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

Abstract

Background: The global impact of the 2009 influenza A (H 1N 1) pandemic (H 1N 1pdm) is not well understood.

Objectives: We estimate overall and age‐specific prevalence of cross‐reactive antibodies to H 1N 1pdm virus and rates of H 1N 1pdm infection during the first year of the pandemic using data from published and unpublished H 1N 1pdm seroepidemiological studies.

Methods: Primary aggregate H 1N 1pdm 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 H 1N 1pdm 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 H 1N 1pdm virus was estimated for studies using sera collected prior to the start of the pandemic (between 2004 and A pril 2009); H 1N 1pdm cumulative incidence was estimated for studies in which collected both pre‐ and post‐pandemic sera; and H 1N 1pdm seropositivity was calculated from studies with post‐pandemic sera only (collected between D ecember 2009–J une 2010).

Results: Data from 27 published/unpublished studies from 19 countries/administrative regions – A ustralia, C anada, C hina, F inland, F rance, G ermany, H ong K ong SAR , I ndia, I ran, I taly, J apan, N etherlands, N ew Z ealand, N orway, R eunion I sland, S ingapore, U nited K ingdom, U nited S tates, and V ietnam – 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 H 1N 1pdm 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 H 1N 1 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%.