by revere, cross-posted from Effect Measure

The spate of swine flu articles in The New England Journal of Medicine last week included an important “Perspective, The Signature Features of Influenza Pandemics — Implications for Policy,” by Miller, Viboud, Baliska and Simonsen. These authors are familiar to flu watchers as experienced flu epidemiologists and analysts of archival and other data. Analysis of archival data is sometimes described as archeo-epidemiologic research. In their NEJM article Miller et al. summarize what they see as some common features in the three flu pandemics of the last century (so the generalization that there are no generalizations about flu pandemics may have some exceptions; I won’t pursue the paradoxes that result). The pertinence for the current swine flu outbreak is striking.

The authors suggest five signature features characgterizing pandemic versus seasonal influenza:

• emergence of a flu virus with which the general population has little previous experience
• peak mortality shifts to younger age groups than seasonal flu
• multiple waves
• enhanced transmissibility
• significant geographic variation

Swine flu has already satisfied the first. It is a novel virus to which most people are not believed to have acquired immunity, although the possibility remains that those of us born before 1957 may have some cross-reactivity. This relates to the second feature. The relative sparing of the older age groups and the increased mortality in younger adults may be related to “antigenic cycling,” immune cross-reaction with a “new” virus by previous experience among the oldest in the population. The virus gains a foothold by rapid spread when most, but perhaps not all, of the population is immunologically naive. There are various hypotheses why young adults may be more at risk of dying, but at the moment we don’t know the reason. It is pertinent that the age distribution of swine flu cases is markedly left-shifted (i.e., shifted to younger age groups). The age distribution also has obvious implications for how to use an initially scarce vaccine.

Of most interest for the present circumstance is the consistent appearance of successive waves of disease:

The third feature, a pattern of multiple waves, characterized all three 20th-century pandemics, each of which caused increased mortality for 2 to 5 years (see chart). The lethal wave in the autumn of 1918 was preceded by a first wave in the summer that led to substantial morbidity but relatively low mortality in both the United States and Europe. Recent studies suggest that these early mild outbreaks partially immunized the population, decreasing the mortality impact of the main pandemic wave in the fall of 1918. In the United States, the 1957 influenza A/H2 pandemic had three waves in the United States, with notable excess mortality in the nonsuccessive winter seasons of 1959 and 1962 — the latter being 5 years after the initial emergence of the pandemic strain. From 1968 through 1970, Eurasia had a mild first influenza season, with the full effects on morbidity and mortality occurring in the second season of pandemic-virus circulation. The reasons for multiple waves of varying impact are not precisely understood, but they probably include adaptation of the virus to its new host, demographic or geographic variation, seasonality, and the overall immunity of the population. The occurrence of multiple waves potentially provides time for health authorities to implement control strategies for successive waves. (Miller et al., NEJM [cites omitted])

 

Figure caption: Proportion of the total influenza-associated mortality burden in each wave for each of four previous pandemics is shown above the blue bars. Mortality waves indicate the timing of the deaths during each pandemic. The 1918 pandemic (Panel B) had a mild first wave during the summer, followed by two severe waves the following winter. The 1957 pandemic (Panel C) had three winter waves during the first 5 years. The 1968 pandemic (Panel D) had a mild first wave in Britain, followed by a severe second wave the following winter. The shaded columns indicate normal seasonal patterns of influenza.

 

Swine flu is currently experiencing a relatively less severe (first?) wave of disease. The virus could disappear or it could reappear as another wave or waves within a year or two (or three). Sometimes subsequent waves are more severe, sometimes not. It doesn’t seem prudent, however, to think this one will disappear or remain a less virulent flu virus. Both are possible, but so are less benign scenarios. Plan for the worst, hope for the best remains good advice.

Enhanced transmissibility is, in my view, the least certain of Miller et al.’s features because its measure, the basic reproductive number R₀, is difficult to estimate (R₀ is the average number of secondary cases in a completely susceptible population). Miller et al. observe that the slim hope a flu pandemic can be contained is based on mathematical model that also suggests that to have any hope of containment, R₀ would need to be below 2.0. Some data suggests that in a pandemic, R₀ routinely exceeds 2.0.

The last feature, significant geographic variation, is also relevant to swine flu. Pandemic flu doesn’t appear everywhere at once. Swine flu in Mexico is waning in some areas and increasing in others, and the same is happening in the rest of North America and Europe. The pandemic experience warns us not to characterize the state of a global outbreak on the basis of local or even national experiences. The swine flu outbreak is still evolving. As for whether it will wane with warmer weather, it is worth noting that in three of the four pandemics depicted in the chart, half or more of the mortality occurred outside “flu season” (the periods marked with the pink shading).

The NEJM swine flu articles appear to be free access. They are all worth reading.