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      Identifying pre-outbreak signals of hand, foot and mouth disease based on landscape dynamic network marker

      research-article
      1 , 2 , 3 , 4 , 3 , , 3 ,
      BMC Infectious Diseases
      BioMed Central
      The 18th Asia Pacific Bioinformatics Conference (APBC 2020)
      18-20 August 2020
      Hand, foot and mouth disease (HFMD) outbreaks, Pre-outbreak signals, Critical transition, City network, Landscape dynamic network marker (L-DNM)

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          Abstract

          Background

          The high incidence, seasonal pattern and frequent outbreaks of hand, foot and mouth disease (HFMD) represent a threat for billions of children around the world. Detecting pre-outbreak signals of HFMD facilitates the timely implementation of appropriate control measures. However, real-time prediction of HFMD outbreaks is usually challenging because of its complexity intertwining both biological systems and social systems.

          Results

          By mining the dynamical information from city networks and horizontal high-dimensional data, we developed the landscape dynamic network marker (L-DNM) method to detect pre-outbreak signals prior to the catastrophic transition into HFMD outbreaks. In addition, we set up multi-level early warnings to achieve the purpose of distinguishing the outbreak scale. Specifically, we collected the historical information of clinic visits caused by HFMD infection between years 2009 and 2018 respectively from public records of Tokyo, Hokkaido, and Osaka, Japan. When applied to the city networks we modelled, our method successfully identified pre-outbreak signals in an average 5 weeks ahead of the HFMD outbreak. Moreover, from the performance comparisons with other methods, it is seen that the L-DNM based system performs better when given only the records of clinic visits.

          Conclusions

          The study on the dynamical changes of clinic visits in local district networks reveals the dynamic or landscapes of HFMD spread at the network level. Moreover, the results of this study can be used as quantitative references for disease control during the HFMD outbreak seasons.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12879-020-05709-w.

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          Most cited references29

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          The largest outbreak of hand; foot and mouth disease in Singapore in 2008: the role of enterovirus 71 and coxsackievirus A strains.

          During 2008, Singapore experienced its largest ever outbreak of hand, foot and mouth disease (HFMD), resulting in 29686 cases, including four cases of encephalitis and one fatality. A total of 51 clinical specimens from 43 patients with suspected HFMD at the National University Hospital, Singapore were collected for virus isolation and identification by reverse transcription polymerase chain reaction (RT-PCR) and sequencing. Enteroviruses were identified in 34 samples (66.7%), with 11 samples (21.6%) being positive for enterovirus 71 (EV71). Other non-EV71 enteroviruses (including coxsackievirus A4, A6, A10, and A16) were identified in 23 samples (45.1%). The most prevalent virus serotypes were CA6, CA10, and EV71. CA6 and CA10 accounted for 35.3% of all HFMD cases, which may explain the high transmissibility and low fatality that characterized this unprecedented epidemic associated with relatively mild disease. Phylogenetic analyses of 10 circulating EV71 strains indicated that they belonged to two subgenogroups, i.e., B5 (80%) and C2 (20%). The VP1 sequences of the 2008 EV71 strains also exhibited continuous mutations during the outbreak, reflecting the relatively high mutation rate of the EV71 capsid protein, which may have implications for future vaccine development. A safe and effective vaccine against EV71 is certainly warranted in view of its potential neurovirulence and its role in HFMD epidemics of recurring frequency with resultant fatalities in Asia, as well as other parts of the world. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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            Neurodevelopment and cognition in children after enterovirus 71 infection.

