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Vaccination leads to dramatic perturbations of the environment of parasite populations and this can have both demographic and evolutionary consequences. We present a theoretical framework for modelling the short- and long-term epidemiological and evolutionary consequences of vaccination. This framework integrates previous theoretical studies of vaccine-induced parasite evolution, and it allows one to make some useful qualitative predictions regarding the outcome of the competition between different types of vaccine-favoured variants. It can also be used to make quantitative predictions about the speed of such evolutionary processes. This work may help define the relevant parameters that need to be measured in specific parasite populations in order to evaluate the potential evolutionary consequences of vaccination. In particular, we argue that more work should be done evaluating the nature and magnitude of parasite fitness costs associated with adaptation to vaccinated hosts.

Much of the existing theory for the evolutionary biology of infectious diseases uses an invasion analysis approach. In this Ideas and Perspectives article, we suggest that techniques from theoretical population genetics can also be profitably used to study the evolutionary epidemiology of infectious diseases. We highlight four ways in which population-genetic models provide benefits beyond those provided by most invasion analyses: (i) they can make predictions about the rate of pathogen evolution; (ii) they explicitly draw out the mechanistic way in which the epidemiological dynamics feed into evolutionary change, and thereby provide new insights into pathogen evolution; (iii) they can make predictions about the evolutionary consequences of non-equilibrium epidemiological dynamics; (iv) they can readily incorporate the effects of multiple host dynamics, and thereby account for phenomena such as immunological history and/or host co-evolution.

Evolutionary biologists have identified several factors that could explain the widespread phenomena of sex and recombination. One hypothesis is that host-parasite interactions favor sex and recombination because they favor the production of rare genotypes. A problem with many of the early models of this so-called Red Queen hypothesis is that several factors are acting together: directional selection, fluctuating epistasis, and drift. It is thus difficult to identify what exactly is selecting for sex in these models. Is one factor more important than the others or is it the synergistic action of these different factors that really matters? Here we focus on the analysis of a simple model with a single mechanism that might select for sex: fluctuating epistasis. We first analyze the evolution of sex and recombination when the temporal fluctuations are driven by the abiotic environment. We then analyze the evolution of sex and recombination in a two-species coevolutionary model, where directional selection is absent (allele frequencies remain fixed) and temporal variation in epistasis is induced by coevolution with the antagonist species. In both cases we contrast situations with weak and strong selection and derive the evolutionarily stable (ES) recombination rate. The ES recombination rate is most sensitive to the period of the cycles, which in turn depends on the strength of epistasis. In particular, more virulent parasites cause more rapid cycles and consequently increase the ES recombination rate of the host. Although the ES strategy is maximized at an intermediate period, some recombination is favored even when fluctuations are very slow. By contrast, the amplitude of the cycles has no effect on the ES level of sex and recombination, unless sex and recombination are costly, in which case higher-amplitude cycles allow the evolution of higher rates of sex and recombination. In the coevolutionary model, the amount of recombination in the interacting species also has a large effect on the ES, with evolution favoring higher rates of sex and recombination than in the interacting species. In general, the ES recombination rate is less than or equal to the recombination rate that would maximize mean fitness. We also discuss the effect of migration when sex and recombination evolve in a metapopulation. We find that intermediate parasite migration rates maximize the degree of local adaptation of the parasite and lead to a higher ES recombination rate in the host.

We explore the potential consequences of vaccination on parasite epidemiology and evolution. Our model combines a microscopic (within-host dynamics) and a macroscopic (epidemiological dynamics) description of the interaction between the parasite and its host. This approach allows relevant epidemiological traits such as parasite transmission, parasite virulence, and host recovery to emerge from a mechanistic model of acute infection describing the interaction between the parasite and the host immune system. We model the effect of a vaccine as an activator of immunity enhancing the replication rate of lymphocytes, their initial density at infection's initiation, their efficacy to kill the parasite, or their activation delay after infection. We analyze the evolution of the replication rate of parasites and show that vaccination may promote the evolution of faster replicating and, consequently, more virulent strains. We also show that intermediate vaccination coverage may lead to the coexistence of two different parasite strategies (a low-virulence strain adapted to naive hosts, and a high-virulence strain, more generalist, adapted to both naive and vaccinated hosts). We discuss the consequences of various vaccination strategies under different epidemiological situations using several distinct measures to evaluate the cost induced by the parasite on individuals and entire host populations.

