Cooperation for malaria control and elimination in the Guiana Shield.

The Guiana Shield, a small region of South America, is currently one of the main hotspots of malaria transmission on the continent. This Amazonian area is characterised by remarkable socioeconomic, cultural, health, and political heterogeneity and a high degree of regional and cross-border population mobility, which has contributed to the increase of malaria in the region in the past few years. In this context, regional cooperation to control malaria represents both a challenge and an indispensable initiative. This Viewpoint advocates for the creation of a regional cooperative mechanism for the elimination of malaria in the Guiana Shield. This strategy would help address operational and political obstacles to successful technical cooperation in the region and could contribute to reversing the regional upsurge in malaria incidence through creating a functional international control and elimination partnership.

Immunogenetic heterogeneity in a widespread ungulate: the European roe deer (Capreolus capreolus).

Understanding how immune genetic variation is shaped by selective and neutral processes in wild populations is of prime importance in both evolutionary biology and epidemiology. The European roe deer (Capreolus capreolus) has considerably expanded its distribution range these last decades, notably by colonizing agricultural landscapes. This range shift is likely to have led to bottlenecks and increased roe deer exposure to a new range of pathogens that until recently predominantly infected humans and domestic fauna. We therefore investigated the historical and contemporary forces that have shaped variability in a panel of genes involved in innate and acquired immunity in roe deer, including Mhc-Drb and genes encoding cytokines or toll-like receptors (TLRs). Together, our results suggest that genetic drift is the main contemporary evolutionary force shaping immunogenetic variation within populations. However, in contrast to the classical view, we found that some innate immune genes involved in micropathogen recognition (e.g. Tlrs) continue to evolve dynamically in roe deer in response to pathogen-mediated positive selection. Most studied Tlrs (Tlr2, Tlr4 and Tlr5) had similarly high levels of amino acid diversity in the three studied populations including one recently established in southwestern France that showed a clear signature of genetic bottleneck. Tlr2 implicated in the recognition of Gram-positive bacteria in domestic ungulates, showed strong evidence of balancing selection. The high immunogenetic variation revealed here implies that roe deer are able to cope with a wide spectrum of pathogens and to respond rapidly to emerging infectious diseases.

Disentangling direct and growth-mediated influences on early survival: a mechanistic approach.

1. Early survival is a key life-history trait that often accounts for a large part of the variation in individual fitness and shapes population dynamics. The factors influencing early survival are multiple in large herbivores, including malnutrition, predation, cohort variation or maternal effects. However, the mechanistic pathways connecting these drivers to variation in early survival are much less studied. Indeed, whether these factors influence early survival directly or indirectly through early growth remains to be disentangled. 2. In this study, we used a path analysis to separate the direct and indirect (i.e. mediated by early growth) pathways through which sex, birth date, cohort and family effects influence early survival. We used a large data set of marked roe deer newborns collected from 1985 to 2010 in the intensively monitored population of Trois Fontaines (France). 3. We found that most drivers have indirect influences on early survival through early growth. Indeed, cohort effects influenced early survival through the indirect effect of precipitation around birth on early growth. Precipitation also had direct effects on early survival. Family effects indirectly influenced early survival. Twins from the same litter grew at about the same rate, so they had the same fate. Moreover, some factors, such as birth date, had both direct and indirect effects on roe deer early survival, with fawns born early in the season benefiting from high early survival both because they have more time to grow before the harsh season and because they grow faster during their first days of life than late-born fawns. 4. These findings suggest that most drivers of early survival previously identified in large mammalian herbivores may affect early survival primarily through their influence on early growth. Disentangling the direct and indirect pathways by which different factors influence early survival is of crucial importance to understand the mechanisms shaping this key component of individual fitness.

High juvenile mortality is associated with sex-specific adult survival and lifespan in wild roe deer.

Male mammals typically have shorter lifespans than females [1]. Sex differences in survival may result, in part, from sex-specific optima in investment in reproduction, with higher male mortality rates from sexual competition selecting for a "live-fast die-young" strategy in this sex [2]. In the wild, lifespan is also influenced by environmental conditions experienced early in life. Poor conditions elevate juvenile mortality, which may selectively remove individuals with a particular phenotype or genotype from a cohort [3], and can alter the subsequent phenotypic condition and fate of those that survive to adulthood [4]. Males and females can respond differently to the same early-life environmental experiences [5, 6], but whether such environmental pressures generate sex differences in lifespan has rarely been considered. We show that sex differences in adult survival and lifespan in cohorts of roe deer (Capreolus capreolus) range from virtually absent in some years to females living 30% longer than males in others. The extent of this sex difference in adult longevity is strongly linked to the level of mortality each cohort experiences as juveniles, with high juvenile mortality generating a strong sex difference in both adult survival and lifespan. In females, high juvenile mortality leads to increased adult survival for those remaining individuals, whereas in males survival is actually reduced. Early environmental conditions and the selective pressures they impose may help to explain variability in sex-specific aging across animal taxa.

