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Can antiviral drugs contain pandemic influenza transmission?

ABSTRACT: Antiviral drugs dispensed during the 2009 influenza pandemic generally failed to contain transmission. This poses the question of whether preparedness for a future pandemic should include plans to use antiviral drugs to mitigate transmission.Simulations using a standard transmission model that allows for infected arrivals and delayed vaccination show that attempts to contain transmission require relatively few antiviral doses. In contrast, persistent use of antiviral drugs when the reproduction number remains above 1 use very many doses and are unlikely to reduce the eventual attack rate appreciably unless the stockpile is very large. A second model, in which the community has a household structure, shows that the effectiveness of a strategy of dispensing antiviral drugs to infected households decreases rapidly with time delays in dispensing the antivirals. Using characteristics of past pandemics it is estimated that at least 80% of primary household cases must present upon show of symptoms to have a chance of containing transmission by dispensing antiviral drugs to households. To determine data needs, household outbreaks were simulated with 50% receiving antiviral drugs early and 50% receiving antiviral drugs late. A test to compare the size of household outbreaks indicates that at least 100-200 household outbreaks need to be monitored to find evidence that antiviral drugs can mitigate transmission of the newly emerged virus.Use of antiviral drugs in an early attempt to contain transmission should be part of preparedness plans for a future influenza pandemic. Data on the incidence of the first 350 cases and the eventual attack rates of the first 200 hundred household outbreaks should be used to estimate the initial reproduction number R and the effectiveness of antiviral drugs to mitigate transmission. Use of antiviral drugs to mitigate general transmission should cease if these estimates indicate that containment of transmission is unlikely.

SUBMITTER: Becker NG

PROVIDER: S-EPMC3065466 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Can antiviral drugs contain pandemic influenza transmission?

Becker Niels G NG Wang Dingcheng D

PloS one 20110328 3

Antiviral drugs dispensed during the 2009 influenza pandemic generally failed to contain transmission. This poses the question of whether preparedness for a future pandemic should include plans to use antiviral drugs to mitigate transmission.Simulations using a standard transmission model that allows for infected arrivals and delayed vaccination show that attempts to contain transmission require relatively few antiviral doses. In contrast, persistent use of antiviral drugs when the reproduction ...[more]

PMID: 21464934

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Project description:BackgroundInfluenza pandemics occur when a novel influenza strain, to which humans are immunologically naïve, emerges to cause infection and illness on a global scale. Differences in the viral properties of pandemic strains, relative to seasonal ones, can alter the effectiveness of interventions typically implemented to control seasonal influenza burden. As a result, annual control activities may not be sufficient to contain an influenza pandemic.PurposeThis study seeks to inform pandemic policy and planning initiatives by reviewing the effectiveness of previous interventions to reduce pandemic influenza transmission and infection. Results will inform the planning and design of more focused in-depth systematic reviews for specific types of interventions, thus providing the most comprehensive and current understanding of the potential for alternative interventions to mitigate the burden of pandemic influenza.MethodsA systematic review and narrative synthesis of existing systematic reviews and meta-analyses examining intervention effectiveness in containing pandemic influenza transmission was conducted using information collected from five databases (PubMed, Medline, Cochrane, Embase, and Cinahl/EBSCO). Two independent reviewers conducted study screening and quality assessment, extracting data related to intervention impact and effectiveness.Results and discussionMost included reviews were of moderate to high quality. Although the degree of statistical heterogeneity precluded meta-analysis, the present systematic review examines the wide variety of interventions that can impact influenza transmission in different ways. While it appears that pandemic influenza vaccination provides significant protection against infection, there was insufficient evidence to conclude that antiviral prophylaxis, seasonal influenza cross-protection, or a range of non-pharmaceutical strategies would provide appreciable protection when implemented in isolation. It is likely that an optimal intervention strategy will employ a combination of interventions in a layered approach, though more research is needed to substantiate this proposition.Trial registrationPROSPERO 42016039803.

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.

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Can antiviral drugs contain pandemic influenza transmission?

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Can antiviral drugs contain pandemic influenza transmission?

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