Vector preference and host defense against infection interact to determine disease dynamics

Vector preference based on host infection status has long been recognized for its importance in disease dynamics. Prior theoretical work has assumed that all hosts are uniformly susceptible to the pathogen. Here we investigated disease dynamics when this assumption is relaxed using a series of vector–host epidemiological compartment models with variable levels of host resistance or tolerance to infection – collectively termed defense. In our models, vectors cannot acquire the infection from resistant hosts but can acquire from tolerant hosts. Specifically, we investigated the interacting effects of vector preference and host defense in a series of single‐ and two‐patch models. Results indicate that resistant host types generally reduce disease prevalence and pathogen spillover, independent of vector preference. The epidemiological consequences of host tolerance, however, depended on vector preference. When vectors preferred diseased hosts, tolerance reduced incidence compared to susceptible hosts; when vectors avoided diseased hosts, tolerance enhanced disease prevalence. Finally, a variation of the model that included preference‐based vector patch leaving rates suggests that both resistance and tolerance can promote pathogen spillover if vectors prefer diseased hosts, because of increased vector dispersal into susceptible patches. Collectively, we found complex, context‐dependent effects of vector preference and host defense on disease dynamics. In the context of management programs for vector‐borne diseases, managers should consider both the precise form of host defense present in a population, breed, or cultivar, as well as vector feeding behavior.     

Disease hotspots or hot species? Infection dynamics in multi‐host metacommunities controlled by species identity,not source location

Pathogen persistence in host communities is influenced by processes operating at the individual host to landscape‐level scale, but isolating the relative contributions of these processes is challenging. We developed theory to partition the influence of host species, habitat patches and landscape connectivity on pathogen persistence within metacommunities of hosts and pathogens. We used this framework to quantify the contributions of host species composition and habitat patch identity on the persistence of an amphibian pathogen across the landscape. By sampling over 11 000 hosts of six amphibian species, we found that a single host species could maintain the pathogen in 91% of observed metacommunities. Moreover, this dominant maintenance species contributed, on average, twice as much to landscape‐level pathogen persistence compared to the most influential source patch in a metacommunity. Our analysis demonstrates substantial inequality in how species and patches contribute to pathogen persistence, with important implications for targeted disease management.     

Spatiotemporal Model of Barley and Cereal Yellow Dwarf Virus Transmission Dynamics with Seasonality and Plant Competition

Many generalist pathogens are influenced by the spatial distributions and relative abundances of susceptible host species. The spatial structure of host populations can influence patterns of infection incidence (or disease outbreaks), and the effects of a generalist pathogen on host community dynamics in a spatially heterogeneous community may differ from predictions derived via simple models. In this paper, we model the transmission of a generalist pathogen within a patch framework that incorporates the movement of vectors between discrete host patches to investigate the effects of local host community composition and vector movement rates on disease dynamics.     

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.     

Movement can mediate temporal mismatches between resource availability and biological events in host–pathogen interactions

Global change is shifting the timing of biological events, leading to temporal mismatches between biological events and resource availability. These temporal mismatches can threaten species’ populations. Importantly, temporal mismatches not only exert strong pressures on the population dynamics of the focal species, but can also lead to substantial changes in pairwise species interactions such as host–pathogen systems. We adapted an established individual‐based model of host–pathogen dynamics. The model describes a viral agent in a social host, while accounting for the host''s explicit movement decisions. We aimed to investigate how temporal mismatches between seasonal resource availability and host life‐history events affect host–pathogen coexistence, that is, disease persistence. Seasonal resource fluctuations only increased coexistence probability when in synchrony with the hosts’ biological events. However, a temporal mismatch reduced host–pathogen coexistence, but only marginally. In tandem with an increasing temporal mismatch, our model showed a shift in the spatial distribution of infected hosts. It shifted from an even distribution under synchronous conditions toward the formation of disease hotspots, when host life history and resource availability mismatched completely. The spatial restriction of infected hosts to small hotspots in the landscape initially suggested a lower coexistence probability due to the critical loss of susceptible host individuals within those hotspots. However, the surrounding landscape facilitated demographic rescue through habitat‐dependent movement. Our work demonstrates that the negative effects of temporal mismatches between host resource availability and host life history on host–pathogen coexistence can be reduced through the formation of temporary disease hotspots and host movement decisions, with implications for disease management under disturbances and global change.     

