Covariation between the physiological and behavioral components of pathogen transmission: host heterogeneity determines epidemic outcomes

Although heterogeneity in contact rate, physiology, and behavioral response to infection have all been empirically demonstrated in host–pathogen systems, little is known about how interactions between individual variation in behavior and physiology scale‐up to affect pathogen transmission at a population level. The objective of this study is to evaluate how covariation between the behavioral and physiological components of transmission might affect epidemic outcomes in host populations. We tested the consequences of contact rate covarying with susceptibility, infectiousness, and infection status using an individual‐based, dynamic network model where individuals initiate and terminate contacts with conspecifics based on their behavioral predispositions and their infection status. Our results suggest that both heterogeneity in physiology and subsequent covariation of physiology with contact rate could powerfully influence epidemic dynamics. Overall, we found that 1) individual variability in susceptibility and infectiousness can reduce the expected maximum prevalence and increase epidemic variability; 2) when contact rate and susceptibility or infectiousness negatively covary, it takes substantially longer for epidemics to spread throughout the population, and rates of epidemic spread remained suppressed even for highly transmissible pathogens; and 3) reductions in contact rate resulting from infection‐induced behavioral changes can prevent the pathogen from reaching most of the population. These effects were strongest for theoretical pathogens with lower transmissibility and for populations where the observed variation in contact rate was higher, suggesting that such heterogeneity may be most important for less infectious, more chronic diseases in wildlife. Understanding when and how variability in pathogen transmission should be modelled is a crucial next step for disease ecology.     

Interactions between host sex and age of exposure modify the virulence–transmission trade‐off

The patterns of immunity conferred by host sex or age represent two sources of host heterogeneity that can potentially shape the evolutionary trajectory of disease. With each host sex or age encountered, a pathogen's optimal exploitative strategy may change, leading to considerable variation in expression of pathogen transmission and virulence. To date, these host characteristics have been studied in the context of host fitness alone, overlooking the effects of host sex and age on the fundamental virulence–transmission trade‐off faced by pathogens. Here, we explicitly address the interaction of these characteristics and find that host sex and age at exposure to a pathogen affect age‐specific patterns of mortality and the balance between pathogen transmission and virulence. When infecting age‐structured male and female Daphnia magna with different genotypes of Pasteuria ramosa, we found that infection increased mortality rates across all age classes for females, whereas mortality only increased in the earliest age class for males. Female hosts allowed a variety of trade‐offs between transmission and virulence to arise with each age and pathogen genotype. In contrast, this variation was dampened in males, with pathogens exhibiting declines in both virulence and transmission with increasing host age. Our results suggest that differences in exploitation potential of males and females to a pathogen can interact with host age to allow different virulence strategies to coexist, and illustrate the potential for these widespread sources of host heterogeneity to direct the evolution of disease in natural populations.     

Host physiological phenotype explains pathogen reservoir potential

Control of emerging infectious diseases often hinges on identifying a pathogen reservoir, the source of disease transmission. The potential to function as a pathogen reservoir can be influenced by host lifespan, geographic provenance and phylogeny. Yet, no study has identified factors that causally determine the reservoir potential of diverse host species. We propose the host physiological phenotype hypothesis, which predicts that hosts with short‐lived, poorly defended, nutrient rich and high metabolism tissue have greater values for three epidemiological parameters that determine reservoir potential: host susceptibility to infection, competence to infect vectors and ability to support vector populations. We experimentally tested these predictions using a generalist vectored virus and six wild grass species. Host physiological phenotype explained why hosts differed in all three epidemiological parameters while host lifespan, provenance and phylogeny could not explain host competence. Thus, a single, general axis describing variation in host physiological phenotype may explain reservoir potential.     

Genotypic and phenotypic variation in transmission traits of a complex life cycle parasite

Characterizing genetic variation in parasite transmission traits and its contribution to parasite vigor is essential for understanding the evolution of parasite life‐history traits. We measured genetic variation in output, activity, survival, and infection success of clonal transmission stages (cercaria larvae) of a complex life cycle parasite (Diplostomum pseudospathaceum). We further tested if variation in host nutritional stage had an effect on these traits by keeping hosts on limited or ad libitum diet. The traits we measured were highly variable among parasite genotypes indicating significant genetic variation in these life‐history traits. Traits were also phenotypically variable, for example, there was significant variation in the measured traits over time within each genotype. However, host nutritional stage had no effect on the parasite traits suggesting that a short‐term reduction in host resources was not limiting the cercarial output or performance. Overall, these results suggest significant interclonal and phenotypic variation in parasite transmission traits that are not affected by host nutritional status.     

