Diverging effects of host density and richness across biological scales drive diversity-disease outcomes.

Understanding how biodiversity affects pathogen transmission remains an unresolved question due to the challenges in testing potential mechanisms in natural systems and how these mechanisms vary across biological scales. By quantifying transmission of an entire guild of parasites (larval trematodes) within 902 amphibian host communities, we show that the community-level drivers of infection depend critically on biological scale. At the individual host scale, increases in host richness led to fewer parasites per host for all parasite taxa, with no effect of host or predator densities. At the host community scale, however, the inhibitory effects of richness were counteracted by associated increases in total host density, leading to no overall change in parasite densities. Mechanistically, we find that while average host competence declined with increasing host richness, total community competence remained stable due to additive assembly patterns. These results help reconcile disease-diversity debates by empirically disentangling the roles of alternative ecological drivers of parasite transmission and how such effects depend on biological scale.

Differential gene expression in response to fungal pathogen exposure in the aquatic invertebrate, Daphnia dentifera.

While vertebrate immune systems are appreciated for their complexity and adaptability, invertebrate immunity is often considered to be less complex. However, immune responses in many invertebrates likely involve sophisticated processes. Interactions between the crustacean host Daphnia dentifera and its fungal pathogen Metschnikowia bicuspidata provide an excellent model for exploring the mechanisms underlying crustacean immunity. To explore the genomic basis of immunity in Daphnia, we used RNA-sequencing technology to quantify differential gene expression between individuals of a single host genotype exposed or unexposed to M. bicuspidata over 24 h. Transcriptomic analyses showed that the number of differentially expressed genes between the control (unexposed) and experimental (exposed) groups increased over time. Gene ontology enrichment analysis revealed that differentially expressed genes were enriched for immune-related molecules and processes, such as cuticle development, prostaglandin, and defense response processes. Our findings provide a suite of immunologically relevant genes and suggest the presence of a rapidly upregulated immune response involving the cuticle in Daphnia. Studies involving gene expression responses to pathogen exposure shine a light on the processes occurring during the course of infection. By leveraging knowledge on the genetic basis for immunity, immune mechanisms can be more thoroughly understood to refine our understanding of disease spread within invertebrate populations.

Partitioning variance in immune traits in a zooplankton host-Fungal parasite system.

Host immune traits arise from both genetic and environmental sources of variation. When immune traits have a strong genetic basis, the presence and severity of disease in a population may influence the distribution of those traits. Our study addressed how two immune-related traits (gut penetrability and the hemocyte response) are shaped by genetic and environmental sources of variation, and how the presence of a virulent disease altered the relative frequency of these traits in natural populations. Daphnia dentifera hosts were sampled from five Indiana lakes between June and December 2017 before and during epidemics of their fungal pathogen, Metschnikowia bicuspidata. Collected Daphnia were experimentally exposed to Metschnikowia and assayed for their gut penetrability, hemocyte response, and multi-locus genotype. Mixed-effects models were constructed to partition variance in immune traits between genetic and environmental sources. We then isolated the genetic sources to produce genotype-specific estimates of immune traits for each multi-locus genotype. Finally, we assessed the relative frequency and dynamics of genotypes during epidemics and asked whether genotypes with more robust immune responses increased in frequency during epidemics. Although genotype was an important source of variation for both gut penetrability and the hemocyte response, environmental factors (e.g., resource availability, Metschnikowia prevalence, and co-infection) still explained a large portion of observed variation, suggesting a high degree of flexibility in Daphnia immune traits. Additionally, no significant associations were detected between a genotype's immune traits and its frequency in a population. Our study highlights the power of variance partitioning in understanding the factors driving variation in Daphnia traits and motivates further research on immunological flexibility and the ecological drivers of immune variation.

Timescale reverses the relationship between host density and infection risk.

Host density shapes infection risk through two opposing phenomena. First, when infective stages are subdivided among multiple hosts, greater host densities decrease infection risk through 'safety in numbers'. Hosts, however, represent resources for parasites, and greater host availability also fuels parasite reproduction. Hence, host density increases infection risk through 'density-dependent transmission'. Theory proposes that these phenomena are not disparate outcomes but occur over different timescales. That is, higher host densities may reduce short-term infection risk, but because they support parasite reproduction, may increase long-term risk. We tested this theory in a zooplankton-disease system with laboratory experiments and field observations. Supporting theory, we found that negative density-risk relationships (safety in numbers) sometimes emerged over short timescales, but these relationships reversed to 'density-dependent transmission' within two generations. By allowing parasite numerical responses to play out, time can shift the consequences of host density, from reduced immediate risk to amplified future risk.

