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[international health regulations, ebola, and emerging infectious diseases in latin america and the caribbean].the world health organization's determination of the ebola virus disease outbreak as a public health event of international concern prompted non affected countries to implement measures to prevent, detect, and manage the introduction of the virus in their territories. the outbreak provided an opportunity to assess the operational implementation of the international health regulations' core capacities and health systems' preparedness to handle a potential or confirmed case of ebola virus disease. ...201627754529
the drug targets and antiviral molecules for treatment of ebola virus infection.ebola virus (ebov) is a highly pathogenic virus causing severe hemorrhagic fever with a high case fatality rate of 50% - 90% in humans. without an approved vaccine or treatments, ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. these approaches, however, have yet to end the 2014 outbreak of ebola after its prolonged presence in west africa. as with the increase of outbreaks, a significant effort has been made to develop promising counterm ...201727572081
ebola virus disease: caring for patients in sierra leone - a qualitative study.the aim of this study was to describe norwegian healthcare staffs' experiences of participating in care of patients with ebola virus disease in sierra leone.201727747916
comparative phylogeography of african fruit bats (chiroptera, pteropodidae) provide new insights into the outbreak of ebola virus disease in west africa, 2014-2016.both ebolavirus and marburgvirus were detected in several fruit bat species of the family pteropodidae, suggesting that this taxon plays a key role in the life cycle of filoviruses. after four decades of zaire ebolavirus (zebov) outbreaks in central africa, the virus was detected for the first time in west africa in 2014. to better understand the role of fruit bats as potential reservoirs and circulating hosts between central and west africa, we examine here the phylogeny and comparative phyloge ...201727746072
ebola virus disease and the eye.the world has witnessed the largest ebola virus disease (evd) epidemic in west africa with an unprecedented number of infected individuals and survivors. many systemic and ocular complications have been reported in survivors. herein, we review the ophthalmic complications associated with ebolavirus.201627585217
the role of fear-related behaviors in the 2013-2016 west africa ebola virus disease outbreak.the 2013-2016 west africa ebola virus disease pandemic was the largest, longest, deadliest, and most geographically expansive outbreak in the 40-year interval since ebola was first identified. fear-related behaviors played an important role in shaping the outbreak. fear-related behaviors are defined as "individual or collective behaviors and actions initiated in response to fear reactions that are triggered by a perceived threat or actual exposure to a potentially traumatizing event. frbs modify ...201627739026
the evolution of ebola virus: insights from the 2013-2016 epidemic.the 2013-2016 epidemic of ebola virus disease in west africa was of unprecedented magnitude and changed our perspective on this lethal but sporadically emerging virus. this outbreak also marked the beginning of large-scale real-time molecular epidemiology. here, we show how evolutionary analyses of ebola virus genome sequences provided key insights into virus origins, evolution and spread during the epidemic. we provide basic scientists, epidemiologists, medical practitioners and other outbreak ...201627734858
global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the global burden of disease study 2015.improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. the global burden of disease 2015 study (gbd 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. these results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.201627733281
a randomized, controlled trial of zmapp for ebola virus infection.background data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail zmapp is a promising immune-based treatment for ebola virus disease (evd). methods beginning in march 2015, we conducted a randomized, controlled trial of zmapp plus the current standard of care as compared with the current standard of care alone in patients with evd that was diagnosed in west africa by polymerase-chain-reaction (pcr) assay. eligible patients of any age were randomly assigned i ...201627732819
predicting subnational ebola virus disease epidemic dynamics from sociodemographic indicators.the recent ebola virus disease (evd) outbreak in west africa has spread wider than any previous human evd epidemic. while individual-level risk factors that contribute to the spread of evd have been studied, the population-level attributes of subnational regions associated with outbreak severity have not yet been considered.201627732614
[ebola virus disease: dramatic past and sinister future]. 201627730381
[the wanderings of the communication on the ebola virus disease].for two reasons, communication is one of the major tools in the fight against any ebola epidemics. firstly, because ebola is one of the most easily preventable of all infectious diseases and the thorough application of health-protection measures by the community of the sick persons is the best tool to fight any ebola epidemic. secondly, because during the two dozens of known ebola epidemics health care workers have often met with people's skepticism, or even hostility. however, our review of ebo ...201627726104
testing modeling assumptions in the west africa ebola outbreak.the ebola virus in west africa has infected almost 30,000 and killed over 11,000 people. recent models of ebola virus disease (evd) have often made assumptions about how the disease spreads, such as uniform transmissibility and homogeneous mixing within a population. in this paper, we test whether these assumptions are necessarily correct, and offer simple solutions that may improve disease model accuracy. first, we use data and models of west african migration to show that evd does not homogene ...201627721505
