Strategies for Introducing Wolbachia to Reduce Transmission of Mosquito-Borne Diseases

Abstract
Certain strains of the endosymbiont Wolbachia have the potential to lower the vectorial capacity of mosquito populations and assist in controlling a number of mosquito-borne diseases. An important consideration when introducing Wolbachia-carrying mosquitoes into natural populations is the minimisation of any transient increase in disease risk or biting nuisance. This may be achieved by predominantly releasing male mosquitoes. To explore this, we use a sex-structured model of Wolbachia-mosquito interactions. We first show that Wolbachia spread can be initiated with very few infected females provided the infection frequency in males exceeds a threshold. We then consider realistic introduction scenarios involving the release of batches of infected mosquitoes, incorporating seasonal fluctuations in population size. For a range of assumptions about mosquito population dynamics we find that male-biased releases allow the infection to spread after the introduction of low numbers of females, many fewer than with equal sex-ratio releases. We extend the model to estimate the transmission rate of a mosquito-borne pathogen over the course of Wolbachia establishment. For a range of release strategies we demonstrate that male-biased release of Wolbachia-infected mosquitoes can cause substantial transmission reductions without transiently increasing disease risk. The results show the importance of including mosquito population dynamics in studying Wolbachia spread and that male-biased releases can be an effective and safe way of rapidly establishing the symbiont in mosquito populations. Wolbachia are symbiotic bacteria that are found in many insect species. Recent laboratory studies show that certain strains of Wolbachia can reduce the capacity of mosquito species to transmit diseases such as dengue fever and malaria, either by directly inhibiting the pathogen or by shortening lifespan. However, little is known about how easily these bacteria will spread in natural mosquito populations or the impact of deliberate Wolbachia introduction on disease transmission. We use a simple model of Wolbachia-mosquito interactions to explore the design of field releases of infected mosquitoes to initiate symbiont spread. A particular concern is how Wolbachia can be introduced while releasing only small numbers of female mosquitoes which may bite humans and transmit disease. The models include explicit mosquito population dynamics including seasonal fluctuations in population size and different forms of population regulation. We find that rapid Wolbachia establishment is possible by releasing predominantly male mosquitoes, though the number of insects introduced may need to be large. This strategy requires the introduction of considerably fewer females compared to equal sex-ratio releases and is unlikely to increase disease transmission throughout the intervention. We demonstrate that once Wolbachia has become established, substantial reductions in disease transmission are possible.