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malaria therapy for ebola virus infection. 201728184408
error baseline rates of five sample preparation methods used to characterize rna virus populations.individual rna viruses typically occur as populations of genomes that differ slightly from each other due to mutations introduced by the error-prone viral polymerase. understanding the variability of rna virus genome populations is critical for understanding virus evolution because individual mutant genomes may gain evolutionary selective advantages and give rise to dominant subpopulations, possibly even leading to the emergence of viruses resistant to medical countermeasures. reverse transcript ...201728182717
febrile illness in healthcare workers caring for ebola virus disease patients in a high-resource setting.ebola virus disease (evd) patients treated in high-resource facilities are cared for by large numbers of healthcare staff. monitoring these healthcare workers (hcws) for any illness that may represent transmission of ebola virus is important both for the individuals and to minimise the community risk. international policies for monitoring hcws vary considerably and their effectiveness is unknown. here we describe the united kingdom (uk) experience of illness in hcws who cared for three patients ...201728182538
ebola virus infection induces autoimmunity against dsdna and hsp60.ebola virus (ebov) survivors are affected by a variety of serious illnesses of unknown origin for years after viral clearance from the circulation. identifying the causes of these persistent illnesses is paramount to develop appropriate therapeutic protocols. in this study, using mouse and non-human primates which survived ebov challenge, elisa, western blot, mass spectrometry and flow cytometry were used to screen for autoantibodies, identify their main targets, investigate the mechanism behind ...201728181533
sequencing of ebola virus genomes using nanopore technology.sequencing of virus genomes during disease outbreaks can provide valuable information for diagnostics, epidemiology, and evaluation of potential countermeasures. however, particularly in remote areas logistical and technical challenges can be significant. nanopore sequencing provides an alternative to classical sanger and next-generation sequencing methods, and was successfully used under outbreak conditions (hoenen et al., 2016; quick et al., 2016). here we describe a protocol used for sequenci ...201628180136
the role of exosomal vp40 in ebola virus disease.ebola virus (ebov) can cause a devastating hemorrhagic disease, leading to death in a short period of time. after infection, the resulting ebov disease results in high levels of circulating cytokines, endothelial dysfunction, coagulopathy, and bystander lymphocyte apoptosis in humans and nonhuman primates. the vp40 matrix protein of ebov is essential for viral assembly and budding from the host cell. recent data have shown that vp40 exists in the extracellular environment, including in exosomes, ...201728177658
non-active site mutations disturb the loop dynamics, dimerization, viral budding and egress of vp40 of the ebola virus.the first account of the dynamic features of the loop region of vp40 of the ebola virus (ebov) using accelerated molecular dynamics (amd) simulations is reported herein. due to its major role in the ebola life cycle, vp40 is considered a promising therapeutic target. the available experimental data on the n-terminal domain (ntd) loop indicates that mutations k127a, t129a and n130a demonstrate an unrecognized role for ntd-plasma membrane (pm) interaction for efficient vp40-pm localization, oligom ...201728170013
chemically modified human serum albumin potently blocks entry of ebola pseudoviruses and viruslike particles.ebola virus (ebov), the causative pathogen of the deadly ebola virus disease (evd), can be transmitted via contact with evd patients, including sexual contact with evd survivors. at present, no licensed vaccine or therapeutic is available. in this study, we compared eight anhydride-modified proteins for their entry-inhibitory activity against the pseudovirus (psv) carrying the envelope glycoprotein (gp) of the ebov zaire or sudan species (zaire psv and sudan psv, respectively). we found that 3-h ...201728167539
detection of lipid induced structural changes of the marburg virus matrix protein vp40 using hydrogen/deuterium exchange mass spectrometry.marburg virus (marv) is a lipid-enveloped virus from the filoviridae family containing a negative sense rna genome. one of the seven marv genes encodes the matrix protein vp40, which forms a matrix layer beneath the plasma membrane inner leaflet to facilitate budding from the host cell. marv vp40 (mvp40) has been shown to be a dimeric peripheral protein with a broad and flat basic surface that can associate with anionic phospholipids such as phosphatidylserine. while a number of mvp40 cationic r ...201728167534
a systematic review of early modelling studies of ebola virus disease in west africa.phenomenological and mechanistic models are widely used to assist resource planning for pandemics and emerging infections. we conducted a systematic review, to compare methods and outputs of published phenomenological and mechanistic modelling studies pertaining to the 2013-2016 ebola virus disease (evd) epidemics in four west african countries - sierra leone, liberia, guinea and nigeria. we searched pubmed, embase and scopus databases for relevant english language publications up to december 20 ...201728166851
beyond ebola treatment units: severe infection temporary treatment units as an essential element of ebola case management during an outbreak.in the course of the ebola outbreak in west africa that was witnessed since early 2014, the response mechanisms showed deficits in terms of timeliness, volume and adequacy. the authors were deployed in the ebola campaign in the west african country liberia, where by september 2014 the changing epidemiological pattern made reconsiderations of guidelines and adopted procedures necessary. a temporary facility set up as a conventional ebola treatment unit in the liberian capital monrovia was re-dedi ...201728166739
