Sadly, bioterrorism is no longer an emerging possibility, but rather a daily fact of American life. Inhalational and gastrointestinal infection with Bacillus anthracis (anthrax) can cause an inflammatory reaction leading to multisystem organ failure and death. Various clinical cues and diagnostic tests are used to confirm suspected anthrax infection, and it is likely that emerging molecular diagnostic techniques will yield more accurate and quicker confirmation of anthrax infection. However, all diagnostic modalities fail in one crucial respect: while they identify the presence of anthrax infection, they do not point to the status of the individual patient nor do they indicate how this person will fare in the immediate future. Drs. Vodovotz, Clermont, and Chow have developed a mathematical model incorporating cellular, molecular, and physiological details of the acute inflammatory responses to infection, and have begun to simulate the response to anthrax infection. This model can be used to predict an individual patient's course of disease, as well as to test the efficacy of a given intervention in a simulated clinical trial. Immunetrics, Inc., is in the process of commercializing the applications of this model to the treatment of sepsis, a healthcare problem affecting over 750,000 Americans each year with a cost of over $17 billion. In this Phase I proposal, we propose the following: 1) to adapt and calibrate, based on existing data, our mathematical model of the innate inflammatory response to an inhalational and gastrointestinal anthrax infection and its treatment; and 2) to develop a software tool designed for the input, visualization, and manipulation of this mathematical model. This model and software tool will be adaptable to incorporate the results of multiple diagnostic and clinical tests. The results of the research proposed herein will not only impact the treatment of victims of anthrax infection, but will also yield a valuable tool for the treatment of sepsis in general
