Using Wolbachia for Dengue Control: Insights from Modelling

Abstract

Dengue is the most common arboviral infection of humans, responsible for a substantial disease burden across the tropics. Traditional insecticide-based vector-control programmes have limited effectiveness, and the one licensed vaccine has a complex and imperfect efficacy profile. Strains of the bacterium Wolbachia, deliberately introduced into Aedes aegyptimosquitoes, have been shown to be able to spread to high frequencies in mosquito populations in release trials, and mosquitoes infected with these strains show markedly reduced vector competence. Thus, Wolbachia represents an exciting potential new form of biocontrol for arboviral diseases, including dengue. Here, we review how mathematical models give insight into the dynamics of the spread of Wolbachia, the potential impact of Wolbachia on dengue transmission, and we discuss the remaining challenges in evaluation and development.

Figure 1. Invasion dynamics of Wolbachia

A. Illustration of how cytoplasmic incompatibility (CI) gives Wolbachia-infected females a reproductive advantage by making the progeny of infected males and wild-type females non-viable. B. CI thus allows Wolbachia-infected mosquitoes to displace wild-type (blue curve) if introduced into a population above a threshold frequency (dashed line) which is determined by the fitness costs of Wolbachia infection. If introduced below this threshold frequency (red curve), Wolbachia-infected insects are out-competed by wild-type, despite CI.

Figure 2. Schematic illustration of factors influencing the spatial spread of Wolbachia in a mosquito population

A. In the initial release area, the frequency of Wolbachia-infected mosquitoes needs to exceed the critical threshold for invasion (see Figure 1B) for invasion to occur. B. Wolbachia is more likely to establish and spread spatially if the initial release area is larger. C. More intense larval stage density-dependent competition slows initial establishment and spatial spread.

Figure 3. Simulated time-series of monthly symptomatic dengue incidence following (or without) Wolbachia release

Results use the deterministic dengue transmission model published in [15]. Mean dengue R₀ set at 4.5 and wMel is assumed to reduce dengue infectiousness of mosquitoes by 40% and to have 90% efficient maternal transmission. Shaded area shows dynamics after the initial release of Wolbachia at time 0.

Figure 4. Predicted long-term impact of large-scale Wolbachia release on symptomatic dengue incidence derived using the deterministic dengue transmission model published in [15]

Four different scenarios using different assumptions regarding Wolbachia maternal transmission and larval competition intensity are shown. Note that the transient impact of Wolbachia release on dengue transmission (i.e. in the first 10–30 years post-release) is much larger (see Figure 3), typically giving a >95% reduction in dengue cases in that timeframe.