To V, R0 to V ?

Outbreaks of infectious disease can be caused by only a few highly infectious individuals. These individuals are produced by variation in traits affecting contact between infected and susceptible individuals, the likelihood that contact results in infection and the duration of infection. High-risk individuals are difficult to predict because traditional assessments of disease transmission, such as R0, rely on population averages that conceal the variation that produces high transmission-risk phenotypes. Contact rate between infected and susceptible individuals, is primarily determined by behaviour whereas physiological immunity is the main determinant of the likelihood that contact causes infection and infection duration. I characterise variation in traits affecting the determinants of disease transmission and use this to predict individual variation in disease transmission, V. Using the fruit fly, Drosophila melanogaster, and its viral pathogen Drosophila C Virus, I have found pervasive and complex effects of genetic and sex-specific variation, mating, and infection on suites of behaviours, physiological traits and outcomes of infection. Many of my results point to an individual’s disease transmission potential being determined by genetic background and sex. Males, for example, typically survive DCV infection longer than females, however the amount of virus they shed is also determined by their genetic background. To predict how this variation could affect disease transmission dynamics, I simulated outbreaks of DCV in theoretical populations. These populations exhibited genetic and sex-specific variation based on my experiments and significantly affected population-level outbreak dynamics. Differences in these dynamics highlight potentially high-risk transmission classes of individuals, defined by their genetic background and sex

Viral infection causes sex-specific changes in fruit fly social aggregation behaviour

Host behavioural changes following infection are common and could be important determinants of host behavioural competence to transmit pathogens. Identifying potential sources of variation in sickness behaviours is therefore central to our understanding of disease transmission. Here, we test how group social aggregation and individual locomotor activity vary between different genotypes of male and female fruit flies (Drosophila melanogaster) following septic infection with Drosophila C Virus. We find genetic-based variation in both locomotor activity and social aggregation but we did not detect an effect of DCV infection on fly activity or sleep patterns within the initial days following infection. However, DCV infection caused sex-specific effects on social aggregation, as male flies in most genetic backgrounds increased the distance to their nearest neighbour when infected. We discuss possible causes for these differences in the context of individual variation in immunity and their potential consequences for disease transmission

Genotype and sex-based host variation in behavior and susceptibility drives population disease dynamics

Host heterogeneity in pathogen transmission is widespread and presents a major hurdle to predicting and minimizing disease outbreaks. Using Drosophila melanogaster infected with Drosophila C virus as a model system, we integrated experimental measurements of social aggregation, virus shedding, and disease-induced mortality from different genetic lines and sexes into a disease modelling framework. The experimentally measured host heterogeneity produced substantial differences in simulated disease outbreaks, providing evidence for genetic and sex-specific effects on disease dynamics at a population level. While this was true for homogeneous populations of single sex/genetic line, the genetic background or sex of the index case did not alter outbreak dynamics in simulated, heterogeneous populations. Finally, to explore the relative effects of social aggregation, viral shedding and mortality, we compared simulations where we allowed these traits to vary, as measured experimentally, to simulations where we constrained variation in these traits to the population mean. In this context, variation in infectiousness, followed by social aggregation, was the most influential component of transmission. Overall, we show that host heterogeneity in three host traits dramatically affects population-level transmission, but the relative impact of this variation depends on both the susceptible population diversity and the distribution of population-level variation

Oral Bacterial Infection and Shedding in <i>Drosophila Melanogaster</i>

International audienceThe fruit fly Drosophila melanogaster is one of the best developed model systems of infection and innate immunity. While most work has focused on systemic infections, there has been a recent increase of interest in the mechanisms of gut immunocompetence to pathogens, which require methods to orally infect flies. Here we present a protocol to orally expose individual flies to an opportunistic bacterial pathogen (Pseudomonas aeruginosa) and a natural bacterial pathogen of D. melanogaster (Pseudomonas entomophila). The goal of this protocol is to provide a robust method to expose male and female flies to these pathogens. We provide representative results showing survival phenotypes, microbe loads, and bacterial shedding, which is relevant for the study of heterogeneity in pathogen transmission. Finally, we confirm that Dcy mutants (lacking the protective peritrophic matrix in the gut epithelium) and Relish mutants (lacking a functional immune deficiency (IMD) pathway), show increased susceptibility to bacterial oral infection. This protocol, therefore, describes a robust method to infect flies using the oral route of infection, which can be extended to the study of a variety genetic and environmental sources of variation in gut infection outcomes and bacterial transmission

The route of infection determines Wolbachia antibacterial protection in Drosophila

International audienceBacterial symbionts are widespread among metazoans and provide a range of beneficial functions. -mediated protection against viral infection has been extensively demonstrated in In mosquitoes that are artificially transinfected with (wMel), protection from both viral and bacterial infections has been demonstrated. However, no evidence for -mediated antibacterial protection has been demonstrated in to date. Here, we show that the route of infection is key for -mediated antibacterial protection. carrying showed reduced mortality during enteric-but not systemic-infection with the opportunist pathogen -mediated protection was more pronounced in male flies and is associated with increased early expression of the antimicrobial peptide , and also increased expression of a reactive oxygen species detoxification gene (). These results highlight that the route of infection is important for symbiont-mediated protection from infection, that can protect hosts by eliciting a combination of resistance and disease tolerance mechanisms, and that these effects are sexually dimorphic. We discuss the importance of using ecologically relevant routes of infection to gain a better understanding of symbiont-mediated protection

Navigating infection risk during oviposition and cannibalistic foraging in a holometabolous insect

Deciding where to eat and raise offspring carries important fitness consequences for all animals, especially if foraging, feeding and reproduction increase pathogen exposure. In insects with complete metamorphosis, foraging mainly occurs during the larval stage, while oviposition decisions are made by adult females. Selection for infection avoidance behaviours may therefore be developmentally uncoupled. Using a combination of experimental infections and behavioral choice assays, we tested if Drosophila melanogaster fruit flies avoid infectious environments at distinct developmental stages. When given conspecific fly carcasses as a food source, larvae did not discriminate between carcasses that were clean or infected with the pathogenic Drosophila C Virus (DCV), even though cannibalism was a viable route of DCV transmission. When laying eggs, DCV-infected females did not discriminate between infectious and non-infectious carcasses. Healthy mothers however, laid more eggs near a clean rather than an infectious carcass. Avoidance during oviposition changed over time: after an initial oviposition period, healthy mothers stopped avoiding infectious carcasses. We attribute this to a trade-off between infection risk and reproduction. Laying eggs near potentially infectious carcasses was always preferred to sites containing only fly food. Our findings suggest infection avoidance contributes to how mothers provision their offspring and underline the need to consider infection avoidance behaviors at multiple life-stages

DAM Summary Statistics

Summary statistics taken from 'DAM_total' datasheet summarising this activity data using three values: (1) Total activity, (2) the Proportion of time spent awake and (3) the average activity when awake

Social Aggregation Body Lengths

Measures of randomly selected flies from an experiment testing the effect of genetic and sex-specific variation on social aggregation before and after infection with DCV

DAM_total

All recorded activity counts for flies measured using the Drosophila Activity Monitor (DAM)

Dmel Activity and Aggregation

R script detailing the R code necessary to analyse and make plots of the data from two experiments on Drosophila activity and social aggregation