Evidence gaps and diversity among potential win-win solutions for conservation and human infectious disease control.

As sustainable development practitioners have worked to "ensure healthy lives and promote well-being for all" and "conserve life on land and below water", what progress has been made with win-win interventions that reduce human infectious disease burdens while advancing conservation goals? Using a systematic literature review, we identified 46 proposed solutions, which we then investigated individually using targeted literature reviews. The proposed solutions addressed diverse conservation threats and human infectious diseases, and thus, the proposed interventions varied in scale, costs, and impacts. Some potential solutions had medium-quality to high-quality evidence for previous success in achieving proposed impacts in one or both sectors. However, there were notable evidence gaps within and among solutions, highlighting opportunities for further research and adaptive implementation. Stakeholders seeking win-win interventions can explore this Review and an online database to find and tailor a relevant solution or brainstorm new solutions.

It's a worm-eat-worm world: Consumption of parasite free-living stages protects hosts and benefits predators.

Predation on parasites is a common interaction with multiple, concurrent outcomes. Free-living stages of parasites can comprise a large portion of some predators' diets and may be important resources for population growth. Predation can also reduce the density of infectious agents in an ecosystem, with resultant decreases in infection rates. While predator-parasite interactions likely vary with parasite transmission strategy, few studies have examined how variation in transmission mode influences contact rates with predators and the associated changes in consumption risk. To understand how transmission mode mediates predator-parasite interactions, we examined associations between an oligochaete predator Chaetogaster limnaei that lives commensally on freshwater snails and nine trematode taxa that infect snails. Chaetogaster is hypothesized to consume active (i.e. mobile), free-living stages of trematodes that infect snails (miracidia), but not the passive infectious stages (eggs); it could thus differentially affect transmission and infection prevalence of parasites, including those with medical or veterinary importance. Alternatively, when infection does occur, Chaetogaster can consume and respond numerically to free-living trematode stages released from infected snails (cercariae). These two processes lead to contrasting predictions about whether Chaetogaster and trematode infection of snails correlate negatively ('protective predation') or positively ('predator augmentation'). Here, we tested how parasite transmission mode affected Chaetogaster-trematode relationships using data from 20,759 snails collected across 4 years from natural ponds in California. Based on generalized linear mixed modelling, snails with more Chaetogaster were less likely to be infected by trematodes that rely on active transmission. Conversely, infections by trematodes with passive infectious stages were positively associated with per-snail Chaetogaster abundance. Our results suggest that trematode transmission mode mediates the net outcome of predation on parasites. For trematodes with active infectious stages, predatory Chaetogaster limited the risk of snail infection and its subsequent pathology (i.e. castration). For taxa with passive infectious stages, no such protective effect was observed. Rather, infected snails were associated with higher Chaetogaster abundance, likely owing to the resource subsidy provided by cercariae. These findings highlight the ecological and epidemiological importance of predation on free-living stages while underscoring the influence of parasite life history in shaping such interactions.

Host Controls of Within-Host Disease Dynamics: Insight from an Invertebrate System.

AbstractWithin-host processes (representing the entry, establishment, growth, and development of a parasite inside its host) may play a key role in parasite transmission but remain challenging to observe and quantify. We develop a general model for measuring host defenses and within-host disease dynamics. Our stochastic model breaks the infection process down into the stages of parasite exposure, entry, and establishment and provides associated probabilities for a host's ability to resist infections with barriers and clear internal infections. We tested our model on Daphnia dentifera and the parasitic fungus Metschnikowia bicuspidata and found that when faced with identical levels of parasite exposure, Daphnia patent (transmitting) infections depended on the strength of internal clearance. Applying a Gillespie algorithm to the model-estimated probabilities allowed us to visualize within-host dynamics, within which signatures of host defense could be clearly observed. We also found that early within-host stages were the most vulnerable to internal clearance, suggesting that hosts have a limited window during which recovery can occur. Our study demonstrates how pairing longitudinal infection data with a simple model can reveal new insight into within-host dynamics and mechanisms of host defense. Our model and methodological approach may be a powerful tool for exploring these properties in understudied host-parasite interactions.

Parasite exposure and host susceptibility jointly drive the emergence of epidemics.