Host size influences the effects of four isolates of an amphibian chytrid fungus

Understanding factors that influence host–pathogen interactions is key to predicting outbreaks in natural systems experiencing environmental change. Many amphibian population declines have been attributed to an amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd). While this fungus is widespread, not all Bd‐positive populations have been associated with declines, which could be attributed to differences in pathogen virulence or host susceptibility. In a laboratory experiment, we examined the effects of Bd isolate origin, two from areas with Bd‐associated amphibian population declines (El Copé, Panama, and California, USA) and two from areas without Bd‐related population declines (Ohio and Maine, USA), on the terrestrial growth and survival of American toad (Anaxyrus americanus) metamorphs reared in larval environments with low or high intraspecific density. We predicted that (1) Bd isolates from areas experiencing declines would have greater negative effects than Bd isolates from areas without declines, and (2) across all isolates, growth and survival of smaller toads from high‐density larval conditions would be reduced by Bd exposure compared to larger toads from low‐density larval conditions. Our results showed that terrestrial survival was reduced for smaller toads exposed to Bd with variation in the response to different isolates, suggesting that smaller size increased susceptibility to Bd. Toads exposed to Bd gained less mass, which varied by isolate. Bd isolates from areas with population declines, however, did not have more negative effects than isolates from areas without recorded declines. Most strikingly, our study supports that host condition, measured by size, can be indicative of the negative effects of Bd exposure. Further, Bd isolates’ impact may vary in ways not predictable from place of origin or occurrence of disease‐related population declines. This research suggests that amphibian populations outside of areas experiencing Bd‐associated declines could be impacted by this pathogen and that the size of individuals could influence the magnitude of Bd's impact.     

Vector within‐host feeding preference mediates transmission of a heterogeneously distributed pathogen

1. Ecological theory predicts that vector preference for certain host species or discrimination between infected versus uninfected hosts impacts disease incidence. However, little information exists on the extent to which vector within‐host feeding preference mediates transmission. This may be particularly important for plant pathogens, such as sharpshooter transmission of the bacterium Xylella fastidiosa, which are distributed irregularly throughout hosts. 2. We documented the within‐host distribution of two vector species that differ in transmission efficiency, the leafhoppers Draeculacephala minerva and Graphocephala atropunctata, and which are free to move throughout entirely caged alfalfa plants. The more efficient vector D. minerva fed preferentially at the base of the plant near the soil surface, whereas the less efficient G. atropunctata preferred overwhelming the top of the plant. 3. Next we documented X. fastidiosa heterogeneity in mechanically inoculated plants. Infection rates were up to 50% higher and mean bacterial population densities were 100‐fold higher near the plant base than at the top or in the taproot. 4. Finally, we estimated transmission efficiency of the two leafhoppers when they were confined at either the base or top of inoculated alfalfa plants. Both vectors were inefficient when confined at the top of infected plants and were 20–60% more efficient when confined at the plant base. 5. These results show that vector transmission efficiency is determined by the interaction between leafhopper within‐plant feeding behaviour and pathogen within‐plant distribution. Fine‐scale vector and pathogen overlap is likely to be a requirement generally for efficient transmission of vector‐borne pathogens.     

GENETIC VARIATION IN RESISTANCE AND FECUNDITY TOLERANCE IN A NATURAL HOST–PATHOGEN INTERACTION

Individuals vary in their ability to defend against pathogens. Determining how natural selection maintains this variation is often difficult, in part because there are multiple ways that organisms defend themselves against pathogens. One important distinction is between mechanisms of resistance that fight off infection, and mechanisms of tolerance that limit the impact of infection on host fitness without influencing pathogen growth. Theory predicts variation among genotypes in resistance, but not necessarily in tolerance. Here, we study variation among pea aphid (Acyrthosiphon pisum) genotypes in defense against the fungal pathogen Pandora neoaphidis. It has been well established that pea aphids can harbor symbiotic bacteria that protect them from fungal pathogens. However, it is unclear whether aphid genotypes vary in defense against Pandora in the absence of protective symbionts. We therefore measured resistance and tolerance to fungal infection in aphid lines collected without symbionts, and found variation among lines in survival and in the percent of individuals that formed a sporulating cadaver. We also found evidence of variation in tolerance to the effects of pathogen infection on host fecundity, but no variation in tolerance of pathogen‐induced mortality. We discuss these findings in light of theoretical predictions about host‐pathogen coevolution.     

