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.

Into the danger zone: How the within-host distribution of parasites controls virulence.

Despite the importance of virulence in epidemiological theory, the relative contributions of host and parasite to virulence outcomes remain poorly understood. Here, we use reciprocal cross experiments to disentangle the influence of host and parasite on core virulence components-infection and pathology-and understand dramatic differences in parasite-induced malformations in California amphibians. Surveys across 319 populations revealed that amphibians' malformation risk was 2.7× greater in low-elevation ponds, even while controlling for trematode infection load. Factorial experiments revealed that parasites from low-elevation sites induced higher per-parasite pathology (reduced host survival and growth), whereas there were no effects of host source on resistance or tolerance. Parasite populations also exhibited marked differences in within-host distribution: ~90% of low-elevation cysts aggregated around the hind limbs, relative to <60% from high-elevation. This offers a novel, mechanistic basis for regional variation in parasite-induced malformations while promoting a framework for partitioning host and parasite contributions to virulence.

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.

Imaging of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

PURPOSE OF REVIEW: The current article reviews obstructive forms of hypertrophic cardiomyopathy and associated morphologic cardiac abnormalities. It focuses on echocardiographic imaging of the left ventricular (LV) outflow tract obstruction, its evaluation, prognostication, and differentiation from other conditions mimicking obstructive hypertrophic cardiomyopathy. RECENT FINDINGS: Symptomatic patients with LV outflow tract (LVOT) gradients at least 50 mmHg on maximally tolerated medical therapy are candidates for advanced therapies. Resting echocardiography may only identify 30% of patients with obstructive physiology. Provocative maneuvers are essential for symptomatic patients with hypertrophic cardiomyopathy (HCM). Exercise echocardiography is recommended if they fail to provoke a gradient. Although dynamic LV tract obstruction is seen with obstructive HCM, it is not specific to this condition and exists in other physiologic and pathophysiologic states. Careful clinical evaluation and imaging techniques aid in the differentiation of HCM from these conditions. SUMMARY: Imaging plays an integral role in the diagnosis, prognosis, and risk stratification of HCM patients. Newer imaging technologies, including 3D transthoracic echocardiography, 3D transesophageal, speckle-derived 2D strain, and cardiac MRI, allow for a better hemodynamic understanding of systolic anterior motion and LV tract obstruction. Evolving techniques, that is, artificial intelligence, will undoubtedly further increase diagnostic capabilities. Newer medical therapies are available with the hope that this will lead to better patient management.

Secondary hypertension: evaluation and management.

PURPOSE OF REVIEW: Hypertension (HTN) that can be attributed to a particular source is known as secondary HTN (SH). Often, SH is difficult to control and thus referred to as resistant HTN, although the two terms are not mutually exclusive. RECENT FINDINGS: A common theme across several contributors to SH are coactivation of the sympathetic drive and hormonal changes, independent of hormonal axis activation. The key to effective management of SH is early recognition and treatment to avoid catastrophic cardiovascular disease effects and mortality. SUMMARY: This review article provides a contemporary summary of the conditions associated with SH and briefly reviews diagnostics and management.

Hypertensive crisis: diagnosis, presentation, and treatment.

PURPOSE OF REVIEW: Hypertensive crisis (HTN-C) is a condition of increasing prevalence. It carries significant morbidity and mortality, and prompt recognition and treatment are crucial. There is a paucity of controlled trials, so a working knowledge of the most recent literature in the area of HTN-C is helpful. RECENT FINDINGS: Novel serological markers, including serum corin, have been found to aid in the early identification of end-organ damage from severely elevated blood pressure (BP). In the area of BP following thrombolysis for ischemic stroke, lower target BP (130-140 mmHg) is associated with some improved outcomes. Two large trials of lower BP following mechanical thrombectomy in stroke have failed to show improved outcomes; however, observed data show benefits at lower than currently recommended levels. Clevidipine, a calcium channel blocker marketed for unique use in HTN-C, was found to be noninferior to the generic less expensive nicardipine. Oral nifedipine was found to be the most effective agent for sustained BP reduction in preeclampsia. SUMMARY: HTN-C remains an area with few prospective randomized trials, but there is active research on identifying lower goals for specific clinical scenarios. Ideal therapeutic agents should be tailored for specific end-organ damage.

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.

Quantification of Resting Myocardial Blood Flow Using Rubidum82 Positron Emission Tomography in Regions with MRI-Confirmed Myocardial Scar.

Background: Resting myocardial blood flow (rMBF) within regions of myocardial scar as measured by positron emission tomography (PET) has not yet been assessed with the radiotracer Rubidium82 (Rb82) or correlated with scar thickness. Cardiac magnetic resonance imaging (cMRI) offers high spatial resolution and identifies myocardial scar with late gadolinium enhancement (LGE). Using Rb82 PET, we sought to characterize rMBF in regions of myocardial scar of varying thicknesses determined by cMRI. Methods/Results: Patients with a history of myocardial infarction, a resting Rb82 PET study and a cMRI were identified. On cMRI, regions of infarction, defined as >50% LGE with akinesis, were sub-categorized as 50-75% LGE or >75% LGE, corresponding with increasing transmural scar thickness. PET zones of infarct based on size and %LGE by cMRI were quantified for mean and minimum rMBF. Mean rMBF (cc/min/g) in infarct zones with >75% LGE was 0.32±0.07 with a minimum rMBF of 0.19±0.03. In infarct zones with 50-75% LGE, rMBF was 0.45±0.14 (50-75% vs. >75%, p=0.002). Conclusions: We identified rMBF within cMRI confirmed regions of myocardial scar of varying thicknesses. rMBF has an inverse relationship with the extent of LGE on cMRI, with the most severe regions (>75% LGE) having mean and minimal rMBF (cc/min/g) of 0.32±0.07 and 0.19±0.03, respectively.

