Characteristics of Mild Dengue Virus Infection in Thai Children

In-Kyu Yoon Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Anon Srikiatkhachorn Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Laura Hermann Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Darunee Buddhari Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Thomas W. Scott Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Richard G. Jarman Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Jared Aldstadt Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Ananda Nisalak Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Suwich Thammapalo Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Piraya Bhoomiboonchoo Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Mammen P. Mammen Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Sharone Green Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Robert V. Gibbons Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Timothy P. Endy Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Alan L. Rothman Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Entomology, University of California, Davis, Davis, California; Department of Geography, University at Buffalo, Buffalo, New York; Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, New York; Institute for Immunology and Informatics, University of Rhode Island, Providence, Rhode Island; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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A four-year longitudinal cohort and geographic cluster study in rural Thailand was conducted to characterize the clinical spectrum of dengue virus (DENV) infection. Symptomatic DENV infections in the cohort were detected by active school absence–based surveillance that triggered cluster investigations around ill cohort children. Data from 189 cohort children with symptomatic DENV infection and 126 contact children in the clusters with DENV infection were analyzed. Of infected contacts, only 19% were asymptomatic; 81% were symptomatic, but only 65.9% reported fever. Symptom-based case definitions were unreliable for diagnosis. Symptomatic infections in contacts were milder with lower DENV RNA levels than the cohort. Infections in contacts with fever history were more likely to have detectable DENV RNA than infections without fever history. Mild infections identified by cluster investigations account for a major proportion of all DENV infections. These findings are relevant for disease burden assessments, transmission modeling, and determination of vaccine impact.

Author Notes

* Address correspondence to In-Kyu Yoon, Department of Virology, U.S. Army Materiel Command, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, APO, AP, USA 96546. E-mail: yooni@afrims.org

Financial support: This research was supported, in part, by the National Institutes of Health (grants P01 AI34533 and R01 GM083224), the U.S. Military Infectious Diseases Research Program (grant S0016-04-AF), the Bill and Melinda Gates Foundation Global Health Program (grant OPP52250), and the Canadian Institutes of Health Research Fellowship (Laura Hermann). The funding source had no role in the study design, data collection, analysis and interpretation, manuscript writing, or manuscript submission for publication.

Authors' addresses: In-Kyu Yoon, Department of Virology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mail: yooni@afrims.org. Anon Srikiatkhachorn, University of Massachusetts Medical School, Worcester, MA, E-mail: anons@afrims.org. Laura Hermann, Ananda Nisalak, Piraya Bhoomiboonchoo, and Robert V. Gibbons, Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mails: laura.hermann@afrims.org, anandaN@afrims.org, pirayaB@afrims.org, and robert.gibbons@afrims.org. Darunee Buddhari, Kamphaeng Phet - AFRIMS Virology Research Unit, Muang District, Kamphaeng Phet, Thailand, E-mail: daruneet@afrims.org. Thomas W. Scott, Department of Entomology, University of California, Davis, Davis, CA, E-mail: twscott@ucdavis.edu. Richard G. Jarman, Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, E-mail: richard.g.jarman.mil@mail.mil. Jared Aldstadt, Department of Geography, University at Buffalo, Buffalo, NY, E-mail: geojared@buffalo.edu. Suwich Thammapalo, Bureau of Epidemiology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand, E-mail: sthammapalo@yahoo.com. Mammen P. Mammen, Vical Incorporated, San Diego, CA, E-mail: mammen.mammen@vical.com. Sharone Green, University of Massachusetts Medical School, Worcester, MA, E-mail: Sharone.Green@umassmed.edu. Timothy P. Endy, Department of Infectious Diseases, State University of New York, Syracuse, Syracuse, NY, E-mail: endyt@upstate.edu. Alan L. Rothman, Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, E-mail: alan_rothman@mail.uri.edu.

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