing of developing LRTI are not well defined. METHODS: We analyzed the data of a prospective cohort study in the Philippines as a birth cohort. We detected LRTI among children who visited healthcare facilities with respiratory symptom, and collected nasopharyngeal swabs for virus detection. We analyzed the incidence rates (IRs) and cumulative proportion of LRTI and severe LRTI by age group and each virus detected. RESULTS: A total of 350 LRTI episodes were observed from 473 child-years yielded from 419 children. The IRs of LRTI were 70.8, 70.7, and 80.8 per 100 child-years for 0-5, 6-11, and 12-23 months of age, respectively. By 12 months of age, 45% of children developed LRTI at least once. Rhinovirus and respiratory syncytial virus were the most frequently detected viruses in all age groups. However, the IRs of influenza virus were low especially at 0-5 months of age. CONCLUSIONS: We identified various patterns of age-specific IRs of LRTI and severe LRTI for different viruses, which should be considered to establish more effective interventions including vaccinations.

  18. Secondary transmission of SARS-CoV-2 during the first two waves in Japan: Demographic characteristics and overdispersion 査読有り

    Yura K Ko, Yuki Furuse, Kota Ninomiya, Kanako Otani, Hiroki Akaba, Reiko Miyahara, Tadatsugu Imamura, Takeaki Imamura, Alex R Cook, Mayuko Saito, Motoi Suzuki, Hitoshi Oshitani

    International Journal of Infectious Diseases　116　365-373　2022年3月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.ijid.2022.01.036 　

    ISSN：1201-9712

  19. COVID-19 case prediction via wastewater surveillance in a low-prevalence urban community: a modeling approach 国際誌 査読有り

    Yifan Zhu, Wakana Oishi, Chikako Maruo, Sewwandi Bandara, Mu Lin, Mayuko Saito, Masaaki Kitajima, Daisuke Sano

    JOURNAL OF WATER AND HEALTH　20　(2)　459-470　2022年2月

    DOI： 10.2166/wh.2022.183 　

    ISSN：1477-8920

    eISSN：1996-7829

  20. Integration of publicly available case-based data for real-time coronavirus disease 2019 risk assessment, Japan. 国際誌 査読有り

    Kota Ninomiya, Mariko Kanamori, Naomi Ikeda, Kazuaki Jindai, Yura K Ko, Kanako Otani, Yuki Furuse, Hiroki Akaba, Reiko Miyahara, Mayuko Saito, Motoi Suzuki, Hitoshi Oshitani

    Western Pacific surveillance and response journal : WPSAR　13　(1)　1-6　2022年

    DOI： 10.5365/wpsar.2022.13.1.889 　

    詳細を見る 詳細を閉じる

    In response to the outbreak of coronavirus disease 2019 (COVID-19) in Japan, a national COVID-19 cluster taskforce (comprising governmental and nongovernmental experts) was established to support the country's Ministry of Health, Labour and Welfare in conducting daily risk assessment. The assessment was carried out using established infectious disease surveillance systems; however, in the initial stages of the pandemic these were not sufficient for real-time risk assessment owing to limited accessibility, delay in data entry and inadequate case information. Also, local governments were publishing anonymized data on confirmed COVID-19 cases on their official web sites as daily press releases. We developed a unique database for nationwide real-time risk assessment that included these case lists from local government web sites and integrated all case data into a standardized format. The database was updated daily and checked systematically to ensure comprehensiveness and quality. Between 15 January 2020 and 15 June 2021, 776 459 cases were logged in the database, allowing for analysis of real-time risk from the pandemic. This semi-automated database was used in daily risk assessments, and to evaluate and update control measures to prevent community transmission of COVID-19 in Japan. The data were reported almost every week to the Japanese Government Advisory Panel on COVID-19 for public health responses.

  21. Enteropathogen Changes After Rotavirus Vaccine Scale-up. 国際誌 査読有り

    Sarah-Blythe Ballard, David Requena, Holger Mayta, Gerardo J Sanchez, Maria G Oyola-Lozada, Fabiola D Colquechagua Aliaga, Lilia Cabrera, Macarena D Vittet Mondonedo, Carmen Taquiri, Capt Drake H Tilley, Cdr Mark P Simons, Rina A Meza, Caryn Bern, Mayuko Saito, Dante A Figueroa-Quintanilla, Robert H Gilman

    Pediatrics　2021年12月17日

    DOI： 10.1542/peds.2020-049884 　

    詳細を見る 詳細を閉じる

    OBJECTIVES: To inform next steps in pediatric diarrhea burden reduction by understanding the shifting enteropathogen landscape after rotavirus vaccine implementation. METHODS: We conducted a case-control study of 1788 medically attended children younger than 5 years, with and without gastroenteritis, after universal rotavirus vaccine implementation in Peru. We tested case and control stools for 5 viruses, 19 bacteria, and parasites; calculated coinfection-adjusted attributable fractions (AFs) to determine pathogen-specific burdens; and evaluated pathogen-specific gastroenteritis severity using Clark and Vesikari scales. RESULTS: Six pathogens were independently positively associated with gastroenteritis: norovirus genogroup II (GII) (AF 29.1, 95% confidence interval [CI]: 28.0-32.3), rotavirus (AF 8.9, 95% CI: 6.8-9.7), sapovirus (AF 6.3, 95% CI: 4.3-7.4), astrovirus (AF 2.8, 95% CI: 0.0-4.0); enterotoxigenic Escherichia coli heat stable and/or heat labile and heat stable (AF 2.4, 95% CI: 0.6-3.1), and Shigella spp. (AF 2.0, 95% CI: 0.4-2.2). Among typeable rotavirus cases, we most frequently identified partially heterotypic strain G12P[8] (54 of 81, 67%). Mean severity was significantly higher for norovirus GII-positive cases relative to norovirus GII-negative cases (Vesikari [12.7 vs 11.8; P < .001] and Clark [11.7 vs 11.4; P = .016]), and cases in the 6- to 12-month age range relative to cases in other age groups (Vesikari [12.7 vs 12.0; P = .0002] and Clark [12.0 vs 11.4; P = .0016]). CONCLUSIONS: Norovirus is well recognized as the leading cause of pediatric gastroenteritis in settings with universal rotavirus vaccination. However, sapovirus is often overlooked. Both norovirus and sapovirus contribute significantly to the severe pediatric disease burden in this setting. Decision-makers should consider multivalent vaccine acquisition strategies to target multiple caliciviruses in similar countries after successful rotavirus vaccine implementation.

  22. Near-Complete Genome Sequencing of Influenza C Virus in the Philippines between 2014 and 2019 国際誌 査読有り

    Daisetsu Fujita, Clyde Dapat, Emmanuel Kagning Tsinda, Mayuko Saito, Michiko Okamoto, Mariko Saito-Obata, Beatriz P. Quiambao, Socorro P. Lupisan, Hitoshi Oshitani

    Microbiology Resource Announcements　10　(49)　e0090021　2021年12月9日

    出版者・発行元： American Society for Microbiology

    DOI： 10.1128/mra.00900-21 　

    eISSN：2576-098X

    詳細を見る 詳細を閉じる

    We report 19 nearly complete genome sequences of influenza C virus isolated from clinical samples recovered from children in the Philippines between 2014 and 2019.

  23. Viral intra-host evolution in immunocompetent children contributes to human norovirus diversification at the global scale. 国際誌 査読有り

    Kentaro Tohma, Mayuko Saito, Monica J Pajuelo, Holger Mayta, Mirko Zimic, Cara J Lepore, Lauren A Ford-Siltz, Robert H Gilman, Gabriel I Parra

    Emerging microbes & infections　10　(1)　1717-1730　2021年12月

    DOI： 10.1080/22221751.2021.1967706 　

    詳細を見る 詳細を閉じる

    Norovirus is a major cause of acute gastroenteritis. Human noroviruses present >30 different genotypes, with a single genotype (GII.4) predominating worldwide. Concurrent outbreaks of norovirus are often associated with the emergence of new viruses. While different hypotheses have been presented, the source of new mutations in noroviruses is still unknown. In this study, we applied high-resolution sequencing to determine the intra-host viral diversity presented by noroviruses during the acute and shedding phase of infection in children. Profiling viral intra-host diversification at nearly full genome level indicated that GII.4 viruses presented dynamic intra-host variation, while non-GII.4 viruses presented minimal variation throughout the infection. Notably, the intra-host genetic variation during the shedding phase recapitulates the genetic diversity observed at the global level, particularly those mapping at the VP1 antigenic sites. Thus the intra-host evolution in healthy children explains the source of norovirus mutations that results in diversification at the global scale.

  24. Epidemiological factors associated with COVID-19 clusters in medical and social welfare facilities.

    Tadatsugu Imamura, Yura K Ko, Yuki Furuse, Takeaki Imamura, Kazuaki Jindai, Reiko Miyahara, Eiichiro Sando, Ikkoh Yasuda, Naho Tsuchiya, Mayuko Saito, Motoi Suzuki, Hitoshi Oshitani

    Japanese journal of infectious diseases　75　(3)　281-287　2021年10月29日

    DOI： 10.7883/yoken.JJID.2021.288 　

    詳細を見る 詳細を閉じる

    Characteristics of COVID-19 clusters in medical and social welfare facilities, and factors associated with cluster size are still not fully understood. We reviewed COVID-19 cases identified from January 15 to April 30 of 2020 in Japan, and analyzed factors associated with cluster size in medical and social welfare facilities. In the study, COVID-19 clusters were identified in 56 medical and 34 social welfare facilities. Numbers of cases in those facilities reached their peaks after the peak of general population. Duration of occurrence of new cases in clusters showed a positive correlation with the number of cases in both types of facilities (rho = 0.44, p < 0.001; and rho = 0.69, p < 0.001, respectively). However, number of days between the first case in the prefecture and the onset of clusters showed a negative correlation with the number of cases only in clusters in social welfare facilities (rho = -0.4, p = 0.004). Our results suggested that COVID-19 cases in those facilities were prevalent in the latter phase of the community transmissions, although the underlying mechanisms for such trend could be different between medical and social welfare facilities.

  25. Complete Genome Sequences of Enterovirus D68 Clade A and D Strains in the Philippines. 国際誌 査読有り

    Michiko Okamoto, Masahiro Sakamoto, Clyde Dapat, Mayuko Saito, Mariko Saito-Obata, Raita Tamaki, Socorro P Lupisan, Beatriz P Quiambao, Hitoshi Oshitani

    Microbiology resource announcements　10　(39)　e0070921　2021年9月30日

    DOI： 10.1128/MRA.00709-21 　

    詳細を見る 詳細を閉じる

    Complete genome sequences were determined for 4 clade A and 12 clade D enterovirus D68 strains detected in nasopharyngeal swabs from children with acute respiratory illness in the Philippines. These sequence data will be useful for future epidemiological monitoring, including watching for viral evolution.

  26. HLA-DR marks recently divided antigen-specific effector CD4 T cells in active tuberculosis patients

    Rashmi Tippalagama, Akul Singhania, Paige Dubelko, Cecilia S. Lindestam Arlehamn, Austin Crinklaw, Mikhail Pomaznoy, Gregory Seumois, Aruna D. deSilva, Sunil Premawansa, Dhammika Vidanagama, Bandu Gunasena, N.D. Suraj Goonawardhana, Dinuka Ariyaratne, Thomas J. Scriba, Robert H. Gilman, Mayuko Saito, Randy Taplitz, Pandurangan Vijayanand, Alessandro Sette, Bjoern Peters, Julie G. Burel

    Journal of Immunology　207　(2)　523-533　2021年7月15日

    出版者・発行元： American Association of Immunologists

    DOI： 10.4049/jimmunol.2100011 　

    ISSN：1550-6606 0022-1767

  27. Genome-wide analyses of human noroviruses provide insights on evolutionary dynamics and evidence of coexisting viral populations evolving under recombination constraints 国際誌 査読有り

    Kentaro Tohma, Cara J. Lepore, Magaly Martinez, Juan I. Degiuseppe, Pattara Khamrin, Mayuko Saito, Holger Mayta, Amy U. Amanda Nwaba, Lauren A. Ford-Siltz, Kim Y. Green, Maria E. Galeano, Mirko Zimic, Juan A. Stupka, Robert H. Gilman, Niwat Maneekarn, Hiroshi Ushijima, Gabriel I. Parra

    PLOS Pathogens　17　(7)　e1009744-e1009744　2021年7月13日

    出版者・発行元： Public Library of Science (PLoS)

    DOI： 10.1371/journal.ppat.1009744 　

    eISSN：1553-7374

    詳細を見る 詳細を閉じる

    Norovirus is a major cause of acute gastroenteritis worldwide. Over 30 different genotypes, mostly from genogroup I (GI) and II (GII), have been shown to infect humans. Despite three decades of genome sequencing, our understanding of the role of genomic diversification across continents and time is incomplete. To close the spatiotemporal gap of genomic information of human noroviruses, we conducted a large-scale genome-wide analyses that included the nearly full-length sequencing of 281 archival viruses circulating since the 1970s in over 10 countries from four continents, with a major emphasis on norovirus genotypes that are currently underrepresented in public genome databases. We provided new genome information for 24 distinct genotypes, including the oldest genome information from 12 norovirus genotypes. Analyses of this new genomic information, together with those publicly available, showed that (i) noroviruses evolve at similar rates across genomic regions and genotypes; (ii) emerging viruses evolved from transiently-circulating intermediate viruses; (iii) diversifying selection on the VP1 protein was recorded in genotypes with multiple variants; (iv) non-structural proteins showed a similar branching on their phylogenetic trees; and (v) contrary to the current understanding, there are restrictions on the ability to recombine different genomic regions, which results in co-circulating populations of viruses evolving independently in human communities. This study provides a comprehensive genetic analysis of diverse norovirus genotypes and the role of non-structural proteins on viral diversification, shedding new light on the mechanisms of norovirus evolution and transmission.

  28. Risk of Transmission and Viral Shedding from the Time of Infection for Respiratory Syncytial Virus in Households 査読有り

    Hirono Otomaru, Johanna Beulah T Sornillo, Taro Kamigaki, Samantha Louise P Bado, Michiko Okamoto, Mariko Saito-Obata, Marianette T Inobaya, Edelwisa Segubre-Mercado, Portia P Alday, Mayuko Saito, Veronica L Tallo, Beatriz P Quiambao, Hitoshi Oshitani, Alex R Cook

    American Journal of Epidemiology　2021年7月3日

    出版者・発行元： Oxford University Press (OUP)

    DOI： 10.1093/aje/kwab181 　

    ISSN：0002-9262

    eISSN：1476-6256

    詳細を見る 詳細を閉じる

    <title>Abstract</title> Respiratory Syncytial Virus (RSV) is a leading cause of lower respiratory tract infection worldwide. The report of temporal changes in the risk of transmission among close contacts has been scarce. This study aims to examine an association between the viral load trajectory and transmission risk to develop a better control strategy for the disease spread. We conducted a household-based prospective cohort study in Biliran Province, the Philippines, and enrolled 451 participants for observing the development of acute respiratory infection. Including the cases found at the health care facility, we analyzed the data of viral loads with symptom records obtained from 172 followed-up participants whose household member was RSV positive with a rapid test during an RSV outbreak in 2018–2019. We developed a model estimating a temporal change of the viral shedding from the infection and evaluated transmission dynamics. We revealed that most transmission events occurred within approximately 7 days from the household exposure, including potential pre-symptomatic transmissions. The inferred risk of infection among those younger than 5 years old was 3.5 times higher than that of those older than 5 years. This finding suggested that the initial week after the household exposure is particularly important for preventing RSV spread.

