Evolution of virulence in a heterogeneous host population

Abstract.— There is a large body of theoretical studies that investigate factors that affect the evolution of virulence, that is parasite-induced host mortality. In these studies the host population is assumed to be genetically homogeneous. However, many parasites have a broad range of host types they infect, and trade-offs between the parasite virulence in different host types may exist. The aim of this paper is to study the effect of host heterogeneity on the evolution of parasite virulence. By analyzing a simple model that describes the replication of different parasite strains in a population of two different host types, we determine the optimal level of virulence in both host types and find the conditions under which strains that specialize in one host type dominate the parasite population. Furthermore, we show that intrahost evolution of the parasite during an infection may lead to stable polymorphisms and could introduce evolutionary branching in the parasite population.     

Evolution of virulence: interdependence, constraints, and selection using nested models

Natural selection acts on virus populations at two distinct but interrelated levels: within individual hosts and between them. Studies of the evolution of virulence typically focus on selection acting at the epidemiological or between-host level and demonstrate the importance of trade-offs between disease transmission and virulence rates. Within-host studies reach similar conclusions regarding trade-offs between transmission and virulence at the level of individual cells. Studies which examine selection at both scales assume that between- and within-host selection are necessarily in conflict. We explicitly examine these ideas and assumptions using a model of within-host viral dynamics nested within a model of between-host disease dynamics. Our approach allows us to evaluate the direction of selection at the within- and between-host levels and identify situations leading to conflict and accord between the two levels of selection.     

Within-host population dynamics and the evolution of microparasites in a heterogeneous host population

Abstract Why do parasites harm their hosts? The general understanding is that if the transmission rate and virulence of a parasite are linked, then the parasite must harm its host to maximize its transmission. The exact nature of such trade‐offs remains largely unclear, but for vertebrate hosts it probably involves interactions between a microparasite and the host immune system. Previous results have suggested that in a homogeneous host population in the absence of super‐ or coinfection, within‐host dynamics lead to selection of the parasite with an intermediate growth rate that is just being controlled by the immune system before it kills the host (Antia et al. 1994). In this paper, we examine how this result changes when heterogeneity is introduced to the host population. We incorporate the simplest form of heterogeneity–random heterogeneity in the parameters describing the size of the initial parasite inoculum, the immune response of the host, and the lethal density at which the parasite kills the host. We find that the general conclusion of the previous model holds: parasites evolve some intermediate growth rate. However, in contrast with the generally accepted view, we find that virulence (measured by the case mortality or the rate of parasite‐induced host mortality) increases with heterogeneity. Finally, we link the within‐host and between‐host dynamics of parasites. We show how the parameters for epidemiological spread of the disease can be estimated from the within‐host dynamics, and in doing so examine the way in which trade‐offs between these epidemiological parameters arise as a consequence of the interaction of the parasite and the immune response of the host.     

Selection and parasite evolution: a reproductive fitness cost associated with virulence in the parthenogenetic nematode <Emphasis Type="Italic">Meloidogyne incognita</Emphasis>

Selection in plant parasites for virulence on resistant hosts and the resulting effects on parasite fitness may be considered as a driving force in host-parasite coevolution. In the present study, we tested the hypothesis that a fitness cost may be associated with nematode virulence, using the interaction between the parthenogenetic species Meloidogyne incognita and tomato as a model system. The reproductive parameters of near-isogenic lines of the nematode, selected for avirulence or virulence against the tomato Mi resistance gene, were analysed and combined into a reproductive index that was taken as a measure of fitness. The lower fitness of the virulent lines on the susceptible tomato cultivar showed for the first time that a measurable fitness cost is associated with unnecessary virulence in the nematode. Although parthenogenesis should theoretically lead to little genetic variability, such cost may impose a direct constraint on the coevolution between the plant and the nematode populations, and suggests an adaptive significance of trade-offs between selected characters and fitness-related traits. These results indicate that, although plant resistance can be broken, it might prove durable in some conditions if the virulent nematodes are counterselected in susceptible plants, which could have important consequences for the management of resistant cultivars in the field.     

