Abstract
Vaccination can delay the peak of a pandemic influenza wave by reducing the number of individuals initially susceptible to influenza infection. Emerging evidence indicates that susceptibility to severe secondary bacterial infections following a primary influenza infection may vary seasonally, with peak susceptibility occurring in winter. Taken together, these two observations suggest that vaccinating to prevent a fall pandemic wave might delay it long enough to inadvertently increase influenza infections in winter, when primary influenza infection is more likely to cause severe outcomes. This could potentially cause a net increase in severe outcomes. Most pandemic models implicitly assume that the probability of severe outcomes does not vary seasonally and hence cannot capture this effect. Here we show that the probability of intensive care unit (ICU) admission per influenza infection in the 2009 H1N1 pandemic followed a seasonal pattern. We combine this with an influenza transmission model to investigate conditions under which a vaccination program could inadvertently shift influenza susceptibility to months where the risk of ICU admission due to influenza is higher. We find that vaccination in advance of a fall pandemic wave can actually increase the number of ICU admissions in situations where antigenic drift is sufficiently rapid or where importation of a cross-reactive strain is possible. Moreover, this effect is stronger for vaccination programs that prevent more primary influenza infections. Sensitivity analysis indicates several mechanisms that may cause this effect. We also find that the predicted number of ICU admissions changes dramatically depending on whether the probability of ICU admission varies seasonally, or whether it is held constant. These results suggest that pandemic planning should explore the potential interactions between seasonally varying susceptibility to severe influenza outcomes and the timing of vaccine-altered pandemic influenza waves.
Highlights
Both seasonal and pandemic influenza are associated with a considerable burden of disease, in the form of absenteeism, hospitalizations, intensive care unit (ICU) admissions, and deaths [1]
The probability of being admitted to ICU due to an influenza infection in the extrapolated model is highest in the months of January and February, which is consistent with what we would expect based on the literature describing peak susceptibility to secondary bacterial infections in these months
There is a single peak in infection prevalence in October, which corresponds to a peak in the number of ICU admissions (Figure 2a)
Summary
Both seasonal and pandemic influenza are associated with a considerable burden of disease, in the form of absenteeism, hospitalizations, intensive care unit (ICU) admissions, and deaths [1]. Data from the influenza pandemics of 1918, 1957 and 1968 are consistent with secondary bacterial pneumonia causing the majority of influenza-associated deaths [4]. Pandemic influenza can be associated with a higher burden of disease than seasonal influenza, if only because more individuals become infected during a pandemic due to lower levels of natural immunity in the population, as compared to typical seasonal influenza [5]. Unlike in previous pandemics, immunization programs may have played a mitigating role, despite late introduction of the vaccine. The use of a vaccine against pandemic influenza for the first time ever suggests that immunization will form a part of mitigation plans for future influenza pandemics.
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