A Century of InfluenzaIs the World Prepared for the Next Pandemic? Michael A Stoto (bio), Normand LeBlanc (bio), Nellie Darling (bio), Julia Gasior (bio), Mikaela Harmsen (bio), and Casey Zipfel (bio) Over the last century, four international public health crises challenged global health-systems and severely damaged communities. Influenza pandemics, or influenza epidemics that spread throughout the world, all stemmed from changing subtypes of the influenza A virus. Although its unassuming popular name—the "flu"—sometimes minimizes public perception of the threat, influenza is a complex, constantly changing threat, and globalization has created both benefits and new challenges for global health-systems in combating it. Despite all we know about the virus' structure, transmissibility, and epidemiology, there is still much to be discovered in order to combat its potential for causing death and global disruption. Leading up to the centennial of the 1918 "Great Influenza," which caused up to 100 million deaths worldwide, public health officials reviewed and commissioned historical analyses. These studies focused on the following: [End Page 163] • Reconstructing the pathogen's epidemiological characteristics as well as the temporal and geographic spread of the pandemic, including its social and health consequences • Understanding the impact and effectiveness of non-pharmaceutical interventions and other population-based control strategies in various US cities • Identifying parameters and other assumptions for pandemic influenza models, which were subsequently used to assess prevention and control strategies This research, along with studies of other 20th-century pandemics, informed global, federal, state, and local preparation for a possible avian influenza pandemic in the 2000s. It was also used to guide the response to the 2009 H1N1 pandemic, which was far different in character from the 1918 pandemic and the expected avian influenza pandemic. Today, this research continues to guide pandemic planning at both the national and global levels. In order to apply findings from research and to gain further insight into possible responses to a global pandemic in the 21st century, we conducted a simulation exercise of a hypothetical, but realistic, pandemic influenza today. Approximately thirty Georgetown medical, graduate, and undergraduate students played the roles of global, national, and local officials as well as medical advisors responding to a pandemic. The exercise included two phases, each of which ended with a presentation by the student participants to a panel of "decision-makers" from public health and other sectors. The simulation highlighted several areas that were key to the simulation, that would likely also arise in the case of an influenza pandemic today: identifying epidemiological characteristics of the novel pandemic strain, coordinating globally in accord with the International Health Regulations, implementing a Public Health Emergency of International Concern, applying non-pharmaceutical interventions, assessing availability and distribution of medical countermeasures, maintaining standards of care in a crisis, and communicating risk information locally. Global Health Challenges The first phase of the simulation focused on global issues following the emergence of a new subtype of influenza in Vietnam. Several unusual influenza cases were identified in rural Vietnam with a high fatality rate. It was initially unclear if the influenza cases were part of the normal influenza season or whether they were due to a novel strain with pandemic potential. Different subtypes of influenza are characterized by proteins on the surface of the virus.1 A novel influenza subtype arises when the proteins on the surface of the virus combine in new ways. It is important to distinguish whether the influenza cases in Vietnam were due to a novel subtype that could cause a pandemic because often large groups of the population tend to be immunologically naive to novel subtypes, meaning that people do not have immunity because they have never been previously infected by the novel subtype. If the novel subtype is easily spread from human to human, the result could be a pandemic, in which the pathogen can rapidly spread throughout the world. Furthermore, if the novel subtype is highly virulent, meaning that the virus causes severe disease and high rates of death, the result can be catastrophic. Currently, there are several subtypes of avian influenza that could potentially result in the next influenza pandemic.2 Fortunately, these viruses are currently not easily transmissible between humans. Yet, if they...