Evolutionary implications for interactions between multiple strains of host and parasite

The interaction between multiple parasite strains within different host types may influence the evolutionary trajectories of parasites. In this article, we formulate a deterministic model with two strains of parasites and two host types in order to investigate how heterogeneities in parasite virulence and host life-history may affect the persistence and spread of diseases in natural systems. We compute the reproductive number of strain i (R(i)) independently, as well as the (conditional) "invasion" reproductive number for strains i (R(i)(j), j not equal i) when strain j is at a positive equilibrium. We show that the disease-free equilibrium is locally asymptotically stable if R(i)<1 for both strains and is unstable if R(i)>1 for one stain. We establish the criterion R(i)(j)>1 for strain i to invade strain j. Subthreshold coexistence driven by coinfection is possible even when R(i) of one strain is below 1. We identify conditions that determine the evolution of parasite specialism or generalism based on the life-history strategies employed by hosts, and investigate how host strains may influence parasite persistence.     

The evolution of virulence: A stochastic simulation model examining parasitism at individual and population levels

We modelled the evolution of virulence when co-infections were permitted and compared patterns generated by our modelling approach with those of other models. In support of current models, we found that strains with virulences above the maximum basic reproductive rate (Ro) were competitively superior, and that both high host density (as indexed by host encounter rate) and high parasite infectiousness favoured evolution of strains with high virulence. However, we found that co-existence typically did not continue indefinitely and that parasites with high virulences, and Ro values approaching unity, often did not persist. We examined the extent to which processes such as stochasticity and positive frequency dependence influenced patterns generated by our model. Also, we examined commonly used indices of parasite fitness [i.e. Ro and rate of spread (ROS)], and found that only ROS was positively related to competitive ability when co-infections were permitted. However, there was considerable variation in competitive ability that was not explained by variation in ROS. We conclude that our modelling approach can significantly influence patterns generated and that conclusions from single models or conclusions based on current indices of parasite fitness should be viewed with caution. We suggest empirical tests that distinguish our model from other models and further examine the impact of mechanisms such as positive frequency dependence on the evolution of virulence. This revised version was published online in July 2006 with corrections to the Cover Date.     

Evolutionary dynamics of predator-prey systems: an ecological perspective

 Evolution takes place in an ecological setting that typically involves interactions with other organisms. To describe such evolution, a structure is needed which incorporates the simultaneous evolution of interacting species. Here a formal framework for this purpose is suggested, extending from the microscopic interactions between individuals – the immediate cause of natural selection, through the mesoscopic population dynamics responsible for driving the replacement of one mutant phenotype by another, to the macroscopic process of phenotypic evolution arising from many such substitutions. The process of coevolution that results from this is illustrated in the context of predator–prey systems. With no more than qualitative information about the evolutionary dynamics, some basic properties of predator–prey coevolution become evident. More detailed understanding requires specification of an evolutionary dynamic; two models for this purpose are outlined, one from our own research on a stochastic process of mutation and selection and the other from quantitative genetics. Much of the interest in coevolution has been to characterize the properties of fixed points at which there is no further phenotypic evolution. Stability analysis of the fixed points of evolutionary dynamical systems is reviewed and leads to conclusions about the asymptotic states of evolution rather different from those of game-theoretic methods. These differences become especially important when evolution involves more than one species. Received 10 November 1993; received in revised form 25 July 1994     

Evolution of microparasites in spatially and genetically structured host populations: The example of RHDV infecting rabbits

