Parasite Exposure Research Articles

The fast-food effect: costs of being a generalist in a human-dominated landscape.

Agricultural expansion in Southeast Asia has converted most natural landscapes into mosaics of forest interspersed with plantations, dominated by the presence of generalist species that benefit from resource predictability. Dietary shifts, however, can result in metabolic alterations and the exposure of new parasites that can impact animal fitness and population survival. Our study focuses on the Asian water monitor lizard (Varanus salvator), one of the largest predators in the Asian wetlands, as a model species to understand the health consequences of living in a human-dominated landscape in Sabah, Malaysian Borneo. We evaluated the effects of dietary diversity on the metabolism of monitor lizards and the impact on the composition of their parasite communities in an oil palm-dominated landscape. Our results showed that (1) rodent-dominated diets were associated with high levels of lipids, proteins and electrolytes, akin to a fast-food-based diet of little representativeness of the full nutritional requirements, but highly available, and (2) lizards feeding on diverse diets hosted more diverse parasite communities, however, at overall lower parasite prevalence. Furthermore, we observed that the effect of diet on lipid concentration differed depending on the size of individual home ranges, suggesting that sedentarism plays an important role in the accumulation of cholesterol and triglycerides. Parasite communities were also affected by a homogeneous dietary behaviour, as well as by habitat type. Dietary diversity had a negative effect on both parasite richness and prevalence in plantations, but not in forested areas. Our study indicates that human-dominated landscapes can pose a negative effect on generalist species and hints to the unforeseen health consequences for more vulnerable taxa using the same landscapes. Thus, it highlights the potential role of such a widely distributed generalist as model species to monitor physiological effects in the ecosystem in an oil palm-dominated landscape.

Land snails can trap trematode cercariae in their shell: Encapsulation as a general response against parasites?

Terrestrial gastropods are hosts of a wide variety of metazoan parasites and can respond to parasite exposure in various ways. One of these defence mechanisms, the ability to trap parasites in the host shell, was previously thought to apply only against nematodes. During a field survey along an urbanisation gradient, we found that the shell of Cornu aspersum and Cepaea nemoralis can contain encapsulated trematode cercariae, with prevalences of 7% and 1%, respectively over the entire sample, and up to 47% at the local population level. To our knowledge, this is the first case study unambiguously showing that land snails can trap non-nematode parasites in their shell at non-negligible prevalences. Shell-encapsulation could be a more general defence mechanism than previously described, and more studies are needed to understand its importance and variability.

Brain‐infecting parasites leave lasting effects on behaviour even in resistant hosts

Abstract Parasites can have profound effects on intra‐ and interspecific interactions at the population and community levels through their influence on host behaviour, physiology and fitness. While host phenotypic changes are typically thought of in terms of established infections, parasite encounters may be sufficient to induce behavioural changes, even when no viable infections are established. Here, we use the Japanese rice fish medaka Oryzias latipes and the brain‐infecting microsporidan parasite Pseudoloma neurophilia to understand how parasite resistance influences behaviour. Although a previous study suggested that medaka are a suitable host for P. neurophilia, an eight‐week parasite exposure regime resulted in no detectable infection in our study. Both parasite‐exposed and control (no parasite exposure) medaka were tested in behavioural assays that assessed boldness, activity and sociality. We detected considerable changes in medaka behaviour following parasite exposure, with parasite‐exposed fish being more active, less bold and more social when compared to control fish. These data indicate that parasite encounters may induce behavioural alterations even in non‐susceptible hosts. In addition to established infection, individual differences in parasite exposure must also be considered in studies of host responses across ecological scales. Read the free Plain Language Summary for this article on the Journal blog.

