Evaluating the impact of Baloxavir on dynamics of influenza within-host infection and within-household transmission

The risk of a new pandemic (an infectious disease that spreads globally) caused by an influenza virus is as high as it has ever been, in particular in the context of the widespread presence of a particular influenza virus called H5N1. H5N1 is an avian influenza virus that can infect humans and cause severe illness and deaths in humans. In this context, it is important to prepare robust plans to respond to influenza pandemics. These plans need to consider non-pharmaceutical (e.g. social distancing measures, closure of specific places etc.) and pharmaceutical measures. Given their ability to reduce symptom severity as well as the transmission of the virus to other people, large scale use of antiviral drugs such as Baloxavir needs to be robustly assessed. Baloxavir works by preventing the release of newly formed virus from infected cells. This assessment requires a thorough evaluation of Baloxavir's impact on the dynamics of the progression of the influenza infection within the infected person (within-host infection) and transmission of the infection to others within a household (within-household transmission).

We aim to reanalyze data from the Centerstone study with sophisticated mathematical and statistical models to derive a more detailed understanding of the impact of Baloxavir, a new treatment with promising impact on transmission. Our approach will rely on “Bayesian data augmentation” methods that can address complex missing data problems (for example we do not know when, where and by whom individuals were infected). Compared to the original analysis, this will ensure that we better account for the multiple routes through which individuals might have been infected in the study. In addition, by combining models that describe the impact of the treatment on both within-host infection dynamics and on within-household transmission dynamics, we will obtain a fuller understanding of Baloxavir’s impact. This study builds on years of experience analyzing data from household transmission studies in the Mathematical Modelling of Infectious Disease Unit at Institut Pasteur. The study will complement the original analysis of the data by providing more thorough modelling of the impact of Baloxavir on within-host infection dynamics and within-household transmission dynamics.

Results of this study will inform mathematical models developed to plan the response to future influenza pandemic.