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      Age Distribution of Influenza Like Illness Cases during Post-Pandemic A(H3N2): Comparison with the Twelve Previous Seasons, in France

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          Abstract

          In France, the 2011–2012 influenza epidemic was characterized by the circulation of antigenically drifted influenza A(H3N2) viruses and by an increased disease severity and mortality among the elderly, with respect to the A(H1N1)pdm09 pandemic and post-pandemic outbreaks. Whether the epidemiology of influenza in France differed between the 2011–2012 epidemic and the previous outbreaks is unclear. Here, we analyse the age distribution of influenza like illness (ILI) cases attended in general practice during the 2011–2012 epidemic, and compare it with that of the twelve previous epidemic seasons. Influenza like illness data were obtained through a nationwide surveillance system based on sentinel general practitioners. Vaccine effectiveness was also estimated. The estimated number of ILI cases attended in general practice during the 2011–2012 was lower than that of the past twelve epidemics. The age distribution was characteristic of previous A(H3N2)-dominated outbreaks: school-age children were relatively spared compared to epidemics (co-)dominated by A(H1N1) and/or B viruses (including the 2009 pandemic and post-pandemic outbreaks), while the proportion of adults over 30 year-old was higher. The estimated vaccine effectiveness (54%, 95% CI (48, 60)) was in the lower range for A(H3N2) epidemics. In conclusion, the age distribution of ILI cases attended in general practice seems to be not different between the A(H3N2) pre-pandemic and post-pandemic epidemics. Future researches including a more important number of ILI epidemics and confirmed virological data of influenza and other respiratory pathogens are necessary to confirm these results.

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          Most cited references29

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          Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.

          A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups. Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults. Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies. 2009 Massachusetts Medical Society
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            Ecological and immunological determinants of influenza evolution.

            In pandemic and epidemic forms, influenza causes substantial, sometimes catastrophic, morbidity and mortality. Intense selection from the host immune system drives antigenic change in influenza A and B, resulting in continuous replacement of circulating strains with new variants able to re-infect hosts immune to earlier types. This 'antigenic drift' often requires a new vaccine to be formulated before each annual epidemic. However, given the high transmissibility and mutation rate of influenza, the constancy of genetic diversity within lineages over time is paradoxical. Another enigma is the replacement of existing strains during a global pandemic caused by 'antigenic shift'--the introduction of a new avian influenza A subtype into the human population. Here we explore ecological and immunological factors underlying these patterns using a mathematical model capturing both realistic epidemiological dynamics and viral evolution at the sequence level. By matching model output to phylogenetic patterns seen in sequence data collected through global surveillance, we find that short-lived strain-transcending immunity is essential to restrict viral diversity in the host population and thus to explain key aspects of drift and shift dynamics.
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              Mortality benefits of influenza vaccination in elderly people: an ongoing controversy.

              Influenza vaccination policy in most high-income countries attempts to reduce the mortality burden of influenza by targeting people aged at least 65 years for vaccination. However, the effectiveness of this strategy is under debate. Although placebo-controlled randomised trials show influenza vaccine is effective in younger adults, few trials have included elderly people, and especially those aged at least 70 years, the age-group that accounts for three-quarters of all influenza-related deaths. Recent excess mortality studies were unable to confirm a decline in influenza-related mortality since 1980, even as vaccination coverage increased from 15% to 65%. Paradoxically, whereas those studies attribute about 5% of all winter deaths to influenza, many cohort studies report a 50% reduction in the total risk of death in winter--a benefit ten times greater than the estimated influenza mortality burden. New studies, however, have shown substantial unadjusted selection bias in previous cohort studies. We propose an analytical framework for detecting such residual bias. We conclude that frailty selection bias and use of non-specific endpoints such as all-cause mortality have led cohort studies to greatly exaggerate vaccine benefits. The remaining evidence base is currently insufficient to indicate the magnitude of the mortality benefit, if any, that elderly people derive from the vaccination programme.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                5 June 2013
                : 8
                : 6
                : e65919
                Affiliations
                [1 ]INSERM, U 707, F-75012, Paris, France
                [2 ]UPMC Univ Paris 06, UMR-S U707, F-75012, Paris, France
                [3 ]INSERM, U 738, F-75018, Paris, France
                [4 ]Université Paris Diderot, UMR-S 738, F-75018, Paris, France
                [5 ]Université Versailles Saint Quentin en Yvelines, Versailles, France
                [6 ]Assistance Publique Hôpitaux de Paris, Paris, France
                [7 ]Service de Médecine Interne, Hôpital Ambroise Paré, Boulogne-Billancourt, France
                [8 ]Laboratoire de Virologie, Université de Corse, Corte, France
                National Institutes of Health, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CT CP AF TB. Performed the experiments: CT CS CP AF. Analyzed the data: CT CS CP AF. Wrote the paper: CT CS CP TH MS TB AF.

                Article
                PONE-D-13-04220
                10.1371/journal.pone.0065919
                3673950
                23755294
                891a3d3b-0d13-439f-ab38-f3a9d562a978
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 January 2013
                : 30 April 2013
                Page count
                Pages: 9
                Funding
                The study was funded by National Institute for Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Clinical Immunology
                Immunity
                Vaccination
                Vaccines
                Clinical Research Design
                Epidemiology
                Epidemiology
                Clinical Epidemiology
                Infectious Disease Epidemiology
                Infectious Diseases
                Viral Diseases
                Influenza
                Non-Clinical Medicine
                Health Care Policy
                Health Statistics
                Health Informatics
                Public Health

                Uncategorized
                Uncategorized

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