Mike Boots

'Small worlds' and the evolution of virulence: infection occurs locally and at a distance.

Why are some diseases more virulent than others? Vector–borne diseases such as malaria and water–borne diseases such as cholera are generally more virulent than diseases spread by direct contagion. One factor that characterizes both vector– and water–borne diseases is their ability to spread over long distances, thus causing infection of susceptible individuals distant from the infected individual. Here we show that this ability of the pathogen to infect distant individuals in a spatially structured host population leads to the evolution of a more virulent pathogen. We use a lattice model in which reproduction is local but infection can vary between completely local to completely global. With completely global infection the evolutionarily stable strategy (ESS) is the same as in mean–field models while a lower virulence is predicted as infection becomes more local. There is characteristically a period of relatively moderate increase in virulence followed by a more rapid rise with increasing proportions of global infection as we move beyond a ‘critical connectivity’. In the light of recent work emphasizing the existence of ‘small world’ networks in human populations, our results suggests that if the world is getting ‘smaller’ (as populations become more connected) diseases may evolve higher virulence.

Trade-Offs with Resistance to a Granulosis Virus in the Indian Meal Moth, Examined by a Laboratory Evolution Experiment

When microbial agents are used as pest-control agents, resistance in the host may be selected for. If resistance occurs there are potentially fitness costs due to trade-offs between resistance and other life-history traits. Genotypic trade-offs with resistance to a virus in a lepidopteran host are examined by a micro-evolutionary selection experiment. Six populations of the Indian meal moth, Plodia interpunctella, were established, three of which supported a granulosis virus infection (selected insects) while the remaining three acted as virus-free controls. After a period of 2 years, bioassays with the virus showed that selected moths were 1.96-fold more resistant to infection (LD 50 s) than those derived from the virus-free control populations

Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok

Dengue virus, the causative agent of dengue fever and its more serious manifestation dengue hemorrhagic fever, is widespread throughout tropical and subtropical regions. The virus exists as four distinct serotypes, all of which have cocirculated in Bangkok for several decades with epidemic outbreaks occurring every 8–10 years. We analyze time-series data of monthly infection incidence, revealing a distinctive pattern with epidemics of serotypes 1, 2, and 3 occurring at approximately the same time and an isolated epidemic of serotype 4 occurring in the intervening years. Phylogenetic analysis of virus samples collected over the same period shows that clade replacement events are linked to the epidemic cycle and indicates that there is an interserotypic immune reaction. Using an epidemic model with stochastic seasonal forcing showing 8- to 10-year epidemic oscillations, we demonstrate that moderate cross-protective immunity gives rise to persistent out-of-phase oscillations similar to those observed in the data, but that strong or weak cross-protection or cross-enhancement only produces in-phase patterns. This behavior suggests that the epidemic pattern observed in Bangkok is the result of cross-protective immunity and may be significantly altered by changes in the interserotypic immune reaction.

The Evolution of Costly Resistance in Host‐Parasite Systems

Pairwise invadability analysis is used to examine the evolutionary dynamics of host resistance to microparasitic infection. A continuum of strains of the host differs in susceptibility to infection, with less susceptible strains paying a cost resulting in a lower intrinsic growth rate. With a combination of analytical and graphical pairwise invadability analysis, we show that the evolutionary outcome depends crucially on the shape of the constraint function between resistance and its assumed cost in intrinsic growth rates. When resistance is increasingly costly, a single evolutionarily stable strategy is predicted. Alternatively, with decreasingly costly resistance, we find that the hosts tend to be maximally resistant or not at all resistant. There are conditions under which dimorphism of both these types exists but intermediate resistances do not occur. Independently of the trade‐off function used, we are always more likely to get resistant strains of the host when the carrying capacity of the host is high. The pathogenicity of the parasite is also important in determining the likelihood and degree of resistance.

Local Interactions Select for Lower Pathogen Infectivity

Theory suggests that the current rapid increase in connectivity and consequential changes in the structure of human, agricultural, and wildlife populations may select for parasite strains with higher infectivity. We carried out a test of this spatial theory by experimentally altering individual host movement rates in a model host/pathogen system by altering the viscosity of their environment. In our microevolutionary selection experiments, the infectivity of the virus was, as predicted by the theory, reduced in the most viscous populations. We therefore provide empirical support for the theory that population structure affects the evolution of infectious organisms.

THE EVOLUTION OF PARASITES IN RESPONSE TO TOLERANCE IN THEIR HOSTS: THE GOOD, THE BAD, AND APPARENT COMMENSALISM

Abstract Tolerance to parasites reduces the harm that infection causes the host (virulence). Here we investigate the evolution of parasites in response to host tolerance. We show that parasites may evolve either higher or lower within-host growth rates depending on the nature of the tolerance mechanism. If tolerance reduces virulence by a constant factor, the parasite is always selected to increase its growth rate. Alternatively, if tolerance reduces virulence in a nonlinear manner such that it is less effective at reducing the damage caused by higher growth rates, this may select for faster or slower replicating parasites. If the host is able to completely tolerate pathogen damage up to a certain replication rate, this may result in apparent commensalism, whereby infection causes no apparent virulence but the original evolution of tolerance has been costly. Tolerance tends to increase disease prevalence and may therefore lead to more, rather than less, disease-induced mortality. If the parasite is selected, even a highly efficient tolerance mechanism may result in more individuals in total dying from disease. However, the evolution of tolerance often, although not always, reduces the individual risk of dying from infection.

