Microfilarial enhancement of Dengue transmission

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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.