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.

Prosthesis-patient mismatch following aortic and mitral valves replacement - A comprehensive review.

Prothesis-patient mismatch (PPM) occurs when there is a mismatch between the effective orifice area (EOA) of the prosthetic valve and the required cardiac output to meet the need of the patient's body surface area (BSA). The clinical threshold for PPM occurs when the indexed effective orifice area (iEOA) is ≤0.65 cm2/m2 for the aortic valve prosthesis, and ≤ 1.20 cm2/m2 for the mitral valve prosthesis. The wide variation of reported incidence of PPM is most likely attributed to the variation in the methods of calculating iEOA [(for e.g., using continuity equation across the prosthesis versus using projected EOA (generated by the industry)]. Newer generation mechanical valves have shown less PPM than older generation, and stentless bioprosthesis have less PPM than stented prosthesis. Long-term clinical outcome of PPM is associated with adverse cardiovascular events especially in the presence of pre-existing left ventricle dysfunction or with concomitant procedure such as coronary artery bypass graft surgery. Strategies to mitigate the risk of PPM such as aortic root replacement in patients with the small aortic annulus should be utilized. Accurate assessment of the patient's annular size and indexing the effective orifice area (EOA) of the prosthesis to patient's BSA at the time of prosthesis implantation are important steps to preventing future PPM.

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.

Context-Dependent Host-Symbiont Interactions: Shifts along the Parasitism-Mutualism Continuum.

AbstractSymbiotic interactions can shift along a mutualism-parasitism continuum. While there are many studies examining dynamics typically considered to be mutualistic that sometimes shift toward parasitism, little is known about conditions underlying shifts from parasitism toward mutualism. In lake populations, we observed that infection by a microsporidian gut symbiont sometimes conferred a reproductive advantage and other times a disadvantage to its Daphnia host. We hypothesized that the microsporidian might benefit its host by reducing infection by more virulent parasites, which attack via the gut. In a laboratory study using field-collected animals, we found that spores of a virulent fungal parasite were much less capable of penetrating the guts of Daphnia harboring the microsporidian gut symbiont. We predicted that this altered gut penetrability could cause differential impacts on host fitness depending on ecological context. Field survey data revealed that microsporidian-infected Daphnia hosts experienced a reproductive advantage when virulent parasites were common while resource scarcity led to a reproductive disadvantage, but only in lakes where virulent parasites were relatively rare. Our findings highlight the importance of considering multiparasite community context and resource availability in host-parasite studies and open the door for future research into conditions driving shifts along parasitism to mutualism gradients.

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.

Chagas Disease: Chronic Chagas Cardiomyopathy.

Chagas disease (CD) is a tropical vector-borne infection caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), also known as American Trypanosomiasis. It is considered endemic in all South and Central America and in this past decades its becoming a burden particularly in the United States and Europe due to human migration. The vast majority of patients during the acute phase are asymptomatic, while chronic symptomatic phase appears years later, with around 30% progressing toward detectable organ damage affecting mainly the cardiovascular and digestive systems. Chagas cardiomyopathy is the leading cause of nonischemic cardiomyopathy (NICM) in Latin America and affects around 30% of infected patients. The foremost characteristics are a diffuse myocarditis with focal fibrosis, mainly located in the apex and basal segments of the posterior and inferior wall, leading to a highly arrhythmogenic disease. Treatment can be etiologic during the parasitic infection, without and established efficacy during the advanced chronic symptomatic phase. Chronic Chagas cardiomyopathy treatment consists in guided medical therapy for non-ischemic cardiomyopathy, but more studies are imperative to improve clinical outcomes, some of them already in progress, and hopefully soon refine treatment and recommendations.

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.

Cardiovascular effects of preeclampsia.

PURPOSE OF REVIEW: Preeclampsia complicates 3-5% of first and 15% of subsequent pregnancies. This study reviews the evidence of increase cardiovascular risk in these women. RECENT FINDINGS: Women with preeclampsia are at two-fold higher risk for development of coronary artery disease, stroke and death, and four-fold increased risk of heart failure. Preeclampsia developed in early part of pregnancy confers greater risk than later in pregnancy. Common factors that predispose women to preeclampsia also confer high risk for developing cardiovascular disease include obesity, metabolic abnormalities, dyslipidaemia, insulin resistance, heightened inflammatory responses, hypercoagulable states and endothelia dysfunction. SUMMARY: Patients with preeclampsia should be screened at regular intervals by a preventive cardiologist and treated accordingly.