structural and mechanistic insights into nuclear transport and delivery of the critical pluripotency factor oct4 to dna.oct4 is a master regulator of the induction and maintenance of cellular pluripotency, and has crucial roles in early stages of differentiation. it is the only factor that cannot be substituted by other members of the same protein family to induce pluripotency. however, although oct4 nuclear transport and delivery to target dna are critical events for reprogramming to pluripotency, little is known about the molecular mechanism. oct4 is imported to the nucleus by the classical nuclear transport me ...201728166455
updates in diagnosis and management of ebola hemorrhagic fever.ebola hemorrhagic fever is a lethal viral disease transmitted by contact with infected people and animals. ebola infection represents a worldwide health threat causing enormous mortality rates and fatal epidemics. major concern is pilgrimage seasons with possible transmission to middle east populations. in this review, we aim to shed light on ebola hemorrhagic fever as regard: virology, transmission, biology, pathogenesis, clinical picture, and complications to get the best results for preventio ...201628163730
comparison of platform technologies for assaying antibody to ebola virus.the recent ebola outbreak in west africa led to the use of a variety of different platform technologies for assaying antibodies because of the difficulties of handling the live virus. the same types of method could be applied rapidly to other infections when they emerge. there is a need to compare quantitative results of different assays, which means that the assays must measure similar parameters and give comparable results.201728161420
molecular modeling, simulation and docking study of ebola virus glycoprotein.ebola virus (ebov) is a filamentous, enveloped, non-segmented, negative-strand ribonucleic acid (rna) virus which belongs to family filoviridae. ebola virus includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. in this study secreted glycoprotein (q7t9e0) of ebola virus was acquired from uniprot. the formation of alpha helix and beta sheets of secondary structures were predicted through online servers. higher flexibility and disordered regions ...201728160722
knowledge of ebola virus disease among a university population: a cross-sectional study.this cross-sectional study aimed to evaluate the knowledge of a pakistani university population (students and employees) regarding ebola virus disease. a total of 2,200 individuals were approached and 1,647 were enrolled in the study. we observed that the vast majority of study participants (91.8%) had inadequate knowledge of ebola virus disease (knowledge score ≤ 12). our findings highlight the need to increase the knowledge of ebola virus disease by using multidimensional approach involving aw ...201728159068
ebola virus disease surveillance and response preparedness in northern ghana.background the recent ebola virus disease (evd) outbreak has been described as unprecedented in terms of morbidity, mortality, and geographical extension. it also revealed many weaknesses and inadequacies for disease surveillance and response systems in africa due to underqualified staff, cultural beliefs, and lack of trust for the formal health care sector. in 2014, ghana had high risk of importation of evd cases. objective the objective of this study was to assess the evd surveillance and resp ...201628156981
successful post-exposure prophylaxis of ebola infected non-human primates using ebola glycoprotein-specific equine igg.herein we describe production of purified equine igg obtained from horses immunized with plasmid dna followed by boosting with kunjin replicon virus-like particles both encoding a modified ebola glycoprotein. administration of the equine igg over 5 days to cynomolgus macaques infected 24 hours previously with a lethal dose of ebola virus suppressed viral loads by more than 5 logs and protected animals from mortality. animals generated their own ebola glycoprotein-specific igg responses 9-15 days ...201728155869
a sensitive in vitro high-throughput screen to identify pan-filoviral replication inhibitors targeting the vp35-np interface.the 2014 ebola outbreak in west africa, the largest outbreak on record, highlighted the need for novel approaches to therapeutics targeting ebola virus (ebov). within the ebov replication complex, the interaction between polymerase cofactor, viral protein 35 (vp35), and nucleoprotein (np) is critical for viral rna synthesis. we recently identified a peptide at the n-terminus of vp35 (termed npbp) that is sufficient for interaction with np and suppresses ebov replication, suggesting that the npbp ...201728152588
safety and immunogenicity of gamevac-combi, a heterologous vsv- and ad5-vectored ebola vaccine: an open phase i/ii trial in healthy adults in russia.ebola hemorrhagic fever, also known as ebola virus disease or evd, is one of the most dangerous viral diseases in humans and animals. in this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. the vaccine consists of live-attenuated recombinant vesicular stomatitis virus (vsv) and adenovirus ser ...201728152326
predicting ebola severity: a clinical prioritization score for ebola virus disease.despite the notoriety of ebola virus disease (evd) as one of the world's most deadly infections, evd has a wide range of outcomes, where asymptomatic infection may be almost as common as fatality. with increasingly sensitive evd diagnosis, there is a need for more accurate prognostic tools that objectively stratify clinical severity to better allocate limited resources and identify those most in need of intensive treatment.201728151955
training ghanaian frontline healthcare workers in public health surveillance and disease outbreak investigation and response.beyond initial formal academic education, the need for continuous professional development through in-service workforce capacity improvement programs that are aimed at enhancing knowledge and skills of public healthcare workers has assumed immense priority worldwide. this has been heightened by the on-going ebola virus disease outbreak, which is exposing the weak public health systems in west africa. in response to this need, the ghana field epidemiology and laboratory program organized a short- ...201628149433
