Containing Bioterroist and Emerging Infectious Diseases

描述(由申请人提供)：这项研究的总体目标是开发、验证和实施生物恐怖主义制剂或自然发生的传染病的传播和宿主内动态的数学模型。这些模型将被用来评估各种干预措施的效力和效力，以帮助分配和分配资源，以应对此类疫情。 具体目标1是为所讨论的传染病的传播开发流行病模拟模型：a.为典型的美国社区开发随机流行病模拟模型；b.使用流行病模拟模型来评估涉及监测和遏制、疫苗接种、抗菌剂、关闭关键机构和其他控制策略的干预措施的有效性；c.开发随机优化方法以找到受可用资源约束的最佳干预策略；d.调整针对天花、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传染病的流行病模拟模型；E.使用流行病模拟模型确定感染传播的重要参数，并利用这些信息设计实地研究和干预研究；F.使用和开发统计方法，从数据中估计重要参数和变量。 具体目标2是建立引起脊椎动物急性感染的病原体在宿主内的动态模型：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，包括利用小鼠淋巴细胞性脉络膜脑膜炎病毒(LCMV)和单核细胞增生性李斯特菌(LM)感染的现有数据；c.使用特定目标2.b.的经验。对具体目标2.a中的模型进行扩展。研究更具挑战性的人类急性感染，包括生物恐怖主义制剂或自然发生的传染病；D.通过抗微生物和抗病毒治疗建立选择性压力下的耐药性发展模型，并通过抗微生物或疫苗预防；E.将随机流行病模拟模型与宿主内产生耐药性的模型相结合，以研究耐药性在宿主群体中的传播。

DESCRIPTION (provided by applicant): The overall objective of this research is to develop, validate, and implement mathematical models for the transmission and within-host dynamics of bioterrorism 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.