Several studies have shown that classical results of microparasite evolution could not extend to the case where the host species shows an important spatial structure. Rabbit haemorrhagic disease virus (RHDV), responsible for rabbit haemorrhagic disease (RHD), which recently emerged in rabbits, has strains within a wide range of virulence, thus providing an interesting example of competition between strains infecting a host species with a metapopulation structure. In addition, rabbits may show a genetic diversity regarding RHDV susceptibility. In the present paper we use the example of the rabbit-RHDV interaction to study the competition between strains of a same microparasite in a host population that is both spatially and genetically structured. Using metapopulation models we show that the evolution of the microparasite is guided by a trade-off between its capacity to invade subpopulations potentially infected by other strains and its capacity to persist within the subpopulation. In such a context, host genetic diversity acts by reducing the number of hosts susceptible to each strain, often favouring more persistent—and generally less virulent—strains. We also show that even in a stochastic context where host genes regularly go locally extinct, the microparasite pressure helps maintain the genetic diversity in the long term while reinforcing gene loss risk in the short term. Finally, we study how different demographic and epidemiologic parameters affect the coevolution between the rabbit and RHDV.     

A competitive exclusion principle for pathogen virulence

For a modified Anderson and May model of host parasite dynamics it is shown that infections of different levels of virulence die out asymptotically except those that optimize the basic reproductive rate of the causative parasite. The result holds under the assumption that infection with one strain of parasite precludes additional infections with other strains. Technically, the model includes an environmental carrying capacity for the host. A threshold condition is derived which decides whether or not the parasites persist in the host population.Supported by a Heisenberg scholarship of Deutsche Forschungsgemeinschaft     

Energy cost of infection burden: an approach to understanding the dynamics of host-pathogen interactions

A mathematical model of long-term immune defense against infection was used to estimate the energy involved in the principal processes of immune resistance during periods of health and infection. From these values, an optimal level of energy was determined for immune response depending on infection burden. The present findings suggest that weak but prevalent pathogens lead to latent or chronic infection, whereas more virulent but less prevalent pathogens result in acute infection. This energy-based approach offers insight into the mechanisms of immune system adaptation leading to the development of chronic infectious diseases and immune deficiencies.     

Consequences of behavioral dynamics for the population dynamics of predator-prey systems with switching

This article explores how different mechanisms governing the rate of change of the predators preference alter the dynamics of predator-prey systems in which the predator exhibits positive frequency-dependent predation. The models assume that individuals of the predator species adaptively adjust a trait that determines their relative capture rates of each of two prey species. The resulting switching behavior does not instantaneously attain the optimum for current prey densities, but instead lags behind it. Several mechanisms producing such lags are discussed and modeled. In all cases examined, our question is whether a realistic behavioral lag can significantly change the dynamics of the system relative to an analogous case in which the predators switching is effectively instantaneous. We also explore whether increasing the rate parameters of dynamic models of behavior results in convergence to the population dynamics of analogous models with instantaneous switching, and whether different behavioral models produce similar population dynamics. The analysis concentrates on systems that undergo endogenously generated predator-prey cycles in the absence of switching behavior. The average densities and the nature of indirect interactions are often sensitive to the rate of behavioral change, and are often qualitatively different for different classes of behavioral models. Dynamics and average densities can be very sensitive to small changes in parameters of either the prey growth or predator switching functions. These differences suggest that an understanding of switching in natural systems will require research into the behavioral mechanisms that govern lags in the response of predator preference to changes in prey density.     

The unavoidable costs and unexpected benefits of parasitism: population and metapopulation models of parasite-mediated competition

When faced with limited resources, organisms have to determine how to allocate their resources to maximize fitness. In the presence of parasites, hosts may be selected for their ability to balance between the two competing needs of reproduction and immunity. These decisions can have consequences not only for host fitness, but also for the ability of parasites to persist within the population, and for the competitive dynamics between different host species. We develop two mathematical models to investigate how resource allocation strategies evolve at both population and metapopulation levels. The evolutionarily stable strategy (ESS) at the population level is a balanced investment between reproduction and immunity that maintains parasites, even though the host has the capacity to eliminate parasites. The host exhibiting the ESS can always invade other host populations through parasite-mediated competition, effectively using the parasites as biological weapons. At the metapopulation level, the dominant strategy is sometimes different from the population-level ESS, and depends on the ratio of local extinction rate to host colonization rate. This study may help to explain why parasites are as common as they are, and can serve as a modeling framework for investigating parasite-mediated ecological invasions. Furthermore, this work highlights the possibility that the ‘introduction of enemies’ process may facilitate species invasion.     

