Nayer Khazeni, MD, MS; David W. Hutton, MS; Alan M. Garber, MD, PhD; Douglas K. Owens, MD, MS
Khazeni N, Hutton DW, Garber AM, Owens DK. Effectiveness and Cost-Effectiveness of Expanded Antiviral Prophylaxis and Adjuvanted Vaccination Strategies for an Influenza A (H5N1) Pandemic. Ann Intern Med. 2009;151:840-853. doi: 10.7326/0000605-200912150-00156
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Published: Ann Intern Med. 2009;151(12):840-853.
The pandemic potential of influenza A (H5N1) virus is a prominent public health concern of the 21st century.
To estimate the effectiveness and cost-effectiveness of alternative pandemic (H5N1) mitigation and response strategies.
Compartmental epidemic model in conjunction with a Markov model of disease progression.
Literature and expert opinion.
Residents of a U.S. metropolitan city with a population of 8.3 million.
3 scenarios: 1) vaccination and antiviral pharmacotherapy in quantities similar to those currently available in the U.S. stockpile (stockpiled strategy), 2) stockpiled strategy but with expanded distribution of antiviral agents (expanded prophylaxis strategy), and 3) stockpiled strategy but with adjuvanted vaccine (expanded vaccination strategy). All scenarios assumed standard nonpharmaceutical interventions.
Infections and deaths averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness.
Expanded vaccination was the most effective and cost-effective of the 3 strategies, averting 68% of infections and deaths and gaining 404Â 030 QALYs at $10Â 844 per QALY gained relative to the stockpiled strategy.
Expanded vaccination remained incrementally cost-effective over a wide range of assumptions.
The model assumed homogenous mixing of cases and contacts; heterogeneous mixing would result in faster initial spread, followed by slower spread. We did not model interventions for children or older adults; the model is not designed to target interventions to specific groups.
Expanded adjuvanted vaccination is an effective and cost-effective mitigation strategy for an influenza A (H5N1) pandemic. Expanded antiviral prophylaxis can help delay the pandemic while additional strategies are implemented.
National Institutes of Health and Agency for Healthcare Research and Quality.
Proper pandemic planning for an influenza A (H5N1) pandemic is a public health priority.
This decision model for pandemic planning suggests that stockpiling sufficient adjuvanted vaccine for immunizing 40% of the population is more effective and cost-effective than immunizing a smaller proportion of the population or providing them with antiviral drugs.
The model makes several assumptions that may not bear out in a real H5N1 pandemic. However, users can test their own assumptions with a model provided by the authors.
Expanding immunization with adjuvanted vaccine may prevent spread of pandemic influenza A (H5N1) better than the U.S. government's current pandemic prevention strategy.
Expanded vaccination results in the shortest-duration pandemic wave and averts the most deaths. Expanded prophylaxis extends the time to the first pandemic wave and modestly reduces mortality compared with the stockpiled strategy. Additional waves occur in all strategies as a result of decreases in voluntary social distancing, as well as a low reinfection rate as the virus undergoes drift changes.
Daily deaths are shown for varying values of R0 (the average number of secondary infections caused by a single infectious individual in a susceptible population) and case-fatality proportions. As the case-fatality proportion rises, deaths increase and subsequent waves become more apparent. However, because of reactive social distancing in response to mortality, the peaks in the waves are not proportional to the increase in case fatality. As mortality increases, the population reacts by reducing social interactions, which reduces the spread of infection. Because reactive social distancing occurs in response to mortality rather than infections, the effects of reactive social distancing are more apparent with high case-fatality proportions. Waves in the pandemic occur because social distancing is in response to average mortality over the past 30 days. As reactive social distancing decreases mortality, the population begins to return to higher, more normal levels of social interaction, causing another upswing in mortality (further described in Appendix 2).
Areas to the right of the curves represent combinations of vaccine effectiveness and population coverage or adjuvant doses under which the pandemic is averted under different R0s (the average number of secondary infections caused by a single infectious individual in a susceptible population).
Expanded vaccination dominates expanded prophylaxis through extended dominance and is cost-effective compared with the stockpiled strategy. Costs are in 2009 U.S. dollars. QALY = quality-adjusted life-year.
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Infectious Disease, High Value Care, Vaccines/Immunization, Prevention/Screening.
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