病原体感染对物种间资源竞争的影响——基于资源竞争理论

病原体感染对种间竞争的影响可能是因为改变了宿主的资源利用过程,然而竞争模型（Lotka-Volterra）由于参数化竞争系数而忽略了资源的动态变化过程,因此基于此类模型的研究无法揭示病原体对宿主资源利用的影响。基于Tilman的资源竞争理论构建了病原体感染一个物种的资源竞争模型,通过分析宿主物种资源利用效率的变化探讨了病原体对种间竞争的影响。结果表明：（1）病原体降低了宿主对资源的消耗率（消费矢量变短）,抬高了对资源的最低需求（零等倾线上移）,这意味着宿主的竞争力减弱;（2）虽然感染影响了竞争物种的密度,但不会改变共存物种的共存状态;（3）病原体可以使宿主物种的竞争对手更容易入侵,形成共存局面,极大地扩大了竞争物种共存的参数范围,本质上促进了物种多样性维持;（4）病原体的传播率和毒性也复杂地影响了竞争物种共存,传播率越大越能促进物种共存,而中等强度毒性最能促进物种共存。研究结果明确了病原体对物种资源利用模式的潜在改变,强调了病原体在物种共存和生物多样性维持中的重要性。     

Evaluating the importance of within- and between-host selection pressures on the evolution of chronic pathogens

Infectious pathogens compete and are subject to natural selection at multiple levels. For example, viral strains compete for access to host resources within an infected host and, at the same time, compete for access to susceptible hosts within the host population. Here we propose a novel approach to study the interplay between within- and between-host competition. This approach allows for a single host to be infected by and transmit two strains of the same pathogen. We do this by nesting a model for the host–pathogen dynamics within each infected host into an epidemiological model. The nesting of models allows the between-host infectivity and mortality rates suffered by infected hosts to be functions of the disease progression at the within-host level. We present a general method for computing the basic reproduction ratio of a pathogen in such a model. We then illustrate our method using a basic model for the within-host dynamics of viral infections, embedded within the simplest susceptible–infected (SI) epidemiological model. Within this nested framework, we show that the virion production rate at the level of the cell–virus interaction leads, via within-host competition, to the presence or absence of between-host level competitive exclusion. In particular, we find that in the absence of mutation the strain that maximizes between-host fitness can outcompete all other strains. In the presence of mutation we observe a complex invasion landscape showing the possibility of coexistence. Although we emphasize the application to human viral diseases, we expect this methodology to be applicable to be many host–parasite systems.     

Population dynamics and sex ratio of a parasitoid altered by fungal-infected diet of host butterfly

Variation of host quality affects population dynamics of parasitoids, even at the landscape scale. What causes host quality to vary and the subsequent mechanisms by which parasitoid population dynamics are affected can be complex. Here, we examine the indirect interaction of a plant pathogen with a parasitoid wasp. Under laboratory conditions, parasitoids from hosts fed fungus-infected plants weighed less than those from hosts fed uninfected plants, indicating that the fungus causes the hosts to be of poor quality. However, parasitoids reared from hosts fed fungal-infected diet also tended to be female, a characteristic associated with high host quality. The pathogen, herbivore and parasitoid persist regionally as metapopulations in a shared landscape in Aland, Finland. In an analysis of the metapopulation dynamics of the parasitoid over 6 years, the probability of colonization of a host population increased by more than twofold in patches occupied by the plant pathogen. While we cannot determine that the relationship is causal, a compelling explanation is that the plant pathogen facilitates the establishment by the parasitoid by increasing the fraction of female offspring. This is a novel mechanism of spatial multi-trophic level interactions.     