the idea model: a single equation approach to the ebola forecasting challenge.mathematical modeling is increasingly accepted as a tool that can inform disease control policy in the face of emerging infectious diseases, such as the 2014-2015 west african ebola epidemic, but little is known about the relative performance of alternate forecasting approaches. the rapidd ebola forecasting challenge (refc) tested the ability of eight mathematical models to generate useful forecasts in the face of simulated ebola outbreaks. we used a simple, phenomenological single-equation mode ...201627717616
[ebola virus disease: clinical presentation, prognosis and treatment].the clinical spectrum of ebola virus disease (evd) ranges from very serious forms with organ failure and death within days to paucisymptomatic forms and perhaps even asymptomatic. the authors propose a focus on the clinical manifestations of evd, on prognosis and on therapeutic aspects (excluding resuscitation). this work extracts from the literature the main data gathered during the 2014-2015 epidemic that raged in guinea conakry and sierra leone. these two countries, even if they are separated ...201727717513
integrating one health in national health policies of developing countries: india's lost opportunities.globally, the threat of infectious diseases, particularly emerging infectious diseases, originating at the human-animal-environment interface, has caught health systems off guard. with forecasts that future pathogen emergence will be centred in hotspots in asia, africa, and latin america, the need to prepare policy frameworks that can combat this threat is urgent.201627716352
ebola virus and arthropods: a literature review and entomological consideration on the vector role.ebola virus is a pathogen responsible for a severe disease that affects humans and several animal species. to date, the natural reservoir of this virus is not known with certainty, although it is believed that fruit bats (chiroptera: pteropodidae) play an important role in maintaining the virus in nature. although information on viral transmission from animals to humans is not clear, the role of arthropods has come under suspicion. in this article, we review the potential role of arthropods in s ...201627714628
more challenges from ebola: infection of the central nervous system.cases of relapsed ebola virus disease involving symptoms in the central nervous system are reminiscent of our past observations with some nonhuman primates (nhps) that survived acute ebola virus infection. we document our findings in detail here and suggest that this phenomenon can be further investigated in nhps.201627707893
laboratory response to 2014 ebola virus outbreak in mali.aware of the rapid spread of ebola virus (ebov) during the current west african epidemic, mali took several proactive steps to rapidly identify cases within its borders. under the mali international center for excellence in research program, a collaboration between the national institute of allergy and infectious diseases and the malian ministry of higher education and scientific research established a national ebov diagnostic site at the university of sciences, techniques and technologies of ba ...201627707892
a cell-based high-throughput protocol to screen entry inhibitors of highly pathogenic viruses with traditional chinese medicines.emerging viruses such as ebola virus (ebov), lassa virus (lasv), and avian influenza virus h5n1 (aiv) are global health concerns. since there is very limited options (either vaccine or specific therapy) approved for humans against these viruses, there is an urgent need to develop prophylactic and therapeutic treatments. previously we reported a high-throughput screening (hts) protocol to identify entry inhibitors for three highly pathogenic viruses (ebov, lasv, and aiv) using a human immunodefic ...201727704591
[revival after ebola: multidisciplinary assessment at 1 year, prospect and follow-up study of surviving patients from ebola in guinea (postebogui cohort)].ebola virus disease (evd) epidemic that spread in west africa from the end of 2013 to early 2016 has reached more people than all past epidemics. beyond care management of acute phase ill patients and measures for the control of the epidemic, the outcome of ebola survivors became an important question as their number increased and raised new issues. a multidisciplinary prospective cohort of survivors in guinea has been launched by ird umi 233 and donka national hospital, conakry, guinea, to asse ...201627704472
computational approach for predicting the conserved b-cell epitopes of hemagglutinin h7 subtype influenza virus.an avian-origin influenza h7n9 virus epidemic occurred in china in 2013-2014, in which >422 infected people suffered from pneumonia, respiratory distress syndrome and septic shock. h7n9 viruses belong to the h7 subtype of avian-origin influenza viruses (aiv-h7). hemagglutinin (ha) is a vital membrane protein of aiv that has an important role in host recognition and infection. the epitopes of ha are significant determinants of the regularity of epidemic and viral mutation and recombination mechan ...201627703505
community-based surveillance to monitor mortality in a malaria-endemic and ebola-epidemic setting in rural guinea.multiple community-based approaches can aid in quantifying mortality in the absence of reliable health facility data. community-based sentinel site surveillance that was used to document mortality and the systems utility for outbreak detection was evaluated. we retrospectively analyzed data from 46 sentinel sites in three sous-préfectures with a reinforced malaria control program and one sous-préfecture without (koundou) in guinea. deaths were recorded by key informants and classified as due to ...201627698277
educating health care providers in treatment of patients with ebola virus disease.nurses manage patients with common infectious diseases by following institutional guidelines based on expert advice, evidence in the literature, and a wealth of experience. today nurses are challenged to provide care to patients with multidrug-resistant organisms and virulent infectious diseases such as ebola virus disease. management of some patients with virulent infectious diseases occurs in the context of minimal experience with the pathogen, course of infection, diagnostics, nursing care, a ...201627694364