  29. Factors associated with the detection of norovirus among asymptomatic adults 査読有り

    Daiki Kobayashi, Kyoko Yokota, Shizuka Yamagata-Uyama, Mayuko Saito

    Clinical Microbiology and Infection　2021年6月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.cmi.2021.06.004 　

    ISSN：1198-743X

  30. Early warning of COVID-19 via wastewater-based epidemiology: potential and bottlenecks. 国際誌 査読有り

    Yifan Zhu, Wakana Oishi, Chikako Maruo, Mayuko Saito, Rong Chen, Masaaki Kitajima, Daisuke Sano

    The Science of the total environment　767　145124-145124　2021年5月1日

    DOI： 10.1016/j.scitotenv.2021.145124 　

    詳細を見る 詳細を閉じる

    An effective early warning tool is of great administrative and social significance to the containment and control of an epidemic. Facing the unprecedented global public health crisis caused by COVID-19, wastewater-based epidemiology (WBE) has been given high expectations as a promising surveillance complement to clinical testing which had been plagued by limited capacity and turnaround time. In particular, recent studies have highlighted the role WBE may play in being a part of the early warning system. In this study, we briefly discussed the basics of the concept, the benefits and critical points of such an application, the challenges faced by the scientific community, the progress made so far, and what awaits to be addressed by future studies to make the concept work. We identified that the shedding dynamics of infected individuals, especially in the form of a mathematical shedding model, and the back-calculation of the number of active shedders from observed viral load are the major bottlenecks of WBE application in the COVID-19 pandemic that deserve more attention, and the sampling strategy (location, timing, and interval) needs to be optimized to fit the purpose and scope of the WBE project.

  31. Familial Clusters of Coronavirus Disease in 10 Prefectures, Japan, February−May 2020 国際誌 査読有り

    Reiko Miyahara, Naho Tsuchiya, Ikkoh Yasuda, Yura K. Ko, Yuki Furuse, Eiichiro Sando, Shohei Nagata, Tadatsugu Imamura, Mayuko Saito, Konosuke Morimoto, Takeaki Imamura, Yugo Shobugawa, Hiroshi Nishiura, Motoi Suzuki, Hitoshi Oshitani

    Emerging Infectious Diseases　27　(3)　915-918　2021年3月

    出版者・発行元： Centers for Disease Control and Prevention (CDC)

    DOI： 10.3201/eid2703.203882 　

    ISSN：1080-6040

    eISSN：1080-6059

    詳細を見る 詳細を閉じる

    The overall coronavirus disease secondary attack rate (SAR) in family members was 19.0% in 10 prefectures of Japan during February 22-May 31, 2020. The SAR was lower for primary cases diagnosed early, within 2 days after symptom onset. The SAR of asymptomatic primary cases was 11.8%.

  32. Gene signature of children with severe respiratory syncytial virus infection. 国際誌 査読有り

    Clyde Dapat, Satoru Kumaki, Hiroki Sakurai, Hidekazu Nishimura, Hannah Karen Mina Labayo, Michiko Okamoto, Mayuko Saito, Hitoshi Oshitani

    Pediatric research　2021年1月28日

    DOI： 10.1038/s41390-020-01347-9 　

    詳細を見る 詳細を閉じる

    BACKGROUND: The limited treatment options for children with severe respiratory syncytial virus (RSV) infection highlights the need for a comprehensive understanding of the host cellular response during infection. We aimed to identify host genes that are associated with severe RSV disease and to identify drugs that can be repurposed for the treatment of severe RSV infection. METHODS: We examined clinical data and blood samples from 37 hospitalized children (29 mild and 8 severe) with RSV infection. We tested RNA from blood samples using next-generation sequencing to profile global mRNA expression and identify cellular processes. RESULTS: Retractions, decreased breath sounds, and tachypnea were associated with disease severity. We observed upregulation of genes related to neutrophil, inflammatory response, blood coagulation, and downregulation of genes related to T cell response in children with severe RSV. Using network-based approach, 43 drugs were identified that are predicted to interact with the gene products of these differentially expressed genes. CONCLUSIONS: These results suggest that the changes in the expression pattern in the innate and adaptive immune responses may be associated with RSV clinical severity. Compounds that target these cellular processes can be repositioned as candidate drugs in the treatment of severe RSV. IMPACT: Neutrophil, inflammation, and blood coagulation genes are upregulated in children with severe RSV infection. Expression of T cell response genes are suppressed in cases of severe RSV. Genes identified in this study can contribute in understanding the pathogenesis of RSV disease severity. Drugs that target cellular processes associated with severe RSV can be repositioned as potential therapeutic options.

  33. ウイルス感染症流行制御のための下水疫学調査のエッセンス

    大石 若菜, Zhu Yifan, 丸尾 知佳子, 斉藤 繭子, 北島 正章, 佐野 大輔

    水環境学会誌　44　(5)　125-133　2021年

    出版者・発行元： 公益社団法人 日本水環境学会

    DOI： 10.2965/jswe.44.125 　

    ISSN：0916-8958

    eISSN：1881-3690

    詳細を見る 詳細を閉じる

    新型コロナウイルス感染症の世界的な大流行の中, 下水疫学調査による感染流行規模の把握や変異株の早期検知が期待されている。本稿では, ウイルス感染症対策における下水疫学調査の実装に必要な要素および課題を解説した。下水疫学調査の実装のためには, 下水試料の採取方法と濃縮方法の最適化および下水中ウイルス濃度に基づく感染者数推定モデルの構築が必須である。日本国内においては, 感染症が定点把握疾患に分類される場合において, 下水処理場の流入下水の分析結果を用いて早期検知が可能である。感染者数推定モデルの構築においては, 感染症に共通の変数と感染症ごとに特有の変数が存在する。感染者のウイルス排出プロファイル等の個人差や処理区域人口の日内変動等に起因する変数の変動性や不確実性に対応可能なモデルの構築に引き続き取り組んでいく必要がある。

  34. Roles of Children and Adolescents in COVID-19 Transmission in the Community: A Retrospective Analysis of Nationwide Data in Japan. 国際誌 査読有り

    Tadatsugu Imamura, Mayuko Saito, Yura K Ko, Takeaki Imamura, Kanako Otani, Hiroki Akaba, Kota Ninomiya, Yuki Furuse, Reiko Miyahara, Eiichiro Sando, Ikkoh Yasuda, Naho Tsuchiya, Motoi Suzuki, Hitoshi Oshitani

    Frontiers in pediatrics　9　705882-705882　2021年

    DOI： 10.3389/fped.2021.705882 　

    詳細を見る 詳細を閉じる

    Background: Roles of children and adolescents in spreading coronavirus disease 2019 (COVID-19) in the community is not fully understood. Methods: We analyzed the data of 7,758 children and adolescents with COVID-19 and characteristics of secondary transmission generated by these cases using case information published by local governments. Ratio of pediatric and adolescent cases generating secondary transmission was calculated for various social settings. Results: The incidence of COVID-19 was 24.8 cases per 105 population aged between 0 and 9 years, and 59.2 among those aged between 10 and 19 years, which was lower than that among individuals of all age groups (79.6 per 105 population) between January 15 and October 31, 2020. The proportion of cases generating secondary cases was 8.3% among infants and young children in nursery schools and kindergartens, 16% among children and adolescents attending primary schools, 34% among those attending junior high schools, 43% among those attending high schools, 31% among those attending professional training colleges, and 24% in those attending universities. Households were the most common setting for secondary transmission. Conclusion: The risk of generating secondary cases might be limited among pediatric and adolescent cases with COVID-19, especially in settings outside households. Effectiveness of traditional mitigation measures (e.g., school closures) to suppress COVID-19 transmissions should be carefully evaluated.

  35. Early Warning of COVID-19 in Tokyo via Wastewater-based Epidemiology: How Feasible It Really Is? 査読有り

    Yifan Zhu, Wakana Oishi, Mayuko Saito, Masaaki Kitajima, Daisuke Sano

    Journal of Water and Environment Technology　19　(3)　170-183　2021年

    出版者・発行元： Japan Society on Water Environment

    DOI： 10.2965/jwet.21-024 　

    eISSN：1348-2165

  36. Norovirus-specific immunoglobulin A in breast milk for protection against norovirus-associated diarrhea among infants. 国際誌 査読有り

    Hannah Karen Mina Labayo, Monica J Pajuelo, Kentaro Tohma, Lauren A Ford-Siltz, Robert H Gilman, Lilia Cabrera, Holger Mayta, Gerardo J Sanchez, Anniuska Toledo Cornejo, Caryn Bern, Clyde Dapat, Tomonori Nochi, Gabriel I Parra, Hitoshi Oshitani, Mayuko Saito

    EClinicalMedicine　27　100561-100561　2020年10月

    DOI： 10.1016/j.eclinm.2020.100561 　

    詳細を見る 詳細を閉じる

    Background: Norovirus (NV) causes acute gastroenteritis in infants. Humoral and fecal immunoglobulin A (IgA) responses have been correlated with protection against NV; however, the role of breast milk IgA against NV infection and associated diarrhea is still unknown. This study aimed to evaluate the protective role of NV-specific IgA (NV-IgA) in breast milk. Methods: Ninety-five breast milk samples collected from mothers enrolled in a 2016-2017 Peruvian birth cohort study were tested for total IgA and NV-IgA by ELISA using GII·4 variants and non-GII·4 genotype virus-like particles (VLPs). Breast milk samples were grouped according to the NV infection and diarrheal status of infants: NV positive with diarrhea (NV+D+, n=18); NV positive without diarrhea (NV+D-, n=37); and NV negative without diarrhea (NV-D-, n=40). The percent positivity and titer of NV-IgA were compared among groups. The cross-reactivity was estimated based on the correlation of ratio between NV-IgA against GII·4 variants and non-GII·4 genotype VLPs. Findings: NV-IgA had high positivity rates against different VLPs, especially against GII (89-100%). The NV+D- group had higher percent positivity (89% vs. 61%, p=0·03) and median titer (1:100 vs 1:50, p=0·03) of NV-IgA than the NV+D+ group against GI·1 VLPs. A relatively high correlation between different GII·4 variants (0·87) and low correlation between genogroups (0·23-0·37) were observed. Interpretation: Mothers with high positivity rates and titers of NV-IgA in breast milk had NV infected infants with reduced diarrheal symptoms. Antigenic relatedness to the genetic diversity of human norovirus was suggested.Funding National Institute of Allergy and Infectious Diseases, National Institute of Health: 1R01AI108695-01A1 and the Japan Society for the Promotion of Science (Fostering Joint International Research B):19KK0241.

  37. Genetic analysis of sapoviruses detected in outbreaks and sporadic cases of acute gastroenteritis in Miyagi Prefecture, Japan. 国際誌 査読有り

    Akie Sakagami, Yo Ueki, Clyde Dapat, Mayuko Saito, Hitoshi Oshitani

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology　132　104648-104648　2020年9月19日

    DOI： 10.1016/j.jcv.2020.104648 　

    詳細を見る 詳細を閉じる

    BACKGROUND: Human sapovirus (SaV) causes sporadic and endemic acute gastroenteritis worldwide. However, little is known about the relationship between the mode of transmission and genetic characteristics of SaV. OBJECTIVE: To investigate the molecular characteristics of SaV-associated acute gastroenteritis among sporadic cases, foodborne, and nonfoodborne outbreaks. STUDY DESIGN: We performed a systematic review of publications and genetic analysis of SaV in fecal specimens from 98 outpatients with acute gastroenteritis, 32 stool samples from 8 foodborne outbreaks, and 63 stool samples from 23 nonfoodborne outbreaks in Miyagi Prefecture, Japan from 1993 and between 2004 and 2020. Reverse transcription polymerase chain reaction (RT-PCR) was employed for the detection of SaV, and the partial capsid gene was sequenced for genotyping and phylogenetic analysis. RESULTS: The overall detection rate of SaV in sporadic cases, foodborne, and nonfoodborne outbreaks was 5.8, 1.7, and 4.3%, respectively. Genotypic analysis revealed GI.1 to be the predominant genotype in sporadic cases (31.5%) and nonfoodborne outbreaks (52.1%), whereas it was not detected in foodborne outbreaks. Some outbreaks occurred following sporadic cases with the same genotype. CONCLUSIONS: The distribution of SaV genotypes was different between foodborne outbreaks and other settings. The effective SaV infection control may differ depending on the genomic characteristics.

  38. Epidemiological and clinical characteristics of children with acute respiratory viral infections in the Philippines: a prospective cohort study. 国際誌 査読有り

    Yuki Furuse, Raita Tamaki, Akira Suzuki, Taro Kamigaki, Michiko Okamoto, Mariko Saito-Obata, Emiko Nakagawa, Mayuko Saito, Edelwisa Segubre-Mercado, Veronica Tallo, Socorro Lupisan, Hitoshi Oshitani

    Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases　27　(7)　1037.e9-1037.e14　2020年9月17日

    DOI： 10.1016/j.cmi.2020.09.017 　

    詳細を見る 詳細を閉じる

    OBJECTIVES: Viral acute respiratory infection (ARI) remains a major global health problem, especially among children in low- and middle-income countries. The study was conducted to reveal aetiological significance of respiratory viruses among both non-hospitalized and hospitalized children. METHODS: A cohort study of children with ARI at the household, primary healthcare facility, and hospital levels was conducted alongside a hospital-based study including non-cohort children from 2014 to 2016 in the Philippines. The ARI cases were recorded at households and healthcare facilities, and a clinical investigation was performed. Nasopharyngeal swabs were collected from the symptomatic children and tested for respiratory viruses via polymerase chain reaction. Then, the association between healthcare facility utilization and viral detection was investigated. RESULTS: Overall, 18,514 ARI cases were enrolled in the cohort study, and samples were collected from 4735 of these cases. The hospital-based study detected 648 ARI cases, all of which were sampled. Rhinovirus (22.2%; 1052/4735) was most frequently detected followed by respiratory syncytial virus (12.0%; 566/4735). Enterovirus (adjusted odds ratio, 1.8; 95% confidence interval, 1.1-2.8), human metapneumovirus (2.1, 1.4-3.2), rhinovirus (2.1, 1.8-2.6), and respiratory syncytial virus (1.6, 1.2-1.9) were significantly more prevalent in the ARI cases at healthcare facilities than in those in households. Of all ARI cases, 0.6% required hospitalization while 1.8% were hospitalized among the respiratory syncytial virus-positive cases (3.8, 3.0-4.9). CONCLUSIONS: We determined the prevalence of respiratory viruses among children with ARIs at the household, primary healthcare facility, and hospital levels and the association with clinical characteristics. In particular, we discovered a significant disease burden and impact of respiratory syncytial virus infections as well as a considerable aetiological implication of rhinovirus infections.