Relative importance of chemical attractiveness to parasites for susceptibility to trematode infection

While the host immune system is often considered the most important physiological mechanism against parasites, precontact mechanisms determining exposure to parasites may also affect infection dynamics. For instance, chemical cues released by hosts can attract parasite transmission stages. We used the freshwater snail Lymnaea stagnalis and its trematode parasite Echinoparyphium aconiatum to examine the role of host chemical attractiveness, physiological condition, and immune function in determining its susceptibility to infection. We assessed host attractiveness through parasite chemo‐orientation behavior; physiological condition through host body size, food consumption, and respiration rate; and immune function through two immune parameters (phenoloxidase‐like and antibacterial activity of hemolymph) at an individual level. We found that, although snails showed high variation in chemical attractiveness to E. aconiatum cercariae, this did not determine their overall susceptibility to infection. This was because large body size increased attractiveness, but also increased metabolic activity that reduced overall susceptibility. High metabolic rate indicates fast physiological processes, including immune activity. The examined immune traits, however, showed no association with susceptibility to infection. Our results indicate that postcontact mechanisms were more likely to determine snail susceptibility to infection than variation in attractiveness to parasites. These may include localized immune responses in the target tissue of the parasite. The lack of a relationship between food consumption and attractiveness to parasites contradicts earlier findings that show food deprivation reducing snail attractiveness. This suggests that, although variation in resource level over space and time can alter infection dynamics, variation in chemical attractiveness may not contribute to parasite‐induced fitness variation within populations when individuals experience similar environmental conditions.     

Host–parasite coevolution: genetic variation in a virus population and the interaction with a host gene

Host–parasite coevolution is considered to be an important factor in maintaining genetic variation in resistance to pathogens. Drosophila melanogaster is naturally infected by the sigma virus, a vertically transmitted and host‐specific pathogen. In fly populations, there is a large amount of genetic variation in the transmission rate from parent to offspring, much of which is caused by major‐effect resistance polymorphisms. We have found that there are similarly high levels of genetic variation in the rate of paternal transmission among 95 different isolates of the virus as in the host. However, when we examined a transmission‐blocking gene in the host, we found that it was effective across virus isolates. Therefore, the high levels of genetic variation observed in this system do not appear to be maintained because of coevolution resulting from interactions between this host gene and parasite genes.     

The influence of host demography, pathogen virulence, and relationships with pathogen virulence on the evolution of pathogen transmission in a spatial context

A major challenge in evolutionary ecology is to explain extensive natural variation in transmission rates and virulence across pathogens. Host and pathogen ecology is a potentially important source of that variation. Theory of its effects has been developed through the study of non-spatial models, but host population spatial structure has been shown to influence evolutionary outcomes. To date, the effects of basic host and pathogen demography on pathogen evolution have not been thoroughly explored in a spatial context. Here we use simulations to show that space produces novel predictions of the influence of the shape of the pathogen’s transmission–virulence tradeoff, as well as host reproduction and mortality, on the pathogen’s evolutionary stable transmission rate. Importantly, non-spatial models predict that neither the slope of linear transmission–virulence relationships, nor the host reproduction rate will influence pathogen evolution, and that host mortality will only influence it when there is a transmission–virulence tradeoff. We show that this is not the case in a spatial context, and identify the ecological conditions under which spatial effects are most influential. Thus, these results may help explain observed natural variation among pathogens unexplainable by non-spatial models, and provide guidance about when space should be considered. We additionally evaluate the ability of existing analytical approaches to predict the influence of ecology, namely spatial moment equations closed with an improved pair approximation (IPA). The IPA is known to have limited accuracy, but here we show that in the context of pathogens the limitations are substantial: in many cases, IPA incorrectly predicts evolution to pathogen-driven extinction. Despite these limitations, we suggest that the impact of ecology can still be understood within the conceptual framework arising from spatial moment equations, that of “self-shading’’, whereby the spread of highly transmissible pathogens is impeded by local depletion of susceptible hosts.     