molecular docking based screening of compounds against vp40 from ebola virus.ebola virus causes severe and often fatal hemorrhagic fevers in humans. the 2014 ebola epidemic affected multiple countries. the virus matrix protein (vp40) plays a central role in virus assembly and budding. since there is no fda-approved vaccine or medicine against ebola viral infection, discovering new compounds with different binding patterns against it is required. therefore, we aim to identify small molecules that target the arg 134 rna binding and active site of vp40 protein. 1800 molecul ...201628149054
disinfection of ebola virus in sterilized municipal wastewater.concerns have been raised regarding handling of ebola virus contaminated wastewater, as well as the adequacy of proposed disinfection approaches. in the current study, we investigate the inactivation of ebola virus in sterilized domestic wastewater utilizing sodium hypochlorite addition and ph adjustment. no viral inactivation was observed in the one-hour tests without sodium hypochlorite addition or ph adjustment. no virus was recovered after 20 seconds (i.e. 4.2 log10 unit inactivation to dete ...201728146555
vp40 of the ebola virus as a target for ebov therapy: comprehensive conformational and inhibitor binding landscape from accelerated molecular dynamics.the first account of the dynamic features of the loop region of vp40 of the ebola virus was studied using accelerated molecular dynamics simulations and reported herein. among the proteins of the ebola virus, the matrix protein (vp40) plays a significant role in the virus lifecycle thereby making it a promising therapeutic target. of interest is the newly elucidated n-terminal domain loop region of vp40 comprising residues k127, t129, and n130 which when mutated to alanine have demonstrated an u ...201728144904
ebola virus and marburg virus in human milk are inactivated by holder pasteurization.potential donors of human milk are screened for ebola virus (ebov) using standard questions, but testing for ebov and marburg virus (marv) is not part of routine serological testing performed by milk banks. research aim: this study tested the hypothesis that ebov would be inactivated in donor human milk (dhm) by standard pasteurization techniques (holder) used in all north american nonprofit milk banks.201728135118
therapeutic potential of the heme oxygenase-1 inducer hemin against ebola virus infection.promising drugs to treat ebola virus (ebov) infection are currently being developed, but so far none has shown efficacy in clinical trials. drugs that can stimulate host innate defense responses may retard the progression of ebov disease. we report here the dramatic effect of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (ho-1), in the reduction of ebov replication. treatment of primary monocyte-derived macrophages (mdm), vero e6 cells, hela cells, and human foreskin f ...201628133423
implementation of a non-human primate model of ebola disease: infection of mauritian cynomolgus macaques and analysis of virus populations.ebola virus (ebov) haemorrhagic fever remains a threat to global public health with an urgent need for an effective treatment. in order to achieve these goals, access to non-human primate (nhp) laboratory models is an essential requirement. here, we present the first nhp-ebov laboratory model readily available to the european scientific community, based on infection of mauritian cynomolgus macaques using a central-african ebov strain and increasing virus challenge dose (10, 100, or 1000 focus fo ...201728132865
membrane insertion of fusion peptides from ebola and marburg viruses studied by replica-exchange molecular dynamics simulations.this work presents replica-exchange molecular dynamics simulations of inserting a 16-residue ebola virus fusion peptide into a membrane bilayer. a computational approach is applied for modeling the peptide at the explicit all-atom level and the membrane-aqueous bilayer by a generalized born continuum model with a smoothed switching function (gbsw). we provide an assessment of the model calculations in terms of three metrics: (1) the ability to reproduce the nmr structure of the peptide determine ...201728130780
multitask matrix completion for learning protein interactions across diseases.disease-causing pathogens such as viruses introduce their proteins into the host cells in which they interact with the host's proteins, enabling the virus to replicate inside the host. these interactions between pathogen and host proteins are key to understanding infectious diseases. often multiple diseases involve phylogenetically related or biologically similar pathogens. here we present a multitask learning method to jointly model interactions between human proteins and three different but re ...201728128642
aerosolization of ebola virus surrogates in wastewater systems.recent studies have shown that ebola virus can persist in wastewater. we evaluated the potential for ebola virus surrogates to be aerosolized from three types of wastewater systems: toilets, a lab-scale model of an aeration basin, and a lab-scale model of converging sewer pipes. we measured the aerosol size distribution generated by each system, spiked ebola virus surrogates (ms2 and phi6) into each system, and determined the emission rate of viruses into the air. the number of aerosols released ...201728125778
discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine c-nucleoside (gs-5734) for the treatment of ebola and emerging viruses.the recent ebola virus (ebov) outbreak in west africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. a focused screening and lead optimization effort identified 4b (gs-5734) with anti-ebov ec50 = 86 nm in macrophages as the clinical candidate. structure activity relationships established that the 1'-cn group and c-linked nucleobase were critical for optimal anti-ebov potency and selectivity against host polymerases. a ro ...201728124907
community event-based surveillance for ebola virus disease in sierra leone: implementation of a national-level system during a crisis.there are few documented examples of community networks that have used unstructured information to support surveillance during a health emergency. in january 2015, the ebola response consortium rapidly implemented community event-based surveillance for ebola virus disease at a national scale in sierra leone.201628123860
