Dataset Information

Reactive strategies for containing developing outbreaks of pandemic influenza.

ABSTRACT:

Background

In 2009 and the early part of 2010, the northern hemisphere had to cope with the first waves of the new influenza A (H1N1) pandemic. Despite high-profile vaccination campaigns in many countries, delays in administration of vaccination programs were common, and high vaccination coverage levels were not achieved. This experience suggests the need to explore the epidemiological and economic effectiveness of additional, reactive strategies for combating pandemic influenza.

Methods

We use a stochastic model of pandemic influenza to investigate realistic strategies that can be used in reaction to developing outbreaks. The model is calibrated to documented illness attack rates and basic reproductive number (R0) estimates, and constructed to represent a typical mid-sized North American city.

Results

Our model predicts an average illness attack rate of 34.1% in the absence of intervention, with total costs associated with morbidity and mortality of US$81 million for such a city. Attack rates and economic costs can be reduced to 5.4% and US$37 million, respectively, when low-coverage reactive vaccination and limited antiviral use are combined with practical, minimally disruptive social distancing strategies, including short-term, as-needed closure of individual schools, even when vaccine supply-chain-related delays occur. Results improve with increasing vaccination coverage and higher vaccine efficacy.

Conclusions

Such combination strategies can be substantially more effective than vaccination alone from epidemiological and economic standpoints, and warrant strong consideration by public health authorities when reacting to future outbreaks of pandemic influenza.

SUBMITTER: Andradottir S

PROVIDER: S-EPMC3317583 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

Reactive strategies for containing developing outbreaks of pandemic influenza.

Andradóttir Sigrún S Chiu Wenchi W Goldsman David D Lee Mi Lim ML Tsui Kwok-Leung KL Sander Beate B Fisman David N DN Nizam Azhar A

BMC public health 20110225

<h4>Background</h4>In 2009 and the early part of 2010, the northern hemisphere had to cope with the first waves of the new influenza A (H1N1) pandemic. Despite high-profile vaccination campaigns in many countries, delays in administration of vaccination programs were common, and high vaccination coverage levels were not achieved. This experience suggests the need to explore the epidemiological and economic effectiveness of additional, reactive strategies for combating pandemic influenza.<h4>Meth ...[more]

PMID: 21356128

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Project description:BackgroundAs seen during past pandemic influenza outbreaks, pharmaceutical interventions (PHIs) with vaccines and antivirals are the most effective methods of mitigation. However, availability of PHIs is unlikely to be adequate during the early stages of a pandemic. Hence, for early mitigation and possible containment, non-pharmaceutical interventions (NPIs) offer a viable alternative. Also, NPIs may be the only available interventions for most underdeveloped countries. In this paper we present a comprehensive methodology for design of effective NPI strategies.MethodsWe develop a statistical ANOVA-based design approach that uses a detailed agent-based simulation as an underlying model. The design approach obtains the marginal effect of the characteristic parameters of NPIs, social behavior, and their interactions on various pandemic outcome measures including total number of contacts, infections, and deaths. We use the marginal effects to establish regression equations for the outcome measures, which are optimized to obtain NPI strategies. Efficacy of the NPI strategies designed using our methodology is demonstrated using simulated pandemic influenza outbreaks with different levels of virus transmissibility.ResultsOur methodology was able to design effective NPI strategies, which were able to contain outbreaks by reducing infection attack rates (IAR) to below 10% in low and medium virus transmissibility scenarios with 33% and 50% IAR, respectively. The level of reduction in the high transmissibility scenario (with 65% IAR) was also significant. As noted in the published literature, we also found school closure to be the single most effective intervention among all NPIs.ConclusionsIf harnessed effectively, NPIs offer a significant potential for mitigation of pandemic influenza outbreaks. The methodology presented here fills a gap in the literature, which, though replete with models on NPI strategy evaluation, lacks a treatise on optimal strategy design.

Project description:With the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.We extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.We demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.Our findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.

Project description:BackgroundThe threat of emergence of a human-to-human transmissible strain of highly pathogenic influenza A(H5N1) is very real, and is reinforced by recent results showing that genetically modified A(H5N1) may be readily transmitted between ferrets. Public health authorities are hesitant in introducing social distancing interventions due to societal disruption and productivity losses. This study estimates the effectiveness and total cost (from a societal perspective, with a lifespan time horizon) of a comprehensive range of social distancing and antiviral drug strategies, under a range of pandemic severity categories.MethodsAn economic analysis was conducted using a simulation model of a community of ~30,000 in Australia. Data from the 2009 pandemic was used to derive relationships between the Case Fatality Rate (CFR) and hospitalization rates for each of five pandemic severity categories, with CFR ranging from 0.1% to 2.5%.ResultsFor a pandemic with basic reproduction number R0 = 1.8, adopting no interventions resulted in total costs ranging from $441 per person for a pandemic at category 1 (CFR 0.1%) to $8,550 per person at category 5 (CFR 2.5%). For severe pandemics of category 3 (CFR 0.75%) and greater, a strategy combining antiviral treatment and prophylaxis, extended school closure and community contact reduction resulted in the lowest total cost of any strategy, costing $1,584 per person at category 5. This strategy was highly effective, reducing the attack rate to 5%. With low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, whereas higher severity pandemic costs are dominated by healthcare costs and costs arising from productivity losses due to death.ConclusionsFor pandemics in high severity categories the strategies with the lowest total cost to society involve rigorous, sustained social distancing, which are considered unacceptable for low severity pandemics due to societal disruption and cost.

Project description:BACKGROUND: All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. METHODOLOGY: We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. PRINCIPAL FINDINGS: The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4-0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. CONCLUSIONS: The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines.

Dataset Information

Reactive strategies for containing developing outbreaks of pandemic influenza.

Background

Methods

Results

Conclusions

Publications

Reactive strategies for containing developing outbreaks of pandemic influenza.

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