Development of physiologically based pathogen transport and kinetics model for inhalation of Bacillus anthracis spores

The current quantitative microbial risk assessment paradigm relies heavily on the dose response assessment phase. This phase fits a mathematical model to available dose response data for the pathogen of concern. In current dose response model fitting the dose that is used is the dose to which the host organism (typically test animals) is exposed to. This dose does not take into account the natural sinks of the respiratory system, or the infection processes. This work has successfully modeled the bulk fluid transport and deposition as well as the pathogenesis of inhaled Bacillus anthracis (B. anthracis) spores. The two stages of the infection process (transport and deposition being the first stage and the pathogenesis process being the second) have been modeled as a coupled two stage model, with a stochastic model for transport and deposition, and a deterministic model for the pathogenesis process. The first stage stochastic model allows for an estimation of the dose delivered to a sensitive location (alveolus for B. anthracis spores) by developing a constant correction factor from exposed dose to the delivered dose. The coupled model allows an estimation of the pathogen burden after 60 minutes of inhalation simulated by the first stage, again by the development of a constant correction factor from exposed dose to the pathogen burden. This framework is analogous to physiologically based physiochemical (PBPK) models which changed chemical risk assessment over 20 years ago, which model the transport and metabolism of chemical contaminants post exposure. PBPK models allow for a more complete picture as to what the body is experiencing post exposure to chemical contaminants in the natural or built environment. This framework has been developed for inhalation of B. anthracis spores, but can be adapted to other pathogens with the first stage remaining unchanged if the pathogen can be considered to behave as a particle in bulk fluid, and adapting the second stage to the pathogenesis unique to the pathogen.