登革热是由伊蚊传播登革病毒(DENV)引起的一种蚊媒传播疾病，在我国乃至世界时有发生。目前不仅缺乏有效疫苗，而且在个体内病毒感染和人群间振荡传播的规律仍未充分理解。本项目拟通过建立DENV在个体内感染和群体间疾病传播的动力学模型，综合运用微分动力系统理论、数值模拟等方法，来研究DENV感染和振荡传播的动力学行为。首先，依据DENV感染个体过程中抗体和免疫复合物的作用，借助病毒动力学和免疫动力学的方法，建立DENV感染动力学模型，以探讨其引起重症的原因；其次，根据DENV传播过程中不同毒株的感染特性和抗体增强效应以及气候环境的变化对蚊卵滞育、病毒贮存等影响，建立DENV传播动力学模型，探寻引起DENV振荡传播现象的形成原因；最后基于DENV个体内感染与群体传播的相互依赖性，建立登革热免疫-传染病动力学模型，分析体内抗体变化对疾病传播的影响。研究成果为控制DENV感染和传播提供新的理论基础和依据。

Dengue fever is a mosquito-borne disease caused by the dengue viruses (DENV), which are transmitted to human by the bite of Aedes female mosquitoes. Significant outbreaks of dengue fever occur from time to time in mainland China and mainly subtropical and tropical regions in the world. Currently, the effective vaccine, which has been developed to prevent the transmission of DENV, is still not available. And it can not be fully understood that the dynamical behavior of virus infection within host and the diseases oscillating transmission between individuals. In the presented project, by applying the theory of dynamical system and numerical simulations, we study the mechanisms of the infection, spread and oscillating transmission of DENV by establishing the dynamical models of infection within host and transmission between human population. Firstly, according to the effect of the neutralizing antibodies and the virus-immunity complexes on DENV infection within host, by means of viral dynamics and immune dynamics, we will propose some dynamical models of DENV infection with-host to explore the mechanism of DENV infection causing severe dengue fever. Secondly, based on the characteristics of multi-strain infection and the role of antibody dependent enhancement for infection and the effect of climatic and environmental change on the diapauses of Aedes eggs and the maintenance of dengue viruses in nature, a series of DENV transmission dynamical models are proposed and investigated to explore the mechanisms leading to the oscillations of the disease transmission. Finally, by analyzing the interdependence between the infection within host and spread among individuals of DENV, we will formulate a series of dengue immuno-epidemiology dynamical models to understand the effect of change of antibody levels in the body on the disease spread among individuals. The obtained results will provide the novel theoretical foundation and guidance for controlling the spread of DENV infection.