  39. Genetic diversity of species A rotaviruses detected in clinical and environmental samples, including porcine-like rotaviruses from hospitalized children in the Philippines. 国際誌 査読有り

    Toshifumi Imagawa, Mayuko Saito, Dai Yamamoto, Mariko Saito-Obata, Yoshifumi Masago, Adrianne C Ablola, Amado O Tandoc 3rd, Edelwisa Segubre-Mercado, Socorro P Lupisan, Hitoshi Oshitani

    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases　85　104465-104465　2020年7月17日

    DOI： 10.1016/j.meegid.2020.104465 　

    詳細を見る 詳細を閉じる

    Rotaviruses are the major cause of severe acute diarrhea in infants and young children. Rotaviruses exhibit zoonosis and thereby infect both humans and animals. Viruses detected in urban rivers possibly reflect the presence of circulating viruses in the catchment. The present study investigates the genetic diversity of species A rotaviruses detected from river water and stool of hospitalized children with acute diarrhea in Tacloban City, the Philippines. Species A rotaviruses were detected by real-time RT-PCR and their genotypes were identified by multiplex PCR and sequencing of partial regions of VP7 and VP4. Rotaviruses were detected in 85.7% (30/35) of the river water samples and 62.7% (151/241) of the clinical samples. Genotypes of VP7 in the river water samples were G1, G2, G3, G4, G5, and G9, and those of VP4 were P[3], P[4], P[6], P[8], and P[13]. Genotypes of viruses from the clinical samples were G2P[4], G1P[8], G3P[8], G4P[6], G5P[6], and G9P[8]. Among those, G2P[4] in clinical samples (77.9%, 81/104) and P[4] of VP4 in river water samples (67.5%, 56/83)) were the most frequently detected rotavirus genotypes. However, G5 was the more frequently detected than G2 in the river water samples (42% vs. 13%) which may be originated from porcine rotavirus. Sequence analyses of eleven gene segments revealed one G5P[6] and two G4P[6] rotaviruses in the clinical samples, wherein, several gene segments were closely related to porcine rotaviruses. The constellation of these rotavirus genes suggests the emergence of reassortment between human and porcine rotavirus due to interspecies transmission. Although two commercial rotavirus vaccines are available now, these vaccines are designed to confer immunity against the major human rotaviruses. Constant monitoring of viral variety in populated areas where humans and domestic animals live in close proximity provides vital information related to the diversity of rotaviruses in a human population.

  40. Clusters of Coronavirus Disease in Communities, Japan, January-April 2020. 国際誌 査読有り

    Yuki Furuse, Eiichiro Sando, Naho Tsuchiya, Reiko Miyahara, Ikkoh Yasuda, Yura K Ko, Mayuko Saito, Konosuke Morimoto, Takeaki Imamura, Yugo Shobugawa, Shohei Nagata, Kazuaki Jindai, Tadatsugu Imamura, Tomimasa Sunagawa, Motoi Suzuki, Hiroshi Nishiura, Hitoshi Oshitani

    Emerging infectious diseases　26　(9)　2176-9　2020年6月10日

    DOI： 10.3201/eid2609.202272 　

    詳細を見る 詳細を閉じる

    We analyzed 3,184 cases of coronavirus disease in Japan and identified 61 case-clusters in healthcare and other care facilities, restaurants and bars, workplaces, and music events. We also identified 22 probable primary case-patients for the clusters; most were 20-39 years of age and presymptomatic or asymptomatic at virus transmission.

  41. Quantitative and Qualitative Perturbations of CD8+ MAITs in Healthy Mycobacterium tuberculosis-Infected Individuals. 国際誌 査読有り

    Mikhail Pomaznoy, Rebecca Kuan, Mikaela Lindvall, Julie G Burel, Grégory Seumois, Pandurangan Vijayanand, Randy Taplitz, Robert H Gilman, Mayuko Saito, David M Lewinsohn, Alessandro Sette, Bjoern Peters, Cecilia S Lindestam Arlehamn

    ImmunoHorizons　4　(6)　292-307　2020年6月4日

    DOI： 10.4049/immunohorizons.2000031 　

    詳細を見る 詳細を閉じる

    CD8 T cells are considered important contributors to the immune response against Mycobacterium tuberculosis, yet limited information is currently known regarding their specific immune signature and phenotype. In this study, we applied a cell population transcriptomics strategy to define immune signatures of human latent tuberculosis infection (LTBI) in memory CD8 T cells. We found a 41-gene signature that discriminates between memory CD8 T cells from healthy LTBI subjects and uninfected controls. The gene signature was dominated by genes associated with mucosal-associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in individuals with LTBI. There was no evidence for a conventional CD8 T cell-specific signature between the two cohorts. We, therefore, investigated MAITs in more detail based on Vα7.2 and CD161 expression and staining with an MHC-related protein 1 (MR1) tetramer. This revealed two distinct populations of CD8+Vα7.2+CD161+ MAITs: MR1 tetramer+ and MR1 tetramer-, which both had distinct gene expression compared with memory CD8 T cells. Transcriptomic analysis of LTBI versus noninfected individuals did not reveal significant differences for MR1 tetramer+ MAITs. However, gene expression of MR1 tetramer- MAITs showed large interindividual diversity and a tuberculosis-specific signature. This was further strengthened by a more diverse TCR-α and -β repertoire of MR1 tetramer- cells as compared with MR1 tetramer+ Thus, circulating memory CD8 T cells in subjects with latent tuberculosis have a reduced number of conventional MR1 tetramer+ MAITs as well as a difference in phenotype in the rare population of MR1 tetramer- MAITs compared with uninfected controls.

  42. Urban informal settlements as hotspots of antimicrobial resistance and the need to curb environmental transmission. 国際誌 査読有り

    Maya L Nadimpalli, Sara J Marks, Maria Camila Montealegre, Robert H Gilman, Monica J Pajuelo, Mayuko Saito, Pablo Tsukayama, Sammy M Njenga, John Kiiru, Jenna Swarthout, Mohammad Aminul Islam, Timothy R Julian, Amy J Pickering

    Nature microbiology　5　(6)　787-795　2020年6月

    DOI： 10.1038/s41564-020-0722-0 　

    詳細を見る 詳細を閉じる

    Antimicrobial resistance (AMR) is a growing public health challenge that is expected to disproportionately burden lower- and middle-income countries (LMICs) in the coming decades. Although the contributions of human and veterinary antibiotic misuse to this crisis are well-recognized, environmental transmission (via water, soil or food contaminated with human and animal faeces) has been given less attention as a global driver of AMR, especially in urban informal settlements in LMICs-commonly known as 'shanty towns' or 'slums'. These settlements may be unique hotspots for environmental AMR transmission given: (1) the high density of humans, livestock and vermin living in close proximity; (2) frequent antibiotic misuse; and (3) insufficient drinking water, drainage and sanitation infrastructure. Here, we highlight the need for strategies to disrupt environmental AMR transmission in urban informal settlements. We propose that water and waste infrastructure improvements tailored to these settings should be evaluated for their effectiveness in limiting environmental AMR dissemination, lowering the community-level burden of antimicrobial-resistant infections and preventing antibiotic misuse. We also suggest that additional research is directed towards developing economic and legal incentives for evaluating and implementing water and waste infrastructure in these settings. Given that almost 90% of urban population growth will occur in regions predicted to be most burdened by the AMR crisis, there is an urgent need to build effective, evidence-based policies that could influence massive investments in the built urban environment in LMICs over the next few decades.

  43. Epidemiology of COVID-19 Outbreak in Japan, January-March 2020. 査読有り

    Yuki Furuse, Yura K Ko, Mayuko Saito, Yugo Shobugawa, Kazuaki Jindai, Tomoya Saito, Hiroshi Nishiura, Tomimasa Sunagawa, Motoi Suzuki

    Japanese journal of infectious diseases　73　(5)　391-393　2020年4月30日

    DOI： 10.7883/yoken.JJID.2020.271 　

  44. Environmental Presence and Genetic Characteristics of Carbapenemase-Producing Enterobacteriaceae from Hospital Sewage and River Water in the Philippines. 国際誌 査読有り

    Yuki Suzuki, Pearl Joy Nazareno, Ryuichi Nakano, Melisa Mondoy, Akiyo Nakano, Mark Philip Bugayong, Josie Bilar, Mauricio Perez 5th, Emarld Julian Medina, Mariko Saito-Obata, Mayuko Saito, Kazutoshi Nakashima, Hitoshi Oshitani, Hisakazu Yano

    Applied and environmental microbiology　86　(2)　2020年1月7日

    DOI： 10.1128/AEM.01906-19 　

    詳細を見る 詳細を閉じる

    This study aimed to evaluate the prevalence and genetic characteristics of carbapenemase-producing Enterobacteriaceae (CPE) in hospital sewage and river water in the Philippines, which has a typical tropical maritime climate. We collected 83 water samples from 7 hospital sewage and 10 river water sites. CPE were identified using CHROMagar mSuperCARBA, and Gram-negative strains were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) or 16S rRNA gene sequencing. Resistance genes in Enterobacteriaceae strains were identified using PCR and DNA sequencing, and transferability of carbapenemase genes from the CPE was investigated with conjugation experiments. Genotyping was performed using multilocus sequence typing (MLST) for Escherichia coli and Klebsiella pneumoniae Out of 124 Enterobacteriaceae isolates, we identified 51 strains as CPE and divided these into 7 species, 11 E. coli, 14 Klebsiella spp., 15 Enterobacter spp., and 11 others, including 4 additional species. Conjugation experiments via broth mating and using E. coli J53 revealed that 24 isolates can transfer carbapenemase-encoding plasmids. MLST analysis showed that 6 of 11 E. coli isolates belonged to clonal complex 10 (CC10). Of 11 K. pneumoniae strains, 9 unique sequence types (STs) were identified, including ST147. Five types of carbapenemase genes were identified, with the most prevalent being NDM (n = 39), which is epidemic in clinical settings in the Philippines. E. coli CC10 and K. pneumoniae ST147, which are often detected in clinical settings, were the dominant strains. In summary, our results indicate that hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.IMPORTANCE Carbapenemase-producing Enterobacteriaceae (CPE) cause severe health care-associated infections, and their increasing prevalence is a serious concern. Recently, natural ecosystems have been recognized as important reservoirs of antibiotic resistance genes. We investigated the prevalence and genetic characteristics of CPE isolated from the environment (hospital sewage and river water) in the Philippines and found several CPE, including Escherichia coli and other species, with different carbapenemases. The most prevalent carbapenemase gene type was NDM, which is endemic in clinical settings. This study revealed that isolates belonging to carbapenemase-producing E. coli CC10 and K. pneumoniae sequence type 147 (ST147), which are often detected in clinical settings, were dominant in the natural environment. Our work here provides a report on the presence and characteristics of CPE in the environment in the Philippines and demonstrates that both hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.

  45. Recombinant Nontypeable Genotype II Human Noroviruses in the Americas. 国際誌 査読有り

    Kentaro Tohma, Cara J Lepore, Juan I Degiuseppe, Juan A Stupka, Mayuko Saito, Holger Mayta, Mirko Zimic, Lauren A Ford-Siltz, Robert H Gilman, Gabriel I Parra

    Emerging infectious diseases　26　(1)　157-159　2020年1月

    DOI： 10.3201/eid2601.190626 　

    詳細を見る 詳細を閉じる

    We report multiple nontypeable genotype II noroviruses circulating in South America; nucleotides differed by >25% from those of other genotypes. These viruses have been circulating in the Americas for ≈20 years and show recombination with other genotypes. Clues to norovirus natural history can guide development of treatment and prevention plans.

  46. Development of a novel in vitro assay to evaluate environmental water using an IL-8 reporter cell line. 国際誌 査読有り

    Yutaka Kimura, Chizu Fujimura, Toshifumi Imagawa, Socorro P Lupisan, Mariko Saito-Obata, Mayuko Saito, Hitoshi Oshitani, Setsuya Aiba

    EXCLI journal　19　1054-1063　2020年

    DOI： 10.17179/excli2020-2104 　

    詳細を見る 詳細を閉じる

    The IL-8 luciferase reporter cell line, THP-G8 cells, used in the in vitro sensitization test, OECD442E, can respond to a variety of stimuli other than haptens, such as lipopolysaccharide (LPS), other bacterial toxins, and detergents. Considering these characteristics, we examined the ability of the IL-8 luciferase assay using THP-G8 cells to evaluate water pollution. We first stimulated THP-G8 cell with various Toll-like receptor (TLR) agonists and nucleotide-binding oligomerization domain-like receptor (NLR) agonists, and found that TLR1, 2, 4, 5, 6 agonists and NOD 1, 2 agonists significantly augmented IL-8 luciferase activity (IL8LA). Then, we examined the detection threshold of LPS by THP-G8 cells, and found it 0.4 EU/ml. Next, we examined whether THP-G8 cells can differently respond to a variety of sources of environmental water around Sendai, Japan and Manila, Philippine and whether there is a correlation between the IL8LA of different sources of water and their level of endotoxin assessed by the LAL assay. There was a clear trend that the IL8LA was lower in the upper stream and higher in the downstream in both Japan and Philippine. Moreover, there was a strong correlation between the IL8LA of the environmental water and its endotoxin level. Finally, using N-acetyl-L-cysteine, an antioxidant/radical scavenger, and polymyxin B that neutralizes endotoxin, we demonstrated that there was a difference in the suppressive effects by them between the water from Japan and that from Philippine. These data suggest the potential of the IL-8 luciferase assay for evaluating environmental water pollution both quantitatively and qualitatively.

  47. Potential underestimation of influenza virus burden in infants. 国際誌 査読有り

    Takeaki Imamura, Mayuko Saito, Hitoshi Oshitani

    The Lancet. Child & adolescent health　3　(11)　751-752　2019年11月

    DOI： 10.1016/S2352-4642(19)30278-0 　

  48. Age-specific incidence rates and risk factors for respiratory syncytial virus-associated lower respiratory tract illness in cohort children under 5 years old in the Philippines. 国際誌 査読有り

    Fumihiko Ueno, Raita Tamaki, Mayuko Saito, Michiko Okamoto, Mariko Saito-Obata, Taro Kamigaki, Akira Suzuki, Edelwisa Segubre-Mercado, Hananiah D Aloyon, Veronica Tallo, Socorro P Lupisan, Hitoshi Oshitani

    Influenza and other respiratory viruses　13　(4)　339-353　2019年7月

    DOI： 10.1111/irv.12639 　

    ISSN：1750-2640

    詳細を見る 詳細を閉じる

    BACKGROUND: Respiratory syncytial virus (RSV) is one of the main viral causes of lower respiratory tract illness (LRTI), especially in young children. RSV vaccines, including maternal and infant vaccines, are under development; however, more epidemiological studies are needed to develop effective vaccination strategies. OBJECTIVES: To estimate detailed age-specific incidence rates and severity of RSV-associated LRTI (RSV-LRTI) using data from a community-based prospective cohort study in the Philippines. PATIENTS/METHODS: Cohort children who visited health facilities due to acute respiratory symptoms were identified, and nasopharyngeal swabs were collected to detect RSV. The severity of RSV-LRTI was assessed using the severity definition proposed by the World Health Organization. Risk factors for developing RSV-LRTI and contribution of SpO2 measurement were also evaluated. RESULTS: A total of 395 RSV episodes which occurred in children aged 2-59 months were categorised as 183 RSV-LRTI, 72 as severe RSV-LRTI and 29 as very severe RSV-LRTI. Children aged 3-5 months had the highest incidence rate of RSV-LRTI, at 207.4 per 1000 child-years (95% CI: 149.0-279.5). Younger age group, place of living and low educational level of caregivers were associated with developing RSV-LRTI. Clinical manifestations had low levels of agreement with hypoxaemia as measured by pulse oximeter. CONCLUSION: The highest burden of RSV was observed in young infants aged 3-5 months, whereas the burden was also high in those aged 12-20 months. Future vaccination strategies should consider the protection of older children, especially those aged one year, as well as young infants.

