Elsevier

The Lancet

Volume 375, Issue 9720, 27 March–2 April 2010, Pages 1100-1108
The Lancet

Articles
Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study

https://doi.org/10.1016/S0140-6736(09)62126-7Get rights and content

Summary

Background

Knowledge of the age-specific prevalence of immunity from, and incidence of infection with, 2009 pandemic influenza A H1N1 virus is essential for modelling the future burden of disease and the effectiveness of interventions such as vaccination.

Methods

In this cross-sectional serological survey, we obtained 1403 serum samples taken in 2008 (before the first wave of H1N1 infection) and 1954 serum samples taken in August and September, 2009 (after the first wave of infection) as part of the annual collection for the Health Protection Agency seroepidemiology programme from patients accessing health care in England. Antibody titres were measured by use of haemagglutination inhibition and microneutralisation assays. We calculated the proportion of samples with antibodies to pandemic H1N1 virus in 2008 by age group and compared the proportion of samples with haemagglutination inhibition titre 1:32 or more (deemed a protective response) before the first wave of infection with the proportion after the first wave.

Findings

In the baseline serum samples from 2008, haemagglutination inhibition and microneutralisation antibody titres increased significantly with age (F test p<0·0001). The proportion of samples with haemagglutination inhibition titre 1:32 or more ranged from 1·8% (three of 171; 95% CI 0·6–5·0) in children aged 0–4 years to 31·3% (52 of 166; 24·8–38·7) in adults aged 80 years or older. In London and the West Midlands, the difference in the proportion of samples with haemagglutination inhibition titre equal to or above 1:32 between baseline and September, 2009, was 21·3% (95% CI 8·8–40·3) for children younger than 5 years of age, 42·0% (26·3–58·2) for 5–14-year-olds, and 20·6% (1·6–42·4) for 15–24-year-olds, with no difference between baseline and September in older age groups. In other regions, only children younger than 15 years showed a significant increase from baseline (6·3%, 1·8–12·9).

Interpretation

Around one child in every three was infected with 2009 pandemic H1N1 in the first wave of infection in regions with a high incidence, ten times more than estimated from clinical surveillance. Pre-existing antibody in older age groups protects against infection. Children have an important role in transmission of influenza and would be a key target group for vaccination both for their protection and for the protection of others through herd immunity.

Funding

National Institute for Health Research Health Technology Assessment Programme.

Introduction

On June 11, 2009, WHO declared that the rapidly spreading swine-origin influenza A H1N1 influenza virus constituted a global pandemic. Many countries have made detailed plans to mitigate the clinical and societal effects of the pandemic. A key component of the UK's pandemic influenza plan was the construction of real-time disease transmission models. These models would allow the likely effect of the pandemic on health-care resources and the effect of interventions such as school closure and vaccination to be predicted sufficiently rapidly to inform national policy.

Construction of disease transmission models requires an understanding of the epidemiology of the pandemic virus, in particular its potential for spread in the population. Knowledge of baseline age-specific immunity in the population and how this is changing as the pandemic progresses is essential for defining model parameters. Without a direct serological measure, the immunity profile must be estimated from clinical attack rates, adjusted for age-specific differences in the likelihood of exposure that result from different contact patterns within and between age groups.1 Reliance on routine data sources to estimate age-specific attack rates during an emerging pandemic is hampered by changes in the sensitivity and specificity of clinical surveillance schemes that arise throughout the epidemic, especially when public awareness of the risk of influenza is intensified and consultation with health-care practitioners is increased. Another limitation of clinical surveillance is that it is based on individuals presenting with influenza-like illness and therefore does not capture asymptomatic or mild infections. Without a direct measure of the baseline age-specific immunity profile of the population and the changes that result from 2009 H1N1 infection as the pandemic progresses, predictions about future disease incidence are necessarily subject to substantial uncertainty.

We report the results of a large seroepidemiological survey in England to document the age-specific prevalence of neutralising antibodies2 to 2009 pandemic H1N1 virus before and after the first wave of the pandemic to provide a direct measure of the incidence of infection in the population. These direct incidence estimates are compared with those derived from clinical surveillance and modelling to provide a novel insight into the epidemiology and clinical expression of 2009 pandemic H1N1 infection.

Section snippets

Source of samples

To establish the baseline prevalence of antibodies to 2009 pandemic H1N1 virus, we used serum samples taken in 2008 from individuals aged less than 1 year to 87 years in eight of the nine regions in England as part of the annual collection for the Health Protection Agency (HPA) seroepidemiology programme.3 The samples were obtained by the HPA Seroepidemiology Unit (SEU) at the HPA Manchester Regional Microbiology Unit (Manchester, UK) and were residual samples from sera submitted to 16

Results

1403 serum samples taken in 2008 or in the first 4 months of 2009 (n=13) in eight regions in England were selected to establish the baseline prevalence of antibodies to 2009 pandemic H1N1 virus. Similar numbers of samples were tested in each of the following age groups: 0–4, 5–15, 15–24, 25–49, 50–64, 65–74, 75–79, and ≥80 years. Data for age and region were available for all samples; of the 1400 samples with data for sex, 704 (50·3%) were from women. All 1403 samples were tested by

Discussion

This large serological survey in England before and after the first wave of 2009 pandemic influenza A H1N1 infection highlights the value of serological data as an addition to clinical surveillance. We showed that a substantial proportion of older adults had pre-existing immunity to 2009 pandemic H1N1 virus, presumably as a result of previous exposure to antigenically related H1N1 influenza viruses circulating in earlier decades or a lifetime of exposure to influenza A, which has resulted in

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