The overall aim of this proposal is to provide qualitative and quantitative data on transmission of avian influenza to humans in contact with infected animals, through an in-depth analysis of data collected during an outbreak of HPAI H7N7 in The Netherlands with novel virological and epidemiological tools. This data will be essential to design future control strategies including surveillance, early detection of potential pandemic strains, and evidence based infection prevention. In the project we propose the following lines of research: 1. provide better estimates for the extent of transmission of HPAI H7N7 to humans by developing improved methods for measurement of antibodies in humans following infection with non-human adapted avian influenza viruses. 2. providing estimates for the level of virus exposure of humans in direct contact with poultry during HPAI outbreaks on commercial poultry farms by studying the within herd dynamics of Al in poultry flocks. 3. using the combined data from research lines 1 and 2 to study which activities during culling operations are associated with increased risk of infection in humans 4. gain insight into the dose response relationship for human infection with an avian influenza virus to allow better prediction of the risks associated with specific activities (e.g. handling live birds, slaughtering, stable disinfection) ? 5. develop rapid methods for detection of (infection with) HPAI and specific virulence traits for human ? infection to be incorporated in enhanced surveillance for HPAI infections of humans during outbreaks. Avian influenza viruses can infect humans that become in contact with infected animals, especially birds. The greatest risk is that an avian influenza virus develops into a new pandemic flu strain. Through the work in this project we seek to understand exactly what happens when people come into contact with infected poultry, which types of activities form the greatest risks of getting infected. In order to do that, we will develop sensitive methods to detect infection of humans, also if they do not become ill, study how exactly the viruses behave in a poultry flock, and how that information can be used to determine when people have the greatest chance of becoming infected when they get into contact with these animals. We do this by studying data and samples collected during outbreaks of avian influenza in The Netherlands and China. ? ? ? ?