Helminths as vectors of pathogens in vertebrate hosts: a theoretical approach

Pathogens frequently use vectors to facilitate transmission between hosts and, for vertebrate hosts, the vectors are typically ectoparasitic arthropods. However, other parasites that are intimately associated with their hosts may also be ideal candidate vectors; namely the parasitic helminths. Here, we present empirical evidence that helminth vectoring of pathogens occurs in a range of vertebrate systems by a variety of helminth taxa. Using a novel theoretical framework we explore the dynamics of helminth vectoring and determine which host-helminth-pathogen characteristics may favour the evolution of helminth vectoring. We use two theoretical models: the first is a population dynamic model amalgamated from standard macro- and microparasite models, which serves as a framework for investigation of within-host interactions between co-infecting pathogens and helminths. The second is an evolutionary model, which we use to predict the ecological conditions under which we would expect helminth vectoring to evolve. We show that, like arthropod vectors, helminth vectors increase pathogen fitness. However, unlike arthropod vectors, helminth vectoring increases the pathogenic impact on the host and may allow the evolution of high pathogen virulence. We show that concomitant infection of a host with a helminth and pathogen are not necessarily independent of one another, due to helminth vectoring of microparasites, with profound consequences for pathogen persistence and the impact of disease on the host population.     

Evaluating the importance of within- and between-host selection pressures on the evolution of chronic pathogens

Infectious pathogens compete and are subject to natural selection at multiple levels. For example, viral strains compete for access to host resources within an infected host and, at the same time, compete for access to susceptible hosts within the host population. Here we propose a novel approach to study the interplay between within- and between-host competition. This approach allows for a single host to be infected by and transmit two strains of the same pathogen. We do this by nesting a model for the host-pathogen dynamics within each infected host into an epidemiological model. The nesting of models allows the between-host infectivity and mortality rates suffered by infected hosts to be functions of the disease progression at the within-host level. We present a general method for computing the basic reproduction ratio of a pathogen in such a model. We then illustrate our method using a basic model for the within-host dynamics of viral infections, embedded within the simplest susceptible-infected (SI) epidemiological model. Within this nested framework, we show that the virion production rate at the level of the cell-virus interaction leads, via within-host competition, to the presence or absence of between-host level competitive exclusion. In particular, we find that in the absence of mutation the strain that maximizes between-host fitness can outcompete all other strains. In the presence of mutation we observe a complex invasion landscape showing the possibility of coexistence. Although we emphasize the application to human viral diseases, we expect this methodology to be applicable to be many host-parasite systems.     

A hyperparasite affects the population dynamics of a wild plant pathogen

Assessing the impact of natural enemies of plant and animal pathogens on their host's population dynamics is needed to determine the role of hyperparasites in affecting disease dynamics, and their potential for use in efficient control strategies of pathogens. Here, we focus on the long‐term study describing metapopulation dynamics of an obligate pathogen, the powdery mildew (Podosphaera plantaginis) naturally infecting its wild host plant (Plantago lanceolata) in the fragmented landscape of the Åland archipelago (southwest Finland). Regionally, the pathogen persists through a balance of extinctions and colonizations, yet factors affecting extinction rates remain poorly understood. Mycoparasites of the genus Ampelomyces appear as good candidates for testing the role of a hyperparasite, i.e. a parasite of other parasites, in the regulation of their fungal hosts' population dynamics. For this purpose, we first designed a quantitative PCR assay for detection of Ampelomyces spp. in field‐collected samples. This newly developed molecular test was then applied to a large‐scale sampling within the Åland archipelago, revealing that Ampelomyces is a widespread hyperparasite in this system, with high variability in prevalence among populations. We found that the hyperparasite was more common on leaves where multiple powdery mildew strains coexist, a pattern that may be attributed to differential exposure. Moreover, the prevalence of Ampelomyces at the plant level negatively affected the overwinter survival of its fungal host. We conclude that this hyperparasite may likely impact on its host population dynamics and argue for increased focus on the role of hyperparasites in disease dynamics.     

A general host–pathogen model with free–living infective stages and differing rates of uptake of the infective stages by infected and susceptible hosts

In addition to their lethal effects, pathogens can cause a number of other debilitating effects on infected hosts. A population dynamical model of the interaction between an invertebrate host and a pathogen is constructed to examine the importance of one such debilitating effect on the host population dynamics. Specifically the feeding rate and therefore the uptake of pathogen free-living infective particles by infected individuals is reduced as a consequence of the pathogen infection. The pathogen is more likely to regulate the host and the equilibrium population density of the host is reduced. Less intuitively there is also an increased chance of the pathogen causing cyclic population dynamics in the host. Received: December 8, 1997 / Accepted: March 23, 1999     

Heterogeneity,Mixing, and the Spatial Scales of Mosquito-Borne Pathogen Transmission