  49. Circulating T cell-monocyte complexes are markers of immune perturbations. 国際誌 査読有り

    Julie G Burel, Mikhail Pomaznoy, Cecilia S Lindestam Arlehamn, Daniela Weiskopf, Ricardo da Silva Antunes, Yunmin Jung, Mariana Babor, Veronique Schulten, Gregory Seumois, Jason A Greenbaum, Sunil Premawansa, Gayani Premawansa, Ananda Wijewickrama, Dhammika Vidanagama, Bandu Gunasena, Rashmi Tippalagama, Aruna D deSilva, Robert H Gilman, Mayuko Saito, Randy Taplitz, Klaus Ley, Pandurangan Vijayanand, Alessandro Sette, Bjoern Peters

    eLife　8　2019年6月25日

    DOI： 10.7554/eLife.46045 　

    詳細を見る 詳細を閉じる

    Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artifacts and thus ignored in data acquisition and analysis, are the result of biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell-monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be re-visited.

  50. The association between consuming bivalves, and acute gastroenteritis and norovirus in Tokyo, Japan. 国際誌 査読有り

    Daiki Kobayashi, Mayuko Saito, Yuji Heike, Kyoko Yokota, Hiroko Arioka, Hitoshi Oshitani

    Journal of medical virology　91　(6)　986-996　2019年6月

    DOI： 10.1002/jmv.25416 　

    ISSN：0146-6615

    詳細を見る 詳細を閉じる

    A prospective matched case-control study was conducted to evaluate associations between dietary histories, including consumption of bivalves, diarrhea, and norovirus positive diarrhea in adult ambulatory patients at an outpatient clinic of a hospital in Tokyo, Japan. Ambulatory cases with diarrhea were matched with nondiarrheal control patients, who visited the same clinic. A standardized questionnaire was used to obtain patients' information, including histories of food consumption and clinical information. Norovirus infection was confirmed using real-time reverse transcription polymerase chain reaction. A total of 207 patients, including 69 diarrheal cases and 138 nondiarrheal cases were included in the analysis. Among them, 60 (29.0%) participants reported consuming bivalves. Norovirus was detected in 35% (24/69) of diarrheal cases. Of those, 10 (41.7%) reported consumption of bivalves and of those, 6 (60.0%) consumed raw bivalves. The proportion of those who consumed raw bivalves was significantly higher in norovirus-positive diarrheal cases than in norovirus-negative diarrheal cases (25.0% vs 6.7%; odds ratio [OR], 4.67; 95% confidence interval [CI], 1.1-20.7) and matched nondiarrheal controls (25.0% vs 6.3%, OR: 5.00; 95% CI, 1.1-22.2). The attributable fraction of consuming raw bivalves for norovirus-associated diarrhea to matched nondiarrheal controls was 20.0%. Consuming raw bivalves was substantially attributed to norovirus-associated diarrhea in adult ambulatory patients and preventive measures for reducing the risk associated with consumption of raw bivalves could decrease the incidence of norovirus-associated diarrhea.

  51. Aetiology and risks factors associated with the fatal outcomes of childhood pneumonia among hospitalised children in the Philippines from 2008 to 2016: a case series study. 国際誌 査読有り

    Bindongo Price Polycarpe Dembele, Taro Kamigaki, Clyde Dapat, Raita Tamaki, Mariko Saito, Mayuko Saito, Michiko Okamoto, Mary Ann U Igoy, Edelwisa Segubre Mercado, Melisa Mondoy, Veronica L Tallo, Socorro P Lupisan, Shinichi Egawa, Hitoshi Oshitani

    BMJ open　9　(3)　e026895　2019年3月30日

    DOI： 10.1136/bmjopen-2018-026895 　

    詳細を見る 詳細を閉じる

    OBJECTIVE: Pneumonia remains the leading cause of hospitalisations and deaths among children aged <5 years. Diverse respiratory pathogens cause acute respiratory infections, including pneumonia. Here, we analysed viral and bacterial pathogens and risk factors associated with death of hospitalised children. DESIGN: A 9-year case series study. SETTING: Two secondary-care hospitals, one tertiary-care hospital and one research centre in the Philippines. PARTICIPANTS: 5054 children aged <5 years hospitalised with severe pneumonia. METHODS: Nasopharyngeal swabs for virus identification, and venous blood samples for bacterial culture were collected. Demographic, clinical data and laboratory findings were collected at admission time. Logistic regression analyses were performed to identify the factors associated with death. RESULTS: Of the enrolled patients, 57% (2876/5054) were males. The case fatality rate was 4.7% (238/5054), showing a decreasing trend during the study period (p<0.001). 55.0% of the patients who died were either moderately or severely underweight. Viruses were detected in 61.0% of the patients, with respiratory syncytial virus (27.0%) and rhinovirus (23.0%) being the most commonly detected viruses. In children aged 2-59 months, the risk factors significantly associated with death included age of 2-5 months, sensorial changes, severe malnutrition, grunting, central cyanosis, decreased breath sounds, tachypnoea, fever (≥38.5°C), saturation of peripheral oxygen <90%, infiltration, consolidation and pleural effusion on chest radiograph.Among the pathogens, adenovirus type 7, seasonal influenza A (H1N1) and positive blood culture for bacteria were significantly associated with death. Similar patterns were observed between the death cases and the aforementioned factors in children aged <2 months. CONCLUSION: Malnutrition was the most common factor associated with death and addressing this issue may decrease the case fatality rate. In addition, chest radiographic examination and oxygen saturation measurement should be promoted in all hospitalised patients with pneumonia as well as bacteria detection to identify patients who are at risk of death.

  52. Distribution of norovirus and sapovirus genotypes with emergence of NoV GII.P16/GII.2 recombinant strains in Chiang Mai, Thailand. 国際誌 査読有り

    Kanittapon Supadej, Pattara Khamrin, Kattareeya Kumthip, Rungnapa Malasao, Natthawan Chaimongkol, Mayuko Saito, Hitoshi Oshitani, Hiroshi Ushijima, Niwat Maneekarn

    Journal of medical virology　91　(2)　215-224　2019年2月

    DOI： 10.1002/jmv.25261 　

    ISSN：0146-6615

    詳細を見る 詳細を閉じる

    Norovirus (NoV) and sapovirus (SaV) are recognized as the causative agents of acute gastroenteritis, and NoV is one of the leading pathogens reported worldwide. This study reports on the distribution of NoV and SaV genotypes in children hospitalized with acute gastroenteritis in Chiang Mai, Thailand, from January 2015 to February 2017. From a total of 843 stool samples, 170 (20.2%) and 16 (1.9%) were identified as having NoV and SaV infections, respectively. Two samples (0.2%) were positive for both NoV and SaV. Of these, NoV GII.4 (57.2%) was the dominant genotype, followed by GII.2, GII.3, GII.17, GII.6, GII.7, GII.13, GII.14, GII.15, GII.21, GI.6, and GI.5. Among the NoV GII.4 variants, Sydney 2012 was the dominant variant during the period 2015-2016, while the other variants detected in this study were Asia 2003 and New Orleans 2009. Interestingly, an increase of NoV GII.2 was observed in 2016 and 2017. Characterization of partial RNA-dependent RNA polymerase and VP1 nucleotide sequences of GII.2 strains revealed that more than half of the GII.2 strains circulating in 2016 and 2017 were recombinant strains of GII.P16/GII.2. For SaV, the majority of strains belonged to GI.1 (55.6%) and GI.2 (33.3%), while GII.5 accounted for 11.1%. In conclusion, this study demonstrates the diversity of NoV and SaV, and the emergence of NoV GII.P16/GII.2 recombinant strains in 2016 and 2017 in Chiang Mai, Thailand.

  53. Use of antibiotics for common illnesses among children aged under 5 years in a rural community in Indonesia: a cross-sectional study. 査読有り

    Alkaff RN, Kamigaki T, Saito M, Ariyanti F, Iriani DU, Oshitani H

    Tropical medicine and health　47　45-45　2019年

    DOI： 10.1186/s41182-019-0173-6 　

    ISSN：1348-8945

  54. Complete Genome Sequences of 12 Human Respiratory Syncytial Virus (Human Orthopneumovirus) Strains Detected in Children with Repeated Subgroup B Infections in the Philippines. 国際誌 査読有り

    Michiko Okamoto, Masahiro Sakamoto, Clyde Dapat, Mayuko Saito, Mariko Saito-Obata, Raita Tamaki, Socorro P Lupisan, Hitoshi Oshitani

    Microbiology resource announcements　7　(22)　2018年12月

    DOI： 10.1128/MRA.01017-18 　

    詳細を見る 詳細を閉じる

    Complete genome sequences were determined for 12 human respiratory syncytial virus strains collected from nasopharyngeal samples obtained from children with repeated subgroup B infections. Eight common amino acid polymorphisms in the G, F, and L proteins were identified between the viruses detected in initial and subsequent infections.

  55. Molecular Characterization of Respiratory Syncytial Virus in Children With Repeated Infections With Subgroup B in the Philippines. 国際誌 査読有り

    Michiko Okamoto, Clyde P Dapat, Ann Marie D Sandagon, Leilanie P Batangan-Nacion, Irene C Lirio, Raita Tamaki, Mayuko Saito, Mariko Saito-Obata, Socorro P Lupisan, Hitoshi Oshitani

    The Journal of infectious diseases　218　(7)　1045-1053　2018年8月24日

    DOI： 10.1093/infdis/jiy256 　

    ISSN：0022-1899

    詳細を見る 詳細を閉じる

    Background: Human respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes. Methods: We conducted a cohort study of children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between initial and subsequent RSV infections. Results: We examined 1802 children from May 2014 to January 2016 and collected 3471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein. Conclusions: Amino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.

  56. Comprehensive Etiological and Epidemiological Study on Acute Respiratory Infections in Children: Providing Evidence for the Prevention and Control of Childhood Pneumonia in the Philippines

    13　(4)　740-750　2018年8月1日

    出版者・発行元：

    DOI： 10.20965/jdr.2018.p0740 　

    ISSN：1881-2473

    eISSN：1883-8030

  57. Genetic diversity of human sapovirus across the Americas. 国際誌 査読有り

    Marta Diez-Valcarce, Christina J Castro, Rachel L Marine, Natasha Halasa, Holger Mayta, Mayuko Saito, Laura Tsaknaridis, Chao-Yang Pan, Filemon Bucardo, Sylvia Becker-Dreps, Maria Renee Lopez, Laura Cristal Magaña, Terry Fei Fan Ng, Jan Vinjé

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology　104　65-72　2018年7月

    DOI： 10.1016/j.jcv.2018.05.003 　

    ISSN：1386-6532

    詳細を見る 詳細を閉じる

    BACKGROUND: Sapoviruses are responsible for sporadic and epidemic acute gastroenteritis worldwide. Sapovirus typing protocols have a success rate as low as 43% and relatively few complete sapovirus genome sequences are available to improve current typing protocols. OBJECTIVE/STUDY DESIGN: To increase the number of complete sapovirus genomes to better understand the molecular epidemiology of human sapovirus and to improve the success rate of current sapovirus typing methods, we used deep metagenomics shotgun sequencing to obtain the complete genomes of 68 sapovirus samples from four different countries across the Americas (Guatemala, Nicaragua, Peru and the US). RESULTS: VP1 genotyping showed that all sapovirus sequences could be grouped in the four established genogroups (GI (n = 13), GII (n = 30), GIV (n = 23), GV (n = 2)) that infect humans. They include the near-complete genome of a GI.6 virus and a recently reported novel GII.8 virus. Sequences of the complete RNA-dependent RNA polymerase gene could be grouped into three major genetic clusters or polymerase (P) types (GI.P, GII.P and GV.P) with all GIV viruses harboring a GII polymerase. One (GII.P-GII.4) of the new 68 sequences was a recombinant virus with the hotspot between the NS7 and VP1 regions. CONCLUSIONS: Analyses of this expanded database of near-complete sapovirus sequences showed several mismatches in the genotyping primers, suggesting opportunities to revisit and update current sapovirus typing methods.

  58. Epidemiology of Sapovirus Infections in a Birth Cohort in Peru. 国際誌 査読有り

    Gerardo J Sánchez, Holger Mayta, Monica J Pajuelo, Karen Neira, Liu Xiaofang, Lilia Cabrera, Sarah Blythe Ballard, Jean E Crabtree, Dermot Kelleher, Vitaliano Cama, Caryn Bern, Hitoshi Oshitani, Robert H Gilman, Mayuko Saito

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America　66　(12)　1858-1863　2018年6月1日

    DOI： 10.1093/cid/cix1103 　

    ISSN：1058-4838

    詳細を見る 詳細を閉じる

    Background: Sapovirus is one of the primary viral causes of acute gastroenteritis (AGE), especially where rotavirus vaccination has been implemented. The characteristics and impact of natural infection at the community level, however, have not been well documented. Methods: Stool samples were analyzed from 100 children randomly selected from a community-based birth cohort study in Peru. All diarrheal and 1 nondiarrheal stools collected trimonthly from children up to age 2 years (n = 1669) were tested for sapovirus detection. Viral shedding duration was determined by testing additional weekly samples (n = 440) collected before and after a sapovirus-positive sample. Results: The incidence of sapovirus infection in the first and second years of life was 4.3 and 11.1 per 100 child-months, respectively. By age 2 years, 82% of children had at least 1 sapovirus infection, and 64% had at least 1 sapovirus-associated diarrhea episode. The median shedding period was 18.5 days. In 112 of 175 infections, 14 genotypes from 4 genogroups (GI, GII, GIV, and GV) were determined. Among genogroups, GI were more frequently found in symptomatic infections than in asymptomatic infections (odds ratio, 3.1; 95% confidence interval, 1.3-7.4). Fifty-nine children had serial sapovirus infections, but only 3 had repeated infection of the same genotype. Conclusions: Sapovirus was frequently detected in children with AGE at the community level during the first 2 years of life. Serial sapovirus infections by multiple genotypes in a child suggest genotype-specific immunity from each infection, which needs to be taken into account for vaccine development.

  59. Transcriptomic Analysis of CD4+ T Cells Reveals Novel Immune Signatures of Latent Tuberculosis. 国際誌 査読有り

    Julie G Burel, Cecilia S Lindestam Arlehamn, Nabeela Khan, Grégory Seumois, Jason A Greenbaum, Randy Taplitz, Robert H Gilman, Mayuko Saito, Pandurangan Vijayanand, Alessandro Sette, Bjoern Peters

    Journal of immunology (Baltimore, Md. : 1950)　200　(9)　3283-3290　2018年5月1日

    DOI： 10.4049/jimmunol.1800118 　

    ISSN：0022-1767

    詳細を見る 詳細を閉じる

    In the context of infectious diseases, cell population transcriptomics are useful to gain mechanistic insight into protective immune responses, which is not possible using traditional whole-blood approaches. In this study, we applied a cell population transcriptomics strategy to sorted memory CD4 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and gain insight into the phenotype of tuberculosis (TB)-specific CD4 T cells. We found a 74-gene signature that could discriminate between memory CD4 T cells from healthy latently Mycobacterium tuberculosis-infected subjects and noninfected controls. The gene signature presented a significant overlap with the gene signature of the Th1* (CCR6+CXCR3+CCR4-) subset of CD4 T cells, which contains the majority of TB-specific reactivity and is expanded in LTBI. In particular, three Th1* genes (ABCB1, c-KIT, and GPA33) were differentially expressed at the RNA and protein levels in memory CD4 T cells of LTBI subjects compared with controls. The 74-gene signature also highlighted novel phenotypic markers that further defined the CD4 T cell subset containing TB specificity. We found the majority of TB-specific epitope reactivity in the CD62L-GPA33- Th1* subset. Thus, by combining cell population transcriptomics and single-cell protein-profiling techniques, we identified a CD4 T cell immune signature of LTBI that provided novel insights into the phenotype of TB-specific CD4 T cells.

