Burke leads the development of computational models and simulations of epidemic infectious diseases to evaluate prevention and control strategies. His research includes the development of diagnostics, clinical vaccine trials, population-based field studies, and computational modeling of epidemic control efforts. He has also studied prevention and control of infectious diseases of global concern, including HIV/AIDS, influenza, dengue, and emerging infectious diseases, and has performed field epidemiology and vaccine studies across various developing countries.
His recent research has focused on the development of strategies for containing an emerging influenza pandemic and on interruption of virus transmission to humans from animals among central African bushmeat hunters. Burke spent six years on active duty with the U.S. Army conducting disease research at the Armed Forces Research Institute of Medical Sciences in Bangkok. He also led military disease research at the Walter Reed Army Institute of Research.