innate immune responses of bat and human cells to filoviruses: commonalities and distinctions.marburg (marv) and ebola (ebov) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. the natural reservoir of marv is the egyptian rousette bat (rousettus aegyptiacus); that of ebov is unknown but believed to be another bat species. the egyptian rousette develops subclinical productive infection with marv but is refractory to ebov. interaction of filoviruses with hosts is greatly affected by the viral interferon (ifn)-inhibiting domains (iid). our study was aimed at char ...201728122983
monitoring travellers from ebola-affected countries in new south wales, australia: what is the impact on travellers?amidst an ebola virus disease (evd) epidemic of unprecedented magnitude in west africa, concerns about the risk of importing evd led to the introduction of programs for the screening and monitoring of travellers in a number of countries, including australia. emerging reports indicate that these programs are feasible to implement, however rigorous evaluations are not yet available. we aimed to evaluate the program of screening and monitoring travellers in new south wales.201728118827
immunobiology of ebola and lassa virus infections.two of the most important contemporary emerging viruses that affect human health in africa are ebola virus (ebov) and lassa virus (lasv). the 2013-2016 west african outbreak of ebov was responsible for more than 11,000 deaths, primarily in guinea, sierra leone and liberia. lasv is constantly emerging in these and surrounding west african countries, with an estimate of more than 500,000 cases of lassa fever, and approximately 5,000 deaths, annually. both ebov and lasv are zoonotic, and human infe ...201728111475
print media coverage of ebola virus disease, middle east respiratory syndrome and pertussis. 201728110493
label free checkerboard assay to determine overlapping epitopes of ebola virus vp-40 antibodies using surface plasmon resonance.immunoassay formats, in which antibodies provide sensitivity and specificity, are often utilized to provide rapid and simple diagnostic tests. surface plasmon resonance is frequently used to evaluate the suitability of antibodies by determining binding kinetics to agents or surrogate antigens. we used spr to evaluate a number of commercial monoclonal antibodies as well as single domain antibodies produced in-house. all the antibodies targeted the ebola virus viral protein 40 (vp40). we determine ...201728109682
an update on the 2014 ebola outbreak in western africa.the recent ebola outbreak in western africa was the most devastating outbreak witnessed in recent times. there have been remarkable local and international efforts to control the crisis. ebola virus disease is the focus of immense research activity. the progression of events in the region has been evolving swiftly and it is of paramount importance to the medical community to be acquainted with the situation. over 28000 people were inflicted with the condition, over 11000 have died. novel data ha ...201728107867
transcriptomic signatures differentiate survival from fatal outcomes in humans infected with ebola virus.in 2014, western africa experienced an unanticipated explosion of ebola virus infections. what distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. we used transcriptome data for peripheral blood taken from infected and convalescent recovering patients to identify early stage host factors that are associated with acute illness and those that differentiate patient survival from fatality.201728100256
a systems approach reveals mavs signaling in myeloid cells as critical for resistance to ebola virus in murine models of infection.the unprecedented 2013-2016 outbreak of ebola virus (ebov) resulted in over 11,300 human deaths. host resistance to rna viruses requires rig-i-like receptor (rlr) signaling through the adaptor protein, mitochondrial antiviral signaling protein (mavs), but the role of rlr-mavs in orchestrating anti-ebov responses in vivo is not known. here we apply a systems approach to mavs(-/-) mice infected with either wild-type or mouse-adapted ebov. mavs controlled ebov replication through the expression of ...201728099857
multidisciplinary assessment of post-ebola sequelae in guinea (postebogui): an observational cohort study.the high number of survivors from the 2013-16 west african outbreak of ebola virus disease (evd) has raised several new issues: long-term clinical complications, psychosocial consequences, risks of evd reactivation, and secondary transmission due to viral persistence in body fluids. we aimed to assess long-term clinical, psychosocial, and viral outcomes in evd survivors in guinea.201728094208
ebola virus disease sequelae: a challenge that is not going away. 201728094207
use of convalescent plasma in ebola virus infection.the recent ebola virus epidemics which threatened three west african countries (dec.2014-apr.2016) has urged global collaborative health organizations and countries to set up measures to stop the infection and to treat patients, near half of them being at risk of death. convalescent plasma-recovered from rescued west africans-was considered a feasible therapeutic option. efficacy was difficult to evaluate because of numerous unknowns (especially evolution of neutralizing antibodies), prior to th ...201728094110
functional mutations in spike glycoprotein of zaire ebolavirus associated with an increase in infection efficiency.ebola virus (ebov) is extremely virulent, and its glycoprotein is necessary for viral entry. ebov may adapt to its new host humans during outbreaks by acquiring mutations especially in glycoprotein, which allows ebov to spread more efficiently. to identify these evolutionary selected mutations and examine their effects on viral infectivity, we used experimental-phylogenetic-structural interdisciplinary approaches. in evolutionary analysis of all available zaire ebolavirus glycoprotein sequences, ...201728084671
chaperone-mediated autophagy protein bag3 negatively regulates ebola and marburg vp40-mediated egress.ebola (ebov) and marburg (marv) viruses are members of the filoviridae family which cause outbreaks of hemorrhagic fever. the filovirus vp40 matrix protein is essential for virus assembly and budding, and its ppxy l-domain motif interacts with ww-domains of specific host proteins, such as nedd4 and itch, to facilitate the late stage of virus-cell separation. to identify additional ww-domain-bearing host proteins that interact with vp40, we used an ebov ppxy-containing peptide to screen an array ...201728076420
experimental therapies for ebola virus disease: what have we learned? 201728073859