  60. Complete Genome Sequence of a Nontypeable GII Norovirus Detected in Peru. 国際誌 査読有り

    Kentaro Tohma, Mayuko Saito, Holger Mayta, Mirko Zimic, Cara J Lepore, Lauren A Ford-Siltz, Robert H Gilman, Gabriel I Parra

    Genome announcements　6　(10)　2018年3月8日

    DOI： 10.1128/genomeA.00095-18 　

    詳細を見る 詳細を閉じる

    Norovirus, a leading cause of acute gastroenteritis in humans, is a highly diverse virus. Here, we report the complete genome sequence of a nontypeable genogroup II (GII) norovirus that was detected in a symptomatic Peruvian child in 2008. This virus showed low nucleotide sequence identities (≤82%) against all known genotypes.

  61. Complete Genome Sequences of 13 Human Respiratory Syncytial Virus Subgroup A Strains of Genotypes NA1 and ON1 Isolated in the Philippines. 国際誌 査読有り

    Rungnapa Malasao, Yuki Furuse, Michiko Okamoto, Clyde Dapat, Mayuko Saito, Mariko Saito-Obata, Raita Tamaki, Edelwisa Segubre-Mercado, Socorro Lupisan, Hitoshi Oshitani

    Genome announcements　6　(10)　2018年3月8日

    DOI： 10.1128/genomeA.00151-18 　

    詳細を見る 詳細を閉じる

    Complete genome sequences of 13 human respiratory syncytial virus strains were determined from samples obtained from children hospitalized in the Philippines between 2012 and 2013 because of acute respiratory infection. We identified amino acid polymorphisms between the NA1 and ON1 genotypes in the P, G, F, and L proteins.

  62. Complete Coding Genome Sequences of Uncommon GII.8 Sapovirus Strains Identified in Diarrhea Samples Collected from Peruvian Children. 国際誌 査読有り

    Emmanuel Kagning Tsinda, Rungnapa Malasao, Yuki Furuse, Robert H Gilman, Xiaofang Liu, Sonia Apaza, Susan Espetia, Vitaliano Cama, Hitoshi Oshitani, Mayuko Saito

    Genome announcements　5　(43)　2017年10月26日

    DOI： 10.1128/genomeA.01137-17 　

    詳細を見る 詳細を閉じる

    We report here two complete coding genome sequences of novel genotype GII.8 sapovirus strains identified in diarrhea samples collected from two Peruvian children. The complete coding genome sequences of both GII.8 variants were determined using the Sanger sequencing method.

  63. Environmental Surveillance of Norovirus Genogroups I and II for Sensitive Detection of Epidemic Variants. 国際誌 査読有り

    Shinobu Kazama, Takayuki Miura, Yoshifumi Masago, Yoshimitsu Konta, Kentaro Tohma, Takafumi Manaka, Xiaofang Liu, Daisuke Nakayama, Takashi Tanno, Mayuko Saito, Hitoshi Oshitani, Tatsuo Omura

    Applied and environmental microbiology　83　(9)　2017年5月1日

    DOI： 10.1128/AEM.03406-16 　

    ISSN：0099-2240

    eISSN：1098-5336

  64. An Integrated Workflow To Assess Technical and Biological Variability of Cell Population Frequencies in Human Peripheral Blood by Flow Cytometry. 国際誌 査読有り

    Julie G Burel, Yu Qian, Cecilia Lindestam Arlehamn, Daniela Weiskopf, Jose Zapardiel-Gonzalo, Randy Taplitz, Robert H Gilman, Mayuko Saito, Aruna D de Silva, Pandurangan Vijayanand, Richard H Scheuermann, Alessandro Sette, Bjoern Peters

    Journal of immunology (Baltimore, Md. : 1950)　198　(4)　1748-1758　2017年2月15日

    DOI： 10.4049/jimmunol.1601750 　

    ISSN：0022-1767

    eISSN：1550-6606

  65. Bordetella pertussis infection in children with severe pneumonia, Philippines, 2012–2015

    Alexander Sadiasa, Mariko Saito-Obata, Clyde Dapat, Mayuko Saito, Reynaldo Frederick Quicho, Mauricio Perez, Daryl Joy Almonia, Lea De Leon-Asi, Raita Tamaki, Lydia Sombrero, Socorro Lupisan, Hitoshi Oshitani

    Vaccine　35　(7)　993-996　2017年2月

    DOI： 10.1016/j.vaccine.2016.11.087 　

    ISSN：0264-410X

    eISSN：1873-2518

  66. Laboratory Diagnosis for Outbreak-Prone Infectious Diseases after Typhoon Yolanda (Haiyan), Philippines. 国際誌 査読有り

    Mariko Saito-Obata, Mayuko Saito, Titus C Tan, Inez Andrea P Medado, Clyde Dapat, Michiko Okamoto, Raita Tamaki, Rowena C Capistrano, Edelwisa Segubre-Mercado, Socorro P Lupisan, Hitoshi Oshitani

    PLoS currents　8　2016年10月21日

    DOI： 10.1371/currents.dis.9c3cb7b01ec2d04eef2406dbe03d253d 　

    eISSN：2157-3999

    詳細を見る 詳細を閉じる

    INTRODUCTION: Typhoon Yolanda (Haiyan) hit the central part of the Philippines on November 8, 2013. To identify possible outbreaks of communicable diseases after the typhoon, nasopharyngeal swabs, stool and blood samples were collected from patients who visited the Eastern Visayas Regional Medical Center due to acute respiratory infection (ARI), acute gastroenteritis (AGE) or other febrile illness (OFI) including suspected dengue fever, between November 28, 2013 and February 5, 2014.   Methods: Samples were tested on-site for selected pathogens using rapid diagnostic tests. Confirmation and further analysis were conducted at the Research Institute for Tropical Medicine (RITM) in Manila using polymerase chain reaction (PCR) and sequencing. Residues of the rapid diagnostic tests and samples collected in the filter papers (FTATM card) were transported to Manila under suboptimal conditions. PCR results were compared between the kit residues and the filter papers.   Results: A total of 185 samples were collected. Of these, 128 cases were ARI, 17 cases were AGE and 40 cases were OFI. For nasopharyngeal swab samples, detection rates for enterovirus and rhinovirus residues were higher than the filter papers. For stool samples, rotavirus positive rate for the filter paper was higher than the kit residues. We also managed to obtain the sequence data from some of the kit residues and filter papers.   Discussion: Our results confirmed the importance of PCR for the laboratory diagnosis of infectious diseases in post-disaster situations when  diagnostic options are limited.

  67. Comparative Evaluation of Real-Time PCR Methods for Human Noroviruses in Wastewater and Human Stool 査読有り

    Yoshifumi Masago, Yoshimitsu Konta, Shinobu Kazama, Manami Inaba, Toshifumi Imagawa, Kentaro Tohma, Mayuko Saito, Akira Suzuki, Hitoshi Oshitani, Tatsuo Omura

    PLOS ONE　11　(8)　e0160825　2016年8月

    DOI： 10.1371/journal.pone.0160825 　

    ISSN：1932-6203

  68. Differences in viral load among human respiratory syncytial virus genotypes in hospitalized children with severe acute respiratory infections in the Philippines. 国際誌 査読有り

    Francois Marie Ngako Kadji, Michiko Okamoto, Yuki Furuse, Raita Tamaki, Akira Suzuki, Irene Lirio, Clyde Dapat, Rungnapa Malasao, Mariko Saito, Gay Anne Granada Pedrera-Rico, Veronica Tallo, Socorro Lupisan, Mayuko Saito, Hitoshi Oshitani

    Virology journal　13　113-113　2016年6月27日

    DOI： 10.1186/s12985-016-0565-8 　

    詳細を見る 詳細を閉じる

    BACKGROUND: Human respiratory syncytial virus (HRSV) is a leading viral etiologic agent of pediatric lower respiratory infections, including bronchiolitis and pneumonia. Two antigenic subgroups, HRSV-A and B, each contain several genotypes. While viral load may vary among HRSV genotypes and affect the clinical course of disease, data are scarce regarding the actual differences among genotypes. Therefore, this study estimated and compared viral load among NA1 and ON1 genotypes of HRSV-A and BA9 of HRSV-B. ON1 is a newly emerged genotype with a 72-nucleotide duplication in the G gene as observed previously with BA genotypes in HRSV-B. FINDINGS: Children <5 years of age with an initial diagnosis of severe or very severe pneumonia at a hospital in the Philippines from September 2012 to December 2013 were enrolled. HRSV genotypes were determined and the viral load measured from nasopharyngeal swabs (NPS). The viral load of HRSV genotype NA1 were significantly higher than those of ON1 and BA9. Regression analysis showed that both genotype NA1 and younger age were significantly associated with high HRSV viral load. CONCLUSIONS: The viral load of NA1 was higher than that of ON1 and BA9 in NPS samples. HRSV genotypes may be associated with HRSV viral load. The reasons and clinical impacts of these differences in viral load among HRSV genotypes require further evaluation.

  69. Etiological Role and Repeated Infections of Sapovirus among Children Aged Less than 2 Years in a Cohort Study in a Peri-urban Community of Peru. 国際誌 査読有り

    Xiaofang Liu, Helena Jahuira, Robert H Gilman, Alicia Alva, Lilia Cabrera, Michiko Okamoto, Hang Xu, Henry J Windle, Dermot Kelleher, Marco Varela, Manuela Verastegui, Maritza Calderon, Gerardo Sanchez, Vanessa Sarabia, Sarah B Ballard, Caryn Bern, Holger Mayta, Jean E Crabtree, Vitaliano Cama, Mayuko Saito, Hitoshi Oshitani

    Journal of clinical microbiology　54　(6)　1598-1604　2016年6月

    DOI： 10.1128/JCM.03133-15 　

    ISSN：0095-1137

    eISSN：1098-660X

  70. Temporal dynamics of norovirus determined through monitoring of municipal wastewater by pyrosequencing and virological surveillance of gastroenteritis cases 査読有り

    Shinobu Kazama, Yoshifumi Masago, Kentaro Tohma, Nao Souma, Toshifumi Imagawa, Akira Suzuki, Xiaofang Liu, Mayuko Saito, Hitoshi Oshitani, Tatsuo Omura

    WATER RESEARCH　92　244-253　2016年4月

    DOI： 10.1016/j.watres.2015.10.024 　

    ISSN：0043-1354

    eISSN：1879-2448

  71. 感染性胃腸炎流行の早期検知を目的とした下水中ノロウイルスモニタリングの有用性

    三浦 尚之, 大村 達夫, 風間 しのぶ, 今田 義光, 真砂 佳史, 当广 謙太郎, 真中 太佳史, 劉 暁芳, 斉藤 繭子, 押谷 仁

    土木学会論文集G（環境）　72　(7)　III_285-III_294　2016年

    出版者・発行元： 公益社団法人 土木学会

    詳細を見る 詳細を閉じる

    下水道が整備された都市域においては，感染者から排出されたノロウイルスは下水処理場に流入する．本研究では，感染性胃腸炎の流行を早期に検知するために下水中のノロウイルスをモニタリングすることの有用性を評価した．2013年4月から2015年10月までの期間，流入下水試料を毎週収集し，下水中ノロウイルス濃度と地域の感染性胃腸炎患者報告数の相互相関分析を行った．さらに，下水中に検出されたノロウイルスの遺伝子型をパイロシーケンサーを用いて網羅的に解析し，地域の感染性胃腸炎患者便試料から検出された遺伝子型及び株と比較した．その結果，下水中ノロウイルスGII濃度は患者報告数と遅れが±1週未満の範囲で有意に相関すること（&lt;i&gt;R&lt;/i&gt; = 0.57～0.72），及び下水中には患者便試料と同一の遺伝子型及び株が含まれ，それらが経時的に変化することが実証された．患者報告数が集計・公表されるには1～2週間の時間を要することから，下水中のウイルス濃度をモニタリングすることで，医療機関の報告に基づく現行の監視システムよりも早期に流行を検知できる可能性が示された．

  72. Burden of Norovirus and Rotavirus in Children After Rotavirus Vaccine Introduction, Cochabamba, Bolivia. 国際誌 査読有り

    Casey L McAtee, Rachel Webman, Robert H Gilman, Carolina Mejia, Caryn Bern, Sonia Apaza, Susan Espetia, Mónica Pajuelo, Mayuko Saito, Roxanna Challappa, Richard Soria, Jose P Ribera, Daniel Lozano, Faustino Torrico

    The American journal of tropical medicine and hygiene　94　(1)　212-7　2016年1月

    DOI： 10.4269/ajtmh.15-0203 　

    ISSN：0002-9637

    eISSN：1476-1645

  73. Modelling subject-specific childhood growth using linear mixed-effect models with cubic regression splines. 国際誌 査読有り

    Laura M Grajeda, Andrada Ivanescu, Mayuko Saito, Ciprian Crainiceanu, Devan Jaganath, Robert H Gilman, Jean E Crabtree, Dermott Kelleher, Lilia Cabrera, Vitaliano Cama, William Checkley

    Emerging themes in epidemiology　13　1-1　2016年

    DOI： 10.1186/s12982-015-0038-3 　

    詳細を見る 詳細を閉じる

    BACKGROUND: Childhood growth is a cornerstone of pediatric research. Statistical models need to consider individual trajectories to adequately describe growth outcomes. Specifically, well-defined longitudinal models are essential to characterize both population and subject-specific growth. Linear mixed-effect models with cubic regression splines can account for the nonlinearity of growth curves and provide reasonable estimators of population and subject-specific growth, velocity and acceleration. METHODS: We provide a stepwise approach that builds from simple to complex models, and account for the intrinsic complexity of the data. We start with standard cubic splines regression models and build up to a model that includes subject-specific random intercepts and slopes and residual autocorrelation. We then compared cubic regression splines vis-à-vis linear piecewise splines, and with varying number of knots and positions. Statistical code is provided to ensure reproducibility and improve dissemination of methods. Models are applied to longitudinal height measurements in a cohort of 215 Peruvian children followed from birth until their fourth year of life. RESULTS: Unexplained variability, as measured by the variance of the regression model, was reduced from 7.34 when using ordinary least squares to 0.81 (p < 0.001) when using a linear mixed-effect models with random slopes and a first order continuous autoregressive error term. There was substantial heterogeneity in both the intercept (p < 0.001) and slopes (p < 0.001) of the individual growth trajectories. We also identified important serial correlation within the structure of the data (ρ = 0.66; 95 % CI 0.64 to 0.68; p < 0.001), which we modeled with a first order continuous autoregressive error term as evidenced by the variogram of the residuals and by a lack of association among residuals. The final model provides a parametric linear regression equation for both estimation and prediction of population- and individual-level growth in height. We show that cubic regression splines are superior to linear regression splines for the case of a small number of knots in both estimation and prediction with the full linear mixed effect model (AIC 19,352 vs. 19,598, respectively). While the regression parameters are more complex to interpret in the former, we argue that inference for any problem depends more on the estimated curve or differences in curves rather than the coefficients. Moreover, use of cubic regression splines provides biological meaningful growth velocity and acceleration curves despite increased complexity in coefficient interpretation. CONCLUSIONS: Through this stepwise approach, we provide a set of tools to model longitudinal childhood data for non-statisticians using linear mixed-effect models.