The Ross-Macdonald model has dominated theory for mosquito-borne pathogen transmission dynamics and control for over a century. The model, like many other basic population models, makes the mathematically convenient assumption that populations are well mixed; i.e., that each mosquito is equally likely to bite any vertebrate host. This assumption raises questions about the validity and utility of current theory because it is in conflict with preponderant empirical evidence that transmission is heterogeneous. Here, we propose a new dynamic framework that is realistic enough to describe biological causes of heterogeneous transmission of mosquito-borne pathogens of humans, yet tractable enough to provide a basis for developing and improving general theory. The framework is based on the ecological context of mosquito blood meals and the fine-scale movements of individual mosquitoes and human hosts that give rise to heterogeneous transmission. Using this framework, we describe pathogen dispersion in terms of individual-level analogues of two classical quantities: vectorial capacity and the basic reproductive number, . Importantly, this framework explicitly accounts for three key components of overall heterogeneity in transmission: heterogeneous exposure, poor mixing, and finite host numbers. Using these tools, we propose two ways of characterizing the spatial scales of transmission—pathogen dispersion kernels and the evenness of mixing across scales of aggregation—and demonstrate the consequences of a model''s choice of spatial scale for epidemic dynamics and for estimation of , both by a priori model formulas and by inference of the force of infection from time-series data.     

Heterogeneity in patch quality buffers metapopulations from pathogen impacts

Many wildlife species persist on a network of ephemerally occupied habitat patches connected by dispersal. Provisioning of food and other resources for conservation management or recreation is frequently used to improve local habitat quality and attract wildlife. Resource improvement can also facilitate local pathogen transmission, but the landscape-level consequences of provisioning for pathogen spread and habitat occupancy are poorly understood. Here, we develop a simple metapopulation model to investigate how heterogeneity in patch quality resulting from resource improvement influences long-term metapopulation occupancy in the presence of a virulent pathogen. We derive expressions for equilibrium host–pathogen outcomes in terms of provisioning effects on individual patches (through decreased patch extinction rates) and at the landscape level (the fraction of high-quality, provisioned patches), and highlight two cases of practical concern. First, if occupancy in the unprovisioned metapopulation is sufficiently low, a local maximum in occupancy occurs for mixtures of high- and low-quality patches, such that further increasing the number of high-quality patches both lowers occupancy and allows pathogen invasion. Second, if the pathogen persists in the unprovisioned metapopulation, further provisioning can result in all patches becoming infected and in a global minimum in occupancy. This work highlights the need for more empirical research on landscape-level impacts of local resource provisioning on pathogen dynamics.     

Populations and infectious diseases: Dynamics and evolution

The host-parasite or host-pathogen system was analyzed from dynamical and evolutionary viewpoints using simple mathematical models incorporating vertical transmission, immunity and its loss. We first analyzed a model without density regulation of host population. In the analysis on dynamics, the condition for the pathogen to work as a density regulating factor was obtained. In the analysis on evolution, criteria for the evolution of host and pathogen were proposed. These criteria implies that the evolution of hosts should result in an increase in infected host density, whereas the evolution of pathogens a decrease in susceptible host density. The direction of evolution at some parameters of host and that of pathogen were examined when the parameters were independently and freely changeable. Among the parameters, only reduction in additional mortality due to infection was the evolutionary trend common to both host and pathogen. In all the other parameters examined, trend of evolution predicted in host is reversed in pathogen. We then analyzed whether the obtained criteria still hold in models with density regulation of hosts. Using randomly generated parameter sets, we obtained the result that the criteria should hold very likely though they do not always hold. We discussed evolution of virulence when there is a constraint between the traits.     

The interaction between plant competition and disease

It is well documented that pathogens can affect the survival, reproduction, and growth of individual plants. Drawing together insights from diverse studies in ecology and agriculture, we evaluate the evidence for pathogens affecting competitive interactions between plants of both the same and different species. Our objective is to explore the potential ecological and evolutionary consequences of such interactions. First, we address how disease interacts with intraspecific competition and present a simple graphical model suggesting that diverse outcomes should be expected. We conclude that the presence of pathogens may have either large or minimal effects on population dynamics depending on many factors including the density-dependent compensatory ability of healthy plants and spatial patterns of infection. Second, we consider how disease can alter competitive abilities of genotypes, and thus may affect the genetic composition of populations. These genetic processes feed back on population dynamics given trade-offs between disease resistance and other fitness components. Third, we examine how the effect of disease on interspecific plant interactions may have potentially far-reaching effects on community composition. A host-specific pathogen, for example, may alter a competitive hierarchy that exists between host and non-host species. Generalist pathogens can also induce indirect competitive interactions between host species. We conclude by highlighting lacunae in our current understanding and suggest that future studies should (1) examine a broader taxonomic range of pathogens since work to date has largely focused on fungal pathogens; (2) increase the use of field competition studies; (3) follow interactions for multiple generations; (4) characterize density-dependent processes; and (5) quantify pathogen, as well as plant, population and community dynamics.     

