Potential role of human challenge studies for investigation of influenza transmission

The importance of different routes of influenza transmission (including the role of bioaerosols) and the ability of masks and hand hygiene to prevent transmission remain poorly understood. Interest in transmission of influenza has grown as the effectiveness of prevention measures implemented during the 2009 H1N1 pandemic are questioned and as plans to better prepare for the next pandemic are debated. Recent studies of naturally infected patients have encountered difficulties and have fallen short of providing definitive answers. Human challenge studies with influenza virus date back to the 1918 pandemic. In more recent decades they have been undertaken to investigate the efficacy of antiviral agents and vaccines. Could experimental challenge studies, in which volunteers are deliberately infected with influenza virus, provide an alternative approach to the study of transmission? Here, we review the latest intervention studies and discuss the potential of challenge studies to address the remaining gaps in our knowledge.