  74. A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents. 国際誌 査読有り

    Chelsea Carpenter, John Sidney, Ravi Kolla, Kaustuv Nayak, Helena Tomiyama, Claudia Tomiyama, Oscar A Padilla, Virginie Rozot, Syed F Ahamed, Carlos Ponte, Valeria Rolla, Paulo R Antas, Anmol Chandele, John Kenneth, Seetha Laxmi, Edward Makgotlho, Valentina Vanini, Giuseppe Ippolito, Alexandra S Kazanova, Alexander V Panteleev, Willem Hanekom, Harriet Mayanja-Kizza, David Lewinsohn, Mayuko Saito, M Juliana McElrath, W Henry Boom, Delia Goletti, Robert Gilman, Irina V Lyadova, Thomas J Scriba, Esper G Kallas, Kaja Murali-Krishna, Alessandro Sette, Cecilia S Lindestam Arlehamn

    Tuberculosis (Edinburgh, Scotland)　95　(6)　713-721　2015年12月

    DOI： 10.1016/j.tube.2015.07.001 　

    ISSN：1472-9792

  75. Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013 査読有り

    Rungnapa Malasao, Michiko Okamoto, Natthawan Chaimongkol, Tadatsugu Imamura, Kentaro Tohma, Isolde Dapat, Clyde Dapat, Akira Suzuki, Mayuko Saito, Mariko Saito, Raita Tamaki, Gay Anne Granada Pedrera-Rico, Rapunzel Aniceto, Reynaldo Frederick Negosa Quicho, Edelwisa Segubre-Mercado, Socorro Lupisan, Hitoshi Oshitani

    PLOS ONE　10　(11)　e0142192　2015年11月

    DOI： 10.1371/journal.pone.0142192 　

    ISSN：1932-6203

  76. Tropical and travel-associated norovirus: current concepts. 国際誌 査読有り

    Sarah-Blythe Ballard, Mayuko Saito, Andrew J Mirelman, Caryn Bern, Robert H Gilman

    Current opinion in infectious diseases　28　(5)　408-16　2015年10月

    DOI： 10.1097/QCO.0000000000000197 　

    ISSN：0951-7375

    eISSN：1473-6527

  77. Molecular detection and characterization of sapovirus in hospitalized children with acute gastroenteritis in the Philippines 査読有り

    Xiaofang Liu, Dai Yamamoto, Mariko Saito, Toshifumi Imagawa, Adrianne Ablola, Amado O. Tandoc, Edelwisa Segubre-Mercado, Socorro P. Lupisan, Michiko Okamoto, Yuki Furuse, Mayuko Saito, Hitoshi Oshitani

    JOURNAL OF CLINICAL VIROLOGY　68　83-88　2015年7月

    DOI： 10.1016/j.jcv.2015.05.001 　

    ISSN：1386-6532

    eISSN：1873-5967

  78. Cost-effectiveness of norovirus vaccination in children in Peru. 国際誌 査読有り

    Andrew J Mirelman, Sarah Blythe Ballard, Mayuko Saito, Margaret N Kosek, Robert H Gilman

    Vaccine　33　(27)　3084-91　2015年6月17日

    DOI： 10.1016/j.vaccine.2015.05.004 　

    ISSN：0264-410X

    eISSN：1873-2518

  79. Incidence and Risk Factors of Childhood Pneumonia-Like Episodes in Biliran Island, Philippines-A Community-Based Study 査読有り

    Hisato Kosai, Raita Tamaki, Mayuko Saito, Kentaro Tohma, Portia Parian Alday, Alvin Gue Tan, Marianette Tawat Inobaya, Akira Suzuki, Taro Kamigaki, Soccoro Lupisan, Veronica Tallo, Hitoshi Oshitani

    PLOS ONE　10　(5)　e0125009　2015年5月

    DOI： 10.1371/journal.pone.0125009 　

    ISSN：1932-6203

  80. Genome-level determination of Plasmodium falciparum blood-stage targets of malarial clinical immunity in the Peruvian Amazon. 国際誌 査読有り

    Katherine J Torres, Carlos E Castrillon, Eli L Moss, Mayuko Saito, Roy Tenorio, Douglas M Molina, Huw Davies, Daniel E Neafsey, Philip Felgner, Joseph M Vinetz, Dionicia Gamboa

    The Journal of infectious diseases　211　(8)　1342-51　2015年4月15日

    DOI： 10.1093/infdis/jiu614 　

    ISSN：0022-1899

    eISSN：1537-6613

  81. Molecular Epidemiology of Enterovirus D68 from 2013 to 2014 in Philippines 査読有り

    Yuki Furuse, Natthawan Chaimongkol, Michiko Okamoto, Tadatsugu Imamura, Mariko Saito, Raita Tamaki, Mayuko Saito, Socorro P. Lupisan, Hitoshi Oshitani

    JOURNAL OF CLINICAL MICROBIOLOGY　53　(3)　1015-1018　2015年3月

    DOI： 10.1128/JCM.03362-14 　

    ISSN：0095-1137

    eISSN：1098-660X

  82. Human G3P[4] rotavirus obtained in Japan, 2013, possibly emerged through a human-equine rotavirus reassortment event 査読有り

    Rungnapa Malasao, Mayuko Saito, Akira Suzuki, Toshifumi Imagawa, Nao Nukiwa-Soma, Kentaro Tohma, Xiaofang Liu, Michiko Okamoto, Natthawan Chaimongkol, Clyde Dapat, Kazuhisa Kawamura, Yasuko Kayama, Yoshifumi Masago, Tatsuo Omura, Hitoshi Oshitani

    VIRUS GENES　50　(1)　129-133　2015年2月

    DOI： 10.1007/s11262-014-1135-z 　

    ISSN：0920-8569

    eISSN：1572-994X

  83. Seroprevalence and molecular characteristics of hepatitis E virus in household-raised pig population in the Philippines 査読有り

    Xiaofang Liu, Mariko Saito, Yusuke Sayama, Ellie Suzuki, Fedelino F. Malbas, Hazel O. Galang, Yuki Furuse, Mayuko Saito, Tiancheng Li, Akira Suzuki, Hitoshi Oshitani

    BMC VETERINARY RESEARCH　11　11　2015年1月

    DOI： 10.1186/s12917-015-0322-z 　

    ISSN：1746-6148

  84. A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru. 国際誌 査読有り

    Richard A Oberhelman, Giselle Soto-Castellares, Robert H Gilman, Maria E Castillo, Lenka Kolevic, Trinidad Delpino, Mayuko Saito, Eduardo Salazar-Lindo, Eduardo Negron, Sonia Montenegro, V Alberto Laguna-Torres, Paola Maurtua-Neumann, Sumona Datta, Carlton A Evans

    PloS one　10　(4)　e0120915　2015年

    DOI： 10.1371/journal.pone.0120915 　

    ISSN：1932-6203

  85. Epidemiology and Genetic Characterization of Noroviruses among Adults in an Endemic Setting, Peruvian Amazon Basin, 2004-2011. 国際誌 査読有り

    Sarah-Blythe Ballard, Erik J Reaves, C Giannina Luna, Maria E Silva, Claudio Rocha, Kristen Heitzinger, Mayuko Saito, Sonia Apaza, Susan Espetia, David L Blazes, Drake H Tilley, Rene C Guzmán Aguilar, Robert H Gilman, Daniel G Bausch

    PloS one　10　(7)　e0131646　2015年

    DOI： 10.1371/journal.pone.0131646 　

    ISSN：1932-6203

  86. First detected Helicobacter pylori infection in infancy modifies the association between diarrheal disease and childhood growth in Peru. 国際誌 査読有り

    Devan Jaganath, Mayuko Saito, Robert H Gilman, Dulciene M M Queiroz, Gifone A Rocha, Vitaliano Cama, Lilia Cabrera, Dermot Kelleher, Henry J Windle, Jean E Crabtree, William Checkley

    Helicobacter　19　(4)　272-9　2014年8月

    DOI： 10.1111/hel.12130 　

    ISSN：1083-4389

    eISSN：1523-5378

  87. A Protein-Conjugate Approach to Develop a Monoclonal Antibody-Based Antigen Detection Test for the Diagnosis of Human Brucellosis 査読有り

    Kailash P. Patra, Mayuko Saito, Vidya L. Atluri, Hortensia G. Rolan, Briana Young, Tobias Kerrinnes, Henk Smits, Jessica N. Ricaldi, Eduardo Gotuzzo, Robert H. Gilman, Renee M. Tsolis, Joseph M. Vinetz

    PLOS NEGLECTED TROPICAL DISEASES　8　(6)　2014年6月

    DOI： 10.1371/journal.pntd.0002926 　

    ISSN：1935-2735

  88. Multiple Norovirus Infections in a Birth Cohort in a Peruvian Periurban Community 査読有り

    Mayuko Saito, Sonia Goel-Apaza, Susan Espetia, Daniel Velasquez, Lilia Cabrera, Sebastian Loli, Jean E. Crabtree, Robert E. Black, Margaret Kosek, William Checkley, Mirko Zimic, Caryn Bern, Vitaliano Cama, Robert H. Gilman

    CLINICAL INFECTIOUS DISEASES　58　(4)　483-491　2014年2月

    DOI： 10.1093/cid/cit763 　

    ISSN：1058-4838

    eISSN：1537-6591

  89. Neurocysticercosis as a cause of epilepsy and seizures in two community-based studies in a cysticercosis-endemic region in Peru. 査読有り

    Moyano LM, Saito M, Montano SM, Gonzalvez G, Olaya S, Ayvar V, González I, Larrauri L, Tsang VC, Llanos F, Rodríguez S, Gonzalez AE, Gilman RH, Garcia HH, Cysticercosis Working, Group in Peru

    PLoS neglected tropical diseases　8　(2)　e2692　2014年2月

    DOI： 10.1371/journal.pntd.0002692 　

    ISSN：1935-2727

  90. Brucella melitensis T Cell Epitope Recognition in Humans with Brucellosis in Peru 査読有り

    Anthony P. Cannella, Cecilia S. Lindestam Arlehamn, John Sidney, Kailash P. Patra, Katherine Torres, Renee M. Tsolis, Li Liang, Philip L. Felgner, Mayuko Saito, Eduardo Gotuzzo, Robert H. Gilman, Alessandro Sette, Joseph M. Vinetz

    INFECTION AND IMMUNITY　82　(1)　124-131　2014年1月

    DOI： 10.1128/IAI.00796-13 　

    ISSN：0019-9567

    eISSN：1098-5522

  91. Helicobacter pylori infection in infants and toddlers in South America: concordance between [13C]urea breath test and monoclonal H. pylori stool antigen test. 査読有り

    Queiroz DM, Saito M, Rocha GA, Rocha AM, Melo FF, Checkley W, Braga LL, Silva IS, Gilman RH, Crabtree JE

    Journal of clinical microbiology　51　(11)　3735-3740　2013年11月

    DOI： 10.1128/JCM.01752-13 　

    ISSN：0095-1137

  92. Changes in Tuberculin Skin Test Positivity Over 20 Years in Periurban Shantytowns in Lima, Peru 査読有り

    Leonardo Martinez, Alyssa Arman, Nathan Haveman, Ashley Lundgren, Lilia Cabrera, Carlton A. Evans, Tom F. Pelly, Mayuko Saito, David Callacondo, Richard Oberhelman, Gisela Collazo, Andres M. Carnero, Robert H. Gilman

    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE　89　(3)　507-515　2013年9月

    DOI： 10.4269/ajtmh.13-0005 　

    ISSN：0002-9637

    eISSN：1476-1645

  93. A foodborne outbreak of brucellosis at a police station cafeteria, Lima, Peru. 査読有り

    Román K, Castillo R, Gilman RH, Calderón M, Vivar A, Céspedes M, Smits HL, Meléndez P, Gotuzzo E, Guerra H, Maves RC, Matthias MA, Vinetz JM, Saito M

    The American journal of tropical medicine and hygiene　88　(3)　552-558　2013年3月

    DOI： 10.4269/ajtmh.12-0606 　

    ISSN：0002-9637

  94. Ex vivo innate immune cytokine signature of enhanced risk of relapsing brucellosis. 査読有り

    Feldman KE, Loriaux PM, Saito M, Tuero I, Villaverde H, Siva T, Gotuzzo E, Gilman RH, Hoffmann A, Vinetz JM

    PLoS neglected tropical diseases　7　(9)　e2424　2013年

    DOI： 10.1371/journal.pntd.0002424 　

    ISSN：1935-2727

  95. Detection and Genogrouping of Noroviruses from Children's Stools By Taqman One-step RT-PCR 査読有り

    Sonia Apaza, Susan Espetia, Robert H. Gilman, Sonia Montenegro, Susana Pineda, Fanny Herhold, Romeo Pomari, Margaret Kosek, Nancy Vu, Mayuko Saito

    JOVE-JOURNAL OF VISUALIZED EXPERIMENTS　(65)　2012年7月

    DOI： 10.3791/3232 　

    ISSN：1940-087X

  96. Antigen-specific acquired immunity in human brucellosis: implications for diagnosis, prognosis, and vaccine development 査読有り

    Anthony P. Cannella, Renee M. Tsolis, Li Liang, Philip L. Felgner, Mayuko Saito, Alessandro Sette, Eduardo Gotuzzo, Joseph M. Vinetz

    FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY　2　1　2012年2月

    DOI： 10.3389/fcimb.2012.00001 　

    ISSN：2235-2988

  97. Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans 査読有り

    Li Liang, Xiaolin Tan, Silvia Juarez, Homarh Villaverde, Jozelyn Pablo, Rie Nakajima-Sasaki, Eduardo Gotuzzo, Mayuko Saito, Gary Hermanson, Douglas Molina, Scott Felgner, W. John W. Morrow, Xiaowu Liang, Robert H. Gilman, D. Huw Davies, Renee M. Tsolis, Joseph M. Vinetz, Philip L. Felgner

    JOURNAL OF PROTEOME RESEARCH　10　(10)　4813-4824　2011年10月

    DOI： 10.1021/pr200619r 　

    ISSN：1535-3893

    eISSN：1535-3907

  98. Epidemiology of potentially inappropriate medication use in elderly patients in Japanese acute care hospitals 査読有り

    Mio Sakuma, Takeshi Morimoto, Kunihiko Matsui, Susumu Seki, Nobuo Kuramoto, Jinichi Toshiro, Junji Murakami, Tsuguya Fukui, Mayuko Saito, Atsushi Hiraide, David W. Bates

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY　20　(4)　386-392　2011年4月

    DOI： 10.1002/pds.2110 　

    ISSN：1053-8569

    eISSN：1099-1557

  99. Incidence of Adverse Drug Events and Medication Errors in Japan: the JADE Study 査読有り

    Takeshi Morimoto, Mio Sakuma, Kunihiko Matsui, Nobuo Kuramoto, Jinichi Toshiro, Junji Murakami, Tsuguya Fukui, Mayuko Saito, Atsushi Hiraide, David W. Bates

    JOURNAL OF GENERAL INTERNAL MEDICINE　26　(2)　148-153　2011年2月

    DOI： 10.1007/s11606-010-1518-3 　

    ISSN：0884-8734

  100. Diagnostic approaches for paediatric tuberculosis by use of different specimen types, culture methods, and PCR: a prospective case-control study 査読有り

