Abstract
Stockpiling neuraminidase inhibitors (NAIs) such as oseltamivir and zanamivir is part of a global effort to be prepared for an influenza pandemic. However, the contribution of NAIs for the treatment and prevention of influenza and its complications is largely debatable due to constraints in the ability to control for confounders and to explore unobserved areas of the drug effects. For this study, we used a mathematical model of influenza infection which allowed transparent analyses. The model recreated the oseltamivir effects and indicated that: (i) the efficacy was limited by design, (ii) a 99% efficacy could be achieved by using high drug doses (however, taking high 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 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.
Highlights
Influenza A virus (IAV) infection affects about 20% of the worldwide population annually [1].The 2009 influenza pandemic showed that the pandemic could cause major adverse health and economic outcomes [2]
Assuming an idealistic scenario of instantaneous absorption of neuraminidase inhibitors (NAIs), it was shown that the drug concentration stabilized to well-defined lower (Dl ) and upper (Du ) bounds after a few doses, as illustrated in Figure 3
Oseltamivir works, but with a limited efficacy that is constrained by its intrinsic pharmacokinetic parameters and influenza host dynamics
Summary
Influenza A virus (IAV) infection affects about 20% of the worldwide population annually [1]. The 2009 influenza pandemic showed that the pandemic could cause major adverse health and economic outcomes [2]. While vaccines remain the primary means to prevent outbreaks, the effects of influenza vaccines are mild and regularly outpaced by the antigenic drift of the virus [3]. As a result, stockpiling antiviral drugs in anticipation of a pandemic has been recommended, among other public health routines [4]. The benefits of this approach, have been debated in terms of treating and preventing epidemic spread [5,6].
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