Evolution of virulence when transmission occurs before disease

Most models of virulence evolution assume that transmission and virulence are constant during an infection. In many viral (HIV and influenza), bacterial (TB) and prion (BSE and CWD) systems, disease-induced mortality occurs long after the host becomes infectious. Therefore, we constructed a model with two infected classes that differ in transmission rate and virulence in order to understand how the evolutionarily stable strategy (ESS) depends on the relative difference in transmission and virulence between classes, on the transition rate between classes and on the recovery rate from the second class. We find that ESS virulence decreases when expressed early in the infection or when transmission occurs late in an infection. When virulence occurred relatively equally in each class and there was disease recovery, ESS virulence increased with increased transition rate. In contrast, ESS virulence first increased and then decreased with transition rate when there was little virulence early in the infection and a rapid recovery rate. This model predicts that ESS virulence is highly dependent on the timing of transmission and pathology after infection; thus, pathogen evolution may either increase or decrease virulence after emergence in a new host.     

Ecological conditions that favor the evolution of intermediate-virulence in an environmentally transmitted parasite

In this paper we develop and analyze several populaion-dynamic models of an environmentally transmitted symbiotic parasite infecting an isolated population of susceptible hosts. In our most basic model infection acts only to decrease the average lifetime of the infected host, parasites are only transmitted to uninfected hosts, there is no recovery from infection, and the rate of parasite transmission is an increasing function of the level of parasite virulence. It is shown that invasion of the parasite-free equilibrium cannot occur for virulence levels that are either too high or too low. We then incorporate a number of modifications to the model, among them the possibility that host fertility is reduced by infection, and that transmission rate depends additionally on susceptible host density. It is shown that the essential nature of the conditions for invasion are preserved. Thus, natural selection for intermediate virulence is a generic property of a broad class of population models.     

Crayfish population size under different routes of pathogen transmission

We present an epidemiological model for the crayfish plague, a disease caused by an invasive oomycete Aphanomyces astaci, and its general susceptible freshwater crayfish host. The pathogen shows high virulence with resulting high mortality rates in freshwater crayfishes native to Europe, Asia, Australia, and South America. The crayfish plague occurrence shows complicated dynamics due to the several types of possible infection routes, which include cannibalism and necrophagy. We explore this complexity by addressing the roles of host cannibalism and the multiple routes of transmission through (1) environment, (2) contact, (3) cannibalism, and (4) scavenging of infected carcasses. We describe a compartment model having six classes of crayfish and a pool of crayfish plague spores from a single nonevolving strain. We show that environmental transmission is the decisive factor in the development of epidemics. Compared with a pathogen-free crayfish population, the presence of the pathogen with a low environmental transmission rate, regardless of the contact transmission rate, decreases the crayfish population size with a low risk of extinction. Conversely, a high transmission rate could drive both the crayfish and pathogen populations to extinction. High contact transmission rate with a low but nonzero environmental transmission rate can have mixed outcomes from extinction to large healthy population, depending on the initial values. Scavenging and cannibalism have a relevant role only when the environmental transmission rate is low, but scavenging can destabilize the system by transmitting the pathogen from a dead to a susceptible host. To the contrary, cannibalism stabilizes the dynamics by decreasing the proportion of infected population. Our model provides a simple tool for further analysis of complex host parasite dynamics and for the general understanding of crayfish disease dynamics in the wild.     

Empirical support for optimal virulence in a castrating parasite

The trade-off hypothesis for the evolution of virulence predicts that parasite transmission stage production and host exploitation are balanced such that lifetime transmission success (LTS) is maximised. However, the experimental evidence for this prediction is weak, mainly because LTS, which indicates parasite fitness, has been difficult to measure. For castrating parasites, this simple model has been modified to take into account that parasites convert host reproductive resources into transmission stages. Parasites that kill the host too early will hardly benefit from these resources, while postponing the killing of the host results in diminished returns. As predicted from optimality models, a parasite inducing castration should therefore castrate early, but show intermediate levels of virulence, where virulence is measured as time to host killing. We studied virulence in an experimental system where a bacterial parasite castrates its host and produces spores that are not released until after host death. This permits estimating the LTS of the parasite, which can then be related to its virulence. We exposed replicate individual Daphnia magna (Crustacea) of one host clone to the same amount of bacterial spores and followed individuals until their death. We found that the parasite shows strong variation in the time to kill its host and that transmission stage production peaks at an intermediate level of virulence. A further experiment tested for the genetic basis of variation in virulence by comparing survival curves of daphniids infected with parasite spores obtained from early killing versus late killing infections. Hosts infected with early killer spores had a significantly higher death rate as compared to those infected with late killers, indicating that variation in time to death was at least in part caused by genetic differences among parasites. We speculate that the clear peak in lifetime reproductive success at intermediate killing times may be caused by the exceptionally strong physiological trade-off between host and parasite reproduction. This is the first experimental study to demonstrate that the production of propagules is highest at intermediate levels of virulence and that parasite genetic variability is available to drive the evolution of virulence in this system.     