    Richard A. Oberhelman, Giselle Soto-Castellares, Robert H. Gilman, Luz Caviedes, Maria E. Castillo, Lenka Kolevic, Trinidad Del Pino, Mayuko Saito, Eduardo Salazar-Lindo, Eduardo Negron, Sonia Montenegro, V. Alberto Laguna-Torres, David A. J. Moore, Carlton A. Evans

    LANCET INFECTIOUS DISEASES　10　(9)　612-620　2010年9月

    DOI： 10.1016/S1473-3099(10)70141-9 　

    ISSN：1473-3099

  101. Large Scale Immune Profiling of Infected Humans and Goats Reveals Differential Recognition of Brucella melitensis Antigens 査読有り

    Li Liang, Diana Leng, Chad Burk, Rie Nakajima-Sasaki, Matthew A. Kayala, Vidya L. Atluri, Jozelyn Pablo, Berkay Unal, Thomas A. Ficht, Eduardo Gotuzzo, Mayuko Saito, W. John W. Morrow, Xiaowu Liang, Pierre Baldi, Robert H. Gilman, Joseph M. Vinetz, Renee M. Tsolis, Philip L. Felgner

    PLOS NEGLECTED TROPICAL DISEASES　4　(5)　e673　2010年5月

    DOI： 10.1371/journal.pntd.0000673 　

    ISSN：1935-2727

  102. Asymptomatic Renal Colonization of Humans in the Peruvian Amazon by Leptospira 査読有り

    Christian A. Ganoza, Michael A. Matthias, Mayuko Saito, Manuel Cespedes, Eduardo Gotuzzo, Joseph M. Vinetz

    PLOS NEGLECTED TROPICAL DISEASES　4　(2)　2010年2月

    DOI： 10.1371/journal.pntd.0000612 　

    ISSN：1935-2735

  103. Comparison of Two Types of Epidemiological Surveys Aimed at Collecting Daily Clinical Symptoms in Community-Based Longitudinal Studies 査読有り

    Gwenyth Lee, Vitaliano Cama, Robert H. Gilman, Lilia Cabrera, Mayuko Saito, William Checkley

    ANNALS OF EPIDEMIOLOGY　20　(2)　151-158　2010年2月

    DOI： 10.1016/j.annepidem.2009.10.004 　

    ISSN：1047-2797

  104. Asymptomatic renal colonization of humans in the peruvian Amazon by Leptospira. 査読有り

    Ganoza CA, Matthias MA, Saito M, Cespedes M, Gotuzzo E, Vinetz JM

    PLoS neglected tropical diseases　4　(2)　e612　2010年2月

    DOI： 10.1371/journal.pntd.0000612 　

    ISSN：1935-2727

  105. Human Leptospirosis Caused by a New, Antigenically Unique Leptospira Associated with a Rattus Species Reservoir in the Peruvian Amazon 査読有り

    Michael A. Matthias, Jessica N. Ricaldi, Manuel Cespedes, M. Monica Diaz, Renee L. Galloway, Mayuko Saito, Arnold G. Steigerwalt, Kailash P. Patra, Carlos Vidal Ore, Eduardo Gotuzzo, Robert H. Gilman, Paul N. Levett, Joseph M. Vinetz

    PLOS NEGLECTED TROPICAL DISEASES　2　(4)　2008年4月

    DOI： 10.1371/journal.pntd.0000213 　

    ISSN：1935-2735

  106. Prevalence of sexually transmitted infections and high-risk sexual Behaviors in heterosexual couples attending sexually transmitted disease clinics in Peru 査読有り

    Amy Nelson, Natasha Press, Christian T. Bautista, Jorge Arevalo, Maritza Calderon, Kalina Campos, Amy Bryant, Julianna Shantz-Dunn, Nabila Dahodwala, Mario Vera, Aldo Vivar, Mayuko Saito, Robert H. Gilman

    SEXUALLY TRANSMITTED DISEASES　34　(6)　344-361　2007年6月

    DOI： 10.1097/01.olq.0000240341.95087.da 　

    ISSN：0148-5717

  107. Hymenolepis nana infection: symptoms and response to nitazoxanide in field conditions 査読有り

    Juan C. Chero, Mayuko Saito, Javier A. Bustos, Eladio M. Blanco, Guillermo Gonzalvez, Hector H. Garcia

    TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE　101　(2)　203-205　2007年2月

    DOI： 10.1016/j.trstmh.2006.04.004 　

    ISSN：0035-9203

  108. Comparison of altitude effect on Mycobacterium tuberculosis infection between rural and urban communities in Peru 査読有り

    Mayuko Saito, William K. Pan, Robert H. Gilman, Christian T. Bautista, Sapna Bamrah, Christopher A. Martin, Simon J. Tsiouris, D. Fermin Arguello, Gabriela Martinez-Carrasco

    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE　75　(1)　49-54　2006年7月

    ISSN：0002-9637

  109. 日本女性の乳癌死を減少させることは可能か 日本人女性の乳癌検診受診行動の促進要因と阻害要因の検討

    小林 志津子, 斉藤 繭子, 片岡 明美, 大野 真司, 中村 清吾, 福井 次夫, 小山 弘, 新保 卓郎

    日本乳癌検診学会誌　15　(1)　69-74　2006年3月

    出版者・発行元： (NPO)日本乳癌検診学会

    DOI： 10.3804/jjabcs.15.69 　

    ISSN：0918-0729

  110. The Number of Lives Saved and Quality-adjusted Life Years Prolonged by Ticlopidine Hydrochloride over the Past 20 years in Japan

    Fukui Tsuguya, Maeda Kenji, Rahman Mahbubur, Morimoto Takeshi, Saito Mayuko, Matsui Kunihiko, Shimbo Takuro

    General Medicine　7　(2)　61-70　2006年

    出版者・発行元： Japan Primary Care Association

    DOI： 10.14442/general2000.7.61 　

    ISSN：1346-0072

    詳細を見る 詳細を閉じる

    PURPOSE: Ticlopidine hydrochloride, an antiplatelet agent, is believed to have saved life years in many patients with ischemic cerebral vascular diseases in Japan. But severe adverse events have also been reported. The current investigation aimed to compare two hypothetical cohorts treated with and without ticlopidine in terms of risks and benefits of ticlopidine treatment using Markov model.<BR>METHODS: We conducted Markov decision analysis to estimate the number of lives saved and the increase in quality-adjusted life years (QALYs) over the past 20 years by ticlopidine in Japan. Two cohorts of 60-year-old male patients with previous histories of cerebral infarction, one of which treated with ticlopidine and the other not treated with ticlopidine, were compared with respect to the number of deaths and quality of life (QOL) . Data incorporated were the probabilities of the recurrence of cerebral infarction and the associated mortality, adverse events of the drug, and the utility of health status treated with ticlopidine.<BR>RESULTS: Approximately 1, 630, 000 patients were estimated to be on ticlopidine for variable periods of time during the past 20 years in Japan. With treatment, 17, 130 lives were saved, while 1, 338 patients died because of cerebral bleeding, agranulocytosis, severe hepatic dysfunction, or thrombotic thrombocytic purpura, resulting in a net benefit of 15, 792 lives saved by ticlopidine over the past 20 years. In terms of QOL, there was a total increase of 382, 191 QALYs. Sensitivity analyses showed that the older the patients when ticlopidine therapy was started, the smaller the benefits that were gained by treatment.<BR>CONCLUSIONS: Ticlopidine is considered to have made a great contribution in savingmany lives and improving QALYs in the past 20 years in Japan. This kind of analysis based on Markov model can be employed to demonstrate effectiveness of drugs and medical technologies in terms of population health outcomes.

  111. High recurrence rate of uterine fibroids on transvaginal ultrasound after abdominal myomectomy in Japanese women 査読有り

    S Nishiyama, M Saito, K Sato, M Kurishita, T Itasaka, K Shioda

    GYNECOLOGIC AND OBSTETRIC INVESTIGATION　61　(3)　155-159　2006年

    DOI： 10.1159/000090628 　

    ISSN：0378-7346

  112. Study designs used by Japanese clinical researchers: A quantitative estimate of randomized controlled trials, cohort studies case-control studies and meta-analysis

    Mahbubur Rahman, Mayuko Saito, Tsuguya Fukui

    Japan Medical Association Journal　48　436-440　2005年9月1日

    ISSN：1346-8650

  113. Articles with high-grade evidence: Trend in the last decade 査読有り

    M Rahman, M Saito, T Fukui

    CONTEMPORARY CLINICAL TRIALS　26　(4)　510-511　2005年8月

    DOI： 10.1016/j.cct.2005.03.001 　

    ISSN：1551-7144

  114. 電子カルテシステムにおける入力しやすい病名マスター改善とPOMRの実践 査読有り

    押見香代子, 脇田紀子, 阿部香代, 斉藤繭子, 阿部眞澄

    診療録管理　16　(16)　26-29　2005年

    ISSN：0916-345X

  115. The value of counting BCG scars for interpretation of tuberculin skin tests in a tuberculosis hyperenclemic shantytown, Peru 査読有り

    M Saito, CT Bautista, RH Gilman, A Bowering, MZ Levy, CA Evans

    INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE　8　(7)　842-847　2004年7月

    ISSN：1027-3719

  116. Effect of maternal anemia at high altitude on infant hematocrit and oxygenation 査読有り

    ME Ramirez-Cardich, M Saito, RH Gilman, LE Escate, JJ Strouse, C Kabrhel, C Johnson, R Galchen, CT Bautista

    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE　70　(4)　420-424　2004年4月

    ISSN：0002-9637

  117. Low prevalence and increased household clustering of Mycobacterium tuberculosis infection in high altitude villages in Peru 査読有り

    S Olender, M Saito, J Apgar, K Gillenwater, CT Bautista, AG Lescano, P Moro, L Caviedes, EJ Hsieh, RH Gilman

    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE　68　(6)　721-727　2003年6月

    ISSN：0002-9637

  118. High risk for tuberculosis in hospital physicians, Peru 査読有り

    N Bonifacio, M Saito, RH Gilman, F Leung, NC Chavez, JC Huarcaya, CV Quispe

    EMERGING INFECTIOUS DISEASES　8　(7)　747-748　2002年7月

    DOI： 10.3201/eid0807.010506 　

    ISSN：1080-6040

  119. 臨床実習中の医学生による臨床倫理に関するエッセイの分析

    浅井 篤, 斎藤 繭子, 酒井 達也

    医学教育　29　(4)　221-225　1998年8月

    出版者・発行元： (一社)日本医学教育学会

    ISSN：0386-9644

  120. めまい,悪心・嘔吐を主徴としneocerebellar syndromeを呈さない小脳の出血性梗塞の一例

    高島 敏伸, 斎藤 繭子, 加藤 博之

    綜合臨床　43　(10)　2517-2519　1994年10月

    出版者・発行元： (株)永井書店

    ISSN：0371-1900

︎全件表示 ︎最初の5件までを表示

MISC 22

  1. ウイルス感染症流行制御のための下水疫学調査のエッセンス

    大石若菜, ZHU Yifan, 丸尾知佳子, 斉藤繭子, 北島正章, 佐野大輔, 佐野大輔

    水環境学会誌(Web)　44　(5)　2021年

    ISSN： 1881-3690

  2. 新潟大学ミャンマー拠点(J-GRID)と振興再興感染症 ノロウイルス疫学研究のつぼ

    斉藤 繭子

    新潟医学会雑誌　132　(7)　276-280　2018年7月

    出版者・発行元： 新潟医学会

    ISSN： 0029-0440

  3. フィリピンの小児呼吸器疾患症例におけるエンテロウイルスD68の疫学的・臨床的解析

    齊藤 麻理子, 小畑, 岡本 道子, 齊藤 繭子, Chaimongkol Natthawan, 玉記 雷太, Lupisan Socorro, 押谷 仁

    グローバルヘルス合同大会プログラム・抄録集　2017　314-314　2017年11月

    出版者・発行元： グローバルヘルス合同大会事務局

  4. 流入下水監視によるノロウイルス感染症発生動向調査

    風間しのぶ, 三浦尚之, 今田義光, 真砂佳史, 当广謙太郎, 真中太佳史, 相馬奈央, 今川稔文, 鈴木陽, LIU Xiaofang, 斉藤繭子, 中山大典, 押谷仁, 大村達夫

    日本水環境学会年会講演集　50th　471　2016年3月10日

  5. THE PREVALENCE AND GENETIC DIVERSITY OF SAPOVIRUS IN A NESTED CASE-CONTROL STUDY OF A PERUVIAN PERI-URBAN COMMUNITY

    Xiaofang Liu, Holger Mayta, Robert H. Gilman, Michiko Okamoto, Lilia Cabrera, Jean E. Crabtree, Vitaliano Cama, Mayuko Saito, Hitoshi Oshitani

    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE　93　(4)　443-443　2015年10月

    ISSN： 0002-9637

    eISSN： 1476-1645

  6. Research activities and responding to typhoon Haiyan (Yolanda): Tohoku-RITM collaborating research center in the Philippines

    Mariko Saito, Mayuko Saito, Tadatsugu Imamura, Taro Kamigaki, Socorro P. Lupisan, Hitoshi Oshitani

    Journal of Disaster Research　9　823-827　2014年10月1日

    DOI： 10.20965/jdr.2014.p0823 　

    ISSN： 1881-2473

  7. ノロウイルスGI,GII群を対象とした定量PCR法の比較

    真砂佳史, 風間しのぶ, 今川稔文, 当广謙太郎, 斉藤繭子, 鈴木陽, 押谷仁, 大村達夫

    日本水環境学会シンポジウム講演集　17th　225-226　2014年9月8日

  8. 次世代シーケンサーを用いた下水モニタリングと感染性胃腸炎サーベイランスによるノロウイルス流行状況の比較

    風間しのぶ, 真砂佳史, 当广謙太郎, 相馬奈央, 今川稔文, 鈴木陽, LIU Xiaofang, 斉藤繭子, 押谷仁, 大村達夫

    日本水環境学会シンポジウム講演集　17th　223-224　2014年9月8日

  9. NEW DIAGNOSTIC APPROACHES FOR PEDIATRIC TB AMONG PERUVIAN CHILDREN

    Richard Oberhelman, Giselle Soto-Castellares, Luz Caviedes, Maria Castillo, Mayuko Saito, Alberto Laguna, Robert Gilman

    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE　79　(6)　235-236　2008年12月

    ISSN： 0002-9637

  10. Tuberculin skin testing has limited diagnostic utility for adult pulmonary tuberculosis in endemic regions

    Antonino G. Curatola, Gurjinder Sandhu, Robert H. Gilman, Giselle Soto, Antonio Bernabe, Mayuko Saito, Tom Pelly, Yvonne Ahn, Marco Tovar, Richard Rodriguez, A. Roderick Escombe, Carlton A. Evans

    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE　77　(5)　194-195　2007年11月

    ISSN： 0002-9637

  11. 【検診-エビデンスと論争点】ガイドラインの現状 基本健診の系統的評価(福井班)

    新保 卓郎, 上塚 芳郎, 内山 伸, 斉藤 繭子, 津下 一代, 田川 一海, 福岡 敏雄, 松井 邦彦, 福井 次矢

    EBMジャーナル　8　(2)　150-156　2007年2月

    出版者・発行元： (株)中山書店

    ISSN： 1345-1898

  12. 研修医の終末期コミュニケーション・意志決定についての態度と診療経験に関する研究

    松村 真司, 井村 洋, 斉藤 繭子, 塩尻 俊明, 武田 裕子, 前野 哲博, Lorenz Karl, Rosenfeld Kenneth, Asch Steven

