S E I R Clinically infected Vaccinated Not clinically infected Not vaccinated[+] Antiviral treatment Primary healthcare No antiviral No healthcare treatment [+] sought Hospitalized Not hospitalized Died Survived Figure 1. Schematic of hybrid transmission and decision analytic economic model. [+] indicates a cloned subtree with the same structure as the branch above. In sensitivity analysis, the probabilities of healthcare utilization and death were independent of each other but dependent on the probability of clinical infection. We assumed those with serious complications would seek primary healthcare. SEIR, susceptible, exposed, infected, removed. in the appendices (online Technical Appendix 1, www. cdc.gov/EID/content/16/2/224-Techapp1.pdf, and online Technical Appendix 2, www.cdc.gov/EID/content/16/2/ 224-Techapp2.pdf). Strategies We considered prepandemic inﬂuenza vaccination in isolation and in combination with antiviral treatment. Four strategies for pandemic mitigation were examined (Table 1). In all strategies, a small stockpile of antiviral drugs was used for prophylaxis of case contacts and treatment of clinical cases in an initial containment effort and, after a de- lay of 6 months, a matched vaccine was delivered. In isola- tion, this intervention was labeled strategy 1. Demographics We divided the Australian population into 3 age groups: 0–19 years (26% [5,513,878], 20–64 years (61% [12,744,215], and >65 years (13% [2,759,129]) (15). Rates of mixing were age dependent and based on a recent large study of contact patterns in the European Union (16). Vaccine Parameters Immunogenicity data provide evidence of prepandem- ic vaccine efﬁcacy (VE) in humans (17). However, this ef- ﬁcacy will also depend on how closely the prepandemic vaccine strain matches the pandemic strain that emerges. We assumed that 2 doses of prepandemic vaccine would reduce susceptibility (relative hazard of infection) by 40% in persons <65 years of age. For the >65 years of age group, VE may be reduced (18). Thus, in our base-case model, we halved the VE for this age group. Modeled efﬁcacy was also dependent on the number of doses, time since the last dose, and vaccine type (prepandemic or matched). The ﬁrst dose of prepandemic vaccine was assumed to be given coincident with the ﬁrst local case-patient, fol- Pandemic Inﬂuenza Mitigation Strategies lowed 21 days later by the second dose. In all strategies, the ﬁrst dose of matched vaccine was provided 180 days after the ﬁrst local case was identiﬁed in Australia; the second dose was administered 21 days later in strategies 1 and 2 only. Although 2 doses of a matched vaccine would be ordered under all strategies, in base-case only 1 dose of matched vaccine was administered in strategies involving 2 doses of a prepandemic vaccine (strategies 3 and 4). Popu- lation vaccine coverage (both prepandemic and matched) was assumed to be 80% (19). Antiviral Drug Parameters In the base-case model, we estimated the efﬁcacy of an- tiviral treatment for preventing hospitalization as 59% (20). We assumed the same antiviral drug efﬁcacy for preventing death as for hospitalization. The effect of antiviral treatment on inﬂuenza transmission in the community is unclear (21), and we assumed no reduction in infectivity of treated cases. When antiviral treatment was given, it was provided to 80% of persons with clinical disease (those who sought primary healthcare). Antiviral drug strategies contained stockpiles to cover 40% of the population (≈8 million courses). However, all strategies assumed a limited antiviral drug stockpile (≈0.2 million courses) to be used in initial containment efforts for treatment of clinical cases and prophylaxis of case contacts. We assumed that the antiviral prophylaxis treatment of con- tacts, during the initial containment effort, reduced suscepti- bility and infectiousness by 70% and 60%, respectively (22). A static percentage (10%) of viruses were assumed resistant to antiviral drugs. Disease Estimates The CAR during a pandemic was determined by using the transmission model and was primarily a function of R0 (1.7) (23–25) and the percentage of asymptomatic infec- tions (50%) (26). The basic reproductive number (R0) rep- resents the number of secondary cases that a representative person with inﬂuenza would infect in a fully susceptible population. Asymptomatic persons were assumed to be two thirds as infectious as symptomatic persons (9,10). We as- sumed that 50% of those with a clinical inﬂuenza infection would seek medical care (27); most primary care would oc- cur in general practice (80%) and the remainder in hospital emergency departments. Table 1. Descriptions of 4 pharmaceutical-based pandemic influenza mitigation strategies* Strategy no. Description 1 Minimum pharmaceutical intervention 2 Antiviral treatment of those clinically infected 3 Population prepandemic vaccination 4 Strategies 2 + 3 *All strategies included an initial antiviral containment effort and distribution of a matched vaccine to the population 180 days after the first locally acquired case. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 2, February 2010 225