Resources, key traits and the size of fungal epidemics in Daphnia populations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111939/1/jane12363.pd

Temperature Drives Epidemics in a Zooplankton-Fungus Disease System: A Trait-Driven Approach Points to Transmission via Host Foraging

Climatic warming will likely have idiosyncratic impacts on infectious diseases, causing some to increase while others decrease or shift geographically. A mechanistic framework could better predict these different temperature-disease outcomes. However, such a framework remains challenging to develop, due to the nonlinear and (sometimes) opposing thermal responses of different host and parasite traits and due to the difficulty of validating model predictions with observations and experiments. We address these challenges in a zooplanktonfungus (Daphnia dentifera–Metschnikowia bicuspidata) system. We test the hypothesis that warmer temperatures promote disease spread and produce larger epidemics. In lakes, epidemics that start earlier and warmer in autumn grow much larger. In a mesocosm experiment, warmer temperatures produced larger epidemics. A mechanistic model parameterized with trait assays revealed that this pattern arose primarily from the temperature dependence of transmission rate (b), governed by the increasing foraging (and, hence, parasite exposure) rate of hosts ( f ). In the trait assays, parasite production seemed sufficiently responsive to shape epidemics as well; however, this trait proved too thermally insensitive in the mesocosm experiment and lake survey to matter much. Thus, in warmer environments, increased foraging of hosts raised transmission rate, yielding bigger epidemics through a potentially general, exposure-based mechanism for ectotherms. This mechanistic approach highlights how a trait-based framework will enhance predictive insight into responses of infectious disease to a warmer world

Habitat, predators, and hosts regulate disease in Daphnia through direct and indirect pathways

Community ecology can link habitat to disease via interactions among habitat, focal hosts, other hosts, their parasites, and predators. However, complicated food web interactions (i.e., trophic interactions among predators and their impacts on host density and diversity) often obscure the important pathways regulating disease. Here, we disentangle community drivers in a case study of planktonic disease, using a two‐step approach. In step one, we tested univariate field patterns linking community interactions directly to two disease metrics. Density of focal hosts (Daphnia dentifera) was related to density but not prevalence of fungal (Metschnikowia bicuspidata) infections. Both disease metrics appeared to be driven by selective predators that cull infected hosts (fish, e.g., Lepomis macrochirus), sloppy predators that spread parasites while feeding (midges, Chaoborus punctipennis), and spore predators that reduce contact between focal hosts and parasites (other zooplankton, especially small‐bodied Ceriodaphnia sp.). Host diversity also negatively correlated with disease, suggesting a dilution effect. However, several of these univariate patterns were initially misleading, due to confounding ecological links among habitat, predators, host density, and host diversity. In step two, path models uncovered and explained these misleading patterns, and grounded them in habitat structure (refuge size). First, rather than directly reducing infection prevalence, fish predation drove disease indirectly through changes in density of midges and frequency of small spore predators (which became more frequent in lakes with small refuges). Second, small spore predators drove the two disease metrics through fundamentally different pathways: they directly reduced infection prevalence, but indirectly reduced density of infected hosts by lowering density of focal hosts (likely via competition). Third, the univariate diversity–disease pattern (signaling a dilution effect) merely reflected the confounding direct effects of these small spore predators. Diversity per se had no effect on disease, after accounting for the links between small spore predators, diversity, and infection prevalence. In turn, these small spore predators were regulated by both size‐selective fish predation and refuge size. Thus, path models not only explain each of these surprising results, but also trace their origins back to habitat structure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134436/1/ecm1222_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134436/2/ecm1222-sup-0001-AppendixS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134436/3/ecm1222.pd

Disease-driven Reduction in Human Mobility Influences Human-Mosquito Contacts and Dengue Transmission Dynamics

Heterogeneous exposure to mosquitoes determines an individual’s contribution to vector-borne pathogen transmission. Particularly for dengue virus (DENV), there is a major difficulty in quantifying human-vector contacts due to the unknown coupled effect of key heterogeneities. To test the hypothesis that the reduction of human out-of-home mobility due to dengue illness will significantly influence population-level dynamics and the structure of DENV transmission chains, we extended an existing modeling framework to include social structure, disease-driven mobility reductions, and heterogeneous transmissibility from different infectious groups. Compared to a baseline model, naïve to human pre-symptomatic infectiousness and disease-driven mobility changes, a model including both parameters predicted an increase of 37% in the probability of a DENV outbreak occurring; a model including mobility change alone predicted a 15.5% increase compared to the baseline model. At the individual level, models including mobility change led to a reduction of the importance of out-of-home onward transmission (R, the fraction of secondary cases predicted to be generated by an individual) by symptomatic individuals (up to -62%) at the expense of an increase in the relevance of their home (up to +40%). An individual’s positive contribution to R could be predicted by a GAM including a non-linear interaction between an individual’s biting suitability and the number of mosquitoes in their home (\u3e10 mosquitoes and 0.6 individual attractiveness significantly increased R). We conclude that the complex fabric of social relationships and differential behavioral response to dengue illness cause the fraction of symptomatic DENV infections to concentrate transmission in specific locations, whereas asymptomatic carriers (including individuals in their pre-symptomatic period) move the virus throughout the landscape. Our findings point to the difficulty of focusing vector control interventions reactively on the home of symptomatic individuals, as this approach will fail to contain virus propagation by visitors to their house and asymptomatic carriers

