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

Maria D. Van Kerkhove, Siddhivinayak Hirve, Artemis Koukounari, Anthony W. Mounts*, Regina Allwinn, D. Don Bandaranayake, A. Antonino Bella, Angie Bone, Fabrice Carrat, Mandeep S. Chadha, Mark Chen, Chia Yu Chi, C. M.Chad M. Cox, Michelle Cretikos, Natasha Crowcroft, Jeffery Cutter, Christl A. Donnelly, Xavier de Lamballerie, K. Koussay Dellagi, George DoukasSandra Dudareva-Vizule, Neil M. Ferguson, Alicia M. Fry, Gwendolyn L. Gilbert, Walter Haas, Pia Hardelid, Peter Horby, Q. Sue Huang, Olav Hungnes, Niina Ikonen, Kyoko Iwatsuki-Horimoto, Iikka Julkunen, Jacqueline Katz, Yoshi Kawaoka, Ajit Lalvani, Daniel Levy-Bruhl, Helena C. Maltezou, Jodie McVernon, Elizbeth Miller, A. C. Mishra, Mohsen Moghadami, Shailesh D. Pawar, Carrie Reed, Steven Riley, Caterina Rizzo, Laura Rosella, Ted M. Ross, Yuelong Shu, Danuta M. Skowronski, Saranya Sridhar, Anneke Steens, Babasaheb V. Tandale, Maria Theodoridou, Michiel van Boven, Kristian Waalen, Jen Ren Wang, Joseph T. Wu, Cuiling Xu, Shanta Zimmer

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

155 Citations (Scopus)


Background: The global impact of the 2009 influenza A(H1N1) pandemic (H1N1pdm) is not well understood. Objectives: We estimate overall and age-specific prevalence of cross-reactive antibodies to H1N1pdm virus and rates of H1N1pdm infection during the first year of the pandemic using data from published and unpublished H1N1pdm seroepidemiological studies. Methods: Primary aggregate H1N1pdm serologic data from each study were stratified in standardized age groups and evaluated based on when sera were collected in relation to national or subnational peak H1N1pdm activity. Seropositivity was assessed using well-described and standardized hemagglutination inhibition (HI titers ≥32 or ≥40) and microneutralization (MN ≥ 40) laboratory assays. The prevalence of cross-reactive antibodies to the H1N1pdm virus was estimated for studies using sera collected prior to the start of the pandemic (between 2004 and April 2009); H1N1pdm cumulative incidence was estimated for studies in which collected both pre- and post-pandemic sera; and H1N1pdm seropositivity was calculated from studies with post-pandemic sera only (collected between December 2009-June 2010). Results: Data from 27 published/unpublished studies from 19 countries/administrative regions - Australia, Canada, China, Finland, France, Germany, Hong Kong SAR, India, Iran, Italy, Japan, Netherlands, New Zealand, Norway, Reunion Island, Singapore, United Kingdom, United States, and Vietnam - were eligible for inclusion. The overall age-standardized pre-pandemic prevalence of cross-reactive antibodies was 5% (95%CI 3-7%) and varied significantly by age with the highest rates among persons ≥65 years old (14% 95%CI 8-24%). Overall age-standardized H1N1pdm cumulative incidence was 24% (95%CI 20-27%) and varied significantly by age with the highest in children 5-19 (47% 95%CI 39-55%) and 0-4 years old (36% 95%CI 30-43%). Conclusions: Our results offer unique insight into the global impact of the H1N1 pandemic and highlight the need for standardization of seroepidemiological studies and for their inclusion in pre-pandemic preparedness plans. Our results taken together with recent global pandemic respiratory-associated mortality estimates suggest that the case fatality ratio of the pandemic virus was approximately 0·02%.

Original languageEnglish
Pages (from-to)872-886
Number of pages15
JournalInfluenza and other Respiratory Viruses
Issue number5
Publication statusPublished - Sept 2013


  • A(H1N1)pdm09
  • Cross-reactive antibodies
  • Cumulative incidence
  • H1N1pdm
  • Seroprevalence


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