Moving beyond standard toxicological metrics: The effect of diclofenac on planktonic host-parasite interactions

Pharmaceuticals are increasingly released into surface waters and therefore ubiquitous in aquatic systems. While pharmaceuticals are known to influence species interactions, their effect on host-parasite interactions is still underexplored despite potential ecosystem-level consequences. Here, we ask whether diclofenac, a widely used non-steroid anti-inflammatory drug, affects the interaction between a phytoplankton host (Staurastrum sp.; green alga) and its obligate fungal parasite (Staurastromyces oculus; chytrid fungus). We hypothesized that the effect of increasing diclofenac concentration on the host-parasite system depends on parasite exposure. We assessed acute and chronic effects of a wide range of diclofenac concentrations (0–150 mg/L) on host and parasite performance using a replicated long gradient design in batch cultures. Overall system response summarizing parameters related to all biotic components in an experimental unit i.e., number of bacteria and phytoplankton host cells along with photosynthetic yield (a measure of algal cell fitness), depended on diclofenac concentration and presence/absence of parasite. While host standing biomass decreased at diclofenac concentrations >10 mg/L in non-parasite-exposed treatments, it increased at ≥10 mg/L in parasite-exposed treatments since losses due to infection declined. During acute phase (0–48 h), diclofenac concentrations <0.1 mg/L had no effect on host net-production neither in parasite-exposed nor non-parasite-exposed treatments, but parasite infection ceased at 10 mg/L. During chronic phase (0–216 h), host net-production declined only at concentrations >10 mg/L in non-parasite-exposed cultures, while it was overall close to zero in parasite-exposed cultures. Our results suggest that chytrid parasites are more sensitive to diclofenac than their host, allowing a window of opportunity for growth of phytoplankton hosts, despite exposure to a parasite. Our work provides a first understanding about effects of a pharmaceutical on a host-parasite interaction beyond those defined by standard toxicological metrics.

Can predators stabilize host-parasite interactions? Changes in aquatic predator identity alter amphibian responses and parasite abundance across life stages.

The role of parasites can change depending on the food web community. Predators, for instance, can amplify or dilute parasite effects on their hosts. Likewise, exposure to parasites or predators at one life stage can have long-term consequences on individual performance and survival, which can influence population and disease dynamics. To understand how predators affect amphibian parasite infections across life stages, we manipulated exposure of northern leopard frog (Rana pipiens) tadpoles to three predators (crayfish [Orconectes rusticus], bluegill [Lepomis macrochirus], or mosquitofish [Gambusia affinis]) and to trematode parasites (Echinostoma spp.) in mesocosms and followed juveniles in outdoor terrestrial enclosures through overwintering. Parasites and predators both had strong impacts on metamorphosis with bluegill and parasites individually reducing metamorph survival. However, when fish were present, the negative effects of parasites on survival was not apparent, likely because fish altered community composition via increased algal food resources. Bluegill also reduced snail abundance, which could explain reduced abundance of parasites in surviving metamorphs. Bluegill and parasite exposure increased mass at metamorphosis, which increased metamorph jumping, swimming, and feeding performance, suggesting that larger frogs would experience better terrestrial survival. Effects on size at metamorphosis persisted in the terrestrial environment but did not influence overwintering survival. Based on our results, we constructed stage-structured population models to evaluate the lethal and sublethal effects of bluegill and parasites on population dynamics. Our models suggested that positive effects of bluegill and parasites on body size may have greater effects on population growth than the direct effects of mortality. This study illustrates how predators can alter the outcome of parasitic infections and highlights the need for long-term experiments that investigate how changes in host-parasite systems alter population dynamics. We show that some predators reduce parasite effects and have indirect positive effects on surviving individuals potentially increasing host population persistence.

Sterile protection against relapsing malaria with a single-shot vaccine

Vaccine development for Plasmodium vivax, an important human relapsing malaria, is lagging behind. In the case of the most deadly human malaria P. falciparum, unprecedented high levels of protection have been obtained by immunization with live sporozoites under accompanying chemoprophylaxis, which prevents the onset of blood-stage malaria. Such an approach has not been fully evaluated for relapsing malaria. Here, in the P. cynomolgi-rhesus macaque model for relapsing malaria, we employ the parasites’ natural relapsing phenotype to self-boost the immune response against liver-stage parasites, following a single-shot high-dose live sporozoite vaccination. This approach resulted in sterile protection against homologous sporozoite challenge in three out of four animals in the group that was also exposed for several days to blood stages during primary infection and relapses. One out of four animals in the group that received continuous chemoprophylaxis to abort blood-stage exposure was also protected from sporozoite challenge. Although obtained in a small number of animals as part of a Proof-of-Concept study, these results suggest that limited blood-stage parasite exposure may augment protection in this model. We anticipate our data are a starting point for further research into correlates of protection and extrapolation of the single-shot approach to develop efficacious malaria vaccines against relapsing human malaria.

Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure.

Assessment of serological Plasmodium falciparum–specific antibodies in highly endemic areas provides valuable information about malaria status and parasite exposure in the population. Although serological evidence of Plasmodium exposure is commonly determined by Plasmodium-specific immunoglobulin G (IgG) levels; IgM and IgA are likely markers of malaria status that remain relatively unexplored. Previous studies on IgM and IgA responses have been based on their affinity for single antigens with shortage of immune responses analysis against the whole Plasmodium proteome. Here, we provide evidence of how P. falciparum infection triggers the production of specific IgM and IgA in plasma and its relationship with parasite density and changes in hematological parameters. A total of 201 individuals attending a hospital in Breman Asikuma, Ghana, were recruited into this study. Total and P. falciparum–specific IgM, IgA, and IgG were assessed by ELISA and examined in relation to age (0–5, 14–49, and ≥50 age ranges); infection (submicroscopic vs. microscopic malaria); pregnancy and hematological parameters. Well-known IgG response was used as baseline control. P. falciparum–specific IgM and IgA levels increased in the population with the age, similarly to IgG. These data confirm that acquired humoral immunity develops by repeated infections through the years endorsing IgM and IgA as exposure markers in endemic malaria regions. High levels of specific IgA and IgM in children were associated with microscopic malaria and worse prognosis, because most of them showed severe anemia. This new finding shows that IgM and IgA may be used as diagnostic markers in this age group. We also found an extremely high prevalence of submicroscopic malaria (46.27% on average) accompanied by IgM and IgA levels indistinguishable from those of uninfected individuals. These data, together with the observed lack of sensitivity of rapid diagnostic tests (RDTs) compared to PCR, invoke the urgent need to implement diagnostic markers for submicroscopic malaria. Overall, this study opens the potential use of P. falciparum–specific IgM and IgA as new serological markers to predict malaria status in children and parasite exposure in endemic populations. The difficulties in finding markers of submicroscopic malaria are highlighted, emphasizing the need to explore this field in depth.

Serologic and Cytokine Profiles of Children with Concurrent Cerebral Malaria and Severe Malarial Anemia Are Distinct from Other Subtypes of Severe Malaria.

We used a protein microarray featuring Plasmodium falciparum field variants of a merozoite surface antigen to examine malaria exposure in Malian children with different severe malaria syndromes. Unlike children with cerebral malaria alone or severe malarial anemia alone, those with concurrent cerebral malaria and severe malarial anemia had serologic responses demonstrating a broader prior parasite exposure pattern than matched controls with uncomplicated disease. Comparison of levels of malaria-related cytokines revealed that children with the concurrent phenotype had elevated levels of interleukin (IL)-6, IL-8, and IL-10. Our results suggest that the pathophysiology of this severe subtype is unique and merits further investigation.

Chronic Chagas Disease-the Potential Role of Reinfections in Cardiomyopathy Pathogenesis.

Chagas disease is a neglected anthropozoonosis of global importance with significant cardiovascular-associated mortality. This review focuses on the Trypanosoma cruzi reinfections' role in chronic Chagas cardiomyopathy pathogenesis. We discuss and summarize the available data related to pathology, pathogenesis, diagnosis, and treatment of reinfections. Reinfections influence the genetic and regional diversity of T. cruzi, tissue tropism, modulation of the host's immune system response, clinical manifestations, the risk for congenital infections, differences in diagnostics performances, response to antiparasitic therapy, and the natural history of the disease. Animal models suggest that reinfections lead to worse outcomes and increased mortality, while other studies showed an association between reinfections and lower parasitemia levels and subsequent infection protection. In some regions, the human risk of reinfections is 14% at 5years. Evidence has shown that higher anti-T. cruzi antibodies are correlated with an increased rate of cardiomyopathy and death, suggesting that a higher parasite exposure related to reinfections may lead to worse outcomes. Based on the existing literature, reinfections may play a role in developing and exacerbating chronic Chagas cardiomyopathy and are linked to worse outcomes. Control efforts should be redirected to interventions that address structural poverty for the successful and sustainable prevention of Chagas disease.

The influence of biological, epidemiological, and treatment factors on the establishment and spread of drug-resistant Plasmodium falciparum.