inappropriate bradycardia in ebola virus disease.as part of french assistance for the outbreak of ebola virus disease in west africa, a military treatment center for infected healthcare workers was deployed in conakry, guinea. although some cases of bradycardia have been reported since the first ebola outbreak, they have never been documented to our knowledge. we studied heart rhythm in patients with ebola virus disease to analyze inappropriate bradycardia and discuss its mechanism.201627694085
successful implementation of a multicountry clinical surveillance and data collection system for ebola virus disease in west africa: findings and lessons learned.the 2014 outbreak of ebola virus disease (evd) in west africa was the largest ever recorded. starting in september 2014, international medical corps (imc) managed 5 ebola treatment units (etus) in liberia and sierra leone, which cumulatively cared for about 2,500 patients. we conducted a retrospective cohort study of patient data collected at the 5 etus over 1 year of operations.201627688716
strengthening health systems while responding to a health crisis: lessons learned by a nongovernmental organization during the ebola virus disease epidemic in sierra leone.an epidemic of ebola virus disease (evd) beginning in 2013 has claimed an estimated 11 310 lives in west africa. as the evd epidemic subsides, it is important for all who participated in the emergency ebola response to reflect on strengths and weaknesses of the response. such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (ngos), survivors of ebola ...201627688219
[back to the future. vaccine trials against ebola in the history of resistance to immunization].vaccine trials against ebola virus have been conceived and organized, in august 2014, after the epidemic started in three countries of west africa. if the preparedness had been missing, the planners tried to anticipate the resistance to vaccination, in guinea, sierra leone and liberia. this article offers a retrospective view on the resistances to vaccination throughout its history, from smallpox inoculation to anti-polio vaccine. resistances have been linked to the political contexts and the re ...201627686081
toward an effective ebola virus vaccine.long-term control of viral outbreaks requires the use of vaccines to impart acquired resistance and ensuing protection. in the wake of an epidemic, established immunity against a particular disease can limit spread and significantly decrease mortality. creation of a safe and efficacious vaccine against ebola virus (ebov) has proven elusive so far, but various inventive strategies are now being employed to counteract the threat of outbreaks caused by ebov and related filoviruses. here, we present ...201727686015
adeno-associated virus serotype 9-expressed zmapp in mice confers protection against systemic and airway-acquired ebola virus infection.adeno-associated viral vectors can be used as a platform for delivering biological countermeasures against pandemic and biological threats. we show that vector delivery of two antibody components of the zmapp product is effective in mice against systemic and airway challenge with a mouse-adapted strain of ebola virus. this platform provides a generic manufacturing solution and overcomes some of the delivery challenges associated with repeated administration of the protective protein.201627683818
monoclonal antibodies for the treatment of ebola virus disease.to date, the management of patients with suspected or confirmed ebolavirus disease (evd) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. however, accelerated by the recent large outbreak in west africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. areas covered: we describe recent developments in mono ...201627676206
could bat cell temperature and filovirus filament length explain the emergence of ebola virus in mammals? predictions of a thermodynamic model.the host reservoir of zaire ebolavirus (ebov) remains elusive. one suggestion is that ebov emerges in mammals when the precursor virus jumps from mayflies (or other riverine insects) to insectivorous bats. however, this does not fit with the current view that filoviruses cannot infect arthropods. here, it is first argued that the evidence that arthropods are refractory is not definitive. second, it is proposed that a combination of filovirus filament length and the high temperature (~42°c) exper ...201627670273
a highly sensitive assay using synthetic blood containing test microbes for evaluation of the penetration resistance of protective clothing material under applied pressure.to prevent nosocomial infections caused by even either ebola virus or methicillin-resistant staphylococcus aureus (mrsa), healthcare workers must wear the appropriate protective clothing which can inhibit contact transmission of these pathogens. therefore, it is necessary to evaluate the performance of protective clothing for penetration resistance against infectious agents. in japan, some standard methods were established to evaluate the penetration resistance of protective clothing fabric mate ...201627667519
zero health worker infection: experiences from the china ebola treatment unit during the ebola epidemic in liberia.in november 2014, a total of 164 health care workers were dispatched by the chinese government as the first medical assistance team to liberia. the tasks of this team were to establish a china ebola treatment unit (etu), to commence the initial admission and treatment of suspected and confirmed ebola patients, and to provide public health and infection control training for relevant local personnel. overall, during the 2-month stay of this first medical assistance team in liberia, 112 ebola-suspe ...201627666397
characterization of the unconventional secretion of the ebola matrix protein vp40.while most secreted proteins use the classical endoplasmic reticulum (er)-golgi secretion pathway to reach the extracellular medium, a few proteins are secreted through unconventional secretary pathways. viral proteins can be secreted through unconventional secretion pathways. here, we describe how we have recently demonstrated that the ebola virus (ebov) matrix protein vp40 is released from transfected and infected cells in a soluble form through an unconventional secretion pathway.201627665561
