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Center for Nonlinear Studies |
Lethal Synergism Between Influenza & Streptococcus pneumoniae: The Control Models
Killing more people in the United States than any other infectious disease, influenza-associated pneumonia results in 60,000+ deaths each year. The lethal synergism evident between the Influenza virus and the Streptococcus pneumoniae bacteria plays a large role in the morbidity and mortality associated with influenza pandemics and yearly epidemics. Understanding the interactions between these pathogens is crucial; though, relatively little is known about the contributing factors. The deadliest influenza pandemic, killing 50 million people, was the 1918 "Spanish-Flu" where the unparalleled virulence was likely due to strain novelty, intrinsic viral properties, and secondary bacterial infections. Some hypotheses for the interaction include effects of the Influenza virus proteins PB1-F2 and neuraminidase (NA), and pathogen-induced immune dysfunctions. We have completed in vivo mouse experiments and are developing mathematical models for the control infections to understand the within-host dynamics of each individual pathogen first before we investigate how the two interact. We pay particular attention to the effect PB1-F2 had in the 1918 pandemic by comparing a common strain to one that was genetically engineered to possess the 1918 PB1-F2 protein. Using a mathematical model, we estimate infection parameters and determine which of these are most likely altered by PB1-F2. Additionally, we focus on the early immune response to S. pneumoniae which seems to significantly influence the outcome of the infection. We are currently developing mathematical models to describe the kinetics and identify the factors impacting clearance or persistence of bacteria.