With no intervention, the average overall illness attack rate is 34.1%, with an estimated total cost of $81.1 million (Table ). Pre-vaccination of 35% of the population with a low-efficacy vaccine reduces the average overall illness attack rate to 26.1% (total cost $71.1 million), and with a moderate-efficacy vaccine to 18.8% (total cost $53.7 million). Not surprisingly, pre-vaccination of 70% of the population is more effective (overall average illness attack rate 12.0%, total cost $47.0 million for a low-efficacy vaccine; and 0.2% and $19.3 million with a moderate-efficacy vaccine; see Table ).
Reactive vaccination alone, of 35% of the population with a low-efficacy vaccine delivered in three batches, reduces the overall average illness attack rate to 28.8% (or 22.8% with a moderate-efficacy vaccine), with a total cost of $77.7 million ($63.1 million with a moderate-efficacy vaccine). Thirty- and 60-day delays in initiation of reactive vaccination, with vaccines delivered in three batches, result in attack rates of 29.5% (total cost $79.3 million) and 32.2% (total cost $86.0 million), respectively, for a low-efficacy vaccine, and 24.6% (total cost $67.5 million) and 30.8% (total cost $82.5 million), respectively, for a moderate-efficacy vaccine. Clearly, with a 60-day delay, interventions occur too late in the epidemic to have any meaningful effect (see Figure ).
Figure 4 Daily attack rates for (i) the case of 70% coverage of low-efficacy vaccine with 60-day initial delay, and (ii) the baseline case. For case (i), the vaccine is given on the 60th day followed by receipt of vaccine after two additional two-week delays (see (more ...)
Antiviral use at low (10%) coverage alone results in an overall attack rate of 31.3% (total cost $75.9 million). School closure and social distancing alone result in an attack rate of 24.0%, with a total cost of $125.0 million.
Suppose we combine reactive low-efficacy vaccination of 35% of the population delivered in three batches, antivirals (10% coverage), and school closure and social distancing. Then the overall average illness attack rate is 4.5% (total cost $32.2 million) if no delays occur in the initiation of vaccination, and 5.4% (total cost $36.8 million) if a 60-day delay occurs. With a moderate-efficacy vaccine, the attack rate for this last scenario reduces to 2.4% (total cost $22.0 million). Similar relationships between interventions are apparent for interventions with 70% vaccination coverage, shown in Table . Vaccination coverage of 70% with a moderate-efficacy vaccine, combined with antiviral treatment and school closure, is highly effective, even with an initial 60-day delay and additional supply-chain disruptions (average illness attack rate 1.4%, total cost $27.4 million).
We note that the results when all vaccines are available at the same time are better than those involving delivery in batches, and sometimes significantly so, especially for a moderate-efficacy vaccine (Tables and ). Figures through illustrate the comparative illness attack rates of the various intervention strategies discussed above for all combinations of low/moderate-efficacy vaccine delivered in three batches and at 35% / 70% coverage as a function of the initial delay in vaccination implementation due to supply-chain disruptions. The impact of vaccinating 70% of the population, rather than 35%, ranges from moderate to substantial, with the increased coverage being most beneficial when the vaccine is delivered in a timely manner, and the vaccine is either of moderate efficacy or of low efficacy applied in combination with other intervention strategies.
Figure 5 Average overall illness attack rates (%) for modeled interventions. Average overall illness attack rates for the following scenarios: no intervention; pre-vaccination; reactive vaccination with delays in initiation of 0, 30, and 60 days after the intervention (more ...)
Complete (age-stratified and overall) average illness attack results for all modeled interventions are given in Supplementary Data Table S1. The comparative effectiveness of interventions is similar when age-group-specific results are studied.
Figure illustrates attack rate and total cost combinations for interventions that result in at least a 75% reduction in cost compared to no intervention. The closer to the origin, the more desirable an intervention is in terms of total cost and average illness attack rate. Aside from pre-vaccination strategies, we see that 70% reactive vaccination with a moderate-efficacy vaccine and school closure and social distancing, or even 35% reactive vaccination with a moderate-efficacy vaccine, antiviral use, and school closure, also result in substantial reductions in cost and attack rates. Figure illustrates attack rate and cost results for interventions that result in more-modest 50%–75% reductions in cost compared to no intervention. Once again, several strategies combining vaccination, antiviral use, and school closure/social distancing are competitive with pre-vaccination.
Figure 6 Total cost of modeled intervention strategies (US$m) vs. average illness attack rate (%) Figure shows results for interventions with cost reductions of more than 75% compared with no intervention, and Figure shows (more ...)