Researcher Database

Hiroshi Nishiura
Faculty of Medicine Social Medicine Social Medicine
Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Medicine Social Medicine Social Medicine

Job Title

  • Professor

Degree

  • Ph.D.(Hiroshima University Graduate School of Health Sciences)
  • M.D.(Miyazaki Medical College (presently University of Miyazaki School of Medicine))

URL

J-Global ID

Profile

  • Studying infectious disease modelling, especially on the derivation of likelihood function from an explicitly structured population model, thereby bridging the gap that has existed between practitioners and modelling experts.


    http://plaza.umin.ac.jp/~infepi/hnishiura.htm


    http://www.ghp.m.u-tokyo.ac.jp/profile/staff/hnishiura/


    http://orcid.org/0000-0003-0941-8537


    http://www.tbiomed.com/about/edboard/userprofile/1470359116678138


    http://scholar.google.com/citations?user=toSTNkkAAAAJ&hl=en

Research Interests

  • 危機管理   Statistical modeling   Biostatistics   疫学   数理モデル   感染症   Mathematical model   Mathematical Statistics   Theoretical Epidemiology   Infectious disease epidemiology   

Research Areas

  • Life sciences / Healthcare management, medical sociology
  • Life sciences / Hygiene and public health (non-laboratory)
  • Life sciences / Hygiene and public health (laboratory)
  • Life sciences / Hygiene and public health (non-laboratory)
  • Life sciences / Hygiene and public health (laboratory)
  • Life sciences / Healthcare management, medical sociology
  • Social infrastructure (civil Engineering, architecture, disaster prevention) / Safety engineering
  • Social infrastructure (civil Engineering, architecture, disaster prevention) / Social systems engineering
  • Informatics / Statistical science

Academic & Professional Experience

  • 2016/04 - Today Hokkaido University Graduate School of Medicine Professor
  • 2013/06 - 2016/03 The Unviersity of Tokyo Graduate School of Medicine Associate Professor
  • 2011/04 - 2013/04 School of Public Health, The University of Hong Kong Assistant Professor
  • 2007/09 - 2011/03 Theoretical Epidemiology, University of Utrecht Postdoctoral Research Fellow, PRESTO project PI
  • 2006/04 - 2007/08 Nagasaki University Institute of Tropical Medicine Research Associate Professor
  • 2005/04 - 2007/08 Department of Medical Biometry, University of Tuebingen Research Fellow
  • 2004/04 - 2006/03 Graduate School of Health Sciences, Hiroshima University PhD Candidate
  • 2004/04 - 2005/03 Department of Infectious Disease Epidemiology, Imperial College London Academic visitor
  • 2003/04 - 2003/10 Bangkok School of Tropical Medicine, Mahidol Unviersity Graduate student
  • 2002/05 - 2003/03 Tokyo Metropolitan Ebara Hospital Clinical resident

Education

  • 2004/04 - 2006/03  Hiroshima University  Graduate School of Health Sciences
  • 1996/04 - 2002/03  Miyazaki University  School of Medicine

Association Memberships

  • Society for Mathematical Biology   European Society for Mathematical and Theoretical Biology   International Epidemiological Association   American Statistical Association   

Research Activities

Published Papers

  • Miura F, Matsuyama R, Nishiura H
    Journal of epidemiology 28 (9) 382 - 387 0917-5040 2018/09 [Refereed][Not invited]
  • Kinoshita R, Shimizu K, Nishiura H
    Travel medicine and infectious disease 1477-8939 2018/08 [Refereed][Not invited]
  • Matsuyama R, Miura F, Tsuzuki S, Nishiura H
    The Journal of international medical research 46 (7) 2866 - 2874 0300-0605 2018/07 [Refereed][Not invited]
  • Sakamoto Y, Yamaguchi T, Yamamoto N, Nishiura H
    Theoretical biology & medical modelling 15 (1) 9  2018/07 [Refereed][Not invited]
  • Belser JA, Barclay W, Barr I, Fouchier RAM, Matsuyama R, Nishiura H, Peiris M, Russell CJ, Subbarao K, Zhu H, Yen HL
    Emerging infectious diseases 24 (6) 965 - 971 1080-6040 2018/06 [Refereed][Not invited]
  • Yamamoto N, Ejima K, Nishiura H
    Theoretical biology & medical modelling 15 (1) 6  2018/05 [Refereed][Not invited]
  • Saito MM, Ejima K, Kinoshita R, Nishiura H
    International journal of environmental research and public health 15 (4) 1661-7827 2018/03 [Refereed][Not invited]
  • Nishiura H, Lee H, Yuan B, Endo A, Akhmetzhanov AR, Chowell G
    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 66 22 - 25 1201-9712 2018/01 [Refereed][Not invited]
  • Matsuyama R, Akhmetzhanov AR, Endo A, Lee H, Yamaguchi T, Tsuzuki S, Nishiura H
    PeerJ 6 e4583  2018 [Refereed][Not invited]
  • Endo A, Nishiura H
    The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale 2018 3420535  1712-9532 2018 [Refereed][Not invited]
  • Yuan B, Nishiura H
    PloS one 13 (6) e0198734  2018 [Refereed][Not invited]
  • Tsuzuki S, Lee H, Miura F, Chan YH, Jung SM, Akhmetzhanov AR, Nishiura H
    Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 22 (46) 2 - 7 1025-496X 2017/11/16 [Refereed][Not invited]
  • Hyojung Lee, Hiroshi Nishiura
    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES 64 90 - 92 1201-9712 2017/11 [Refereed][Not invited]
     
    Objectives: There have been errors in determining the end of the Ebola virus disease (EVD) epidemic when adhering to the criteria of the World Health Organization. The present study aimed to review and learn from all known recrudescence events in West Africa occurring in 2014-2016. Methods: Background mechanisms of five erroneous declarations in Guinea, Liberia, and Sierra Leone during 2014-2016 were reviewed. Results: Three cases of recrudescence were suspected to have been caused by sexual contact with survivors, one to be due to international migration, and one was linked to a potentially immunocompromised mother. The three sexual transmission events involving survivors-the first two in Liberia and one in Sierra Leone-required 164 days, > 150 days, and approximately 180 days, respectively, from discharge of the survivors to confirmation of the recrudescent case. Conclusions: The events of recrudescence were associated with relatively uncommon routes of transmission other than close contact during burial or care-giving, including sexual transmission, possible immunocompromise, and migration. Recognition of the sexual transmission risk among survivors could potentially involve discrimination, which may lead to under-ascertainment. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license
  • Kentaro Yoshii, Reiji Kojima, Hiroshi Nishiura
    EMERGING INFECTIOUS DISEASES 23 (10) 1753 - 1754 1080-6040 2017/10 [Refereed][Not invited]
     
    During early 2017, we conducted a seroepidemiologic investigation for tickborne encephalitis virus among 291 Japan Self-Defense Forces members in Hokkaido. Two (0.7%) tested positive. Neither had clinically apparent symptoms after removing ticks.
  • Hiroshi Nishiura, Kenji Mizumoto, Yusuke Asai
    EPIDEMICS 20 67 - 72 1755-4365 2017/09 [Refereed][Not invited]
     
    Objectives: Despite the verification of measles elimination, Japan experienced multiple generations of measles transmission following importation events in 2016. The purpose of the present study was to analyze the transmission dynamics of measles in Japan, 2016, estimating the transmission potential in the partially vaccinated population. Methods: All diagnosed measles cases were notified to the government, and the present study analyzed two pieces of datasets independently, i.e., the transmission tree of the largest outbreak in Osaka (n =49) and the final size distribution of all importation events (n = 23 events). Branching process model was employed to estimate the effective reproduction number Rv, and the analysis of transmission tree in Osaka enabled us to account for the timing of introducing contact tracing and case isolation. Results: Employing a negative binomial distribution for the offspring distribution, the model with time dependent decline in Rv due to interventions appeared to best fit to the transmission tree data with Rv of 9.20 (95% CI (confidence interval): 2.08, 150.68) and the dispersion parameter 0.32 (95% CI: 0.07, 1.17) before interventions were introduced. The relative transmissibility in the presence of interventions from week 34 was estimated at 0.005. Analyzing the final size distribution, models for subcritical and supercritical processes fitted equally well to the observed data, and the estimated reproduction number from both models did not exclude the possibility that Rv >1. Conclusions: Our results likely reflect the highly contagious nature of measles, indicating that Japan is at risk of observing multiple generations of measles transmission given imported cases. Considering that importation events may continue in the future, supplementary vaccination of adults needs to be considered. (C) 2017 The Author( s). Published by Elsevier B.V.
  • Kyeongah Nah, Hiroshi Nishiura, Naho Tsuchiya, Xiaodan Sun, Yusuke Asai, Akifumi Imamura
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 14 (1) 16  1742-4682 2017/09 [Refereed][Not invited]
     
    The public benefit of test-and-treat has induced a need to justify goodness for the public, and mathematical modeling studies have played a key role in designing and evaluating the test-and-treat strategy for controlling HIV/AIDS. Here we briefly and comprehensively review the essence of contemporary understanding of the test-and-treat policy through mathematical modeling approaches and identify key pitfalls that have been identified to date. While the decrease in HIV incidence is achieved with certain coverages of diagnosis, care and continued treatment, HIV prevalence is not necessarily decreased and sometimes the test-and-treat is accompanied by increased long-term cost of antiretroviral therapy (ART). To confront with the complexity of assessment on this policy, the elimination threshold or the effective reproduction number has been proposed for its use in determining the overall success to anticipate the eventual elimination. Since the publication of original model in 2009, key issues of test-and-treat modeling studies have been identified, including theoretical problems surrounding the sexual partnership network, heterogeneities in the transmission dynamics, and realistic issues of achieving and maintaining high treatment coverage in the most hard-to-reach populations. To explicitly design country-specific control policy, quantitative modeling approaches to each single setting with differing epidemiological context would require multi-disciplinary collaborations among clinicians, public health practitioners, laboratory technologists, epidemiologists and mathematical modelers.
  • Hiroshi Nishiura, Shinya Tsuzuki, Baoyin Yuan, Takayuki Yamaguchi, Yusuke Asai
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 14 (1) 14  1742-4682 2017/07 [Refereed][Not invited]
     
    Background: A large epidemic of cholera, caused by Vibrio cholerae, serotype Ogawa, has been ongoing in Yemen, 2017. To improve the situation awareness, the present study aimed to forecast the cholera epidemic, explicitly addressing the reporting delay and ascertainment bias. Methods: Using weekly incidence of suspected cases, updated as a revised epidemic curve every week, the reporting delay was explicitly incorporated into the estimation model. Using the weekly case fatality risk as calculated by the World Health Organization, ascertainment bias was adjusted, enabling us to parameterize the family of logistic curves (i.e., logistic and generalized logistic models) for describing the unbiased incidence in 2017. Results: The cumulative incidence at the end of the epidemic, was estimated at 790,778 (95% CI: 700,495, 914,442) cases and 767,029 (95% CI: 690,877, 871,671) cases, respectively, by using logistic and generalized logistic models. It was also estimated that we have just passed through the epidemic peak by week 26, 2017. From week 27 onwards, the weekly incidence was predicted to decrease. Conclusions: Cholera epidemic in Yemen, 2017 was predicted to soon start to decrease. If the weekly incidence is reported in the up-to-the-minute manner and updated in later weeks, not a single data point but the entire epidemic curve must be precisely updated.
  • Ryo Kinoshita, Hiroshi Nishiura
    VACCINE 35 (25) 3309 - 3317 0264-410X 2017/06 [Refereed][Not invited]
     
    Background: Routine vaccination against measles in Japan started in 1978. Whereas measles elimination was verified in 2015, multiple chains of measles transmission were observed in 2016. We aimed to reconstruct the age-dependent susceptibility to measles in Japan so that future vaccination strategies can be elucidated. Methods: An epidemiological model was used to quantify the age-dependent immune fraction using datasets of vaccination coverage and seroepidemiological survey. The second dose was interpreted in two different scenarios, i.e., booster and random shots. The effective reproduction number, the average number of secondary cases generated by a single infected individual, and the age at infection were explored using the age-dependent transmission model and the next generation matrix. Results: While the herd immunity threshold of measles likely ranges from 90% to 95%, assuming that the basic reproductive number ranges from 10 to 20, the estimated immune fraction in Japan was below those thresholds in 2016, despite the fact that the estimates were above 80% for all ages. If the second dose completely acted as the booster shot, a proportion immune above 90% was achieved only among those aged 5 years or below in 2016. Alternatively, if the second dose was randomly distributed regardless of primary vaccination status, a proportion immune over 90% was achieved among those aged below 25 years. The effective reproduction number was estimated to range from 1.50 to 3.01 and from 1.50 to 3.00, respectively, for scenarios 1 and 2 in 2016; if the current vaccination schedule were continued, the reproduction number is projected to range from 1.50 to 3.01 and 1.39 to 2.78, respectively, in 2025. Conclusion: Japan continues to be prone to imported cases of measles. Supplementary vaccination among adults aged 20-49 years would be effective if the chains of transmission continue to be observed in that age group. (C) 2017 Elsevier Ltd. All rights reserved.
  • Ryota Matsuyama, Fuminari Miura, Hiroshi Nishiura
    PLOS ONE 12 (3) e0173996  1932-6203 2017/03 [Refereed][Not invited]
     
    In Japan, the fraction of norovirus outbreaks attributable to human-to-human transmission has increased with time, and the timing of the increased fraction has coincided with the increase in the observed fraction of genogroup II genotype 4 (GII.4). The present study aimed to estimate the time-dependent changes in the transmissibility of noroviruses. The effective reproduction number (R-y), for year y, was estimated by analyzing the time series surveillance data for outbreak events from 2000 to 2016. R-y was estimated by using the fraction of outbreak events that were attributable to human-to-human transmission and by employing three different statistical models that are considered to mechanistically capture the possible data-generating process in different ways. The R-y estimates ranged from 0.14 to 4.15 in value, revealing an overall increasing trend (p< 0.05 for all three models). The proportion of outbreaks caused by GII and GII.4 viruses among the total events also increased with time, and positive correlations were identified between transmissibility and these proportions. Parametric modeling of R-y indicated that the time-dependent patterns of R-y were better described by a step function plus linear trend rather than the step function alone that reflects the widespread use of reverse transcriptase PCR (RT-PCR) in and after 2007 for laboratory diagnosis. Accordingly, we conclude that norovirus transmissibility has increased over the past 16 years in Japan. The change is at least partially explained by the time-dependent domination of the contagious GII genogroup (e.g., GII.4), indicating that noroviruses better fitted to humans have selectively caused the human-to-human transmissions, thereby altering the epidemiology of this pathogen.
  • Linh Dinh, Gerardo Chowell, Kenji Mizumoto, Hiroshi Nishiura
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 13 (1) 20  1742-4682 2016/11 [Refereed][Not invited]
     
    Background: Florida State has reported autochthonous transmission of Zika virus since late July 2016. Here we assessed the transmissibility associated with the outbreak and generated a short-term forecast. Methods: Time-dependent dynamics of imported cases reported in the state of Florida was approximated by a logistic growth equation. We estimated the reproduction number using the renewal equation in order to predict the incidence of local cases arising from both local and imported primary cases. Using a bootstrap method together with the logistic and renewal equations, a short-term forecast of local and imported cases was carried out. Results: The reproduction number was estimated at 0.16 (95 % Confidence Interval: 0.13, 0.19). Employing the logistic equation to capture a drastic decline in the number of imported cases expected through the course of 2016, together with the low estimate of the local reproduction number in Florida, the expected number of local reported cases was demonstrated to show an evident declining trend for the remainder of 2016. Conclusions: The risk of local transmission in the state of Florida is predicted to dramatically decline by the end of 2016.
  • Ryota Matsuyama, Hiroshi Nishiura, Satoshi Kutsuna, Kayoko Hayakawa, Norio Ohmagari
    BMC PUBLIC HEALTH 16 (1) 1203  1471-2458 2016/11 [Refereed][Not invited]
     
    Background: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. The present study aimed to systematically review the risk of death associated with MERS as well as risk factors for associated complications. Methods: PubMed and Web of Science databases were searched for clinical and epidemiological studies on confirmed cases of MERS. Eligible articles reported clinical outcomes, especially severe complications or death associated with MERS. Risks of admission to intensive care unit (ICU), mechanical ventilation and death were estimated. Subsequently, potential associations between MERS-associated death and age, sex, underlying medical conditions and study design were explored. Results: A total of 25 eligible articles were identified. The case fatality risk ranged from 14.5 to 100%, with the pooled estimate at 39.1%. The risks of ICU admission and mechanical ventilation ranged from 44.4 to 100% and from 25.0 to 100%, with pooled estimates at 78.2 and 73.0%, respectively. These risks showed a substantial heterogeneity among the identified studies, and appeared to be the highest in case studies focusing on ICU cases. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. In ICU case studies, the expected odds ratios (OR) of death among patients with underlying heart disease or renal disease to patients without such comorbidities were 0.6 (95% Confidence Interval (CI): 0.1, 4.3) and 0.6 (95% CI: 0.0, 2.1), respectively, while the ORs were 3.8 (95% CI: 3.4, 4.2) and 2.4 (95% CI: 2.0, 2.9), respectively, in studies with other types of designs. Conclusions: The heterogeneity for the risk of death and severe manifestations was substantially high among the studies, and varying study designs was one of the underlying reasons for this heterogeneity. A statistical estimation of the risk of MERS death and identification of risk factors must be conducted, particularly considering the study design and potential biases associated with case detection and diagnosis.
  • Shiori Otsuki, Hiroshi Nishiura
    PLOS ONE 11 (9) e0163418  1932-6203 2016/09 [Refereed][Not invited]
     
    Background An epidemic of Ebola virus disease (EVD) from 2013-16 posed a serious risk of global spread during its early growth phase. A post-epidemic evaluation of the effectiveness of travel restrictions has yet to be conducted. The present study aimed to estimate the effectiveness of travel restrictions in reducing the risk of importation from mid-August to September, 2014, using a simple hazard-based statistical model. Methodology/Principal Findings The hazard rate was modeled as an inverse function of the effective distance, an excellent predictor of disease spread, which was calculated from the airline transportation network. By analyzing datasets of the date of EVD case importation from the 15 th of July to the 15 th of September 2014, and assuming that the network structure changed from the 8 th of August 2014 because of travel restrictions, parameters that characterized the hazard rate were estimated. The absolute risk reduction and relative risk reductions due to travel restrictions were estimated to be less than 1% and about 20%, respectively, for all models tested. Effectiveness estimates among African countries were greater than those for other countries outside Africa. Conclusions The travel restrictions were not effective enough to expect the prevention of global spread of Ebola virus disease. It is more efficient to control the spread of disease locally during an early phase of an epidemic than to attempt to control the epidemic at international borders. Capacity building for local containment and coordinated and expedited international cooperation are essential to reduce the risk of global transmission.
  • Kyeongah Nah, Shiori Otsuki, Gerardo Chowell, Hiroshi Nishiura
    BMC INFECTIOUS DISEASES 16 356  1471-2334 2016/07 [Refereed][Not invited]
     
    Background: The Middle East respiratory syndrome (MERS) associated coronavirus has been imported via travelers into multiple countries around the world. In order to support risk assessment practice, the present study aimed to devise a novel statistical model to quantify the country-level risk of experiencing an importation of MERS case. Methods: We analyzed the arrival time of each reported MERS importation around the world, i.e., the date on which imported cases entered a specific country, which was modeled as a dependent variable in our analysis. We also used openly accessible data including the airline transportation network to parameterize a hazard-based risk prediction model. The hazard was assumed to follow an inverse function of the effective distance (i.e., the minimum effective length of a path from origin to destination), which was calculated from the airline transportation data, from Saudi Arabia to each country. Both country-specific religion and the incidence data of MERS in Saudi Arabia were used to improve our model prediction. Results: Our estimates of the risk of MERS importation appeared to be right skewed, which facilitated the visual identification of countries at highest risk of MERS importations in the right tail of the distribution. The simplest model that relied solely on the effective distance yielded the best predictive performance (Area under the curve (AUC) = 0. 943) with 100 % sensitivity and 79.6 % specificity. Out of the 30 countries estimated to be at highest risk of MERS case importation, 17 countries (56.7 %) have already reported at least one importation of MERS. Although model fit measured by Akaike Information Criterion (AIC) was improved by including country-specific religion (i.e. Muslim majority country), the predictive performance as measured by AUC was not improved after accounting for this covariate. Conclusions: Our relatively simple statistical model based on the effective distance derived from the airline transportation network data was found to help predicting the risk of importing MERS at the country level. The successful application of the effective distance model to predict MERS importations, particularly when computationally intensive large-scale transmission models may not be immediately applicable could have been benefited from the particularly low transmissibility of the MERS coronavirus.
  • Hiroshi Nishiura, Kenji Mizumoto, Kat S. Rock, Yohei Yasuda, Ryo Kinoshita, Yuichiro Miyamatsu
    EPIDEMICS 15 66 - 70 1755-4365 2016/06 [Refereed][Not invited]
     
    Objectives: There has been a growing concern over Zika virus (ZIKV) infection, particularly since a probable link between ZIKV infection during pregnancy and microcephaly in the baby was identified. The present study aimed to estimate a theoretical risk of microcephaly during pregnancy with ZIKV infection in Northeastern Brazil in 2015. Methods: Temporal distributions of microcephaly, reported dengue-like illness and dengue seropositive in Brazil were extracted from secondary data sources. Using an integral equation model and a back calculation technique, we estimated the risk of microcephaly during pregnancy with Zika virus infection. Results: If the fraction of Zika virus infections among a total of seronegative dengue-like illness cases is 30%, the risk of microcephaly following infection during the first trimester was estimated at 46.7% (95% CI: 9.1, 84.2), comparable to the risk of congenital rubella syndrome. However, the risk of microcephaly was shown to vary widely from 14.0% to 100%. The mean gestational age at delivery with microcephaly was estimated at 37.5 weeks (95% CI: 36.9, 39.3). Conclusions: The time interval between peaks of reported dengue-like illness and microcephaly was consistent with cause-outcome relationship. Our modeling framework predicts that the incidence of microcephaly is expected to steadily decline in early 2016, Brazil. (C) 2016 The Authors. Published by Elsevier B.V.
  • Hiroshi Nishiura, Kenji Mizumoto, Wilmer E. Villamil-Gomez, Alfonso J. Rodriguez-Morales
    TRAVEL MEDICINE AND INFECTIOUS DISEASE 14 (3) 274 - 276 1477-8939 2016/05 [Refereed][Not invited]
  • Hiroshi Nishiura, Ryo Kinoshita, Kenji Mizumoto, Yohei Yasuda, Kyeongah Nah
    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES 45 95 - 97 1201-9712 2016/04 [Refereed][Not invited]
     
    Objectives: Zika virus has spread internationally through countries in the South Pacific and Americas. The present study aimed to estimate the basic reproduction number, R-0, of Zika virus infection as a measurement of the transmission potential, reanalyzing past epidemic data from the South Pacific. Methods: Incidence data from two epidemics, one on Yap Island, Federal State of Micronesia in 2007 and the other in French Polynesia in 2013-2014, were reanalyzed. R-0 of Zika virus infection was estimated from the early exponential growth rate of these two epidemics. Results: The maximum likelihood estimate (MLE) of R-0 for the Yap Island epidemic was in the order of 4.3-5.8 with broad uncertainty bounds due to the small sample size of confirmed and probable cases. The MLE of R-0 for French Polynesia based on syndromic data ranged from 1.8 to 2.0 with narrow uncertainty bounds. Conclusions: The transmissibility of Zika virus infection appears to be comparable to those of dengue and chikungunya viruses. Considering that Aedes species are a shared vector, this finding indicates that Zika virus replication within the vector is perhaps comparable to dengue and chikungunya. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • Kyeongah Nah, Kenji Mizumoto, Yuichiro Miyamatsu, Yohei Yasuda, Ryo Kinoshita, Hiroshi Nishiura
    PEERJ 4 e1904  2167-8359 2016/04 [Refereed][Not invited]
     