Host-parasite dynamics and the evolution of host immunity and parasite fecundity strategies

We explore evolutionarily stable co-evolution of host-macroparasite interactions in a discrete-time two-species population dynamics model, in which the dynamics may be stable, cyclic or chaotic. The macroparasites are assumed to harm host individuals through decreased reproductive output. Hosts may develop costly immune responses to defend themselves against parasites. Parasites compete with conspecifics by adjusting their fecundities. Overall, the presence of both parasites and the immune response in hosts produces more stable dynamics and lower host population sizes than that observed in the absence of the parasites. In our evolutionary analyses, we show that maximum parasite fecundity is always an evolutionarily stable strategy (ESS), irrespective of the type of population interaction, and that maximum parasite fecundity generally induces a minimum parasite population size through over-exploitation of the host. Phenotypic polymorphisms with respect to immunity in the host species are common and expected in ESS host strategies: the benefits of immunication depend on the frequency of the immune hosts in the population. In particular, the steady-state proportions of immune hosts depend, in addition to all the parameters of the parasite dynamics only on the cost of immunity and on the virulence of parasites in susceptible hosts. The implicit ecological dynamics of the host-parasite interaction affect the proportion of immune host individuals in the population. Furthermore, when changes in certain population parameters cause the dynamics of the host-parasite interaction to move from stability to cyclicity and then to chaos, the proportion of immune hosts tends to decrease; however, we also detected counter-examples to this result. As a whole, incorporating immunological and genetic aspects, as well as life-history trade-offs, into host-macroparasite dynamics produces a rich extension to the patterns observed in the models of ecological interactions and epidemics, and deserves more attention than is currently the case.     

A kin selection model for the evolution of virulence.

The costs and benefits of parasite virulence are analysed in an evolutionarily stable strategy (ESS) model. Increased host mortality caused by disease (virulence) reduces a parasite's fitness by damaging its food supply. The fitness costs of high virulence may be offset by the benefits of increased transmission or ability to withstand the host's defences. It has been suggested that multiple infections lead to higher virulence because of competition among parasite strains within a host. A quantitative prediction is given for the ESS virulence rate as a function of the coefficient of relatedness among co-infecting strains. The prediction depends on the quantitative relation between the costs of virulence and the benefits of transmission or avoidance of host defences. The particular mechanisms by which parasites can increase their transmission or avoid host defences also have a key role in the evolution of virulence when there are multiple infections.     

The effect of aggregative overwintering on an insect sexually transmitted parasite system

In contrast to the extensively studied sexually transmitted diseases (STDs) of humans, little is known of the ecology or evolutionary biology of sexually transmitted parasites in natural systems. This study of a sexually transmitted parasite on an insect host augments our understanding of both the parasite's population dynamics and virulence effects. The impact of overwintering was assessed on the prevalence of the parasitic mite Coccipolipus hippodamiae on the two-spot ladybird, Adalia bipunctata. First, the effect of infection on host survival was examined during the stressful overwintering period. Box experiments in the field revealed that the infected ladybirds, especially males, are less likely to survive overwintering. The study provides the first evidence that the parasite harms males and suggests revisions of theories on the adaptive virulence of sexually transmitted parasites. It also indicates the importance of using a range of experimental conditions because virulence can be dependent on host condition and sex. Box experiments were also used to examine whether transmission of the parasite occurs within overwintering aggregations. These revealed that substantial transmission does not occur in aggregations and that transmission is predominantly sexual. Overall, the virulence effects and the lack of transmission mean that the overwintering period acts to diminish parasite prevalence and will retard the spring epidemic associated with host reproductive activity.     