Parasite transmission is thought to depend on both parasite exposure and host susceptibility to infection; however, the relative contribution of these two factors to epidemics remains unclear. We used interactions between an aquatic host and its fungal parasite to evaluate how parasite exposure and host susceptibility interact to drive epidemics. In six lakes, we tracked the following factors from pre-epidemic to epidemic emergence: (1) parasite exposure (measured observationally as fungal spores attacking wild-caught hosts), (2) host susceptibility (measured experimentally as the number of fungal spores required to produce terminal infection), (3) host susceptibility traits (barrier resistance and internal clearance, both quantified with experimental assays), and (4) parasite prevalence (measured observationally from wild-caught hosts). Tracking these factors over 6 months and in almost 7,000 wild-caught hosts provided key information on the drivers of epidemics. We found that epidemics depended critically on the interaction of exposure and susceptibility; epidemics only emerged when a host population's level of exposure exceeded its individuals' capacity for recovery. Additionally, we found that host internal clearance traits (the hemocyte response) were critical in regulating epidemics. Our study provides an empirical demonstration of how parasite exposure and host susceptibility interact to inhibit or drive disease in natural systems and demonstrates that epidemics can be delayed by asynchronicity in the two processes. Finally, our results highlight how individual host traits can scale up to influence broad epidemiological patterns.

Towards a mechanistic understanding of competence: a missing link in diversity-disease research.

Biodiversity loss may increase the risk of infectious disease in a phenomenon known as the dilution effect. Circumstances that increase the likelihood of disease dilution are: (i) when hosts vary in their competence, and (ii) when communities disassemble predictably, such that the least competent hosts are the most likely to go extinct. Despite the central role of competence in diversity-disease theory, we lack a clear understanding of the factors underlying competence, as well as the drivers and extent of its variation. Our perspective piece encourages a mechanistic understanding of competence and a deeper consideration of its role in diversity-disease relationships. We outline current evidence, emerging questions and future directions regarding the basis of competence, its definition and measurement, the roots of its variation and its role in the community ecology of infectious disease.

Indirect effects in a planktonic disease system.

Indirect effects, both density- and trait-mediated, have been known to act in tandem with direct effects in the interactions of numerous species. They have been shown to affect populations embedded in competitive and mutualistic networks alike. In this work, we introduce a four-dimensional system of ordinary differential equations and investigate the interplay between direct density-effects and density- and trait-mediated indirect effects that take place in a yeast parasite-zooplankton host-incompetent competitor system embedded in a food web which also includes resources and predators. Among our main findings is the demonstration that indirect effects cause qualitative and quantitative changes almost indistinguishable from direct effects and the corroboration through our analysis of the fact that the effects of direct and indirect mechanisms cannot be disentangled. Our results underpin the conclusions of past studies calling for comprehensive models that incorporate both direct and indirect effects to better describe field data.

Variation in Immune Defense Shapes Disease Outcomes in Laboratory and Wild Daphnia.

Host susceptibility may be critical for the spread of infectious disease, and understanding its basis is a goal of ecological immunology. Here, we employed a series of mechanistic tests to evaluate four factors commonly assumed to influence host susceptibility: parasite exposure, barriers to infection, immune responses, and body size. We tested these factors in an aquatic host-parasite system (Daphnia dentifera and the fungal parasite, Metschnikowia bicuspidata) using both laboratory-reared and field-collected hosts. We found support for each factor as a driver of infection. Elevated parasite exposure, which occurs through consumption of infectious fungal spores, increased a host's probability of infection. The host's gut epithelium functioned as a barrier to infection, but in the opposite manner from which we predicted: thinner anterior gut epithelia were more resistant to infectious spores than thick epithelia. This relationship may be mediated by structural attributes associated with epithelial cell height. Fungal spores that breached the host's gut barrier elicited an intensity-dependent hemocyte response that decreased the probability of infection for some Daphnia. Although larger body sizes were associated with increased levels of spore ingestion, larger hosts also had lower frequencies of parasite attack, less penetrable gut barriers, and stronger hemocyte responses. After investigating which mechanisms underlie host susceptibility, we asked: do these four factors contribute equally or asymmetrically to the outcome of infection? An information-theoretic approach revealed that host immune defenses (barriers and immune responses) played the strongest roles in mediating infection outcomes. These two immunological traits may be valuable metrics for linking host susceptibility to the spread of infectious disease.