Emergence of Drug-Resistant Influenza Virus: Population Dynamical Considerations
Roland R. Regoes and
Sebastian Bonhoeffer*
Institute of Integrative Biology, ETH Zürich, ETH Zentrum CHN K12.1, Universitätsstrasse 16, CH 8092 Zürich, Switzerland.
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Fig. 1. Epidemic curves as predicted by the model of Stilianakis et al. (34) for parameters characterizing interventions with oseltamivir. [For model equations and parameter values, see the SOM (35).] (A) Number of infected individuals using treatment only (red) or using prophylaxis in addition to treatment (blue) over the first 30 days of the epidemic. The gray line shows the course of the epidemic without any intervention. The solid lines depict the total number of infected individuals, whereas the dashed lines depict the number of individuals infected with resistant virus. The total number of illnesses during the 30-day period is 247, 227, or 26 in the epidemic with no intervention, with treatment, or with prophylaxis, respectively. (We assume that there is no pre-existing immunity in the population.) All symptomatic individuals receive treatment on average 1.4 days after the onset of symptoms. Prophylaxis starts at day 7. (B) Fraction of individuals infected with resistant virus under treatment (red) and prophylaxis (blue).
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Fig. 2. Fraction of resistant cases as a function of the relative transmission fitness of resistant virus and the rate at which treatment generates de novo resistance with (A) treatment of symptomatic individuals and (B) prophylaxis in addition to treatment. The top of the z axis corresponds to 100%, which is the theoretical maximum. The relative transmission fitness ranges from 0 to 1, and the rate of de novo resistance ranges from 0 to 0.072 per day. For other parameters, see the SOM (35). The most likely parameter ranges for oseltamivir (violet) and amantadine (cyan) are indicated on the resistance surfaces. (For oseltamivir, these are also the parameters used in Fig. 1.) Because of our rudimentary knowledge with regard to these parameters, these ranges need to be regarded with caution.
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