Symbiont‐mediated phenotypic variation without co‐evolution in an insect–fungus association

Recent studies have shown that symbionts can be a source of adaptive phenotypic variation for their hosts. It is assumed that co‐evolution between hosts and symbionts underlies these ecologically significant phenotypic traits. We tested this assumption in the ectosymbiotic fungal associate of the gall midge Asteromyia carbonifera. Phylogenetic analysis placed the fungal symbiont within a monophyletic clade formed by Botryosphaeria dothidea, a typically free‐living (i.e. not associated with an insect host) plant pathogen. Symbiont isolates from four divergent midge lineages demonstrated none of the patterns common to heritable microbial symbioses, including parallel diversification with their hosts, substitution rate acceleration, or A+T nucleotide bias. Amplified fragment length polymorphism genotyping of the symbiont revealed that within‐lineage genetic diversity was not clustered along host population lines. Culture‐based experiments demonstrated that the symbiont‐mediated variation in gall phenotype is not borne out in the absence of the midge. This study shows that symbionts can be important players in phenotypic variation for their hosts, even in the absence of a co‐evolutionary association.     

AN EXPERIMENTAL TEST OF THE TRANSMISSION‐VIRULENCE TRADE‐OFF HYPOTHESIS IN A PLANT VIRUS

The transmission–virulence trade‐off hypothesis is one of the few adaptive explanations of virulence evolution, and assumes that there is an overall positive correlation between parasite transmission and virulence. The shape of the transmission–virulence relationship predicts whether virulence should evolve toward either a maximum or to an intermediate optimum. A positive correlation between each of these traits and within‐host growth is often suggested to underlie the relationship between virulence and transmission. There are few experimental tests of this hypothesis; this study reports on the first empirical test on a plant pathogen. We infected Brassica rapa plants with nine natural isolates of Cauliflower mosaic virus and then estimated three traits: transmission, virulence, and within‐host viral accumulation. As predicted by the trade‐off hypothesis, we observed a positive correlation between transmission and virulence, suggestive of the existence of an intermediate optimum. We discovered the unexpected existence of two groups of within‐host accumulation, differing by at least an order of magnitude. When accumulation groups were not accounted for, within‐host accumulation was correlated neither to virulence nor transmission, although our results suggest that within each group these correlations exist.     

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.     

Temperature checks the Red Queen? Resistance and virulence in a fluctuating environment

Numerous studies have revealed genetic variation in resistance and susceptibility in host–parasite interactions and therefore the potential for frequency‐dependent selection (Red Queen dynamics). Few studies, if any, have considered the abiotic environment as a mediating factor in these interactions. Using the pea aphid, Acyrthosiphon pisum, and its fungal pathogen, Erynia neoaphidis, as a model host–parasite system, we demonstrate how temperature can mediate the expression of genotypic variation for susceptibility and virulence. Whilst previous studies have revealed among‐clone variation in aphid resistance to this pathogen, we show that resistance rankings derived from assessments at one temperature, are not conserved across differing temperature regimes. We suggest that variation in environmental temperature, through its nonlinear impact on parasite virulence and host defence, may contribute to the general lack of evidence for frequency‐dependent selection in field systems.     

Linking predator–prey interactions with exposure to a trophically transmitted parasite using PCR‐based analyses

Parasite transmission is determined by the rate of contact between a susceptible host and an infective stage and susceptibility to infection given an exposure event. Attempts to measure levels of variation in exposure in natural populations can be especially challenging. The level of exposure to a major class of parasites, trophically transmitted parasites, can be estimated by investigating the host's feeding behaviour. Since the parasites rely on the ingestion of infective intermediate hosts for transmission, the potential for exposure to infection is inherently linked to the definitive host's feeding ecology. Here, we combined epidemiological data and molecular analyses (polymerase chain reaction) of the diet of the definitive host, the white‐footed mouse (Peromyscus leucopus), to investigate temporal and individual heterogeneities in exposure to infection. Our results show that the consumption of cricket intermediate hosts accounted for much of the variation in infection; mice that had consumed crickets were four times more likely to become infected than animals that tested negative for cricket DNA. In particular, pregnant female hosts were three times more likely to consume crickets, which corresponded to a threefold increase in infection compared with nonpregnant females. Interestingly, males in breeding condition had a higher rate of infection even though breeding males were just as likely to test positive for cricket consumption as nonbreeding males. These results suggest that while heterogeneity in host diet served as a strong predictor of exposure risk, differential susceptibility to infection may also play a key role, particularly among male hosts. By combining PCR analyses with epidemiological data, we revealed temporal variation in exposure through prey consumption and identified potentially important individual heterogeneities in parasite transmission.     

