Mapping the zoonotic niche of Marburg virus disease in Africa.

BACKGROUND: Marburg virus disease (MVD) describes a viral haemorrhagic fever responsible for a number of outbreaks across eastern and southern Africa. It is a zoonotic disease, with the Egyptian rousette (Rousettus aegyptiacus) identified as a reservoir host. Infection is suspected to result from contact between this reservoir and human populations, with occasional secondary human-to-human transmission. METHODS: Index cases of previous human outbreaks were identified and reports of infection in animals recorded. These data were modelled within a species distribution modelling framework in order to generate a probabilistic surface of zoonotic transmission potential of MVD across sub-Saharan Africa. RESULTS: Areas suitable for zoonotic transmission of MVD are predicted in 27 countries inhabited by 105 million people. Regions are suggested for exploratory surveys to better characterise the geographical distribution of the disease, as well as for directing efforts to communicate the risk of practices enhancing zoonotic contact. CONCLUSIONS: These maps can inform future contingency and preparedness strategies for MVD control, especially where secondary transmission is a risk. Coupling this risk map with patient travel histories could be used to guide the differential diagnosis of highly transmissible pathogens, enabling more rapid response to outbreaks of haemorrhagic fever

Predicting the distribution of canine leishmaniasis in western Europe based on environmental variables.

The domestic dog is the reservoir host of Leishmania infantum, the causative agent of zoonotic visceral leishmaniasis endemic in Mediterranean Europe. Targeted control requires predictive risk maps of canine leishmaniasis (CanL), which are now explored. We databased 2187 published and unpublished surveys of CanL in southern Europe. A total of 947 western surveys met inclusion criteria for analysis, including serological identification of infection (504, 369 dogs tested 1971-2006). Seroprevalence was 23 2% overall (median 10%). Logistic regression models within a GIS framework identified the main environmental predictors of CanL seroprevalence in Portugal, Spain, France and Italy, or in France alone. A 10-fold cross-validation approach determined model capacity to predict point-values of seroprevalence and the correct seroprevalence class (20%). Both the four-country and France-only models performed reasonably well for predicting correctly the 20% seroprevalence classes (AUC >0 70). However, the France-only model performed much better for France than the four-country model. The four-country model adequately predicted regions of CanL emergence in northern Italy (<5% seroprevalence). Both models poorly predicted intermediate point seroprevalences (5-20%) within regional foci, because surveys were biased towards known rural foci and Mediterranean bioclimates. Our recommendations for standardizing surveys would permit higher-resolution risk mapping

The Role of Histone Methylation and H2A.Z Occupancy during Rapid Activation of Ethylene Responsive Genes

Ethylene signaling pathway leads to rapid gene activation by two hierarchies of transcription factors with EIN3/EIL proteins as primary ones and ERF proteins as secondary ones. The role of chromatin modifications during the rapid gene activation is not known. In this work we studied trimethylated histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3), two opposite histone methylation marks for gene activity, during the induction course of three ethylene-responsive genes (ERF1, AtERF14 and ChiB). We found that the three genes displayed different histone modification profiles before induction. After induction, H3K4me3 was increased in the 5′ region and the gene body of ERF1, while H3K27me3 was decreased in the promoter of AtERF14. But the modification changes were later than the gene activation. Analysis of other rapidly inducible ERF genes confirmed the observation. In addition, histone H2A.Z occupancy on the three genes and the association of the H3K27me3-binding protein LHP1 with AtERF14 and ChiB were not affected by the inductive signal. However, the mutation of genes encoding H2A.Z and LHP1 attenuated and enhanced respectively the induction of target genes and altered H3K4me3. These results indicate that the induction of ethylene-responsive genes does not require immediate modulation of H3K4me3 and H3K27me3 and dissociation of LHP1 and H2A.Z from the targets, and suggest that the chromatin structure of the genes before induction is committed for transcriptional activation and that H3K4me3 is not required for ethylene-responsive gene activation, but may serve as a mark for gene activity

Control of Flowering and Cell Fate by LIF2, an RNA Binding Partner of the Polycomb Complex Component LHP1

Polycomb Repressive Complexes (PRC) modulate the epigenetic status of key cell fate and developmental regulators in eukaryotes. The chromo domain protein LIKE HETEROCHROMATIN PROTEIN1 (LHP1) is a subunit of a plant PRC1-like complex in Arabidopsis thaliana and recognizes histone H3 lysine 27 trimethylation, a silencing epigenetic mark deposited by the PRC2 complex. We have identified and studied an LHP1-Interacting Factor2 (LIF2). LIF2 protein has RNA recognition motifs and belongs to the large hnRNP protein family, which is involved in RNA processing. LIF2 interacts in vivo, in the cell nucleus, with the LHP1 chromo shadow domain. Expression of LIF2 was detected predominantly in vascular and meristematic tissues. Loss-of-function of LIF2 modifies flowering time, floral developmental homeostasis and gynoecium growth determination. lif2 ovaries have indeterminate growth and produce ectopic inflorescences with severely affected flowers showing proliferation of ectopic stigmatic papillae and ovules in short-day conditions. To look at how LIF2 acts relative to LHP1, we conducted transcriptome analyses in lif2 and lhp1 and identified a common set of deregulated genes, which showed significant enrichment in stress-response genes. By comparing expression of LHP1 targets in lif2, lhp1 and lif2 lhp1 mutants we showed that LIF2 can either antagonize or act with LHP1. Interestingly, repression of the FLC floral transcriptional regulator in lif2 mutant is accompanied by an increase in H3K27 trimethylation at the locus, without any change in LHP1 binding, suggesting that LHP1 is targeted independently from LIF2 and that LHP1 binding does not strictly correlate with gene expression. LIF2, involved in cell identity and cell fate decision, may modulate the activity of LHP1 at specific loci, during specific developmental windows or in response to environmental cues that control cell fate determination. These results highlight a novel link between plant RNA processing and Polycomb regulation