model-informed risk assessment and decision making for an emerging infectious disease in the asia-pacific region.effective response to emerging infectious disease (eid) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. the asia-pacific region contains low and middle income countries in which the risk of eid outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. the absence of comprehensive data on populations, health care systems and disea ...201627661978
evolutionary conservation of ebola virus proteins predicts important functions at residue level.the recent outbreak of ebola virus disease (evd) resulted in a large number of human deaths. due to this devastation, the ebola virus has attracted renewed interest as model for virus evolution. recent literature on ebola virus (ebov) has contributed substantially to our understanding of the underlying genetics and its scope with reference to the 2014 outbreak. but no study yet, has focused on the conservation patterns of ebov proteins.201727659453
ebola virus - from neglected threat to global emergency state.this review aims to update knowledge about ebola virus disease (evd) and recent advances in its diagnosis, treatment and prevention.201627656857
identification of novel vp35 inhibitors: virtual screening driven new scaffolds.ebola virus is a single-stranded, negative-sense rna virus that causes acute and serious life-threatening illness. in recent years the ebola virus has spread through several countries in africa, highlighting the need to develop new treatments for this disease and boosting a new research effort on this subject. however, so far there is no valid treatment for disease created by this pathogen. the ebola virus viral protein 35 (vp35) is a multifunctional protein which is critical for virus replicati ...201627657828
ebola nurse 'relieved' after nmc clears her of misconduct in airport screening process.scottish nurse pauline cafferkey (pictured right), who recovered from the ebola virus, spoke of her relief after being cleared of misconduct by the nursing and midwifery council.201627654520
pathogenicity comparison between the kikwit and makona ebola virus variants in rhesus macaques.enhanced virulence and/or transmission of west african ebola virus (ebov) variants, which are divergent from their central african counterparts, are suspected to have contributed to the sizable toll of the recent ebola virus disease (evd) outbreak. this study evaluated the pathogenicity and shedding in rhesus macaques infected with 1 of 2 west african isolates (ebov-c05 or ebov-c07) or a central african isolate (ebov-k). all animals infected with ebov-c05 or ebov-c07 died of evd, whereas 2 of 3 ...201627651412
in vitro assembly of ebola virus nucleocapsid-like complex expressed in e. coli.ebola virus (ebov) harbors an rna genome encapsidated by nucleoprotein (np) along with other viral proteins to form a nucleocapsid complex. previous cryo-eletron tomography and biochemical studies have shown the helical structure of ebov nucleocapsid at nanometer resolution and the first 450 amino-acid of np (npδ451-739) alone is capable of forming a helical nucleocapsid-like complex (nlc). however, the structural basis for np-np interaction and the dynamic procedure of the nucleocapsid assembly ...201627650953
survey of emergency department staff on disaster preparedness and training for ebola virus disease.in the domestic response to the outbreak of ebola virus disease from 2013 to 2015, many us hospitals developed and implemented specialized training programs to care for patients with ebola. this research reports on the effects of targeted training on emergency department (ed) staff's ebola-related perceptions and attitudes.201627649747
ebola virus disease in children, sierra leone, 2014-2015.little is known about potentially modifiable factors in ebola virus disease in children. we undertook a retrospective cohort study of children <13 years old admitted to 11 ebola holding units in the western area, sierra leone, during 2014-2015 to identify factors affecting outcome. primary outcome was death or discharge after transfer to ebola treatment centers. all 309 ebola virus-positive children 2 days-12 years old were included; outcomes were available for 282 (91%). case-fatality was 57%, ...201627649367
knowledge and attitude regarding ebola virus disease among medical students of rawalpindi: a preventable threat not yet confronted.to assess the knowledge and attitude regarding ebola virus disease (evd) among medical students of rawalpindi.201727648059
fluid resuscitation in ebola virus disease: witch method of intravascular access choice? 201627647377
[emerging infectious agents].emergence of many emerging or re-emerging infectious diseases have occurred over the past decade, some of which are major public threat. sars, mers-cov, highly pathogenic avian influenza a(h5n1), ebola virus disease have raised concerns because of their virulence, their mortality, and/or their modality of transmission, or their impact on maternofoetal transmission (zika virus). the witness of these emergences have conducted health authorities to have policies and plans and to imagine new organiz ...201627644171
in silico and in vitro methods to identify ebola virus vp35-dsrna inhibitors.ebola virus continues to be problematic as sporadic outbreaks in africa continue to arise, and as terrorist organizations have considered the virus for bioterrorism use. several proteins within the virus have been targeted for antiviral chemotherapy, including vp35, a dsrna binding protein that promotes viral replication, protects dsrna from degradation, and prevents detection of the viral genome by immune complexes. to augment the scope of our antiviral research, we have now employed molecular ...201627642076
ebola nurse pauline cafferkey accused of concealing high temperature.pauline cafferkey, the nurse who was infected with the ebola virus while caring for sick people in west africa, has been accused of concealing her temperature during checks on her return to the uk.201627641552
