Why is sterility virulence most common in sexually transmitted infections? Examining the role of epidemiology

Sterility virulence, or the reduction in host fecundity due to infection, occurs in many host–pathogen systems. Notably, sterility virulence is more common for sexually transmitted infections (STIs) than for directly transmitted pathogens, while other forms of virulence tend to be limited in STIs. This has led to the suggestion that sterility virulence may have an adaptive explanation. By focusing upon finite population models, we show that the observed patterns of sterility virulence can be explained by consideration of the epidemiological differences between STIs and directly transmitted pathogens. In particular, when pathogen transmission is predominantly density invariant (as for STIs), and mortality is density dependent, sterility virulence can be favored by demographic stochasticity, whereas if pathogen transmission is predominantly density dependent, as is common for most directly transmitted pathogens, sterility virulence is disfavored. We show these conclusions can hold even if there is a weak selective advantage to sterilizing.     

Pathogen evolution under host avoidance plasticity

Host resistance consists of defences that limit pathogen burden, and can be classified as either adaptations targeting recovery from infection or those focused upon infection avoidance. Conventional theory treats avoidance as a fixed strategy which does not vary from one interaction to the next. However, there is increasing empirical evidence that many avoidance strategies are triggered by external stimuli, and thus should be treated as phenotypically plastic responses. Here, we consider the implications of avoidance plasticity for host–pathogen coevolution. We uncover a number of predictions challenging current theory. First, in the absence of pathogen trade-offs, plasticity can restrain pathogen evolution; moreover, the pathogen exploits conditions in which the host would otherwise invest less in resistance, causing resistance escalation. Second, when transmission trades off with pathogen-induced mortality, plasticity encourages avirulence, resulting in a superior fitness outcome for both host and pathogen. Third, plasticity ensures the sterilizing effect of pathogens has consequences for pathogen evolution. When pathogens castrate hosts, selection forces them to minimize mortality virulence; moreover, when transmission trades off with sterility alone, resistance plasticity is sufficient to prevent pathogens from evolving to fully castrate.     

Fecundity compensation and tolerance to a sterilizing pathogen in Daphnia

Hosts are armed with several lines of defence in the battle against parasites: they may prevent the establishment of infection, reduce parasite growth once infected or persevere through mechanisms that reduce the damage caused by infection, called tolerance. Studies on tolerance in animals have focused on mortality, and sterility tolerance has not been investigated experimentally. Here, we tested for genetic variation in the multiple steps of defence when the invertebrate Daphnia magna is infected with the sterilizing bacterial pathogen Pasteuria ramosa: anti-infection resistance, anti-growth resistance and the ability to tolerate sterilization once infected. When exposed to nine doses of a genetically diverse pathogen inoculum, six host genotypes varied in their average susceptibility to infection and in their parasite loads once infected. How host fecundity changed with increasing parasite loads did not vary between genotypes, indicating that there was no genetic variation for this measure of fecundity tolerance. However, genotypes differed in their level of fecundity compensation under infection, and we discuss how, by increasing host fitness without targeting parasite densities, fecundity compensation is consistent with the functional definition of tolerance. Such infection-induced life-history shifts are not traditionally considered to be part of the immune response, but may crucially reduce harm (in terms of fitness loss) caused by disease, and are a distinct source of selection on pathogens.     

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.     

The evolution of virulence in pathogens with frequency-dependent transmission

Frequency-dependent transmission is an important feature of diseases that are sexually transmitted or transmitted by a vector that actively searches for hosts. Here I describe the evolution of virulence in pathogens that have frequency-dependent transmission. I consider two components of virulence--an increase in host mortality due to infection, as is classically described, and a decrease in host fecundity due to infection, because frequency dependence is common among diseases that fully or partially sterilize their hosts. Theoretical predictions pertaining to host-pathogen numerical dynamics can be quite different between pathogens with frequency-dependent transmission and those with density-dependent transmission. In contrast, this study suggests that the principles governing the evolution of virulence that have been established in the context of density-dependent pathogens may also apply (qualitatively) to frequency-dependent pathogens. I examine the evolutionary trajectories of the mortality and sterility components of virulence as well as the role of spatial population structure in the evolution of the sterility component of virulence.     

