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.
Highlights
The threat from avian influenza H1N5 prompted many countries to establish a stockpile of antiviral drugs, [1,2,3,4], such as oseltamivir and zananivir
Transmission: contained or not contained The model given by equations (1)–(3) was used, with a range of plausible parameters values, to determine the eventual attack rate
For all parameter values, increasing m from zero decreases the transmission rate bfm and this is reflected in a decline in the eventual attack rate (AR)
Summary
The threat from avian influenza H1N5 prompted many countries to establish a stockpile of antiviral drugs, [1,2,3,4], such as oseltamivir and zananivir. Observed are reduced levels of virus shedding [5,6,10,11,12,13,14], which suggests a reduction in infectivity in the event of a breakthrough infection Use of these observations in modeling studies suggests that stockpiles of antiviral drugs held by some nations are sufficiently large to defer the peak of the epidemic until a newly developed vaccine is available to control transmission [15,16,17,18]. These results could be expected to apply to pandemic H1N1 since, with a reproduction number estimated to be of the order 1.2-1.5 in some localities [19,20], its transmissibility is relatively modest
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