Sarah A. Budischak

Due to long co-evolutionary histories, many zoonotic pathogens are thought to exert little or no negative effects on their wildlife reservoir hosts. However, there remains a lack of rigorous investigations in natural settings. We conducted a 3-year factorial field experiment to investigate how survival of the Puumala hantavirus (PUUV) reservoir, the bank vole, is impacted by PUUV infection, nematode infections, and food availability. We hypothesized that PUUV would not impact survival, but that coinfection with nematodes would negatively impact survival, and that increased food availability would mitigate the negative effects of coinfection. Surprisingly, we demonstrated that PUUV infected voles had substantially reduced survival when compared to uninfected voles, and this strong negative effect manifested in young voles. Nematode removal increased survival of young voles and food supplementation interacted with movement rather than survival. Our results provide empirical evidence in a natural system for infection reducing survival of its reservoir host.

Anthropogenic food subsidies can have profound influences on wildlife behavior and health, including exposure to parasites. In many host–macroparasite systems, parasite exposure is tied to foraging behavior, but how different distributions of food subsidy shape macroparasite encounter and population‐level impacts is poorly understood. Here we modify a mathematical model of macroparasite transmission to explore how food subsidies could change parasite encounter rates and between‐host variation in parasite burdens, reflecting changes in host foraging and conspecific overlap. Hosts experience the highest average parasite abundance and associated reductions in population size when food subsidies increase and homogenize parasite encounter rates, for example when hosts center their home ranges on a point food source and overlap with many conspecifics. Conversely, hosts experience the lowest parasite abundance and impacts when subsidies result in lower and more heterogeneous parasite encounter rates, for example when multiple patchily distributed subsidies subdivide host populations and increase host commute times to food at the expense of time spent foraging. Even when resources affect other processes such as improving host immunity or fecundity, the overall effect of subsidies on infection is more strongly driven by changes in parasite encounter rates through altered foraging behavior. These patterns are robust to different effect sizes of resource subsidy on foraging and nonforaging parameters. Our findings demonstrate that resource‐driven shifts in host foraging behavior could play an integral role in determining infection dynamics for parasites with environmental (free‐living) infectious stages, with consequences for wildlife provisioning in recreational, conservation, and management contexts.

Anthropogenic changes to the environment, including altered food resource availability, influence host physiology, behaviour, and population dynamics, which can have strong downstream consequences on wildlife disease dynamics. Additionally, some individuals within a population contribute disproportionately to infection as ‘super-shedders’ of infection, but the extent to which food availability alters the likelihood of super-shedding and overall parasite infection patterns is poorly understood. We conducted a three-year field experiment in southern Finland to investigate how food supplementation and parasite removal affect nematode infection measures and the relationship between nematode infection and fitness of wild bank voles ( Clethrionomys glareolus ). Using a factorial design across 12 populations, we manipulated food availability and administered anthelmintic treatments to assess effects on nematode infection status, intensity, and two measures of super-shedding (abundance super-shedding, intensity super-shedding). We also examined parasite impacts on host fitness, including apparent survival probability and reproductive status. Food supplementation did not affect likelihood of infection, intensity or intensity super-shedding, but did reduce the likelihood of abundance super-shedding, suggesting an effect of food availability on infection heterogeneity. We also identified an interaction between nematode infection status and host age on fitness. Notably, infected younger individuals had reduced survival and reproduction, but infected older individuals had greater survival and reproduction compared to their uninfected counterparts. Our study provides novel empirical evidence on how anthropogenic changes in food availability can influence parasite transmission dynamics and the fitness consequences of these sub-lethal parasites in a wildlife system.

Spatial overlap between animals in wildlife populations can have important implications for pathogen transmission. Ecological factors and animal demographic traits can influence animal space use and spatial overlap, but it is unclear how these interactions drive pathogen transmission. We experimentally manipulated wild bank vole populations via resource supplementation and anthelmintic treatment. Using network analysis, we investigated the relationship between spatial overlap and infection likelihood of an endemic zoonotic hantavirus, including how vole sex and reproductive status interact with spatial behaviour to affect infection likelihood. Spatial overlap in a previous month drove the likelihood of current hantavirus infection, and food supplementation and anthelmintic treatment altered the effects of spatial overlap on infection likelihood. Vole sex and reproductive status were important factors determining whether spatial overlap increased or decreased the likelihood of hantavirus infection and interacted with resource supplementation and anthelmintic treatment, generating different infection dynamics in each treatment. Our research provides rare empirical evidence linking previous spatial overlap to current infection status in wildlife populations, with implications for understanding disease dynamics and persistence as well as developing effective management efforts. We further highlight the importance of incorporating variation in ecological factors and host demography when studying pathogen transmission in wildlife systems.

