Effective, robust design of community mitigation for pandemic influenza: a systematic examination of proposed US guidance

Abstract

Background: The US government proposes pandemic influenza mitigation guidance that includes isolation and antiviral treatment of ill persons, voluntary household member quarantine and antiviral prophylaxis, social distancing of individuals, school closure, reduction of contacts at work, and prioritized vaccination. Is this the best strategy combination? Is choice of this strategy robust to pandemic uncertainties? What are critical enablers of community resilience?

Methods and findings: We systematically simulate a broad range of pandemic scenarios and mitigation strategies using a networked, agent-based model of a community of explicit, multiply-overlapping social contact networks. We evaluate illness and societal burden for alterations in social networks, illness parameters, or intervention implementation. For a 1918-like pandemic, the best strategy minimizes illness to <1% of the population and combines network-based (e.g. school closure, social distancing of all with adults' contacts at work reduced), and case-based measures (e.g. antiviral treatment of the ill and prophylaxis of household members). We find choice of this best strategy robust to removal of enhanced transmission by the young, additional complexity in contact networks, and altered influenza natural history including extended viral shedding. Administration of age-group or randomly targeted 50% effective pre-pandemic vaccine with 7% population coverage (current US H5N1 vaccine stockpile) had minimal effect on outcomes. In order, mitigation success depends on rapid strategy implementation, high compliance, regional mitigation, and rigorous rescinding criteria; these are the critical enablers for community resilience.

Conclusions: Systematic evaluation of feasible, recommended pandemic influenza interventions generally confirms the US community mitigation guidance yields best strategy choices for pandemic planning that are robust to a wide range of uncertainty. The best strategy combines network- and case-based interventions; network-based interventions are paramount. Because strategies must be applied rapidly, regionally, and stringently for greatest benefit, preparation and public education is required for long-lasting, high community compliance during a pandemic.

Figure 1. Percentage of population infected.

S = schools closed; CTsd = child/teenager social distancing; ASsd = adult/senior socials distancing; Q = household quarantine; T = antiviral treatment; P = antiviral prophylaxis of household members; PEx = extended antiviral prophylaxis. For Ferguson-like disease manifestation and implementation threshold when 10 cases are diagnosed. Case-based interventions are applied directly to or around diagnosed individuals to limit transmission and are: Q, T, P, and PEx. Network-based interventions are applied to affect links and contacts between individuals throughout the entire network and are: S, CTsd, ASsd (where adults continue to attend work, although at a 50% reduction in contacts at the workplace). Case-based interventions vertical; network-based interventions horizontal. Green shading denotes infection rates ≤10 percent of population. Pink shading denotes infection rates between 10 and 25 percent.

Figure 2. Average adult days at home.

S = schools closed; CTsd = child/teenager social distancing; ASsd = adult/senior socials distancing; Q = household quarantine; T = antiviral treatment; P = antiviral prophylaxis of household members; PEx = extended antiviral prophylaxis. For Ferguson-like disease manifestation and implementation threshold when 10 cases are diagnosed. Case-based interventions are applied directly to or around diagnosed individuals to limit transmission and are: Q, T, P, and PEx. Network-based interventions are applied to affect links and contacts between individuals throughout the entire network and are: S, CTsd, ASsd (where adults continue to attend work, although at a 50% reduction in contacts at the workplace). Case-based interventions vertical; network-based interventions horizontal. Green shading denotes infection rates ≤10 percent of population. Pink shading denotes infection rates between 10 and 25 percent.

Figure 3. Population antiviral coverage.

S = schools closed; CTsd = child/teenager social distancing; ASsd = adult/senior socials distancing; Q = household quarantine; T = antiviral treatment; P = antiviral prophylaxis of household members; PEx = extended antiviral prophylaxis. For Ferguson-like disease manifestation and implementation threshold when 10 cases are diagnosed. Case-based interventions are applied directly to or around diagnosed individuals to limit transmission and are: Q, T, P, and PEx. Network-based interventions are applied to affect links and contacts between individuals throughout the entire network and are: S, CTsd, ASsd (where adults continue to attend work, although at a 50% reduction in contacts at the workplace). Case-based interventions vertical; network-based interventions horizontal. Green shading denotes infection rates ≤10 percent of population. Pink shading denotes infection rates between 10 and 25 percent.

Figure 4. Epidemic effects without and with various mitigation strategies.

