Details of the Researcher

PHOTO

Mayuko Saito
Section
Graduate School of Medicine
Job title
Professor
Degree

  • 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 No.
20598031

Professional Memberships 3

  • American Society of Tropical Medicine & Hygiene

  • JAPANESE SOCIETY FOR BACTERIOLOGY

  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE

Research Interests 4

  • International Health

  • viral gastroenteritis

  • sapovirus

  • norovirus

Research Areas 2

  • Life sciences / Infectious disease / Viral gastroenteritis

  • Life sciences / Hygiene and public health (laboratory) / Internationl Health

Papers 120

  1. Norovirus-associated diarrhea and asymptomatic infection in children aged under 4 years: a community-cohort study in the Philippines. International-journal Peer-reviewed

    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　2025/03

    DOI： 10.1016/j.ijregi.2024.100549 　

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    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. International-journal Peer-reviewed

    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　2024/12/01

    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. International-journal Peer-reviewed

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

    IJID regions　13　100485-100485　2024/12

    DOI： 10.1016/j.ijregi.2024.100485 　

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    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. International-journal Peer-reviewed

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

    The Science of the total environment　949　175055-175055　2024/11/01

    DOI： 10.1016/j.scitotenv.2024.175055 　

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    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. International-journal Peer-reviewed

    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　2024/10/10

    DOI： 10.1016/j.scitotenv.2024.174214 　

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    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. International-journal Peer-reviewed

    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　2024/06

    DOI： 10.1016/j.ijregi.2024.03.009 　

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    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. International-journal Peer-reviewed

    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　2024/06

    DOI： 10.1111/irv.13340 　

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    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 Peer-reviewed

    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　2024/03/22

    Publisher: Frontiers Media SA

    DOI： 10.3389/fpubh.2024.1332319 　

    eISSN： 2296-2565

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    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. International-journal Peer-reviewed

    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　2024/01/26

    DOI： 10.1038/s41467-024-45058-9 　

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    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. International-journal Peer-reviewed

    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

    DOI： 10.1080/19490976.2024.2309681 　

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    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. International-journal Peer-reviewed

    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　2023/08/14

    DOI： 10.1038/s41598-023-38007-x 　

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    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. International-journal Peer-reviewed

    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　2023/07/20

    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. International-journal Peer-reviewed

    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)　2023/05/26

    DOI： 10.3390/v15061254 　

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    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 Peer-reviewed

    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　2023/02/24

    Publisher: American Medical Association (AMA)

    DOI： 10.1001/jamanetworkopen.2023.0589 　

    eISSN： 2574-3805

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    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. International-journal Peer-reviewed

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

    Scientific reports　13　(1)　2310-2310　2023/02/09

    DOI： 10.1038/s41598-023-29072-3 　

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    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. International-journal Peer-reviewed

    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　2022/10

    DOI： 10.1093/ofid/ofac387 　

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    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. International-journal Peer-reviewed

    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　2022/03/30

    DOI： 10.1186/s12879-022-07289-3 　

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    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 Peer-reviewed

    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　2022/03

    Publisher: 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 International-journal Peer-reviewed

    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　2022/02

    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. International-journal Peer-reviewed

    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

    DOI： 10.5365/wpsar.2022.13.1.889 　

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    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. International-journal Peer-reviewed

    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　2021/12/17

    DOI： 10.1542/peds.2020-049884 　

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    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 International-journal Peer-reviewed

    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　2021/12/09

    Publisher: American Society for Microbiology

    DOI： 10.1128/mra.00900-21 　

    eISSN： 2576-098X

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    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. International-journal Peer-reviewed

    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　2021/12

    DOI： 10.1080/22221751.2021.1967706 　

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    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　2021/10/29

    DOI： 10.7883/yoken.JJID.2021.288 　

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    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. International-journal Peer-reviewed

    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　2021/09/30

    DOI： 10.1128/MRA.00709-21 　

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    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　2021/07/15

    Publisher: 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 International-journal Peer-reviewed

    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　2021/07/13

    Publisher: Public Library of Science (PLoS)