            Enterovirus 71 is a common cause of hand, foot, and mouth disease and encephalitis in Asia and elsewhere. The long-term neurologic and psychiatric effects of this viral infection on the central nervous system (CNS) are not well understood. We conducted long-term follow-up of 142 children after enterovirus 71 infection with CNS involvement - 61 who had aseptic meningitis, 53 who had severe CNS involvement, and 28 who had cardiopulmonary failure after CNS involvement. At a median follow-up of 2.9 years (range, 1.0 to 7.4) after infection, the children received physical and neurologic examinations. We administered the Denver Developmental Screening Test (DDST II) to children 6 years of age or younger and the Wechsler intelligence test to children 4 years of age or older. Nine of the 16 patients with a poliomyelitis-like syndrome (56%) and 1 of the 5 patients with encephalomyelitis (20%) had sequelae involving limb weakness and atrophy. Eighteen of the 28 patients with cardiopulmonary failure after CNS involvement (64%) had limb weakness and atrophy, 17 (61%) required tube feeding, and 16 (57%) required ventilator support. Among patients who underwent DDST II assessment, delayed neurodevelopment was found in only 1 of 20 patients (5%) with severe CNS involvement and in 21 of 28 patients (75%) with cardiopulmonary failure (P<0.001 for the overall comparison). Children with cardiopulmonary failure after CNS involvement scored lower on intelligence tests than did children with CNS involvement alone (P=0.003). Enterovirus 71 infection with CNS involvement and cardiopulmonary failure may be associated with neurologic sequelae, delayed neurodevelopment, and reduced cognitive functioning. Children with CNS involvement without cardiopulmonary failure did well on neurodevelopment tests. (ClinicalTrials.gov number, NCT00172393 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
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              Detecting early-warning signals for sudden deterioration of complex diseases by dynamical network biomarkers

              Considerable evidence suggests that during the progression of complex diseases, the deteriorations are not necessarily smooth but are abrupt, and may cause a critical transition from one state to another at a tipping point. Here, we develop a model-free method to detect early-warning signals of such critical transitions, even with only a small number of samples. Specifically, we theoretically derive an index based on a dynamical network biomarker (DNB) that serves as a general early-warning signal indicating an imminent bifurcation or sudden deterioration before the critical transition occurs. Based on theoretical analyses, we show that predicting a sudden transition from small samples is achievable provided that there are a large number of measurements for each sample, e.g., high-throughput data. We employ microarray data of three diseases to demonstrate the effectiveness of our method. The relevance of DNBs with the diseases was also validated by related experimental data and functional analysis.
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                Author and article information

                Contributors
                201820132541@mail.scut.edu.cn
                rongxie2005@qq.com
                liuzhr@scut.edu.cn
                807376553@qq.com
                scliurui@scut.edu.cn
                chenpei@scut.edu.cn
                Conference
                BMC Infect Dis
                BMC Infect Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                15 January 2021
                15 January 2021
                2021
                : 21
                Issue : Suppl 1 Issue sponsor : Publication of this supplement has not been supported by sponsorship. Information about the source of funding for publication charges can be found in the individual articles. The articles have undergone the journal's standard peer review process for supplements. The Supplement Editors declare that they have no competing interests.
                : 6
                Affiliations
                [1 ]GRID grid.79703.3a, ISNI 0000 0004 1764 3838, School of Computer Science and Engineering, , South China University of Technology, ; Guangzhou, 510006 China
                [2 ]GRID grid.443372.5, ISNI 0000 0001 1922 9516, School of Information, , Guangdong University of Finance and Economics, ; Guangzhou, 510320 China
                [3 ]GRID grid.79703.3a, ISNI 0000 0004 1764 3838, School of Mathematics, , South China University of Technology, ; Guangzhou, 510640 China
                [4 ]Guangdong Science and Technology Infrastructure Center, Guangzhou, 510033 China
                Article
                5709
                10.1186/s12879-020-05709-w
                7809731
                33446118
                4e1e3c52-e261-483a-b930-cd04f2bd5289
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                The 18th Asia Pacific Bioinformatics Conference
                APBC 2020
                Seoul, Korea
                18-20 August 2020
                History
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                Research
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                © The Author(s) 2021

                Infectious disease & Microbiology
                hand, foot and mouth disease (hfmd) outbreaks,pre-outbreak signals,critical transition,city network,landscape dynamic network marker (l-dnm)

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