Reduced microsatellite heterozygosity does not affect natal dispersal in three contrasting roe deer populations.

Although theoretical studies have predicted a link between individual multilocus heterozygosity and dispersal, few empirical studies have investigated the effect of individual heterozygosity on dispersal propensity or distance. We investigated this link using measures of heterozygosity at 12 putatively neutral microsatellite markers and natal dispersal behaviour in three contrasting populations of European roe deer (Capreolus capreolus), a species displaying pre-saturation condition-dependent natal dispersal. We found no effect of individual heterozygosity on either dispersal propensity or dispersal distance. Average heterozygosity was similar across the three studied populations, but dispersal propensity and distance differed markedly among them. In Aurignac, dispersal propensity and distance were positively related to individual body mass, whereas there was no detectable effect of body mass on dispersal behaviour in Chizé and Trois Fontaines. We suggest that we should expect both dispersal propensity and distance to be greater when heterozygosity is lower only in those species where dispersal behaviour is driven by density-dependent competition for resources.

Fitness consequences of environmental conditions at different life stages in a long-lived vertebrate.

The predictive adaptive response (PAR) hypothesis proposes that animals adjust their physiology and developmental trajectory during early life in anticipation of their future environments. Accordingly, when environmental conditions in early life match environmental conditions during adulthood, individual fitness should be greater. Here, we test this hypothesis in a long-lived mammal, the roe deer, using data from two contrasting populations, intensively monitored for more than 35 years. In the highly productive site, the fitness of female roe deer increased with the quality of environment during adulthood and, contrary to predictions of PAR, individuals born in good conditions always outperformed those born under poor conditions. In the resource-limited site, the fitness of female roe deer born in poor years was better than those born in good conditions in poor years when the animals were adult, but not in good years. Although consistent with predictions of PAR, we showed that this pattern is likely to be a consequence of increased viability selection during the juvenile stage for animals born in poor years. While PARs are often advanced in evolutionary medicine, our findings suggest that detailed biological processes should be investigated before drawing conclusions about the existence of this phenomenon.

Toxoplasmosis in natural populations of ungulates in France: prevalence and spatiotemporal variations.

Toxoplasmosis is characterized by a complex epidemiology. The risk of infection for humans depends on their contact with infective oocysts in a contaminated environment and on the amount of tissue cysts located within consumed meat. Unfortunately, the prevalence of tissue cysts is largely unknown for game species. Although herbivorous game species are a source of infection for humans, the level of infection found in wildlife can also be used to estimate environmental contamination. The aim of this study was to estimate the prevalence of Toxoplasma gondii infection and analyze its temporal dynamics in one population of chamois (Rupicapra rupicapra), one of mouflon (Ovis gmelini musimon), and two of roe deer (Capreolus capreolus) in France, surveyed during a period of 6 to 28 years. Taking into account individual risk factors, we specifically analyzed the relationship between T. gondii prevalence and meteorological conditions that may influence oocyst survival. Serum samples from 101 chamois, 143 mouflons, and 1155 roe deer were tested for antibodies against T. gondii using the modified agglutination test (MAT), an enzyme-linked immunosorbent assay (ELISA) assay, or both. Using MAT with a threshold of 1:6, seroprevalence was 14.7% in mouflon, 16.8% in chamois, and 43.7% in roe deer. In mouflon and roe deer, seroprevalence was positively correlated with age and/or body mass, in accordance with the hypothesis that antibodies have long-term persistence. In roe deer, seropositivity differed between the two populations and changed linearly over time between 1983 and 2010, increasing by a factor 1.75 every 10 years. Moreover, in this species, the highest prevalences were found during dry and cold years or during warm and moist years, depending on the population. Our results suggest that the risk for people to acquire infection through game meat increases over time, but with high variability according to the population of origin and meteorological conditions of the year.

Relationship between CT air trapping criteria and lung function in small airway impairment quantification.