first newborn baby to receive experimental therapies survives ebola virus disease.a neonate born to an ebola virus-positive woman was diagnosed with ebola virus infection on her first day of life. the patient was treated with monoclonal antibodies (zmapp), a buffy coat transfusion from an ebola survivor, and the broad-spectrum antiviral gs-5734. on day 20, a venous blood specimen tested negative for ebola virus by quantitative reverse-transcription polymerase chain reaction. the patient was discharged in good health on day 33 of life. further follow-up consultations showed ag ...201728073857
multiplexed efficient on-chip sample preparation and sensitive amplification-free detection of ebola virus.an automated microfluidic sample preparation multiplexer (spm) has been developed and evaluated for ebola virus detection. metered air bubbles controlled by microvalves are used to improve bead-solution mixing thereby enhancing the hybridization of the target ebola virus rna with capture probes bound to the beads. the method uses thermally stable 4-formyl benzamide functionalized (4fb) magnetic beads rather than streptavidin coated beads with a high density of capture probes to improve the targe ...201728073029
preparedness planning and care of patients under investigation for or with ebola virus disease: a survey of physicians in north america.the west african ebola virus disease (evd) epidemic of 2014-2015 required north american hospitals to undertake comprehensive planning and training for the potential need to care for patients with evd. here we describe physician contributions to evd preparedness planning and the care of persons under investigation for or patients with evd.201728065333
prevalence of psychological symptoms among ebola survivors and healthcare workers during the 2014-2015 ebola outbreak in sierra leone: a cross-sectional study.the 2014-2015 ebola epidemic was considered to be the largest and most complex outbreak, which caused 11,310 reported deaths. the epidemic disease can cause a mental health crisis, however, there is only a small amount of scientific literature available related to this health issue so far. we evaluated the psychological symptoms of 161 participants including ebola survivors and healthcare workers in sierra leone, analyzed the impact of job classification, education level on psychological status. ...201728061463
modified vaccinia virus ankara: history, value in basic research, and current perspectives for vaccine development.safety tested modified vaccinia virus ankara (mva) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. historically, mva was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. adapted to growth in avian cells mva lost the ability ...201728057259
current and future diagnostic tests for ebola virus disease.ebola virus disease (evd) is a major public health concern with a high mortality rate in infected individuals. outbreaks of ebola have been widespread-there is no rapid, sensitive, specific, and affordable diagnostic test for the virus, nor there is any treatment for the disease. overlapping symptoms of other endemic diseases, such as malaria and cholera, make it difficult to diagnose evd. for clinical management, outbreak investigation, and proper surveillance, evd requires a detection system, ...201728057165
detection of viral rna in tissues following plasma clearance from an ebola virus infected patient.an unprecedented ebola virus (ebov) epidemic occurred in 2013-2016 in west africa. over this time the epidemic exponentially grew and moved to europe and north america, with several imported cases and many health care workers (hcw) infected. better understanding of ebov infection patterns in different body compartments is mandatory to develop new countermeasures, as well as to fully comprehend the pathways of human-to-human transmission. we have longitudinally explored the persistence of ebov-sp ...201728056096
[field assessment of the new rapid diagnostic test ebola ezyscreen®].during the ebola virus disease outbreak in west africa in 2014, the world health organization has pointed out the need for rapid diagnostic tests (rdt) affordable, sensitive, specific, user-friendly, rapid, equipment-free, and deliverable. the rapid diagnostic test (lateral flow assay) ebola ezyscreen® was developed in this emergency frame using monoclonal antibodies against the envelope glycoprotein of the virus. two distinct versions have been industrialized, one for whole-blood samples and th ...201728050868
beating the odds: successful establishment of a phase ii/iii clinical research trial in resource-poor liberia during the largest-ever ebola outbreak.it has been argued that a country such as liberia, not fully recovered from the devastation of decades of civil unrest, lacked the appropriate ethical and regulatory framework, basic human and health care services, and infrastructure to carry out clinical trials according to international standards of quality during a public health emergency. however, as liberia, sierra leone, and guinea were being ravaged by the largest and most devastating ebola virus disease (evd) outbreak ever recorded, the ...201628042619
prevention and nursing care in the first case of ebola virus disease contracted outside africa.after the evacuation from africa to western hospitals of several international workers with the ebola virus disease, the first case of contagion outside africa occurred in madrid, spain. a nursing care assistant who had attended a missionary repatriated from sierra leone contracted the disease. on october 7(th) 2014, the patient arrived at the university hospital la paz-carlos iii in madrid. she remained in the hospital for 30 days, 25 of which were in strict isolation in a negative pressure roo ...201728041818
interest in an ebola vaccine among a u.s. national sample during the height of the 2014-2016 ebola outbreak in west africa.to better understand the association between ebola-related attitudes and interest in receiving an ebola virus vaccine, a survey was administered to a u.s. national sample using gfk's knowledgepanel®. among participants (n=1417), 34.1% expressed interest in an ebola vaccine for themselves. in the subset of participants with children aged 0-17 (n=410), 38.1% expressed interest in an ebola vaccine for their child. in multivariable analyses, vaccine interest for oneself was associated with perceived ...201728040206