The role of ecological feedbacks in the evolution of host defence: what does theory tell us?

Hosts have evolved a diverse range of defence mechanisms in response to challenge by infectious organisms (parasites and pathogens). Whether defence is through avoidance of infection, control of the growth of the parasite once infected, clearance of the infection, tolerance to the disease caused by infection or innate and/or acquired immunity, it will have important implications for the population ecology (epidemiology) of the host–parasite interaction. As a consequence, it is important to understand the evolutionary dynamics of defence in the light of the ecological feedbacks that are intrinsic to the interaction. Here, we review the theoretical models that examine how these feedbacks influence the nature and extent of the defence that will evolve. We begin by briefly comparing different evolutionary modelling approaches and discuss in detail the modern game theoretical approach (adaptive dynamics) that allows ecological feedbacks to be taken into account. Next, we discuss a number of models of host defence in detail and, in particular, make a distinction between ‘resistance’ and ‘tolerance’. Finally, we discuss coevolutionary models and the potential use of models that include genetic and game theoretical approaches. Our aim is to review theoretical approaches that investigate the evolution of defence and to explain how the type of defence and the costs associated with its acquisition are important in determining the level of defence that evolves.

Within and transgenerational immune priming in an insect to a DNA virus

Invertebrates mount a sophisticated immune response with the potential to exhibit a form of immune memory through ‘priming’. Increased immune protection following early exposure to bacteria has been found both later in life (within generation priming) and in the next generation (transgeneration priming) in a number of invertebrates. However, it is unclear how general immune priming is and whether immune priming occurs in response to different parasites, including viruses. Here, using Plodia interpuctella (Lepidoptera) and its natural DNA virus, Plodia interpunctella granulosis virus, we find evidence for both within generation and transgeneration immune priming. Individuals previously exposed to low doses of virus, as well as the offspring of exposed individuals, are subsequently less susceptible to viral challenge. Relatively little is known about the mechanisms that underpin viral immunity but it is probable that the viral immune response is somewhat different to that of bacteria. We show that immune priming may, however, be a characteristic of both responses, mediated through different mechanisms, suggesting that immune memory may be a general phenomenon of insect immunity. This is important because immune priming may influence both host–parasite population and evolutionary dynamics.

Deformed wing virus is a recent global epidemic in honeybees driven by Varroa mites

Varroa-vectored virus pandemic Bees are facing several threats that are causing population collapses. Wilfert et al. found that European honey bees are the primary source of deformed wing virus (DWV) (see the Perspective by Villalobos). However, paradoxically, transmission between bees is inefficient. It seems that parasitic mites can facilitate virus transmission. European honeybees acquired the rapidly spreading Varroa mite from Asian honey bees, possibly via the commercial exchange of queens. Not only do bees suffer direct damage from the mites, but the bees are also efficiently inoculated with DWV. Science, this issue p. 594; see also p. 554 Pandemic virus infection in honeybees has been facilitated by the recent spread of a parasitic mite and by human trade. [Also see Perspective by Villalobos] Deformed wing virus (DWV) and its vector, the mite Varroa destructor, are a major threat to the world’s honeybees. Although the impact of Varroa on colony-level DWV epidemiology is evident, we have little understanding of wider DWV epidemiology and the role that Varroa has played in its global spread. A phylogeographic analysis shows that DWV is globally distributed in honeybees, having recently spread from a common source, the European honeybee Apis mellifera. DWV exhibits epidemic growth and transmission that is predominantly mediated by European and North American honeybee populations and driven by trade and movement of honeybee colonies. DWV is now an important reemerging pathogen of honeybees, which are undergoing a worldwide manmade epidemic fueled by the direct transmission route that the Varroa mite provides.

Maintenance of host variation in tolerance to pathogens and parasites

Tolerance and resistance provide hosts with two distinct defense strategies against parasitism. In resistance the hosts “fight” the parasite directly, whereas in tolerance the hosts fight the disease by ameliorating the damage that infection causes. There is increasing recognition that the two mechanisms may exhibit very different evolutionary behaviors. Although empirical work has often noted considerable variance in tolerance within hosts, theory has predicted the fixation of tolerance due to positive frequency dependence through a feedback with disease prevalence. Here we reconcile these findings through a series of dynamic game theoretical models. We emphasize that there is a crucial distinction between tolerance to the effects of disease-induced mortality and tolerance to the effect of the disease-induced reductions in fecundity. Only mortality tolerance has a positive effect on parasite fitness, whereas sterility tolerance is neutral and may therefore result in polymorphisms. The nature of the costs to defense and their relationship to trade-offs between resistance and tolerance are crucial in determining the likelihood of variation, whereas the co-evolution of the parasite will not affect diversity. Our findings stress that it is important to measure the effects of different mechanisms on characteristics that affect the epidemiology of the parasite to completely understand the evolutionary dynamics of defense.