Local, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis

Summary Background: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean–Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. Methods: In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. Findings: We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. Interpretation Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support. Funding Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development

A comprehensive database of the geographic spread of past human Ebola outbreaks

Ebola is a zoonotic filovirus that has the potential to cause outbreaks of variable magnitude in human populations. This database collates our existing knowledge of all known human outbreaks of Ebola for the first time by extracting details of their suspected zoonotic origin and subsequent human-to-human spread from a range of published and non-published sources. In total, 22 unique Ebola outbreaks were identified, composed of 117 unique geographic transmission clusters. Details of the index case and geographic spread of secondary and imported cases were recorded as well as summaries of patient numbers and case fatality rates. A brief text summary describing suspected routes and means of spread for each outbreak was also included. While we cannot yet include the ongoing Guinea and DRC outbreaks until they are over, these data and compiled maps can be used to gain an improved understanding of the initial spread of past Ebola outbreaks and help evaluate surveillance and control guidelines for limiting the spread of future epidemic

CKD and mortality risk in older people: a community-based population study in the United Kingdom

Background: the prevalence of chronic kidney disease (CKD) increases with age; however, theprognostic significance in older people is uncertain. This study aims to determine the association of CKDwith all-cause and cardiovascular mortality in community-dwelling older people 75 years and older.Study Design: Cohort study of people 75 years and older recruited in 1994 to 1999 to 1 arm of a trialof multidimensional health assessment with mortality follow-up.Setting &amp; Participants: 53 general practices in Great Britain. 15,336 (73%) of those eligibleparticipated. 13,177 (86%) had serum creatinine measured at baseline.Main Factor: estimated glomerular filtration rate (eGFR).Outcomes: All-cause and cardiovascular mortality.Measurements: eGFR derived from serum creatinine level using the 4-variable Modification of Diet inRenal Disease (MDRD) Study equation in milliliters per minute per 1.73 m2; dipstick proteinuria.Mortality by linkage to national death registration and death certification.Results: after a median follow-up of 7.3 years (interquartile range, 5.0), 7,633 (58%) had died, 42% ofcardiovascular causes. In the first 2 years of follow-up, adjusted hazard ratios for all-cause mortality ineGFR bands of 45 to 59, 30 to 44, and less than 30 compared with eGFR greater than 60 mL/min/1.73m2 were 1.13 (95% confidence interval, 0.93 to 1.37), 1.69 (95% confidence interval, 1.26 to 2.28), and3.87 (95% confidence interval, 2.78 to 5.38) in men and 1.14 (95% confidence interval, 0.93 to 1.40),1.33 (95% confidence interval, 1.06 to 1.68), and 2.44 (95% confidence interval, 1.68 to 3.56) in women,respectively. Hazard ratios were greater for cardiovascular mortality and lower after 2 years. Dipstickproteinuria was independently associated with all-cause, but not cardiovascular, mortality risk in bothsexes.Limitations: single serum creatinine measurement, no calibration of serum creatinine, MDRD Studyequation not validated in older people.Conclusion: As kidney function decreases, there is a graded and independent increase in all-causeand cardiovascular mortality risk in older people 75 years and older, especially in men and those witheGFR less than 45 mL/min/1.73 m2. Dipstick proteinuria did not add to cardiovascular mortality risk inthis elderly population. In older people, identification and management of CKD should prioritize thesmaller numbers with more severe CKD

Ebola past outbreak geographic spread GIS polygon data

<p>This Google Earth kmz file contains information about the geographic spread of past Ebola outbreaks. The file is also compatible with other GIS software. This file contains polygon data and is intended to be used in combination with the file: "Ebola past outbreak geographic spread GIS point data" which contains the accompanying point data.</p

Ebola past outbreak geographic spread GIS polygon data (.shp)

<p>This ESRI shp file contains information about the geographic spread of past Ebola outbreaks. The file is also compatible with other GIS software. This file contains polygon data and is intended to be used in combination with the file: "Ebola past outbreak geographic spread GIS point data (.shp)" which contains the accompanying point data.</p

Ebola past outbreak geographic spread GIS point data

<p>This Google Earth kmz file contains information about the geographic spread of past Ebola outbreaks. The file is also compatible with other GIS software. This file contains point data and is intended to be used in combination with the file: "Ebola past outbreak geographic spread GIS polygon data" which contains the accompanying polygon data.</p