Self-harm to preferentially harm the pathogens within: non-specific stressors in innate immunity

Therapies with increasing specificity against pathogens follow the immune system''s evolutionary course in maximizing host defence while minimizing self-harm. Nevertheless, even completely non-specific stressors, such as reactive molecular species, heat, nutrient and oxygen deprivation, and acidity can be used to preferentially harm pathogens. Strategic use of non-specific stressors requires exploiting differences in stress vulnerability between pathogens and hosts. Two basic vulnerabilities of pathogens are: (i) the inherent vulnerability to stress of growth and replication (more immediately crucial for pathogens than for host cells) and (ii) the degree of pathogen localization, permitting the host''s use of locally and regionally intense stress. Each of the various types of non-specific stressors is present during severe infections at all levels of localization: (i) ultra-locally within phagolysosomes, (ii) locally at the infected site, (iii) regionally around the infected site and (iv) systemically as part of the acute-phase response. We propose that hosts strategically use a coordinated system of non-specific stressors at local, regional and systemic levels to preferentially harm the pathogens within. With the rising concern over emergence of resistance to specific therapies, we suggest more scrutiny of strategies using less specific therapies in pathogen control. Hosts'' active use of multiple non-specific stressors is likely an evolutionarily basic defence whose retention underlies and supplements the well-recognized immune defences that directly target pathogens.     

The Relationship between Host Lifespan and Pathogen Reservoir Potential: An Analysis in the System Arabidopsis thaliana-Cucumber mosaic virus

Identification of the determinants of pathogen reservoir potential is central to understand disease emergence. It has been proposed that host lifespan is one such determinant: short-lived hosts will invest less in costly defenses against pathogens, so that they will be more susceptible to infection, more competent as sources of infection and/or will sustain larger vector populations, thus being effective reservoirs for the infection of long-lived hosts. This hypothesis is sustained by analyses of different hosts of multihost pathogens, but not of different genotypes of the same host species. Here we examined this hypothesis by comparing two genotypes of the plant Arabidopsis thaliana that differ largely both in life-span and in tolerance to its natural pathogen Cucumber mosaic virus (CMV). Experiments with the aphid vector Myzus persicae showed that both genotypes were similarly competent as sources for virus transmission, but the short-lived genotype was more susceptible to infection and was able to sustain larger vector populations. To explore how differences in defense against CMV and its vector relate to reservoir potential, we developed a model that was run for a set of experimentally-determined parameters, and for a realistic range of host plant and vector population densities. Model simulations showed that the less efficient defenses of the short-lived genotype resulted in higher reservoir potential, which in heterogeneous host populations may be balanced by the longer infectious period of the long-lived genotype. This balance was modulated by the demography of both host and vector populations, and by the genetic composition of the host population. Thus, within-species genetic diversity for lifespan and defenses against pathogens will result in polymorphisms for pathogen reservoir potential, which will condition within-population infection dynamics. These results are relevant for a better understanding of host-pathogen co-evolution, and of the dynamics of pathogen emergence.     

CD8 T cell responses to viral infections in sequence

Our current understanding of virus-specific T cell responses has been shaped by model systems with mice, where naive animals are infected with a single viral pathogen. Paradigms derived from such models, however, may not always be applicable to a natural setting, where a host is exposed to numerous pathogens over its lifetime. Accumulating data in animal models and with some human diseases indicate that a host's prior history of infections can impact the specificity of future CD8 T cell responses, even to unrelated viruses. This can have both beneficial and detrimental consequences for the host, including altered clearance of virus, distinct forms of immunopathology, and substantial changes in the pool of memory T cells. Here we will describe the characteristics of CD8 T cells and the dynamics of their response to heterologous viral infections in sequence.