Superparasitism refers to the oviposition behavior of parasitoid females who lay their eggs in an already parasitized host. This often yields intense competition among larvae that are sharing the same host. Why would a female oviposit in such hostile habitat instead of looking for a better quality, unparasitized host? Here we present a continuous-time model of host-parasitoid interaction and discuss alternative scenarios. This model is first used to analyze the evolution of the superparasitism behavior of a solitary proovigenic parasitoid under both time and egg limitation. Then, following the recent discovery by Varaldi et al., we allow the parasitoid to be infected by a virus that alters the superparasitism behavior of its host to enhance its own horizontal transmission. The analysis of the coevolution of this manipulative behavior with the oviposition behavior of uninfected females clarifies and quantifies the conflict that emerges between the parasitoid and its virus. The model also yields new testable predictions. For example, we expect that uninfected parasitoids should superparasite less after coevolving with the manipulative virus. More generally, this model provides a theoretical framework for analyzing the evolution of the manipulation of parasitoid life-history traits by microparasites.

Antagonistic coevolution between hosts and parasites in spatially structured populations can result in local adaptation of parasites; that is, the greater infectivity of local parasites than foreign parasites on local hosts. Such parasite specialization on local hosts has implications for human health and agriculture. By contrast with classic single-species population-genetic models, theory indicates that parasite migration between subpopulations might increase parasite local adaptation, as long as migration does not completely homogenize populations. To test this hypothesis we developed a system-specific mathematical model and then coevolved replicate populations of the bacterium Pseudomonas fluorescens and a parasitic bacteriophage with parasite only, with host only or with no migration. Here we show that patterns of local adaptation have considerable temporal and spatial variation and that, in the absence of migration, parasites tend to be locally maladapted. However, in accord with our model, parasite migration results in parasite local adaptation, but host migration alone has no significant effect.

Multihost parasites can infect different types of hosts or even different host species. Epidemiological models have shown the importance of the diversity of potential hosts for understanding the dynamics of infectious disease (e.g., the importance of reservoirs), but the consequences of this diversity for virulence and transmission evolution remain largely overlooked. Here, I present a general theoretical framework for the study of life-history evolution of multihost parasites. This analysis highlights the importance of epidemiology (the relative quality and quantity of different types of infected hosts) and between-trait constraints (both within and between different hosts) to parasite evolution. I illustrate these effects in different transmission scenarios under the simplifying assumption that parasites can infect only two types of hosts. These simple but contrasted evolutionary scenarios yield new insights into virulence evolution and the evolution of transmission routes among different hosts. Because many of the pathogens that have large public-health and agricultural impacts have complex life cycles, an understanding of their evolutionary dynamics could hold substantial benefits for management.

An aim of some vaccination programmes is to reduce the prevalence of an infectious disease and ultimately to eradicate it. We show that eradication success depends on the type of vaccine as well as on the vaccination coverage. Vaccines that reduce the parasite within-host growth rate select for higher parasite virulence and this evolution may both increase the prevalence of the disease and prevent disease eradication. By contrast, vaccines that reduce the probability of infection select against virulence and may lead more easily to eradication. In some cases, epidemiological feedback on parasite evolution yields an evolutionary bistable situation where, for intermediate vaccination coverage, parasites can evolve towards either high or low virulence, depending on the initial conditions. These results have practical implications for the design and use of imperfect vaccines in public- and animal-health programmes.

