Improving Robustness of a Tactical Model of Aedes/Dengue Dynamics

描述(申请人提供)：登革热是一种蚊媒传播的人类病毒性疾病，目前被认为是最重要的节肢动物传播的人类病毒性疾病。据估计，每年发生5000万至1亿例登革热(断骨热)和约50万例威胁生命的登革热出血热。除了对患病个人的直接影响外，城市登革热流行病还使热带国家的公共卫生系统不堪重负。登革热病毒的主要传播媒介是埃及伊蚊，这种蚊子与人类密切相关，以人血为食。目前遏制登革热流行的唯一有效方法是家庭喷洒杀虫剂。如果有效地使用这些喷雾剂可能是有效的，但通常情况并非如此。研究工作正在进行中，以开发登革热疫苗，并创造出具有阻止登革热从蚊子传播到人类的基因的转基因蚊子品系。尽管这些新方法以及改善蚊子的常规化学控制有很大的希望，但登革热的流行病学有许多未知之处，使得人们很难确定如何部署新的疫苗、转基因蚊子或新型杀虫剂。我们也不知道是单独使用最有效的新战术，还是结合使用战术是最有益的。由于对新干预措施有效性的实验研究通常必须在全市范围内进行，因此进行此类实验通常是不可行的，也是不符合道德的。在从太空旅行到全球气候变化等科学领域，计算机模拟研究经常提供一种直接实验的替代方案。数学模型的模拟一直是研究麻疹等直接传播疾病的关键因素，但在昆虫传播疾病的研究中使用较少。我们的总体目标是创建和测试最全面和最强大的埃及伊蚊/登革热动态模拟模型，以便为研究、监管和管理社区提供有效指导蚊子媒介管理和疫苗部署计划的建模工具。我们开发的最终模型将为实证研究人员和公共卫生从业者提供可信的答案，以回答以下问题：1)登革热疫情最有可能通过在小社区内传播还是通过日常人类活动传播到公共场所，以及这如何决定对城市疫情的适当反应？2)释放转基因Ae的最有效选择是什么。具有抗登革热结构的埃及伊蚊菌株？3)将登革热疫苗和Ae结合部署是否会更有效和更可持续？埃及人管理，还是投资于最有效和最经济的单一策略本身？

DESCRIPTION (provided by applicant): Dengue is a mosquito vectored viral disease of humans that is now considered the most important arthropod-borne human viral disease. An estimated 50-100 million cases of dengue fever (break-bone fever) and about 500,000 cases of the more life-threatening dengue hemorrhagic fever occur annually. Beyond direct impact on afflicted individuals, urban dengue epidemics overwhelm public health systems of tropical countries. The principal vector of dengue virus is the mosquito, Aedes aegypti, that lives in close association with humans and feed on human blood. The only currently effective way to suppress dengue epidemics involves household insecticide sprays. These sprays can be effective if used efficiently, but this is commonly not the case. Research efforts are underway to develop vaccines against dengue and to create genetically engineered strains of the mosquitoes with genes that block transmission of the dengue from the mosquito to humans. Although there is great hope for these new approaches as well as for improving conventional chemical control of the mosquito, there are many unknowns about the epidemiology of dengue that make it difficult to determine how one would deploy a new vaccine, engineered mosquito, or novel insecticide. We also don't know if it would be most beneficial to use the single most effective new tactic alone, or to use a combination of tactics. Because experimental studies of the efficacy of a new intervention must typically be conducted at a city-wide level, such experiments are generally not feasible or ethical to conduct. Computer simulation studies have often offered an alternative to direct experimentation in scientific fields ranging from space travel to global climate change. Simulations of mathematical models have been a key factor in studying directly transmitted diseases such as measles, but have been used less in studies of insect-vectored diseases. Our overall goal is to create and test the most comprehensive and robust simulation model of Aedes aegypti/dengue dynamics in order to provide research, regulatory, and management communities with a modeling tool for effectively guiding mosquito vector management and vaccine deployment programs. The final model we develop will provide empirical researchers and public health practitioners with credible answers to questions such as: 1) Are dengue epidemics most likely to start by transmission within small neighborhoods or through daily human movement to public places, and how does that determine appropriate response to urban outbreaks? 2) What are the most efficient options for release of transgenic Ae. aegypti strains with anti-dengue constructs? 3) Would it be more efficient and sustainable to combine deployment of dengue vaccines and Ae. aegypti management, or to invest in the single tactic that is most effective and economical on its own?