Life history and virulence are linked in the ectoparasitic salmon louse Lepeophtheirus salmonis

Models of virulence evolution for horizontally transmitted parasites often assume that transmission rate (the probability that an infected host infects a susceptible host) and virulence (the increase in host mortality due to infection) are positively correlated, because higher rates of production of propagules may cause more damages to the host. However, empirical support for this assumption is scant and limited to microparasites. To fill this gap, we explored the relationships between parasite life history and virulence in the salmon louse, Lepeophtheirus salmonis, a horizontally transmitted copepod ectoparasite on Atlantic salmon Salmo salar. In the laboratory, we infected juvenile salmon hosts with equal doses of infective L. salmonis larvae and monitored parasite age at first reproduction, parasite fecundity, area of damage caused on the skin of the host, and host weight and length gain. We found that earlier onset of parasite reproduction was associated with higher parasite fecundity. Moreover, higher parasite fecundity (a proxy for transmission rate, as infection probability increases with higher numbers of parasite larvae released to the water) was associated with lower host weight gain (correlated with lower survival in juvenile salmon), supporting the presence of a virulence–transmission trade‐off. Our results are relevant in the context of increasing intensive farming, where frequent anti‐parasite drug use and increased host density may have selected for faster production of parasite transmission stages, via earlier reproduction and increased early fecundity. Our study highlights that salmon lice, therefore, are a good model for studying how human activity may affect the evolution of parasite virulence.     

Pathogen invasion and host extinction in lattice structured populations

We examined the propagation of an infectious disease and the eventual extinction of the host population in a lattice-structured population. Both the host colonization and pathogen transmission processes are assumed to be restricted to act between the nearest neighbor sites. The model is analyzed by an improved version of pair approximation (IPA). Pair approximation is a technique to trace the dynamics of the number of nearest neighbor pairs having particular states, and IPA takes account of the clustering property of lattice models more precisely. The results are checked by computer simulations. The analysis shows: (i) in a one-dimensional lattice population, a pathogen cannot invade a host population no matter how large is the transmission rate; (ii) in a two-dimensional lattice population, pathogens will drive the host to extinction if the transmission rate is larger than a threshold. These results indicate that spatially structured population models may give qualitatively different results from conventional population models, such as Lotka-Volterra ones, without spatial structure.     

Complex dynamics of a predator–prey–parasite system: An interplay among infection rate,predator's reproductive gain and preference

Parasites are considered as an important factor in regulating their host populations through trait-mediated effects. On the other hand, predation becomes particularly interesting in host–parasite systems because predation can significantly alter the abundance of parasites and their host population. The combined effects of parasites and predator on host population and community structure therefore may have larger effect. Different field experiments confirm that predators consume disproportionately large number of infected prey in comparison to their susceptible counterpart. There are also substantial evidences that predator has the ability to distinguish prey that have been infected by a parasite and avoid such prey to reduce fitness cost. In this paper we study the predator–prey dynamics, where the prey species is infected by some parasites and predators consume both the susceptible and infected prey with some preference. We demonstrate that complexity in such systems largely depends on the predator's selectivity, force of infection and predator's reproductive gain. If the force of infection and predator's reproductive gain are low, parasites and predators both go to extinction whatever be the predator's preference. The story may be totally different in the opposite case. Survival of species in stable, oscillatory or chaotic states, and their extinction largely depend on the predator's preference. The system may also show two coexistence equilibrium points for some parameter values. The equilibrium with lower susceptible prey density is always stable and the equilibrium with higher susceptible prey density is always unstable. These results suggest that understanding the consequences of predator's selectivity or preference may be crucial for community structure involving parasites.     

