Estimating age specific cumulative incidence for the 2009 influenza pandemic: a meta-analysis of A(H1N1)pdm09 serological studies from 19 countries.

 Estimating age specific cumulative incidence for the 2009 influenza pandemic: a meta-analysis of A(H1N1)pdm09 serological studies from 19 countries. 

 

This meta-analysis, the first of its kind for the 2009 pandemic, had as its objectives estimating overall and age-specific prevalence of cumulative infection (using cross-reactive antibodies to the A(H1N1)pdm09 virus) during the first year of the pandemic.(1) The work was carried out through a collaboration involving investigators studying published and unpublished studies in multiple countries, and it was led by the Global Influenza Programme of WHO and the UK Medical Research Council Centre for Outbreak Analysis and Modelling at Imperial College, London.

 

The objectives were attained through the collection and analysis of all available original standardised serological data from H1N1pdm seroepidemiological studies. It is the first study of this kind to use original data from multiple countries and since it integrates results from low, middle as well as high income countries, it is able to provide a global perspective. This analysis has the potential to provide accurate assessments of cumulative incidence and hence decrease the uncertainty regarding severity of the 2009 or any other pandemic.

 

Seventy-four analyses were initially identified. After applying pre-set inclusion and exclusion criteria 27 of these were used for the meta-analysis, meaning that around 90 000 serological samples were employed from 19 different countries and/or administrative regions.

Pre-pandemic prevalence of cross reactivity

One of the problems of serological analyses of influenza infection is that there is always some pre-existing cross-reactivity, presumably due to prior infections with influenzas that are antigenically similar to the pandemic strain. Hence it is important to establish pre-pandemic base-lines. For the pre-pandemic prevalence of cross reactive antibodies, serological data from 19 studies in 15 countries were assessed (based on around 15 000 sera), showing an age-adjusted pre-pandemic prevalence of cross reactive H1N1pdm antibodies of 5% (95% CI 3-7%).

This figure increased with age; from around 1% in the zero to four age range, through 4%-5% in the age groups from five to 19 years, 20 to 44 years and 45 to 64 year, and increased abruptly to 14% in the 65 years and older age-group. There was also variation by global distribution where significant differences were noted by region. Sera from people in Asia had a lower prevalence of pre-pandemic cross reactive antibodies compared to European sera (OR= 0.098; 95%CI 0.01-0.9%), while a specific location in the African Region (Reunion Island) had higher prevalence (OR=9.2; 95%CI= 1.9-43.8).

Age specific cumulative incidences

The analyses undertaken to assess the age specific cumulative incidence of pandemic influenza infection used data from 12 studies in 11 countries. The incidence, which differed significantly depending on the age, was based on the difference between pre-pandemic and post-pandemic seroprevalence. This was estimated overall as 24% (95%CI 20-27%); with the lowest 11% (5-18%) among the 65 years and older age-group and the highest, 46% (36-56%) among children ranging between five and 19 years old. Another noteworthy result was the association between incidence and region which suggests that the overall incidence in Asia was 28% lower (95%CI 7.7-48.4) than in Europe

Post pandemic seroprevalence

Data from ten studies in nine countries (around 52 000 sera) were used for the estimation of the post-pandemic seroprevalence, which showed an overall age adjusted H1N1pdm seroprevalence of 32% (95%CI 26-95%). From five years of age onwards, there was a general decrease associated with age but this did not reach statistical significance.Overall the results of this study suggested that an estimated 20 to 27% of the global population were infected with the pandemic virus during the first year, with five to 19 year olds experiencing the highest incidence and the lower incidence among the older age groups. At the same time there are indications of important regional differences even among the limited populations investigated. Finally the authors linked the estimates of cumulative incidence with two independent estimates of influenza-related premature mortality in the pandemic (2,3). From that they derive estimates of infection fatality rates of less than 0.02%.(1)

ECDC Comment, 4 February 2013:

This study demonstrates how seroepidemiological work can be of substantial value providing insight on a global perspective into important differences in incidence and severity. The collation of data and publication for the study also demonstrates by example how cooperation and joint work efforts of numerous research groups can and should be undertaken with very careful attention given to attributing contributions.

However there is no room for complacency. An accepted criticism of the response to the 2009 pandemic is that while the seroepidemiological work was valuable and essential, time its results came very late.(4) Here are the first global estimates of overall infections appearing more than three years after the start of the pandemic.(1) Another criticism is that there were no established protocols for this kind of work and that quality control for the serological aspects was poor.(4) Recognising this fact there is now a strong global collaboration, the CONSISE group, that has been established to develop both protocols and improved laboratory quality assurance to ensure that investigations work faster, to a common pattern and with comparable results in the future.(5) This partnership involving more than 20 institutions met recently for a regional meeting in Hong Kong and will be delivering a series of six or more protocols and accompanying laboratory work for the Options conference in South Africa in September 2013. Comments are questions are welcome and should be sent to influenza@ecdc.europa.eu

1. Van Kerkhove, M. D., Siddhivinayak, H., Koukounari, A., & Mounts, A. W. (2013). Estimating age specific cumulative incidence for the 2009 influenza pandemic: a meta-analysis of A(H1N1)pdm09 serological studies from 19 countries. Influenza Journal.
2. Dawood FS, Iuliano AD, Reed C et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis 2012; 12:687–695.
3. WHO. Summary of WHO technical consultation: H1N1pdm mortality estimates, 2011, 25–26 October 2011
4. Laurie K, Huston P, Riley S, Jacqueline M. Katz JM, Willison D,,Tam J, Mounts AW, Hoschler K,Miller E, Vandemaele K Broberg E,Van Kerkhove M, Nicoll A. (2012) Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.0370a.x.
5. Van Kerkhove M, Broberg E, Engelhardt OG, Wood J, Nicoll A on behalf of the CONSISE steering committee. The consortium for the standardization of influenza seroepidemiology (CONSISE): a global partnership to standardize influenza seroepidemiology and develop influenza investigation protocols to inform public health policy Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12068