BACKGROUND: Small airways are regarded as the elective anatomic site of obstruction in most chronic airway diseases. Expiratory computed tomography (CT) is increasingly used to assess obstruction at this level but there is no consensus regarding the best quantification method. We aimed to evaluate software-assisted CT quantification of air trapping for assessing small airway obstruction and determine which CT criteria better predict small airway obstruction on single breath nitrogen test (SBNT). METHODS: Eighty-nine healthy volunteers age from 60 to 90 years old, underwent spirometrically-gated inspiratory (I) and expiratory (E) CT and pulmonary function tests (PFTs) using SBNT, performed on the same day. Air trapping was estimated using dedicated software measuring on inspiratory and expiratory CT low attenuation area (LAA) lung proportion and mean lung density (MLD). CT indexes were compared to SBNT results using the Spearman correlation coefficient and hierarchical dendrogram analysis. In addition, receiver operating characteristic (ROC) curve analysis was performed to determine the optimal CT air-trapping criterion. RESULTS: 43 of 89 subjects (48,3%) had dN2 value above the threshold defining small airway obstruction (i.e. 2.5% N2/l). Expiratory to inspiratory MLD ratio (r = 0.40) and LAA for the range -850 -1024 HU (r = 0.29) and for the range -850 -910 HU (r = 0.37) were positively correlated with SBNT results. E/I MLD was the most suitable criterion for its expression. Expiratory to inspiratory MLD ratio (E/I MLD) showed the highest AUC value (0.733) for small airway obstruction assessment. CONCLUSION: Among all CT criteria, all correlating with small airway obstruction on SBNT, E/I MLD was the most suitable criterion for its expression in asymptomatic subjects with mild small airway obstruction TRIAL REGISTRATION: Registered at Clinicaltrials.gov, identifier: NCT01230879.

Schmallenberg virus infection among red deer, France, 2010-2012.

Schmallenberg virus infection is emerging in European domestic and wild ruminants. We investigated the serologic status of 9 red deer populations to describe virus spread from September 2010 through March 2012 among wildlife in France. Deer in 7 populations exhibited seropositivity, with an average seroprevalence of 20%.

Variation in adult body mass of roe deer: early environmental conditions influence early and late body growth of females.

There is increasing evidence that environmental conditions experienced early in life can markedly affect an organism's life history, but the pathways by which early environment influences adult phenotype are poorly known. We used long-term data from two roe deer (Capreolus capreolus) populations (Chizé and Trois-Fontaines, France) to investigate the direct and indirect (operating through fawn body mass) effects of environmental conditions during early life on adult body mass. We found that environmental conditions (population size and spring temperatures) around birth influenced body mass of adult females through both direct and indirect effects in both populations. The occurrence of direct effects means that, for a given fawn body mass, adult female mass decreases with adverse conditions in early life. In contrast, we found no evidence for direct effects of early-life conditions on adult body mass of males, suggesting the existence of sex-specific long-term responses of body mass to stressful early conditions. Our results provide evidence that early environmental conditions influence the adult phenotype through persistent effects over the body development in wild mammal populations.

Intracoronary administration of darbepoetin-alpha at onset of reperfusion in acute myocardial infarction: results of the randomized Intra-Co-EpoMI trial.

BACKGROUND: Several trials investigating erythropoietin as a novel cytoprotective agent in myocardial infarction (MI) failed to translate promising preclinical results into the clinical setting. These trials could have missed crucial events occurring in the first few minutes of reperfusion. Our study differs by earlier intracoronary administration of a longer-acting erythropoietin analogue at the onset of reperfusion. AIM: To evaluate the ability of intracoronary administration of darbepoetin-alpha (DA) at the very onset of the reperfusion, to decrease infarct size (IS). METHODS: We randomly assigned 56 patients with acute ST-segment elevation MI to receive an intracoronary bolus of DA 150 µg (DA group) or normal saline (control group) at the onset of reflow obtained by primary percutaneous coronary intervention (PCI). IS and area at risk (AAR) were evaluated by biomarkers, cardiac magnetic resonance (CMR) and validated angiographical scores. RESULTS: There was no difference between groups regarding duration of ischemia, Thrombolysis in Myocardial Infarction flow grade at admission and after PCI, AAR size and extent of the collateral circulation, which are the main determinants of IS. The release of creatine kinase was not significantly different between the two groups even when adjusted to AAR size. Between 3-7 days and at 3 months, the area of hyperenhancement on CMR expressed as a percentage of the left ventricular myocardium was not significantly reduced in the DA group even when adjusted to AAR size. CONCLUSION: Early intracoronary administration of a longer-acting erythropoietin analogue in patients with acute MI at the time of reperfusion does not significantly reduce IS.

How does climate change influence demographic processes of widespread species? Lessons from the comparative analysis of contrasted populations of roe deer.

