treatment within 1 day of symptoms of the case patient – substantially reduces the attack rate even at high levels of infectiousness ( _R0_ =2). However, such a policy is unfeasible even in well‐prepared countries in conditions of sustained community transmission. A child‐first pre‐vaccination strategy prioritizing 0‐16 year olds with a pre‐pandemic vaccine (i.e., offering lower efficacy) in combination with antiviral prophylaxis for 90% cases and close contacts is effective in mitigating the U.S. pandemic. This effectiveness rises if NPIs are added to the strategy. In this study, pre‐vaccination policies become more feasible and effective since vaccines can be better matched to the circulating strain and subsequently rapidly produced, with the increase in the delays in importation of the pandemic from abroad (e.g., via 9% effective border controls in the U.S.). 9 Another modeling study of the U.S. (Germann _et al._ 2006)<sup>38</sup> evaluates pre‐ vaccination policies – termed ‘dynamic’ vaccination in the study – that ramp up to cover most of the susceptible population (i.e., those still uninfected) such that there is substantial protection conferred at the point a pandemic begins to spread within the country. They find a child‐first pre‐vaccination policy is effective in reducing the overall attack rate even at infectiousness as high as _R0_ =1.9. Dose requirements for the pre‐pandemic vaccine can dramatically influence the effectiveness of the policy since they change the size of the covered population for fixed resource availability of antigen. Therefore, a pre‐pandemic vaccine requiring two doses is substantially less effective than one requiring a single dose. Given a dosage requirement, the effectiveness of the pre‐vaccination policy rises dramatically when combined in a strategy adding TAP and NPIs. For example, a strategy combining random – as compared to child‐first – pre‐vaccination and NPIs nearly eliminates projected disease incidence in their model even at _R0_ =1.9. The authors observe that delivering a strategy combining NPIs (and/or TAP) and vaccination could be onerous for local governments, even if there are large synergies in terms of delaying the spread of the disease within the country such that more individuals are eligible for the vaccine.

The recommendations of the two modeling studies above that consider mixed strategies are contradicted by studies that consider NPIs in isolation. Of these, Wu _et al._ (2006)<sup>27</sup> also assess the feasibility of these NPIs in terms of the demands on local governments and the social and economic burden imposed (via the proxy of the size of peak quarantined population). The study finds that NPIs – even with conservative assumptions on the proportion of cases reported, and compliance with subsequent case isolation or local quarantines – can halve the overall attack rate at _R0_ =1.8. This result is obtained with the assumption of 30% asymptomatic transmission of pandemic influenza, usually a burden on receiving benefits from contact tracing and early isolation of cases. The use of antivirals can be considered to achieve similar mitigation results – if large stockpiles are available – in lieu of isolation of cases and contacts.

# **Global Policy Implications**

Current policy orientation in secondary risk countries remains focused on mitigation, with the objective to lower the overall attack rate while achieving delays in the peak of the epidemic such that a well‐matched vaccine strategy could become feasible and local health systems are not overwhelmed. In countries where resources allow it, the strategy emphasizes antiviral prophylaxis for cases and contacts during community transmission alongside nonpharmaceutical measures as appropriate. The efficacy of 43