The age distribution of mortality due to influenza: pandemic and peri-pandemic

Abstract

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 A(H2N2) and A(H3N2) 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.

Severe mortality impact of the 1957 influenza pandemic in Chile

“…However, methods for estimating excess mortality data are not free of limitations. 43 For instance, the excess methodology employed in our study does not guarantee that excess mortality estimates are additive by age group. 44 Sensitivity analyses, however, indicate that our estimates are robust to modeling assumptions (Supplement).…”

“…A final caveat relates to our excess mortality calculation approach, which was relatively simple, due to the lack of contemporaneous virologic surveillance and relatively weak temporal resolution of the mortality data. However, methods for estimating excess mortality data are not free of limitations . For instance, the excess methodology employed in our study does not guarantee that excess mortality estimates are additive by age group .…”

RETRACTED ARTICLE: Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components

“…Because vaccination requires regular monitoring to confirm matching between the vaccines and the circulating virus strains, time-consuming generation processes limit its availability. Failures of influenza vaccines have been widely documented, and in the elderly populationin which most mortality occurs-influenza vaccines are only approximately 50% effective (Reichert et al, 2012). In the eventuality of a pandemic infection with a new strain, antiviral drugs also represent the first line of defense.…”

Increased frequency of travel in the presence of cross-immunity may act to decrease the chance of a global pandemic

“…Different types of partial cross-immunity could be considered. Here we have assumed that exposure to the LV strain reduces the probability of infection with the HV strain, whereas for some infections cross-immunity may instead (or also) act to reduce the severity of disease [41,51,52]. As an example, epidemiological isolation royalsocietypublishing.org/journal/rstb Phil.…”