    Background. An international spread of Zika virus (ZIKV) infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed) in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s) have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience.
  • Nishiura H, Matsuyama R, Asai Y
    Uirusu 66 (1) 79 - 82 0042-6857 2016 [Refereed][Not invited]
  • Nahoko Kato-Kogoe, Hideki Ohyama, Soichiro Okano, Koji Yamanegi, Naoko Yamada, Masaki Hata, Hiroshi Nishiura, Yoshimitsu Abiko, Nobuyuki Terada, Keiji Nakasho
    IMMUNOGENETICS 68 (1) 55 - 65 0093-7711 2016/01 [Refereed][Not invited]
     
    Interleukin 12 receptor beta chain (IL12RB2) is a crucial regulatory factor involved in cell-mediated immune responses, and genetic variants of the gene encoding IL12RB2 are associated with susceptibility to various immune-related diseases. We previously demonstrated that haplotypes with single nucleotide polymorphisms (SNPs) in the 5' flanking region of IL12RB2, including -1035A > G (rs3762315) and -1023A > G (rs3762316), affect the expression of IL12RB2, thereby altering susceptibility to leprosy and periodontal diseases. In the present study, we identified transcription factors associated with the haplotype-specific transcriptional activity of IL12RB2 in T cells and NK cells. The -1023G polymorphism was found to create a consensus binding site for the transcription factor activating protein (AP)-1, and enzyme-linked immunosorbent assay (ELISA)-based binding assays showed that these SNPs enhanced AP-1 binding to this region. In reporter assays, suppression of JunB expression using siRNA eliminated differences in the -1035G/-1023G and -1035A/-1023A regions containing IL12RB2 promoter activity in Jurkat T cells and NK3.3 cells. These results suggested that the -1035/-1023 polymorphisms created differential binding affinities for JunB that could lead to differential IL12RB2 expression. Moreover, the -1035G and -1035A alleles formed binding sites for GATA-3 and myocyte enhancer factor-2 (MEF-2), respectively. Our data indicated that in addition to JunB, the SNP at -1035/-1023 influenced GATA-3 and MEF-2 binding affinity, potentially altering IL12RB2 transcriptional activity. These findings confirm the effects of rs3762315 and rs3762316 on IL12RB2 transcription. These genetic variants may alter cellular activation of T cells and NK cells and modify cell-mediated immune responses.
  • Hiroshi Nishiura, Yuichiro Miyamatsu, Kenji Mizumoto
    EMERGING INFECTIOUS DISEASES 22 (1) 146 - 148 1080-6040 2016/01 [Refereed][Not invited]
  • Ryo Kinoshita, Hiroshi Nishiura
    BMJ OPEN 6 (1) e009928  2044-6055 2016 [Refereed][Not invited]
     
    Objective: We aimed to epidemiologically assess rubella herd immunity as a function of time, age and gender in Japan, with reference to the recent 2012-02014 rubella epidemic. Design: This study is a retrospective seroepidemiological analysis. Main outcome measures: The susceptible fraction of the population was examined as a function of age and time. The age at infection was assessed using reported case data. Results: Whereas 30 years ago rubella cases were seen only among children, the median (25-75th centiles) age of cases in 2014 was elevated to 32.0 (17.0-42.0) years among males and 27.0 (7.0-37.0) years among females. Susceptible pockets among male birth cohorts 1989-1993 and 1974-1978 were identified, with seropositive proportions of 70.0% and 68.0%, respectively. The majority of female age groups had greater seropositive proportions than the herd immunity threshold, with a minor susceptible pocket for those born from 1989 to 1993 (78.3% seropositive). The age-standardised seronegative proportion decreased to 18.3% (95% CI 16.8% to 19.8%) among males and 15.6% (95% CI 10.0% to 21.2%) among females in 2013, and the immune fraction was not sufficiently below the herd immunity threshold. While the number of live births born to susceptible mothers in 1983 was estimated at 171 876 across Japan, in 2013 it was reduced to 23 698. Conclusions: An elevated age at rubella virus infection and the presence of susceptible pockets among adults were observed in Japan. Although, overall, the absolute number of rubella cases has steadily declined in Japan, the elevated age of rubella cases, along with increased numbers of susceptible adults, contributed to the observation of as many as 45 congenital rubella syndrome (CRS) cases, which calls for supplementary vaccination among susceptible adults. Assessing herd immunity is considered essential for routinely monitoring the risk of future rubella epidemics and CRS cases.
  • Hiroshi Nishiura, Akira Endo, Masaya Saitoh, Ryo Kinoshita, Ryo Ueno, Shinji Nakaoka, Yuichiro Miyamatsu, Yueping Dong, Gerardo Chowell, Kenji Mizumoto
    BMJ OPEN 6 (2) e009936  2044-6055 2016 [Refereed][Not invited]
     
    Objectives: To investigate the heterogeneous transmission patterns of Middle East respiratory syndrome (MERS) in the Republic of Korea, with a particular focus on epidemiological characteristics of superspreaders. Design: Retrospective epidemiological analysis. Setting: Multiple healthcare facilities of secondary and tertiary care centres in an urban setting. Participants: A total of 185 laboratory-confirmed cases with partially known dates of illness onset and most likely sources of infection. Primary and secondary outcome measures: Superspreaders were identified using the transmission tree. The reproduction number, that is, the average number of secondary cases produced by a single primary case, was estimated as a function of time and according to different types of hosts. Results: A total of five superspreaders were identified. The reproduction number throughout the course of the outbreak was estimated at 1.0 due to reconstruction of the transmission tree, while the variance of secondary cases generated by a primary case was 52.1. All of the superspreaders involved in this outbreak appeared to have generated a substantial number of contacts in multiple healthcare facilities (association: p<0.01), generating on average 4.0 (0.0-8.6) and 28.6 (0.0-63.9) secondary cases among patients who visited multiple healthcare facilities and others. The time-dependent reproduction numbers declined substantially below the value of 1 on and after 13 June 2015. Conclusions: Superspreaders who visited multiple facilities drove the epidemic by generating a disproportionate number of secondary cases. Our findings underscore the need to limit the contacts in healthcare settings. Contact tracing efforts could assist early laboratory testing and diagnosis of suspected cases.
  • Ryutaro Fukami, Hiroshi Nishiura
    JAPAN JOURNAL OF INDUSTRIAL AND APPLIED MATHEMATICS 32 (3) 661 - 673 0916-7005 2015/11 [Refereed][Not invited]
     
    Leishamaniasis is a parasitic disease transmitted by sandfly Phlebotomus spp. and is seen in tropical and subtropical countries in which an estimated 12 million persons are infected. Among various types of leishmaniasis, zoonotic visceral leishmaniasis (ZVL) caused by Leishmania infantum is an important amphixenosis shared by human and other animals. Although identifying the natural reservoir host would help better understand the transmission dynamics of Leishmania spp., little effort has been made to quantitatively clarify the dynamics involving the reservoir host of ZVL. The present study investigated the reservoir potential of four wild animals in maintaining ZVL, using prevalence data from Latin American countries in Amazons and examining the role of crab-eating fox, spiny rat, common opossum and black rat in maintaining the transmission. Reflecting frequent reinfections, a susceptible-infected-susceptible model was employed, enabling us to estimate model parameters from endemic prevalence data. The next generation matrix of the multi-host system was computed, permitting us to theoretically examine the reservoir potential of each animal species. Our estimates indicated that there is no unique reservoir host consisting of single animal species. Crab eating fox was considered to play an important role in maintaining L. infantum transmission, but this was the case only in combination with other hosts. The present study indicates that animal species other than canine play important roles in maintaining transmission of Leishmania infantum, which is different from conventional wisdom that centered on the importance of canine only. Greater sample size with additional entomological and genetic insights into inter-specific contact would be required to implement more explicit assessments.
  • Kenji Mizumoto, Masaya Saitoh, Gerardo Chowell, Yuichiro Miyamatsu, Hiroshi Nishiura
    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES 39 7 - 9 1201-9712 2015/10 [Refereed][Not invited]
     
    Objectives: A large cluster of the Middle East respiratory syndrome (MERS) linked to healthcare setting occurred from May to July 2015 in the Republic of Korea. The present study aimed to estimate the case fatality ratio (CFR) by appropriately taking into account the time delay from illness onset to death. We then compare our estimate against previously published values of the CFR for MERS, i.e., 20% and 40%. Methods: Dates of illness onset and death of the MERS outbreak in the Republic of Korea were extracted from secondary data sources. Using the known distribution of time from illness onset to death and an integral equation model, we estimated the delay-adjusted risk of MERS death for the South Korean cluster. Results: Our most up-to-date estimate of CFR for the MERS outbreak in South Korea was estimated at 20.0% (95% confidence intervals (CI): 14.6, 26.2). During the course of the outbreak, estimate of the CFR in real time appeared to have decreased and become significantly lower than 40%. Conclusions: The risk of MERS death in Korea was consistent with published CFR. The estimate decreased with time perhaps due to time-dependent increase in case ascertainment. Crude ratio of cumulative deaths to cases underestimates the actual risk of MERS death because of time delay from illness onset to death. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license.
  • Hiroshi Nishiura, Koji Yamanegi, Mutsuki Kawabe, Nahoko Kato-Kogoe, Naoko Yamada, Keiji Nakasho
    IMMUNOBIOLOGY 220 (9) 1085 - 1092 0171-2985 2015/09 [Refereed][Not invited]
     
    Cell lifespan is partially regulated by a balance between survival signals via constitutively active G protein-coupled receptors (GPCRs) and death signals via death receptors. We have demonstrated that neutrophils produce a mimic ligand of G protein-coupled C5a receptor (C5aR), ribosomal protein S19 (RP S19) polymer. In contrast to an original ligand C5a, RP S19 polymer induces not only inhibition of the guanine nucleotide exchange factor activity but also initiation of the regulator of G protein signaling 3 (RGS3) promoter in a RP S19 C-terminus dependent manner. To examine an antagonistic effect of the RP S19 C-terminus on G proteins, His-S-tagged CSa or C5a/RP S19, in which an RP S19 C-terminus is bound to the C5a C-terminus, was incubated with neutrophils, and a transcription factor delta lactoferrin (delta Lf) was identified as a specific binding protein via pull-down experiments. The S-tagged C5a-induced agonistic effects on chemotaxis, cytoplasmic Ca2+ influx and p38 mitogen-activated protein kinase phosphorylation were not changed by Lf knockdown and delta Lf overexpression in neutrophil-like or macrophage-like cells, which were differentiated into mature cells from human promyelocytic leukemia HL-60 cells by dimethyl sulfoxide and phorbol-12-myristate-13-acetate, respectively. While, the S-tagged C5a/RP S19-induced antagonistic or agonistic effects on mature HL-60 neutrophil-like or macrophage-like cells were reversed by Lf knockdown and delta Lf overexpression, respectively. Moreover, RGS3 expression was increased in another HL-60 neutrophil-like cells under spontaneous apoptosis induced by an apoptotic inducer MnCl2. The RGS3 expression in apoptotic neutrophil-like cells was delayed not only by Lf knockdown but also by neutralization of the RP S19 polymer or C5aR. The inhibitory extension from G protein of C5aR to G alpha subsets of constitutively active GPCRs along with the RP S19 polymer-induced translocation of delta Lf from the cytoplasmic face of the plasma membrane to the nucleus seems to shorten the neutrophil cell lifespan. (C) 2015 Elsevier GmbH. All rights reserved.
  • Akira Endo, Hiroshi Nishiura
    JOURNAL OF THEORETICAL BIOLOGY 380 499 - 505 0022-5193 2015/09 [Refereed][Not invited]
     
    Background: Vivax malaria with two distinct (short- and long-term) incubation periods has been prevalent in the Republic of Korea since its re-emergence in 1993. As part of countermeasures, mass chemoprophylaxis has been conducted since 1997 among military personnel, a high risk group. To assess the population effectiveness of chemoprophylaxis, the time-dependent reproduction number was estimated in the present study. Methods: A renewal process has been employed, estimating the yearly effective reproduction number (R-y) from 1993 to 2012 using a maximum likelihood estimation method. Akaike Information Criterion (AIC) was computed to identify the best-fit model with a time-dependent trend that coincides with the timing of mass chemoprophylaxis. Results: The estimates of R-y revealed an overall declining trend from 1997 to 2012. Despite small fluctuations in 2005 and 2009, R-y was brought to be close to unity since 2000. An extrapolated model of the time-dependent reproduction number with the smallest AIC indicated that there was an abrupt decline in secondary transmission from 1997 to 1998. Conclusion: The epidemic of vivax malaria in the Republic of Korea has been on the whole brought under control in the last decades. Mass chemoprophylaxis assisted the decline in secondary transmissions from its second year, which presumed to have reflected the effect of long incubation period and expansion of the coverage. (C) 2015 Elsevier Ltd. All rights reserved.
  • Hiroshi Nishiura, Ryo Kinoshita, Yuichiro Miyamatsu, Kenji Mizumoto
    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES 38 16 - 18 1201-9712 2015/09 [Refereed][Not invited]
     
    Objectives: A rubella epidemic occurred in Japan from 2012-14, involving more than 15,000 cases. The present study aimed to estimate the immunizing effect of the epidemic, analyzing seroepidemiological data that were collected over time and age. Methods: Annual nationwide cross-sectional surveys were conducted from July to September, collecting serum from at least 5,400 individuals. The proportions seropositive were estimated before (2012), during (2013) and after (2014) the epidemic. Results: While the cases were mainly seen among men aged from 30-49 years, no significant increase was observed in the proportion seropositive in the corresponding age group. Even after the epidemic, age-standardized proportion seropositive of the total population remained 79.3% (95% confidence interval (CI): 75.2, 83.4) and that among males was as small as 76.7% (95% CI: 73.8, 79.6). Conclusions: Susceptible pockets remain in Japan, exposing the country to risk of additional rubella epidemics. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
  • Gerardo Chowell, Fatima Abdirizak, Sunmi Lee, Jonggul Lee, Eunok Jung, Hiroshi Nishiura, Cecile Viboud
    BMC MEDICINE 13 210  1741-7015 2015/09 [Refereed][Not invited]
     
    Background: The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015. Methods: To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks. Results: A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal-Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %. Conclusions: Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses.
  • Kenji Mizumoto, Akira Endo, Gerardo Chowell, Yuichiro Miyamatsu, Masaya Saitoh, Hiroshi Nishiura
    BMC MEDICINE 13 228  1741-7015 2015/09 [Refereed][Not invited]
     
    Background: An outbreak of the Middle East respiratory syndrome (MERS), comprising 185 cases linked to healthcare facilities, occurred in the Republic of Korea from May to July 2015. Owing to the nosocomial nature of the outbreak, it is particularly important to gain a better understanding of the epidemiological determinants characterizing the risk of MERS death in order to predict the heterogeneous risk of death in medical settings. Methods: We have devised a novel statistical model that identifies the risk of MERS death during the outbreak in real time. While accounting for the time delay from illness onset to death, risk factors for death were identified using a linear predictor tied to a logit model. We employ this approach to (1) quantify the risks of death and (2) characterize the temporal evolution of the case fatality ratio (CFR) as case ascertainment greatly improved during the course of the outbreak. Results: Senior persons aged 60 years or over were found to be 9.3 times (95 % confidence interval (CI), 5.3-16.9) more likely to die compared to younger MERS cases. Patients under treatment were at a 7.8-fold (95 % CI, 4.0-16.7) significantly higher risk of death compared to other MERS cases. The CFR among patients aged 60 years or older under treatment was estimated at 48.2 % (95 % CI, 35.2-61.3) as of July 31, 2015, while the CFR among other cases was estimated to lie below 15 %. From June 6, 2015, onwards, the CFR declined 0.3-fold (95 % CI, 0.1-1.1) compared to the earlier epidemic period, which may perhaps reflect enhanced case ascertainment following major contact tracing efforts. Conclusions: The risk of MERS death was significantly associated with older age as well as treatment for underlying diseases after explicitly adjusting for the delay between illness onset and death. Because MERS outbreaks are greatly amplified in the healthcare setting, enhanced infection control practices in medical facilities should strive to shield risk groups from MERS exposure.
  • Kenji Mizumoto, Akira Endo, Gerardo Chowell, Yuichiro Miyamatsu, Masaya Saitoh, Hiroshi Nishiura
    BMC MEDICINE 13 (1) 1741-7015 2015/09 [Refereed][Not invited]
     
    Background: An outbreak of the Middle East respiratory syndrome (MERS), comprising 185 cases linked to healthcare facilities, occurred in the Republic of Korea from May to July 2015. Owing to the nosocomial nature of the outbreak, it is particularly important to gain a better understanding of the epidemiological determinants characterizing the risk of MERS death in order to predict the heterogeneous risk of death in medical settings. Methods: We have devised a novel statistical model that identifies the risk of MERS death during the outbreak in real time. While accounting for the time delay from illness onset to death, risk factors for death were identified using a linear predictor tied to a logit model. We employ this approach to (1) quantify the risks of death and (2) characterize the temporal evolution of the case fatality ratio (CFR) as case ascertainment greatly improved during the course of the outbreak. Results: Senior persons aged 60 years or over were found to be 9.3 times (95 % confidence interval (CI), 5.3-16.9) more likely to die compared to younger MERS cases. Patients under treatment were at a 7.8-fold (95 % CI, 4.0-16.7) significantly higher risk of death compared to other MERS cases. The CFR among patients aged 60 years or older under treatment was estimated at 48.2 % (95 % CI, 35.2-61.3) as of July 31, 2015, while the CFR among other cases was estimated to lie below 15 %. From June 6, 2015, onwards, the CFR declined 0.3-fold (95 % CI, 0.1-1.1) compared to the earlier epidemic period, which may perhaps reflect enhanced case ascertainment following major contact tracing efforts. Conclusions: The risk of MERS death was significantly associated with older age as well as treatment for underlying diseases after explicitly adjusting for the delay between illness onset and death. Because MERS outbreaks are greatly amplified in the healthcare setting, enhanced infection control practices in medical facilities should strive to shield risk groups from MERS exposure.
  • H. Nishiura, Y. Miyamatsu, G. Chowell, M. Saitoh
    EUROSURVEILLANCE 20 (27) 6 - 11 1560-7917 2015/07 [Refereed][Not invited]
     
    To guide risk assessment, expected numbers of cases and generations were estimated, assuming a case importation of Middle East respiratory syndrome (MERS). Our analysis of 36 importation events yielded the risk of observing secondary transmission events at 22.7% (95% confidence interval: 19.3-25.1). The risks of observing generations 2, 3 and 4 were estimated at 10.5%, 6.1% and 3.9%, respectively. Countries at risk should be ready for highly variable outcomes following an importation of MERS.
  • Koji Yamanegi, Mutsuki Kawabe, Hiroyuki Futani, Hiroshi Nishiura, Naoko Yamada, Nahoko Kato-Kogoe, Hiromitsu Kishimoto, Shinichi Yoshiya, Keiji Nakasho
    INTERNATIONAL JOURNAL OF ONCOLOGY 46 (5) 1994 - 2002 1019-6439 2015/05 [Refereed][Not invited]
     
    The level of vascular endothelial growth inhibitor (VEGI) has been reported to be negatively associated with neovascularization in malignant tumors. The soluble form of VEGI is a potent anti-angiogenic factor due to its effects in inhibiting endothelial cell proliferation. This inhibition is mediated by death receptor 3 (DR3), which contains a death domain in its cytoplasmic tail capable of inducing apoptosis that can be subsequently blocked by decoy receptor 3 (DcR3). We investigated the effects of sodium valproate (VPA) and trichostatin A (TSA), histone deacetylase inhibitors, on the expression of VEGI and its related receptors in human osteosarcoma (OS) cell lines and human microvascular endothelial (HMVE) cells. Consequently, treatment with VPA and TSA increased the VEGI and DR3 expression levels without inducing DcR3 production in the OS cell lines. In contrast, the effect on the HMVE cells was limited, with no evidence of growth inhibition or an increase in the DR3 and DcR3 expression. However, VPA-induced soluble VEGI in the OS cell culture medium markedly inhibited the vascular tube formation of HMVE cells, while VEGI overexpression resulted in enhanced OS cell death. Taken together, the HDAC inhibitor has anti-angiogenesis and antitumor activities that mediate soluble VEGI/DR-3-induced apoptosis via both autocrine and paracrine pathways. This study indicates that the HDAC inhibitor may be exploited as a "therapeutic strategy modulating the soluble VEGI/DR3 pathway in osteosarcoma patients.
  • Hiroshi Nishiura, Gerardo Chowell
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 12 1  1742-4682 2015/01 [Refereed][Not invited]
     
    Background: Ebola virus disease (EVD) has generated a large epidemic in West Africa since December 2013. This mini-review is aimed to clarify and illustrate different theoretical concepts of infectiousness in order to compare the infectiousness across different communicable diseases including EVD. Methods: We employed a transmission model that rests on the renewal process in order to clarify theoretical concepts on infectiousness, namely the basic reproduction number, R-0, which measures the infectiousness per generation of cases, the force of infection (i.e. the hazard rate of infection), the intrinsic growth rate (i.e. infectiousness per unit time) and the per-contact probability of infection (i.e. infectiousness per effective contact). Results: Whereas R-0 of EVD is similar to that of influenza, the growth rate (i.e. the measure of infectiousness per unit time) for EVD was shown to be comparatively lower than that for influenza. Moreover, EVD and influenza differ in mode of transmission whereby the probability of transmission per contact is lower for EVD compared to that of influenza. Conclusions: The slow spread of EVD associated with the need for physical contact with body fluids supports social distancing measures including contact tracing and case isolation. Descriptions and interpretations of different variables quantifying infectiousness need to be used clearly and objectively in the scientific community and for risk communication.
  • Chowell G, Nishiura H
    PLoS biology 13 (1) e1002057  1544-9173 2015/01 [Refereed][Not invited]
  • Gerardo Chowell, Hiroshi Nishiura
    BMC MEDICINE 12 196  1741-7015 2014/10 [Refereed][Not invited]
     
    The complex and unprecedented Ebola epidemic ongoing in West Africa has highlighted the need to review the epidemiological characteristics of Ebola Virus Disease (EVD) as well as our current understanding of the transmission dynamics and the effect of control interventions against Ebola transmission. Here we review key epidemiological data from past Ebola outbreaks and carry out a comparative review of mathematical models of the spread and control of Ebola in the context of past outbreaks and the ongoing epidemic in West Africa. We show that mathematical modeling offers useful insights into the risk of a major epidemic of EVD and the assessment of the impact of basic public health measures on disease spread. We also discuss the critical need to collect detailed epidemiological data in real-time during the course of an ongoing epidemic, carry out further studies to estimate the effectiveness of interventions during past outbreaks and the ongoing epidemic, and develop large-scale modeling studies to study the spread and control of viral hemorrhagic fevers in the context of the highly heterogeneous economic reality of African countries.
  • On the risk of severe dengue during secondary infection: A systematic review coupled with mathematical modeling
    Kenji Mizumoto, Keisuke Ejima, Taro Yamamoto, Hiroshi Nishiura
    JOURNAL OF VECTOR BORNE DISEASES 51 (3) 153 - 164 0972-9062 2014/09 [Refereed][Not invited]
     
