Containing Bioterroist and Emerging Infectious Diseases

本研究的总体目标是开发、验证和实现 生物恐怖主义制剂或自然发生的传染病的传播和宿主内的动态。这些 将使用模型来评估各种干预措施的有效性和有效性，以帮助分发和 分配资源以应对此类疫情。 具体目标1是开发有关传染病传播的流行病模拟模型：a。 为一个典型的美国社区开发随机流行病模拟模型；B.利用流行病 评估干预措施有效性的模拟模型，包括监测和遏制、疫苗接种、 抗菌药、关闭关键机构和其他控制战略；C.开发随机优化方法 在现有资源的约束下，找到最佳干预策略；D.适应疫情模拟 天花、大流行性流感、SARS和其他可能的生物恐怖主义病原体或自然发生的模型 传染病；E.使用流行病模拟模型来确定感染的重要参数 传播并利用这些信息设计实地研究和干预研究；F.使用和开发 从数据中估计重要参数和变量的统计方法。 具体目标2是建立引起急性感染的病原体在宿主内的动态模型。 脊椎动物：a.构建病原体和宿主免疫反应之间相互作用的探索性模型；b. 完善、进一步发展和测试这些致病模型，包括使用现有的数据 小鼠淋巴细胞性脉络膜脑膜炎病毒(LCMV)和单核细胞增多性李斯特菌(LM)感染；C.使用 从具体目标中获得的经验2.对具体目标2.a中的模型进行扩展。考查更具挑战性的 人类的急性感染，包括生物恐怖主义病原体或自然发生的传染病；D.建立模型 选择性压力下抗菌、抗病毒治疗耐药性的产生及预防 抗菌剂或疫苗接种；E.将随机流行模拟模型与宿主内模型相结合 抗药性的产生，以检查抗药性在宿主种群中的传播。

The overall objective of this research is to develop, validate, and implement mathematical models for the transmission and within-host dynamics ofbioterrorism agents or naturally occurring infectious diseases. These models will be used to assess the effectiveness and efficacy of various interventions to aid the distribution and allocation of resources in response to such outbreaks. Specific aim 1 is to develop epidemic simulation models for the transmission of infectious diseases in question: a. to develop stochastic epidemic simulation models for a typical American community; b. to use the epidemic simulation models to evaluate the effectiveness of interventions involving surveillance and containment, vaccination, antimicrobials, closing of key institutions, and other control strategies; c. to develop stochastic optimization methods to find the best intervention strategy, constrained by the resources available; d. to adapt the epidemic simulation models for smallpox, pandemic influenza, SARS, and other possible bioterrorism agents or naturally occurring infectious diseases; e. to use the epidemic simulation models to determine the important parameters for infection transmission and to use this information to design field studies and intervention studies; f. to use and develop statistical methods to estimate the important parameters and variables from data. Specific aim 2 is to develop models of the within-host dynamics of pathogens which cause acute infections in vertebrates: a. to construct exploratory models for the interplay between the pathogen and host immune response; b. to refine, to develop further and to test these models of pathogenesis including the use of existing data on lymphocytic choriomeningitis virus (LCMV) and listeria monocytogenes (LM) infections of mice; c. to use the experience from the specific aim 2.b. to extend the models in the specific aim 2.a. to examine the more challenging acute infections of humans including bioterrorism agents or naturally occurring infectious diseases; d. to model development of resistance under selective pressure by antimicrobial and antiviral treatment and prophylaxis by antimicrobials or vaccination; e. to combine the stochastic epidemic simulation models with models for within-host generation of resistance to examine spread of resistance within the host population.