    DOI： 10.1371/journal.ppat.1009744 　

    eISSN： 1553-7374

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    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 Peer-reviewed

    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　2021/07/03

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/aje/kwab181 　

    ISSN： 0002-9262

    eISSN： 1476-6256

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    <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 Peer-reviewed

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

    Clinical Microbiology and Infection　2021/06

    Publisher: 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. International-journal Peer-reviewed

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

    The Science of the total environment　767　145124-145124　2021/05/01

    DOI： 10.1016/j.scitotenv.2021.145124 　

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    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 International-journal Peer-reviewed

    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　2021/03

    Publisher: Centers for Disease Control and Prevention (CDC)

    DOI： 10.3201/eid2703.203882 　

    ISSN： 1080-6040

    eISSN： 1080-6059

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    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. International-journal Peer-reviewed

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

    Pediatric research　2021/01/28

    DOI： 10.1038/s41390-020-01347-9 　

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    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. Wastewater-based Epidemiology for Infectious Diseases: The Foundations and Future Perspectives

    OISHI Wakana, ZHU Yifan, MARUO Chikako, SAITO Mayuko, KITAJIMA Masaaki, SANO Daisuke

    Journal of Japan Society on Water Environment　44　(5)　125-133　2021

    Publisher: Japan Society on Water Environment

    DOI： 10.2965/jswe.44.125 　

    ISSN： 0916-8958

    eISSN： 1881-3690

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    Wastewater-base epidemiology may be a promising approach to capturing the dynamics of the spread of diseases as well as emerging mutants in a catchment. Herein, we describe the key components of the wastewater-based epidemiology of viral infectious diseases, including the optimization of the methodology of the detection and quantification of viral genomes and the development of a back-calculation model to estimate the number of infected individuals. Early warning based on the influent viral concentration in a wastewater treatment plant may be feasible when it takes longer than one week to tally the number of patients of the target infectious disease by the currently used sentinel surveillance under the infectious diseases control law. The variables of a back-calculation model are categorized into two types: common variables irrespective of the type of infectious disease and variables specific to the infectious disease including shedding profiles of viruses. Greater effort is required to develop a robust back-calculation model against variability and uncertainty due to environmental, geological, and personal differences.

  34. Roles of Children and Adolescents in COVID-19 Transmission in the Community: A Retrospective Analysis of Nationwide Data in Japan. International-journal Peer-reviewed

    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

    DOI： 10.3389/fped.2021.705882 　

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    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? Peer-reviewed

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

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

    Publisher: 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. International-journal Peer-reviewed

    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　2020/10

    DOI： 10.1016/j.eclinm.2020.100561 　

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    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. International-journal Peer-reviewed

    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　2020/09/19

    DOI： 10.1016/j.jcv.2020.104648 　

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    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. International-journal Peer-reviewed

    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　2020/09/17

    DOI： 10.1016/j.cmi.2020.09.017 　

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    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. International-journal Peer-reviewed

    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　2020/07/17

    DOI： 10.1016/j.meegid.2020.104465 　

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    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. International-journal Peer-reviewed

    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　2020/06/10

    DOI： 10.3201/eid2609.202272 　

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    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. International-journal Peer-reviewed

    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　2020/06/04

    DOI： 10.4049/immunohorizons.2000031 　

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    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. International-journal Peer-reviewed

    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　2020/06

    DOI： 10.1038/s41564-020-0722-0 　

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    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. Peer-reviewed

    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　2020/04/30

    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. International-journal Peer-reviewed

    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)　2020/01/07

    DOI： 10.1128/AEM.01906-19 　

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    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. International-journal Peer-reviewed

    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　2020/01

    DOI： 10.3201/eid2601.190626 　

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    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. International-journal Peer-reviewed

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

    EXCLI journal　19　1054-1063　2020

    DOI： 10.17179/excli2020-2104 　

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    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. International-journal Peer-reviewed

    Takeaki Imamura, Mayuko Saito, Hitoshi Oshitani

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

    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. International-journal Peer-reviewed