Global change drivers and the risk of infectious disease

Anthropogenic change is contributing to the rise in emerging infectious diseases, but it remains unclear which global change drivers most increase disease and under what contexts. We amassed a dataset from the literature that includes 1,832 observations of infectious disease responses to global change drivers across 1,202 host-parasite combinations. We found that biodiversity loss, climate change, and introduced species were associated with increases in disease-related endpoints or harm (i.e., enemy release for introduced species), whereas urbanization was associated with decreases in disease endpoints. Natural biodiversity gradients, deforestation, forest fragmentation, and most classes of chemical contaminants had non-significant effects on these endpoints. Overall, these results were consistent across human and non-human diseases. Context-dependent effects of the global change drivers on disease were common and are discussed. These findings will help better target disease management and surveillance efforts towards global change drivers that increase disease.One-Sentence SummaryHere we quantify which global change drivers increase infectious diseases the most to better target global disease management and surveillance efforts

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Towards common ground in the biodiversity–disease debate

The disease ecology community has struggled to come to consensus on whether biodiversity reduces or increases infectious disease risk, a question that directly affects policy decisions for biodiversity conservation and public health. Here, we summarize the primary points of contention regarding biodiversity–disease relationships and suggest that vector-borne, generalist wildlife and zoonotic pathogens are the types of parasites most likely to be affected by changes to biodiversity. One synthesis on this topic revealed a positive correlation between biodiversity and human disease burden across countries, but as biodiversity changed over time within these countries, this correlation became weaker and more variable. Another synthesis—a meta-analysis of generally smaller-scale experimental and field studies—revealed a negative correlation between biodiversity and infectious diseases (a dilution effect) in various host taxa. These results raise the question of whether biodiversity–disease relationships are more negative at smaller spatial scales. If so, biodiversity conservation at the appropriate scales might prevent wildlife and zoonotic diseases from increasing in prevalence or becoming problematic (general proactive approaches). Further, protecting natural areas from human incursion should reduce zoonotic disease spillover. By contrast, for some infectious diseases, managing particular species or habitats and targeted biomedical approaches (targeted reactive approaches) might outperform biodiversity conservation as a tool for disease control. Importantly, biodiversity conservation and management need to be considered alongside other disease management options. These suggested guiding principles should provide common ground that can enhance scientific and policy clarity for those interested in simultaneously improving wildlife and human health

Temperature Drives Epidemics in a Zooplankton-Fungus Disease System: A Trait-Driven Approach Points to Transmission via Host Foraging

Climatic warming will likely have idiosyncratic impacts on infectious diseases, causing some to increase while others decrease or shift geographically. A mechanistic framework could better predict these different temperature-disease outcomes. However, such a framework remains challenging to develop, due to the nonlinear and (sometimes) opposing thermal responses of different host and parasite traits and due to the difficulty of validating model predictions with observations and experiments. We address these challenges in a zooplanktonfungus (Daphnia dentifera–Metschnikowia bicuspidata) system. We test the hypothesis that warmer temperatures promote disease spread and produce larger epidemics. In lakes, epidemics that start earlier and warmer in autumn grow much larger. In a mesocosm experiment, warmer temperatures produced larger epidemics. A mechanistic model parameterized with trait assays revealed that this pattern arose primarily from the temperature dependence of transmission rate (b), governed by the increasing foraging (and, hence, parasite exposure) rate of hosts ( f ). In the trait assays, parasite production seemed sufficiently responsive to shape epidemics as well; however, this trait proved too thermally insensitive in the mesocosm experiment and lake survey to matter much. Thus, in warmer environments, increased foraging of hosts raised transmission rate, yielding bigger epidemics through a potentially general, exposure-based mechanism for ectotherms. This mechanistic approach highlights how a trait-based framework will enhance predictive insight into responses of infectious disease to a warmer world

Assessing the Direct and Indirect Effects of Food Provisioning and Nutrient Enrichment on Wildlife Infectious Disease Dynamics

Anthropogenic resource supplementation can shape wildlife disease directly by altering the traits and densities of hosts and parasites or indirectly by stimulating prey, competitor or predator species. We first assess the direct epidemiological consequences of supplementation, highlighting the similarities and differences between food provisioning and two widespread forms of nutrient input: agricultural fertilization and aquatic nutrient enrichment. We then review an aquatic disease system and a general model to assess whether predator and competitor species can enhance or overturn the direct effects of enrichment. All forms of supplementation can directly affect epidemics by increasing host population size or altering parasite production within hosts, but food provisioning is most likely to aggregate hosts and increase parasite transmission. However, if predators or competitors increase in response to supplementation, they could alter resource-fuelled outbreaks in focal hosts. We recommend identifying the traits of hosts, parasites or interacting species that best predict epidemiological responses to supplementation and evaluating the relative importance of these direct and indirect mechanisms. Theory and experiments should examine the timing of behavioural, physiological and demographic changes for realistic, variable scenarios of supplementation. A more integrative view of resource supplementation and wildlife disease could yield broadly applicable disease management strategies