    Background & objectives: The present study aimed to systematically quantify the well known risk of severe dengue during secondary infection in literature and to understand how epidemiological mechanisms of enhancement during the secondary infection influence the empirically estimated risk of severe dengue by means of mathematical modeling. Methods: Two conditional risks of severe dengue, i.e. symptomatic illness and dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), given secondary infection were explored based on systematically searched prospective studies. A two-strain epidemiological model was employed to simulate the transmission dynamics of dengue and to identify the relevant data gaps in empirical observations. Results: Using the variance-based weighting, the pooled relative risk (RR) of symptomatic illness during secondary infection was estimated at 9.4 [95% confidence interval (CI): 6.1-14.4], and similarly, RR of DHF/DSS was estimated to be 23.7 (95% CI: 15.3-36.9). A variation in the RR of DHF/DSS was observed among prospective studies. Using the mathematical modeling technique, we identified the duration of cross-protective immunity as an important modulator of the time-dependent behaviour of the RR of severe dengue. Different epidemiological mechanisms of enhancement during secondary infection yielded different RR of severe dengue. Interpretation & conclusion: Optimal design of prospective cohort study for dengue should be considered, accounting for the time-dependence in the RR during the course of dengue epidemic. It is critical to statistically infer the duration of cross-protective immunity and clarify how the enhancement influences the epidemiological dynamics during secondary infection.
  • Benjamin J. Cowling, Dennis K. M. Ip, Vicky J. Fang, Piyarat Suntarattiwong, Sonja J. Olsen, Jens Levy, Timothy M. Uyeki, Gabriel M. Leung, J. S. Malik Peiris, Tawee Chotpitayasunondh, Hiroshi Nishiura, J. Mark Simmerman
    PLOS ONE 9 (9) e108850  1932-6203 2014/09 [Refereed][Not invited]
     
    Introduction:While influenza A and B viruses can be transmitted via respiratory droplets, the importance of small droplet nuclei "aerosols'' in transmission is controversial. Methods and Findings: In Hong Kong and Bangkok, in 2008-11, subjects were recruited from outpatient clinics if they had recent onset of acute respiratory illness and none of their household contacts were ill. Following a positive rapid influenza diagnostic test result, subjects were randomly allocated to one of three household-based interventions: hand hygiene, hand hygiene plus face masks, and a control group. Index cases plus their household contacts were followed for 7-10 days to identify secondary infections by reverse transcription polymerase chain reaction (RT-PCR) testing of respiratory specimens. Index cases with RT-PCR-confirmed influenza B were included in the present analyses. We used a mathematical model to make inferences on the modes of transmission, facilitated by apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We estimated that approximately 37% and 26% of influenza B virus transmission was via the aerosol mode in households in Hong Kong and Bangkok, respectively. In the fitted model, influenza B virus infections were associated with a 56%-72% risk of fever plus cough if infected via aerosol route, and a 23%-31% risk of fever plus cough if infected via the other two modes of transmission. Conclusions: Aerosol transmission may be an important mode of spread of influenza B virus. The point estimates of aerosol transmission were slightly lower for influenza B virus compared to previously published estimates for influenza A virus in both Hong Kong and Bangkok. Caution should be taken in interpreting these findings because of the multiple assumptions inherent in the model, including that there is limited biological evidence to date supporting a difference in the clinical features of influenza B virus infection by different modes.
  • Keisuke Ejima, Kazuyuki Aihara, Hiroshi Nishiura
    JOURNAL OF THEORETICAL BIOLOGY 346 47 - 53 0022-5193 2014/04 [Refereed][Not invited]
     
    Middle East respiratory syndrome (MERS) has spread worldwide since 2012. As the clinical symptoms of MERS tend to be non-specific, the incubation period has been shown to complement differential diagnosis, especially to rule out influenza. However, because an infection event is seldom directly observable, the present study aims to construct a diagnostic model that predicts the probability of MERS diagnosis given the time from immigration to illness onset among imported cases which are suspected of MERS. Addressing censoring by considering the transmission dynamics in an exporting country, we demonstrate that the illness onset within 2 days from immigration is suggestive of influenza. Two exceptions to suspect MERS even for those with illness onset within 2 days since immigration are (i) when we observe substantial community transmissions of MERS and (ii) when the cases are at high risk of MERS (e.g. cases with close contact in hospital or household). It is vital to collect the information of the incubation period upon emergence of a novel infectious disease, and moreover, in our model, the fundamental transmission dynamics including the initial growth rate has to be explored to differentiate the disease diagnoses with non-specific symptoms. (C) 2014 Elsevier Ltd. All rights reserved.
  • Koji Nabae, Hiroshi Satoh, Hiroshi Nishiura, Keiko Tanaka-Taya, Nobuhiko Okabe, Kazunori Oishi, Kunichika Matsumoto, Tomonori Hasegawa
    PLOS ONE 9 (3) e92519  1932-6203 2014/03 [Refereed][Not invited]
     
    Background: Seroepidemiological study of parvovirus B19 has not taken place for some 20 years in Japan. To estimate the risk of parvovirus B19 infection in Japan among blood donors and pregnant women in this century, a seroepidemiological survey and statistical modeling of the force of infection were conducted. Methodology/Principal Findings: The time- and age-specific seroprevalence data were suggestive of strong age-dependency in the risk of infection. Employing a piecewise constant model, the highest forces of infection of 0.05 and 0.12 per year were observed among those aged 0-4 and 5-9 years, respectively, while estimates among older individuals were less than 0.01 per year. Analyzing the antigen detection data among blood donors, the age-specific proportion positive was highest among those aged 30-39 years, agreeing with the presence of dip in seroprevalence in this age-group. Among pregnant women, up to 107 fetal deaths and 21 hydrops fetalis were estimated to have occurred annually across Japan. Conclusions: Seroepidemiological profiles of PVB19 infection in Japan was characterized with particular emphasis on the risk of infection in blood donors and the burden of infection among pregnant women. When a vaccine becomes available in the future, a similar seroepidemiological study is expected to play a key role in planning the appropriate immunization policy.
  • Hiroshi Nishiura, Keisuke Ejima, Kenji Mizumoto
    LANCET INFECTIOUS DISEASES 14 (2) 100 - 100 1473-3099 2014/02 [Refereed][Not invited]
  • Hiroshi Nishiura, Keisuke Ejima, Kenji Mizumoto, Shinji Nakaoka, Hisashi Inaba, Seiya Imoto, Rui Yamaguchi, Masaya M. Saito
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 11 5  1742-4682 2014/01 [Refereed][Not invited]
     
    Background: There has been a variation in published opinions toward the effectiveness of school closure which is implemented reactively when substantial influenza transmissions are seen at schools. Parameterizing an age-structured epidemic model using published estimates of the pandemic H1N1-2009 and accounting for the cost effectiveness, we examined if the timing and length of school closure could be optimized. Methods: Age-structured renewal equation was employed to describe the epidemic dynamics of an influenza pandemic. School closure was assumed to take place only once during the course of the pandemic, abruptly reducing child-to-child transmission for a fixed length of time and also influencing the transmission between children and adults. Public health effectiveness was measured by reduction in the cumulative incidence, and cost effectiveness was also examined by calculating the incremental cost effectiveness ratio and adopting a threshold of 1.0 x 10(7) Japanese Yen/life-year. Results: School closure at the epidemic peak appeared to yield the largest reduction in the final size, while the time of epidemic peak was shown to depend on the transmissibility. As the length of school closure was extended, we observed larger reduction in the cumulative incidence. Nevertheless, the cost effectiveness analysis showed that the cost of our school closure scenario with the parameters derived from H1N1-2009 was not justifiable. If the risk of death is three times or greater than that of H1N1-2009, the school closure could be regarded as cost effective. Conclusions: There is no fixed timing and duration of school closure that can be recommended as universal guideline for different types of influenza viruses. The effectiveness of school closure depends on the transmission dynamics of a particular influenza virus strain, especially the virulence (i.e. the infection fatality risk).
  • Zhou Y, Lau EH, Ip DK, Nishiura H, Leung GM, Seto WH, Cowling BJ
    American journal of epidemiology 178 (8) 1313 - 1318 0002-9262 2013/10 [Refereed][Not invited]
  • Nishiura H, Rietman EA, Wu R
    Theoretical biology & medical modelling 10 43  2013/07 [Refereed][Not invited]
  • Mizumoto K, Yamamoto T, Nishiura H
    The Journal of international medical research 3 41 (3) 716 - 724 0300-0605 2013/06 [Refereed][Not invited]
  • Benjamin J. Cowling, Dennis K. M. Ip, Vicky J. Fang, Piyarat Suntarattiwong, Sonja J. Olsen, Jens Levy, Timothy M. Uyeki, Gabriel M. Leung, J. S. Malik Peiris, Tawee Chotpitayasunondh, Hiroshi Nishiura, James Mark Simmerman
    NATURE COMMUNICATIONS 4 1935  2041-1723 2013/06 [Refereed][Not invited]
     
    Influenza A viruses are believed to spread between humans through contact, large respiratory droplets and small particle droplet nuclei (aerosols), but the relative importance of each of these modes of transmission is unclear. Volunteer studies suggest that infections via aerosol transmission may have a higher risk of febrile illness. Here we apply a mathematical model to data from randomized controlled trials of hand hygiene and surgical face masks in Hong Kong and Bangkok households. In these particular environments, inferences on the relative importance of modes of transmission are facilitated by information on the timing of secondary infections and apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We find that aerosol transmission accounts for approximately half of all transmission events. This implies that measures to reduce transmission by contact or large droplets may not be sufficient to control influenza A virus transmission in households.
  • Peng Wu, Benjamin J. Cowling, Joseph T. Wu, Eric H. Y. Lau, Dennis K. M. Ip, Hiroshi Nishiura
    INFLUENZA AND OTHER RESPIRATORY VIRUSES 7 (3) 367 - 382 1750-2640 2013/05 [Refereed][Not invited]
     
    In recent years, Hong Kong has invested in research infrastructure to appropriately respond to novel infectious disease epidemics. Research from Hong Kong made a strong contribution to the international response to the 2009 influenza A (H1N1) pandemic (pH1N1). Summarizing, describing, and reviewing Hong Kong's response to the 2009 pandemic, this article aimed to identify key elements of a real-time research response. A systematic search in PubMed and EMBASE for research into the infection dynamics and natural history, impact, or control of pH1N1 in Hong Kong. Eligible articles were analyzed according to their scope. Fifty-five articles were included in the review. Transmissibility of pH1N1 was similar in Hong Kong to elsewhere, and only a small fraction of infections were associated with severe disease. School closures were effective in reducing pH1N1 transmission, oseltamivir was effective for treatment of severe cases while convalescent plasma therapy has the potential to mitigate future pandemics. There was a rapid and comprehensive research response to pH1N1 in Hong Kong, providing important information on the epidemiology of the novel virus with relevance internationally as well as locally. The scientific knowledge gained through these detailed studies of pH1N1 is now being used to revise and update pandemic plans. The experiences of the research response in Hong Kong could provide a template for the research response to future emerging and reemerging disease epidemics.
  • Nishiura H, Mizumoto K, Ejima K
    Theoretical biology & medical modelling 10 30  2013/05 [Refereed][Not invited]
  • Lau LL, Ip DK, Nishiura H, Fang VJ, Chan KH, Peiris JS, Leung GM, Cowling BJ
    The Journal of infectious diseases 8 207 (8) 1281 - 1285 0022-1899 2013/04 [Refereed][Not invited]
  • Jessica Y. Wong, Peng Wu, Hiroshi Nishiura, Edward Goldstein, Eric H. Y. Lau, Lin Yang, S. K. Chuang, Thomas Tsang, J. S. Malik Peiris, Joseph T. Wu, Benjamin J. Cowling
    AMERICAN JOURNAL OF EPIDEMIOLOGY 177 (8) 834 - 840 0002-9262 2013/04 [Refereed][Not invited]
     
    One measure of the severity of a pandemic influenza outbreak at the individual level is the risk of death among people infected by the new virus. However, there are complications in estimating both the numerator and denominator. Regarding the numerator, statistical estimates of the excess deaths associated with influenza virus infections tend to exceed the number of deaths associated with laboratory-confirmed infection. Regarding the denominator, few infections are laboratory confirmed, while differences in case definitions and approaches to case ascertainment can lead to wide variation in case fatality risk estimates. Serological surveillance can be used to estimate the cumulative incidence of infection as a denominator that is more comparable across studies. We estimated that the first wave of the influenza A(H1N1)pdm09 virus in 2009 was associated with approximately 232 (95 confidence interval: 136, 328) excess deaths of all ages in Hong Kong, mainly among the elderly. The point estimates of the risk of death on a per-infection basis increased substantially with age, from below 1 per 100,000 infections in children to 1,099 per 100,000 infections in those 6069 years of age. Substantial variation in the age-specific infection fatality risk complicates comparison of the severity of different influenza strains.
  • Keisuke Ejima, Kazuyuki Aihara, Hiroshi Nishiura
    PLOS ONE 8 (4) e62062  1932-6203 2013/04 [Refereed][Not invited]
     
    Background: The way we formulate a mathematical model of an infectious disease to capture symptomatic and asymptomatic transmission can greatly influence the likely effectiveness of vaccination in the presence of vaccine effect for preventing clinical illness. The present study aims to assess the impact of model building strategy on the epidemic threshold under vaccination. Methodology/Principal Findings: We consider two different types of mathematical models, one based on observable variables including symptom onset and recovery from clinical illness ( hereafter, the "observable model'') and the other based on unobservable information of infection event and infectiousness ( the "unobservable model''). By imposing a number of modifying assumptions to the observable model, we let it mimic the unobservable model, identifying that the two models are fully consistent only when the incubation period is identical to the latent period and when there is no pre-symptomatic transmission. We also computed the reproduction numbers with and without vaccination, demonstrating that the data generating process of vaccine-induced reduction in symptomatic illness is consistent with the observable model only and examining how the effective reproduction number is differently calculated by two models. Conclusions: To explicitly incorporate the vaccine effect in reducing the risk of symptomatic illness into the model, it is fruitful to employ a model that directly accounts for disease progression. More modeling studies based on observable epidemiological information are called for.
  • Ejima K, Aihara K, Nishiura H
    Theoretical biology & medical modelling 10 17  2013/03 [Refereed][Not invited]
  • Harsha K. K. Perera, Geethani Wickramasinghe, Chung L. Cheung, Hiroshi Nishiura, David K. Smith, Leo L. M. Poon, Aluthgama K. C. Perera, Siu K. Ma, Narapiti P. Sunil-Chandra, Yi Guan, Joseph S. M. Peiris
    EMERGING INFECTIOUS DISEASES 19 (3) 481 - 484 1080-6040 2013/03 [Refereed][Not invited]
     
    To study influenza viruses in pigs in Sri Lanka, we examined samples from pigs at slaughterhouses. Influenza (H3N2) and A(H1N1)pdm09 viruses were prevalent during 2004-2005 and 2009-2012, respectively. Genetic and epidemiologic analyses of human and swine influenza viruses indicated 2 events of A(H1N1)pdm09 virus spillover from humans to pigs.
  • Mizumoto K, Ejima K, Yamamoto T, Nishiura H
    International journal of environmental research and public health 3 10 (3) 816 - 829 1661-7827 2013/02 [Refereed][Not invited]
  • Kenji Mizumoto, Hiroshi Nishiura, Taro Yamamoto
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 10 4  1742-4682 2013/01 [Refereed][Not invited]
     
    Background: During the very early stage of the 2009 pandemic, mass chemoprophylaxis was implemented as part of containment measure. The purposes of the present study were to systematically review the retrospective studies that investigated the effectiveness of antiviral prophylaxis during the 2009 pandemic, and to explicitly estimate the effectiveness by employing a mathematical model. Methods: A systematic review identified 17 articles that clearly defined the cases and identified exposed individuals based on contact tracing. Analysing a specific school-driven outbreak, we estimated the effectiveness of antiviral prophylaxis using a renewal equation model. Other parameters, including the reproduction number and the effectiveness of antiviral treatment and school closure, were jointly estimated. Results: Based on the systematic review, median secondary infection risks (SIRs) among exposed individuals with and without prophylaxis were estimated at 2.1% (quartile: 0, 12.2) and 16.6% (quartile: 8.4, 32.4), respectively. A very high heterogeneity in the SIR was identified with an estimated I-2 statistic at 71.8%. From the outbreak data in Madagascar, the effectiveness of mass chemoprophylaxis in reducing secondary transmissions was estimated to range from 92.8% to 95.4% according to different model assumptions and likelihood functions, not varying substantially as compared to other parameters. Conclusions: Only based on the meta-analysis of retrospective studies with different study designs and exposure settings, it was not feasible to estimate the effectiveness of antiviral prophylaxis in reducing transmission. However, modelling analysis of a single outbreak successfully yielded an estimate of the effectiveness that appeared to be robust to model assumptions. Future studies should fill the data gap that has existed in observational studies and allow mathematical models to be used for the analysis of meta-data.
  • Funk S, Nishiura H, Heesterbeek H, Edmunds WJ, Checchi F
    PLoS computational biology 1 9 (1) e1002855  1553-734X 2013/01 [Refereed][Not invited]
  • Nishiura H, Yen HL, Cowling BJ
    PloS one 1 8 (1) e55358  2013 [Refereed][Not invited]
  • Hiroshi Nishiura, Kenji Mizumoto
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 10 (4) 382 - 384 1449-1907 2013 [Refereed][Not invited]
     
    Epidemiological determinants of successful vaccine development were explored using measurable biological variables including antigenic stability and requirement of T-cell immunity. Employing a logistic regression model, we demonstrate that a high affinity with blood and immune cells and pathogen interactions (e. g. interference) would be the risk factors of failure for vaccine development.
  • Mizumoto K, Yamamoto T, Nishiura H
    Computational and mathematical methods in medicine 2013 637064  1748-670X 2013 [Refereed][Not invited]
  • Wu P, Goldstein E, Ho LM, Yang L, Nishiura H, Wu JT, Ip DK, Chuang SK, Tsang T, Cowling BJ
    The Journal of infectious diseases 12 206 (12) 1862 - 1871 1537-6613 2012/12 [Refereed][Not invited]
  • Gerardo Chowell, Hiroshi Nishiura, Cecile Viboud
    BMC MEDICINE 10 159  1741-7015 2012/12 [Refereed][Not invited]
     
    We discuss models for rapidly disseminating infectious diseases during mass gatherings (MGs), using influenza as a case study. Recent innovations in modeling and forecasting influenza transmission dynamics at local, regional, and global scales have made influenza a particularly attractive model scenario for MG. We discuss the behavioral, medical, and population factors for modeling MG disease transmission, review existing model formulations, and highlight key data and modeling gaps related to modeling MG disease transmission. We argue that the proposed improvements will help integrate infectious-disease models in MG health contingency plans in the near future, echoing modeling efforts that have helped shape influenza pandemic preparedness plans in recent years.
  • Benjamin J. Cowling, Hiroshi Nishiura
    EPIDEMIOLOGY 23 (6) 930 - 931 1044-3983 2012/11 [Refereed][Not invited]
  • Ryosuke Omori, Benjamin J. Cowling, Hiroshi Nishiura
    PLOS ONE 7 (11) e50751  1932-6203 2012/11 [Refereed][Not invited]
     
    Background: Many novel vaccines can cover only a fraction of all antigenic types of a pathogen. Vaccine effectiveness (VE) in the presence of interactions between vaccine strains and others is complicated by the interacting transmission dynamics among all strains. The present study investigated how the VE estimates measured in the field, based on estimated odds ratio or relative risks, are scaled by vaccination coverage and the transmission dynamics in the presence of cross-protective immunity between two strains, i.e. vaccine and non-vaccine strains. Methodology/Principal Findings: Two different types of epidemiological models, i.e. with and without re-infection by the same antigenic type, were investigated. We computed the relative risk of infection and the odds ratio of vaccination, the latter of which has been measured by indirect cohort method as applied to vaccine effectiveness study of Streptococcus pneumoniae. The VE based on the relative risk was less sensitive to epidemiological dynamics such as cross-protective immunity and vaccination coverage than the VE calculated from the odds ratio, and this was especially the case for the model without re-infection. Vaccine-induced (cross-protective) immunity against a non-vaccine strain appeared to yield the highest impact on the VE estimate calculated from the odds ratio of vaccination. Conclusion: It is essential to understand the transmission dynamics of non-vaccine strains so that epidemiological methods can appropriately measure both the direct and indirect population impact of vaccination. For pathogens with interacting antigenic types, the most valid estimates of VE, that are unlikely to be biased by the transmission dynamics, may be obtained from longitudinal prospective studies that permit estimation of the VE based on the relative risk of infection among vaccinated compared to unvaccinated individuals.
  • Eric H. Y. Lau, Hiroshi Nishiura, Benjamin J. Cowling, Dennis K. M. Ip, Joseph T. Wu
    EMERGING INFECTIOUS DISEASES 18 (10) 1700 - 1702 1080-6040 2012/10 [Refereed][Not invited]
  • Gerardo Chowell, Hiroshi Nishiura
    BMC MEDICINE 10 118  1741-7015 2012/10 [Refereed][Not invited]
     
    Providing valid and reliable estimates of the transmissibility and severity of pandemic influenza in real time is key to guide public health policymaking. In particular, early estimates of the transmissibility are indispensable for determining the type and intensity of interventions. A recent study by House and colleagues in BMC Medicine devised a stochastic transmission model to estimate the unbiased risk of transmission within households, applying the method to datasets of the 2009 A/H1N1 influenza pandemic. Here, we discuss future challenges in household transmission studies and underscore the need to systematically collect epidemiological data to decipher the household transmission dynamics. We emphasize the need to consider three critical issues for future improvements: (i) capturing age-dependent heterogeneity within households calls for intensive modeling efforts, (ii) the timeline of observation during the course of an epidemic and the length of follow-up should be aligned with study objectives, and (iii) the use of laboratory methods, especially molecular techniques, is encouraged to distinguish household transmissions from those arising in the community.
  • Nishiura H
    Osong public health and research perspectives 3 (3) 121 - 127 2210-9099 2012/09 [Refereed][Not invited]
  • Lincoln L. H. Lau, Hiroshi Nishiura, Heath Kelly, Dennis K. M. Ip, Gabriel M. Leung, Benjamin J. Cowling
    EPIDEMIOLOGY 23 (4) 531 - 542 1044-3983 2012/07 [Refereed][Not invited]
     
    Background: During the 2009 influenza A (H1N1) pandemic, household transmission studies were implemented to better understand the characteristics of the transmission of the novel virus in a confined setting. Methods: We conducted a systematic review and meta-analysis to assess and summarize the findings of these studies. We identified 27 articles, around half of which reported studies conducted in May and June 2009. Results: In 13 of the 27 studies (48%) that collected respiratory specimens from household contacts, point estimates of the risk of secondary infection ranged from 3% to 38%, with substantial heterogeneity. Meta-regression analyses revealed that a part of the heterogeneity reflected varying case ascertainment and study designs. The estimates of symptomatic secondary infection risk, based on 20 studies identifying febrile acute respiratory illness among household contacts, also showed substantial variability, with point estimates ranging from 4% to 37%. Conclusions: Transmission of the 2009 pandemic virus in households appeared to vary among countries and settings, with differences in estimates of the secondary infection risk also partly due to differences in study designs.
  • Benjamin J. Cowling, Vicky J. Fang, Hiroshi Nishiura, Kwok-Hung Chan, Sophia Ng, Dennis K. M. Ip, Susan S. Chiu, Gabriel M. Leung, J. S. Malik Peiris
    CLINICAL INFECTIOUS DISEASES 54 (12) 1778 - 1783 1058-4838 2012/06 [Refereed][Not invited]
     
    We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.
  • Brendan Klick, Hiroshi Nishiura, Benjamin J. Cowling
    PLOS ONE 7 (4) e35166  1932-6203 2012/04 [Refereed][Not invited]
     
