The Lancet Respiratory Medicine: Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study

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The Lancet Respiratory Medicine, Early Online Publication, 17 March 2014
doi:10.1016/S2213-2600(14)70034-7Cite or Link Using DOI
Copyright ? 2014 Hayward et al. Open Access article distributed under the terms of CC BY Published by Elsevier Ltd. All rights reserved.
Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study
Dr Andrew C Hayward MD a Corresponding AuthorEmail Address, Ellen B Fragaszy MSc a c, Alison Bermingham PhD d, Lili Wang PhD f, Andrew Copas PhD a, W John Edmunds PhD c, Neil Ferguson DPhil h, Nilu Goonetilleke PhD f g, Gabrielle Harvey MPH a, Jana Kovar PhD a, Megan S C Lim PhD a i, Andrew McMichael PhD f, Elizabeth R C Millett MSc a c, Jonathan S Nguyen-Van-Tam DM j, Irwin Nazareth PhD b, Richard Pebody MBChB e, Faiza Tabassum PhD a, John M Watson FRCP e, Fatima B Wurie BSc a, Prof Anne M Johnson MD a ?, Maria Zambon PhD d ?, on behalf of the Flu Watch Group
Summary
Background
Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden.
Methods
Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006?11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable.
Findings
Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16?22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13?34), suggesting most influenza infections are asymptomatic. 25% (18?35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10?26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2.
Interpretation
Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2.
Funding
Medical Research Council and the Wellcome Trust.

http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2814%2970034-7/abstract

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Re: The Lancet Respiratory Medicine: Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study

The Lancet Respiratory Medicine, Early Online Publication, 17 March 2014
doi:10.1016/S2213-2600(14)70053-0Cite or Link Using DOI
Copyright ? 2014 Horby. Open Access article distributed under the terms of CC BY Published by Elsevier Ltd. All rights reserved.
Community studies of influenza: new knowledge, new questions
Peter William Horby aEmail Address
From the 1940s to the early 1980s, a series of prospective, community-based studies provided seminal insights into the epidemiology of common respiratory infections.1 These observational studies consistently showed that influenza is a common cause of respiratory illness in the community, and the findings have been widely used to inform influenza control policies, such as influenza immunisation. In The Lancet Respiratory Medicine, the report of the Flu Watch study by Andrew Hayward and colleagues2 continues in this productive scientific tradition but brings it up to date through the use of molecular diagnostic techniques.
Hayward and colleagues recruited and prospectively studied five successive cohorts of households across England over six periods of influenza transmission between 2006 and 2011. Participants aged 5 years and older provided paired preseason and postseason blood samples for influenza serology and all participating households were contacted weekly to identify any cases of cough, cold, sore throat, or ?flu-like illness?. Any participant reporting such an illness was asked to submit a nasal swab on day 2 of the illness for influenza virus detection by RT-PCR. A particular strength of the Flu Watch study was the analysis of health-care consulting behaviours through linkage with the participant's primary health-care records. The study was therefore able to estimate the incidence of influenza infection, the proportion of influenza infections that were symptomatic, and the proportion of symptomatic infections that resulted in consultation with a primary-care practitioner.
The findings reaffirm earlier reports that there are high rates of serological evidence of influenza infection without corresponding disease. Hayward and colleagues report that roughly 20% of the community shows serological evidence of influenza infection each season, but that most infections (about 75%) are asymptomatic or at least so mild that they are not identified through weekly active surveillance for respiratory illness. Even among individuals with a respiratory illness and PCR-confirmed influenza infection, classical definitions of influenza-like illness have low sensitivity and only 17% of individuals consult a medical practitioner. This low sensitivity shows that surveillance of medically attended illnesses provides a partial and biased picture, and is vulnerable to changes in consulting, testing, or reporting practices. As such, it is clear that reliable estimates of the infection and clinical attack rates during the early stages of an influenza epidemic requires the collection of standardised data across the whole range of disease severity, from the community, primary care, and secondary care.
In view of the undoubtedly high rates of subclinical influenza infection, an important unanswered question is the extent to which mild and asymptomatic influenza infections contribute to transmission. Case-ascertained household transmission studies have shown substantial heterogeneity in the amount and duration of viral shedding and, if the area under the curve of viral shedding is believed to correlate with transmissibility, suggest that 80% of transmission is attributable to 20% of clinically symptomatic cases.3 However, these estimates are not adjusted for differing contact patterns of sick and well individuals.4 What is more, serologically defined infection rates are underestimates, because the widely used four-fold or greater rise in haemagglutination inhibiting (HI) antibody titre between paired serum samples is an overly stringent criterion for defining infection in epidemiological studies5 and a proportion of infected individuals do not produce an appreciable HI antibody response.6 A large number of well individuals mixing widely in the community might, even if only mildly infectious, make a substantial contribution to onward transmission. This might have important implications for the effectiveness of case isolation and social distancing measures in reducing overall transmission rates.
In a global context, the Flu Watch findings are a valuable addition to the data accumulating from contemporary longitudinal community-based influenza studies in other countries. Although there is substantial consistency in serologically defined infection rates per season between settings with very different climates and socioeconomic conditions, the headline figures might obscure important heterogeneities in the timing and intensity of transmission that may affect the feasibility and impact of interventions. For example, in tropical regions the timing of influenza epidemics is less predictable compared with temperate regions, which is problematic for vaccine strain selection and the scheduling of immunisation programmes.7 In regions where several influenza epidemics can occur in a single year, the annual (rather than seasonal) rate of infection might be higher than in regions that experience only one influenza season per year. This might affect the development and maintenance of immunological protection against clinically apparent disease and the strength of immunological selection pressures acting upon the viruses. A direct comparison of data from different cohorts would be an invaluable next step towards a comprehensive understanding of the global epidemiology of influenza.

http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2814%2970053-0/fulltext