Blood samples taken as part of the UK Health Protection Agency's regular annual monitoring programme show that the proportion of children in high risk areas in England infected with H1N1 influenza during the first pandemic wave was 10 times higher than estimated from clinical surveillance. This new research also suggests that children have an important role in the transmission of influenza and would be a key target group for vaccination. The findings are reported in an Article published Online First (www.thelancet.com) and in an upcoming edition of The Lancet—written by Professor Elizabeth Miller, Health Protection Agency, London, UK, and colleagues.
Estimates of the number of cases during the first wave of the H1N1 pandemic in England were based on clinical surveillance, meaning they rely on people presenting to general practitioners with influenza-like illness. However, these estimates will not capture mild or asymptomatic cases or serious cases in which people have not consulted a doctor. The authors say: "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."
In this study, the authors obtained 1403 serum samples taken in 2008 (baseline-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. They then calculated the proportion of samples that had a level of pandemic H1N1 antibodies high enough to confer immunity in each age group, at baseline and in August and September 2009.
In the baseline samples, the proportion of people with immunity varied from 1.8% in the 0-4 year age group to 31.3% in those aged over 80 years. The authors say: "Individuals born before 1957 might have been exposed to influenza H1 strains circulating in the first half of the 20th century, which are more closely related to current swine-origin 2009 pandemic H1N1 viruses."
The proportions of August and September 2009 samples with immunity showed a significant age and geographical variation. The highest increases were in London and the West Midlands, where infection rates were highest. For 0-4 year olds, the immunity rate increased from 1.8% at baseline to 21.3% in September 2009; for 5-14 year olds, the increase was from 3.7% to 42.0%, and for 15-24 year olds, the increase was from 17.5% to 20.6%. For older age groups, there was no increase in the proportions of samples showing immunity.
Combined results for the other four regions of England (East Midlands, North West, South East, and South West) showed that only children younger than 15 years (0-4 and 5-14 years combined) showed a significant increase in terms of proportions showing immunity. This figure rose by 6.3%, from 2.8% to 9.1%.
The authors say: "Rates of infection with 2009 pandemic H1N1 influenza in the first wave were greatest in children younger than 15 years of age, with an estimated 42% of schoolchildren aged 5 years being infected in high incidence regions. This finding is consistent with the high level of susceptibility in children and the increased potential for transmission that occurs within schools. We also showed substantial differences between regions in the extent of infection during the first wave."
The research team adds that this new blood sample based data reveals that infection rates for London (32% in children under 15 years and 20% for 20-24 year olds) is 10 times higher than the original Health Protection Agency estimates based on clinical surveillance. They say: "This serological study shows the true extent of H1N1 infection in the initial wave of the pandemic in England in 2009. Its findings should be applicable to other countries that have experienced a similar first wave."
Findings from a separate mathematical model carried out by the agency—simulating spread of H1N1 infection—have also predicted a higher number of infections during the first wave than previously estimated based on the slow progression of the second wave of the epidemic after the re-opening of the schools in September 2009. The authors say that this new study suggests that vaccinating all children during the second wave of the pandemic would not have generated herd immunity across the whole population, thus supporting a targeted vaccination programme. The authors say: "This model, together with the serological data, would suggest that by the time vaccine became available in the UK in late October, 2009, the potential for mitigating the overall effect of the second wave by vaccination was limited."
They conclude: "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."
Two Comments accompany the study. In the first, Dr Carrie Reed and Dr Jacqueline M Katz, Centers for Disease Control and Prevention, Atlanta, GA, USA, say: "Continued surveys to assess changes in the population seroprevalence over time will further improve our understanding of the transmission of 2009 pandemic H1N1. Timely and reliable serological information will provide more robust data for the modelling of disease burden and intervention strategies and will be important to inform future prevention policies, including recommendations for vaccination."
The second Comment is by Dr Tom Walley, University of Liverpool, UK, and Dr Peter Davison National Institute for Health Research (NIHR) Evaluation Trials and Studies Coordinating Centre (which funded the study), University of Southampton, UK. They say: "The success of NIHR in this particular case shows how it has transformed clinical research in the NHS, although there is still much to do—in particular, continuing to alter the culture of the NHS such that participation in research is seen as a core role, as envisaged in the NHS constitution, and not an optional extra to be discarded in times of budgetary or other difficulties. The NIHR is achieving its promise of delivering research that matters to patients."
Professor Elizabeth Miller, Health Protection Agency, London, UK. T) +44 (0)20 8327 7080 E) cfipressoffice@hpa.org.uk
Dr Carrie Reed, Centers for Disease Control and Prevention, Atlanta, GA, USA. T) +1 404-639-3286 E) ggj2@cdc.gov
Dr Tom Walley, University of Liverpool, UK. T) +44 (0) 151 794 8123 E) twalley@liv.ac.uk
For Article and both Comments, see: http://press.thelancet.com/h1n1inengland.pdf
Note to editors: *The Health Protection Agency seroepidemiology programme is a long-established collaboration between CfI (Colindale) RMN and HPA Manchester Labs (previously Lancashire Teaching Hospitals NHS Trust). Its basis is a large collection of sera approximating the general population of England and Wales, forming a unique and valuable public health resource. Sera used are residues of specimens submitted for diagnostic microbiological testing and are anonymised (retaining age, sex, date of collection and source laboratory only). Collection is continuing through collaboration with laboratories throughout England and Wales and has occurred annually since 1986, with over 150,000 sera now stored and catalogued. The collection is available to anyone wishing to use it for public health purposes.
The programme uses cross-sectional antibody prevalence studies to help in the understanding of the epidemiology and burden of infectious diseases of public health importance, and how this may be changing. This provides key evidence to assist with making informed decisions regarding health policy where intervention is possible. There is also regular serological surveillance for measles, mumps, and rubella as part of the MMR Surveillance Programme.
The HPA Seroepidemiology Programme often works in collaboration with the HPA Modelling and Economics Unit and the European SeroEpidemiology Network (ESEN) project.
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The Lancet