    総合診療医学　10　(1)　145-145　2005年12月

    出版者・発行元： 日本総合診療医学会

    ISSN： 1347-7927

  13. 日本女性の乳癌死を減少させることは可能か 日本人女性の乳癌検診受診行動の促進要因と阻害要因の検討

    小林 志津子, 斉藤 繭子, 片岡 明美, 大野 真司, 中村 清吾, 福井 次矢, 小山 弘, 新保 卓郎

    日本乳癌検診学会誌　14　(3)　347-347　2005年10月

    出版者・発行元： (NPO)日本乳癌検診学会

    ISSN： 0918-0729

    eISSN： 1882-6873

  14. 東海大学医学部付属病院における腹腔鏡下根治的前立腺全摘術56症例の術後病理所見とPartin nomogramによる術前病理予測の比較検討

    小路 直, 臼井 幸男, 河村 好章, 甲野 拓郎, 佐々木 裕, 小林 泰之, 島 正則, 宮北 英司, 斉藤 繭子, 黒川 純, 永田 幹男, 福井 準之助, 寺地 敏郎

    泌尿器外科　18　(臨増)　541-541　2005年5月

    出版者・発行元： 医学図書出版(株)

    ISSN： 0914-6180

  15. 透析患者の高尿酸血症と心・脳血管疾患の関連

    真下 陽子, 小松 康宏, 斉藤 繭子, 大岩 孝誌, 二ツ山 みゆき

    日本透析医学会雑誌　38　(Suppl.1)　862-862　2005年5月

    出版者・発行元： (一社)日本透析医学会

    ISSN： 1340-3451

  16. The ecology of medical care in Japan

    Tsuguya Fukui, Mahbubur Rhaman, Osamu Takahashi, Mayuko Saito, Takuro Shimbo, Hiroyoshi Endo, Hanako Misao, Shunnichi Fukuhara, Shigeaki Hinohara

    Japan Medical Association Journal　48　163-167　2005年4月1日

    ISSN： 1346-8650

  17. 集中治療室入室を必要とした慢性腎疾患(CKD)患者の予後に関する検討

    山本 博之, 小松 康宏, 二ツ山 みゆき, 大岩 孝誌, 斉藤 繭子

    日本透析医学会雑誌　37　(Suppl.1)　943-943　2004年5月

    出版者・発行元： (一社)日本透析医学会

    ISSN： 1340-3451

  18. 聖路加国際病院泌尿器科における前立腺癌症例の診断的検討

    小路 直, 永田 幹男, 斉藤 繭子, 黒川 純, 寺地 敏郎, 福井 準之助

    日本泌尿器科学会雑誌　95　(2)　556-556　2004年3月

    出版者・発行元： (一社)日本泌尿器科学会

    DOI： 10.5980/jpnjurol.95.556_4 　

    ISSN： 0021-5287

  19. PP4-106 聖路加国際病院泌尿器科における前立腺癌症例の診断的検討(一般演題(ポスター))

    小路 直, 永田 幹男, 斉藤 繭子, 黒川 純, 寺地 敏郎, 福井 準之助

    日本泌尿器科学会雑誌　95　(2)　556-556　2004年

    出版者・発行元： 一般社団法人 日本泌尿器科学会

    DOI： 10.5980/jpnjurol.95.556_4 　

    ISSN： 0021-5287

  20. 内科初診外来における問題認知と解決に関する検討

    永田 志津子, 青木 則明, 梶山 徹, 斉藤 繭子, 福井 次矢

    総合診療研究会会誌　3　(1)　36-36　1998年9月

    出版者・発行元： 日本総合診療医学会

    ISSN： 1341-8807

  21. 結核性胸膜炎の診断における臨床疫学的な考え方

    斉藤 繭子, 森本 剛, 平 憲二

    JIM: Journal of Integrated Medicine　8　(2)　145-147　1998年2月

    出版者・発行元： (株)医学書院

    ISSN： 0917-138X

  22. 原発巣不明悪性腹水の臨床疫学的検討

    斎藤 繭子

    日本内科学会雑誌　84　(臨増)　235-235　1995年2月

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

︎全件表示 ︎最初の5件までを表示

共同研究・競争的資金等の研究課題 9

  1. 免疫抑制薬投与下におけるCOVID-19ワクチン接種の有効性と安全性

    岡本 道子, 斉藤 繭子

    2022年4月1日 ～ 2025年3月31日

  2. 都市下水から薬を創り出す：棄てられたヒト免疫細胞由来遺伝子を活用した抗体医薬開発

    佐野 大輔, 野地 智法, 斉藤 繭子, 久保田 健吾

    2021年7月9日 ～ 2025年3月31日

    詳細を見る 詳細を閉じる

    本研究は、都市下水から回収した抗体遺伝子を用いて抗体医薬の合成を行う手法の開発に取り組むものである。研究初年度である令和3年度においては、文献情報をもとに免疫細胞由来遺伝子を増幅するためのプライマーを設計し、都市下水から抽出した総DNAを鋳型として用いたPCRを行い、都市下水から免疫細胞由来遺伝子の増幅産物を取得することを試みた。都市下水は3000xgで30分遠心分離し、得られた沈殿物を下水濃縮サンプルとした。プライマーは複数の組み合わせを合成し、試行錯誤的に下水濃縮サンプルから抽出した総DNAに適用した。その結果、目的遺伝子と思われる増幅産物を得ることに成功した。得られた増幅産物に対して配列解析を行ったところ、ヒト免疫グロブリン由来の遺伝子配列が得られていることが確認された。この結果により、都市下水中に免疫細胞由来遺伝子が存在していることが証明され、本研究のコンセプトが成立可能であることが示された。続いて、得られた増幅産物に対して次世代シーケンシングを行うための前処理を行なった。最終的に、十分な量と純度を持つサンプルが得られたため、次世代シーケンス解析を開始した。

  3. 唾液中細胞外小胞・エクソソーム内の新型コロナウイルス感染を促進する宿主因子の解明

    斉藤 繭子, 岡本 道子

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Challenging Research (Exploratory)

    研究機関：Tohoku University

    2021年7月9日 ～ 2023年3月31日

    詳細を見る 詳細を閉じる

    2021年度は新型コロナウイルス感染症(COVID-19)の原因ウイルスである重症急性呼吸器症候群コロナウイルス2（SARS-CoV-2）のレセプターである唾液中のACE2、ウイルスのスパイク蛋白を活性化させるセリン膜貫通プロテアーゼ(TMRPSS2)の定量化を目的としてELISA法による適性化を行った。保存検体を用いて年齢・性別階層別にのACE2量の比較を行った結果、幼児においては成人に比べてACE2量が低い可能性が示唆された。また、SARS-CoV-2をヒト肺上皮腺がん細胞（Calu-3）に感染させ、細胞外小胞(EV）の回収・分離方法とその確認方法の適性化を行った。EVの回収法としては、ショ糖クッション遠心法を用いて細胞培養液からの回収を行ない、試料中に含まれる粒子の大きさと形状をナノ粒子軌跡解析、電子顕微鏡像にて確認した。さらにEVに特徴的なマーカーとされるAlix, CD9、HSP70をウェスタンブロット法で確認した。これらの結果が国際細胞外小胞学会が推奨するEV回収の確認基準を満たしたことから、Calu-3感染細胞由来のEVが分離されたと判断した。また、この分画から抽出したRNAにSARS-CoV-2遺伝子の一領域が、培養上清や超遠心後の上清に比べて高い濃度で含まれていることを定量PCR法で確認した。これにより、ヒト細胞由来のEV内にSARS-CoV-2関連物質が含まれる可能性が示唆されたが、さらなる検証の反復が必要な状況である。

  4. 乳児期のノロウイルス感染症における母乳成分の免疫学的インパクトの解明

    斉藤 繭子, 野地 智法, 今村 剛朗

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    研究機関：Tohoku University

    2019年10月7日 ～ 2023年3月31日

    詳細を見る 詳細を閉じる

    前年度に引き続きペルー共和国の誕生コホート研究で収集された検体を用い、母乳中のノロウイルスGII.4型に特異的な免疫グロブリンG(IgG)の検出を行った。誕生コホート27名の母親から、児の出生時から6か月間に提供された母乳検体中のノロウイルスGII.4特異的IgGをELISA法を用いて定量し、生後6か月間に①ノロウイルス陽性の下痢症があった、②ノロウイルスが陽性であったものの下痢症を認めなかった（無症候性感染が疑われたもの）、③ノロウイルス感染が否定的であったもの（コントロール群）の3群間で比較した。ノロウイルス感染前1か月以内の検体と同時期のコントロール群では(n=27)、3群間に明らかな差が認められなかったが、生後～感染前（n=124)と感染後（n=91）で比較すると、ノロウイルス陽性下痢症に罹患した乳児の母親の母乳に占めるIgG量は3群間で最も低く(中央値0.023μg/mL)、感染後では3群のうちで唯一IgG量が上昇し(中央値:0.040μg/mL)、コントロール群（中央値:0.036μg/mL）と同等の中央値となっていた。ノロウイルス感染が母乳中のIgG量または臍帯由来のIgG量と相関する可能性、児の感染時に母親も感染し、母乳中のIgG量が増加した可能性が示唆された。さらに、下痢症病原体の診断パネルであるLuminex xTAG GPP RUO Gastrointestinal (GI) Pathogen PanelとFilmArray GI Panel (BioFire Diagnostics) を用い、国内で採取した下痢症便検体57検体中の病原体を調べたところ、ウイルス、細菌の検出結果に差がなかったことを確認した。 昨年度に引き続き、新型コロナウイルスの流行により現地での調査ができなかったため、カエタノ大学の研究者とはオンラインでの情報交換と検体輸送を行った。

  5. グローバルな視点からのRSウイルス制御のための疫学研究

    押谷 仁, 岡本 道子, 斉藤 繭子, 神垣 太郎

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (A)

    研究機関：Tohoku University

    2019年4月1日 ～ 2023年3月31日

    詳細を見る 詳細を閉じる

    RSウイルスの疫学および伝播動態の解析については主にフィリピン・ビリラン島でのコホート研究のデータの解析を行った。この結果、家族内伝播については家庭内の年長児が乳児の感染源となっている可能性を示唆するデータが得られた（Open Forum Infect Dis. 2019 ）。このことは将来のワクチン戦略の策定にも重要な知見であると考えられる。さらに、家庭内伝播についてはシンガポール大学のAlex Cook博士と共同研究を進めており、数理モデル構築に必要なパラメーターなどの検討を行っている。またコホートデータから年齢階層ごとにRSウイルスに関連する下気道疾患の罹患率についての解析も行った。この結果、RSウイルスに関連する下気道疾患の罹患率は3－5か月の乳児で最も高かったが、12‐23か月の小児でも比較的高いことがわかった（Influenza Other Respir Viruses. 2019）。ザンビア・カンボジアでの研究につついては倫理委員会の申請などの準備を行ってきたが、新型コロナウイルスの流行のために渡航ができない状態が続いており、研究は十分に進んでいない。しかし、ザンビアについては検体の採取は始まっており、今後解析を進める予定となっている。

  6. フィリピンにおける包括的小児疾患管理の肺炎診断・治療基準改定に対する費用効果分析

    玉記 雷太, 神垣 太郎, 斉藤 繭子, 押谷 仁, 青年海外協力隊隊員

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (C)

    2016年4月1日 ～ 2019年3月31日

    詳細を見る 詳細を閉じる

    2014年にWHOによって改定された包括的小児疾患管理（Integrated Management of Childhood Illness:IMCI）の肺炎治療ガイド ラインの費用効果分析を実施した。改定版IMCIの治療効果が改定前と同等であり、一疾患あたりの医療費が平均53％削減した。結果は"Health Policy Brief "としてフィリピン保健省に提出され改訂版IMCIの国内導入が検討されている。この成果は、UHCに資するエビデンスとして、資源が限られている低・中所得国で疾病負荷の高い小児肺炎に対して、費用対効果の高い保健政策につながる。

  7. 感染拡大予防を目的とした、健常成人におけるノロウイルス不顕性感染の大規模調査

    小林 大輝, 横田 恭子, 斉藤 繭子, 押谷 仁, 平家 勇司, 宇山 静香, 片倉 加奈栄

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Young Scientists (B)

    研究機関：St. Luke's International University

    2016年4月1日 ～ 2018年3月31日

    詳細を見る 詳細を閉じる

    本研究は、成人健常者を対象としたノロウイルス不顕性感染の大規模調査である。通年で4,536名が研究に参加した。それらのうち、105名(2.3%)に遺伝子グループIのノロウイルスが、116名(2.6%)に遺伝子グループⅡのノロウイルスが不顕性感染していることが分かった。遺伝子グループⅠのノロウイルス感染は、季節や年齢による変化に乏しいことが分かった。

  8. 水環境中の未知ウイルス発見のための選択的メタゲノム解析技術の開発

    真砂 佳史, 原本 英司, 久保田 健吾, 大瀧 雅寛, 斉藤 繭子, 風間 しのぶ

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (B)

    2015年4月1日 ～ 2018年3月31日

    詳細を見る 詳細を閉じる

    本研究は効率的な新興病原ウイルスの発見に適した検出手法の開発を目標とした。下水中のウイルスゲノム群から解析対象のゲノムのみを選択的に回収し，次世代シーケンシング法によりその塩基配列を決定することで，下水中の存在量が低いウイルスであってもゲノム解析を可能にする手法を開発した。また，下水中のウイルスを対象としたメタゲノム解析を行い，得たほとんどの配列がデータベースに近縁配列がないことを確認した。メタゲノムで得た塩基配列で得た塩基配列をもとに，未知のウイルスによると考えられるコンティグを作成し，その配列を持つウイルスゲノムが国内下水に常在する可能性を示した。

  9. アジアにおけるインフルエンザウイルスのトランスミッションダイナミックスと進化

    押谷 仁, 神垣 太郎, 鈴木 陽, 齊藤 麻理子, 岡本 道子, 斉藤 繭子, 玉記 雷太, 古瀬 祐気, 貫和 奈央, 岡田 貴志, 小田切 崇, 今川 稔文, 三村 敬司, 今村 忠嗣, 光齋 久人, 刘 晓芳, 大野 歩, 乙丸 礼乃, 当广 謙太郎, 大谷 可奈子, 霍 翔, 高橋 義博, 藤 直子, 松嵜 葉子, 本郷 誠治

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (A)

    研究機関：Tohoku University

    2012年4月1日 ～ 2016年3月31日

    詳細を見る 詳細を閉じる

    フィリピン・モンゴル・日本の研究サイトにおいてインフルエンザのトランスミッションダイナミックスについての解析を行った。フィリピンではバギオ市およびタクロバン市において、日本の秋田県・大館市においては強化サーベイランスを実施し、モンゴルにおいてはウランバートル市・バガノール地区の地域内コホートを実施した。この結果、地域内でのインフルエンザウイルスの伝播に果たす小児の役割、熱帯地域であるフィリピンにおけるインフルエンザウイルスの伝播維持機構、モンゴルにおける乳児や妊婦での低い罹患率など今後のインフルエンザ対策の確立に有用なデータが得られた。

︎全件表示 ︎最初の5件までを表示