Allocation to sexual versus nonsexual disease transmission

Many diseases have both sexual and nonsexual transmission routes, and closely related diseases often differ in their degree of sexual transmission. We investigate the evolution of transmission mode as a function of host social and mating structure using a model in which disease transmission is explicitly dependent on the numbers of sexual and nonsexual contacts (which are themselves a function of population density) and per-contact infection probabilities. Most generally, and in the absence of trade-offs between the degree of sexual transmission and effects on host fecundity and mortality, nonsexual transmission is favored above the social-sexual crossover point (the host density at which the number of nonsexual contacts exceeds the number of sexual contacts), while sexual transmission is favored below this point. When changes in allocation to the two transmission modes are accompanied by changes in mortality or fecundity, both mixed and pure transmission strategies can be favored. If invading genotypes differ substantially from resident genotypes, genetic polymorphism in transmission mode is possible. The evolutionary outcomes are predictable from a knowledge of the equilibrium population sizes in relation to the social-sexual crossover point. Our results also show that predictions about dynamic outcomes, based on rates of invasion for single pathogens into healthy populations, do not adequately describe the resulting disease prevalence nor predict the subsequent evolutionary dynamics; once invasion of a pathogen has occurred, the conditions for spread of a second pathogen are themselves altered. If the host is considered as a single resource, our results show that two pathogens may coexist on a single resource if they use that resource differentially and have differential feedbacks on resource abundance; such resource feedback effects may be present in other biological systems.     

Nitrate enrichment alters a Daphnia–microparasite interaction through multiple pathways

Nutrient pollution has the potential to alter many ecological interactions, including host–parasite relationships. One of the largest sources of nutrient pollution comes from anthropogenic alteration of the nitrogen (N) cycle, specifically the increased rate of nitrate (NO₃-N) deposition to aquatic environments, potentially altering host–parasite relationships. This study aimed to assess the mechanisms through which nitrate may impact host–pathogen relationships using a fungal pathogen (Metschnikowia bicuspidata) parasitic to crustacean zooplankton (Daphnia dentifera) as a tractable model system. First, the influence of nitrate on host population dynamics was assessed along a gradient of nitrate concentrations. Nitrate decreased host population size and increased infection prevalence. Second, the influence of nitrate on host reproduction, mortality, and infection intensity was assessed at the individual host level by examining the relationship between pathogen dose and infection prevalence at ambient (0.4 mg NO₃-N*L⁻¹) and intermediate (12 mg NO₃-N*L⁻¹) levels of nitrate. Host fecundity and infection intensity both decreased with increasing pathogen dose, but increased nitrate levels corresponded to greater infection intensities. Nitrate had no effect on host growth rate, suggesting that hosts do not alter feeding behavior in nitrate-treated media compared with ambient conditions. This study suggests that nutrient enrichment may enhance disease through increased transmission and infection intensity, but that high levels of nitrate may result in smaller epidemics through reduced transmission caused by smaller population sizes and increased pathogen mortality.     

The trophic vacuum and the evolution of complex life cycles in trophically transmitted helminths

Parasitic worms (helminths) frequently have complex life cycles in which they are transmitted trophically between two or more successive hosts. Sexual reproduction often takes place in high trophic-level (TL) vertebrates, where parasites can grow to large sizes with high fecundity. Direct infection of high TL hosts, while advantageous, may be unachievable for parasites constrained to transmit trophically, because helminth propagules are unlikely to be ingested by large predators. Lack of niche overlap between propagule and definitive host (the trophic transmission vacuum) may explain the origin and/or maintenance of intermediate hosts, which overcome this transmission barrier. We show that nematodes infecting high TL definitive hosts tend to have more successive hosts in their life cycles. This relationship was modest, though, driven mainly by the minimum TL of hosts, suggesting that the shortest trophic chains leading to a host define the boundaries of the transmission vacuum. We also show that alternative modes of transmission, like host penetration, allow nematodes to reach high TLs without intermediate hosts. We suggest that widespread omnivory as well as parasite adaptations to increase transmission probably reduce, but do not eliminate, the barriers to the transmission of helminths through the food web.     