Uncovering drivers of community assembly is a key aspect of learning how biological communities function. Drivers of community similarity can be especially useful in this task as they affect assemblage‐level changes that lead to differences in species diversity between habitats. Concepts of β‐diversity originally developed for use in free‐living communities have been widely applied to parasite communities to gain insight into how infection risk changes with local conditions by comparing parasite communities across abiotic and biotic gradients. Factors shaping β‐diversity in communities of immature parasites, such as larvae, are largely unknown. This is a key knowledge gap as larvae are frequently the infective life‐stage and understanding variation in these larval communities is thus key for disease prevention. Our goal was to uncover links between β‐diversity of parasite communities at different life stages; therefore, we used gastrointestinal nematodes infecting African buffalo in Kruger National Park, South Africa, to investigate within‐host and extra‐host drivers of adult and larval parasite community similarity. We employed a cross‐sectional approach using PERMANOVA that examined each worm community at a single time point to assess independent drivers of β‐diversity in larvae and adults as well as a longitudinal approach with path analysis where adult and larval communities from the same host were compared to better link drivers of β‐diversity between these two life stages. Using the cross‐sectional approach, we generally found that intrinsic, within‐host traits had significant effects on β‐diversity of adult nematode communities, while extrinsic, extra‐host variables had significant effects on β‐diversity of larval nematode communities. However, the longitudinal approach provided evidence that intrinsic, within‐host factors affected the larval community indirectly via the adult community. Our results provide key data for the comparison of community‐level processes where adult and immature stages inhabit vastly different habitats (i.e. within‐host vs. abiotic environment). In the context of parasitism, this helps elucidate host infection risk via larval stages and the drivers that shape persistence of adult parasite assemblages, both of which are useful for predicting and preventing infectious disease.

1. Animal space use and spatial overlap can have important consequences for population-level processes such as social interactions and pathogen transmission. Identifying how environmental variability and inter-individual variation affect spatial patterns and in turn influence interactions in animal populations is a priority for the study of animal behavior and disease ecology. Environmental food availability and macroparasite infection are common drivers of variation, but there are few experimental studies investigating how they affect spatial patterns of wildlife. 2. Bank voles ( Clethrionomys glareolus ) are a tractable study system to investigate spatial patterns of wildlife and are amenable to experimental manipulations. We conducted a replicated, factorial field experiment in which we provided supplementary food and removed helminths in vole populations in natural forest habitat and monitored vole space use and spatial overlap using capture-mark-recapture methods. 3. Using network analysis, we quantified vole space use and spatial overlap. We compared the effects of food supplementation and helminth removal and investigated the impact of season, sex, and reproductive status on space use and spatial overlap. 4. We found that food supplementation decreased vole space use while helminth removal increased space use. Space use also varied by sex, reproductive status, and season. Spatial overlap was similar between treatments despite up to three-fold differences in population size. 5. By quantifying the spatial effects of food availability and macroparasite infection on wildlife populations, we demonstrate the potential for space use and population density to trade off and maintain consistent spatial overlap in wildlife populations. This has important implications for spatial processes in wildlife including pathogen transmission.