Epidemiological models generally explore the evolution of parasite life-history traits, namely, virulence and transmission, against a background of constant host life-history traits. However, life-history models have predicted the evolution of host traits in response to parasitism. The coevolution of host and parasite life-history traits remains largely unexplored. We present an epidemiological model, based on resource allocation theory, that provides an analysis of the coevolution between host reproductive effort and parasite virulence. This model allows for hosts with either a fixed (i.e., genetic) or conditional (i.e., a phenotypically plastic) response to parasitism. It also considers superinfections. We show that parasitism always favors increased allocation to host reproduction, but because of epidemiological feedbacks, the evolutionarily stable host reproductive effort does not always increase with parasite virulence. Superinfection drives the evolution of parasite virulence and acts on the evolution of the host through parasite evolution, generally leading to higher host reproductive effort. Coevolution, as opposed to cases where only one of the antagonists evolves, may generate correlations between host and parasite life-history traits across environmental gradients affecting the fecundity or the survival of the host. Our results provide a theoretical framework against which experimental coevolution outcomes or field observations can be contrasted.

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.

Vaccines rarely provide full protection from disease. Nevertheless, partially effective (imperfect) vaccines may be used to protect both individuals and whole populations. We studied the potential impact of different types of imperfect vaccines on the evolution of pathogen virulence (induced host mortality) and the consequences for public health. Here we show that vaccines designed to reduce pathogen growth rate and/or toxicity diminish selection against virulent pathogens. The subsequent evolution leads to higher levels of intrinsic virulence and hence to more severe disease in unvaccinated individuals. This evolution can erode any population-wide benefits such that overall mortality rates are unaffected, or even increase, with the level of vaccination coverage. In contrast, infection-blocking vaccines induce no such effects, and can even select for lower virulence. These findings have policy implications for the development and use of vaccines that are not expected to provide full immunity, such as candidate vaccines for malaria.

We present a general epidemiological model of host-parasite interactions that includes various forms of superinfection. We use this model to study the effects of different host life-history traits on the evolution of parasite virulence. In particular, we analyze the effects of natural host death rate on the evolutionarily stable parasite virulence. We show that, contrary to classical predictions, an increase in the natural host death rate may select for lower parasite virulence if some form of superinfection occurs. This result is in agreement with the experimental results and the verbal argument presented by Ebert and Mangin (1997). This experiment is discussed in the light of the present model. We also point out the importance of superinfections for the effect of nonspecific immunity on the evolution of virulence. In a broader perspective, this model demonstrates that the occurrence of multiple infections may qualitatively alter classical predictions concerning the effects of various host life-history traits on the evolution of parasite virulence.

We examine the effect of iteroparity on the evolution of dispersal for a species living in a stable but fragmented habitat. We use a kin selection model that incorporates the effects of demographic stochasticity on the local age structure and age-specific genetic identities. We consider two cases: when the juvenile dispersal rate is allowed to change with maternal age and when it is not. In the latter case, we find that the unconditional evolutionarily stable dispersal rate increases when the adult survival rate increases. Two antagonistic forces act upon the evolution of age-specific dispersal rates. First, when the local age structure varies between patches of habitat, the intensity of competition between adults and juveniles in the natal patch is, on average, lower for offspring born to older senescent mothers. This selects for decreasing dispersal with maternal age. Second, offspring born to older parents are on average more related to other juveniles in the same patch and they experience a higher intensity of kin competition, which selects for increasing dispersal with maternal age. We show that the evolutionary outcome results from a balance between these two opposing forces, which depends on the amount of variance in age structure among sub-populations., (Copyright 2000 Academic Press.)

We analysed the effects of two different modes of host resistance on the evolution of parasite virulence. Hosts can either adopt an all-or-nothing qualitative response (i.e. resistant hosts cannot be infected) or a quantitative form of resistance (i.e. which reduces the within-host growth rate of the parasite). We show that the mode of host resistance greatly affects the evolutionary outcome. Specifically, a qualitative form of resistance reduces parasite virulence, while a quantitative form of resistance generally selects for higher virulence.