    Background: Influenza cohort studies, in which participants are monitored for infection over an epidemic period, are invaluable in assessing the effectiveness of control measures such as vaccination, antiviral prophylaxis and non-pharmaceutical interventions (NPIs). Influenza infections and illnesses can be identified through a number of approaches with different costs and logistical requirements. Methodology and Principal Findings: In the context of a randomized controlled trial of an NPI with a constrained budget, we used a simulation approach to examine which approaches to measuring outcomes could provide greater statistical power to identify an effective intervention against confirmed influenza. We found that for a short epidemic season, the optimal design was to collect respiratory specimens at biweekly intervals, as well as following report of acute respiratory illness (ARI), for virologic testing by reverse transcription polymerase chain reaction (RT-PCR). Collection of respiratory specimens only from individuals reporting ARI was also an efficient design particularly for studies in settings with longer periods of influenza activity. Collection of specimens only from individuals reporting a febrile ARI was less efficient. Collection and testing of sera before and after influenza activity appeared to be inferior to collection of respiratory specimens for RT-PCR confirmation of acute infections. The performance of RT-PCR was robust to uncertainty in the costs and diagnostic performance of RT-PCR and serological tests. Conclusions and Significance: Our results suggest that unless the sensitivity or specificity of serology can be increased RTPCR will remain as the preferable outcome measure in NPI studies. Routine collection of specimens for RT-PCR testing even when study participants do not report acute respiratory illness appears to be the most cost efficient design under most scenarios.
  • Hiroshi Nishiura, Ping Yan, Candace K. Sleeman, Charles J. Mode
    JOURNAL OF THEORETICAL BIOLOGY 294 48 - 55 0022-5193 2012/02 [Refereed][Not invited]
     
    Use of the final size distribution of minor outbreaks for the estimation of the reproduction numbers of supercritical epidemic processes has yet to be considered. We used a branching process model to derive the final size distribution of minor outbreaks, assuming a reproduction number above unity, and applying the method to final size data for pneumonic plague. Pneumonic plague is a rare disease with only one documented major epidemic in a spatially limited setting. Because the final size distribution of a minor outbreak needs to be normalized by the probability of extinction, we assume that the dispersion parameter (k) of the negative-binomial offspring distribution is known, and examine the sensitivity of the reproduction number to variation in dispersion. Assuming a geometric offspring distribution with k=1, the reproduction number was estimated at 1.16 (95% confidence interval: 0.97-1.38). When less dispersed with k=2, the maximum likelihood estimate of the reproduction number was 1.14. These estimates agreed with those published from transmission network analysis, indicating that the human-to-human transmission potential of the pneumonic plague is not very high. Given only minor outbreaks, transmission potential is not sufficiently assessed by directly counting the number of offspring. Since the absence of a major epidemic does not guarantee a subcritical process, the proposed method allows us to conservatively regard epidemic data from minor outbreaks as supercritical, and yield estimates of threshold values above unity. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.
  • Keisuke Ejima, Ryosuke Omori, Kazuyuki Aihara, Hiroshi Nishiura
    INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 8 (5) 620 - 629 1449-2288 2012 [Refereed][Not invited]
     
    As part of measles elimination effort, evaluation of the vaccination program and real-time assessment of the epidemic dynamics constitute two important tasks to improve and strengthen the control. The present study aimed to develop an epidemiological modeling method which can be applied to estimating the vaccine efficacy at an individual level while conducting the timely investigation of the epidemic. The multivariate renewal process model was employed to describe the temporal evolution of infection by vaccination history, jointly estimating the time-dependent reproduction number and the vaccine efficacy. Analyzing the enhanced surveillance data of measles in Aichi prefecture, Japan from 2007-08, the vaccine efficacy was estimated at 96.7% (95% confidence interval: 95.8, 97.4). Using an age structured model, the vaccine efficacy among those aged from 5-19 years was shown to be smaller than that among those from 0-4 years. The age-dependent vaccine efficacy estimate informs the age-groups to be targeted for revaccination. Because the estimation method can rest on readily available epidemiological data, the proposed model has a potential to be integrated with routine surveillance.
  • Keisuke Ejima, Ryosuke Omori, Benjamin J. Cowling, Kazuyuki Aihara, Hiroshi Nishiura
    COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2012 978901  1748-670X 2012 [Refereed][Not invited]
     
    Estimating the case fatality ratio (CFR) of a novel strain of influenza virus during the early stage of the pandemic is one of key epidemiological tasks to be conducted as rapid research response. Past experience during the epidemics of severe acute respiratory syndrome (SARS) and influenza A (H1N1-2009) posed several technical challenges in estimating the CFR in real time. The present study aimed to develop a simple method to estimate the CFR based on readily available datasets, that is, confirmed cases and deaths, while addressing some of the known technical issues. To assess the reliability and validity of the proposed method, we examined the minimum length of time required for the assigned CFR to be included within the 95% confidence intervals and for the estimated CFR to be below a prespecified cut-off value by means of Monte Carlo simulations. Overall, the smaller the transmission potential was, the longer it took to compare the estimated CFR against the cut-off value. If policymaking and public health response have to be made based on the CFR estimate derived from the proposed method and readily available data, it should be noted that the successful estimation may take longer than a few months.
  • Welling Oei, Hiroshi Nishiura
    COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2012 124861  1748-670X 2012 [Refereed][Not invited]
     
    The epidemiological mechanisms behind the W-shaped age-specific influenza mortality during the Spanish influenza (H1N1) pandemic 1918-19 have yet to be fully clarified. The present study aimed to develop a formal hypothesis: tuberculosis (TB) was associated with the W-shaped influenza mortality from 1918-19. Three pieces of epidemiological information were assessed: (i) the epidemic records containing the age-specific numbers of cases and deaths of influenza from 1918-19, (ii) an outbreak record of influenza in a Swiss TB sanatorium during the pandemic, and (iii) the age-dependent TB mortality over time in the early 20th century. Analyzing the data (i), we found that the W-shaped pattern was not only seen in mortality but also in the age-specific case fatality ratio, suggesting the presence of underlying age-specific risk factor(s) of influenza death among young adults. From the data (ii), TB was shown to be associated with influenza death (P = 0.09), and there was no influenza death among non-TB controls. The data (iii) were analyzed by employing the age-period-cohort model, revealing harvesting effect in the period function of TB mortality shortly after the 1918-19 pandemic. These findings suggest that it is worthwhile to further explore the role of TB in characterizing the age-specific risk of influenza death.
  • Brendan Klick, Hiroshi Nishiura, Sophia Ng, Vicky J. Fang, Gabriel M. Leung, J. S. Malik Peiris, Benjamin J. Cowling
    EPIDEMIOLOGY 22 (6) 793 - 796 1044-3983 2011/11 [Refereed][Not invited]
     
    Background: The household secondary attack proportion (SAP) is commonly used to measure the transmissibility of an infectious disease. Methods: We analyzed the final outbreak size distributions of pandemic A(H1N1), seasonal A(H1N1), and A(H3N2) infections identified in paired sera collected from members of 117 Hong Kong households in April and in August-October 2009. Results: The estimated community probability of infection overall was higher for children than adults; the probability was similar for pandemic A(H1N1) and seasonal A(H3N2) influenza. The household SAP for pandemic A(H1N1) was higher in children than in adults, whereas for seasonal A(H3N2), it was similar in children and adults. The estimated SAPs were similar for seasonal A(H3N2) and pandemic A(H1N1) after excluding persons with higher baseline antibody titers from analysis. Conclusions: Pandemic and seasonal influenza A viruses had similar age-specific transmissibility in a cohort of initially uninfected households, after adjustment for baseline immunity.
  • Elson H. Y. Lam, Benjamin J. Cowling, Alex R. Cook, Jessica Y. T. Wong, Max S. Y. Lau, Hiroshi Nishiura
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 8 44  1742-4682 2011/11 [Refereed][Not invited]
     
    Background: Epidemiological studies have shown that imposing travel restrictions to prevent or delay an influenza pandemic may not be feasible. To delay an epidemic substantially, an extremely high proportion of trips (similar to 99%) would have to be restricted in a homogeneously mixing population. Influenza is, however, strongly influenced by age-dependent transmission dynamics, and the effectiveness of age-specific travel restrictions, such as the selective restriction of travel by children, has yet to be examined. Methods: A simple stochastic model was developed to describe the importation of infectious cases into a population and to model local chains of transmission seeded by imported cases. The probability of a local epidemic, and the time period until a major epidemic takes off, were used as outcome measures, and travel restriction policies in which children or adults were preferentially restricted were compared to age-blind restriction policies using an age-dependent next generation matrix parameterized for influenza H1N1-2009. Results: Restricting children from travelling would yield greater reductions to the short-term risk of the epidemic being established locally than other policy options considered, and potentially could delay an epidemic for a few weeks. However, given a scenario with a total of 500 imported cases over a period of a few months, a substantial reduction in the probability of an epidemic in this time period is possible only if the transmission potential were low and assortativity (i.e. the proportion of contacts within-group) were unrealistically high. In all other scenarios considered, age-structured travel restrictions would not prevent an epidemic and would not delay the epidemic for longer than a few weeks. Conclusions: Selectively restricting children from traveling overseas during a pandemic may potentially delay its arrival for a few weeks, depending on the characteristics of the pandemic strain, but could have less of an impact on the economy compared to restricting adult travelers. However, as long as adults have at least a moderate potential to trigger an epidemic, selectively restricting the higher risk group (children) may not be a practical option to delay the arrival of an epidemic substantially.
  • Don Klinkenberg, Hiroshi Nishiura
    JOURNAL OF THEORETICAL BIOLOGY 284 (1) 52 - 60 0022-5193 2011/09 [Refereed][Not invited]
     
    The generation time of an infectious disease is the time between infection of a primary case and infection of a secondary case by the primary case. Its distribution plays a key role in understanding the dynamics of infectious diseases in populations, e.g. in estimating the basic reproduction number. Moreover, the generation time and incubation period distributions together characterize the effectiveness of control by isolation and quarantine. In modelling studies, a relation between the two is often not made specific, but a correlation is biologically plausible. However, it is difficult to establish such correlation, because of the unobservable nature of infection events. We have quantified a joint distribution of generation time and incubation period by a novel estimation method for household data with two susceptible individuals, consisting of time intervals between disease onsets of two measles cases. We used two such datasets, and a separate incubation period dataset. Results indicate that the mean incubation period and the generation time of measles are positively correlated, and that both lie in the range of 11-12 days, suggesting that infectiousness of measles cases increases significantly around the time of symptom onset. The correlation between times from infection to secondary transmission and to symptom onset could critically affect the predicted effectiveness of isolation and quarantine. (c) 2011 Elsevier Ltd. All rights reserved.
  • Heath Kelly, Heidi A. Peck, Karen L. Laurie, Peng Wu, Hiroshi Nishiura, Benjamin J. Cowling
    PLOS ONE 6 (8) e21828  1932-6203 2011/08 [Refereed][Not invited]
     
    Background: During the influenza pandemic of 2009 estimates of symptomatic and asymptomatic infection were needed to guide vaccination policies and inform other control measures. Serological studies are the most reliable way to measure influenza infection independent of symptoms. We reviewed all published serological studies that estimated the cumulative incidence of infection with pandemic influenza H1N1 2009 prior to the initiation of population-based vaccination against the pandemic strain. Methodology and Principal Findings: We searched for studies that estimated the cumulative incidence of pandemic influenza infection in the wider community. We excluded studies that did not include both pre- and post-pandemic serological sampling and studies that included response to vaccination. We identified 47 potentially eligible studies and included 12 of them in the review. Where there had been a significant first wave, the cumulative incidence of pandemic influenza infection was reported in the range 16%-28% in pre-school aged children, 34%-43% in school aged children and 12%-15% in young adults. Only 2%-3% of older adults were infected. The proportion of the entire population infected ranged from 11%-18%. We re-estimated the cumulative incidence to account for the small proportion of infections that may not have been detected by serology, and performed direct age-standardisation to the study population. For those countries where it could be calculated, this suggested a population cumulative incidence in the range 11%-21%. Conclusions and Significance: Around the world, the cumulative incidence of infection (which is higher than the cumulative incidence of clinical disease) was below that anticipated prior to the pandemic. Serological studies need to be routine in order to be sufficiently timely to provide support for decisions about vaccination.
  • Sophia Ng, Peng Wu, Hiroshi Nishiura, Dennis K. M. Ip, Esther S. T. Lee, Benjamin J. Cowling
    BMC INFECTIOUS DISEASES 11 230  1471-2334 2011/08 [Refereed][Not invited]
     
    Background: Vaccination is generally considered to be the best primary prevention measure against influenza virus infection. Many countries encourage specific target groups of people to undertake vaccination, often with financial subsidies or a priority list. To understand differential patterns of national target groups for influenza vaccination before, during and after the 2009 influenza pandemic, we reviewed and analyzed the country-specific policies in the corresponding time periods. Methods: Information on prioritized groups targeted to receive seasonal and pandemic influenza vaccines was derived from a multi-step internet search of official health department websites, press releases, media sources and academic journal articles. We assessed the frequency and consistency of targeting 20 different groups within populations which are associated with age, underlying medical conditions, role or occupations among different countries and vaccines. Information on subsidies provided to specific target groups was also extracted. Results: We analyzed target groups for 33 (seasonal 2009 and 2009-10 vaccines), 72 (monovalent pandemic 200910 vaccine) and 34 (seasonal 2010 and 2010-11 vaccines) countries. In 2009-10, the elderly, those with chronic illness and health care workers were common targets for the seasonal vaccine. Comparatively, the elderly, care home residents and workers, animal contacts and close contacts were less frequently targeted to receive the pandemic vaccine. Pregnant women, obese persons, essential community workers and health care workers, however, were more commonly targeted. After the pandemic, pregnant women, obese persons, health care and care home workers, and close contacts were more commonly targeted to receive the seasonal vaccine compared to 2009-10, showing continued influence from the pandemic. Many of the countries provided free vaccines, partial subsidies, reimbursements or national health insurance coverage to specific target groups and over one-third of the countries offered universal subsidy regarding the pandemic vaccine. There was also some inconsistency between countries in target groups. Conclusions: Differences in target groups between countries may reflect variable objectives as well as uncertainties regarding the transmission dynamics, severity and age-specific immunity against influenza viruses before and after vaccination. Clarification on these points is essential to elucidate optimal and object-oriented vaccination strategies.
  • Hiroshi Nishiura
    EUROPEAN JOURNAL OF EPIDEMIOLOGY 26 (7) 583 - 584 0393-2990 2011/07 [Refereed][Not invited]
  • Thai KT, Nishiura H, Hoang PL, Tran NT, Phan GT, Le HQ, Tran BQ, Nguyen NV, de Vries PJ
    PLoS neglected tropical diseases 6 5 (6) e1180  1935-2727 2011/06 [Refereed][Not invited]
  • Hiroshi Nishiura, Kazuko Kamiya
    BMC INFECTIOUS DISEASES 11 111  1471-2334 2011/05 [Refereed][Not invited]
     
    Background: Entry screening tends to start with a search for febrile international passengers, and infrared thermoscanners have been employed for fever screening in Japan. We aimed to retrospectively assess the feasibility of detecting influenza cases based on fever screening as a sole measure. Methods: Two datasets were collected at Narita International Airport during the 2009 pandemic. The first contained confirmed influenza cases (n = 16) whose diagnosis took place at the airport during the early stages of the pandemic, and the second contained a selected and suspected fraction of passengers (self-reported or detected by an infrared thermoscanner; n = 1,049) screened from September 2009 to January 2010. The sensitivity of fever (38.0 degrees C) for detecting H1N1-2009 was estimated, and the diagnostic performances of the infrared thermoscanners in detecting hyperthermia at cut-off levels of 37.5 degrees C, 38.0 degrees C and 38.5 degrees C were also estimated. Results: The sensitivity of fever for detecting H1N1-2009 cases upon arrival was estimated to be 22.2% (95% confidence interval: 0, 55.6) among nine confirmed H1N1-2009 cases, and 55.6% of the H1N1-2009 cases were under antipyretic medications upon arrival. The sensitivity and specificity of the infrared thermoscanners in detecting hyperthermia ranged from 50.8-70.4% and 63.6-81.7%, respectively. The positive predictive value appeared to be as low as 37.3-68.0%. Conclusions: The sensitivity of entry screening is a product of the sensitivity of fever for detecting influenza cases and the sensitivity of the infrared thermoscanners in detecting fever. Given the additional presence of confounding factors and unrestricted medications among passengers, reliance on fever alone is unlikely to be feasible as an entry screening measure.
  • Michael George Roberts, Hiroshi Nishiura
    PLOS ONE 6 (5) e17835  1932-6203 2011/05 [Refereed][Not invited]
     
    We analyse data from the early epidemic of H1N1-2009 in New Zealand, and estimate the reproduction number R. We employ a renewal process which accounts for imported cases, illustrate some technical pitfalls, and propose a novel estimation method to address these pitfalls. Explicitly accounting for the infection-age distribution of imported cases and for the delay in transmission dynamics due to international travel, R was estimated to be 1: 25 (95% confidence interval: 1: 07,1: 47). Hence we show that a previous study, which did not account for these factors, overestimated R. Our approach also permitted us to examine the infection-age at which secondary transmission occurs as a function of calendar time, demonstrating the downward bias during the beginning of the epidemic. These technical issues may compromise the usefulness of a well-known estimator of R - the inverse of the moment-generating function of the generation time given the intrinsic growth rate. Explicit modelling of the infection-age distribution among imported cases and the examination of the time dependency of the generation time play key roles in avoiding a biased estimate of R, especially when one only has data covering a short time interval during the early growth phase of the epidemic.
  • Hiroshi Nishiura, Hitoshi Oshitani
    EMERGING INFECTIOUS DISEASES 17 (4) 746 - 747 1080-6040 2011/04 [Refereed][Not invited]
  • Hiroshi Nishiura, Gerardo Chowell, Carlos Castillo-Chavez
    PLOS ONE 6 (3) e17908  1932-6203 2011/03 [Refereed][Not invited]
     
    Background: Seroepidemiological studies before and after the epidemic wave of H1N1-2009 are useful for estimating population attack rates with a potential to validate early estimates of the reproduction number, R, in modeling studies. Methodology/Principal Findings: Since the final epidemic size, the proportion of individuals in a population who become infected during an epidemic, is not the result of a binomial sampling process because infection events are not independent of each other, we propose the use of an asymptotic distribution of the final size to compute approximate 95% confidence intervals of the observed final size. This allows the comparison of the observed final sizes against predictions based on the modeling study (R = 1.15, 1.40 and 1.90), which also yields simple formulae for determining sample sizes for future seroepidemiological studies. We examine a total of eleven published seroepidemiological studies of H1N1-2009 that took place after observing the peak incidence in a number of countries. Observed seropositive proportions in six studies appear to be smaller than that predicted from R = 1.40; four of the six studies sampled serum less than one month after the reported peak incidence. The comparison of the observed final sizes against R = 1.15 and 1.90 reveals that all eleven studies appear not to be significantly deviating from the prediction with R = 1.15, but final sizes in nine studies indicate overestimation if the value R = 1.90 is used. Conclusions: Sample sizes of published seroepidemiological studies were too small to assess the validity of model predictions except when R = 1.90 was used. We recommend the use of the proposed approach in determining the sample size of post-epidemic seroepidemiological studies, calculating the 95% confidence interval of observed final size, and conducting relevant hypothesis testing instead of the use of methods that rely on a binomial proportion.
  • Hiroshi Nishiura, Hisashi Inaba
    JOURNAL OF THEORETICAL BIOLOGY 272 (1) 123 - 130 0022-5193 2011/03 [Refereed][Not invited]
     
    Empirical estimates of the incubation period of influenza A (H1N1-2009) have been limited. We estimated the incubation period among confirmed imported cases who traveled to Japan from Hawaii during the early phase of the 2009 pandemic (n=72). We addressed censoring and employed an infection-age structured argument to explicitly model the daily frequency of illness onset after departure. We assumed uniform and exponential distributions for the frequency of exposure in Hawaii, and the hazard rate of infection for the latter assumption was retrieved, in Hawaii, from local outbreak data. The maximum likelihood estimates of the median incubation period range from 1.43 to 1.64 days according to different modeling assumptions, consistent with a published estimate based on a New York school outbreak. The likelihood values of the different modeling assumptions do not differ greatly from each other, although models with the exponential assumption yield slightly shorter incubation periods than those with the uniform exposure assumption. Differences between our proposed approach and a published method for doubly interval-censored analysis highlight the importance of accounting for the dependence of the frequency of exposure on the survival function of incubating individuals among imported cases. A truncation of the density function of the incubation period due to an absence of illness onset during the exposure period also needs to be considered. When the data generating process is similar to that among imported cases, and when the incubation period is close to or shorter than the length of exposure, accounting for these aspects is critical for long exposure times. (c) 2010 Elsevier Ltd. All rights reserved.
  • Hiroshi Nishiura
    BIOMEDICAL ENGINEERING ONLINE 10 15  1475-925X 2011/02 [Refereed][Not invited]
     
    Background: Real-time forecasting of epidemics, especially those based on a likelihood-based approach, is understudied. This study aimed to develop a simple method that can be used for the real-time epidemic forecasting. Methods: A discrete time stochastic model, accounting for demographic stochasticity and conditional measurement, was developed and applied as a case study to the weekly incidence of pandemic influenza (H1N1-2009) in Japan. By imposing a branching process approximation and by assuming the linear growth of cases within each reporting interval, the epidemic curve is predicted using only two parameters. The uncertainty bounds of the forecasts are computed using chains of conditional offspring distributions. Results: The quality of the forecasts made before the epidemic peak appears largely to depend on obtaining valid parameter estimates. The forecasts of both weekly incidence and final epidemic size greatly improved at and after the epidemic peak with all the observed data points falling within the uncertainty bounds. Conclusions: Real-time forecasting using the discrete time stochastic model with its simple computation of the uncertainty bounds was successful. Because of the simplistic model structure, the proposed model has the potential to additionally account for various types of heterogeneity, time-dependent transmission dynamics and epidemiological details. The impact of such complexities on forecasting should be explored when the data become available as part of the disease surveillance.
  • Nishiura H, Cook AR, Cowling BJ
    Interdisciplinary perspectives on infectious diseases 2011 194507  1687-708X 2011 [Refereed][Not invited]
  • Hiroshi Nishiura
    MATHEMATICAL BIOSCIENCES AND ENGINEERING 8 (1) 49 - 64 1547-1063 2011/01 [Refereed][Not invited]
     
    The influenza A (H1N1) pandemic 2009 posed an epidemiological challenge in ascertaining all cases. Although the counting of all influenza cases in real time is often not feasible, empirical observations always involve diagnostic test procedures. This offers an opportunity to jointly quantify transmission dynamics and diagnostic accuracy. We have developed a joint estimation procedure that exploits parsimonious models to describe the epidemic dynamics and that parameterizes the number of test positives and test negatives as a function of time. Our analyses of simulated data and data from the empirical observation of interpandemic influenza A (H1N1) from 2007-08 in Japan indicate that the proposed approach permits a more precise quantification of the transmission dynamics compared to methods that rely on test positive cases alone. The analysis of entry screening data for the H1N1 pandemic 2009 at Tokyo-Narita airport helped us quantify the very limited specificity of influenza-like illness in detecting actual influenza cases in the passengers. The joint quantification does not require us to condition diagnostic accuracy on any pre-defined study population. Our study suggests that by consistently reporting both test positive and test negative cases, the usefulness of extractable information from routine surveillance record of infectious diseases would be maximized.
  • Ryosuke Omori, Hiroshi Nishiura
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 8 2  1742-4682 2011/01 [Refereed][Not invited]
     