The effectiveness of artemisinin-based combination therapies (ACTs) to treat Plasmodium falciparum malaria is threatened by resistance. The complex interplay between sources of selective pressure-treatment properties, biological factors, transmission intensity, and access to treatment-obscures understanding how, when, and why resistance establishes and spreads across different locations. We developed a disease modelling approach with emulator-based global sensitivity analysis to systematically quantify which of these factors drive establishment and spread of drug resistance. Drug resistance was more likely to evolve in low transmission settings due to the lower levels of (i) immunity and (ii) within-host competition between genotypes. Spread of parasites resistant to artemisinin partner drugs depended on the period of low drug concentration (known as the selection window). Spread of partial artemisinin resistance was slowed with prolonged parasite exposure to artemisinin derivatives and accelerated when the parasite was also resistant to the partner drug. Thus, to slow the spread of partial artemisinin resistance, molecular surveillance should be supported to detect resistance to partner drugs and to change ACTs accordingly. Furthermore, implementing more sustainable artemisinin-based therapies will require extending parasite exposure to artemisinin derivatives, and mitigating the selection windows of partner drugs, which could be achieved by including an additional long-acting drug.

Contrasting haemoparasite prevalence in larid species with divergent ecological niches and migration patterns.

Haemoparasites represent a diverse group of vector-borne parasites that infect a wide range of vertebrate hosts. In birds, haemoparasite infection rates may be associated with various ecological and life history traits, including habitat choice, colony size and migration distance. Here, we molecularly assessed the prevalence of 3 main haemoparasite genera (Plasmodium, Haemoproteus and Leucocytozoon) in 2 bird species with different habitat preferences and migratory behaviour: black-headed gulls (Chroicocephalus ridibundus) and common terns (Sterna hirundo). We found that gulls showed a much higher prevalence and diversity of Plasmodium or Haemoproteus (ca. 60% of individuals infected) than terns (zero prevalence). The prevalence of Leucocytozoon was low in both species (<3%). The differences in haemoparasite prevalences may be primarily driven by varying vector encounter rate resulting from different habitat preferences, as black-headed gulls mainly use vector-rich vegetated freshwater habitats, whereas common terns often use vector-poor coastal and brackish habitats. Since common terns migrate further than black-headed gulls, our results did not provide support for an association between haemoparasite prevalence and migratory distance. In gulls, we found a negative association between colony size and infection rates, suggestive of an ideal despotic distribution, and phylogenetic analyses of detected haemoparasite lineages provided evidence for higher host specificity in Haemoproteus than Plasmodium. Our results suggest that the preference for coastal areas and less vegetated habitats in terns may reduce haemoparasite infection rates compared to other larids, regardless of their migratory distance, emphasizing the role of ecological niches in parasite exposure.

Praziquantel Reduces Maternal Mortality and Offspring Morbidity by Enhancing Anti-Helminthic Immune Responses.

Alongside the wide distribution throughout sub Saharan Africa of schistosomiasis, the morbidity associated with this chronic parasitic disease in endemic regions is often coupled with infection-driven immunomodulatory processes which modify inflammatory responses. Early life parasite exposure is theorized to drive immune tolerance towards cognate infection as well as bystander immune responses, beginning with in utero exposure to maternal infection. Considering that 40 million women of childbearing-age are at risk of infection worldwide, treatment with Praziquantel during pregnancy as currently recommended by WHO could have significant impact on disease outcomes in these populations. Here, we describe the effects of anthelminthic treatment on parasite-induced changes to fetomaternal cross talk in a murine model of maternal schistosomiasis. Praziquantel administration immediately prior to mating lead to clear re-awakening of maternal anti-parasite immune responses, with persistent maternal immune activation that included enhanced anti-schistosome cytokine responses. Clearance of parasites also improved capacity of dams to endure the additional pressure of pregnancy during infection. Maternal treatment also drove lasting functional alterations to immune system development of exposed offspring. Prenatal anthelminthic treatment skewed offspring immune responses towards parasite clearance and reduced morbidity during cognate infection. Maternal treatment also restored offspring protective IgE antibody responses directed against schistosome antigens, which were otherwise suppressed following exposure to untreated maternal infection. This was further associated with enhanced anti-schistosome cytokine responses from treatment-exposed offspring during infection. In the absence of cognate infection, exposed offspring further demonstrated imprinting across cellular populations. We provide further evidence that maternal treatment can restore a more normalized immune profile to such offspring exposed in utero to parasite infection, particularly in B cell populations, which may underlie improved responsiveness to cognate infection, and support the WHO recommendation of anthelminthic treatment during pregnancy.

