Can antiviral drugs contain pandemic influenza transmission?

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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. © 2011 Becker, Wang.

Figures

  • Figure 1. Baseline transmission model. Mass vaccination and arrival of infected individuals from other locations has been added to the standard SIR transmission model. doi:10.1371/journal.pone.0017764.g001
  • Table 1. Baseline values for model parameters.
  • Figure 2. Eventual attack rate (AR ). Percentage of the population infected, as predicted by the baseline model with (a) a~0:5 and (b) a~0:75, for different k0 (stockpile size, as a proportion of the population size) and m (number of antiviral doses dispensed per case). Colours on the graphs range from dark blue (low values) to dark red (high values). doi:10.1371/journal.pone.0017764.g002
  • Figure 3. Doses used per imported case. Mean number of doses used to contain each outbreak initiated by one infected arrival, when m doses are dispensed for every case. doi:10.1371/journal.pone.0017764.g003
  • Figure 4. Curves for which the reproduction number for household outbreaks (RH) equals 1. The three RH~1 curves correspond to (a) antivirals are dispensed at onset of symptoms in the primary household case, (b) antivirals are dispensed two days after symptom onset in the primary case, and (c) no antiviral drugs are dispensed. For each of these three intervention scenarios, RHv1 for every parameter point (h,m) that lies below the RH~1 curve and RHw1 when (h,m) lies above the RH~1 curve. doi:10.1371/journal.pone.0017764.g004
  • Figure 5. How the possibility to contain transmission depends on the proportion who fail to present early. Transmission can be contained for values of p below the curve, where p is the proportion of primary household cases who fail to present early, RH is the household reproduction number when all infected households receive antiviral drugs and the household reproduction number without antiviral drugs is RH0~1:5 for curve (a) and RH0~2:5 for curve (b). doi:10.1371/journal.pone.0017764.g005
  • Figure 6. Power of a test to determine whether antiviral drugs are effective. Power of a test to compare the mean outbreak size in n households who receive antiviral drugs early and n households who do not, for each of the household sizes 2, 3 and 4 (i.e. observations on 6n household outbreaks). A modified version of the Alexander-Govern test is used and power is estimated by applying the test to each of 500 data sets for each n and each effect scenario. In curves (a), (b) and (c) the simulations assume that antiviral drugs partially reduce infectivity and their effect on susceptibility is to induce full, partial and zero protection, respectively. Simulations for curve (d) assume no effect on infectivity and a partial effect on susceptibility. doi:10.1371/journal.pone.0017764.g006

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CITATION STYLE

APA

Becker, N. G., & Wang, D. (2011). Can antiviral drugs contain pandemic influenza transmission? PLoS ONE, 6(3). https://doi.org/10.1371/journal.pone.0017764

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