Mitigation strategies for pandemic influenza in the United States

Abstract

Recent human deaths due to infection by highly pathogenic (H5N1) avian influenza A virus have raised the specter of a devastating pandemic like that of 1917-1918, should this avian virus evolve to become readily transmissible among humans. We introduce and use a large-scale stochastic simulation model to investigate the spread of a pandemic strain of influenza virus through the U.S. population of 281 million individuals for R(0) (the basic reproductive number) from 1.6 to 2.4. We model the impact that a variety of levels and combinations of influenza antiviral agents, vaccines, and modified social mobility (including school closure and travel restrictions) have on the timing and magnitude of this spread. Our simulations demonstrate that, in a highly mobile population, restricting travel after an outbreak is detected is likely to delay slightly the time course of the outbreak without impacting the eventual number ill. For R(0) < 1.9, our model suggests that the rapid production and distribution of vaccines, even if poorly matched to circulating strains, could significantly slow disease spread and limit the number ill to <10% of the population, particularly if children are preferentially vaccinated. Alternatively, the aggressive deployment of several million courses of influenza antiviral agents in a targeted prophylaxis strategy may contain a nascent outbreak with low R(0), provided adequate contact tracing and distribution capacities exist. For higher R(0), we predict that multiple strategies in combination (involving both social and medical interventions) will be required to achieve similar limits on illness rates.

Fig. 1.

Two simulated pandemic influenza outbreaks with R₀ = 1.9, initiated by the daily entry of a small number of infected individuals through 14 major international airports in the continental U.S. (beginning on day 0). The tract-level prevalence of symptomatic cases at any point in time is indicated on a logarithmic color scale, from 0.03% (green) to 3% (red) of the population. No mitigation strategies are used in the baseline simulation (Left), resulting in a 43.5% attack rate. (Right) A 60% TAP intervention begins at day 31, or 7 days after the pandemic alert. At day 99, the nationwide supply of 20 million antiviral courses is exhausted, leading to a nationwide pandemic.

Fig. 2.

Epidemic curves (note the logarithmic scale) demonstrating the effectiveness of several different mitigation strategies, as compared to the baseline scenario without any intervention, for different values of R₀. See Table 2 for details of each intervention. In the case of vaccination, results shown here are for a uniform coverage of the entire population with a single-dose regimen.