fcγ-receptor iia-mediated src signaling pathway is essential for the antibody-dependent enhancement of ebola virus infection.antibody-dependent enhancement (ade) of ebola virus (ebov) infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-ebov antibodies. ade has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface fc receptors, leading to enhanced infection. however, little is known about the molecular mechanisms underlying this phenomenon. here we show that fcγ-receptor iia (fcγriia)-mediated intracellular ...201628036370
perception of measures for dealing with ebola disease in primary care.an epidemic of ebola virus disease (evd) occurred in west africa in 2014. in catalonia, primary care is the first level of healthcare so it has a key role in the detection and initial management of possible cases of evd and in identifying contacts.201628029089
production, purification and immunogenicity of recombinant ebola virus proteins - a comparison of freund's adjuvant and adjuvant system 03.there is an urgent need for ebola virus (ebov) proteins, ebov-specific antibodies and recombinant antigens to be used in diagnostics and as potential vaccine candidates. our objective was to produce and purify recombinant proteins for immunological assays and for the production of polyclonal ebov specific antibodies. in addition, a limited comparison of the adjuvant effects of freund's complete adjuvant (fca) and adjuvant system 03 (as03) was carried out. recombinant ebov gst-vp24, -vp30, -vp35, ...201728025125
real-time dynamic modelling for the design of a cluster-randomized phase 3 ebola vaccine trial in sierra leone.declining incidence and spatial heterogeneity complicated the design of phase 3 ebola vaccine trials during the tail of the 2013-16 ebola virus disease (evd) epidemic in west africa. mathematical models can provide forecasts of expected incidence through time and can account for both vaccine efficacy in participants and effectiveness in populations. determining expected disease incidence was critical to calculating power and determining trial sample size.201728024952
ebola virus infection among western healthcare workers unable to recall the transmission route.introduction. during the 2014-2016 west-african ebola virus disease (evd) outbreak, some hcws from western countries became infected despite proper equipment and training on evd infection prevention and control (ipc) standards. despite their high awareness toward evd, some of them could not recall the transmission routes. we explored these incidents by recalling the stories of infected western hcws who had no known directly exposures to blood/bodily fluids from evd patients. methodology. we carr ...201628018915
immunity duration of a recombinant adenovirus type-5 vector-based ebola vaccine and a homologous prime-boost immunisation in healthy adults in china: final report of a randomised, double-blind, placebo-controlled, phase 1 trial.the 2013-15 ebola virus disease epidemic in west africa greatly accelerated the development of ebola vaccine. we aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in china.201728017642
efficacy and effectiveness of an rvsv-vectored vaccine in preventing ebola virus disease: final results from the guinea ring vaccination, open-label, cluster-randomised trial (ebola ça suffit!).rvsv-zebov is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of zaire ebolavirus. we tested the effect of rvsv-zebov in preventing ebola virus disease in contacts and contacts of contacts of recently confirmed cases in guinea, west africa.201728017403
first ebola virus vaccine to protect human beings? 201728017402
safety and immunogenicity of a recombinant adenovirus type-5 vector-based ebola vaccine in healthy adults in sierra leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial.a recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of ebola zaire makona variant showed good safety and immunogenicity in a phase 1 trial of healthy chinese adults. we aimed to assess the safety and immunogenicity of this vaccine in healthy adults in sierra leone and to determine the optimal dose.201728017399
ebola virus vp35 blocks stress granule assembly.stress granules (sgs) are dynamic cytoplasmic aggregates of translationally silenced mrnas that assemble in response to environmental stress. sgs appear to play an important role in antiviral innate immunity and many viruses have evolved to block or subvert sgs components for their own benefit. here, we demonstrate that intracellular ebola virus (ebov) replication and transcription-competent virus like particles (trvlp) infection does not lead to sg assembly but leads to a blockade to arsenite-i ...201728013103
an enzymatic assay based on luciferase ebola virus-like particles for evaluation of virolytic activity of antimicrobial peptides.antimicrobial peptides are currently considered as promising antiviral compounds. current assays to evaluate the effectivity of peptides against enveloped viruses based on liposomes or hemolysis are encumbered by the artificial nature of liposomes or distinctive membrane composition of used erythrocytes. we propose a novel assay system based on enzymatic ebola virus-like particles containing sensitive luciferase reporter. the assay was validated with several cationic and anionic peptides and com ...201728012857
human transmission of ebola virus.ever since the first recognised outbreak of ebolavirus in 1976, retrospective epidemiological analyses and extensive studies with animal models have given us insight into the nature of the pathology and transmission mechanisms of this virus. in this review focusing on ebolavirus, we present an outline of our current understanding of filovirus human-to-human transmission and of our knowledge concerning the molecular basis of viral transmission and potential for adaptation, with particular focus o ...201728012412
detection of ebola virus rna through aerosol sampling of animal biosafety level 4 rooms housing challenged nonhuman primates.ebola virus disease is a serious illness of humans and nonhuman primates (nhps). direct contact has been shown to be the primary source of ebola (ebov) transmission. we utilized a high volume air sampler to determine if ebov could be detected during three independent studies with ebov challenged nhps. viral rna was recovered during days 9 and 10 of study i and days 7 and 8 of study iii. viral rna levels were below lod during all other collections. the results demonstrate that the bsl-4 suit prot ...201628011922