How parasite-mediated costs drive the evolution of disease state-dependent dispersal

The process of dispersal is central to population biology and evolutionary ecology. Because of negative impacts on host fitness, parasite infection generates potential costs of dispersal. However, theoretical predictions that address this issue are lacking. Here, we develop a mathematical model to demonstrate how the dispersal rate of hosts evolves under the influence of parasites in ecological scenarios incorporating pre-, during-, and post-dispersal infection/recovery events. We show that (1) the dispersal tendency is strongly biased towards either infected individuals or susceptible individuals, (2) the bias is inherently determined by the parasite-mediated relative cost of dispersal, and (3) the dispersal costs are determined by the autocorrelation of disease states (susceptible and infected) between pre- and post-dispersal. Our results suggest that parasite virulence in concert with the timing of infection drive the evolution of disease state-biased dispersal. To understand the evolutionary processes in spatial host–parasite systems, the parasite-induced costs of dispersal need to be taken into account.     

The evolution of parasite virulence, superinfection, and host resistance

We analyze the evolutionary consequences of host resistance (the ability to decrease the probability of being infected by parasites) for the evolution of parasite virulence (the deleterious effect of a parasite on its host). When only single infections occur, host resistance does not affect the evolution of parasite virulence. However, when superinfections occur, resistance tends to decrease the evolutionarily stable (ES) level of parasite virulence. We first study a simple model in which the host does not coevolve with the parasite (i.e., the frequency of resistant hosts is independent of the parasite). We show that a higher proportion of resistant host decreases the ES level of parasite virulence. Higher levels of the efficiency of host resistance, however, do not always decrease the ES parasite virulence. The implications of these results for virulence management (evolutionary consequences of public health policies) are discussed. Second, we analyze the case where host resistance is allowed to coevolve with parasite virulence using the classical gene-for-gene (GFG) model of host-parasite interaction. It is shown that GFG coevolution leads to lower parasite virulence (in comparison with a fully susceptible host population). The model clarifies and relates the different components of the cost of parasitism: infectivity (ability to infect the host) and virulence (deleterious effect) in an evolutionary perspective.     

Parasite evolution and extinctions

We examine the evolution of diseases that show the frequency‐dependent transmission process that is commonly applied to sexually and vector‐transmitted infections. As is commonly found, the basic reproductive ratio (R₀) of the parasite is maximized by evolution. This has important implications, as it implies that for a wide range of circumstances diseases that show frequency‐dependent transmission may be selected to evolve towards driving their hosts to extinction. This contrasts with the results obtained in spatially explicit models where although parasite‐driven host extinction may occur, it is unlikely to evolve. We further show that an evolutionary constraint between transmission and virulence is required for evolution to lead to an endemic coexistence of both the host and the disease. Furthermore, this constraint needs to be saturating, such that transmission is ‘bought’ at an increasing cost in terms of virulence, to avoid evolution to extinction.     

Parasite-driven extinction in spatially explicit host-parasite systems

General host-parasite theory suggests that parasites may be implicated in the extinction of their hosts by causing instability that leads to increased risk of stochastic extinction. In contrast, spatially explicit models suggest that the parasite may directly drive the host population to extinction. Here we examine the ecological characteristics of host-parasite interactions that favor parasite-driven host extinction. Pair approximations and simulations show that parasites only drive their hosts to extinction when they significantly reduce host reproduction. As a matter of interest, parasites that have a relatively small effect on host death rate are more likely to cause host extinction. Parasite-driven host extinction occurs at any population size, whereas extinction caused by stochastic effects is less likely to occur in large host populations. Populations may therefore be under threat from parasites that stop host reproduction, and this type of parasite may prove to be the most effective biological pesticide.     

Epizootiology of blood parasites in an Australian lizard: a mark-recapture study of a natural population

The dynamics of a naturally endemic blood parasite (Hepatozoon hinuliae) were studied in a lizard (Eulamprus quoyii) host population, using 2 years of longitudinal data. We investigated how parasite abundance in the population varied over time, examined whether certain host sub-populations were more prone to infection, and compared parasite loads in relation to host reproductive behaviour. We recorded blood parasite infections of 331 individuals, obtained in 593 captures. Prevalence (the proportion of the host population infected) of blood parasites was high; approximately 66% of the lizard population was infected. Probability of infection increased with host age and size, but did not differ between the sexes. Within individuals, parasite load (the intensity of infection within individuals) did not vary over time, and was independent of host reproductive behaviour. Parasite load was significantly higher in males compared to females.     

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

Why are some discases 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.     