    Background: While many pandemic preparedness plans have promoted disease control effort to lower and delay an epidemic peak, analytical methods for determining the required control effort and making statistical inferences have yet to be sought. As a first step to address this issue, we present a theoretical basis on which to assess the impact of an early intervention on the epidemic peak, employing a simple epidemic model. Methods: We focus on estimating the impact of an early control effort (e. g. unsuccessful containment), assuming that the transmission rate abruptly increases when control is discontinued. We provide analytical expressions for magnitude and time of the epidemic peak, employing approximate logistic and logarithmic-form solutions for the latter. Empirical influenza data (H1N1-2009) in Japan are analyzed to estimate the effect of the summer holiday period in lowering and delaying the peak in 2009. Results: Our model estimates that the epidemic peak of the 2009 pandemic was delayed for 21 days due to summer holiday. Decline in peak appears to be a nonlinear function of control-associated reduction in the reproduction number. Peak delay is shown to critically depend on the fraction of initially immune individuals. Conclusions: The proposed modeling approaches offer methodological avenues to assess empirical data and to objectively estimate required control effort to lower and delay an epidemic peak. Analytical findings support a critical need to conduct population-wide serological survey as a prior requirement for estimating the time of peak.
  • Bethany J. Hoye, Vincent J. Munster, Hiroshi Nishiura, Marcel Klaassen, Ron A. M. Fouchier
    EMERGING INFECTIOUS DISEASES 16 (12) 1827 - 1834 1080-6040 2010/12 [Refereed][Not invited]
     
    Recent demand for increased understanding of avian influenza virus in its natural hosts, together with the development of high-throughput diagnostics has heralded a new era in wildlife disease surveillance However survey design sampling and interpretation in the context of host populations still present major challenges We critically reviewed current surveillance to distill a series of considerations pertinent to avian influenza virus surveillance in wild birds including consideration of what when where and how many to sample in the context of survey objectives Recognizing that wildlife disease surveillance is logistically and financially constrained we discuss pragmatic alternatives for achieving probability-based sampling schemes that capture this host pathogen system We recommend hypothesis-driven surveillance through standardized local surveys that are in turn strategically compiled over broad geographic areas Rethinking the use of existing surveillance infrastructure can thereby greatly enhance our global understanding of avian influenza and other zoonotic diseases
  • Nishiura H
    Nippon Hoshasen Gijutsu Gakkai zasshi 66 (11) 1485 - 1491 0369-4305 2010/11 [Refereed][Not invited]
  • Hiroshi Nishiura
    MATHEMATICAL BIOSCIENCES AND ENGINEERING 7 (4) 851 - 869 1547-1063 2010/10 [Refereed][Not invited]
     
    Although the generation time of an infectious disease plays a key role in estimating its transmission potential, the impact of the sampling time of generation times on the estimation procedure has yet to be clarified. The present study defines the period and cohort generation times, both of which are time-inhomogeneous, as a function of the infection time of secondary and primary cases, respectively. By means of analytical and numerical approaches, it is shown that the period generation time increases with calendar time, whereas the cohort generation time decreases as the incidence increases. The initial growth phase of an epidemic of Asian influenza A (H2N2) in the Netherlands in 1957 was reanalyzed, and estimates of the basic reproduction number, R-0, from the Lotka-Euler equation were examined. It was found that the sampling time of generation time during the course of the epidemic introduced a time-effect to the estimate of R-0. Other historical data of a primary pneumonic plague in Manchuria in 1911 were also examined to help illustrate the empirical evidence of the period generation time. If the serial intervals, which eventually determine the generation times, are sampled during the course of an epidemic, direct application of the sampled generation-time distribution to the Lotka-Euler equation leads to a biased estimate of R-0. An appropriate quantification of the transmission potential requires the estimation of the cohort generation time during the initial growth phase of an epidemic or adjustment of the time-effect (e.g., adjustment of the growth rate of the epidemic during the sampling time) on the period generation time. A similar issue also applies to the estimation of the effective reproduction number as a function of calendar time. Mathematical properties of the generation time distribution in a heterogeneously mixing population need to be clarified further.
  • Nishiura H
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 51 (1) 117 - 8; author reply 118 1058-4838 2010/07 [Refereed][Not invited]
  • Hiroshi Nishiura
    JOURNAL OF TRAVEL MEDICINE 17 (4) 269 - 270 1195-1982 2010/07 [Refereed][Not invited]
     
    Age distribution of 4,986 cases of influenza A (H1N1) 2009 in Japan was analyzed. Cases with a travel history within 10 days preceding the illness onset were significantly older than indigenous cases (p < 0.01) reflecting age-specific travel patterns. Border controls should account for the high frequency of infection among adults.
  • Hiroshi Nishiura
    LANCET INFECTIOUS DISEASES 10 (7) 443 - 444 1473-3099 2010/07 [Refereed][Not invited]
  • Koji Wada, Hiroshi Nishiura, Akihiko Kawana
    INFLUENZA AND OTHER RESPIRATORY VIRUSES 4 (4) 179 - 186 1750-2640 2010/07 [Refereed][Not invited]
     
    Background The age distribution of confirmed cases with influenza A (H1N1) 2009 has shifted toward children and young adults, in contrast to interpandemic influenza, because of the age specificities in immunological reactions and transmission characteristics. Objectives Descriptive epidemiological analysis of severe cases in Japan was carried out to characterize the pandemic's impact and clinical features. Methods First, demographic characteristics of hospitalized cases (n = 12 923), severe cases (n = 894) and fatal cases (n = 116) were examined. Second, individual records of the first 120 severe cases, including 23 deaths, were analyzed to examine potential associations of influenza death with demographic variables, medical treatment and underlying conditions. Among severe cases, we compared proportions of specific characteristics of survivors with those of fatal cases to identify predictors of death. Results Age distribution of hospitalized cases shifted toward those aged < 20 years; this was also the case for deaths without underlying medical conditions. Deaths in adults were mainly seen among those with underlying medical conditions, resulting in an increased risk of death as a function of age. According to individual records, the time from onset to death in Japan appeared rather short compared with that in other countries. Conclusion The age specificity of severe cases and their underlying medical conditions were consistent with other countries. To identify predictors of death in influenza A (H1N1) 2009 patients, more detailed clinical characteristics need to be examined according to different age groups and types of manifestations, which should ideally include mild cases as subjects.
  • Nishiura H
    Expert review of respiratory medicine 4 (3) 329 - 338 1747-6348 2010/06 [Refereed][Not invited]
  • Benjamin J. Cowling, Lincoln L. H. Lau, Peng Wu, Helen W. C. Wong, Vicky J. Fang, Steven Riley, Hiroshi Nishiura
    BMC INFECTIOUS DISEASES 10 82  1471-2334 2010/03 [Refereed][Not invited]
     
    Background: After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission. Methods: We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case. Results: Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays. Conclusions: Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.
  • The Relationship between the Cumulative Numbers of Cases and Deaths Reveals the Confirmed Case Fatality Ratio of a Novel Influenza A (H1N1) Virus
    Hiroshi Nishiura
    JAPANESE JOURNAL OF INFECTIOUS DISEASES 63 (2) 154 - 156 1344-6304 2010/03 [Refereed][Not invited]
  • Hiroshi Nishiura, Gerardo Chowell, Hans Heesterbeek, Jacco Wallinga
    JOURNAL OF THE ROYAL SOCIETY INTERFACE 7 (43) 297 - 307 1742-5689 2010/02 [Refereed][Not invited]
     
    The reporting interval of infectious diseases is often determined as a time unit in the calendar regardless of the epidemiological characteristics of the disease. No guidelines have been proposed to choose the reporting interval of infectious diseases. The present study aims at translating coarsely reported epidemic data into the reproduction number and clarifying the ideal reporting interval to offer detailed insights into the time course of an epidemic. We briefly revisit the dispersibility ratio, i.e. ratio of cases in successive reporting intervals, proposed by Clare Oswald Stallybrass, detecting technical flaws in the historical studies. We derive a corrected expression for this quantity and propose simple algorithms to estimate the effective reproduction number as a function of time, adjusting the reporting interval to the generation time of a disease and demonstrating a clear relationship among the generation-time distribution, reporting interval and growth rate of an epidemic. Our exercise suggests that an ideal reporting interval is the mean generation time, so that the ratio of cases in successive intervals can yield the reproduction number. When it is impractical to report observations every mean generation time, we also present an alternative method that enables us to obtain straightforward estimates of the reproduction number for any reporting interval that suits the practical purpose of infection control.
  • Tom Reichert, Gerardo Chowell, Hiroshi Nishiura, Ronald A. Christensen, Jonathan A. McCullers
    BMC INFECTIOUS DISEASES 10 5  1471-2334 2010/01 [Refereed][Not invited]
     
    Background: A pandemic novel H1N1 swine-origin influenza virus has emerged. Most recently the World Health Organization has announced that in a country-dependent fashion, up to 15% of cases may require hospitalization, often including respiratory support. It is now clear that healthy children and young adults are disproportionately affected, most unusually among those with severe respiratory disease without underlying conditions. One possible explanation for this case age distribution is the doctrine of Original Antigenic Sin, i.e., novel H1N1 may be antigenically similar to H1N1 viruses that circulated at an earlier time. Persons whose first exposure to influenza viruses was to such similar viruses would be relatively immune. However, this principle is not sufficient to explain the graded susceptibility between ages 20 and 60, the reduced susceptibility in children below age 10, and the unusual toxicity observed. Methods: We collected case data from 11 countries, about 60% of all cases reported through mid-July 2009. We compared sequence data for the hemagglutinin of novel H1N1 with sequences of H1N1 viruses from 1918 to the present. We searched for sequence differences that imply loss of antigenicity either directly through amino acid substitution or by the appearance of sites for potential glycosylation proximal to sites known to be antigenic in humans. We also considered T-cell epitopes. Results: In our composite, over 75% of confirmed cases of novel H1N1 occurred in persons <= 30 years old, with peak incidence in the age range 10-19 years. Less than 3% of cases occurred in persons over 65, with a gradation in incidence between ages 20 and 60 years. The sequence data indicates that novel H1N1 is most similar to H1N1 viruses that circulated before 1943. Novel H1N1 lacks glycosylation sites on the globular head of hemagglutinin (HA1) near antigenic regions, a pattern shared with the 1918 pandemic strain and H1N1 viruses that circulated until the early 1940s. Later H1N1 viruses progressively added new glycosylation sites likely to shield antigenic epitopes, while T-cell epitopes were relatively unchanged. Conclusions: In this evolutionary context, Original Antigenic Sin exposure should produce an immune response increasingly mismatched to novel H1N1 in progressively younger persons. We suggest that it is this mismatch that produces both the gradation in susceptibility and the unusual toxicity. Several murine studies suggest specific cell types as a likely basis of the unusual toxicity. These studies also point to widely available pharmaceutical agents as plausible candidates for mitigating the toxic effects. The principle of Original Antigenic Sin modified by glycosylation appears to explain both the case age distribution and the unusual toxicity pattern of the novel H1N1 pandemic. In addition, it suggests pharmaceutical agents for immediate investigation for mitigation potential, and provides strategic guidance for the distribution of pandemic mitigation resources of all types.
  • Hiroshi Nishiura, Gerardo Chowell, Muntaser Safan, Carlos Castillo-Chavez
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 7 1  1742-4682 2010/01 [Refereed][Not invited]
     
    Background: In many parts of the world, the exponential growth rate of infections during the initial epidemic phase has been used to make statistical inferences on the reproduction number, R, a summary measure of the transmission potential for the novel influenza A (H1N1) 2009. The growth rate at the initial stage of the epidemic in Japan led to estimates for R in the range 2.0 to 2.6, capturing the intensity of the initial outbreak among school-age children in May 2009. Methods: An updated estimate of R that takes into account the epidemic data from 29 May to 14 July is provided. An age-structured renewal process is employed to capture the age-dependent transmission dynamics, jointly estimating the reproduction number, the age-dependent susceptibility and the relative contribution of imported cases to secondary transmission. Pitfalls in estimating epidemic growth rates are identified and used for scrutinizing and re-assessing the results of our earlier estimate of R. Results: Maximum likelihood estimates of R using the data from 29 May to 14 July ranged from 1.21 to 1.35. The next-generation matrix, based on our age-structured model, predicts that only 17.5% of the population will experience infection by the end of the first pandemic wave. Our earlier estimate of R did not fully capture the population-wide epidemic in quantifying the next-generation matrix from the estimated growth rate during the initial stage of the pandemic in Japan. Conclusions: In order to quantify R from the growth rate of cases, it is essential that the selected model captures the underlying transmission dynamics embedded in the data. Exploring additional epidemiological information will be useful for assessing the temporal dynamics. Although the simple concept of R is more easily grasped by the general public than that of the next-generation matrix, the matrix incorporating detailed information (e.g., age-specificity) is essential for reducing the levels of uncertainty in predictions and for assisting public health policymaking. Model-based prediction and policymaking are best described by sharing fundamental notions of heterogeneous risks of infection and death with non-experts to avoid potential confusion and/or possible misuse of modelling results.
  • Nishiura H
    International journal of environmental research and public health 7 (1) 291 - 302 1661-7827 2010/01 [Refereed][Not invited]
  • Hiroshi Nishiura
    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY 147 (1) 115 - 115 0301-2115 2009/11 [Refereed][Not invited]
  • Hiroshi Nishiura, Don Klinkenberg, Mick Roberts, Johan A. P. Heesterbeek
    PLOS ONE 4 (8) e6852  1932-6203 2009/08 [Refereed][Not invited]
     
    Background: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. Methodology/Principal Findings: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16-4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. Conclusions: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public.
  • Estimating the reproduction number of the novel influenza A virus (H1N1) in a Southern Hemisphere setting: preliminary estimate in New Zealand.
    Nishiura H, Wilson N, Baker MG
    The New Zealand medical journal 122 (1299) 73 - 77 0028-8446 2009/07 [Refereed][Not invited]
  • Transmission dynamics of the 1918 influenza pandemic in New Zealand: analyses of national and city data.
    Nishiura H, Wilson N
    The New Zealand medical journal 122 (1296) 81 - 86 0028-8446 2009/06 [Refereed][Not invited]
  • Hiroshi Nishiura, Bethany Hoye, Marcel Klaassen, Silke Bauer, Hans Heesterbeek
    EPIDEMICS 1 (2) 118 - 128 1755-4365 2009/06 [Refereed][Not invited]
     
    The transmission dynamics of infectious diseases critically depend on reservoir hosts, which can sustain the pathogen (or maintain the transmission) in the population even in the absence of other hosts. Although a theoretical foundation of the transmission dynamics in a multi-host population has been established, no quantitative methods exist for the identification of natural reservoir hosts. For a host to maintain the transmission alone, the host-specific reproduction number (U), interpreted as the average number of secondary transmissions caused by a single primary case in the host(s) of interest in the absence of all other hosts, must be greater than unity. If the host-excluded reproduction number (Q), representing the average number of secondary transmissions per single primary case in other hosts in the absence of the host(s) of interest, is below unity, transmission cannot be maintained in the multi-host population in the absence of the focal host(s). The present study proposes a simple method for the identification of reservoir host(s) from observed endemic prevalence data across a range of host species. As an example, we analyze an aggregated surveillance dataset of influenza A virus in wild birds among which dabbling ducks exhibit higher prevalence compared to other bird species. Since the heterogeneous contact patterns between different host species are not directly observable, we test four different contact structures to account for the uncertainty. Meeting the requirements of U>1 and Q<1 for all four different contact structures, mallards and other dabbling ducks most likely constitute the reservoir community which plays a predominant role in maintaining the transmission of influenza A virus in the water bird population. We further discuss epidemiological issues which are concerned with the interpretation of influenza prevalence data, identifying key features to be fully clarified in the future. (C) 2009 Elsevier Inc. All rights reserved.
  • Hiroshi Nishiura, Nick Wilson, Michael G. Baker
    BMC INFECTIOUS DISEASES 9 27  1471-2334 2009/03 [Refereed][Not invited]
     
    Background: Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure. Methods: Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered. Results: We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals). Conclusion: Quarantine at the borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available).
  • Nishiura H, Kashiwagi T
    Interdisciplinary perspectives on infectious diseases 2009 591935  1687-708X 2009 [Refereed][Not invited]
  • Hiroshi Nishiura
    INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH 212 (1) 97 - 104 1438-4639 2009/01 [Refereed][Not invited]
     
    Determination of the most appropriate quarantine period for those exposed to smallpox is crucial to the construction of an effective preparedness program against a potential bioterrorist attack. This study reanalyzed data on the incubation period distribution of smallpox to allow the optimal quarantine period to be objectively calculated. In total, 131 cases of smallpox were examined; incubation periods were extracted from Four different sets of historical data and only cases arising from exposure for a single day were considered. The mean (median and standard deviation (SD)) incubation period was 12.5 (12.0, 2.2) days. Assuming lognormal and gamma distributions for the incubation period, maximum likelihood estimates (and corresponding 95% confidence interval (Cl)) of the 95th percentile were 16.4 (95% CI: 15.6, 17.9) and 16.2 (95% Cl: 15.5, 17.4) days, respectively. Using a non-parametric method, the 95th percentile point was estimated as 16 (95% Cl: 15, 17) days. The upper 95% CIs of the incubation periods at the 90th, 95th and 99th percentiles were shorter than 17, 18 and 23 days, respectively, using both parametric and non-parametric methods. These results suggest that quarantine measures can ensure non-infection among those exposed to smallpox with probabilities higher than 95 99%, if the exposed individuals are quarantined for 18-23 days after the date of contact tracing. (C) 2007 Elsevicr GmbH. All rights reserved.
  • Hisashi Inaba, Hiroshi Nishiura
    MATHEMATICAL BIOSCIENCES 216 (1) 77 - 89 0025-5564 2008/11 [Refereed][Not invited]
     
    In this paper, we develop the theory of a state-reproduction number for a multistate class age structured epidemic system and apply it to examine the asymptomatic transmission model. We formulate a renewal integral equation system to describe the invasion of infectious diseases into a multistate class age structured host population. We define the state-reproduction number for a class age structured system, which is the net reproduction number of a specific host type and which plays an analogous role to the type-reproduction number [M.G. Roberts, J.A.P. Heesterbeek, A new method for estimating the effort required to control an infectious disease, Proc. R. Soc. Lond. B 270 (2003) 1359; J.A.P. Heesterbeek, M.G. Roberts, The type-reproduction number T in models for infectious disease control, Math. Biosci. 206 (2007) 3] in discussing the critical level of public health intervention. The renewal equation formulation permits computations not only of the state-reproduction number, but also of the generation time and the intrinsic growth rate of infectious diseases. Subsequently, the basic theory is applied to capture the dynamics of a directly transmitted disease within two types of infected populations, i.e., asymptomatic and symptomatic individuals, in which the symptomatic class is observable and hence a target host of the majority of interventions. The state-reproduction number of the symptomatic host is derived and expressed as a measurable quantity, leading to discussion on the critical level of case isolation. The serial interval and other epidemiologic indices are computed, clarifying the parameters on which these indices depend. As a practical example, we illustrate the eradication threshold for case isolation of smallpox. The generation time and serial interval are comparatively examined for pandernic influenza. (c) 2008 Elsevier Inc. All rights reserved.
  • Hiroshi Nishiura
    2008/10/09 [Not refereed][Not invited]
     
    Aim: To assess the frequency of secondary transmissions of primary pneumonic plague relative to the onset of fever. Methods: A simple backcalculation method was employed to estimate the frequency of secondary transmissions relative to disease-age. A likelihood-based procedure was taken using observed distributions of the serial interval (n = 177) and incubation period (n = 126). Furthermore, an extended model was developed to account for the survival probability of cases. Results: The simple backcalculation suggested that 31.0% (95% confidence intervals (CI): 11.6, 50.4) and 28.0 % (95% CI:...
  • Rurality and pandemic influenza: geographic heterogeneity in the risks of infection and death in Kanagawa, Japan (1918-1919).
    Nishiura H, Chowell G
    The New Zealand medical journal 121 (1284) 18 - 27 0028-8446 2008/10 [Refereed][Not invited]
  • Hiroshi Nishiura, Stefan O. Brockmann, Martin Eichner
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 5 20  1742-4682 2008/08 [Refereed][Not invited]
     
    Background: Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data. Main findings: First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1) The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2) The highest frequency (61.8%) of secondary transmissions occurs 3-5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3) The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions. Conclusion: Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e. g. case isolation and contact tracing) taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.
  • Gerardo Chowell, Hiroshi Nishiura
    PHYSICS OF LIFE REVIEWS 5 (1) 50 - 77 1571-0645 2008/03 [Refereed][Not invited]
     
    This article reviews quantitative methods to estimate the basic reproduction number of pandemic influenza, a key threshold quantity to help determine the intensity of interventions required to control the disease. Although it is difficult to assess the transmission potential of a probable future pandemic, historical epidemiologic data is readily available from previous pandemics, and as a reference quantity for future pandemic planning, mathematical and statistical analyses of historical data are crucial. In particular, because many historical records tend to document only the temporal distribution of cases or deaths (i.e. epidemic curve), our review focuses on methods to maximize the utility of time-evolution data and to clarify the detailed mechanisms of the spread of influenza. First, we highlight structured epidemic models and their parameter estimation method which can quantify the detailed disease dynamics including those we cannot observe directly. Duration-structured epidemic systems are subsequently presented, offering firm understanding of the definition of the basic and effective reproduction numbers. When the initial growth phase of an epidemic is investigated, the distribution of the generation time is key statistical information to appropriately estimate the transmission potential using the intrinsic growth rate. Applications of stochastic processes are also highlighted to estimate the transmission potential using similar data. Critically important characteristics of influenza data are subsequently summarized, followed by our conclusions to suggest potential future methodological improvements. (C) 2008 Elsevier B.V. All rights reserved.
  • Hiroshi Nishlura, Martin Eichner
    INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH 211 (1-2) 219 - 226 1438-4639 2008/03 [Refereed][Not invited]
     
    Six historical studies were investigated to clarify the obtainable information on postexposure vaccination against smallpox. Using the distribution of incubation period, the frequency of cases by time from exposure to vaccination was obtained. More than half of all failures happened within 7d after exposure in all six records investigated. Based on two studies (n = 36 and 28), the probability of escaping severe smallpox was further analyzed using logistic regression, showing an inverse association between severe smallpox and time from vaccination to onset (p < 0.01 and p = 0.04, respectively). Whereas the relationship between the probability of developing severe disease and the time from vaccination to onset could be analyzed with the available information, our findings indicate that previous epidemiologic records showing cases alone, rather than also showing individuals probably protected, are not useful for clarifying the effectiveness of postexposure vaccination by time after exposure. (c) 2007 Elsevier GmbH. All rights reserved.
  • Household and community transmission of the Asian influenza A (H2N2) and influenza B viruses in 1957 and 1961.
    Nishiura H, Chowell G
    The Southeast Asian journal of tropical medicine and public health 38 (6) 1075 - 1083 0125-1562 2007/11 [Refereed][Not invited]
  • Nishiura H
    Epidemiologic perspectives & innovations : EP+I 4 3  2007/06 [Refereed][Not invited]
  • Satou K, Nishiura H
    BMC veterinary research 3 9  2007/05 [Refereed][Not invited]
  • Nishiura H
    Emerging themes in epidemiology 4 2  2007/05 [Refereed][Not invited]
  • Hiroshi Nishiura, Scott B. Halstead
    JOURNAL OF INFECTIOUS DISEASES 195 (7) 1007 - 1013 0022-1899 2007/04 [Refereed][Not invited]
     
