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      The Spectrum of Influenza in Children

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          Abstract

          Background

          Children constitute an important component of the influenza burden and community transmission, but the frequency of asymptomatic infection and post-influenza sequelae at the community level is poorly understood.

          Methods

          Two community-based prospective cohort studies (2011–2020, 2017–2020) and 1 case-ascertained study (2012–2017) were conducted in Managua, Nicaragua. Non-immunocompromised children aged 0–14 years with ≥1 influenza infections, determined by polymerase chain reaction and hemagglutination inhibition assay, were included.

          Results

          A total of 1272 influenza infections occurred in the household-based portion of the study. Influenza infection was asymptomatic in 84 (6.6%) infections, and the asymptomatic fraction increased with age (1.7%, 3.5%, and 9.1% for ages 0–1, 2–4, and 5–14, respectively; P < .001). Of asymptomatic children, 43 (51.2%) shed virus, compared to 1099 (92.5%) symptomatic children ( P < .001). Also, 2140 cases of influenza occurred in the primary care portion of the study. Sequelae of influenza were rare, with the most common being pneumonia (52, 2.4%) and acute otitis media (71, 3.3%). A/H1N1 had higher age-adjusted odds of acute otitis media (odds ratio [OR] 1.99, 95% confidence interval [CI]: 1.14–3.48; P = .015) and hospitalization (OR 3.73, 95% CI: 1.68–8.67; P = .002) than A/H3N2. B/Victoria had higher age-adjusted odds of pneumonia (OR 10.99, 95% CI: 1.34–90.28; P = .026) than B/Yamagata.

          Conclusions

          Asymptomatic influenza infection is much less common in children than adults, although viral shedding still occurs in asymptomatic children. Post-influenza sequelae are rare in children in the community setting, and virus strain may be important in understanding the risk of sequelae.

          Abstract

          The full clinical spectrum of influenza in children, including frequency of asymptomatic infection and sequelae, is poorly understood. We found that asymptomatic infection in children is rare and age-dependent, and that the risk of sequelae depends on virus strain.

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          Most cited references34

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          Adaptive linear step-up procedures that control the false discovery rate

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            Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis.

            The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. WHO; Bill & Melinda Gates Foundation. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Estimating household and community transmission parameters for influenza.

              A maximum likelihood procedure is given for estimating household and community transmission parameters from observed influenza infection data. The estimator for the household transmission probability is an improvement over the classical secondary attack rate calculations because it factors out community-acquired infections from true secondary infections. The mathematical model used does not require the specification of infection onset times and, therefore, can be used with serologic data which detect asymptomatic infections. Infection data were derived by serology and virus isolation from the Tecumseh Respiratory Illness Study and the Seattle Flu Study for the years 1975-1979. Included were seasons of influenza B and influenza A subtypes H1N1 and H3N2. The transmission characteristics of influenza B and influenza A(H3N2) and A(H1N1) outbreaks during this period are compared. Influenza A(H1N1), A(H3N2) and influenza B are found to be in descending order both in terms of ease of spread in the household and intensity of the epidemic in the community. Children are found to be the main introducers of influenza into households. the degree of estimation error from the misclassification of infected and susceptible individuals is illustrated with a stochastic simulation model. This model simulates the expected number of detected infections at different levels of sensitivity and specificity for the serologic tests used. Other sources of estimation error, such as deviation from the model assumption of uniform community exposure and the possible presence of superspreaders, are also discussed.
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                Author and article information

                Contributors
                Journal
                Clin Infect Dis
                Clin Infect Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                01 February 2023
                07 September 2022
                07 September 2022
                : 76
                : 3
                : e1012-e1020
                Affiliations
                Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor, Michigan, USA
                Sustainable Sciences Institute , Managua, Nicaragua
                Centro de Salud Sócrates Flores Vivas, Ministry of Health , Managua, Nicaragua
                Sustainable Sciences Institute , Managua, Nicaragua
                Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health , Managua, Nicaragua
                Sustainable Sciences Institute , Managua, Nicaragua
                Sustainable Sciences Institute , Managua, Nicaragua
                Sustainable Sciences Institute , Managua, Nicaragua
                Centro de Salud Sócrates Flores Vivas, Ministry of Health , Managua, Nicaragua
                Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor, Michigan, USA
                Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor, Michigan, USA
                Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor, Michigan, USA
                Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor, Michigan, USA
                Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor, Michigan, USA
                Sustainable Sciences Institute , Managua, Nicaragua
                Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health , Managua, Nicaragua
                Department of Epidemiology, School of Public Health, University of Michigan , Ann Arbor, Michigan, USA
                Author notes
                Correspondence: A. Gordon, 5622 SPH I, Department of Epidemology, School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA ( gordonal@ 123456umich.edu ).

                Potential conflicts of interest. A. G. serves on a scientific advisory board for Janssen Pharmaceuticals and has consulted for Gilead Sciences. G. H. reports support for attending meeting and/or travel from NIAID contract number HHSN272201400006. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

                Author information
                https://orcid.org/0000-0002-9352-7877
                Article
                ciac734
                10.1093/cid/ciac734
                9907523
                36069178
                68793bce-de0e-426b-8b5d-0ac9be7c1890
                © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 29 June 2022
                : 30 August 2022
                : 26 September 2022
                Page count
                Pages: 9
                Funding
                Funded by: National Institute for Allergy;
                Award ID: U01 AI088654
                Award ID: R01 AI120997
                Award ID: U01 AI144616
                Funded by: National Institutes of Health, doi 10.13039/100000002;
                Award ID: T32GM007863
                Categories
                Major Article
                Original Article
                AcademicSubjects/MED00290

                Infectious disease & Microbiology
                influenza,pediatrics,clinical presentation,asymptomatic influenza,global health

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