    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　2019/07

    DOI： 10.1111/irv.12639 　

    ISSN： 1750-2640

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    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. International-journal Peer-reviewed

    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　2019/06/25

    DOI： 10.7554/eLife.46045 　

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    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. International-journal Peer-reviewed

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

    Journal of medical virology　91　(6)　986-996　2019/06

    DOI： 10.1002/jmv.25416 　

    ISSN： 0146-6615

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    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. International-journal Peer-reviewed

    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　2019/03/30

    DOI： 10.1136/bmjopen-2018-026895 　

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    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. International-journal Peer-reviewed

    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　2019/02

    DOI： 10.1002/jmv.25261 　

    ISSN： 0146-6615

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    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. Peer-reviewed

    Raihana Nadra Alkaff, Taro Kamigaki, Mayuko Saito, Fajar Ariyanti, Dewi Utami Iriani, Hitoshi Oshitani

    Tropical medicine and health　47　45-45　2019

    DOI： 10.1186/s41182-019-0173-6 　

    ISSN： 1348-8945

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    Background: The incidence of antimicrobial resistance has been increasing worldwide in the past decades, which includes resistance to bacteria that cause common childhood illnesses, such as acute respiratory infections and diarrhea. Numerous children with those common illnesses are treated with antibiotics. However, in such cases, antibiotic treatment is not required. Community-based studies focusing on antibiotic use among children are still limited. This study aimed to identify the prevalence of antibiotic use for common childhood illnesses and to investigate factors associated with antibiotic use in children under 5 years old as well as female caregivers in a rural community in Indonesia. Methods: A cross-sectional study of 334 children in three villages of Banten Province, located in the western part of Java Island, was conducted in May 2018. Female caregivers who were responsible for providing medications to children were interviewed. We obtained information such as demographic data, any common clinical illness within the last 30 days, and antibiotic usage during an episode of illness. We excluded children with underlying disease that require a regular follow-up and children who were hospitalized in the last 30 days in the analysis. Antibiotic use answered by female caregivers was verified by checking its package or showing photos of various antibiotics to the female caregivers. Crushed antibiotics were confirmed with health professionals. Results: A total of 203 children had clinical symptoms, and the most common symptom was fever and respiratory symptoms. In total, 49.3% received antibiotics, and 66% of them were prescribed by private health professionals. Only two children received antibiotics without a prescription. The most common antibiotic used among children was amoxicillin. Conclusions: The high prevalence of antibiotic use was observed in children under 5 years of age, and the major source to obtain antibiotics was to consult health professionals. Training on appropriate antibiotic use must be conducted for health professionals in not only public but also private sectors.

  54. Complete Genome Sequences of 12 Human Respiratory Syncytial Virus (Human Orthopneumovirus) Strains Detected in Children with Repeated Subgroup B Infections in the Philippines. International-journal Peer-reviewed

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

    Microbiology resource announcements　7　(22)　2018/12

    DOI： 10.1128/MRA.01017-18 　

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    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. International-journal Peer-reviewed

    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　2018/08/24

    DOI： 10.1093/infdis/jiy256 　

    ISSN： 0022-1899

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    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

    Raita Tamaki, Veronica L. Tallo, Alvin G. Tan, Mark Donald C. Reñosa, Portia P. Alday, Jhoys M. Landicho, Marianette T. Inobaya, Mayuko Saito, Taro Kamigaki, Michiko Okamoto, Mariko Saito, Clyde Dapat, Bindongo P. P. Dembele, Mary Lorraine S. Mationg, Melisa U. Mondoy, Socorro P. Lupisan, Hitoshi Oshitani

    Journal of Disaster Research　13　(4)　740-750　2018/08/01

    Publisher: Fuji Technology Press Ltd.

