Mathematical Modeling of Anthrax Infection

描述（申请人提供）：可悲的是，生物恐怖主义不再是一个新兴的可能性，而是美国生活的日常事实。炭疽杆菌的吸入性和胃肠道感染可引起炎症反应，导致多系统器官衰竭和死亡。各种临床线索和诊断测试用于确认疑似炭疽感染，新兴的分子诊断技术可能会更准确和更快地确认炭疽感染。然而，所有的诊断方法都在一个关键方面失败了：虽然它们确定了炭疽感染的存在，但它们并没有指出个别病人的状况，也没有指出这个人在不久的将来会如何。Vodovotz、Clermont和Chow博士开发了一个数学模型，结合了感染急性炎症反应的细胞、分子和生理细节，并开始模拟炭疽感染的反应。该模型可用于预测个体患者的病程，以及在模拟临床试验中测试给定干预措施的有效性。Immunetrics，Inc.，正在将该模型应用于治疗脓毒症的商业化过程中，脓毒症是每年影响超过750，000名美国人的医疗保健问题，成本超过170亿美元。在第一阶段的建议中，我们提出了以下建议：1）根据现有数据，调整和校准我们对吸入性和胃肠道炭疽感染及其治疗的先天炎症反应的数学模型; 2）开发一种软件工具，用于输入，可视化和操作该数学模型。该模型和软件工具将能够适应多种诊断和临床测试的结果。本文提出的研究结果不仅将影响炭疽感染受害者的治疗，而且还将为一般败血症的治疗提供有价值的工具。

DESCRIPTION (provided by applicant): 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.