early and repeated use of plasma for the management of ebola patients: reflection around a case.in december 2013, the most widespread epidemic of ebola virus disease began in guinea and continued for over 2 years. at the request of the guinean state, france deployed a military field hospital to treat ebola infected healthcare workers. from january to july 2015, our center supported 26 healthcare workers suffering from ebola virus disease. despite an individualized care and optimal treatment, the fatality rate remained high at 30.7%. improved therapies are required to reduce mortality risk ...201727640108
molecular diagnostic field test for point-of-care detection of ebola virus directly from blood.a molecular diagnostic method for robust detection of ebola virus (ebov) at the point of care (poc) directly from blood samples is described. this assay is based on reverse transcriptase loop-mediated isothermal amplification (rt-lamp) of the glycoprotein gene of ebov. complete reaction formulations were lyophilized in 0.2-ml polymerase chain reaction tubes. rt-lamp reactions were performed on a battery-operated isothermal instrument. limit of detection of this rt-lamp assay was 2.8 × 10(2) plaq ...201627638947
analysis of diagnostic findings from the european mobile laboratory in guéckédou, guinea, march 2014 through march 2015.a unit of the european mobile laboratory (emlab) consortium was deployed to the ebola virus disease (evd) treatment unit in guéckédou, guinea, from march 2014 through march 2015.201627638946
human transbodies to vp40 inhibit cellular egress of ebola virus-like particles.a direct acting anti-ebola agent is needed. vp40, a conserved protein across ebolavirus (ebov) species has several pivotal roles in the virus life cycle. inhibition of vp40 functions would lessen the virion integrity and interfere with the viral assembly, budding, and spread. in this study, cell penetrable human scfvs (huscfvs) that bound to ebov vp40 were produced by phage display technology. gene sequences coding for vp40-bound-huscfvs were subcloned from phagemids into protein expression plas ...201627638305
pregnancy outcomes in liberian women who conceived after recovery from ebola virus disease. 201627633422
implementation of a national semen testing and counseling program for male ebola survivors - liberia, 2015-2016.according to world health organization (who) data, the ebola virus disease (ebola) outbreak that began in west africa in 2014 has resulted in 28,603 cases and 11,301 deaths (1). in march 2015, epidemiologic investigation and genetic sequencing in liberia implicated sexual transmission from a male ebola survivor, with ebola virus detected by reverse transcription-polymerase chain reaction (rt-pcr) 199 days after symptom onset (2,3), far exceeding the 101 days reported from an earlier ebola outbre ...201627632552
ebola virus lingers longer than scientists thought. 201627629619
eukaryotic-like virus budding in archaea.similar to many eukaryotic viruses (and unlike bacteriophages), viruses infecting archaea are often encased in lipid-containing envelopes. however, the mechanisms of their morphogenesis and egress remain unexplored. here, we used dual-axis electron tomography (et) to characterize the morphogenesis of sulfolobus spindle-shaped virus 1 (ssv1), the prototype of the family fuselloviridae and representative of the most abundant archaea-specific group of viruses. our results show that ssv1 assembly an ...201627624130
ebolavirus glycoprotein fc fusion protein protects guinea pigs against lethal challenge.ebola virus (ebov), a member of the filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. currently, there are no licensed vaccines or therapeutics to prevent and treat ebov infection. several vaccines based on the ebov glycoprotein (gp) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. we previously demonstrated that a subunit vaccine containing the extracellular do ...201627622456
screening of fda-approved drugs for treatment of emerging pathogens.the current outbreaks of middle east respiratory syndrome (mers) and ebolavirus (ebov) have revealed a gap in the development and availability of drugs to treat these infections. to date, there are no approved treatments for patients infected with mers coronavirus (mers-cov), a virus that continues to infect new patients and that has now spread from the middle east to asia. despite a downward trend in the number of new ebov cases in west africa, new infections are still occurring, and many patie ...201527617922
chemical targeting of a g-quadruplex rna in the ebola virus l gene.in the present study, our bioinformatics analysis first reveals the existence of a conserved guanine-rich sequence within the zaire ebolavirus l gene. using various methods, we show that this sequence tends to fold into g-quadruplex rna. tmpyp4 treatment evidently inhibits l gene expression at the rna level. moreover, the mini-replicon assay demonstrates that tmpyp4 effectively inhibits the artificial zaire ebolavirus mini-genome and is a more potent inhibitor than ribavirin. although tmpyp4 tre ...201627617851
experimental treatment of ebola virus disease with brincidofovir.the nucleotide analogue brincidofovir was developed to prevent and treat infections caused by double-stranded dna viruses. based on in vitro data suggesting an antiviral effect against ebola virus, brincidofovir was included in the world health organisation list of agents that should be prioritised for clinical evaluation in patients with ebola virus disease (evd) during the west african epidemic.201627611077
a "trojan horse" bispecific-antibody strategy for broad protection against ebolaviruses.there is an urgent need for monoclonal antibody (mab) therapies that broadly protect against ebola virus and other filoviruses. the conserved, essential interaction between the filovirus glycoprotein, gp, and its entry receptor niemann-pick c1 (npc1) provides an attractive target for such mabs but is shielded by multiple mechanisms, including physical sequestration in late endosomes. here, we describe a bispecific-antibody strategy to target this interaction, in which mabs specific for npc1 or t ...201627608667
