Mathematical Modeling for the Assessment of the Pandemic Potential of Influenza A: the Present State and Future Possibilities

The most lethal influenza pandemic in human history occurred in 1918 in Spain and resulted in the death of over 50 million people. The influenza A/H1N1 virus responsible for these deaths was both exceptionally pathogenic and highly infectious, a deadly combination that the world has not seen since (7). Therefore, when news emerged that a new highly pathogenic strain of influenza H5N1 was crossing over from birds to humans in East Asia, it became necessary to assess its pandemic potential. Two teams---one at the University of Wisconsin-Madison and one at the Erasmus Medical Center in Rotterdam---used different methods to mutate the H5N1 virus into an easily transmissible strain and both were successful. They discovered that only five mutations are needed for this highly pathogenic virus to become transmissible between humans and concluded that H5N1 poses a risk for human pandemic influenza (1-3). It is therefore of increasing importance that the mechanisms that underlie H5N1's virulence and transmission capabilities are better understood. Mathematical modeling has emerged in the last two decades as an innovative means of analyzing biological systems, including virus-host interactions. It can reveal important dynamical relationships and possibly predict the pandemic potential of emerging viral strains. Here I summarize the major factors that are believed to affect the virulence and transmission capabilities of influenza strains with pandemic potential and review the models of influenza A that have been developed in recent decades, focusing on the each models usefulness in assessing pandemic influenza. I discuss the research and modeling efforts that are necessary to better capture the dynamics of highly pathogenic serotypes in a mathematical model and the challenges that await those who attempt to do so. Finally, I explore the possibility of creating a mathematical model that can predict whether or not a particular strain of virus is a pandemic threat.