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种新兴的可能性，而是美国人生活中的日常事实。吸入性和胃肠道感染炭疽杆菌可引起炎症反应，导致多系统器官衰竭和死亡。各种临床线索和诊断试验被用来确认疑似炭疽感染，新兴的分子诊断技术很可能会产生更准确和更快的炭疽感染确认。然而，所有的诊断模式在一个关键方面都失败了：虽然它们识别了炭疽感染的存在，但它们没有指出单个患者的状况，也没有表明此人在不久的将来会如何。Vodovotz博士、Clermont博士和Chow博士开发了一个数学模型，其中包含了对感染的急性炎症反应的细胞、分子和生理细节，并已开始模拟对炭疽感染的反应。该模型可用于预测单个患者的病程，以及在模拟临床试验中测试给定干预措施的有效性。免疫公司正在将这种模式的应用商业化，用于治疗败血症。败血症是一种医疗保健问题，每年影响超过75万美国人，耗资超过170亿美元。在这个第一阶段的提案中，我们建议如下：1)基于现有的数据，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；以及2)开发一个软件工具，设计用于输入、可视化和操纵该数学模型。该模型和软件工具将适用于合并多个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患者的治疗，而且还将为一般脓毒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.