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BMC Medicine

, 10:162

First Online: 12 December 2012Received: 06 May 2012Accepted: 12 December 2012


BackgroundPandemic influenza is said to -shift mortality- to younger age groups; but also to spare a subpopulation of the elderly population. Does one of these effects dominate? Might this have important ramifications?

MethodsWe estimated age-specific excess mortality rates for all-years for which data were available in the 20th century for Australia, Canada, France, Japan, the UK, and the USA for people older than 44 years of age. We modeled variation with age, and standardized estimates to allow direct comparison across age groups and countries. Attack rate data for four pandemics were assembled.

ResultsFor nearly all seasons, an exponential model characterized mortality data extremely well. For seasons of emergence and a variable number of seasons following, however, a subpopulation above a threshold age invariably enjoyed reduced mortality. -Immune escape-, a stepwise increase in mortality among the oldest elderly, was observed a number of seasons after both the AH2N2 and AH3N2 pandemics. The number of seasons from emergence to escape varied by country. For the latter pandemic, mortality rates in four countries increased for younger age groups but only in the season following that of emergence. Adaptation to both emergent viruses was apparent as a progressive decrease in mortality rates, which, with two exceptions, was seen only in younger age groups. Pandemic attack rate variation with age was estimated to be similar across four pandemics with very different mortality impact.

ConclusionsIn all influenza pandemics of the 20th century, emergent viruses resembled those that had circulated previously within the lifespan of then-living people. Such individuals were relatively immune to the emergent strain, but this immunity waned with mutation of the emergent virus. An immune subpopulation complicates and may invalidate vaccine trials. Pandemic influenza does not -shift- mortality to younger age groups; rather, the mortality level is reset by the virulence of the emerging virus and is moderated by immunity of past experience. In this study, we found that after immune escape, older age groups showed no further mortality reduction, despite their being the principal target of conventional influenza vaccines. Vaccines incorporating variants of pandemic viruses seem to provide little benefit to those previously immune. If attack rates truly are similar across pandemics, it must be the case that immunity to the pandemic virus does not prevent infection, but only mitigates the consequences.

KeywordsPandemic influenza mortality due to influenza recycling pandemic attack rates vaccination protective immunity AbbreviationsAARPAbove the age of recycling persons

ACAll-cause used for both mortality due to all causes and excess mortality due to all causes

ACxsMRAll-cause excess mortality rate

B-typeInfluenza subtype B

CandSCentering and scaling

H1H1N1: Influenza subtype AH1N1

H2H2N2: influenza subtype AH2N2

H3H3N2: Influenza subtype AH3N2

N2Influenza type A neuraminidase type 2

OASOriginal antigenic sin.

Electronic supplementary materialThe online version of this article doi:10.1186-1741-7015-10-162 contains supplementary material, which is available to authorized users.

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Autor: Tom Reichert - Gerardo Chowell - Jonathan A McCullers


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