Summary1. Field release of endosymbiotic Wolbachia bacteria into wild Aedes aegypti mosquito populations is a promising strategy for biocontrol of dengue. This strategy requires successful Wolbachia invasion through the mosquito vector population. Natural variation in mosquito fitness due to density-dependent competition for limited food resources may influence Wolbachia invasion. We know little about these effects, largely because our understanding of density-dependent dynamics in mosquito populations is limited. 2. We developed an empirical model of A. aegypti-Wolbachia dynamics where food resources available to the developing larvae are limited. We assessed the extent of density-dependent regulation in our A. aegypti population using a Bayesian statistical model that estimates the temporal variation in mosquito fitness components. We monitored the spread of Wolbachia and assessed the effect of the bacteria on larval fitness components. 3. We demonstrate that mosquito population growth is regulated by strong larval densitydependent variation in mosquito fitness components. Wolbachia spread was slowed by this heterogeneity in mosquito fitness, which reduces the capacity of the bacteria to invade. However, we found no evidence that Wolbachia affects larval fitness components. 4. Synthesis and applications. We demonstrate that the extent and form of density-dependent dynamics in the host population can have a major influence on Wolbachia invasion. These findings help explain slow Wolbachia invasion rates and indicate that the success of field release strategies for dengue control can depend on attaining high Wolbachia frequencies in the mosquito population.

Wolbachia are endosymbionts that are found in many insect species and can spread rapidly when introduced into a naive host population. Most Wolbachia spread when their infection frequency exceeds a threshold normally calculated using purely population genetic models. However, spread may also depend on the population dynamics of the insect host. We develop models to explore interactions between host population dynamics and Wolbachia infection frequency for an age-structured insect population regulated by larval density dependence. We first derive a new expression for the threshold frequency that extends existing theory to incorporate important details of the insect's life history. In the presence of immigration and emigration, the threshold also depends on the form of density-dependent regulation. We show how the type of immigration (constant or pulsed) and the temporal dynamics of the host population can strongly affect the spread of Wolbachia. The results help understand the natural dynamics of Wolbachia infections and aid the design of programs to introduce Wolbachia to control insects that are disease vectors or pests.

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.

BackgroundArbovirus transmission by the mosquito Aedes aegypti can be reduced by the introduction and establishment of the endosymbiotic bacteria Wolbachia in wild populations of the vector. Wolbachia spreads by increasing the fitness of its hosts relative to uninfected mosquitoes. However, mosquito fitness is also strongly affected by population size through density-dependent competition for limited food resources. We do not understand how this natural variation in fitness affects symbiont spread, which limits our ability to design successful control strategies.ResultsWe develop a mathematical model to predict A. aegypti–Wolbachia dynamics that incorporates larval density-dependent variation in important fitness components of infected and uninfected mosquitoes. Our model explains detailed features of the mosquito–Wolbachia dynamics observed in two independent experimental A. aegypti populations, allowing the combined effects on dynamics of multiple density-dependent fitness components to be characterized. We apply our model to investigate Wolbachia field release dynamics, and show how invasion outcomes can depend strongly on the severity of density-dependent competition at the release site. Specifically, the ratio of released relative to wild mosquitoes required to attain a target infection frequency (at the end of a release program) can vary by nearly an order of magnitude. The time taken for Wolbachia to become established following releases can differ by over 2 years. These effects depend on the relative fitness of field and insectary-reared mosquitoes.ConclusionsModels of Wolbachia invasion incorporating density-dependent demographic variation in the host population explain observed dynamics in experimental A. aegypti populations. These models predict strong effects of density-dependence on Wolbachia dynamics in field populations, and can assist in the effective use of Wolbachia to control the transmission of arboviruses such as dengue, chikungunya and zika.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0319-5) contains supplementary material, which is available to authorized users.

SignificanceMalaria control programs rely on chemical insecticides to target mosquito vectors and are potentially threatened by the emergence of insecticide resistance in African vector populations. Insecticide resistance management initiatives require comprehensive quantification of resistance in field populations to the set of insecticides used in vector control. We analyzed patterns of variation and covariation in resistance to these insecticides, using statistical methods that handle the sparse spatiotemporal distribution of the available data. We found relationships across different insecticide types that are consistent across large parts of Africa, allowing prediction of resistance to be improved by incorporating observations across multiple insecticide types. We also found large-scale relationships between phenotypic resistance and patterns of genetic variation, demonstrating the potential utility of genetic markers.