Plots of numbers of individuals infected, symptomatic, given antivirals, and adult days at home by day of pandemic without mitigation strategies and with mitigation strategies applied for an I_F 1.5 (1918-like; Pandemic Severity Index [PSI] 4–5 pandemic); with Ferguson-like disease manifestation and strategies implemented at 90% compliance with regional mitigation. Plots are averages of all 100 simulations done. Comparisons are to the plot with no mitigation strategies applied. a—no mitigation strategies applied. Note the early peak of 1500 symptomatic cases at day 28 and that approximately 900 adults (9% of the population) are at home from illness at peak. Epidemic effects end by day 60. b—all case-based interventions applied (Q+PEx). Note the significant requirements for antiviral drugs (>30% of population receives antivirals at peak). Symptomatic cases are contained to <250 at peak and adult days at home peak at 500 from illness or home quarantine. The epidemic effects last for 160 days. c—all network-based interventions applied (S+CTsd+ASsd). Note the significant, sustained increase in adult days at home because of the school closings and childcare required, peaking at approximately 1400 adults home/day and tapering off slowly. However, symptomatic cases are contained to <200 at peak. The epidemic effects last approximately 120 days. d—the best strategy we found in these simulations (P+S+CTsd+ASsd). Ill persons are treated with antivirals, household members of ill persons receive antiviral prophylaxis, schools are closed and children's and teenagers' contacts are reduced by 90%, adults' and seniors' non-work contacts are decreased by 90% and workplace contacts by 50%. Note the similar peak of adult days at home (at around 1400) as when only network-based strategies are applied, but with rapid fall-off, with nearly no adult days at home required after approximately day 50. Symptomatic cases are minimized to <200 at peak. Epidemic effects end around day 100. e—the best strategy (P+S+CTsd+ASsd) with Q added. Note that the addition of Q does not change the number of symptomatic cases, but does extend required adult days at home and lengthens the epidemic effects to approximately 120 days.

Figure 5. Epidemic effects with perturbed parameter assumptions.

Plots of I_F 1.5 epidemics (Ferguson-like disease manifestation) with best strategy applied showing effects of reduced compliance, local-only mitigation, reduced compliance and local-only mitigation, delayed implementation threshold to 100 cases, and relaxed (3-case/7day) rescinding threshold. Plots are averages of all 100 simulations. Comparisons are to the best strategy plot. a—the best strategy found in these simulations (P+S+CTsd+ASsd). b—best strategy applied at 60% compliance. Note the extended duration of epidemic effects (>160 days), length of time antivirals are required, and greatly increased requirements for adult days at home. c—best strategy applied at 90% compliance with local-only mitigation. Note the increase in use of antivirals, extended epidemic effects and increase in adult days at home. d—best strategy applied at 60% compliance with local-only mitigation. Note the higher peaks in numbers of infected and symptomatic near day 40, the increased use and longer duration of need for antivirals and the longer duration of epidemic effects to nearly 160 days. e—best strategy applied with delayed implementation (when 100 cases have occurred). Note the high, early peak of cases and accompanying need for antivirals until the strategy controls the epidemic at day 120. f—best strategy applied with the 3-case/7 day rescinding threshold. Note the extended duration of the epidemic and the erratic downslope of adult days at home as the mitigation strategy cycles off when the rescinding threshold is met and on again when 10 cases occur (the implementation threshold).

Figure 6. Epidemic effects with extended parameter assumptions.

Plots of I_F 1.5 epidemics (Ferguson-like disease manifestation, at 90% compliance, with regional mitigation) showing extensions of parameter assumptions. Plots are averages of all 100 simulations. Comparisons are to the best strategy plot. a—the best strategy found in these simulations (P+S+CTsd+ASsd). b—best strategy under Longini-like assumptions of influenza natural history. Note the similar peak in numbers of infected and symptomatic, but there are additional and extended requirements for antiviral use, adult days at home and longer duration of epidemic effects. c—best strategy with Longini-like with extended period of infectiousness. Note the elongated downslope (and overall increase) of required adult days at home and long duration of epidemic effects. d—best strategy with similar transmission across age classes. Note the minimal increase in duration of adult days at home and duration of epidemic effects. e—best strategy with augmented social networks. Note the slight increase in duration of adult days at home and the significantly increased duration of epidemic effects. f—best strategy with pre-pandemic vaccine targeted to children and teenagers. Note the similarity in curves of required adult days at home and the slightly decreased duration of epidemic effects (from 100 days to 90 days). g—best strategy and pre-pandemic vaccine targeted to adults. Note the lack of benefit on numbers of infected, symptomatic, adult days at home and the increased duration of epidemic effects (from 100 days to 130 days).