    DOI： 10.20965/jdr.2018.p0740 　

    ISSN： 1881-2473

    eISSN： 1883-8030

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    Childhood pneumonia has been the leading cause of morbidity and mortality for decades. Although substantial progress in the understanding of risk factors and etiology of pneumonia has been made, childhood pneumonia remains the major cause of death in children, accounting for 900,000 of the estimated 6.3 million child deaths worldwide in 2013. More than 90% of all episodes of clinical childhood pneumonia worldwide occur in low and middle-income countries. More effective and feasible interventions need to be developed and made widely available for such countries, including the Philippines. Comprehensive research, including etiological and epidemiological studies for assessments of risk factors and thereby, intervention studies to reduce the impact of childhood pneumonia are required in hospital settings, as well as community settings, consistently. A research project entitled “comprehensive etiological and epidemiological study on acute respiratory infections in children: providing evidence for the prevention and control of childhood pneumonia, the Philippines” was conducted under SATREPS (Science and Technology Research Partnership for Sustainable Development), which is a funding scheme to promote international joint research focusing on global issues. This project was implemented in four sentinel hospitals, with some community settings, in the Philippines between April 2011 and March 2017, incorporating five sub-components: etiological study, disease burden study, risk factor analysis, intervention study, and its evaluation. In this paper, we introduce the research project of SATREPS focusing on the methodologies, progress, and obtained evidence.

  57. Genetic diversity of human sapovirus across the Americas. International-journal Peer-reviewed

    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　2018/07

    DOI： 10.1016/j.jcv.2018.05.003 　

    ISSN： 1386-6532

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    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. International-journal Peer-reviewed

    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　2018/06/01

    DOI： 10.1093/cid/cix1103 　

    ISSN： 1058-4838

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    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. International-journal Peer-reviewed

    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　2018/05/01

    DOI： 10.4049/jimmunol.1800118 　

    ISSN： 0022-1767

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    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. International-journal Peer-reviewed

    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)　2018/03/08

    DOI： 10.1128/genomeA.00095-18 　

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    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. International-journal Peer-reviewed

    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)　2018/03/08

    DOI： 10.1128/genomeA.00151-18 　

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    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. International-journal Peer-reviewed

    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)　2017/10/26

    DOI： 10.1128/genomeA.01137-17 　

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    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. International-journal Peer-reviewed

    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)　2017/05/01

    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. International-journal Peer-reviewed

    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　2017/02/15

    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

    VACCINE　35　(7)　993-996　2017/02

    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. International-journal Peer-reviewed

    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　2016/10/21

    DOI： 10.1371/currents.dis.9c3cb7b01ec2d04eef2406dbe03d253d 　

    eISSN： 2157-3999

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    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 Peer-reviewed

    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　2016/08

    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. International-journal Peer-reviewed

    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　2016/06/27

    DOI： 10.1186/s12985-016-0565-8 　

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    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. International-journal Peer-reviewed

    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　2016/06

    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 Peer-reviewed

    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　2016/04

    DOI： 10.1016/j.watres.2015.10.024 　

    ISSN： 0043-1354

    eISSN： 1879-2448

  71. APPLICABILITY OF NOROVIRUS MONITORING IN SEWAGE AS AN EARLY WARNING SYSTEM OF INFECTIOUS GASTROENTERITIS

    MIURA Takayuki, OMURA Tatsuo, KAZAMA Shinobu, KONTA Yoshimitsu, MASAGO Yoshifumi, TOHMA Kentaro, MANAKA Takafumi, LIU Xiaofang, SAITO Mayuko, OSHITANI Hitoshi

    Journal of Japan Society of Civil Engineers, Ser. G (Environmental Research)　72　(7)　III_285-III_294　2016