management of ebola virus disease: is environmental decontamination effective? 201728011909
characteristics and outcomes of pediatric patients with ebola virus disease admitted to treatment units in liberia and sierra leone: a retrospective cohort study.the clinical and virologic characteristics of ebola virus disease (evd) in children have not been thoroughly documented.201728011610
assessment and optimization of the genexpert diagnostic platform for detection of ebola virus rna in seminal fluid.recent studies have suggested that ebola virus (ebov) rna potentially present in the semen of a large number of survivors of ebola virus disease (evd) in western africa may contribute to sexual transmission of evd and generate new clusters of cases in regions previously declared ebov free. these findings drive the immediate need for a reliable, rapid, user-friendly assay for detection of ebov rna in semen that is deployable to multiple sites across western africa. in this study, we optimized the ...201628003349
a new strategy for full-length ebola virus glycoprotein expression in e.coli.ebola virus (ebov) causes severe hemorrhagic fever in humans and non-human primates with high rates of fatality. glycoprotein (gp) is the only envelope protein of ebov, which may play a critical role in virus attachment and entry as well as stimulating host protective immune responses. however, the lack of expression of full-length gp in escherichia coli hinders the further study of its function in viral pathogenesis. in this study, the vp40 gene was fused to the full-length gp gene and cloned i ...201628000060
"ebola kills generations": qualitative discussions with liberian healthcare providers.the purpose of this study was to explore healthcare providers' perceptions and reactions to the ebola virus disease (evd) epidemic.201727998827
ocular complications in survivors of the ebola outbreak in guinea.the ebola outbreak of 2013-2016 severely affected west africa and resulted in 2544 deaths and 1270 survivors in guinea, the country where it began. this ebola virus was the zaire strain of the virus family filoviridae. in this outbreak the case fatality rate was about 67%. the survivors, declared cured after 2 negative blood polymerase chain reaction (pcr) results, face psychosocial disorders and rheumatic, ear-nose-throat, neurocognitive, and ophthalmologic complications. the goal of this study ...201727998698
australia's response to ebola virus disease in west africa, 2014-15.in march 2016, the world health organization declared the 2014-15 ebola virus disease (evd) outbreak officially over. with around 29 000 cases and 11 000 deaths in 27 months, this evd outbreak was more than 60 times larger than any before, and unique in its cross-border spread and involvement of urban centres. local and international responses were slow and initially inadequate, but establishment of the united nations mission for ebola emergency response, 9 months after the outbreak began, allow ...201627997940
assessment of ebola virus disease preparedness in the who south-east asia region.to conduct assessments of ebola virus disease preparedness in countries of the world health organization (who) south-east asia region.201627994284
rapid visual screening and programmable subtype classification of ebola virus biomarkers.the massive outbreaks of the highly transmissible and lethal ebola virus disease were caused by infection with one of the ebolavirus species. it is vital to develop cost-effective, highly sensitive and selective multitarget biosensing platforms that allow for both the detection and phenotyping. here, a highly programmable, cost-efficient and multianalyte sensing approach is reported that enables visual detection and differentiation of conserved oligonucleotide regions of all ebolavirus subtypes ...201727990771
coupling sensitive nucleic acid amplification with commercial pregnancy test strips.the detection of nucleic acid biomarkers for point-of-care (poc) diagnostics is currently limited by technical complexity, cost, and time constraints. to overcome these shortcomings, we have combined loop-mediated isothermal amplification (lamp), programmable toehold-mediated strand-exchange signal transduction, and standard pregnancy test strips. the incorporation of an engineered hcg-snap fusion reporter protein (human chorionic gonadotropin-o(6) -alkylguanine-dna alkyltransferase) led to lamp ...201727990727
is plasmodium species parasitemia really associated with increased survival in ebola virus-infected patients? 201727986678
comparison of n- and o-linked glycosylation patterns of ebolavirus glycoproteins.ebolaviruses are emerging pathogens that cause severe and often fatal viral hemorrhagic fevers. four distinct ebolaviruses are known to cause ebola virus disease in humans. the ebolavirus envelope glycoprotein (gp1,2) is heavily glycosylated, but the precise glycosylation patterns of ebolaviruses are largely unknown. here we demonstrate that approximately 50 different n-glycan structures are present in gp1,2 derived from the four pathogenic ebolaviruses, including high mannose, hybrid, and bi-, ...201727984785
sequelae and other conditions in ebola virus disease survivors, sierra leone, 2015.we rapidly assessed the health of ebola virus disease (evd) survivors in kenema, sierra leone, by reviewing medical charts of all patients attending the survivor clinic of kenema government hospital. data were abstracted on signs and symptoms at every attendance. as of november 2015, a total of 621 attendances by 115 survivors with laboratory-confirmed evd were made to the survivor clinic. most (60.9%) survivors were women. survivors' median age was 28 years (range 0.25-70 years). survivors atte ...201727983503
media messages and perception of risk for ebola virus infection, united states.news media have been blamed for sensationalizing ebola in the united states, causing unnecessary alarm. to investigate this issue, we analyzed us-focused news stories about ebola virus disease during july 1-november 30, 2014. we found frequent use of risk-elevating messages, which may have contributed to increased public concern.201727983495