How populations respond to climate change depends on the interplay between life history, resource availability, and the intensity of the change. Roe deer are income breeders, with high levels of allocation to reproduction, and are hence strongly constrained by the availability of high quality resources during spring. We investigated how recent climate change has influenced demographic processes in two populations of this widespread species. Spring began increasingly earlier over the study, allowing us to identify 2 periods with contrasting onset of spring. Both populations grew more slowly when spring was early. As expected for a long-lived and iteroparous species, adult survival had the greatest potential impact on population growth. Using perturbation analyses, we measured the relative contribution of the demographic parameters to observed variation in population growth, both within and between periods and populations. Within periods, the identity of the critical parameter depended on the variance in growth rate, but variation in recruitment was the main driver of observed demographic change between periods of contrasting spring earliness. Our results indicate that roe deer in forest habitats cannot currently cope with increasingly early springs. We hypothesise that they should shift their distribution to richer, more heterogeneous landscapes to offset energetic requirements during the critical rearing stage.

Immune phenotype and body condition in roe deer: individuals with high body condition have different, not stronger immunity.

An efficient immunity is necessary for host survival, but entails energetic costs. When energy is limited, immunocompetence and body condition should co-vary positively among individuals and, depending on body condition, individuals should allocate more either in innate immunity or in adaptive response. We tested whether immune phenotype depends on body condition in large mammals, using data from two contrasted populations of roe deer Capreolus capreolus in France. Roe deer living at Chizé, a forest with poor habitat quality, were expected to show lower values for body condition and immune parameters than roe deer at Trois Fontaines, a forest with high habitat quality. From 285 blood samples collected between December 2009 and March 2011, we measured seven metabolic parameters and ten immunological parameters. A Principal Component Analysis showed that all indicators of body condition co-varied positively and were lowest at Chizé. Several immunological indicators correlated to body condition and differed between Trois Fontaines and Chizé. However, high body condition was not associated to a high average level of immunocompetence, but instead to high levels of indicators of acute inflammatory innate response, while low body condition was associated to high levels of monocytes and lymphocytes, possibly reflecting adaptive immunity. Limited data suggest that the difference between populations was not related to the presence of specific parasite species, however parasite exposure and stress have to be investigated to gain a more complete understanding of the determinants of immunity.

Environmental factors associated with the seroprevalence of Toxoplasma gondii in Wild Boars (Sus scrofa), France.

Toxoplasma gondii is a protozoan parasite infecting humans and animals. Wild boars Sus scrofa are a potential source of human infection and an appropriate biological model for analyzing T. gondii dynamics in the environment. Here, we aimed to identify environmental factors explaining the seroprevalence of toxoplasmosis in French wild boar populations. Considering 938 individuals sampled from 377 'communes', overall seroprevalence was 23% (95% confidence interval: [22-24]). Using a Poisson regression, we found that the number of seropositive wild boars detected per 'commune' was positively associated with the presence of European wildcats (Felis silvestris) and moderate winter temperatures.

Transarterial ethylene vinyl alcohol copolymer visualization and penetration after embolization of life-threatening hemoptysis: technical and clinical outcomes.

OBJECTIVES: This study was designed to evaluate the feasibility of using ethylene vinyl alcohol copolymer (EVAC) for bronchial artery embolization (BAE) in patients with life-threatening hemoptysis and to compare the visualization and transarterial penetration of EVAC under fluoroscopy and computed tomography (CT). METHODS: Fifteen patients (mean age, 62.9 (range, 24-82) years) who were referred for life-threatening hemoptysis (27 month period) underwent BAE using EVAC. All patients had thoracic CT examination before and after BAE. Technical and clinical results were evaluated. Visibility and extent of cast penetration (graded 1-4) on fluoroscopy and postprocedure CT were assessed and compared. RESULTS: BAE was feasible in all but one artery (due to spasm; n=27; 96.4%). No procedure-related complications or deaths were detected. Two patients had recurrent bleeding in the following day (13.3%). Immediate clinical success was achieved in 14 cases (93.3%) after reembolization of pulmonary artery pseudoaneurysm in one patient (mean follow-up, 43.5 (range, 14-148) days). Visibility of the cast was possible in 73.3% of patients (n=11) under fluoroscopy (mean cast penetration 1.66) and in all patients under CT (mean cast penetration 2.06). The postinjection fluoroscopic visibility in 6 of 15 (40%) patients was inferior to CT (P<0.02). CONCLUSIONS: BAE with EVAC seems to be feasible and safe with immediate control of hemoptysis in most patients. The postinjection fluoroscopic visibility of EVAC under fluoroscopy was inferior to CT.

Population density and phenotypic attributes influence the level of nematode parasitism in roe deer.