    Publisher: 公益社団法人 土木学会

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    &amp;nbsp;In urbanized areas where sewage system has been developed, noroviruses excreted from patients are collected in sewage treatment plants. Therefore, the concentration of noroviruses in sewage has been proposed as an indicator of gastroenteritis cases in the treatment area. In this study, we tested the applicability of norovirus monitoring in sewage as an early warning system of infectious gastroenteritis. Sewage samples were collected weekly from April 2013 to October 2015, and the temporal relation between norovirus concentration in sewage and the number of gastroenteritis cases reported in the study area was evaluated using cross correlation analysis. We also compared norovirus genotypes detected in sewage by pyrosequencing and those detected in clinical samples. As a result, significant correlation was observed between norovirus GII concentration in sewage and the number of gastroenteritis cases without a lag time (&lt;i&gt;R&lt;/i&gt; = 0.57&amp;ndash;0.72), implying that the concentration of noroviruses reflects the number of infected people when the sample was collected. Most of the norovirus genotypes or strains detected in stool samples were also found in sewage samples and they changed similarly over time during the study period. Considering that it takes one or two weeks for the number of gastroenteritis cases to be released to the public, norovirus monitoring in sewage is a promising alternative for the early warning system of gastroenteritis.

  72. Burden of Norovirus and Rotavirus in Children After Rotavirus Vaccine Introduction, Cochabamba, Bolivia. International-journal Peer-reviewed

    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　2016/01

    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. International-journal Peer-reviewed

    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

    DOI： 10.1186/s12982-015-0038-3 　

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    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. International-journal Peer-reviewed

    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　2015/12

    DOI： 10.1016/j.tube.2015.07.001 　

    ISSN： 1472-9792

  75. Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013 Peer-reviewed

    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　2015/11

    DOI： 10.1371/journal.pone.0142192 　

    ISSN： 1932-6203

  76. Tropical and travel-associated norovirus: current concepts. International-journal Peer-reviewed

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

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

    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 Peer-reviewed

    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　2015/07

    DOI： 10.1016/j.jcv.2015.05.001 　

    ISSN： 1386-6532

    eISSN： 1873-5967

  78. Cost-effectiveness of norovirus vaccination in children in Peru. International-journal Peer-reviewed

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

    Vaccine　33　(27)　3084-91　2015/06/17

    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 Peer-reviewed

    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　2015/05

    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. International-journal Peer-reviewed

    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　2015/04/15

    DOI： 10.1093/infdis/jiu614 　

    ISSN： 0022-1899

    eISSN： 1537-6613

  81. Molecular Epidemiology of Enterovirus D68 from 2013 to 2014 in Philippines Peer-reviewed

    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　2015/03

    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 Peer-reviewed

    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　2015/02

    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 Peer-reviewed

    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　2015/01

    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. International-journal Peer-reviewed

    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

    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. International-journal Peer-reviewed

    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

    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. International-journal Peer-reviewed

    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　2014/08

    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 Peer-reviewed

    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)　2014/06

    DOI： 10.1371/journal.pntd.0002926 　

    ISSN： 1935-2735

  88. Multiple Norovirus Infections in a Birth Cohort in a Peruvian Periurban Community Peer-reviewed

    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　2014/02

    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. Peer-reviewed

    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　2014/02

    DOI： 10.1371/journal.pntd.0002692 　

    ISSN： 1935-2727

  90. Brucella melitensis T Cell Epitope Recognition in Humans with Brucellosis in Peru Peer-reviewed

    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　2014/01

    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. Peer-reviewed

    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　2013/11

    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 Peer-reviewed

    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　2013/09

    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. Peer-reviewed

    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　2013/03

    DOI： 10.4269/ajtmh.12-0606 　

    ISSN： 0002-9637

  94. Ex vivo innate immune cytokine signature of enhanced risk of relapsing brucellosis. Peer-reviewed

    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

    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 Peer-reviewed

    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)　2012/07

    DOI： 10.3791/3232 　

    ISSN： 1940-087X

  96. Antigen-specific acquired immunity in human brucellosis: implications for diagnosis, prognosis, and vaccine development Peer-reviewed