We present a general model of the evolution of dispersal in a population with any distribution of dispersal distance. We use this model to analyse evolutionarily stable (ES) dispersal rates for the classical island model of dispersal and for three different stepping-stone models. Using general techniques to compute relatedness coefficients in the different dispersal models which we consider, we find that the distribution of dispersal distance may affect the ES dispersal rate when the cost of dispersal is low. In this case the ES dispersal rate increases with the number of demes that can be reached by one dispersal event. However, for increasing cost the ES dispersal rate converges to a value independent of the distribution of dispersal distance. These results are in contrast to previous analyses of similar models. The effects of the size (number of demes) and shape (ratio between the width and the length) of the population on the evolution of dispersal are also studied. We find that larger and more elongated populations lead generally to higher ES dispersal rates. However, both of these effects can only be observed for extreme parameter values (i.e. for very small and very elongated populations). The direct fitness method and the analytical techniques used here to compute relatedness coefficients provide an efficient way to analyse ES strategies in subdivided populations.

Dispersal is often presented as a mechanism to avoid competition among relatives and inbreeding depression. However, the formal analysis of the effects of both these factors on the evolution of dispersal has only been conducted in few studies with strong restrictive assumptions. In this paper, I first derive the evolutionary stable dispersal rate as a function of three parameters: (1) the cost of dispersal, c, (2) the coefficient of relatedness among randomly chosen offspring, R, and (3) the cost of inbreeding, delta. In a second step, relatedness is used as a dynamical variable for the derivation of the evolutionarily stable dispersal rate. Finally, in a third step, relatedness and the cost of inbreeding are assumed to be dynamical variables. This allows to analyse the more realistic situation where dispersal, relatedness and the cost of inbreeding are coevolving simultaneously. Several subcases are considered depending on the genetic determinism (haploid or diploid), the control of the dispersal strategy (parent or offspring control of dispersal) and the plasticity of dispersal with sexes (with or without sex-specific dispersal rates). This analysis clarifies the role of the cost of inbreeding and kin competition on the evolution of dispersal (in particular on the evolution of sex-biased dispersal rates) and leads to quantitative and testable predictions. Copyright 1999 Academic Press.

We derive an analytic expression for the evolutionarily stable dispersal rate that formalizes the balance between the effects of four factors: the cost of dispersal, the extinction rate, the coefficient of relatedness and the mode of dispersal (i.e. the probability of common origin of immigrants). This result allows us to study the effects of each factor and, more interestingly, the interactions between them. In particular, we show that the evolutionarily stable dispersal rate is not always a decreasing function of the cost of dispersal and an increasing function of relatedness. These counter-intuitive results are discussed in the light of kin selection theory. We also present the results of numerical simulations in which relatedness is not a fixed parameter but depends on different parameters including dispersal itself. We discuss these results and show how the evolutionarily stable dispersal rate is affected by the environment and the life history traits of the species. More generally, this paper presents a simple formalism allowing the study of the effects of kin selection in unstable environments (i.e. with extinctions and recolonizations). The implications of this formalism for the understanding of the evolution of other life history traits is briefly discussed. Copyright 1999 Academic Press.