    Background. The natural history of wild-type dengue virus (DENV) infections of humans, including incubation and infectious periods, requires further study. Methods. Two experimental studies in the Philippines of DENV-4 (1924-1925) and DENV-1 (1929-1930) were reexamined. The intrinsic incubation periods were fitted to log-normal distribution using the maximum likelihood method, and the infectious and extrinsic incubation periods were assessed by proportions of successful transmissions causing clinically apparent dengue. Correlations between the intrinsic incubation period and other variables and univariate associations between clinical severity and serotype were also examined. Results. Mean +/- SD incubation periods were 6.0 +/- 1.4 and 5.7 +/- 1.5 days for DENV-4 and DENV-1, respectively. Significant negative correlations were observed between the incubation period and duration of fever (r = -0.43 and -0.33). Even 1 and 2 days before the onset of fever, 80.0% (95% confidence interval [CI], 44.9%-100%) and 25.0% (CI, 0%-67.4%) of biting experiments caused clinically apparent dengue. DENV-1 infections resulted in a significantly longer duration of fever than DENV-4 infections (P < .01). Conclusions. Incubation period was negatively correlated with disease severity, potentially reflecting a dose-response mechanism. The historical data provided useful details concerning serotype differences in the natural history of primary DENV infections.
  • Kunio Satou, Hiroshi Nishiura
    ANNALS OF EPIDEMIOLOGY 17 (4) 271 - 277 1047-2797 2007/04 [Refereed][Not invited]
     
    PURPOSE: To evaluate the partial effects of vaccination against equine Japanese encephalitis (JE) and characterize other prognostic factors based on previous outbreak records in Japan from 1953 to 1960. METHODS: Individual case records, which included demographic information, vaccination history, and clinical information (dates of onset, recovery and death, and symptoms), were investigated. The relations between two outcomes, JE death and symptomatic period, and other variables were examined. RESULTS: Of a total reported 803 cases during the observation period, 453 (56.5%) were diagnosed with either serological, histopathological, or epizootiological methods. Vaccination (adjusted odds ratio = 0.77, 95% confidence interval: 0.61, 0.97) and an older age (adjusted odds ratio = 0.83, 95% confidence interval: 0.71, 0.96) significantly reduced the risk of JE death. The symptomatic period was also significantly shortened with vaccination (p < 0.001). CONCLUSIONS: The risk of JE death was lowered and the symptomatic period of survivors shortened with inactivated JE vaccination. These findings demonstrate the partial effects of vaccination in reducing the burden of this disease.
  • Hiroshi Nishiura, Hyeong-Woo Lee, Shin-Hyeong Cho, Wook-Gyo Lee, Tae-Suk In, Sung-Ung Moon, Gyung Tae Chung, Tong-Soo Kim
    TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE 101 (4) 338 - 343 0035-9203 2007/04 [Refereed][Not invited]
     
    With the current epidemic of vivax malaria closely associated with the demilitarised zone along the border between North and South Korea, it has been suggested that the incubation period tends, in part, to be prolonged. Based on the detailed travel history of cases from 2000 to 2003 who reside in non-malarious areas, statistical estimates of the incubation periods were obtained. The data suggest that cases fall into two categories with short- and long-term incubation periods, respectively. Of 416 cases with available information, 72 and 79 successfully met our criteria for inferring the durations of short- and long-term incubation periods. The mean short- and tong-term incubation periods were estimated to be 26.6 days (95% CI 21.0-32.2) and 48.2 weeks (95% CI 46.8-49.5), respectively. The maximum likelihood method was used to fit gamma and normal distributions to the short- and tong-term incubation periods, assisting prediction of the frequency distribution of the overall incubation period, which exhibited a bimodal pattern. We postulate that the observed distribution reflects adaptation of the parasite to the seasonal population dynamics of the vector, Anopheles sinensis, ensuring continued transmission of vivax malaria in this temperate zone. (C) 2006 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
  • Gerardo Chowell, Hiroshi Nishiura, Luis M. A. Bettencourt
    JOURNAL OF THE ROYAL SOCIETY INTERFACE 4 (12) 155 - 166 1742-5689 2007/02 [Refereed][Not invited]
     
    The reproduction number, R, defined as the average number of secondary cases generated by a primary case, is a crucial quantity for identifying the intensity of interventions required to control an epidemic. Current estimates of the reproduction number for seasonal influenza show wide variation and, in particular, uncertainty bounds for R for the pandemic strain from 1918 to 1919 have been obtained only in a few recent studies and are yet to be fully clarified. Here, we estimate R using daily case notifications during the autumn wave of the influenza pandemic (Spanish flu) in the city of San Francisco, California, from 1918 to 1919. In order to elucidate the effects from adopting different estimation approaches, four different methods are used: estimation of R using the early exponential-growth rate (Method 1), a simple susceptible exposed - infectious - recovered (SEIR) model (Method 2), a more complex SEIR-type model that accounts for asymptomatic and hospitalized cases ( Method 3), and a stochastic susceptible - infectious - removed (SIR) with Bayesian estimation (Method 4) that determines the effective reproduction number R-t at a given time t. The first three methods. t the initial exponential-growth phase of the epidemic, which was explicitly determined by the goodness-of-fit test. Moreover, Method 3 was also fitted to the whole epidemic curve. Whereas the values of R obtained using the first three methods based on the initial growth phase were estimated to be 2.98 (95% confidence interval (CI): 2.73, 3.25), 2.38 (2.16, 2.60) and 2.20 (1.55, 2.84), the third method with the entire epidemic curve yielded a value of 3.53 (3.45, 3.62). This larger value could be an overestimate since the goodness-of-fit to the initial exponential phase worsened when we fitted the model to the entire epidemic curve, and because the model is established as an autonomous system without time-varying assumptions. These estimates were shown to be robust to parameter uncertainties, but the theoretical exponential-growth approximation (Method 1) shows wide uncertainty. Method 4 provided a maximum-likelihood effective reproduction number 2.10 (1.21, 2.95) using the first 17 epidemic days, which is consistent with estimates obtained from the other methods and an estimate of 2.36 (2.07, 2.65) for the entire autumn wave. We conclude that the reproduction number for pandemic influenza (Spanish flu) at the city level can be robustly assessed to lie in the range of 2.0 3.0, in broad agreement with previous estimates using distinct data.
  • Nishiura H, Eichner M
    The Journal of infectious diseases 195 (1) 160 - 1; author reply 161 0022-1899 2007/01 [Refereed][Not invited]
  • Hiroshi Nishiura, Hisashi Inaba
    JOURNAL OF THEORETICAL BIOLOGY 244 (2) 357 - 364 0022-5193 2007/01 [Refereed][Not invited]
  • Hiroshi Nishiura
    THEORETICAL BIOLOGY AND MEDICAL MODELLING 4 20  1742-4682 2007 [Refereed][Not invited]
     
    Background: Time variations in transmission potential have rarely been examined with regard to pandemic influenza. This paper reanalyzes the temporal distribution of pandemic influenza in Prussia, Germany, from 1918-19 using the daily numbers of deaths, which totaled 8911 from 29 September 1918 to 1 February 1919, and the distribution of the time delay from onset to death in order to estimate the effective reproduction number, Rt, defined as the actual average number of secondary cases per primary case at a given time. Results: A discrete-time branching process was applied to back-calculated incidence data, assuming three different serial intervals (i.e. 1, 3 and 5 days). The estimated reproduction numbers exhibited a clear association between the estimates and choice of serial interval; i.e. the longer the assumed serial interval, the higher the reproduction number. Moreover, the estimated reproduction numbers did not decline monotonically with time, indicating that the patterns of secondary transmission varied with time. These tendencies are consistent with the differences in estimates of the reproduction number of pandemic influenza in recent studies; high estimates probably originate from a long serial interval and a model assumption about transmission rate that takes no account of time variation and is applied to the entire epidemic curve. Conclusion: The present findings suggest that in order to offer robust assessments it is critically important to clarify in detail the natural history of a disease (e. g. including the serial interval) as well as heterogeneous patterns of transmission. In addition, given that human contact behavior probably influences transmissibility, individual countermeasures (e. g. household quarantine and mask-wearing) need to be explored to construct effective non-pharmaceutical interventions.
  • Nishiura H, Leary CC
    Lancet 368 (9539) 913; author reply 914 - 5 0140-6736 2006/09 [Refereed][Not invited]
  • Hiroshi Nishiura, Markus Schwehm, Martin Eichner
    EPIDEMIOLOGY 17 (5) 576 - 581 1044-3983 2006/09 [Refereed][Not invited]
     
    Background: Although the potential for bioterrorism has led to discussions on the durability of vaccine-induced immunity, the actual duration of protection against smallpox is still unknown. It has previously been suggested that at least partial protection against severe and fatal smallpox may persist throughout life. Methods: In this article, we analyzed 6 major smallpox outbreaks that occurred before and after 1900 in the United Kingdom. These analyses are based on the age-dependent incidence of smallpox and the fraction of severe manifestations among individuals with or without prior vaccination. We. used. a likelihood-based approach to estimate the duration of immunity from the age-specific frequencies. Results: The expected median duration of protection from disease ranged from 11.7 to 28.4 Years after primary vaccination, and the qualitative pattern of duration could be described using Gompertz's Law. Vaccinated individuals appear to have been protected from severe disease with more than 50% probability even 50 years aft er successful primary vaccination. Conclusions: These findings suggest that successful primary vaccination offered full protection for a few decades, with partial protection from severe smallpox possibly lasting a lifetime, for a substantial fraction of the population.
  • Hiroshi Nishiura, Klaus Dietz, Martin Eichner
    JOURNAL OF THEORETICAL BIOLOGY 241 (4) 964 - 967 0022-5193 2006/08 [Refereed][Not invited]
  • Hiroshi Nishiura
    INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 35 (4) 1059 - 1065 0300-5771 2006/08 [Refereed][Not invited]
     
    Background Among the potential uses of Yersinia pesos, intentional release of its aerosolized form, causing person-to-person transmission, is thought to be the most threatening. With the current rarity of pneumonic plague epidemics, our epidemiological knowledge remains insufficient for detailed characterization of effective control measures. Methods Temporal patterns and key biological parameters of a pneumonic plague epidemic in Manchuria from 1910 to 1911 were analysed based on historical records collected by Kanto Totokufu, the administration of the Japanese Empire in Manchuria at that time. The serial intervals were fitted to gamma distribution using the maximum likelihood method, and time-delay distributions from onset-to-admission, admission-to-death, and onset-to-death were investigated. Results Whereas a total of 228 cases were diagnosed with pneumonic plague in areas under direct control of the Japanese Empire, 4781 cases were also recorded in surrounding areas. Although the epidemic grew exponentially in the early phase, the average doubling time steadily increased reflecting successful control efforts. The estimated mean serial interval (and standard deviation) was 5.7 (3.6) days. All cases with known dates of onset were admitted to hospital within 4 days after onset, and the mean time from onset to admission was 1.1 (0.4) days. Conclusions The increase in doubling time demonstrates the efficient and rapid countermeasures employed. Since the short interval from onset to death implies the importance of rapid responses, the challenge in confronting a future bioterrorist attack is to implement rapid and appropriate integration of control measures both at the individual and community level to prevent further transmissions as well as lower case fatality.
  • Analysis of a previous smallpox vaccination study: estimation of the time period required to acquire vaccine-induced immunity as assessed by revaccination.
    Nishiura H
    The Southeast Asian journal of tropical medicine and public health 37 (4) 673 - 680 0125-1562 2006/07 [Refereed][Not invited]
  • H Nishiura
    EMERGING INFECTIOUS DISEASES 12 (7) 1119 - 1121 1080-6040 2006/07 [Refereed][Not invited]
     
    Pregnant women are at special risk for complications of smallpox vaccination (1); therefore, vaccination is not recommended for pregnant women in the absence of a reemergence of smallpox (2). Smallpox in pregnancy is believed to be more severe than in nonpregnant women or adult men (3), but this consensus is based on a limited number of studies conducted during the mid-20th century (4-6). This article examines the outcomes of pregnancy complicated by smallpox in historical records from the 19th and 20th centuries.
  • H Nishiura, M Schwehm, M Kakehashi, M Eichner
    JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH 60 (7) 640 - 645 0143-005X 2006/07 [Refereed][Not invited]
     
    Background: The transmission potential of primary pneumonic plague, caused by Yersinia pestis, is one of the key epidemiological determinants of a potential biological weapon, and requires clarification and time dependent interpretation. Method: This study estimated the reproduction number and its time dependent change through investigations of outbreaks in Mukden, China ( 1946), and Madagascar ( 1957). Reconstruction of an epidemic tree, which shows who infected whom, from the observed dates of onset was performed using the serial interval. Furthermore, a likelihood based approach was used for the time inhomogeneous evaluation of the outbreaks for which there was scarcity of cases. Results: According to the estimates, the basic reproduction number, R-0, was on the order of 2.8 to 3.5, which is higher than previous estimates. The lower 95% confidence intervals of R-0 exceeded unity. The effective reproduction number declined below unity after control measures were introduced in Mukden, and before the official implementation in Madagascar. Conclusion: While the time course of the latter outbreak could be explained by intrinsic factors and stochasticity in this remote and scarcely populated area, the former in Mukden suggests the possible continued chains of transmission in highly populated areas. Using the proposed methods, the who infected whom information permitted the evaluation of the time inhomogeneous transmission potential in relation to public health measures. The study also tackles the problem of statistical estimation of R0 based on similar information, which was previously performed simply by counting the number of secondary transmissions regardless of time.
  • M Tsutsumi, H Nishiura, T Kobayashi
    BMC INFECTIOUS DISEASES 5 85  1471-2334 2005/10 [Refereed][Not invited]
     
    Background: Although senile dementia patients in long-term care facilities are at leading risk of scabies, the epidemiologic characteristics of this disease have yet to be fully clarified. This study documents the findings of a ward-scale nosocomial outbreak in western Japan from 1989 - 90, for which permission to publish was only recently obtained. Methods: A retrospective epidemiologic study was performed to identify specific risk factors of scabies among patients with dementia. Analyses were based on a review of medical and nursing records. All inpatients in the affected ward at the time of the outbreak were included in the study. Observational and analytical approaches were employed to assess the findings. Results: Twenty of 65 inpatients in the ward met the case definition of scabies. The outbreak lasted for almost 10 months and as a result, the spatial distribution of infections showed no localized patterns in the latter phase of the outbreak. The duration of illness significantly decreased after initiation of control measures ( P = 0.0067). Movement without assistance ( Odds Ratio [ OR] = 11.3; 95% Confidence Interval [CI]: 2.9, 44.8) and moving beyond the room ( but within the ward) ( OR = 4.1; 95% CI: 1.4, 12.5) were significantly associated with infection, while types of room ( Western or Japanese) and sleeping arrangement ( on beds or futons laid directly on the floor) appeared not to be risk factors. Conclusion: Univariate analysis demonstrated the importance of patients' behaviours during daily activities in controlling scabies among senile dementia patients. The findings also support previous evidence that catching scabies from fomites is far less common. Moreover, since cognitive disorders make it difficult for individuals to communicate and understand the implications of risky contacts as well as treatment method, and given the non-specific nature of individual contacts that are often unpredictable, real-time observations might help improve control practices.
  • Rapid awareness and transmission of severe acute respiratory syndrome in Hanoi French Hospital, Vietnam
    H Nishiura, T Kuratsuji, T Quy, NC Phi, Van Ban, V, LD Ha, HT Long, H Yanai, N Keicho, T Kirikae, T Sasazuki, RM Anderson
    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE 73 (1) 17 - 25 0002-9637 2005/07 [Refereed][Not invited]
     
    A case-control study was conducted to examine the relationship between severe acute respiratory syndrome (SARS) and the time-dependent precautionary behaviors taken during an outbreak of SARS in Hanoi French Hospital (HFH), Vietnam. Masks (odds ratio [OR] = 0.3; 95% confidence interval [Cl]: 0.1, 0.7) and gowns (OR = 0.2; 95% CI: 0.0, 0.8) appeared to prevent SARS transmission. The proportion of doctors and nurses who undertook each measure significantly improved (chi(2) = 9.8551, P = 0.043) after the onset of secondary cases. The impact of individual behaviors on an outbreak was investigated through mathematical approaches. The reproduction number decreased from 4.1 to 0.7 after notification. The basic reproduction number was estimated, and the use of masks alone was shown to be insufficient in containing an epidemic. Intuitive results obtained by means of stochastic individual-based simulations showed that rapid improvements in behavior and isolation would increase the probability of extinction.
  • Health inequalities in Thailand: geographic distribution of medical supplies in the provinces.
    Nishiura H, Barua S, Lawpoolsri S, Kittitrakul C, Leman MM, Maha MS, Muangnoicharoen S
    The Southeast Asian journal of tropical medicine and public health 35 (3) 735 - 740 0125-1562 2004/09 [Refereed][Not invited]
  • Predicting the future trend of drug-resistant tuberculosis in Thailand: assessing the impact of control strategies.
    Nishiura H, Patanarapelert K, Tang IM
    The Southeast Asian journal of tropical medicine and public health 35 (3) 649 - 656 0125-1562 2004/09 [Refereed][Not invited]
  • Simple approximate backcalculation method applied to estimate HIV prevalence in Japan
    H Nishiura, H Yanai, T Yoshiyama, M Kakehashi
    JAPANESE JOURNAL OF INFECTIOUS DISEASES 57 (3) 133 - 135 1344-6304 2004/06 [Refereed][Not invited]
  • Nishiura H, Tang IM
    Journal of epidemiology / Japan Epidemiological Association 14 (2) 41 - 50 0917-5040 2004/03 [Refereed][Not invited]
  • Nishiura H, Tsunoda T, Akao N
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 77 677 - 681 0387-5911 2003/09 [Refereed][Not invited]
  • Nishiura H
    Kekkaku : [Tuberculosis] 78 (6) 419 - 426 0022-9776 2003/06 [Refereed][Not invited]
  • Hiroshi Nishiura, Hirohisa Imai, Hiroyuki Nakao, Hiromasa Tsukino, Yoshiki Kuroda, Takahiko Katoh
    [Nippon kōshū eisei zasshi] Japanese journal of public health 49 (11) 1135 - 1141 0546-1766 2002/11 [Refereed][Not invited]
     
    Current and future trends regarding genetically modified (GM) crops and food stuffs were reviewed, with a particular focus on public acceptance and safety assessment. While GM foods, foods derived from biotechnology, are popular with growers and producers, they are still a matter of some concern among consumers. In fact, our recent surveys showed that Japanese consumers had become uneasy about the potential health risks of genetically modified foods. Many Japanese consumers have only vague ideas about the actual health risks, and they appear to be making decisions simply by rejecting GM food because of non-informed doubts. Although the debate about GM foods has increased in the mass media and scientific journals, few articles concerning direct studies on the potential toxicity or adverse health effects of GM foods have appeared. The roles of relevant international regulatory bodies in ensuring that GM crops and food are safe are therefore have summarized. Finally, the current debate on use of GM crops in agriculture and future trends for development of GM foods with enriched nutrients, better functionality, and medicinal ingredients, which will be of direct benefit to the consumer, are covered.
  • H Nishiura, H Imai, H Nakao, H Tsukino, MA Changazi, GA Hussain, Y Kuroda, T Katoh
    ACTA TROPICA 83 (3) 223 - 231 0001-706X 2002/09 [Refereed][Not invited]
     
    The prevalence and intensity of Ascaris lumbricoides in 492 children from five rural villages in the Northern Area of Pakistan was examined. The overall prevalence of A. lumbricoides was 91% (95%CI 88.6-93.6) with geometric mean (GM) egg count intensities of 3985 eggs per g (epg). The most intense A. lumbricoides infections were found in children aged 5-8 years. We also investigated selected socio-cultural and behavioral variables for A. lumbricoides infections that might be relevant for the design of appropriate prevention and control programs. Univariate analysis associated A. lumbricoides intensity with age (P = 0.004), location of household (P < 0.01), defecation practices (P = 0.02), soil eating habit (P < 0.01), hand washing after defecation (P < 0.01), and living with children under 5 years old (P = 0.02). Multivariate analysis identified the children's age 5-8 (P < 0.01), location of household in Surngo, Askole, and Stakchun where the pilot health care model activities were not done (P < 0.01), and living with children under 5 years old (P = 0.03) as variables statistically associated with the intensity of A. lumbricoides. The results indicated that there were certain clear risk factors in A. lumbricoides transmission, and that its intensity was influenced by age-related behavioral and environmental factors that contribute to exposure. (C) 2002 Elsevier Science B.V. All rights reserved.