Phenotypic plasticity of host-parasite interactions in response to the route of infection

The microsporidium Octosporea bayeri can infect its host, the planktonic crustacean Daphnia magna, vertically and horizontally. The two routes differ greatly in the way the parasite leaves the harbouring host (transmission) and in the way it enters a new, susceptible host (infection). Infections resulting from each route may thus vary in the way they affect host and parasite life-histories and, subsequently, host and parasite fitness. We conducted a life-table experiment to compare D. magna infected with O. bayeri either horizontally or vertically, using three different parasite isolates. Both the infection route and the parasite isolate had significant effects on host life-history. Hosts matured at different ages depending on the parasite isolate, and at a size that varied with infection route. The frequency of host sterility and the host's life-time reproductive success were affected by both the infection route and the parasite isolate. The infection route also affected parasite life-history. The production of parasite spores was much higher in vertically than in horizontally infected hosts. We found a trade-off between the production of spores (the parasite's horizontal fitness component) and the production of infected host offspring (the parasite's vertical fitness component). This study shows that hosts and parasites can react plastically to different routes of infection, suggesting that ecological factors that may influence the relative importance of horizontal and vertical transmission can shape the evolution of host and parasite life histories, and, consequently, the evolution of virulence.     

Host-parasite population dynamics under combined frequency- and density-dependent transmission

Many host‐parasite models assume that transmission increases linearly with host population density (‘density‐dependent transmission’), but various alternative transmission functions have been proposed in an effort to capture the complexity of real biological systems. The most common alternative (usually applied to sexually transmitted parasites) assumes instead that the rate at which hosts contact one another is independent of population density, leading to ‘frequency‐dependent’ transmission. This straight‐forward distinction generates fundamentally different dynamics (e.g. deterministic, parasite‐driven extinction with frequency‐ but not density‐dependence). Here, we consider the situation where transmission occurs through two different types of contact, one of which is density‐dependent (e.g. social contacts), the other density‐independent (e.g. sexual contacts). Drawing on a range of biological examples, we propose that this type of contact structure may be widespread in natural populations. When our model is characterized mainly by density‐dependent transmission, we find that allowing even small amounts of transmission to occur through density‐independent contacts leads to the possibility of deterministic, parasite‐driven extinction (and lowers the threshold for parasite persistence). Contrastingly, allowing some density‐dependent transmission to occur in a model characterized mainly by density‐independent contacts (i.e. by frequency‐dependent transmission) does not affect the extinction threshold, but does increase the likelihood of parasite persistence. The idea that directly transmitted parasites exploit different types of host contact is not new, but here we show that the impact on dynamics can be fundamental even in the simplest cases. For example, in systems where density‐dependent transmission is normally assumed de facto, we show that parasite‐driven extinction can occur if a small amount of transmission occurs through density‐independent contacts. Many empirical studies are still guided by the traditional density/frequency dichotomy, but our combined transmission function may provide a better model for systems in which both types of transmission occur.     

Cooperation,virulence and siderophore production in bacterial parasites

Kin selection theory predicts that the damage to a host resulting from parasite infection (parasite virulence) will be negatively correlated to the relatedness between parasites within the host. This occurs because a lower relatedness leads to greater competition for host resources, which favours rapid growth to achieve greater relative success within the host, and that higher parasite growth rate leads to higher virulence. We show that a biological feature of bacterial infections can lead to the opposite prediction: a positive correlation between relatedness and virulence. This occurs because a high relatedness can favour greater (cooperative) production of molecules that scavenge iron (siderophores), which results in higher growth rates and virulence. More generally, the same underlying idea can predict a positive relationship between relatedness and virulence in any case where parasites can cooperate to increase their growth rate; other examples include immune suppression and the production of biofilms to aid colonization.     

Fatal disease and demographic Allee effect: population persistence and extinction

If a healthy stable host population at the disease-free equilibrium is subject to the Allee effect, can a small number of infected individuals with a fatal disease cause the host population to go extinct? That is, does the Allee effect matter at high densities? To answer this question, we use a susceptible–infected epidemic model to obtain model parameters that lead to host population persistence (with or without infected individuals) and to host extinction. We prove that the presence of an Allee effect in host demographics matters even at large population densities. We show that a small perturbation to the disease-free equilibrium can eventually lead to host population extinction. In addition, we prove that additional deaths due to a fatal infectious disease effectively increase the Allee threshold of the host population demographics.