Title Epidemiological characteristics of 2009 ( H 1 N 1 ) pandemic influenza based on paired sera from a longitudinal community cohort study

Background: While patterns of incidence of clinical influenza have been well described, much uncertainty remains over patterns of incidence of infection. The 2009 pandemic provided both the motivation and opportunity to investigate patterns of mild and asymptomatic infection using serological techniques. However, to date, only broad epidemiological patterns have been defined, based on largely cross-sectional study designs with convenience sampling frameworks. Methods and Findings: We conducted a paired serological survey of a cohort of households in Hong Kong, recruited using random digit dialing, and gathered data on severe confirmed cases from the public hospital system (.90% inpatient days). Paired sera were obtained from 770 individuals, aged 3 to 103, along with detailed individual-level and household-level risk factors for infection. Also, we extrapolated beyond the period of our study using time series of severe cases and we simulated alternate study designs using epidemiological parameters obtained from our data. Rates of infection during the period of our study decreased substantially with age: for 3–19 years, the attack rate was 39% (31%–49%); 20–39 years, 8.9% (5.3%–14.7%); 40–59 years, 5.3% (3.5%–8.0%); and 60 years or older, 0.77% (0.18%–4.2%). We estimated parameters for a parsimonious model of infection in which a linear age term and the presence of a child in the household were used to predict the log odds of infection. Patterns of symptom reporting suggested that children experienced symptoms more often than adults. The overall rate of confirmed pandemic (H1N1) 2009 influenza (H1N1pdm) deaths was 7.6 (6.2–9.5) per 100,000 infections. However, there was substantial and progressive increase in deaths per 100,000 infections with increasing age from 0.66 (0.65–0.86) for 3–19 years up to 220 (50–4,000) for 60 years and older. Extrapolating beyond the period of our study using rates of severe disease, we estimated that 56% (43%–69%) of 3–19 year olds and 16% (13%–18%) of people overall were infected by the pandemic strain up to the end of January 2010. Using simulation, we found that, during 2009, larger cohorts with shorter follow-up times could have rapidly provided similar data to those presented here. Conclusions: Should H1N1pdm evolve to be more infectious in older adults, average rates of severe disease per infection could be higher in future waves: measuring such changes in severity requires studies similar to that described here. The benefit of effective vaccination against H1N1pdm infection is likely to be substantial for older individuals. Revised pandemic influenza preparedness plans should include prospective serological cohort studies. Many individuals, of all ages, remained susceptible to H1N1pdm after the main 2009 wave in Hong Kong. Please see later in the article for the Editors’ Summary. Citation: Riley S, Kwok KO, Wu KM, Ning DY, Cowling BJ, et al. (2011) Epidemiological Characteristics of 2009 (H1N1) Pandemic Influenza Based on Paired Sera from a Longitudinal Community Cohort Study. PLoS Med 8(6): e1000442. doi:10.1371/journal.pmed. 1000442 Academic Editor: Lone Simonsen, George Washington University, United States of America Received August 25, 2010; Accepted May 10, 2011; Published June 21, 2011 Copyright: 2011 Riley 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. Funding: This project was supported by: the Research Fund for the Control of Infectious Disease, Food and Health Bureau, Government of the Hong Kong SAR (PHE-21); the RAPIDD program from Fogarty International Centre with the Science & Technology Directorate, Department of Homeland Security; R01 TW00824601 from Fogarty International Centre; the Area of Excellence Scheme of the Hong Kong University Grants Committee (AoE/M-12/06); US National Institutes of Health Models of Infectious Disease Agent Study program; and a Wellcome Trust University Award 093488/Z/10/Z. The funding bodies had no role in study design, data collection and analysis, preparation of the manuscript, or the decision to publish. Competing Interests: BJC has received research funding from MedImmune Inc., a manufacturer of influenza vaccines. JSMP declares research support from GlaxoSmithKline, Baxter, Cruxell, Combinatorix, and DIVA Solutions. No other conflicts were declared. Dr J.S Malik Peiris is a PLoS Medicine Editorial Board Member. Abbreviations: AIC, Akaike Information Criterion; H1N1pdm, H1N1 pandemic influenza; ICU, intensive care unit; ILI, influenza-like illness. * E-mail: s.riley@imperial.ac. uk PLoS Medicine | www.plosmedicine. org 1 June 2011 | Volume 8 | Issue 6 | e1000442