Improving Robustness of a Tactical Model of Aedes/Dengue Dynamics

描述（由申请人提供）：登革热是一种蚊子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50万例更危及生命的登革出血热。除了对受影响的个人的直接影响外，城市登革热流行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蚊子，埃及伊蚊，它与人类密切相关，以人类血液为食。目前抑制登革热流行的唯一有效方法是家庭杀虫剂喷雾。如果有效使用，这些喷雾剂可能是有效的，但通常情况并非如此。目前正在进行研究工作，以开发针对登革热的疫苗，并创造具有阻止登革热从蚊子传播给人类的基因的蚊子基因工程菌株。尽管这些新方法以及改进传统的蚊子化学控制有很大的希望，但登革热的流行病学仍有许多未知数，因此很难确定如何部署新疫苗，工程蚊子或新型杀虫剂。我们也不知道是单独使用一种最有效的新战术，还是使用多种战术的组合。由于新干预措施的有效性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不可行或不符合道德。在从太空旅行到全球气候变化的科学领域，计算机模拟研究往往提供了一种替代直接实验的方法。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埃及伊蚊/登革热动态的最全面和最强大的模拟模型，以便为研究，监管和管理社区提供有效指导蚊媒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人员提供可信的答案，例如：1）登革热流行最有可能通过小社区内的传播或通过日常人类活动到公共场所开始，以及如何确定对城市疫情的适当反应？2)释放转基因Ae的最有效的选择是什么？埃及菌株与抗登革热结构？3)将登革热疫苗和禽流感疫苗的联合收割机部署结合起来是否会更有效、更可持续。埃及管理，或投资于单一的战术，是最有效和最经济的本身？

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?