Conventional wisdom holds that parasites evolve more rapidly than their hosts and are therefore locally adapted, that is, better at exploiting sympatric than allopatric hosts. We studied local adaptation in the insect-transmitted fungal pathogen Microbotryum violaceum and its host plant Silene latifolia. Infection success was tested in sympatric (local) and allopatric (foreign) combinations of pathogen and host from 14 natural populations from a metapopulation. Seedlings from up to 10 seed families from each population were exposed to sporidial suspensions from each of four fungal strains derived from the same population, from a near-by population (< 10 km distance), and from two populations at an intermediate (< 30 km) and remote (< 170 km) distance, respectively. We obtained significant pathogen X plant interactions in infection success (proportion of diseased plants) at both fungal population and strain level. There was an overall pattern of local maladaptation of this pathogen: average fungal infection success was significantly lower on sympatric hosts (mean proportion of diseased plants = 0.32 ± 0.03 SE) than on allopatric hosts (0.40 ± 0.02). Five of the 14 fungal populations showed no strong reduction in infection success on sympatric hosts, and three even tended to perform better on sympatric hosts. This pattern is consistent with models of time-lagged cycles predicting patterns of local adaptation in host-parasite systems to emerge only on average. Several factors may restrict the evolutionary potential of this pathogen relative to that of its host. First, a predominantly selfing breeding system may limit its ability to generate new virulence types by sexual recombination, whereas the obligately outcrossing host 5. latifolia may profit from rearrangement of resistance alleles by random mating. Second, populations often harbor only a few infected individuals, so virulence variation may be further reduced by drift. Third, migration rates among host plant populations are much higher than among pathogen populations, possibly because pollinators prefer healthy over diseased plants. Migration among partly isolated populations may therefore introduce novel host plant resistance variants more often than novel parasite virulence variants. That migration contributes to the coevolutionary dynamics in this system is supported by the geographic pattern of infectivity. Infection success increased over the first 10-km range of host-pathogen population distances, which is likely the natural range of gene exchange., (© 1999 The Society for the Study of Evolution.)

The 'curse of the pharaoh' has been used as a metaphor for the hypothesis that higher parasite propagule survival selects for higher virulence. Indeed, the mysterious death of Lord Carnavon after entering the tomb of the Egyptian pharaoh Tutankhamen could potentially be explained by an infection with a highly virulent and very long-lived pathogen. In this paper, I investigate whether parasite virulence increases with high propagule survival. In this respect, I derive an analytic expression of the evolutionarily stable level of parasite virulence as a function of propagule survival rate when the host-parasite system has reached a stable ecological equilibrium. This result shows that, if multiple infection occurs, higher propagule survival generally increases parasite virulence. This effect is enhanced when parasite dispersal coevolves with parasite virulence. In a more general perspective, the model shows the importance of taking into account the combination of direct and indirect effects (which I call inclusive effects) of higher transmission ability on the evolution of parasite virulence. The recognition of these effects has several practical implications for virulence management.

We reviewed 59 cases of ureteropelvic junction obstruction diagnosed in 55 fetuses by echographic examination during prenatal period between 1981 and 1987. Postnatal excretory urograms and voiding cysto urethrography were obtained in all patients. Quantitative renal scans with 99 m technetium labeled dimercaptosuccinic acid or 99 m technetium labeled diethylenetriamine penta acetic acid were used in 49 patients and demonstrated a renal impairment in 19 cases (38%). 8 neonates were not operated, 1 required unilateral nephrectomy and 50 were treated by the Anderson-Hynes surgical procedure. 46 (92%) among those 50 obtained a significant improvement of pelvi-caliceal dilatation or excretion; 4 (8%) only a stabilisation. Early recognition of congenital hydronephrosis is now very common. After birth renal scans provided better estimation of renal function than excretory urograms but for the graduation of the obstruction the data did not appear to be always reliable (10% of false negatives in this study). The real problem is to know within which period of time the neonates whose renal function is impaired need surgery. In our study that question cannot be given a definitive answer because of too few post operative renal scans. However, we think, just as literature data tend to prove, that those neonates required early surgery if normal renal function is to be obtained.

The authors report their experience of the Gil Vernet procedure in the surgical management of primary vesico-ureteral reflux in children. 30 children were operated by this technique. Follow up studies range from 6 months to 30 months. All cases were successful. Therefore this technique was not performed routinely for all vesico-ureteral reflux and there is no grade IV reflux, no reflux secondary to neuropathic bladder in this study.