Exploring biocultural determinants of intestinal health: Do resource access and parasite exposure contribute to intestinal inflammation among a preliminary sample of children in rural Mississippi?

AbstractObjectivesBiocultural perspectives combining methods and theories from biological and cultural anthropology are needed to better understand socioeconomic and race‐based health inequities in the United States. For example, the developmental trajectories of gastrointestinal health disparities based on embodied (i.e., internalized) inequities in resource access and environmental pathogen exposure are poorly understood. Here, we present a preliminary exploration of these relationships among 20 children (aged 3–14 years) from 12 families living in a low‐resource, predominantly Black, rural Mississippi community.MethodsRelationships between fecal calprotectin levels (FC; biomarker of intestinal inflammation measured from stool samples), BMI‐for‐age/Height‐for‐age z‐scores (calculated from standard anthropometric measures), household income/size (from parent interviews), and parasitic worm (helminth) infection status (detected in stool samples by 18 s rRNA gene amplification/sequencing) were tested using bootstrap linear regression and ANOVA/ANCOVA tests.ResultsAbout 80% of sampled children had clinically elevated FC (&gt; 50 μg/g). BMI z‐scores (95%CI = −154.63; −7.34) and household income (95%CI = −135.90; −16.44) were negatively associated with FC levels. Household size was positively associated with FC levels (95%CI = 4.65, 101.61). Helminth infections were detected (n = 6), with positive associations between infection and the FC level (p &lt; 0.05) that were likely driven by two infected children with very high FC levels.ConclusionThe high levels of intestinal inflammation in this small sample of children suggest that gastrointestinal health disparities may appear in childhood. We explore how these disparities may be related to inequities in environmental exposures, nutritional and socioeconomic status, and barriers to medical care and resource access.

Beyond single host, single parasite interactions: Quantifying competence for complete multi‐host, multi‐parasite communities

Abstract Understanding parasite transmission in communities requires knowledge of each species' capacity to support transmission. This property, ‘competence’, is a critical currency for modelling transmission under community change and for testing diversity–disease theory. Despite the central role of competence in disease ecology, we lack a clear understanding of the factors that generate competence and drive its variation. We developed novel conceptual and quantitative approaches to systematically quantify competence for a multi‐host, multi‐parasite community. We applied our framework to an extensive dataset: five amphibian host species exposed to four parasitic trematode species across five ecologically realistic exposure doses. Together, this experimental design captured 20 host–parasite interactions while integrating important information on variation in parasite exposure. Using experimental infection assays, we measured multiple components of the infection process and combined them to produce competence estimates for each interaction. With directly estimated competence values, we asked which components of the infection process best explained variation in competence: barrier resistance (the initial fraction of administered parasites blocked from infecting a host), internal clearance (the fraction of established parasites lost over time) or pre‐transmission mortality (the probability of host death prior to transmission). We found that variation in competence among the 20 interactions was best explained by differences in barrier resistance and pre‐transmission mortality, underscoring the importance of host resistance and parasite pathogenicity in shaping competence. We also produced dose‐integrated estimates of competence that incorporated natural variation in exposure to address questions on the basis and extent of variation in competence. We found strong signals that host species identity shaped competence variation (as opposed to parasite species identity). While variation in infection outcomes across hosts, parasites, individuals and doses was considerable, individual heterogeneity was limited compared to among‐species differences. This finding highlights the robustness of our competence estimates and suggests that species‐level values may be strong predictors for community‐level transmission in natural systems. Competence emerges from distinct underlying processes and can have strong species‐level characteristics; thus, this property has great potential for linking mechanisms of infection to epidemiological patterns. Read the free Plain Language Summary for this article on the Journal blog.