ebola virus derived g-quadruplexes: thiazole orange interaction.the ebola and marburg viruses are some of the deadliest viruses in the world. in this study a series of g-rich dna sequences derived from these types of viruses which possess the potential to form g-quadruplex structures are analyzed. a set of dna oligonucleotides derived from original viral isolates was used as a representative modeling sequence with which to demonstrate the influence of thiazole orange on circular dichroism (cd) spectral profiles. the results show the unique profile of the ind ...201627979676
monitoring of persons with risk for exposure to ebola virus - united states, november 3, 2014-december 27, 2015.during november 3, 2014-december 27, 2015, cdc implemented guidance on movement and monitoring of persons in the united states with potential exposure to ebola virus (ebola) (1). monitoring was concluded in december 2015. after cdc modified the guidance for monitoring travelers from guinea (the last country for which monitoring of travelers was recommended) in late december 2015, jurisdictional reports were no longer collected by cdc. this report documents the number of persons monitored as part ...201627977641
a hamster model for marburg virus infection accurately recapitulates marburg hemorrhagic fever.marburg virus (marv), a close relative of ebola virus, is the causative agent of a severe human disease known as marburg hemorrhagic fever (mhf). no licensed vaccine or therapeutic exists to treat mhf, and marv is therefore classified as a tier 1 select agent and a category a bioterrorism agent. in order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. here we describe the development of a novel, uniformly lethal syria ...201627976688
vp24-karyopherin alpha binding affinities differ between ebolavirus species, influencing interferon inhibition and vp24 stability.zaire ebolavirus (ebov), bundibugyo ebolavirus (bdbv), and reston ebolavirus (restv) belong to the same genus but exhibit different virulence properties. vp24 protein, a structural protein present in all family members, blocks interferon (ifn) signaling and likely contributes to virulence. inhibition of ifn signaling by ebov vp24 (evp24) involves its interaction with the npi-1 subfamily of karyopherin alpha (kpna) nuclear transporters. here, we evaluated evp24, bdbv vp24 (bvp24), and restv vp24 ...201727974555
ebola preparedness: diagnosis improvement using rapid approaches for proficiency testing.the unprecedented 2015 ebolavirus (ebov) outbreak in west africa was declared a public health emergency, making diagnosis and quality of testing a global issue. the accuracy of laboratory diagnostic capacity for ebov was assessed in 2014 to 2016 using a proficiency testing (pt) strategy developed by the royal college of pathologists of australasia quality assurance programs (rcpaqap) in biosecurity. following a literature search, ebov-specific gene targets were ranked according to the frequency ...201727974537
survey of nursing students' self-reported knowledge of ebola virus disease, willingness to treat, and perceptions of their duty to treat.the purpose of this study was to explore nursing students' self-reported knowledge of ebola virus disease (evd), willingness to treat patients with evd, and student perceptions of duty to treat patients with evd. the researchers developed the survey of nursing student self-reported knowledge of evd, willingness to treat, and perceptions of duty to treat, a quantitative tool with open-ended questions to inform the responses. on-line survey software was used for gathering anonymous data. a mixture ...201627964818
efficacy of convalescent plasma in relation to dose of ebola virus antibodies. 201627959686
the pathogenesis of ebola virus disease.for almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the african continent to cause epidemics of highly fatal hemorrhagic fever. the 2013-2015 west african epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in ebola's history, presented an enormous international public health challenge, but it also provided insights into ebola's pathogenesis and natural history, clinical expression, ...201727959626
will there be a cure for ebola?despite the unprecedented ebola virus outbreak response in west africa, no ebola medical countermeasures have been approved by the us food and drug administration. however, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk-pathogen setting. numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (bcx4430, brincidofovir, favipiravir, and gs-5734), nucleic ac ...201727959624
the cuban response to the ebola epidemic in west africa: lessons in solidarity.in december 2013 the first case of ebola appeared in guinea. in september 2014 the united nations (un) and its specialized agency the world health organization (who) issued a call for medical collaboration in response to the medical crisis and social disaster caused by the ebola virus epidemic in west africa. cuban authorities responded immediately to the call by offering specialized help for the epidemic, in collaboration with who. a group of 256 cuban doctors, nurses and other health professio ...201727956578
persistence and clearance of ebola virus rna from seminal fluid of ebola virus disease survivors: a longitudinal analysis and modelling study.by january, 2016, all known transmission chains of the ebola virus disease (evd) outbreak in west africa had been stopped. however, there is concern about persistence of ebola virus in the reproductive tract of men who have survived evd. we aimed to use biostatistical modelling to describe the dynamics of ebola virus rna load in seminal fluid, including clearance parameters.201727955791
screening of genital fluid for ebola virus - authors' reply. 201727955779
screening of genital fluid for ebola virus. 201727955778
persistence of ebola virus rna in seminal fluid. 201727955770
expression of an immunogenic ltb-based chimeric protein targeting zaire ebolavirus epitopes from gp1 in plant cells.an antigenic protein targeting two epitopes from the zaire ebolavirus gp1 protein was expressed in plant cells rendering an antigen capable of inducing humoral responses in mouse when administered subcutaneously or orally. the 2014 ebola outbreak made clear that new treatments and prophylactic strategies to fight this disease are needed. since vaccination is an intervention that could achieve the control of this epidemic disease, exploring the production of new low-cost vaccines is a key path to ...201727942840
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