ebola virus replication and disease without immunopathology in mice expressing transgenes to support human myeloid and lymphoid cell engraftment.the study of ebola virus (ebov) pathogenesis in vivo has been limited to nonhuman primate models or use of an adapted virus to cause disease in rodent models. herein we describe wild-type ebov (makona variant) infection of mice engrafted with human hematopoietic cd34(+) stem cells (hu-nsg™-sgm3 mice; hereafter referred to as sgm3 humice). sgm3 humice support increased development of myeloid immune cells, which are primary ebov targets. in sgm3 humice, ebov replicated to high levels, and disease ...201627601621
spatiotemporal dynamics of the ebola epidemic in guinea and implications for vaccination and disease elimination: a computational modeling analysis.among the three countries most affected by the ebola virus disease outbreak in 2014-2015, guinea presents an unusual spatiotemporal epidemic pattern, with several waves and a long tail in the decay of the epidemic incidence.201627600737
development of a liquid chromatography high resolution mass spectrometry method for the quantitation of viral envelope glycoprotein in ebola virus-like particle vaccine preparations.ebola virus like particles (ebov vlps, evlps), are produced by expressing the viral transmembrane glycoprotein (gp) and structural matrix protein vp40 in mammalian cells. when expressed, these proteins self-assemble and bud from 'host' cells displaying morphology similar to infectious virions. several studies have shown that rodents and non-human primates vaccinated with evlps are protected from lethal ebov challenge. the mucin-like domain of envelope glycoprotein gp1 serves as the major target ...201627597813
the liberia men's health screening program for ebola virus: win-win-win for survivor, scientist, and public health. 201627596040
prevention of sexual transmission of ebola in liberia through a national semen testing and counselling programme for survivors: an analysis of ebola virus rna results and behavioural data.ebola virus has been detected in semen of ebola virus disease survivors after recovery. liberia's men's health screening program (mhsp) offers ebola virus disease survivors semen testing for ebola virus. we present preliminary results and behavioural outcomes from the first national semen testing programme for ebola virus.201627596037
in vivo ebola virus infection leads to a strong innate response in circulating immune cells.ebola virus is the causative agent of a severe syndrome in humans with a fatality rate that can approach 90 %. during infection, the host immune response is thought to become dysregulated, but the mechanisms through which this happens are not entirely understood. in this study, we analyze rna sequencing data to determine the host response to ebola virus infection in circulating immune cells.201627595844
lujo viral hemorrhagic fever: considering diagnostic capacity and preparedness in the wake of recent ebola and zika virus outbreaks.lujo virus is a novel old world arenavirus identified in southern africa in 2008 as the cause of a viral hemorrhagic fever (vhf) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). whereas this outbreak was limited, the unprecedented ebola virus disease outbreak in west africa, and recent zika virus disease epidemic in the americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoon ...201627593704
peptides for anti-ebolavirus vaccines.two main factors can affect the development of ebolavirus immunotherapeutics: the vast peptide commonality between ebolavirus and human proteins, and the high rate of spontaneous mutation of ebolavirus within its human host. indeed, the viral versus human peptide overlap may represent a relevant source of autoimmune crossreactions following vaccination, while ebolavirus genome mutations can limit and/or nullify a vaccine response.201627593388
analytical validation of the reebov antigen rapid test for point-of-care diagnosis of ebola virus infection.ebola virus disease (evd) is a severe viral illness caused by ebola virus (ebov). the 2013-2016 evd outbreak in west africa is the largest recorded, with >11 000 deaths. development of the reebov antigen rapid test (reebov rdt) was expedited to provide a point-of-care test for suspected evd cases.201627587634
ebola virus disease diagnostics, sierra leone: analysis of real-time reverse transcription-polymerase chain reaction values for clinical blood and oral swab specimens.during the ebola virus outbreak of 2013-2016, the viral special pathogens branch field laboratory in sierra leone tested approximately 26 000 specimens between august 2014 and october 2015. analysis of the b2m endogenous control ct values showed its utility in monitoring specimen quality, comparing results with different specimen types, and interpretation of results. for live patients, blood is the most sensitive specimen type and oral swabs have little diagnostic utility. however, swabs are hig ...201627587631
infectious disease physicians' perceptions about ebola preparedness early in the us response: a qualitative analysis and lessons for the future.on september 30, 2014, the first us patient with ebola virus disease was diagnosed. hospitals and healthcare systems identified many complex issues that needed to be addressed to prepare for possible future outbreaks. here we summarize themes identified in free text responses from a query of infectious disease physicians from the infectious disease society of america's (idsa) emerging infections network (ein) early in the domestic ebola response and place them into the context of biopreparedness ...201627584854
releasing the genomic rna sequestered in the mumps virus nucleocapsid.in a negative strand rna virus, the genomic rna is sequestered inside the nucleocapsid when the viral rna-dependent rna polymerase uses it as the template for viral rna synthesis. it must require a conformational change in the nucleocapsid protein (np) to make the rna accessible by the viral polymerase during this process. the structure of an empty mumps virus nucleocapsid-like particle is determined to 10.4 å resolution by cryoem image reconstruction. by modeling the crystal structure of parain ...201627581981
ebola outbreak preparedness and preventive measures among healthcare providers in saudi arabia.as medical professionals on the front lines in the outbreaks of infectious disease like ebola virus disease (evd), healthcare providers must have sufficient knowledge, skills, and best practices to protect themselves and the public from the disease. the purpose of this study is to identify the level of awareness, attitudes and practices among healthcare workers in relation to precautionary measures to evd.201627580328