    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　2012/02

    DOI： 10.3389/fcimb.2012.00001 　

    ISSN： 2235-2988

  97. Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans Peer-reviewed

    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　2011/10

    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 Peer-reviewed

    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　2011/04

    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 Peer-reviewed

    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　2011/02

    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 Peer-reviewed

    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　2010/09

    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 Peer-reviewed

    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　2010/05

    DOI： 10.1371/journal.pntd.0000673 　

    ISSN： 1935-2727

  102. Asymptomatic Renal Colonization of Humans in the Peruvian Amazon by Leptospira Peer-reviewed

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

    PLOS NEGLECTED TROPICAL DISEASES　4　(2)　2010/02

    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 Peer-reviewed

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

    ANNALS OF EPIDEMIOLOGY　20　(2)　151-158　2010/02

    DOI： 10.1016/j.annepidem.2009.10.004 　

    ISSN： 1047-2797

  104. Asymptomatic renal colonization of humans in the peruvian Amazon by Leptospira. Peer-reviewed

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

    PLoS neglected tropical diseases　4　(2)　e612　2010/02

    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 Peer-reviewed

    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)　2008/04

    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 Peer-reviewed

    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　2007/06

    DOI： 10.1097/01.olq.0000240341.95087.da 　

    ISSN： 0148-5717

  107. Hymenolepis nana infection: symptoms and response to nitazoxanide in field conditions Peer-reviewed

    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　2007/02

    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 Peer-reviewed

    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　2006/07

    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　2006/03

    Publisher: (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

    Gen. Med.　7　(2)　61-70　2006

    Publisher: Japan Primary Care Association

    DOI： 10.14442/general2000.7.61 　

    ISSN： 1346-0072

    More details Close

    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 Peer-reviewed

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

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

    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　2005/09/01

    ISSN： 1346-8650

  113. Articles with high-grade evidence: Trend in the last decade Peer-reviewed

    M Rahman, M Saito, T Fukui

    CONTEMPORARY CLINICAL TRIALS　26　(4)　510-511　2005/08

    DOI： 10.1016/j.cct.2005.03.001 　

    ISSN： 1551-7144

  114. Disease name master improvement and POMR practice for integrated electronic health record system Peer-reviewed

    OSHIMI Kayoko, WAKITA Noriko, ABE Kayo, SAITO Mayuko, ABE Masumi

    16　(16)　26-29　2005

    ISSN： 0916-345X

  115. The value of counting BCG scars for interpretation of tuberculin skin tests in a tuberculosis hyperenclemic shantytown, Peru Peer-reviewed

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

    INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE　8　(7)　842-847　2004/07

    ISSN： 1027-3719

  116. Effect of maternal anemia at high altitude on infant hematocrit and oxygenation Peer-reviewed

    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　2004/04

    ISSN： 0002-9637

  117. Low prevalence and increased household clustering of Mycobacterium tuberculosis infection in high altitude villages in Peru Peer-reviewed

    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　2003/06

    ISSN： 0002-9637

  118. High risk for tuberculosis in hospital physicians, Peru Peer-reviewed

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

    EMERGING INFECTIOUS DISEASES　8　(7)　747-748　2002/07

    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　1998/08

    Publisher: (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　1994/10

    Publisher: (株)永井書店

    ISSN： 0371-1900

Show all ︎Show first 5

Misc. 22

  1. Wastewater-based Epidemiology for Infectious Diseases: The Foundations and Future Perspectives

    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

    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　2018/07

    Publisher: 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　2017/11

    Publisher: 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　2016/03/10

  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　2015/10

    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　2014/10/01

    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　2014/09/08

  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　2014/09/08

  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　2008/12

    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　2007/11

    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　2007/02

    Publisher: (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　2005/12

    Publisher: 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　2005/10

    Publisher: (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　2005/05

    Publisher: 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　2005/05

    Publisher: (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　2005/04/01

    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　2004/05

    Publisher: (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　2004/03

    Publisher: (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

    Publisher: 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　1998/09

    Publisher: 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　1998/02

    Publisher: (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　1995/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

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Research Projects 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

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  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

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(開拓)

    Institution: 東北大学

    2021/07/09 - 2025/03/31

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    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. Detection of host risk factors of SARS CoV-2 infection in exosomes and other extracellular vesicles in saliva

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Research (Exploratory)

    Institution: Tohoku University

    2021/07/09 - 2023/03/31

  4. Immunological impact of factors in breast milk on norovirus infection among infants

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Institution: Tohoku University

