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Optimizing tactics for use of the U.S. antiviral strategic national stockpile for pandemic influenza.

ABSTRACT: In 2009, public health agencies across the globe worked to mitigate the impact of the swine-origin influenza A (pH1N1) virus. These efforts included intensified surveillance, social distancing, hygiene measures, and the targeted use of antiviral medications to prevent infection (prophylaxis). In addition, aggressive antiviral treatment was recommended for certain patient subgroups to reduce the severity and duration of symptoms. To assist States and other localities meet these needs, the U.S. Government distributed a quarter of the antiviral medications in the Strategic National Stockpile within weeks of the pandemic's start. However, there are no quantitative models guiding the geo-temporal distribution of the remainder of the Stockpile in relation to pandemic spread or severity. We present a tactical optimization model for distributing this stockpile for treatment of infected cases during the early stages of a pandemic like 2009 pH1N1, prior to the wide availability of a strain-specific vaccine. Our optimization method efficiently searches large sets of intervention strategies applied to a stochastic network model of pandemic influenza transmission within and among U.S. cities. The resulting optimized strategies depend on the transmissability of the virus and postulated rates of antiviral uptake and wastage (through misallocation or loss). Our results suggest that an aggressive community-based antiviral treatment strategy involving early, widespread, pro-rata distribution of antivirals to States can contribute to slowing the transmission of mildly transmissible strains, like pH1N1. For more highly transmissible strains, outcomes of antiviral use are more heavily impacted by choice of distribution intervals, quantities per shipment, and timing of shipments in relation to pandemic spread. This study supports previous modeling results suggesting that appropriate antiviral treatment may be an effective mitigation strategy during the early stages of future influenza pandemics, increasing the need for systematic efforts to optimize distribution strategies and provide tactical guidance for public health policy-makers.

SUBMITTER: Dimitrov NB

PROVIDER: S-EPMC3023704 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Optimizing tactics for use of the U.S. antiviral strategic national stockpile for pandemic influenza.

Dimitrov Nedialko B NB Goll Sebastian S Hupert Nathaniel N Pourbohloul Babak B Meyers Lauren Ancel LA

PloS one 20110119 1

In 2009, public health agencies across the globe worked to mitigate the impact of the swine-origin influenza A (pH1N1) virus. These efforts included intensified surveillance, social distancing, hygiene measures, and the targeted use of antiviral medications to prevent infection (prophylaxis). In addition, aggressive antiviral treatment was recommended for certain patient subgroups to reduce the severity and duration of symptoms. To assist States and other localities meet these needs, the U.S. Go ...[more]

PMID: 21283514

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Project description:BACKGROUND: Wide-scale use of antiviral agents in the event of an influenza pandemic is likely to promote the emergence of drug resistance, with potentially deleterious effects for outbreak control. We explored factors promoting resistance within a dynamic infection model, and considered ways in which one or two drugs might be distributed to delay the spread of resistant strains or mitigate their impact. METHODS AND FINDINGS: We have previously developed a novel deterministic model of influenza transmission that simulates treatment and targeted contact prophylaxis, using a limited stockpile of antiviral agents. This model was extended to incorporate subclinical infections, and the emergence of resistant virus strains under the selective pressure imposed by various uses of one or two antiviral agents. For a fixed clinical attack rate, R(0) rises with the proportion of subclinical infections thus reducing the number of infections amenable to treatment or prophylaxis. In consequence, outbreak control is more difficult, but emergence of drug resistance is relatively uncommon. Where an epidemic may be constrained by use of a single antiviral agent, strategies that combine treatment and prophylaxis are most effective at controlling transmission, at the cost of facilitating the spread of resistant viruses. If two drugs are available, using one drug for treatment and the other for prophylaxis is more effective at preventing propagation of mutant strains than either random allocation or drug cycling strategies. Our model is relatively straightforward, and of necessity makes a number of simplifying assumptions. Our results are, however, consistent with the wider body of work in this area and are able to place related research in context while extending the analysis of resistance emergence and optimal drug use within the constraints of a finite drug stockpile. CONCLUSIONS: Combined treatment and prophylaxis represents optimal use of antiviral agents to control transmission, at the cost of drug resistance. Where two drugs are available, allocating different drugs to cases and contacts is likely to be most effective at constraining resistance emergence in a pandemic scenario.