a mathematical model with quarantine states for the dynamics of ebola virus disease in human populations.a deterministic ordinary differential equation model for the dynamics and spread of ebola virus disease is derived and studied. the model contains quarantine and nonquarantine states and can be used to evaluate transmission both in treatment centres and in the community. possible sources of exposure to infection, including cadavers of ebola virus victims, are included in the model derivation and analysis. our model's results show that there exists a threshold parameter, r 0, with the property th ...201627579053
epidemiology and management of the 2013-16 west african ebola outbreak.the 2013-16 west african ebola outbreak is the largest, most geographically dispersed, and deadliest on record, with 28,616 suspected cases and 11,310 deaths recorded to date in guinea, liberia, and sierra leone. we provide a review of the epidemiology and management of the 2013-16 ebola outbreak in west africa aimed at stimulating reflection on lessons learned that may improve the response to the next international health crisis caused by a pathogen that emerges in a region of the world with a ...201627578439
clinical profile and containment of the ebola virus disease outbreak in two large west african cities, nigeria, july-september 2014.the ebola virus disease (evd) outbreak in nigeria began when an infected diplomat from liberia arrived in lagos, the most populous city in africa, with subsequent transmission to another large city.201627575939
decontamination of a field laboratory dedicated to ebola virus-infected patients.in 2015, the french armed forces deployed a biosafety level 3 (bsl3) field laboratory as a part of an ebola treatment center in guinea. when closing the center, laboratory decontamination operations were necessary. we present the decontamination protocols applied for the bsl3 field laboratory, making the entire module ready for a future use.201627575772
ebola virus is unlikely to become endemic in west africa. 201627572170
passive immunotherapy: assessment of convalescent serum against ebola virus makona infection in nonhuman primates.convalescent serum and blood were used to treat patients during outbreaks of zaire ebolavirus (zebov) infection in 1976 and 1995, with inconclusive results. during the recent 2013-2016 west african epidemic, serum/plasma from survivors of zebov infection was used to treat patients in the affected countries and several repatriated patients. the effectiveness of this strategy remains unknown.201627571900
inactivation of zaire ebolavirus variant makona in human serum samples analyzed by enzyme-linked immunosorbent assay.personnel deployed to remote areas during infectious disease outbreaks have limited access to mechanical and chemical inactivation resources. the inactivation of infectious agents present in diagnostic samples is critical to ensure the safety of personnel and the containment of the disease. we evaluated the efficacy of thermal inactivation (exposure to 56°c for 1 hour) and chemical inactivation with 0.5% tween-20 against a high titer of ebola virus (species zaire ebolavirus) variant makona in sp ...201627571899
compact, polyvalent mannose quantum dots as sensitive, ratiometric fret probes for multivalent protein-ligand interactions.a highly efficient cap-exchange approach for preparing compact, dense polyvalent mannose-capped quantum dots (qds) has been developed. the resulting qds have been successfully used to probe multivalent interactions of hiv/ebola receptors dc-sign and dc-signr (collectively termed as dc-sign/r) using a sensitive, ratiometric förster resonance energy transfer (fret) assay. the qd probes specifically bind dc-sign, but not its closely related receptor dc-signr, which is further confirmed by its speci ...201627563159
structures of ebola virus gp and sgp in complex with therapeutic antibodies.the ebola virus (ebov) gp gene encodes two glycoproteins. the major product is a soluble, dimeric glycoprotein (sgp) that is secreted abundantly. despite the abundance of sgp during infection, little is known regarding its structure or functional role. a minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (gp). gp mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. because lar ...201627562261
bayesian uncertainty quantification for transmissibility of influenza, norovirus and ebola using information geometry.infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. viral shedding data are collected during human studies-either where volunteers are infected with a disease or where existing cases are recruited-in which the levels of live virus produced over time are measured. these have traditionally been difficult to analyse due to strong, ...201627558850
epidemiological data management during an outbreak of ebola virus disease: key issues and observations from sierra leone.sierra leone experienced intense transmission of ebola virus disease (evd) from may 2014 to november 2015 during which a total of 8,704 confirmed cases and over 3,589 confirmed deaths were reported. our field observation showed many issues in the evd data management system, which may have contributed to the magnitude and long duration of the outbreak. in this perspective article, we explain the key issues with evd data management in the field, and the resulting obstacles in analyzing key epidemi ...201627551675
clues to the mechanism of cholesterol transfer from the structure of npc1 middle lumenal domain bound to npc2.export of ldl-derived cholesterol from lysosomes requires the cooperation of the integral membrane protein niemann-pick c1 (npc1) and a soluble protein, niemann-pick c2 (npc2). mutations in the genes encoding these proteins lead to niemann-pick disease type c (npc). npc2 binds to npc1's second (middle), lumenally oriented domain (mld) and transfers cholesterol to npc1's n-terminal domain (ntd). here, we report the 2.4-å resolution crystal structure of a complex of human npc1-mld and npc2 bearing ...201627551080