    2019/10/07 - 2023/03/31

  5. Epidemiological study for control of respiratory syncytial virus from a global perspective

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2019/04/01 - 2023/03/31

  6. Cost-effectiveness analysis of revised Integrated Management of Childhood Illness (IMCI) guidelines for childhood pneumonia in the Philippines

    TAMAKI RAITA, Tallo Vicky, Tan Alvin, Alday Portia, Lanbucho Jhoys, Donald Mark

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    2016/04/01 - 2019/03/31

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    Cost-effectiveness analysis of revised Integrated Management of Childhood Illness (IMCI) guidelines for childhood pneumonia was conducted in the Philippines. There was equal effectiveness between the revised IMCI and the original IMCI. The treatment cost of pneumonia with the revised IMCI was significantly reduced by 53%. The results were discussed with the department of health for possible implantation in the Philippines. The evidence can be utilized for resource poor settings in the low and middle income countries with high burden of childhood pneumonia, which may contribute to UHC.

  7. The prevalence of asymptomatic norovirus infection among adults in Japan: Large scale prospective cross-sectional survey

    KOBAYASHI Daiki, YOKOTA Kyoko, SAITO Mayuko, OSHITANI Hitoshi, HEIKE Yuji, UYAMA Shizuka, KATAKURA Kanae

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: St. Luke's International University

    2016/04/01 - 2018/03/31

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    This study is a large scale survey which evaluated the prevalence of asymptomatic norovirus infection among healthy adult. We included 4,536 participant, where 105 (2.3%) were positive for genotype I norovirus and 116 (2.6%) were positive for negotype II norovirus. The prevalences for positive result of genotype I norovirus were similar over month or age group.

  8. Selective metagenomic analysis of novel viruses in water environment

    Masago Yoshifumi, SAITO Mayuko, KAZAMA Shinobu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    2015/04/01 - 2018/03/31

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    This study aimed at developing effective detection methods for novel human RNA viruses from domestic wastewater using selective metagenomic analysis. Capture probe-based selection followed by next-generation sequencing using illumina MiSeq platform enabled to detect virus genome with relatively low concentration in wastewater. Viral metagenomic analysis revealed that most viral genome sequences are not homologous to any sequences in the database. Based on the metagenome, we constructed contigs that are expected to be from novel viruses. We also confirmed that virus genome with the contig sequence are present in wastewater samples throughout the study period.

  9. Transmission dynamics and evolution of influenza viruses in Asia

    Oshitani Hitoshi, KAMIGAKI Taro, SUZUKI Akira, SAITO Mariko, OKAMOTO Michiko, SAITO Mayuko, TAMAKI Raita, FURUSE Yuki, NUKIWA Nao, KHANDAKER Irona, OKADA Takashi, ODAGIRI Takashi, IMAGAWA Toshifumi, MIMURA Satoshi, IMAMURA Tadatsugu, KOSAI Hisato, CHAW Liling, Liu XIAOFANG, Ngako Kadji Francois Marie, OHNO Ayumu, OTOMARU Hisano, TOHMA Kentaro, OHTANI Kanako, Huo Xiang, TAKAHASHI Yoshihiro, FUJI Naoko, MATSUZAKI Yoko, HONGO Seiji, Lupisan S., Tandoc A., Tallo V., Tan A., Alday P., Nymadawa P., Nyamaa G., Burmaa A., Darmaa B., Bayasgalan N., Od I., Tsatsral S., Maitsetseg C.

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2012/04/01 - 2016/03/31

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    Transmission dynamics of influenza viruses were analyzed in study sites in three countries; Philippines, Mongolia and Japan. Enhanced surveillance was conducted in Baguio City and Tacloban City in the Philippines and Odate City of Akita Prefecture in Japan, while the community-based cohort study was conducted in Baganuur District of Ulaanbataar City in Mongolia. Through these studies some important epidemiological findings have been obtained, which include; 1) significant role of children in transmission of influenza viruses, 2) transmission and maintenance mechanism of influenza viruses in the Philippines, which is located in tropical area, 3) low incidence of influenza in infants and pregnant women in Mongolia.

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