Mitigation strategies for pandemic influenza in the United States
- *Los Alamos National Laboratory, Los Alamos, NM 87545; and
- ‡Program of Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center and Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98109
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Communicated by G. Balakrish Nair, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh, February 16, 2006 (received for review January 10, 2006)
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.
Footnotes
- †To whom correspondence should be addressed. E-mail: tcg{at}lanl.gov
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Author contributions: T.C.G., K.K., I.M.L., and C.A.M. designed research, performed research, contributed new reagents/analytic tools, analyzed data, and wrote the paper.
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↵ § In fact, efficacy of experimental vaccines against a novel pandemic strain cannot be ascertained in the absence of actual viral challenge; immunogenicity alone can be determined. Experimental vaccines based on avian influenza virus have required much greater amounts of antigen for acceptable levels of immunogenicity than standard human vaccines. This discrepancy does not enter into our calculations of required doses of vaccine. We assume that pandemic vaccines will have the same relationship between efficacy and immunogenicity as that for standard vaccines against human influenza virus.
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↵ ¶ R 0 is a difficult quantity to estimate during an actual epidemic, because it depends critically upon the disease serial interval (or generation time) and to a somewhat lesser extent on the relative durations of the latent and infectious periods (19, 20). Because our model assumes particular values for these quantities, R 0 is a useful measure of transmissibility, but care needs to be taken when comparing results for different models or epidemiological data.
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Conflict of interest statement: No conflicts declared.
- Abbreviations:
- TAP,
- targeted antiviral prophylaxis;
- NAI,
- neuraminidase inhibitor.
Abbreviations:
- © 2006 by The National Academy of Sciences of the USA