Sensitivity and specificity for malaria classification of febrile persons by rapid diagnostic test, microscopy, parasite DNA, histidine-rich protein 2, and IgG: Dakar, Senegal 2015

ObjectivesDifferent methods for detecting Plasmodium parasite infection or exposure are available, but a systematic comparison of all these methodologies to predict malaria infection is lacking. Understanding the characteristics of respective tests is helpful in choosing the most appropriate tests for epidemiological or research purposes. MethodsWe performed microscopy, rapid diagnostic tests (RDTs), and polymerase chain reaction (PCR) for 496 patients presenting with febrile illness in Dakar, Senegal, in 2015. Blood samples had laboratory multiplex assays performed for Immunoglobin G serology and detection of histidine-rich protein 2 (HRP2) antigen. Sensitivity (Se) and specificity (Sp) for different tests were calculated using PCR as the gold standard for detecting active infection. Modeling through latent class analysis compared each test to a modeled gold standard for Se/Sp estimates. ResultsAgainst PCR, Se/Sp were 95.2%/93.7% for RDT, 90.4%/100.0% for microscopy, and 97.9%/48.1% for laboratory HRP2 detection. Compared with the modeled gold standard, Se of microscopy was 93.5% and Se of RDT, PCR, and laboratory HRP2 detection were all greater than 99%. Se/Sp of Immunoglobin G serology were substantially lower for detecting active infection. ConclusionsCompared with single tests, a combinatorial latent class analysis approach of multiple biomarkers for detecting malaria infection from patient samples provides greater sensitivity and specificity for epidemiological estimates and research objectives.

Divergent water requirements partition exposure risk to parasites in wild equids.

For grazing herbivores, dung density in feeding areas is an important determinant of exposure risk to fecal‐orally transmitted parasites. When host species share the same parasite species, a nonrandom distribution of their cumulative dung density and/or nonrandom ranging and feeding behavior may skew exposure risk and the relative selection pressure parasites impose on each host. The arid‐adapted Grevy's zebra (Equus grevyi) can range more widely than the water‐dependent plains zebra (Equus quagga), with which it shares the same species of gastrointestinal nematodes. We studied how the spatial distribution of zebra dung relates to ranging and feeding behavior to assess parasite exposure risk in Grevy's and plains zebras at a site inhabited by both zebra species. We found that zebra dung density declined with distance from water, Grevy's zebra home ranges (excluding those of territorial males) were farther from water than those of plains zebras, and plains zebra grazing areas had higher dung density than random points while Grevy's zebra grazing areas did not, suggesting a greater exposure risk in plains zebras associated with their water dependence. Fecal egg counts increased with home range proximity to water for both species, but the response was stronger in plains zebras, indicating that this host species may be particularly vulnerable to the elevated exposure risk close to water. We further ran experiments on microclimatic effects on dung infectivity and showed that fewer nematode eggs embryonated in dung in the sun than in the shade. However, only 5% of the zebra dung on the landscape was in shade, indicating that the microclimatic effects of shade on the density of infective larvae is not a major influence on exposure risk dynamics. Ranging constraints based on water requirements appear to be key mediators of nematode parasite exposure in free‐ranging equids.

Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response

BackgroundIndividuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought to assess the controlled human malaria infection (CHMI) model as a means of studying naturally acquired immunity in Kenyan adults with varying malaria exposure.MethodsWe analysed data from 142 Kenyan adults from three locations representing distinct areas of malaria endemicity (Ahero, Kilifi North and Kilifi South) enrolled in a CHMI study with Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify the in vivo outcomes that most closely reflected naturally acquired immunity, parameters based on qPCR measurements were compared with anti-schizont antibody levels and residence as proxy markers of naturally acquired immunity.ResultsTime to endpoint correlated more closely with anti-schizont antibodies and location of residence than other parasite parameters such as growth rate or mean parasite density. Compared to observational field-based studies in children where 0.8% of the variability in malaria outcome was observed to be explained by anti-schizont antibodies, in the CHMI model the dichotomized anti-schizont antibodies explained 17% of the variability.ConclusionsThe CHMI model is highly effective in studying markers of naturally acquired immunity to malaria.Trial registration Clinicaltrials.gov number NCT02739763. Registered 15 April 2016

Is overwintering mortality driving enigmatic declines? Evaluating the impacts of trematodes and the amphibian chytrid fungus on an anuran from hatching through overwintering.

