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      Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009

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          Abstract

          Background

          To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season.

          Methodology/Principal Findings

          A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20–59 years) and 73.3% in the elderly (≥60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive.

          Conclusions

          Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.

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          Most cited references45

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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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            The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses.

            The intranasal inoculation of volunteers with living partially attenuated strains of influenza A and B viruses offers a new opportunity to determine the protective effect of serum haemagglutin-inhibiting antibody against a strictly homologous virus, under conditions where the time and dosage of the infective challenge can be controlled, the scoring of proven infections can be more precise and higher rates of infection can be achieved than in most natural epidemics.In 1032 adult volunteers, whose serum HI antibody titre was determined immediately before virus challenge, there was a consistent inverse quantitative relationship between the HI titre and the likelihood of infection. The PD 50 (50% protective dose) of HI antibody was 1/18-1/36, but an unusual finding was that volunteers with no detectable pre-challenge antibody often seem to be less susceptible to infection than those with pre-challenge antibody in low titre.In one group of volunteers challenged with an influenza B strain there was no evidence that pre-challenge antibody titres against viral neuraminidase had any significant protective effect against challenge infection.
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              Comparative epidemiology of pandemic and seasonal influenza A in households.

              There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and cocirculating seasonal influenza A viruses in community settings. We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses. Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for the pandemic influenza virus (8%; 95% confidence interval [CI], 3 to 14) and seasonal influenza viruses (9%; 95% CI, 5 to 15). The patterns of viral shedding and the course of illness among index patients were also similar for the pandemic and seasonal influenza viruses. In a subgroup of patients for whom baseline and convalescent serum samples were available, 36% of household contacts who had serologic evidence of pandemic influenza virus infection did not shed detectable virus or report illness. Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting. Copyright 2010 Massachusetts Medical Society.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                29 September 2011
                : 6
                : 9
                : e25738
                Affiliations
                [1 ]GIS CRVOI, Centre de Recherche et de Veille sur les Maladies Emergentes dans l'Océan Indien, Saint-Denis, La Réunion
                [2 ]Institut de Recherche pour le Développement (IRD), Marseille, France
                [3 ]Centre d'Investigation Clinique-Epidémiologie Clinique (CIC-EC) de La Réunion (INSERM/CHR/Université/URMLR), Centre Hospitalier Régional, Saint-Pierre, La Réunion
                [4 ]Ecologie Microbienne (UMR 5557) CNRS-Université de Lyon, Lyon, France
                [5 ]Unité des Virus Emergents (UMR-S 190), IRD-Université de la Méditerranée, Marseille, France
                [6 ]Epidémiologie des Maladies Infectieuses et Modélisation (UMR-S 707), INSERM-Université Pierre et Marie Curie, Paris, France
                [7 ]Chaire mixte CNRS INEE-Université de La Réunion, Saint Denis, La Réunion
                [8 ]Département de Microbiologie, Centre Hospitalier Régional, Saint Denis, La Réunion
                [9 ]Cellule Interrégionale d'Epidémiologie (CIRE) Réunion-Mayotte (InVS), Saint-Denis, La Réunion
                [10 ]Ecole des Hautes Etudes en Santé Publique, EHESP, Rennes-Sorbonne Paris Cité, Paris, France
                Statens Serum Institute, Denmark
                Author notes

                Conceived and designed the experiments: FC A. Flahault XdL FF KD. Performed the experiments: FF ST HP NS. Analyzed the data: KD FF A. Fianu A. Flahault FC XdL OR VG ST HP NL. Wrote the paper: KD. Reviewed/edited the manuscript: FF A. Flahault FC XdL A. Fianu OR VG PG LF MCJB PT NL. Selected the samples: A. Fianu. Coordinated the recruitment of the cohort: NN. Data management and quality control: KB.

                ¶ These authors also contributed equally to this work.

                Article
                PONE-D-11-01569
                10.1371/journal.pone.0025738
                3183080
                21980532
                c46f6c03-1632-43f8-9e6c-3636cb5aecc9
                Dellagi et al. 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
                : 18 January 2011
                : 11 September 2011
                Page count
                Pages: 10
                Categories
                Research Article
                Medicine
                Clinical Research Design
                Clinical Trials
                Cohort Studies
                Epidemiology
                Survey Research
                Epidemiology
                Clinical Epidemiology
                Infectious Disease Epidemiology
                Infectious Diseases
                Viral Diseases
                Influenza

                Uncategorized
                Uncategorized

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