This was calculated based on the pandemic regimen of 150 mg oseltamivir twice daily and the minimum price for oseltamivir in large purchases: 1

This was calculated based on the pandemic regimen of 150 mg oseltamivir twice daily and the minimum price for oseltamivir in large purchases: 1.6 US cents per mg as of 2006 Cephapirin Benzathine [22]. doses of drug 48 h post-infection could only yield a maximum of 1.6-day reduction in the time to symptom alleviation), and (iii) contributions of oseltamivir to epidemic control could Rabbit polyclonal to FBXO42 be high, but were observed only in fragile settings. In a typical influenza infection, NAIs efficacy is inherently not high, and even if their efficacy is improved, the effect can be negligible in practice. and have a mean lifespan of 1/ days. The free virus, in turn, is cleared at a constant rate per day. The intensity of the symptoms, denoted by , increases with the proportion of infected cellsdue to the release of cytokines [16,17]at a rate and has a constant resolving Cephapirin Benzathine rate and the symptom score. The former assumption is due to the drug blocking the release of the virus, and the latter is the result of the reduction in the hosts induction of cytokines [17]. In Cephapirin Benzathine general, four parameters governed the effect of the NAIs: (i) the drug concentration elimination rate per day, (ii) the intake frequency (a constant interval was assumed), (iii) the dose in mg, and (iv) the concentration at which the drug reached a 50% efficacy (EC50). The two parameters, intake frequency and dose, defined the treatment regimen; the elimination rate and half-maximal concentration constituted the drug-specific parameters. The exploration of the sensitivity of the drugs efficacy with respect to the above four parameters provided a complete efficacy landscape for the NAIs. The full system of equations and analytical analyses are given in the Appendix (illustrated in Figure 1). 2.2. Population Model To assess the prophylactic effects of NAIs in an epidemic context, the within-host model was used to generate the infection dynamics of an individual-based network model of influenza transmission (as illustrated in Figure 2 and detailed in Section 2.3). The following two conditions were assumed to determine the between-host transmission from the within-host dynamics: (i) the transmission potential of an infected subject at any given time is defined by its viral load at that time divided by the maximum viral load [18] (this leads to a more realistic time-dependent transmission potential based on the viral load dynamics) and (ii) the infectious period starts when the viral load crosses the threshold Vc = 1.35 TCID50/mL, as defined previously in Lukens et al. [18]. Open in a separate window Figure 2 Illustration of the epidemic network model simulations. Based on empirical contact distribution data, the number of contacts (edges) was sampled and assigned to each subject (node). Based on the coverage and duration of the intervention, the nodes were assigned to either taking the drug in the defined period or not. Based on the within-host model, each infected node xth (colored red in the network) will have its own viral dynamics (red area in the dynamic) depending on whether it Cephapirin Benzathine was already taking the drug at the time of infection or not. The transmission between infected and uninfected nodes (colored blue in the network) was evaluated in every simulation time step (e.g., i and j), during which the transmission probability varied (indicated by the edges color intensity) following the infection dynamics of the infected subject under consideration (see Section 2.3, Software and Algorithms, for further details). All epidemic simulations were conducted in settings that were Cephapirin Benzathine tailored to detect the drugs effectiveness in the models: (i) all infected individuals responded similarly to the drug (i.e., a uniform efficacy among treated individuals); (ii) uninfected individuals were equally susceptible to the infection; (iii) the drugs were assumed to be readily available and delivered to all intended recipients uniformly in time; (iv) all recipients took the drugs with complete adherence to the implemented treatment regimen; (v) all infected cases were known, including asymptomatic cases, in calculating the drug effect on reducing the epidemic size; and (vi) there were no other interventions in place and the contact network remained unchanged during the epidemic. While these conditions are unrealistic, changes observed under these conditions in the epidemic trajectory could be attributed solely to the drugs effect. Simulated scenarios were created based on the assumption that the interventions were constrained by a fixed amount of resources (US dollars). This was calculated based on the pandemic regimen of 150 mg oseltamivir twice daily and the minimum price for oseltamivir in large purchases: 1.6 US cents per mg as of 2006 [22]. Based.