The impact of parasites on population dynamics is well documented, but less is known on how host population density affects parasite spread. This relationship is difficult to assess because of confounding effects of social structure, population density, and environmental conditions that lead to biased among-population comparisons. Here, we analyzed the infestation by two groups of nematodes (gastro-intestinal (GI) strongyles and Trichuris) in the roe deer (Capreolus capreolus) population of Trois Fontaines (France) between 1997 and 2007. During this period, we experimentally manipulated population density through changes in removals. Using measures collected on 297 individuals, we quantified the impact of density on parasite spread after taking into account possible influences of date, age, sex, body mass, and weather conditions. The prevalence and abundance of eggs of both parasites in females were positively related to roe deer density, except Trichuris in adult females. We also found a negative relationship between parasitism and body mass, and strong age and sex-dependent patterns of parasitism. Prime-age adults were less often parasitized and had lower fecal egg counts than fawns or old individuals, and males were more heavily and more often infected than females. Trichuris parasites were not affected by weather, whereas GI strongyles were less present after dry and hot summers. In the range of observed densities, the observed effect of density likely involves a variation of the exposure rate, as opposed to variation in host susceptibility.

No difference between the sexes in fine-scale spatial genetic structure of roe deer.

BACKGROUND: Data on spatial genetic patterns may provide information about the ecological and behavioural mechanisms underlying population structure. Indeed, social organization and dispersal patterns of species may be reflected by the pattern of genetic structure within a population. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the fine-scale spatial genetic structure of a roe deer (Capreolus capreolus) population in Trois-Fontaines (France) using 12 microsatellite loci. The roe deer is weakly polygynous and highly sedentary, and can form matrilineal clans. We show that relatedness among individuals was negatively correlated with geographic distance, indicating that spatially proximate individuals are also genetically close. More unusually for a large mammalian herbivore, the link between relatedness and distance did not differ between the sexes, which is consistent with the lack of sex-biased dispersal and the weakly polygynous mating system of roe deer. CONCLUSIONS/SIGNIFICANCE: Our results contrast with previous reports on highly polygynous species with male-biased dispersal, such as red deer, where local genetic structure was detected in females only. This divergence between species highlights the importance of socio-spatial organization in determining local genetic structure of vertebrate populations.

High red deer density depresses body mass of roe deer fawns.

Many previous studies have pointed out that, when resources are limited, the potential for competition should be high among sympatric species that display overlaps in habitat and nutritional niches. However, reliable evidence of competition between red deer (Cervus elaphus) and roe deer (Capreolus capreolus) has not been yet reported for life history traits directly measuring performance such as body mass, reproduction, or survival. From long-term monitoring of deer populations in the reserve of La Petite Pierre (France), we measured the sex-specific responses of roe deer fawn body mass to changes in red deer density after accounting for possible confounding effects of date of shooting, climatic conditions, and roe deer density. As expected under the hypothesis of competition, red deer density in a given year had a marked negative influence on body mass of roe deer fawns born the same year and the following year. Fawn mass of roe deer males and females responded in similar ways to changes in red deer density. Our study provides the first evidence of a negative response of roe deer performance to high red deer density.

Heterozygosity-fitness correlations revealed by neutral and candidate gene markers in roe deer from a long-term study.

Heterozygosity-fitness correlations (HFCs) are increasingly reported but the underlying mechanisms causing HFCs are generally poorly understood. Here, we test for HFCs in roe deer (Capreolus capreolus) using 22 neutral microsatellites widely distributed in the genome and four microsatellites in genes that are potentially under selection. Juvenile survival was used as a proxy for individual fitness in a population that has been intensively studied for 30 years in northeastern France. For 222 juveniles, we computed two measures of genetic diversity: individual heterozygosity (H), and mean d(2) (relatedness of parental genomes). We found a relationship between genetic diversity and fitness both for the 22 neutral markers and two candidate genes: IGF1 (Insulin-like Growth Factor I) and NRAMP (natural resistance-associated macrophage protein). Statistical evidence and the size of genetic effects on juvenile survival were comparable to those reported for early development and cohort variation, suggesting a substantial influence of genetic components on fitness in this roe deer population. For the 22 neutral microsatellites, a correlation with fitness was revealed for mean d(2), but not for H, suggesting a possible outbreeding advantage. This heterosis effect could have been favored by introduction of genetically distant (Hungarian) roe deer to the population in recent times and, possibly, by the structuring of the population into distinct clans. The locus-specific correlations with fitness may be driven by growth rate advantages and resistance to diseases known to exist in the studied population. Our analyses of neutral and candidate gene markers both suggest that the observed HFCs are likely mainly due to linkage with dominant or overdominant loci that affect fitness ("local" effect) rather than to a genome-wide relationship with homozygosity due to inbreeding ("general" effect).