Microfilarial enhancement of Dengue transmission

描述(申请人提供)：自然界中，虫媒病毒的脊椎动物宿主 经常被其他寄生生物感染。实验室研究表明 证实脊椎动物同时感染微丝虫和 虫媒病毒可以加强蚊子对虫媒病毒的传播。当被摄取时， 微丝状线虫穿透蚊子中肠，并允许立即传播 病毒进入蚊子的体腔。这大大增加并加速了 蚊子的病毒传染性。这被称为虫媒病毒的MF增强。 它可能会产生两个重要的流行病学后果。第一, 通常对病毒感染具有抵抗力的蚊子种类，因为 病毒感染性的中肠屏障现在可能会发展为感染。因此， 否则，不称职的媒介物种可以转化为有能力的媒介 物种，增加病毒涉及的媒介物种的数量 传输周期。第二，微丝虫病的加强会加速病毒传播。 在蚊子体内发育，极大地缩短了 受感染的蚊子变成有感染力的蚊子 周期弹性公网IP])。由于弹性公网IP以指数方式影响传输，因此 EIP的减少可以导致矢量容量的大幅增加，即使是在 自然向量系统。假设：微丝虫病增强现象 可能会影响登革热病毒在世界某些地区的传播 登革热和人类丝虫病的分布是重叠的。这样做的目的是 建议是了解人类丝虫病可能影响的程度 不同条件下的登革热传播模式。实验性的 方法是利用现有的登革热计算机模拟模型 传播(DENSiM)预测人类不同类型和流行率 丝虫病可改变伊蚊传播登革热病毒的动态。 蚊子。传输的重要参数(例如弹性公网IP)将是 通过使用成对的蚊子饲料进行实验测定。病毒式传播 开发和传播将在双重曝光(即， 病毒加MF)与单独暴露(即仅病毒)的蚊子相比，检查 不同血清型的登革热病毒和不同种类的丝虫 寄生虫。使用实验室得出的数据和计算机的组合 模拟，预计可以建立基本原则 这通常适用于任何虫媒病毒传播周期，在 虫媒病毒和微丝虫感染同时发生。

DESCRIPTION (provided by applicant): In nature, vertebrate hosts of arboviruses are often infected with other parasitic organisms. Laboratory studies have established that vertebrates concurrently infected with microfilariae and arboviruses can enhance mosquito transmission of arboviruses. When ingested, microfilariae penetrate the mosquito midgut and allow immediate dissemination of virus into the mosquito body cavity. This greatly increases and accelerates viral infectivity of mosquitoes. This is termed mf enhancement of arboviral transmission and it can have 2 important epidemiological consequences. First, mosquito species that are normally refractory to viral infection because of midgut barriers to viral infectivity may now develop infections. Thus, otherwise incompetent vector species can be transformed into competent vector species, increasing the number of vector species involved in a virus transmission cycle. Second, microfilarial enhancement can accelerate viral development within the mosquito, significantly shortening the time required for infected mosquitoes to become infectious mosquitoes (=extrinsic incubation period EIP]). Since EIP affects transmission in an exponential fashion, small reductions in EIP can lead to large increases in vectorial capacity, even with natural vector systems. Hypothesis: the phenomenon of microfilarial enhancement may affect the transmission of dengue virus in certain areas of the world where the distribution of dengue and human filariasis overlap. The objective of this proposal is to understand the magnitude to which human filariasis can affect patterns of dengue transmission under varying conditions. The experimental approach is to utilize an existing computer simulation model for dengue transmission (DENSiM) to predict how different types and prevalence's of human filariasis can alter transmission dynamics of dengue virus by Aedes spp. mosquitoes. Important parameters for transmission (e.g., EIP) will be determined experimentally with the use of paired mosquito feedings. Viral development and transmission will be compared between dually exposed (i.e., virus plus mf) versus singly exposed (i.e., virus only) mosquitoes, examining different serotypes of dengue viruses and different species of filarial parasites. Using a combination of laboratory-derived data and computer simulation, it is anticipated that fundamental principles can be established that will be generally applicable to any arboviral transmission cycle where arboviral and micro filarial infections occurs together.