昆虫病原微生物对其寄主行为的调控作用研究进展

昆虫病原微生物是调控昆虫种群数量动态的重要因子,其作为生物防治害虫的重要手段被广泛应用。昆虫病原物往往通过调控其寄主行为来提高自身的适应性,而有些寄主行为的改变却是其应对病原物侵染的免疫反应。发烧行为被证明可抑制病原增殖并延长寄主死亡;取食行为变化影响病原物或寄主的适应性;繁殖行为主要表现在产卵力、交配行为和性信息素等方面的变化;社会性行为改变对整个社会群体的适应性或病原物传播有影响;病原物所引起的寄主防卫和群集能力下降被认为对病原传播不利;病虫趋光和趋地行为、顶峰行为和活体寄主传病行为等被认为是病原物操纵的有利于病原微生物扩散和传播的行为。明确昆虫病原物调控其寄主行为的策略和机制对于寻找到新的害虫防治方法有指导意义。     

RESISTANCE IS FUTILE BUT TOLERANCE CAN EXPLAIN WHY PARASITES DO NOT ALWAYS CASTRATE THEIR HOSTS

The disease caused by parasites and pathogens often causes sublethal effects that reduce host fecundity. Theory suggests that if parasites can "target" the detrimental effects of their growth on either host mortality or fecundity, they should always fully sterilize. This is because a reduction in host fecundity does not reduce the infectious period and is therefore neutral to a horizontally transmitted infectious organism. However, in nature fully castrating parasites are relatively rare, no doubt in part because of defense mechanisms in the host. Here, we examine in detail the evolution of host defense to the sterilizing effects of parasites and show that intermediate levels of sterility tolerance are found to evolve for a wide range of cost structures. Our key result arises when the host and parasite coevolve. Investment in tolerance by the host may prevent castration, but if host defense is through resistance (by controlling the parasite's growth rate) coevolution by the parasite results in the complete loss of infected host fecundity. Resistance is therefore a waste of resources, but tolerance can explain why parasites do not castrate their hosts. Our results further emphasize the importance of tolerance as opposed to resistance to parasites.     

Reproductive consequences of transient pathogen exposure across host genotypes and generations

To maximize fitness upon pathogenic infection, host organisms might reallocate energy and resources among life‐history traits, such as reproduction and defense. The fitness costs of infection can result from both immune upregulation and direct pathogen exploitation. The extent to which these costs, separately and together, vary by host genotype and across generations is unknown. We attempted to disentangle these costs by transiently exposing wild isolates and a lab‐domesticated strain of Caenorhabditis elegans nematodes to the pathogen Staphylococcus aureus, using exposure to heat‐killed pathogens to distinguish costs due to immune upregulation and pathogen exploitation. We found that host nematodes exhibit a short‐term delay in offspring production when exposed to live and heat‐killed pathogen, but their lifetime fecundity (total offspring produced) recovered to control levels. We also found genetic variation between host isolates for both cumulative offspring production and magnitude of fitness costs. We further investigated whether there were maternal pathogen exposure costs (or benefits) to offspring and revealed a positive correlation between the magnitude of the pathogen‐induced delay in the parent''s first day of reproduction and the cost to offspring population growth. Our findings highlight the capacity for hosts to recover fecundity after transient exposure to a pathogen.     

Imperfect vaccines and the evolution of pathogens causing acute infections in vertebrates

A study by Gandon et al. (2001) considered the potential ways pathogens may evolve in response to vaccination with imperfect vaccines. In this paper, by focusing on acute infections of vertebrate hosts, we examine whether imperfect vaccines that do not completely block a pathogen's replication (antigrowth) or transmission (antitransmission) may lead to evolution of more or less virulent pathogen strains. To address this question, we use models of the within-host dynamics of the pathogen and the host's immune responses. One advantage of the use of this within-host approach is that vaccination can be easily incorporated in the models and the trade-offs between pathogen transmissibility, host recovery, and virulence that drive evolution of pathogens in these models can be easily estimated. We find that the use of either antigrowth or antitransmission vaccines leads to the evolution of pathogens with an increased within-host growth rate; infection of unvaccinated hosts with such evolved pathogens results in high host mortality and low pathogen transmission. Vaccination of only a fraction of hosts with antigrowth vaccines may prevent pathogens from evolving high virulence due to pathogen adaptation to unvaccinated hosts and thus protection of vaccinated hosts from pathogen-induced disease. In contrast, antitransmission vaccines may be beneficial only if they are effective enough to cause pathogen extinction. Our results suggest that particular mechanisms of action of vaccines and their efficacy are crucial in predicting longterm evolutionary consequences of the use of imperfect vaccines.     

