Effectiveness and cost-effectiveness of expanded antiviral prophylaxis and adjuvanted vaccination strategies for an influenza A (H5N1) pandemic

Abstract

Background: The pandemic potential of influenza A (H5N1) virus is a prominent public health concern of the 21st century.

Objective: To estimate the effectiveness and cost-effectiveness of alternative pandemic (H5N1) mitigation and response strategies.

Design: Compartmental epidemic model in conjunction with a Markov model of disease progression.

Data sources: Literature and expert opinion.

Target population: Residents of a U.S. metropolitan city with a population of 8.3 million.

Time horizon: Lifetime.

Perspective: Societal.

Interventions: 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.

Outcome measures: Infections and deaths averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness.

Results of base-case analysis: Expanded vaccination was the most effective and cost-effective of the 3 strategies, averting 68% of infections and deaths and gaining 404 030 QALYs at $10 844 per QALY gained relative to the stockpiled strategy.

Results of sensitivity analysis: Expanded vaccination remained incrementally cost-effective over a wide range of assumptions.

Limitations: 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.

Conclusion: 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.

Primary funding source: National Institutes of Health and Agency for Healthcare Research and Quality.

Figure 1. Basic states of the compartmental model

The infection rate is dynamically related to the number of susceptible, infected, recovered, and dead individuals in the population. All individuals entered the model susceptible to infection. Infected individuals first entered an asymptomatic incubation period and could then progress either to symptomatic or asymptomatic infection. Those with symptomatic infection either isolated or continued to circulate and infect others. Infected individuals either recovered or died. The majority of those who recovered developed complete immunity to the virus; a small minority was susceptible to recurrent infection from a drifted viral strain.

Figure 2. Pandemic waves and cumulative mortality for a city of 8.3 million individuals under different strategies

Expanded adjuvanted vaccination results in the shortest duration pandemic wave with the smallest area under the curve. Expanded antiviral prophylaxis extends time to the first pandemic wave and modestly reduces mortality as compared with stockpiled strategy. Additional waves occur in all strategies as a result of decreases in voluntary social distancing as well as a low re-infection rate as the virus undergoes drift changes

Figure 3. Health outcomes for a city of 8.3 million individuals with varying pandemic severity

Daily deaths are shown for varying values of R₀ 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).

Figure 4. Combinations of vaccine effectiveness and population coverage/adjuvant doses required to avert the pandemic for a city of 8.3 million individuals

Areas to the right of the curves represent combinations of vaccine effectiveness and population coverage/adjuvant doses under which the pandemic is averted under different R₀s.

Figure 5. Cost-effectiveness of strategies for a city of 8.3 million individuals

Expanded adjuvanted vaccination dominates expanded antiviral prophylaxis strategy through extended dominance and is cost-effective as compared with stockpiled strategy. (QALY = Quality-Adjusted Life-Year)