Evolution of feeding structure plasticity in marine invertebrate larvae: a possible trade-off between arm length and stomach size

The ability of an organism to alter its morphology in response to environmental conditions (phenotypic plasticity) occurs in several species of marine invertebrates. Examples are sea urchin and sand dollar larvae (plutei). When food is scarce, plutei produce longer food-gathering structures (larval arms and a ciliary band) and smaller stomachs than when food is abundant. However, it is unclear whether stomach size is actually induced through changes in morphogenesis or simply by food distending the stomach. Distinguishing between these two hypotheses is possible because plutei morphologically respond to food concentrations and change the length of their food-gathering structures before they are capable of feeding. More importantly, these two hypotheses provide insights to whether a trade-off exists between the response in food-gathering structures and the response in stomach size—a possible explanation for the evolution of feeding-structure plasticity in marine invertebrate larvae. In this study, I investigated whether sea urchin larvae (Strongylocentrotus purpuratus and S. franciscanus) reared in different amounts of food produced stomachs of different sizes before they were capable of feeding. Prior to having the ability to ingest food, larvae produced larger stomachs and shorter arms when food was abundant than when food was scarce, consistent with the hypothesis that food induced changes in morphogenesis. In addition, there was a strong negative correlation between the magnitude of plasticity in larval arm length and the magnitude of plasticity in stomach size. These results are consistent with the idea that a trade-off exists between the response in arm length and the response in stomach size, and at least in part, explains the evolution of feeding structure plasticity in plutei. This may also explain why feeding-structure plasticity has evolved in larvae of other taxa (e.g. other echinoderms and gastropods).     

Spatial structure,host heterogeneity and parasite virulence: implications for vaccine‐driven evolution

Natural host‐parasite interactions exhibit considerable variation in host quality, with profound consequences for disease ecology and evolution. For instance, treatments (such as vaccination) may select for more transmissible or virulent strains. Previous theory has addressed the ecological and evolutionary impact of host heterogeneity under the assumption that hosts and parasites disperse globally. Here, we investigate the joint effects of host heterogeneity and local dispersal on the evolution of parasite life‐history traits. We first formalise a general theoretical framework combining variation in host quality and spatial structure. We then apply this model to the specific problem of parasite evolution following vaccination. We show that, depending on the type of vaccine, spatial structure may select for higher or lower virulence compared to the predictions of non‐spatial theory. We discuss the implications of our results for disease management, and their broader fundamental relevance for other causes of host heterogeneity in nature.     

Replicator-mutator equation, universality property and population dynamics of learning

Replicator-mutator equation is used to describe the dynamics of complex adaptive systems in population genetics, biochemistry and models of language learning. We study "localized", or "coherent", solutions, which are especially relevant in the context of learning and correspond to the existence of a predominant language in the population. There is a coherence threshold for learning fidelity, above which coherent communication can be maintained. We prove the following surprising universality property of coherence threshold: for typical realizations of random coefficients in the fitness matrix, the value of the coherence threshold does not depend on the size of the system.     