Emerging infectious diseases are increasing globally and are an additional challenge to species dealing with native parasites and pathogens. Therefore, understanding the combined effects of infectious agents on hosts is important for species' conservation and population management. Amphibians are hosts to many parasites and pathogens, including endemic trematode flatworms (e.g., Echinostoma spp.) and the novel pathogenic amphibian chytrid fungus (Batrachochytrium dendrobatidis [Bd]). Our study examined how exposure to trematodes during larval development influenced the consequences of Bd pathogen exposure through critical life events. We found that prior exposure to trematode parasites negatively impacted metamorphosis but did not influence the effect of Bd infection on terrestrial growth and survival. Bd infection alone, however, resulted in significant mortality during overwintering-an annual occurrence for most temperate amphibians. The results of our study indicated overwintering mortality from Bd could provide an explanation for enigmatic declines and highlights the importance of examining the long-term consequences of novel parasite exposure.

A meta-analysis of impacts of immune response and infection on oxidative status in vertebrates.

Inferring from patterns observed in biomedical research, ecoimmunological theory predicts that oxidative stress is a ubiquitous physiological cost that contributes to generating variation in immune function between individuals or species. This prediction is, however, often challenged by empirical studies testing the relationship between immune response or infection and oxidative status markers. This points out the importance of combining ecological immunology and oxidative stress ecology to further our understanding of the proximate causes and fitness consequences of individual variation in health, and adaptability to natural and anthropogenic environmental changes. I reviewed evidence and performed phylogenetic meta-analyses of changes in oxidative status markers owing to either injection of an antigen or infection in captive and free-living vertebrates (141 studies, 1262 effect sizes, 97 species). The dataset was dominated by studies on fish, birds and mammals, which provided 95.8% of effect sizes. Both antigen injection and parasite exposure were associated with changes of oxidative status. There were significant effects of taxonomic class and experimental environment (captivity vs. wild). In contrast with my predictions, age category (young vs. adult), study design (correlational vs. experimental) and proxies of pace of life (clutch size, litter size, and body mass; for birds and mammals only) were negligible in this dataset. Several methodological aspects (type of immunostimulant, laboratory assay, tissue analysed) showed significant effects on both strength and direction of effect. My results suggest that alterations of oxidative status are a widespread consequence of immune function across vertebrates. However, this work also identified heterogeneity in strength and direction of effect sizes, which suggests that immune function does not necessarily result in oxidative stress. Finally, this work identifies methodological caveats that might be relevant for the interpretation and comparability of results and for the application in conservation programs.

Qiviut cortisol is associated with metrics of health and other intrinsic and extrinsic factors in wild muskoxen (Ovibos moschatus).

Glucocorticoid (GC) levels are increasingly and widely used as biomarkers of hypothalamic–pituitary–adrenal (HPA) axis activity to study the effects of environmental changes and other perturbations on wildlife individuals and populations. However, identifying the intrinsic and extrinsic factors that influence GC levels is a key step in endocrinology studies to ensure accurate interpretation of GC responses. In muskoxen, qiviut (fine woolly undercoat hair) cortisol concentration is an integrative biomarker of HPA axis activity over the course of the hair’s growth. We gathered data from 219 wild muskoxen harvested in the Canadian Arctic between October 2015 and May 2019. We examined the relationship between qiviut cortisol and various intrinsic (sex, age, body condition and incisor breakage) and extrinsic biotic factors (lungworm and gastrointestinal parasite infections and exposure to bacteria), as well as broader non-specific landscape and temporal features (geographical location, season and year). A Bayesian approach, which allows for the joint estimation of missing values in the data and model parameters estimates, was applied for the statistical analyses. The main findings include the following: (i) higher qiviut cortisol levels in males than in females; (ii) inter-annual variations; (iii) higher qiviut cortisol levels in a declining population compared to a stable population; (iv) a negative association between qiviut cortisol and marrow fat percentage; (v) a relationship between qiviut cortisol and the infection intensity of the lungworm Umingmakstrongylus pallikuukensis, which varied depending on the geographical location; and (vi) no association between qiviut cortisol and other pathogen exposure/infection intensity metrics. This study confirmed and further identified important sources of variability in qiviut cortisol levels, while providing important insights on the relationship between GC levels and pathogen exposure/infection intensity. Results support the use of qiviut cortisol as a tool to monitor temporal changes in HPA axis activity at a population level and to inform management and conservation actions.