Within‐host parasite interactions can be mediated by the host and changes in host phenotypes often serve as indicators of the presence or intensity of parasite interactions. Parasites like helminths induce a range of physiological, morphological and immunological changes in hosts that can drive bottom‐up (resource‐mediated) or top‐down (immune‐mediated) interactions with co‐infecting parasites. Although top‐down and bottom‐up interactions are typically studied in isolation, the diverse phenotypic changes induced by parasite infection may serve as a useful tool for understanding if, and when, these processes act in concert. Using an anthelmintic treatment study of African buffalo, Syncerus caffer, we tracked changes in host immunological and morphological phenotypes during helminth‐coccidia co‐infection to investigate their role in driving independent and combinatorial bottom‐up and top‐down parasite interactions. We also examined repercussions for host fitness. Clearance of a blood‐sucking helminth, Haemonchus, from the host gastrointestinal tract induced a systemic Th2 immune phenotype, while clearance of a tissue‐feeding helminth, Cooperia, induced a systemic Th1 phenotype. Furthermore, the Haemonchus‐associated systemic Th2 immune phenotype drove simultaneous top‐down and bottom‐up effects that increased coccidia shedding by changing the immunological and morphological landscapes of the intestine. Higher coccidia shedding was associated with lower host body condition, a lower chance of pregnancy and older age at first pregnancy, suggesting that coccidia infection imposed significant condition and reproductive costs on the host. Our findings suggest that top‐down and bottom‐up interactions may commonly co‐occur and that tracking key host phenotypes that change in response to infection can help uncover complex pathways by which parasites interact. Read the free Plain Language Summary for this article on the Journal blog.

Many high-profile outbreaks are driven by super-spreading, including HIV, MERS, Ebola, and the SARS-Cov-2 pandemic. That super-spreading is a common feature of epidemics is immutable, however, the relative importance of 2super-spreaders to the outcome of an epidemic, and the individual-level traits that lead to super-spreading, is less clear. For example, an individual may contribute disproportionately to transmission by way of an extremely high contact rate or by way of low recovery, but how these two super-spreaders differ in their effect on epidemiological dynamics is unclear. Furthermore, epidemiological traits may often covary with one another in ways that promote or inhibit super-spreading. What patterns of covariation, and between what traits, are most likely to lead to large epidemics driven by super-spreading? Using stochastic individual-based simulations of an SIR epidemiological model, we explore how variation and covariation between transmission-related traits (contact rate and infectiousness) and duration-related traits (virulence and recovery) of infected individuals affects super-spreading and peak epidemic size. We show that covariation matters when contact rate and infectiousness covary: peak epidemic size is largest when they covary positively and smallest when they covary negatively. We did not see that more super-spreading always leads to larger epidemics, rather, we show that the relationship between super-spreading and peak epidemic size is dependent on which traits are covarying. This suggests that there may not necessarily be any general relationship between the frequency of super-spreading and the size of an epidemic.

Whether, when, and how genetic diversity buffers individuals and populations against infectious disease risk is a critical and open question for understanding wildlife disease and zoonotic disease risk. Several, but not all, studies have found negative relationships between infection and heterozygosity in wildlife. Since they can host multiple zoonotic infections, we sampled a population of wild deer mice (Peromyscus maniculatus), sequenced their genomes, and examined their fecal samples for coccidia and nematode eggs. We analyzed coccidia infection status, abundance, and coinfection status in relation to per-locus and per-individual measures of heterozygosity, as well as identified SNPs associated with infection status. Since heterozygosity might affect host condition, and condition is known to affect immunity, it was included as a co-variate in the per-individual analyses and as response variable in relation to heterozygosity. Not only did coccidia-infected individuals have lower levels of genome-wide per-locus diversity across all metrics, but we found an inverse relationship between genomic diversity and severity of coccidia infection. We also found weaker evidence that coinfected individuals had lower levels of private allelic variation than all other groups. In the per-individual analyses, relationships between heterozygosity and infection were marginal but followed the same negative trends. Condition was negatively correlated with infection, but was not associated with heterozygosity, suggesting that effects of heterozygosity on infection were not mediated by host condition in this system. Association tests identified multiple loci involved in the inflammatory response, with a particular role for NF-κB signaling, supporting previous work on the genetic basis of coccidia resistance. Taken together, we find that increased genome-wide neutral diversity, the presence of specific genetic variants, and improved condition positively impact infection status. Our results underscore the importance of considering host genomic variation as a buffer against infection, especially in systems that can harbor zoonotic diseases.

Significance: Interactions between pathogens can have substantial negative effects on host health. Therefore, identifying the causes of these interactions is integral for effective disease management and control. Interactions between two pathogens that simultaneously or sequentially infect the same host are common. We show that interactions also arise when genetically based defenses against one pathogen affect responses to another, even when the first pathogen is concurrently absent. This mode of pathogen interaction provides insight for understanding patterns of variation in disease severity in natural populations. It also implies that, under some conditions, control strategies that rely on selecting for resistance to one pathogen, in livestock for example, might jeopardize control of another.