Fungal pathogens as selective forces in plant populations and communities*

Pathogens are potent selective forces whose importance in shaping the size and structure of individual plant populations and whole communities has been underestimated. Even in situations where host and pathogen have been associated over long periods of time, pathogens regularly affect host fitness by reducing fecundity and increasing mortality either directly or indirectly through reductions in competitive ability. The genetic consequences of such disease-induced reductions in fitness are profound. On a broad geographic scale, race-specific resistance generally occurs more frequently in regions characterized by environments favourable for disease development. Within such areas, however, the distribution of resistant plant genotypes is often very patchy. This probably reflects the importance of extinction and colonization events in the continuing co-evolutionary dynamics of host-pathogen associations. At a demographic level, pathogen-induced reductions in host fitness may lead to changes in the size of populations. In turn, this may lead to changes in the relative diversity of whole communities. Documentation of this scale of interaction is poor, but the devastating consequences of the introduction of pathogens into alien environments provides a salutary reminder of their power to change plant communities radically.     

Consistency of host responses to parasitic infection in the three‐spined stickleback fish infected by the diphyllobothriidean cestode Schistocephalus solidus

Among populations of the three‐spined stickleback fish in Alaska, females appear to show two forms of sterility tolerance to infection by the diphyllobothriidean cestode Schistocephalus solidus. In contrast to sticklebacks in other regions of the northern hemisphere, female fish are capable of producing clutches of eggs despite supporting large parasite burdens. Nonetheless, nutrient loss to the parasite, coupled with the energetic demands of host reproduction, eventually curtails spawning among infected females. Host females in Walby Lake experience ‘fecundity reduction’ resulting from nutrient theft as a side effect of infection. In Scout Lake, infected females show ‘fecundity compensation’, an adaptive, inducible response allowing them to increase current fecundity to compensate for reduction or loss of future reproduction. This multi‐year study of sticklebacks from each lake addresses two empirical questions for a better understanding of the dynamic interplay between host and parasite. First, is there is any annual variation within the two responses to parasitism in each host population; and, if so, is it related to parasite burden? Second, do the two host responses show consistent differences between the populations of sticklebacks despite any yearly variation in them? We found annual, intra‐population variation within the response shown by each population of stickleback which appears to have been influenced by the parasite : host mass ratio and possibly by unknown environmental conditions affecting the reproductive physiology of stickleback females. Moreover, the data support the hypothesis that ovum mass is more sensitive to parasitism (parasite burden) than clutch size in females from Walby Lake which exhibit fecundity reduction. Notwithstanding the intra‐population variation within each host response, the responses to infection occurred consistently within each respective stickleback population and appear to reflect stable, fundamental characteristics of the populations. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 113 , 958–968.     

Pathogen fitness components and genotypes differ in their sensitivity to nutrient and temperature variation in a wild plant-pathogen association

Understanding processes maintaining variation in pathogen life-history stages affecting infectivity and reproduction is a key challenge in evolutionary ecology. Models of host-parasite coevolution are based on the assumption that genetic variation for host-parasite interactions is a significant cause of variation in infection, and that variation in environmental conditions does not overwhelm the genetic basis. However, surprisingly little is known about the stability of genotype-genotype interactions under variable environmental conditions. Here, using a naturally occurring plant-pathogen interaction, I tested whether the two distinct aspects of the infection process - infectivity and transmission potential - vary over realistic nutrient and temperature gradients. I show that the initial pathogen infectivity and host resistance responses are robust over the environmental gradients. However, for compatible responses there were striking differences in how different pathogen life-history stages and host and pathogen genotypes responded to environmental variation. For some pathogen genotypes even slight changes in temperature arrested spore production, rendering the developing infection ineffectual. The response of pathogen genotypes to environmental gradients varied in magnitude and even direction, so that their rankings changed across the abiotic gradients. Hence, the variable environment of spatially structured host-parasite interactions may strongly influence the maintenance of polymorphism in pathogen life-history stages governing transmission, whereas evolutionary trajectories of infectivity may be unaffected by the surrounding environment.     