ROLE OF EVOLVED HOST BREADTH IN THE INITIAL EMERGENCE OF AN RNA VIRUS

Understanding how evolution promotes pathogen emergence would aid disease management, and prediction of future host shifts. Increased pathogen infectiousness of different hosts may occur through direct selection, or fortuitously via indirect selection. However, it is unclear which type of selection tends to produce host breadth promoting pathogen emergence. We predicted that direct selection for host breadth should foster emergence by causing higher population growth on new hosts, lower among‐population variance in growth on new hosts, and lower population variance in growth across new hosts. We tested the predictions using experimentally evolved vesicular stomatitis virus populations, containing groups of host‐use specialists, directly selected generalists, and indirectly selected generalists. In novel‐host challenges, viruses directly selected for generalism showed relatively higher or equivalent host growth, lower among‐population variance in host growth, and lower population variance in growth across hosts. Thus, two of three outcomes supported our prediction that directly selected host breadth should favor host colonization. Also, we observed that indirectly selected generalists were advantaged over specialist viruses, indicating that fortuitous changes in host breadth may also promote emergence. We discuss evolution of phenotypic plasticity versus environmental robustness in viruses, virus avoidance of extinction, and surveillance of pathogen niche breadth to predict future likelihood of emergence.     

Age-dependent rates of infection of cassava green mites by a fungal pathogen in Brazil

Age-specific effects of invertebrate pathogens on their hosts can greatly influence the population dynamics in such interactions. Explanations for such differences are usually sought within differing intrinsic susceptibilities of the host life stages but we present data which indicate that host size, behaviour and life history may be the overriding factors determining age-specific effects of a fungal pathogen, Neozygites floridana (Entomophthorales: Neozygitaceae) on spider mites (Mononychellus tanajoa Bondar, Acari: Tetranychidae). Epizootics of N. floridana in spider mites are characterised by much greater relative mortality of adult females compared with other life stages (ca. 99%), despite similar physiological susceptibilities. We present empirical data that demonstrate encounter rates of mites with N. floridana increasing with life stage during an epizootic on cassava in northeastern Brazil. Estimates of the size, walking speeds and patterns, and life history of different life stages (and adult sexes) were used to calculate expected relative encounter rates which were found not to be different from the observed values (although not testable for larvae). This helps explain the different apparent susceptibility of host life stages in the field. Given the low ecological susceptibility of younger life stages to this pathogen, we predict that the interaction time between host and pathogen, determined by climatic conditions, will be critical in determining the degree of host population control in an epizootic. We further hypothesise that such variation in ecological susceptibility to pathogens can generate selection pressures on basic host traits, contributing to the sessile nature of many microarthropods. This revised version was published online in July 2006 with corrections to the Cover Date.     

Expanding host specificity and pathogen sharing beyond viruses

Most emerging pathogens of humans can infect multiple host species (Woolhouse & Gowtage‐Sequeria, 2005). This simple fact has motivated multiple large‐scale, comparative analyses of the drivers of pathogen sharing and zoonotic pathogen richness among hosts as well as the factors determining the zoonotic potential of pathogens themselves. However, most of this work focuses on viruses, limiting a broader understanding of how host range varies within and between pathogen groups. In this issue of Molecular Ecology, Shaw et al. (2020) compile a comprehensive data set of host–pathogen associations across viruses and bacteria and test whether previous patterns observed in the former occur in the latter. They find most viruses and bacteria are specialists, and viruses are more likely to be generalists; however, generalist bacteria encompass multiple host orders, whereas viral sharing occurs more within host orders. Lastly, the authors demonstrate that many factors previously identified as predictors of zoonotic richness for viruses occur for bacteria and that host phylogenetic similarity is a primary determinant of cross‐species transmission. However, pathogen sharing with humans was more common and more weakly related to phylogenetic distance to Homo sapiens for bacteria compared to viruses, suggesting the former could pose greater spillover risks across host orders. This work represents a key advance in our understanding of host specificity and pathogen sharing beyond viruses.