Books etc

MISC

  • 西浦博  日本公衆衛生学会総会抄録集  76th-  85  2017/10/15  [Not refereed][Not invited]
  • 西浦博  臨床化学  46-  113  2017/09/01  [Not refereed][Not invited]
  • 西浦博, 水本憲治, 宮松雄一郎, 国谷紀良, NAH Kyeongah, 木下諒, 斎藤正也  豊田研究報告  (70)  255‐257  2017/05/29  [Not refereed][Not invited]
  • 西浦博  日本産業衛生学会北海道地方会プログラム・抄録  2017-  6  2017  [Not refereed][Not invited]
  • 西浦博  日本エイズ学会誌  18-  (4)  472  2016/11/20  [Not refereed][Not invited]
  • 斎藤正也, 木下諒, 西浦博  日本熱帯医学会大会プログラム抄録集  57th-  54  2016/11/05  [Not refereed][Not invited]
  • 水本憲治, 西浦博  日本公衆衛生学会総会抄録集  75th-  303  2016/10/15  [Not refereed][Not invited]
  • 西浦博  大和証券ヘルス財団研究業績集  39-  37‐40  2016/03/10  [Not refereed][Not invited]
  • 西浦博, ナ ギョンア  日本応用数理学会年会講演予稿集(CD-ROM)  2016-  ROMBUNNO.9GATSU13NICHI,13:30,2D,4  2016  [Not refereed][Not invited]
  • 斎藤正也, 木下諒, 西浦博  日本計量生物学会年会講演予稿集  2016-  17‐21  2016  [Not refereed][Not invited]
  • 斎藤正也, 木下諒, 西浦博  日本応用数理学会年会講演予稿集(CD-ROM)  2016-  ROMBUNNO.9GATSU14NICHI,16:30,2D,3  2016  [Not refereed][Not invited]
  • 西浦博  発生動向を理解するためのHIV感染者数の推定手法の開発 平成27年度 総括研究報告書  9‐15  2016  [Not refereed][Not invited]
  • 西浦博  発生動向を理解するためのHIV感染者数の推定手法の開発 平成27年度 総括研究報告書  19‐22  2016  [Not refereed][Not invited]
  • 西浦博  ストレス科学研究  31-  86‐87(J‐STAGE)  2016  [Not refereed][Not invited]
  • 西浦博, 木下諒  システム/制御/情報  59-  (12)  446  -451  2015/12/15  [Not refereed][Not invited]
  • 【感染症 いま何が起きているのか 基礎研究、臨床から国際支援まで】 (第2章)感染症研究のいま メカニズムから予防・治療まで マクロ生物学からのアプローチ 感染症流行の数理モデルへの招待
    西浦 博  実験医学  33-  (17)  2798  -2804  2015/11  [Not refereed][Not invited]
     
    感染症の数理モデル研究では、各感染個体が他の感染個体を再生産するメカニズムを理論的に記述することで流行の予測や予防策の評価が行われる。基本再生産数(R0)は1人の感染者が生み出す2次感染者数の平均値のことを指し、感染症別の感染性を与える疫学的指標として利用される。R0は予防接種率や接触者追跡調査の目標値を与えるため、実践的な流行対策の政策策定において広く参照されている。R0は便利な指標である一方、伝播の異質性が顕著なときは、予防接種率や流行規模の予測などにおいて、1人の感染者が生み出す2次感染者数のバラつきも考慮することが必須となる。また、再感染が頻繁に起こる場合や強い季節性を認める場合など、R0には技術的な落とし穴も存在し、取り扱いには十分な数理的理解が求められる。(著者抄録)
  • HIV/AIDS流行のリアルタイム予測(Real-time forecasting of HIV/AIDS epidemic in Japan)
    西浦 博  日本エイズ学会誌  17-  (4)  410  -410  2015/11  [Not refereed][Not invited]
  • 西浦博  日本公衆衛生学会総会抄録集  74th-  446  2015/10/15  [Not refereed][Not invited]
  • 水本憲治, 西浦博  日本公衆衛生学会総会抄録集  74th-  470  2015/10/15  [Not refereed][Not invited]
  • 西浦博, 西浦博  インフルエンザ  16-  (3)  195  -201  2015/10/01  [Not refereed][Not invited]
  • インフルエンザ伝播動態の疫学研究への招待
    西浦 博  インフルエンザ  16-  (3)  195  -201  2015/10  [Not refereed][Not invited]
     
    インフルエンザの疫学に関する重要な科学的疑問点は、いまだに確実に解明されていないものが多い。ワクチン接種の有効性や免疫の持続などはもちろんだが、流行対策の有効性を考える以前に、毎年インフルエンザに何人の方が感染しているのか、日本では十分に明らかにされていない。また、異なるウイルス株がどのような重化症プロファイル(例:致命割合)に影響を与えているのかも疫学的に明らかでない。本稿では伝播動態にかかわる疑問点について、その研究手法と最近までに得られた研究成果をご紹介する。致命割合は、死亡前(計算前)にどのような状態が与えられたかによって推定値が大きく変動するため、最も理論的に頑健と考えられる感染者致命割合について紹介する。同指標の計算には超過死亡者数と血清疫学調査に基づく感染者数の推定を要する。社会医学上の要請に応じて理論的定義を明確にしつつ各指標を使用することが求められる。(著者抄録)
  • 渡航制限に伴うエボラ出血熱の地理的流行拡大の抑止効果推定
    西浦 博  日本公衆衛生学会総会抄録集  74回-  446  -446  2015/10  [Not refereed][Not invited]
  • 季節性インフルエンザの疾病負荷に関する推定
    水本 憲治, 西浦 博  日本公衆衛生学会総会抄録集  74回-  470  -470  2015/10  [Not refereed][Not invited]
  • 西浦博  日本応用数理学会年会講演予稿集(CD-ROM)  2015-  ROMBUNNO.9GATSU9NICHI,13:30,D,2  2015/09/02  [Not refereed][Not invited]
  • 斎藤正也, 江島啓介, 木下諒, 西浦博  日本応用数理学会年会講演予稿集(CD-ROM)  2015-  ROMBUNNO.9GATSU9NICHI,13:30,D,1  2015/09/02  [Not refereed][Not invited]
  • 西浦博, 斎藤正也  日本進化学会大会プログラム・講演要旨集(Web)  17th-  ROMBUNNO.S4‐1 (WEB ONLY)  2015/08/20  [Not refereed][Not invited]
  • 西浦博  生体の科学  66-  (4)  364  -367  2015/08/15  [Not refereed][Not invited]
  • 西浦 博  生体の科学  66-  (4)  364  -367  2015/08  [Not refereed][Not invited]
  • 西浦博  医療と社会  25-  (2)  226  2015/07/21  [Not refereed][Not invited]
  • 流行中の感染症の必要予防接種数の推定と優先的接種対象の最適化
    西浦 博  医療と社会  25-  (2)  226  -226  2015/07  [Not refereed][Not invited]
  • 西浦博  豊田研究報告  (68)  127  -128  2015/05/25  [Not refereed][Not invited]
  • 西浦博  発生動向を理解するためのHIV感染者数の推定手法の開発 平成26年度 総括研究報告書  17‐20  2015  [Not refereed][Not invited]
  • 西浦博  感染症対策における政策判断のための数理モデル研究基盤の構築と発展 平成26年度 委託業務成果報告書  24‐26  2015  [Not refereed][Not invited]
  • 西浦博  感染症対策における政策判断のための数理モデル研究基盤の構築と発展 平成26年度 委託業務成果報告書  5‐11  2015  [Not refereed][Not invited]
  • 西浦博  感染症対策における政策判断のための数理モデル研究基盤の構築と発展 平成26年度 委託業務成果報告書  39‐40  2015  [Not refereed][Not invited]
  • 西浦博  発生動向を理解するためのHIV感染者数の推定手法の開発 平成26年度 総括研究報告書  9‐14  2015  [Not refereed][Not invited]
  • 西浦博  感染症対策における政策判断のための数理モデル研究基盤の構築と発展 平成26年度 委託業務成果報告書  18‐23  2015  [Not refereed][Not invited]
  • 西浦博, 江島啓介  日本応用数理学会年会講演予稿集(CD-ROM)  2014-  ROMBUNNO.9GATSU5NICHI,11:00,D,2  2014/08/27  [Not refereed][Not invited]
  • 西浦博  日本獣医学会学術集会講演要旨集  157th-  207  2014/08/11  [Not refereed][Not invited]
  • 人獣共通感染症の先回り対策策定に向けた情報戦略 感染症数理モデルを利用したパンデミックの予兆の探知
    西浦 博  日本獣医学会学術集会講演要旨集  157回-  207  -207  2014/08  [Not refereed][Not invited]
  • 感染症の数理モデルを利用したインフルエンザ予防接種の最適化 費用対効果に優れた高齢者予防方法の特定
    西浦 博  未病と抗老化  23-  51  -57  2014/07  [Not refereed][Not invited]
     
    高齢者の中には、インフルエンザ感染時に重症化するリスクが高い者が多い。そのため、日本における現行の予防接種法では、高齢者の定期接種が定められている。他方、日本では小児のインフルエンザワクチンの接種は任意であり、最近に同年齢群を定期接種の対象に含む政策を採用した英国や米国と異なる。本研究は、インフルエンザの年齢・時刻に依存する感染リスク及び死亡リスクを描写する数理モデルを用いて、ワクチン接種の集団的効果と費用対効果について接種対象の年齢群別にシナリオ分析を実施した。その結果、高齢者のみを対象とした定期接種は強毒株の流行など一部シナリオにおいてのみ費用対効果が支持されるが、例外を除いて集団的効果および費用対効果に乏しく、むしろ小児のみにワクチンを接種したほうが有効であることが示された。高齢者のインフルエンザによる死亡を予防するには小児の定期接種によって集団免疫を最大限に高めることが効果的であり、それがコスト面でも最も優れていることが明らかにされた。また、小児と高齢者でワクチンを均等配分するシナリオも費用対効果に優れていることが明らかにされ、今後の日本におけるインフルエンザ予防接種の方針として小児を定期接種の対象に加えることも有効かつ費用対効果に優れているものと考えられた。(著者抄録)
  • 西浦博, 江島啓介  最新医学  69-  (4)  786  -794  2014/04/10  [Not refereed][Not invited]
  • 【次世代型感染症ワクチン】 感染症流行の数理モデルを利用した予防接種の政策判断
    西浦 博, 江島 啓介  最新医学  69-  (4)  786  -794  2014/04  [Not refereed][Not invited]
     
    感染症流行の数理モデルは,仮想的条件のもとで流行動態を検討することに役立つ.20世紀後半以降,予防接種を含む公衆衛生政策の判断や最適化に数理モデルを用いる機会が増えている.基本再生産数を利用した集団免疫度の計算はもちろんのこと,被害規模の最小化を目指した接種割合の最適化や接種による感染年齢上昇の落とし穴など,ダイナミクスを理解することで予防接種政策に新しい地平を見いだすことが可能である.インフルエンザワクチン接種の年齢別優先度に代表されるような理論的理解と現行政策との間に認めるギャップを埋める方法を模索することも今後求められる.(著者抄録)
  • 西浦博  日本数理生物学会ニュースレター  (71)  4  -7  2013/09  [Not refereed][Not invited]
  • 江島啓介, 西浦博, 合原一幸, EICHNER Martin  日本数理生物学会大会講演要旨集  23rd-  67  2013  [Not refereed][Not invited]
  • 西浦博, 水本憲治, 江島啓介  日本数理生物学会大会講演要旨集  23rd-  71  2013  [Not refereed][Not invited]
  • 水本憲治, 江島啓介, 山本太郎, 西浦博  日本数理生物学会大会講演要旨集  23rd-  69  2013  [Not refereed][Not invited]
  • 西浦 博, 稲葉 寿  統計数理  59-  (2)  267  -286  2011/12  [Not refereed][Not invited]
  • 西浦博, 西浦博, 西浦博, 稲葉寿  統計数理  59-  (2)  267-286  -286  2011/12  [Not refereed][Not invited]
  • NISHIURA Hiroshi  Japanese Journal of Radiological Technology  66-  (11)  1485  -1491  2010/11/20  [Not refereed][Not invited]
     
    Understanding inter-observer variability in clinical diagnosis is crucial for reliability studies. As the statistical measurements of reliability, the kappa statistic and its extensions have been widely adopted in medical research, but it has been discussed that kappa is vulnerable to prevalence and presence of bias. As an alternative robust statistic, AC1 has attracted recent statistical attentions. This article describes fundamental ideas and quantitative features of AC1. The reliability of infrared thermoscanner as an application in detecting febrile patients of pandemic influenza is dis...
  • 西浦博, 合原一幸  数学セミナー  49-  (4)  52  -59  2010/04  [Not refereed][Not invited]
  • 西浦博, 合原一幸  数学セミナー  49-  (3)  58  -64  2010/03  [Not refereed][Not invited]
  • 西浦博, 合原一幸  数学セミナー  49-  (2)  48  -53  2010/02  [Not refereed][Not invited]
  • 西浦博  数学セミナー  49-  (1)  64  -71  2010/01  [Not refereed][Not invited]
  • Jan van den Broek, Hiroshi Nishiura  ANNALS OF APPLIED STATISTICS  3-  (4)  1505  -1520  2009/12  [Not refereed][Not invited]
     
    This study proposes a nonhomogeneous birth-death model which captures the dynamics of a directly transmitted infectious disease. Our model accounts for an important aspect of observed epidemic data in which only symptomatic infecteds are observed. The nonhomogeneous birth-death process depends on survival distributions of reproduction and removal, which jointly yield an estimate of the effective reproduction number R(t) as a function of epidemic time. We employ the Burr distribution family for the survival functions and, as special cases, proportional rate and accelerated event-time models are also employed for the parameter estimation procedure. As an example, our model is applied to an outbreak of avian influenza (H7N7) in the Netherlands, 2003, confirming that the conditional estimate of R(t) declined below unity for the first time on day 23 since the detection of the index case.
  • 西浦博  日本オペレーションズ・リサーチ学会和文論文誌  52-  20  -37  2009/12  [Not refereed][Not invited]
  • 西浦博  数学セミナー  48-  (12)  42  -48  2009/12  [Not refereed][Not invited]
  • Nishiura Hiroshi  Transactions of the Operations Research Society of Japan  52-  (0)  20  -37  2009/12  [Not refereed][Not invited]
     
    This study proposes a few different methods to determine the length of quarantine against infectious diseases and develops their theoretical foundation. Quarantine measure, which refers to compulsory physical separation, including restriction of movement, of healthy indiviuduals who have been potentially exposed to an infectious disease, is one of the essential countermeasures as a border control against newly emerging infectious diseases. Although diagnostic tests and legal enforcement of quarantine have been discussed, little has been done on the determination of the optimal length. Pract...
  • 西浦博  科学  79-  (11)  1234  -1240  2009/11/01  [Not refereed][Not invited]
  • 西浦博  数学セミナー  48-  (7)  40  -46  2009/07  [Not refereed][Not invited]
  • 西浦博  統計数理  57-  (1)  139  -158  2009/06  [Not refereed][Not invited]
  • 西浦博  Proceedings of the Institute of Statistical Mathematics  57-  (1)  139  -158  2009  [Not refereed][Not invited]
  • NISHIURA Hiroshi, AIHARA Kazuyuki  SEISAN KENKYU  61-  (4)  797  -803  2009  [Not refereed][Not invited]
     
    An emerging influenza pandemic has been observed, and devastating recurrent waves are anticipated. Although production of a pandemic vaccine has already started, an upper limit of production-capacity exists, and moreover, the seasonal influenza vaccine also has to be manufactured. The present study proposes an optimization method for resource allocation of vaccine production. If immunization coverage of the pandemic vaccine can achieve close to its own threshold, spending all resources for the pandemic vaccine is not optimal. Provided that our model sufficiently captures the realism,...
  • 西浦博  未病と抗老化  17-  (1)  59  -62  2008/04  [Not refereed][Not invited]
  • 西浦博  Proceedings of the Institute of Statistical Mathematics  56-  (2)  235  -252  2008  [Not refereed][Not invited]
  • Hiroshi Nishiura, Scott B. Halstead  JOURNAL OF INFECTIOUS DISEASES  195-  (7)  1007  -1013  2007/04  [Not refereed][Not invited]
     
    Background. The natural history of wild-type dengue virus (DENV) infections of humans, including incubation and infectious periods, requires further study. Methods. Two experimental studies in the Philippines of DENV-4 (1924-1925) and DENV-1 (1929-1930) were reexamined. The intrinsic incubation periods were fitted to log-normal distribution using the maximum likelihood method, and the infectious and extrinsic incubation periods were assessed by proportions of successful transmissions causing clinically apparent dengue. Correlations between the intrinsic incubation period and other variables and univariate associations between clinical severity and serotype were also examined. Results. Mean +/- SD incubation periods were 6.0 +/- 1.4 and 5.7 +/- 1.5 days for DENV-4 and DENV-1, respectively. Significant negative correlations were observed between the incubation period and duration of fever (r = -0.43 and -0.33). Even 1 and 2 days before the onset of fever, 80.0% (95% confidence interval [CI], 44.9%-100%) and 25.0% (CI, 0%-67.4%) of biting experiments caused clinically apparent dengue. DENV-1 infections resulted in a significantly longer duration of fever than DENV-4 infections (P < .01). Conclusions. Incubation period was negatively correlated with disease severity, potentially reflecting a dose-response mechanism. The historical data provided useful details concerning serotype differences in the natural history of primary DENV infections.
  • Hiroshi Nishiura, Hyeong-Woo Lee, Shin-Hyeong Cho, Wook-Gyo Lee, Tae-Suk In, Sung-Ung Moon, Gyung Tae Chung, Tong-Soo Kim  TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE  101-  (4)  338  -343  2007/04  [Not refereed][Not invited]
     
    With the current epidemic of vivax malaria closely associated with the demilitarised zone along the border between North and South Korea, it has been suggested that the incubation period tends, in part, to be prolonged. Based on the detailed travel history of cases from 2000 to 2003 who reside in non-malarious areas, statistical estimates of the incubation periods were obtained. The data suggest that cases fall into two categories with short- and long-term incubation periods, respectively. Of 416 cases with available information, 72 and 79 successfully met our criteria for inferring the durations of short- and long-term incubation periods. The mean short- and tong-term incubation periods were estimated to be 26.6 days (95% CI 21.0-32.2) and 48.2 weeks (95% CI 46.8-49.5), respectively. The maximum likelihood method was used to fit gamma and normal distributions to the short- and tong-term incubation periods, assisting prediction of the frequency distribution of the overall incubation period, which exhibited a bimodal pattern. We postulate that the observed distribution reflects adaptation of the parasite to the seasonal population dynamics of the vector, Anopheles sinensis, ensuring continued transmission of vivax malaria in this temperate zone. (C) 2006 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
  • Nishiura Hiroshi  RIMS Kokyuroku  1551-  (0)  1  -3  2007/04  [Not refereed][Not invited]
  • Gerardo Chowell, Hiroshi Nishiura, Luis M. A. Bettencourt  JOURNAL OF THE ROYAL SOCIETY INTERFACE  4-  (12)  155  -166  2007/02  [Not refereed][Not invited]
     
    The reproduction number, R, defined as the average number of secondary cases generated by a primary case, is a crucial quantity for identifying the intensity of interventions required to control an epidemic. Current estimates of the reproduction number for seasonal influenza show wide variation and, in particular, uncertainty bounds for R for the pandemic strain from 1918 to 1919 have been obtained only in a few recent studies and are yet to be fully clarified. Here, we estimate R using daily case notifications during the autumn wave of the influenza pandemic (Spanish flu) in the city of San Francisco, California, from 1918 to 1919. In order to elucidate the effects from adopting different estimation approaches, four different methods are used: estimation of R using the early exponential-growth rate (Method 1), a simple susceptible exposed - infectious - recovered (SEIR) model (Method 2), a more complex SEIR-type model that accounts for asymptomatic and hospitalized cases ( Method 3), and a stochastic susceptible - infectious - removed (SIR) with Bayesian estimation (Method 4) that determines the effective reproduction number R-t at a given time t. The first three methods. t the initial exponential-growth phase of the epidemic, which was explicitly determined by the goodness-of-fit test. Moreover, Method 3 was also fitted to the whole epidemic curve. Whereas the values of R obtained using the first three methods based on the initial growth phase were estimated to be 2.98 (95% confidence interval (CI): 2.73, 3.25), 2.38 (2.16, 2.60) and 2.20 (1.55, 2.84), the third method with the entire epidemic curve yielded a value of 3.53 (3.45, 3.62). This larger value could be an overestimate since the goodness-of-fit to the initial exponential phase worsened when we fitted the model to the entire epidemic curve, and because the model is established as an autonomous system without time-varying assumptions. These estimates were shown to be robust to parameter uncertainties, but the theoretical exponential-growth approximation (Method 1) shows wide uncertainty. Method 4 provided a maximum-likelihood effective reproduction number 2.10 (1.21, 2.95) using the first 17 epidemic days, which is consistent with estimates obtained from the other methods and an estimate of 2.36 (2.07, 2.65) for the entire autumn wave. We conclude that the reproduction number for pandemic influenza (Spanish flu) at the city level can be robustly assessed to lie in the range of 2.0 3.0, in broad agreement with previous estimates using distinct data.
  • 西浦博  数学セミナー  46-  (2)  18  -23  2007/02  [Not refereed][Not invited]
  • Hiroshi Nishiura, Hisashi Inaba  JOURNAL OF THEORETICAL BIOLOGY  244-  (2)  357  -364  2007/01  [Not refereed][Not invited]
  • H. Nishiura  EPIDEMIOLOGY AND INFECTION  135-  (1)  126  -130  2007/01  [Not refereed][Not invited]
     
    This study investigated 21 foodborne type-E botulism outbreaks, without antitoxin administration, from 1951 to 1965 in Hokkaido, Japan, to characterize the descriptive epidemiology and evaluate the relationship between case fatality and incubation period. The median (25-75% quartile) attack rate and case fatality, which were evaluated by outbreak, were 58 center dot 3% (38 center dot 0-73 center dot 2) and 25 center dot 7% (0 center dot 1-50 center dot 0) respectively. Individual records of 64 diagnoses, including 31 deaths, were also examined using logistic regression analysis, revealing that a shorter incubation period is likely to result in a significantly higher risk of death (P=0-01). The observed case fatality was more than 50% for those who developed symptoms within the first 18h after exposure, possibly reflecting underlying dose-dependent mechanisms. In the event of intentional contamination of food with botulinum toxin, rapidly determining the incubation periods may be critical for guiding public health response efforts.
  • 西浦博, 稲葉寿  統計数理  54-  (2)  461  -480  2006/12  [Not refereed][Not invited]
  • H. Nishiura, M. Eichner  INFECTION  34-  (5)  241  -246  2006/10  [Not refereed][Not invited]
     
    Background: Understanding the loss of vaccine-induced immunity against smallpox is essential in determining the fraction of those who are still protected in the present population and in constructing effective countermeasures against bioterrorist attacks. Method: Three small Australian outbreaks from the 1880s to early 1900s were investigated. Each documented individual age at infection. The case records for Launceston, 1903, further documented the age at vaccination and disease severity, enabling estimates of the duration of protection against severe and fatal smallpox. Results: A significant association between vaccination and death was observed in the outbreak in Sydney, 1881 (odds ratio of death among vaccinated individuals = 0.3; 95% confidence interval (CI): 0.1, 0.8; p = 0.02), where the time since last vaccination was similar for all vaccinated cases. In Launceston, 1903, where the age at vaccination varied widely, the median duration of partial protection against severe and fatal smallpox was estimated to be 31.7 (95% CI: 13.2, 116.2) and 53.9 (95% CI: 25.6, 123.5) years after vaccination, respectively. Whereas those in their 20s are expected to have the highest frequency of vulnerability to smallpox death in the present population, infections among those in their 30s or 40s are expected to be much less fatal. Conclusion: Long lasting partial protection was suggested from the outbreak records, the estimated durations of which were roughly consistent with those reported previously. In the event of a bioterrorist attack, those involved in emergency tasks before emergency vaccination practices are re-established should ideally be previously vaccinated individuals in their 30s or 40s.
  • Hiroshi Nishiura, Markus Schwehm, Martin Eichner  EPIDEMIOLOGY  17-  (5)  576  -581  2006/09  [Not refereed][Not invited]
     
    Background: Although the potential for bioterrorism has led to discussions on the durability of vaccine-induced immunity, the actual duration of protection against smallpox is still unknown. It has previously been suggested that at least partial protection against severe and fatal smallpox may persist throughout life. Methods: In this article, we analyzed 6 major smallpox outbreaks that occurred before and after 1900 in the United Kingdom. These analyses are based on the age-dependent incidence of smallpox and the fraction of severe manifestations among individuals with or without prior vaccination. We. used. a likelihood-based approach to estimate the duration of immunity from the age-specific frequencies. Results: The expected median duration of protection from disease ranged from 11.7 to 28.4 Years after primary vaccination, and the qualitative pattern of duration could be described using Gompertz's Law. Vaccinated individuals appear to have been protected from severe disease with more than 50% probability even 50 years aft er successful primary vaccination. Conclusions: These findings suggest that successful primary vaccination offered full protection for a few decades, with partial protection from severe smallpox possibly lasting a lifetime, for a substantial fraction of the population.
  • Hiroshi Nishiura, Klaus Dietz, Martin Eichner  JOURNAL OF THEORETICAL BIOLOGY  241-  (4)  964  -967  2006/08  [Not refereed][Not invited]
  • H Nishiura, M Schwehm, M Kakehashi, M Eichner  JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH  60-  (7)  640  -645  2006/07  [Not refereed][Not invited]
     
    Background: The transmission potential of primary pneumonic plague, caused by Yersinia pestis, is one of the key epidemiological determinants of a potential biological weapon, and requires clarification and time dependent interpretation. Method: This study estimated the reproduction number and its time dependent change through investigations of outbreaks in Mukden, China ( 1946), and Madagascar ( 1957). Reconstruction of an epidemic tree, which shows who infected whom, from the observed dates of onset was performed using the serial interval. Furthermore, a likelihood based approach was used for the time inhomogeneous evaluation of the outbreaks for which there was scarcity of cases. Results: According to the estimates, the basic reproduction number, R-0, was on the order of 2.8 to 3.5, which is higher than previous estimates. The lower 95% confidence intervals of R-0 exceeded unity. The effective reproduction number declined below unity after control measures were introduced in Mukden, and before the official implementation in Madagascar. Conclusion: While the time course of the latter outbreak could be explained by intrinsic factors and stochasticity in this remote and scarcely populated area, the former in Mukden suggests the possible continued chains of transmission in highly populated areas. Using the proposed methods, the who infected whom information permitted the evaluation of the time inhomogeneous transmission potential in relation to public health measures. The study also tackles the problem of statistical estimation of R0 based on similar information, which was previously performed simply by counting the number of secondary transmissions regardless of time.
  • Kunio Satou, Hiroshi Nishiura  JOURNAL OF EQUINE VETERINARY SCIENCE  26-  (7)  310  -316  2006/07  [Not refereed][Not invited]
     