Host sexual dimorphism affects the outcome of within‐host pathogen competition

Natural infections often consist of multiple pathogens of the same or different species. When coinfections occur, pathogens compete for access to host resources and fitness is determined by how well a pathogen can reproduce compared to its competitors. Yet not all hosts provide the same resource pool. Males and females, in particular, commonly vary in both their acquisition of resources and investment in immunity, but their ability to modify any competition between different pathogens remains unknown. Using the Daphnia magna–Pasteuria ramosa model system, we exposed male and female hosts to either a single genotype infection or coinfections consisting of two pathogen genotypes of varying levels of virulence. We found that coinfections within females favored the transmission of the more virulent pathogen genotype, whereas coinfections within male hosts resulted in equal transmission of competing pathogen genotypes. This contrast became less pronounced when the least virulent pathogen was able to establish an infection first, suggesting that the influence of host sex is shaped by priority effects. We suggest that sex is a form of host heterogeneity that may influence the evolution of virulence within coinfection contexts and that one sex may be a reservoir for pathogen genetic diversity in nature.     

Mutualistic Wolbachia infection in Aedes albopictus: accelerating cytoplasmic drive

Maternally inherited rickettsial symbionts of the genus Wolbachia occur commonly in arthropods, often behaving as reproductive parasites by manipulating host reproduction to enhance the vertical transmission of infections. One manipulation is cytoplasmic incompatibility (CI), which causes a significant reduction in brood hatch and promotes the spread of the maternally inherited Wolbachia infection into the host population (i.e., cytoplasmic drive). Here, we have examined a Wolbachia superinfection in the mosquito Aedes albopictus and found the infection to be associated with both cytoplasmic incompatibility and increased host fecundity. Relative to uninfected females, infected females live longer, produce more eggs, and have higher hatching rates in compatible crosses. A model describing Wolbachia infection dynamics predicts that increased fecundity will accelerate cytoplasmic drive rates. To test this hypothesis, we used population cages to examine the rate at which Wolbachia invades an uninfected Ae. albopictus population. The observed cytoplasmic drive rates were consistent with model predictions for a CI-inducing Wolbachia infection that increases host fecundity. We discuss the relevance of these results to both the evolution of Wolbachia symbioses and proposed applied strategies for the use of Wolbachia infections to drive desired transgenes through natural populations (i.e., population replacement strategies).     

Understanding the dynamics of Salmonella infections in dairy herds: a modelling approach

There is evidence of variation in the infection dynamics of different Salmonella serotypes in cattle--ranging from transient epidemics to long term persistence and recurrence. We seek to identify possible causes of these differences. In this study we present mathematical models which describe both managed population dynamics and epidemiology and use these to investigate the effects of demographic and epidemiological factors on epidemic behaviour and threshold for invasion. In particular, when the system is perturbed by higher culling or pathogen-induced mortality we incorporate mechanisms to constrain the lactating herd size to remain constant in the absence of pathogen or to lie within a fairly small interval in the presence of pathogen. A combination of numerical and analytical techniques is used to analyse the models. We find that the epidemiologically dominating management group can change from the dry/lactating cycle to the weaned group with increasing culling rate. Pseudovertical transmission is found to have little effect on the invasion criteria, while indirect transmission has significant influence. Pathogen-induced mortality, recovery, immune response and pathogen removal are found to be factors inducing damped oscillations; variation in these factors between Salmonella serotypes may be responsible for some of the observed differences in within herd dynamics. Specifically, higher pathogen-induced mortality, shorter infectious period, more persistent immune response and more rapid removal of faeces result in a lower number of infectives and smaller epidemics but a greater tendency for damped oscillations.     

The evolution of covert,silent infection as a parasite strategy

Many parasites and pathogens cause silent/covert infections in addition to the more obvious infectious disease-causing pathology. Here, we consider how assumptions concerning superinfection, protection and seasonal host birth and transmission rates affect the evolution of such covert infections as a parasite strategy. Regardless of whether there is vertical infection or effects on sterility, overt infection is always disadvantageous in relatively constant host populations unless it provides protection from superinfection. If covert infections are protective, all individuals will enter the covert stage if there is enough vertical transmission, and revert to overt infections after a ‘latent’ period (susceptible, exposed, infected epidemiology). Seasonal variation in transmission rates selects for non-protective covert infections in relatively long-lived hosts with low birth rates typical of many mammals. Variable host population density caused by seasonal birth rates may also select for covert transmission, but in this case it is most likely in short-lived fecund hosts. The covert infections of some insects may therefore be explained by their outbreak population dynamics. However, our models consistently predict proportions of covert infection, which are lower than some of those observed in nature. Higher proportions of covert infection may occur if there is a direct link between covert infection and overt transmission success, the covert infection is protective or the covert state is the result of suppression by the host. Relatively low proportions of covert transmission may, however, be explained as a parasite strategy when transmission opportunities vary.