parental presence during treatment of ebola or other highly consequential infection.this clinical report offers guidance to health care providers and hospitals on options to consider regarding parental presence at the bedside while caring for a child with suspected or proven ebola virus disease (ebola) or other highly consequential infection. options are presented to help meet the needs of the patient and the family while also posing the least risk to providers and health care organizations. the optimal way to minimize risk is to limit contact between the person under investiga ...201627550981
cardiac mri findings suggest myocarditis in severe ebola virus disease. 201627544899
ebola virus disease: awareness among dental students in hungary.the ebola epidemic has claimed thousands of lives in africa, and there has been a mounting pressure on the healthcare systems around the globe to prepare for the showing up of patients infected with this virus. junior clinicians are at the forefront of medical teams, often coming into contact with patients first, during clerking and admissions. this study assesses the level of knowledge of ebola virus disease (evd) among dental students at semmelweis university, budapest, hungary.201627539229
ethical considerations surrounding the response to ebola: the spanish experience.the recent ebola virus disease (evd) outbreak, with 28,646 reported cases and 11,323 deaths, was declared a public health emergency of international interest by the world health organisation. in spain, a single reported case triggered a public health crisis of a markedly media-centred nature. the approach to the first evd epidemic has given rise to various ethical considerations around the world. we address the most relevant ethical considerations emanating from the management of evd in spain.201627538685
defective interfering genomes and ebola virus persistence. 201627533436
a helping hand to overcome solubility challenges in chemical protein synthesis.although native chemical ligation (ncl) and related chemoselective ligation approaches provide an elegant method to stitch together unprotected peptides, the handling and purification of insoluble and aggregation-prone peptides and assembly intermediates create a bottleneck to routinely preparing large proteins by completely synthetic means. in this work, we introduce a new general tool, fmoc-ddae-oh, n-fmoc-1-(4,4-dimethyl-2,6-dioxocyclo-hexylidene)-3-[2-(2-aminoethoxy)ethoxy]-propan-1-ol, a he ...201627532670
plasmodium parasitemia associated with increased survival in ebola virus-infected patients.the ongoing ebola outbreak in west africa has resulted in 28 646 suspected, probable, and confirmed ebola virus infections. nevertheless, malaria remains a large public health burden in the region affected by the outbreak. a joint centers for disease control and prevention/national institutes of health diagnostic laboratory was established in monrovia, liberia, in august 2014, to provide laboratory diagnostics for ebola virus.201627531847
computational analysis of ebolavirus data: prospects, promises and challenges.the ongoing ebola virus (also known as zaire ebolavirus, a member of the ebolavirus family) outbreak in west africa has so far resulted in >28000 confirmed cases compared with previous ebolavirus outbreaks that affected a maximum of a few hundred individuals. hence, ebolaviruses impose a much greater threat than we may have expected (or hoped). an improved understanding of the virus biology is essential to develop therapeutic and preventive measures and to be better prepared for future outbreaks ...201627528741
erratum: smither, s.; et al. effectiveness of four disinfectants against ebola virus on different materials. viruses 2016, 8, 185.the viruses editorial office wishes to notify its readers of corrections in [1].[...].201627527208
defining antigen-specific plasmablast and memory b cell subsets in human blood after viral infection or vaccination.antigen-specific b cells bifurcate into antibody-secreting cells (ascs) and memory b cells (mbcs) after infection or vaccination. ascs (plasmablasts) have been extensively studied in humans, but less is known about b cells that become activated but do not differentiate into plasmablasts. here we have defined the phenotype and transcriptional program of a subset of antigen-specific b cells, which we have called 'activated b cells' (abcs), that were distinct from ascs and were committed to the mbc ...201627525369
stochasticity and the limits to confidence when estimating r0 of ebola and other emerging infectious diseases.dynamic models - often deterministic in nature - were used to estimate the basic reproductive number, r0, of the 2014-5 ebola virus disease (evd) epidemic outbreak in west africa. estimates of r0 were then used to project the likelihood for large outbreak sizes, e.g., exceeding hundreds of thousands of cases. yet fitting deterministic models can lead to over-confidence in the confidence intervals of the fitted r0, and, in turn, the type and scope of necessary interventions. in this manuscript we ...201627524644
pharmacodynamics and systems pharmacology approaches to repurposing drugs in the wake of global health burden.there are emergent needs for cost-effective treatment worldwide, for which repurposing to develop a drug with existing marketing approval of disease(s) for new disease(s) is a valid option. although strategic mining of electronic health records has produced real-world evidences to inform drug repurposing, using omics data (drug and disease), knowledge base of protein interactions, and database of transcription factors have been explored. structured integration of all the existing data under the ...201627522921
ebola virus disease is characterized by poor activation and reduced levels of circulating cd16+ monocytes.a number of previous studies have identified antigen-presenting cells (apcs) as key targets of ebola virus (ebov), but the role of apcs in human ebola virus disease (evd) is not known. we have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (dcs) in peripheral blood of patients for whom evd was diagnosed by the european mobile laboratory in guinea. acute evd was characterized by reduced levels of circulating nonclassical cd16(+) monocytes with a poor activatio ...201627521367
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