Analysing hierarchically-structured fitness and modular dynamics in plants: integration of concepts from population dynamics

This paper analyses the reproductive strategies of a modular organism by means of demographic analysis of its reproductive units. The buds of the reproductive structure of Retama sphaerocarpa (L.) Boiss., a perennial shrub with a simple modular structure, were considered as ‘individuals’ of a population of modules within each individual plant. The development of the buds leads to the production of subpopulations of new units (inflorescences, flowers, fruits) of a lower hierarchical level. Fitness and hierarchical fitness (defined by the integration of developmental hierarchical levels in the plant) were analysed at the shoot module level, starting from the analogy provided by classical population dynamics and taking into account the different subpopulations of modules that take part in the reproductive process. Consideration of the dynamics of such subpopulations reveals the way in which demographic strategies partitioning the reproductive effort are exerted throughout the plant, and their consequences for fitness. The analysis of the reproductive process in R. sphaerocarpa shows a critical developmental transition from flowering to fruiting buds, which is a consequence of a low survival rate of the subpopulation of flowers. Despite the specificity of the empirical information used in this investigation, the fitness analyses proposed in this paper are fully applicable to any hierarchically-structured biological system, either modular or unitary.     

Coupled population dynamics of two Neotropical marsupials driven by mesopredator's abundance

According to the mesopredator release theory, when top predators are eradicated from an area, mesopredators become overabundant. Didelphis aurita is the largest marsupial in the Atlantic Rainforest, and it occurs in higher abundances in the absence of top predators. This mesopredator has similar ecological requirements to the sympatric marsupial Metachirus nudicaudatus. Considering the similar requirements, and that D. aurita is about three times the size of M. nudicaudatus, our hypothesis is that the increase in D. aurita's abundance may negatively affect M. nudicaudatus' population. To test this hypothesis, we conducted a two-year capture-mark-recapture study in an area in the Southeast of Brazil where top predator community is depauperated. The relationship between the population dynamics of these two marsupials was analyzed by including abundance of D. aurita and environmental conditions as explanatory variables of the population parameters of M. nudicaudatus. We observed that all demographic parameters of M. nudicaudatus fluctuated over time and responded negatively to D. aurita abundance. Our conclusion is that, at least on a monthly timescale, the interspecific relationship with D. aurita seems to influence more M. nudicaudatus' population than any other environmental covariate. These findings suggest that mesopredator release can promote negative effects on population parameters of other species within the same trophic level. Considering that top predators are no longer present in most of the remaining Atlantic Rainforest fragments, the marsupial D. aurita has become a key species in this biome, with relevant consequences arising from its interspecific interactions.     

A simple model for the dynamics of a host-parasite-hyperparasite interaction

Hyperparasites can play a crucial role in the control of a host-parasite interaction if they are successfully established in the community. We investigated the specific traits of the hyperparasite and those of the release event which allow a successful regulation of primary parasite populations. This study has been motivated by the case study of chestnut-Cryphonectria parasitica-Cryphonectria Hypovirus interaction. We use a model of SIR/SIS type which assumes a limited diffusion of the parasite. Our model emphasizes the thresholds for invasion linked to the ecological specificities of both the pathogen and the hyperparasite (transmission rates and virulence) and to the initial conditions of the system (population sizes of the different categories). The predictions are consistent with data on the observed spread of the virus. "Mild" strains of the hyperparasite, characterized by a high vertical transmission rate and low virulence, are more prone to establish than "severe" strains. It also demonstrates that the horizontal transmission of the virus, which is controlled by a vegetative incompatibility system in the fungus, is not the unique constraint for the virus establishment. This study may contribute to theoretical and practical aspects of the biological control of plant diseases with a hyperparasite and to the ecology of biological invasions.     

Within-host parasite dynamics,emerging trade-off,and evolution of virulence with immune system

Abstract.— Virulence is an evolutionary paradox because parasites never benefit from their host's death. The adaptive explanation of virulence is classically based upon the existence of physiological constraints that create a trade-off between parasites' epidemiological traits (virulence, transmissibility, and clearance). Here we develop an epidemiological model where infections are dynamic processes and we demonstrate how these dynamics generate a trade-off between emerging epidemiological parameters. We then study how host's immune strength modifies this trade-off and hence influences virulence evolution. We found that in acute infections, where parasites are engaged in a race with immune cells, immunity restrains more the duration of the infection than its intensity. As a consequence parasites evolve to provoke more virulent but shorter infections in strongly immunized hosts.