Modeling the impact on virus transmission of Wolbachia mediated blocking of dengue virus infection of Aedes aegypti
Experimental work and modeling studies reveal that Aedes aegypti infected with the Wolbachia bacterium have reduced vector competence for the transmission of dengue viruses. Use a bug to fight a bug Dengue is the most common mosquito borne viral infection in humans. In this new work, Ferguson et al. have assessed the extent to which infecting mosquitoes with a bacterium called Wolbachia was able to prevent those mosquitoes from being infected with dengue virus after they were fed with blood collected from dengue patients. One Wolbachia strain (wMelPop) almost completely prevented dengue infection. A second strain (wMel) partially blocked dengue infection. A mathematical model fitted to the data collected on the wMel strain suggested that wMel could reduce the transmissibility of dengue by 66 to 75% enough to eliminate dengue in low or moderate transmission settings. Dengue is the most common arboviral infection of humans and is a public health burden in more than 100 countries. Aedes aegypti mosquitoes stably infected with strains of the intracellular bacterium Wolbachia are resistant to dengue virus (DENV) infection and are being tested in field trials. To mimic field conditions, we experimentally assessed the vector competence of A. aegypti carrying the Wolbachia strains wMel and wMelPop after challenge with viremic blood from dengue patients. We found that wMelPop conferred strong resistance to DENV infection of mosquito abdomen tissue and largely prevented disseminated infection. wMel conferred less resistance to infection of mosquito abdomen tissue, but it did reduce the prevalence of mosquitoes with infectious saliva. A mathematical model of DENV transmission incorporating the dynamics of viral infection in humans and mosquitoes was fitted to the data collected. Model predictions suggested that wMel would reduce the basic reproduction number, R0, of DENV transmission by 66 to 75% Our results suggest that establishment of wMelPop infected A. aegypti at a high frequency in a dengue endemic setting would result in the complete abatement of DENV transmission. Establishment of wMel infected A. aegypti is also predicted to have a substantial effect on transmission that would be sufficient to eliminate dengue in low or moderate transmission settings but may be insufficient to achieve complete control in settings where R0 is high. These findings develop a framework for selecting Wolbachia strains for field releases and for calculating their likely impact.
Science Translational Medicine