    Characterizing the epidemiologic determinants of equine influenza to facilitate effective control measures, including determining the critical proportion of the population that must be immunized to achieve containment, is critical. Through the use of counting process and martingale method, the basic reproduction number (R-0; a measure of transmission potential) of equine-2 influenza A virus (H3N8) infection was estimated based on outbreak data recorded in 1971. The final attack rate ranged from 81.9% to 99.4%. Our estimate of R-0 was in the order of 2 to 5, which was smaller than the previously suggested estimate. Numerical analysis supported airborne spread as the major mode of transmission. Given that simple threshold vaccination coverage might not be realistic within racing stables, the combination of movement restrictions, isolation, and other countermeasures alongside vaccination is recommended to contain outbreaks of equine influenza.
  • Nishiura H  International Journal of Epidemiology  35-  (4)  1059  -1065  2006  [Not refereed][Not invited]
  • Smallpox during Pregnancy and Maternal Outcomes
    Nishiura H  Emerging Infectious Diseases  12-  (7)  1119  -1121  2006  [Not refereed][Not invited]
  • 吉山崇, 西浦博  アジア太平洋地域における国際人口移動から見た危機管理としてのHIV感染症対策に関する研究 平成15-17年度 総合研究報告書  9  -13  2006  [Not refereed][Not invited]
  • 吉山崇, 西浦博  アジア太平洋地域における国際人口移動から見た危機管理としてのHIV感染症対策に関する研究 平成15-17年度 総合研究報告書  14  -18  2006  [Not refereed][Not invited]
  • 西浦博  統計関連学会連合大会講演報告集  2006-  (CD-ROM)  9GATSU8NICHI.GOZEN1.FKAIJO.2  2006  [Not refereed][Not invited]
  • 西浦博  長崎大学熱帯医学研究所共同研究報告集  18-  52  -55  2006  [Not refereed][Not invited]
     
    これまでの熱帯医学研究所の共同研究・研究集会が母体となって「感染症理論疫学研究会」が発足し,平成17年度は東京において「熱帯病の数学モデルの構築と予防制圧への応用」についての研究集会を東京大学と共同で開催した。本年度は「健康危機管理における感染症数理モデルの有用性の検討」を中心テーマとして「感染症理論疫学」のワークショップを2006年10月に長崎で開催された第47回日本熱帯医学会・第21回日本国際保健医療学会合同大会において開催し,高病原性トリインフルエンザ,天然痘等についての数理モデルを利用した研究についての研究集会を実施した。
  • 西浦博, 稲葉寿  統計数理  54-  (2)  461  -480  2006  [Not refereed][Not invited]
  • M Tsutsumi, H Nishiura, T Kobayashi  BMC INFECTIOUS DISEASES  5-  85 (paper ID)  2005/10  [Not refereed][Not invited]
     
    Background: Although senile dementia patients in long-term care facilities are at leading risk of scabies, the epidemiologic characteristics of this disease have yet to be fully clarified. This study documents the findings of a ward-scale nosocomial outbreak in western Japan from 1989 - 90, for which permission to publish was only recently obtained. Methods: A retrospective epidemiologic study was performed to identify specific risk factors of scabies among patients with dementia. Analyses were based on a review of medical and nursing records. All inpatients in the affected ward at the time of the outbreak were included in the study. Observational and analytical approaches were employed to assess the findings. Results: Twenty of 65 inpatients in the ward met the case definition of scabies. The outbreak lasted for almost 10 months and as a result, the spatial distribution of infections showed no localized patterns in the latter phase of the outbreak. The duration of illness significantly decreased after initiation of control measures ( P = 0.0067). Movement without assistance ( Odds Ratio [ OR] = 11.3; 95% Confidence Interval [CI]: 2.9, 44.8) and moving beyond the room ( but within the ward) ( OR = 4.1; 95% CI: 1.4, 12.5) were significantly associated with infection, while types of room ( Western or Japanese) and sleeping arrangement ( on beds or futons laid directly on the floor) appeared not to be risk factors. Conclusion: Univariate analysis demonstrated the importance of patients' behaviours during daily activities in controlling scabies among senile dementia patients. The findings also support previous evidence that catching scabies from fomites is far less common. Moreover, since cognitive disorders make it difficult for individuals to communicate and understand the implications of risky contacts as well as treatment method, and given the non-specific nature of individual contacts that are often unpredictable, real-time observations might help improve control practices.
  • 嶋田雅暁, 浜田芳樹, 門司和彦, 西浦博, 稲葉寿, 竹内昌平, 大日康史, 中澤港, 増田直紀, 加茂将史  長崎大学熱帯医学研究所共同研究報告集  2004-  73  -77  2005/08  [Not refereed][Not invited]
  • Rapid awareness and transmission of severe acute respiratory syndrome in Hanoi French Hospital, Vietnam
    H Nishiura, T Kuratsuji, T Quy, NC Phi, Van Ban, V, LD Ha, HT Long, H Yanai, N Keicho, T Kirikae, T Sasazuki, RM Anderson  AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE  73-  (1)  17  -25  2005/07  [Not refereed][Not invited]
     
    A case-control study was conducted to examine the relationship between severe acute respiratory syndrome (SARS) and the time-dependent precautionary behaviors taken during an outbreak of SARS in Hanoi French Hospital (HFH), Vietnam. Masks (odds ratio [OR] = 0.3; 95% confidence interval [Cl]: 0.1, 0.7) and gowns (OR = 0.2; 95% CI: 0.0, 0.8) appeared to prevent SARS transmission. The proportion of doctors and nurses who undertook each measure significantly improved (chi(2) = 9.8551, P = 0.043) after the onset of secondary cases. The impact of individual behaviors on an outbreak was investigated through mathematical approaches. The reproduction number decreased from 4.1 to 0.7 after notification. The basic reproduction number was estimated, and the use of masks alone was shown to be insufficient in containing an epidemic. Intuitive results obtained by means of stochastic individual-based simulations showed that rapid improvements in behavior and isolation would increase the probability of extinction.
  • 藤田一寿, 西浦博, 石川洋文  日本寄生虫学会大会プログラム・抄録集  74th-  59  2005/02  [Not refereed][Not invited]
  • 門司和彦, 錦織信幸, 富尾淳, 西浦博, 國井修  国際的な健康危機管理に必要なスキル獲得のための人材育成のあり方に関する研究 平成16年度 総括・分担研究報告書  69-83,85-111,113-123,125-145  2005  [Not refereed][Not invited]
  • 吉山崇, 西浦博  アジア太平洋地域における国際人口移動から見た危機管理としてのHIV感染症対策に関する研究 平成16年度総括・分担研究報告書  9  -15  2005  [Not refereed][Not invited]
  • 西浦博  長崎大学熱帯医学研究所共同研究報告集  17-  2005  [Not refereed][Not invited]
     
    研究集会は,平成18年1月28日に東京大学生産技術研究所コンベンションホールで「感染症理論疫学研究大会2006:数理疫学・数理生態学・数理統計学の融合」というタイトルで,合原複雑数理モデルプロジェクト・東京大学21世紀COEプログラム「情報科学技術戦略コア」超ロバスト計算原理プロジェクトとの共催という形で実施され,以下に掲げる16演題が発表された。1.稲葉寿(東京大学数理科学研究科)Age-Structured Homogeneous Epidemic Systems with Application to the MSEIR Epidemic Model 2.竹内康博(静岡大学工学部システム工学科)Global dynamics of SIS model with transport-related infection 3.杉峰伸明(独立行政法人科学技術振興機構ERATO合原複雑数理モデルプロジェクト)ツリー上の拡張型コンタクトプロセスの大域的臨界値と局所的臨界値について 4.加茂将史(産業技術総合研究所化学物質リスク管理研究センター)空間構造を伴う集団での病原性の進化 5.瀬野裕美(広島大学大学院理学研究科数理分子生命理学専攻)伝染媒介体の空間分布に依存した伝染病汚染地域の拡大速度に関する確立過程モデル 6.大塚一路(東京大学先端科学技術研究センター)多状態確立粒子モデル...
  • NISHIURA Hiroshi, TSUTSUI Toshiyuki, KAKEHASHI Masayuki  The Journal of veterinary epidemiology  8-  (2)  85  -94  2004/12/20  [Not refereed][Not invited]
  • NISHIURA Hiroshi, KAKEHASHI Masayuki  The Journal of veterinary epidemiology  8-  (2)  65  -76  2004/12/20  [Not refereed][Not invited]
  • 西浦博, 今津里沙, 吉山崇  The Journal of population studies  0-  (35)  1  -11  2004/11  [Not refereed][Not invited]
  • H Nishiura, IM Tang  JOURNAL OF EPIDEMIOLOGY  14-  (2)  41  -50  2004/03  [Not refereed][Not invited]
     
    BACKGROUND: There has been concern that variola virus might be held clandestinely elsewhere. Through constructing mathematical model based on the detailed epidemiologic data, we focused on simulating the various possible scenarios arising from a bioterrorist attack whereby smallpox virus was introduced into Japan, and sought to develop the most effective way of nationwide vaccination policy based on the theory of residual immunity. METHOD: The analysis is based on a deterministic mathematical model which predicted the epidemiologic outcome while simultaneously evaluating the effect of any specified control strategy of the smallpox epidemic. To clarify the required amount of vaccines, we performed mathematical analysis for hypothetical population to acquire herd immunity based on long-lasting vaccinal immunity. RESULTS: It is demonstrated that the crude size of the potential epidemic could be greatly affected by possible level of residual immunity. The results also suggest the possibility to develop optimal distribution of nationwide vaccination according to the immune status. The prevalence at 50th day among population without immunity in our simulation would be approximately 405 times greater than expected population with residual immunity, and required amount of vaccines for equal distribution would be 3.13 times more than optimal distribution. CONCLUSION: The mathematical model formulated could determine the vaccination priority based on the real status of immunity which required much less amount of vaccinations than would be calculated using an equal distribution program. It is therefore crucial to determine the real immunity status of the population via epidemiologic studies.
  • H Nishiura, K Patanarapelert, M Sriprom, W Sarakorn, S Sriyab, IM Tang  JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH  58-  (3)  186  -191  2004/03  [Not refereed][Not invited]
     
    Background: There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. With the use of detailed epidemiological data from other countries, this article describes the possible reason for the SARS epidemic not appearing in Japan, and simulates the impact of different control strategies that can break the transmission cycle of SARS associated coronavirus. Method: Mathematical modelling is used for predicting the epidemiological outcome and simultaneously for evaluating the effect of interventions on SARS. The study estimates the initial attack size that would result in failed invasion. Three different interventions have been incorporated into the public health response policies; precautionary public health measures, isolation of infected people, and quarantine of exposed humans. Results: The maximum number of humans newly infected could be roughly estimated on the basis of the initial attack size, using simple formulas. It is seen that the introduction of only a few cases into certain communities would not lead easily to an epidemic. The possible trajectories of SARS epidemic depend on the levels of public health interventions as quarantine and precautionary public health measures greatly affected the transmissibility of the disease. It is shown that there exist threshold levels of interventions at which the SARS epidemic settles down. Conclusion: Initial attack size is one of the determinants of whether SARS can successfully invade the community or not. Two of the most effective policy procedures to prevent new infections would be to apply stringent precautionary measures and to impose quicker and more effective quarantine of the exposed populace.
  • 吉山崇, 西浦博  アジア太平洋地域における国際人口移動から見た危機管理としてのHIV感染症対策に関する研究 平成15年度 総括研究報告書(総括・分担研究報告書)  100  -105  2004  [Not refereed][Not invited]
  • 嶋田雅暁, 西浦博, 稲葉寿, 竹内昌平, 大日康史, 中澤港, 増田直紀, 加茂将史  長崎大学熱帯医学研究所共同研究報告集  16-  73  -77  2004  [Not refereed][Not invited]
     
    熱帯感染症の効果的な抑制政策には数理疫学(感染症数理モデル)に基づく研究手法による理論的理解が欠かせない。流行に関わる諸要因の影響探索や抑止対策の評価,サーベイランス等のフィールド疫学で用いられる手法の諸評価,そして将来予測に至るまで,数理生態学や数理統計学を中心とした数理的諸研究の貢献度は非常に高い。本共同研究は昨年度の共同研究(15-A-25)を継続して実施され,2004年2月の研究集会「熱帯疫学における観察データと複数数理モデルの対峙(15-B-4:研究代表:門司和彦)」を発展して研究集会が開催された。共同研究集会は科学的分野を区別しない学際的研究に関して,国際的レベルの先端的研究を牽引する研究者による基礎的理解の浸透と実際の社会貢献度の高い研究内容に関する活発な議論を目的として行われた。ロンドン大学インペリアルカレッジ感染症疫学の西浦博氏(現チュービンゲン大学医学部研究員・熱研非常勤講師)および中澤港氏(群馬大学大学院生態情報学助教授・熱研非常勤講師)らの尽力により,多くの感染症数理モデル研究者が研究内容を発表・議論し,共同研究を実施することができた。
  • 西浦博, 角田隆文, 赤尾信明  感染症学雑誌  77-  (9)  677  -681  2003/09/20  [Not refereed][Not invited]
  • NISHIURA Hiroshi, TSUNODA Takafumi, AKAO Nobuaki  感染症学雑誌 : 日本伝染病学会機関誌 : the journal of the Japanese Association for Infectious Diseases  77-  (9)  677  -681  2003/09/20  [Not refereed][Not invited]
  • NISHIURA Hiroshi  Kekkaku(Tuberculosis)  78-  (6)  419  -426  2003/06/15  [Not refereed][Not invited]
     
    We investigated selected socioeconomic variables for incidence of tuberculosis and its rate of changes that might be relevant for the design of appropriate prevention and control programs. Retrospective ecological analysis was done to examine the association between eight socioeconomic measures from the 1992 census and both the average rate and the rate of change of standardized annual notification rates for tuberculosis from 1988 to 1997 for each of the 23 wards in Tokyo. Multivariate analysis identified the proportion of households with livelihood aid (p<0.001), number of public bath per ...
  • 今井博久, 西浦博, 中尾裕之, 月野浩昌, 黒田嘉紀, 加藤貴彦  日本農村医学会雑誌  51-  (6)  945  -946  2003/03/30  [Not refereed][Not invited]
  • 西浦博, 金子明, 美田敏宏  地域環境保健福祉研究  6-  (2)  1  -6  2003  [Not refereed][Not invited]
  • NISIURA Hiroshi, IMAI Hirohisa, NAKAO Hiroyuki, TSUKINO Hiromasa, KURODA Yoshiki, KATOH Takahiko  Japanese journal of public health  49-  (11)  1135  -1141  2002/11/15  [Not refereed][Not invited]
  • H Nishiura, H Imai, H Nakao, H Tsukino, MA Changazi, GA Hussain, Y Kuroda, T Katoh  ACTA TROPICA  83-  (3)  223  -231  2002/09  [Not refereed][Not invited]
     
    The prevalence and intensity of Ascaris lumbricoides in 492 children from five rural villages in the Northern Area of Pakistan was examined. The overall prevalence of A. lumbricoides was 91% (95%CI 88.6-93.6) with geometric mean (GM) egg count intensities of 3985 eggs per g (epg). The most intense A. lumbricoides infections were found in children aged 5-8 years. We also investigated selected socio-cultural and behavioral variables for A. lumbricoides infections that might be relevant for the design of appropriate prevention and control programs. Univariate analysis associated A. lumbricoides intensity with age (P = 0.004), location of household (P < 0.01), defecation practices (P = 0.02), soil eating habit (P < 0.01), hand washing after defecation (P < 0.01), and living with children under 5 years old (P = 0.02). Multivariate analysis identified the children's age 5-8 (P < 0.01), location of household in Surngo, Askole, and Stakchun where the pilot health care model activities were not done (P < 0.01), and living with children under 5 years old (P = 0.03) as variables statistically associated with the intensity of A. lumbricoides. The results indicated that there were certain clear risk factors in A. lumbricoides transmission, and that its intensity was influenced by age-related behavioral and environmental factors that contribute to exposure. (C) 2002 Elsevier Science B.V. All rights reserved.
  • 西浦博, 田村真希, 黒石恒  食の科学  (292)  33  -37  2002/06  [Not refereed][Not invited]
  • 西浦博, 今井博久, 中尾裕之, 月野浩昌, 黒田嘉紀, 加藤貴彦  九州農村医学会雑誌  (11)  4  -12  2002/03/31  [Not refereed][Not invited]
  • 西浦博, 今井博久  食の科学  (289)  52  -58  2002/03  [Not refereed][Not invited]
  • 西浦博, 今井博久  食の科学  (289)  52  -58  2002/03  [Not refereed][Not invited]

Awards & Honors

  • 2014/02 FOUNDATION TOKYO KENBIKYO-IN TOOYAMA PRIZE FOR HELAHT AND PREVENTIVE MEDICINE
     
    受賞者: Hiroshi Nishiura
  • 2011/12 Takemi Memorial Trust for Life Science Research 21st (2011) Takemi Award for Young Scientist
     
    受賞者: Hiroshi Nishiura
  • 2008/12 Hakujikai Foundation Institute of Gerontology Award for Research Article
     
    受賞者: Hiroshi Nishiura
  • 2007 第24回(平成19年度)井上研究奨励賞
  • 2007 日本数理生物学会研究奨励賞
  • 2007 JSMB Young Scholar Award, 2007 (JSMB; Japanese Society for Mathematical Biology)
  • 2006 統計関連学会連合大会優秀報告賞
  • 2006 Award for Reports in the 2006 Japanese Joint Statistical Meeting

Research Grants & Projects

  • 歴史統計を活用した非特異的感染症対策の予防効果推定
    JST戦略的創造研究推進制度(個人研究型) (個人研究推進事業:さきがけ研究21‐PRESTO)
    Date (from‐to) : 2009 -2013 
    これまでに見られたことのない新たな感染症の流行拡大を防ぐためには、検疫や隔離、接触者を追跡する疫学的調査などといった非特異的な(非医学的な)公衆衛生対策を駆使することが求められる。本研究は、過去の膨大な感染症流行の統計資料を利用して、個々の非特異的対策の有効性を定量的に明らかにする。予防効果の統計学的推定だけに留まらず、推定作業や流行予測のために必要な観察データの種類と特性を明らかにする。
  • Statistical modelling of infectious diseases and their non-pharmaceutical interventions using existing informative data
    JST Basic Research Programs (Precursory Research for Embryonic Science and Technology :PRESTO)
    Date (from‐to) : 2009 -2013 
    When an novel infectious disease emerges, the world does not have specific (medical) countermeasures against it, and thus, non-pharmaceutical interventions, e.g. quarantine, isolation and contact tracing, are called for. The present research project quantifies the efficacy and effectiveness of non-pharmaceutical interventions by means of statistical modelling. Existing informative data, especially historical materials, are effectively utilized. The study will not only estimate preventive performance of those interventions, but also clarify the details and characteristics of epidemiological observations which permit us to implement statistical estimation and short-term prediction.
  • Quantitative modeling of infectious disease epidemics
    Date (from‐to) : 2007 -2012
  • 文部科学省:科学研究費補助金(基盤研究(C))
    Date (from‐to) : 2007 -2008 
    地域社会を対象に感染症対策の実験を行うと莫大な時間・費用を要するばかりではなく、失敗は倫理的に許されないという大きな制限が発生する。そのため、この代替手段として、コンピュータの中に地域社会を再現して、そのなかで感染症対策実験を行うシミュレータの開発を目的とした。本研究におけるシミュレータは、地域社会における感染症流行を忠実に再現するレベルまでに達しておらず、シミュレータ開発は継続中である。
  • 非線形モデルを利用することによる、感染症流行を決定する主要パラメータの推定
    その他の研究制度
    Date (from‐to) : 2006 -2008 
    ヒトの生活に脅威となる感染症について、最も重要な情報をデータから抽出する作業を実施する。
  • 文部科学省:科学研究費補助金(若手研究(スタートアップ))
    Date (from‐to) : 2006 -2007 
    ヒトの行動がどのように感染症流行に影響を与えるかについて、現存するデータを系統的に収集し、数理モデル及び統計モデルを利用して分析した。有用な天然痘及び肺ペストのデータについては、昨年より個別データベース構築を継続した。 論文報告をした特定研究成果として、まず潜伏期間を利用した統計モデルが挙げられる。発症時刻に基づいて伝播能力や感染時刻を推定する理論疫学研究を報告した。同研究手法の発展によって、通常は発症時刻しか記録されていない観察データを分析しやすい感染時刻データに変換する方法を提案した。また、最近データ採集が実施されたブタE型肝炎の血清調査結果を対象にして、本研究計画で提案した感染力推定モデルの応用事例を報告した。感染力が高く、流行がまん延している感染症について、どのように集団レベルでの感染力を推定できるかについて、データ特性に対応した手法を提案した。 インフルエンザの研究成果としては、プルシア(ドイツ)における1918年の流行データを数理モデルを用いて分析し、論文報告した。流行時刻によってインフルエンザ伝播が変化する様を検討する単純化モデルを構築し、流行途中にヒト行動がどのように変化したのかを客観的に分析・解釈する方法を提案した。スペイン風邪流行途中ではヒトの接触回避行動が伝播動態に大きく影響した可能性が高く、パンデミックインフルエンザ発生時には適切なヒトの危険回避行動が...

Educational Activities

Teaching Experience

  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • Biomedical Informatics
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 遺伝子情報、 医療情報、 バイオイバンク、 数理解析、 統計解析
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • Advanced Environmental Health Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Advanced Biostatistics
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Inter-Graduate School Classes(Educational Program):Health, Society and Environment
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
  • 基盤医学研究Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Inter-Graduate School Classes(Educational Program):Health, Society and Environment
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : 産業保健、産業医学、労働衛生
  • 基盤医学研究Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Inter-Graduate School Classes(Educational Program):Health, Society and Environment
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : 人口学、人口転換、少子高齢化、疫学転換
  • 社会医学研究Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Inter-Graduate School Classes(Educational Program):Health, Society and Environment
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : 保健医療政策、医療保険、医療経済、政策評価
  • 社会医学研究Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Advanced Environmental Health Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 産業保健、産業医学、労働衛生
  • 医学総論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Advanced Health Services Administration
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 人口学、人口転換、少子高齢化、疫学転換
  • 研究発表技法Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • Basic Environmental Health Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 環境医学、毒性学、化学物質
  • 研究発表技法Ⅱ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • Basic Health Services Administration
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 保健医療政策、医療保険、医療経済、政策評価
  • Master's Thesis Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 社会医学、研究発表、論文発表
  • Basic Principles of Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 衛生学、環境保健学、環境リスクアセスメント、疫学、社会医学
  • Master's Thesis Research in Public Health
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 社会医学、研究発表、学会発表、論文発表、系統的レビュー発表
  • Inter-Graduate School Classes(Educational Program):Health, Society and Environment
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : 環境医学、毒性学、化学物質
  • Inter-Graduate School Classes(General Subject):Natural and Applied Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
  • Advanced Health Services Administration
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 衛生学、環境保健学、環境リスクアセスメント、疫学、社会医学
  • Dissertation Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 社会医学、研究発表、論文発表
  • Dissertation Research in Social Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 社会医学、研究発表、学会発表、系統的レビュー発表
  • Hygiene & Public Health Practice
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
  • Hygiene & Environmental Biology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 衛生学、環境医学、感染症、毒性学、化学物質、産業保健、労働衛生

Campus Position History

  • 2017年4月1日 
    Present 
    教育改革室室員

Position History

  • 2017年4月1日 
    Present 
    教育改革室室員


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