The main objective of this PhD was to define a set of methodological tools to describe and study the time course of influenza and its natural history parameters. The principal work was the development of a model to describe influenza infection and illness timeline. Influenza virus kinetics (VK) is used as a surrogate of infectiousness, while the natural history of influenza is described by symptom dynamics (SD). We developped an original virus kinetics/symptom dynamics (VKSD) model based on a population approach. Our approach extends previous works by including the innate response and providing realistic estimates of infection and illness parameters, taking into account the strong interindividual variability. The choice of the study design is crucial to accurately estimate the model parameters. For this purpose we performed an optimal design analysis to propose cost-effective and practical designs. A set of designs adapted to study influenza VK, innate immune response and/or SD was elaborated and could help design further studies on influenza viral kinetics with decreased discomfort and cost. Finally, we realised an in silico analysis studying the effect of neuraminidase inhibitors on influenza infection and illness and on resistance emergence. We explored oseltamivir efficacy through simulated pharmacokinetics for differents regimens, in immunocompetent or immunodeficient subjects. We identified the situations leading to a balance between efficacy and resistance emergence. This work point out the importance of learning as much as we can about dealing with influenza infection and mitigating its impact
