Mathematical modelling to investigate a Wolbachia intervention to reduce dengue transmission

The introduction of Wolbachia-carrying mosquitoes into the population has recently been proposed as an alternative strategy against dengue. Although laboratory experiments have shown that the Wolbachia bacterium can reduce the levels of dengue virus in mosquitoes, it is also important to assess the performance of Wolbachia in reducing the incidence of dengue in human populations. In this thesis, deterministic mathematical models of human and mosquito populations in which either one or two dengue serotypes circulate are developed. We adapt these models to enable the investigation of dengue disease dynamics in the absence and presence of Wolbachia in order to assess the performance of Wolbachia as a strategy to reduce human dengue incidence. When studying the situation in which a single dengue serotype is present in the population, we consider scenarios where dengue is introduced into the human population once and multiple times. We find that when mosquitoes infected with the Wolbachia strain WMel, which reduces the mosquito lifespan by at most 10%, are released into the population, the Wolbachia-carrying mosquitoes persist. The ranges of the reproductive and death rates for Wolbachia-carrying mosquitoes which allow mosquitoes carrying Wolbachia to persist in competition with non-Wolbachia carrying mosquitoes are also found. Furthermore, the transmission probability, the biting rate and the average death rate are the parameters exerting the most influence on the cumulative number of infectious individuals in the population. An analysis of the basic reproduction number, ℛ₀, for the model considering the absence and presence of Wolbachia-carrying mosquitoes shows that the presence of Wolbachia-carrying mosquitoes reduces the number of days for which ℛ₀ > 1. When multiple introductions of dengue are considered, it is found that the presence of Wolbachia reduces the potential lengths of the seasons in which epidemics are likely to occur. The strength of seasonality also affects the reduction in dengue incidence caused by the introduction of Wolbachia: if seasonality is strong, then there are some seasons when mosquitoes have longer life spans and more individuals are infected in each outbreak so that Wolbachia becomes less effective in reducing dengue incidence. Our two-serotype dengue models are used to investigate dengue serotypes with symmetric and asymmetric characteristics. For serotypes with symmetric characteristics, we investigate the performance of Wolbachia in reducing dengue incidence under different disease introduction scenarios, and find that a difference in the disease introduction scenario does not affect the performance of Wolbachia in reducing dengue incidence. Furthermore, the transmission probability is a more influential parameter regulating dengue dynamics than antibody-dependent enhancement. When dengue serotype characteristics differ (asymmetry), the more transmissible dengue serotype will dominate the primary infection, while the other serotype will dominate the secondary infections. The number of secondary infections caused by the more transmissible serotype can still be reduced by the introduction of Wolbachia-carrying mosquitoes, but the proportional reduction in dengue cases is not as high. Our findings suggest that Wolbachia intervention can be used as an effective alternative strategy against dengue. Wolbachia should reduce the number of primary dengue cases in areas with moderate transmission levels, and can provide an even greater reduction in the number of secondary cases. Given the higher risk of severe outcomes in secondary cases, Wolbachia has great potential for improving public health.