Microfilarial enhancement of Dengue transmission

描述（申请人提供）：在自然界中，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 确定脊椎动物同时感染微丝蚴， 虫媒病毒可以增强蚊子传播虫媒病毒。当摄入时， 微丝蚴穿透蚊子的中肠， 病毒进入蚊子的体腔。这大大增加和加速了 蚊子的病毒传染性。这被称为虫媒病毒的mf增强 它可以传播，并可能产生两个重要的流行病学后果。第一、 蚊子物种通常对病毒感染是难治的， 中肠对病毒传染性的屏障现在可能发展为感染。因此，在本发明中， 否则不合格的载体物种可以转化为合格的载体 种，增加了病毒所涉及的病媒种的数量 传输周期第二，微丝蚴增强可以加速病毒 蚊子体内的发育，大大缩短了 受感染的蚊子变成有传染性的蚊子 期间EIP]）。由于EIP以指数方式影响传输， EIP的减少可以导致矢量容量的大幅增加，即使 天然载体系统假说：微丝蚴增强现象 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重叠。的目的 建议是了解人类丝虫病可以影响的程度， 登革热在不同条件下的传播模式。实验 一种方法是利用现有的登革热计算机模拟模型 传播（DENSiM），以预测不同类型和流行的人类 丝虫病可改变伊蚊传播登革病毒的动力学。 蚊子传输的重要参数（例如，EIP）将在 通过使用成对的蚊子喂食实验确定。病毒 将在双重曝光（即， 病毒加MF）与单独暴露（即，病毒）蚊子，检查 不同血清型的登革热病毒和不同种类的丝虫 寄生虫利用实验室数据和计算机 通过模拟，预计可以建立基本原理 这将普遍适用于任何虫媒病毒传播周期， 虫媒病毒和微丝蚴感染同时发生。

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.