Project description:Policy Points Reflecting on current response deficiencies, we offer a model for a national contingency supply chain cell (NCSCC) construct to manage the medical materials supply chain in support of emergencies, such as COVID-19. We develop the following: a framework for governance and response to enable a globally independent supply chain; a flexible structure to accommodate the requirements of state and county health systems for receiving and distributing materials; and a national material "control tower" to improve transparency and real-time access to material status and location.ContextMuch of the discussion about the failure of the COVID-19 supply chain has centered on personal protective equipment (PPE) and the degree of vulnerability of care. Prior research on supply chain risks have focused on mitigating the risk of disruptions of specific purchased materials within a bounded region or on the shifting status of cross-border export restrictions. But COVID-19 has impacted every purchase category, region, and border. This paper is responsive to the National Academies of Sciences, Engineering and Medicine recommendation to study and monitor disasters and to provide governments with course of action to satisfy legislative mandates.MethodsOur analysis draws on our observations of the responses to COVID-19 in regard to acquisition and contracting problem-solving, our review of field discussions and interactions with experts, a critique of existing proposals for managing the strategic national stockpile in the United States a mapping of the responses to national contingency planning phases, and the identification of gaps in current national healthcare response policy frameworks and proposals.FindingsCurrent proposals call for augmenting a system that has failed to deliver the needed response to COVID-19. These proposals do not address the key attributes for pandemic plan renewal: flexibility, traceability and transparency, persistence and responsiveness, global independence, and equitable access. We offer a commons-based framework for achieving the opportunities and risks which are responsive to a constellation of intelligence assets working in and across focal targets of global supply chain risk.ConclusionsThe United States needs a "commons-based strategy" that is not simply a stockpile repository but instead is a network of repositories, fluid inventories, and analytic monitoring governed by the experts. We need a coordinated effort, a "commons" that will direct both conventional and new suppliers to meet demands and to eliminate hoarding and other behaviors.

Project description:ObjectiveTo describe changes in reported influenza activity associated with the 2009 H1N1 pandemic in European countries and determine whether there is a correlation between these changes and completeness of national strategic pandemic preparedness.DesignA retrospective correlational study.SettingCountries were included if their national strategic plans had previously been analysed and if weekly influenza-like illness (ILI) data from sentinel networks between week 21, 2006 and week 20, 2010 were more than 50% complete.Outcome measuresFor each country we calculated three outcomes: the percentage change in ILI peak height during the pandemic relative to the prepandemic mean; the timing of the ILI peak and the percentage change in total cases relative to the prepandemic mean. Correlations between these outcomes and completeness of a country's national strategic pandemic preparedness plan were assessed using the Pearson product-moment correlation coefficient.ResultsNineteen countries were included. The ILI peak occurred earlier than the mean seasonal peak in 17 countries. In 14 countries the pandemic peak was higher than the seasonal peak, though the difference was large only in Norway, the UK and Greece. Nine countries experienced more total ILI cases during the pandemic compared with the mean for prepandemic years. Five countries experienced two distinct pandemic peaks. There was no clear pattern of correlation between overall completeness of national strategic plans and pandemic influenza outcome measures and no evidence of association between these outcomes and components of pandemic plans that might plausibly affect influenza outcomes (public health interventions, vaccination, antiviral use, public communication). Amongst the 17 countries with a clear pandemic peak, only the correlation between planning for essential services and change in total ILI cases significantly differed from zero: correlation coefficient (95% CI) 0.50 (0.02, 0.79).ConclusionsThe diversity of pandemic influenza outcomes across Europe is not explained by the marked variation in the completeness of pandemic plans.

Project description:BackgroundThe response to the next influenza pandemic will likely include extensive use of antiviral drugs (mainly oseltamivir), combined with other transmission-reducing measures. Animal and in vitro studies suggest that some strains of influenza may become resistant to oseltamivir while maintaining infectiousness (fitness). Use of antiviral agents on the scale anticipated for the control of pandemic influenza will create an unprecedented selective pressure for the emergence and spread of these strains. Nonetheless, antiviral resistance has received little attention when evaluating these plans.Methods and findingsWe designed and analyzed a deterministic compartmental model of the transmission of oseltamivir-sensitive and -resistant influenza infections during a pandemic. The model predicts that even if antiviral treatment or prophylaxis leads to the emergence of a transmissible resistant strain in as few as 1 in 50,000 treated persons and 1 in 500,000 prophylaxed persons, widespread use of antivirals may strongly promote the spread of resistant strains at the population level, leading to a prevalence of tens of percent by the end of a pandemic. On the other hand, even in circumstances in which a resistant strain spreads widely, the use of antivirals may significantly delay and/or reduce the total size of the pandemic. If resistant strains carry some fitness cost, then, despite widespread emergence of resistance, antivirals could slow pandemic spread by months or more, and buy time for vaccine development; this delay would be prolonged by nondrug control measures (e.g., social distancing) that reduce transmission, or use of a stockpiled suboptimal vaccine. Surprisingly, the model suggests that such nondrug control measures would increase the proportion of the epidemic caused by resistant strains.ConclusionsThe benefits of antiviral drug use to control an influenza pandemic may be reduced, although not completely offset, by drug resistance in the virus. Therefore, the risk of resistance should be considered in pandemic planning and monitored closely during a pandemic.

Dataset Information

Optimizing tactics for use of the U.S. antiviral strategic national stockpile for pandemic influenza.

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Optimizing tactics for use of the U.S. antiviral strategic national stockpile for pandemic influenza.

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