25 May 2012
Influenza serological studies to inform public health action: best practices to optimise timing, quality and Reporting
Influenza serology measures the immune system’s antibody response to viral antigen exposure, including both infection and immunization. Despite the demonstrated epidemiological value of serological studies in influenza, more improvements are needed in the standardization of methods to detect subtype-specific antibodies (1, 2). Influenza serology can help predict the public health impact of successive influenza and provide public health authorities with a better understanding of the proportion of susceptible persons remaining in a population; critical data for planning early responses against the transmission of novel influenza viruses. This report describes the recommendations of a group of interdisciplinary experts that met on February 2012 in Toronto, Canada to develop a consensus on the best practices to standardize and implement influenza virus serology for epidemic and pandemic influenza (3).
As Laurie et al, describe in their meeting report, serological studies have not only proven useful to confirm pre-existing cross-reactive antibodies but also to measure age-specific infection rates and predict the impact of influenza infection and disease (3). Furthermore, this experts group highlighted that after the influenza A(H1N1) pandemic in 2009, different research groups established standard virus strains, sera, and serological correlates of infection, and made important contributions to estimating the burden of infection and determining the vulnerable populations worldwide (4-6). However, methods used for estimating the prevalence of antibodies anti-influenza A(H1N1)2009 were heterogeneous and some countries found challenges in the preparation and implementation of research protocols, development and standardisation of viral serology assays, and variability in the collection and reporting of data. The non-standardization of approach and data collection, precluded direct comparisons between countries and left many gaps in our understanding of the actual impact of the pandemic. Laurie et al, present a consensus developed by the expert committee to improve and optimize the timing, quality and reporting of influenza serological studies during outbreaks and pandemics.
The practices or strategies outlined in this report provide a structure for the adoption of a common framework for serological studies, systematized methodology and reporting practices, the coordination and standardisation of an international laboratory serological response to allow the rapid development of serological assays, and other proposals to include serological studies in pandemic preparedness plans and ensure their timely implementation.
Influenza sero-epidemiological studies are valuable tools for pandemic assessment. They can provide information on the population risk, infection rates, transmission parameters, and other key metrics that facilitate appropriate mitigation and response. However, much work is needed to standardize both laboratory methods and the epidemiological component of these studies. Serological investigation can complement epidemiological and clinical studies to provide a more complete evidence-based guidance to health policy-makers. Previous studies have reported some limitations of serologic assays for influenza surveillance in terms of their reproducibility and comparability between laboratories (7, 8), hence, the recommendation to standardize testing methods. However, standardization of epidemiological investigation methodologies and protocols is also needed. Standardization would greatly improve the interpretability and comparability of study results. As Laurie et al point out, global preparedness will also require capacity building in many countries which can only be achieved by ensuring support from technical experts and funding organizations.
(1) Broberg E, Nicoll A, Amato-Gauci A. Seroprevalence to influenza A(H1N1) 2009 virus--where are we? Clinical and vaccine immunology : CVI. 2011;18(8):1205-12. Epub 2011/06/10.
(2) Stephenson I, Heath A, Major D, Newman RW, Hoschler K, Junzi W, et al. Reproducibility of serologic assays for influenza virus A (H5N1). Emerging infectious diseases. 2009;15(8):1252-9. Epub 2009/09/16.
(3) Laurie KL, Huston P, Riley S, Katz JM, Willison DJ, Tam JS, et al. Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting. Influenza and other respiratory viruses. 2012. Epub 2012/05/03.
(4) Miller E, Hoschler K, Hardelid P, Stanford E, Andrews N, Zambon M. Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study. Lancet. 2010;375(9720):1100-8. Epub 2010/01/26.
(5) Chen MI, Barr IG, Koh GC, Lee VJ, Lee CP, Shaw R, et al. Serological response in RT-PCR confirmed H1N1-2009 influenza a by hemagglutination inhibition and virus neutralization assays: an observational study. PloS one. 2010;5(8):e12474. Epub 2010/09/04.
(6) Iwasenko JM, Cretikos M, Paterson DL, Gibb R, Webb SA, Smith DW, et al. Enhanced diagnosis of pandemic (H1N1) 2009 influenza infection using molecular and serological testing in intensive care unit patients with suspected influenza. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2010;51(1):70-2. Epub 2010/05/21.
(7) Wood JM, Major D, Heath A, Newman RW, Hoschler K, Stephenson I, et al. Reproducibility of serology assays for pandemic influenza H1N1: collaborative study to evaluate a candidate WHO International Standard. Vaccine. 2012;30(2):210-7. Epub 2011/11/22.
(8) Wood JM, Montomoli E, Newman RW, Daas A, Buchheit KH, Terao E. Collaborative study on influenza vaccine clinical trial serology - part 2: reproducibility study. Pharmeuropa bio & scientific notes. 2011;2011(1):36-54. Epub 2011/05/31.