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clinical evaluation of quicknavitm-ebola in the 2018 outbreak of ebola virus disease in the democratic republic of the congo.the recent large outbreaks of ebola virus disease (evd) in west africa and the democratic republic of the congo (drc) have highlighted the need for rapid diagnostic tests to control this disease. in this study, we clinically evaluated a previously developed immunochromatography-based kit, quicknavitm-ebola. during the 2018 outbreaks in drc, 928 blood samples from evd-suspected cases were tested with quicknavitm-ebola and the who-approved genexpert. the sensitivity and specificity of quicknavitm- ...201931261668
distinct genome replication and transcription strategies within the growing filovirus family.research on filoviruses has historically focused on the highly pathogenic ebola- and marburgviruses. indeed, until recently, these were the only two genera in the filovirus family. recent advances in sequencing technologies have facilitated the discovery of not only a new ebolavirus, but also three new filovirus genera and a sixth proposed genus. while two of these new genera are similar to the ebola- and marburgviruses, the other two, discovered in saltwater fishes, are considerably more divers ...201931260690
personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.in epidemics of highly infectious diseases, such as ebola virus disease (evd) or severe acute respiratory syndrome (sars), healthcare workers (hcw) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. contact precautions by means of personal protective equipment (ppe) can reduce the risk. it is unclear which type of ppe protects best, what is the best way to remove ppe, and how to make sure hcw use ppe as instructed.201931259389
filovirus disease outbreaks: a chronological overview.filoviruses cause outbreaks which lead to high fatality in humans and non-human primates, thus tagging them as major threats to public health and species conservation. in this review, we give account of index cases responsible for filovirus disease outbreaks that have occurred over the past 52 years in a chronological fashion, by describing the circumstances that led to the outbreaks, and how each of the outbreaks broke out. since the discovery of marburg virus and ebola virus in 1967 and 1976, ...201931258326
dynamics of the humoral immune response to a prime-boost ebola vaccine: quantification and sources of variation.the ebola vaccine based on ad26.zebov/mva-bn-filo prime-boost regimens is being evaluated in multiple clinical trials. the long-term immune response to the vaccine is unknown, including factors associated with the response and variability around the response. we analyzed data from three phase 1 trials performed by the ebovac1 consortium in four countries: the united kingdom, kenya, tanzania, and uganda. participants were randomized into four groups based on the interval between prime and boost i ...201931243126
tim-1 serves as a receptor for ebola virus in vivo, enhancing viremia and pathogenesis.t cell immunoglobulin mucin domain-1 (tim-1) is a phosphatidylserine (ps) receptor, mediating filovirus entry into cells through interactions with ps on virions. tim-1 expression has been implicated in ebola virus (ebov) pathogenesis; however, it remains unclear whether this is due to tim-1 serving as a filovirus receptor in vivo or, as others have suggested, tim-1 induces a cytokine storm elicited by t cell/virion interactions. here, we use a bsl2 model virus that expresses ebov glycoprotein to ...201931242184
care of pregnant women: experience from a maternity-specific ebola isolation unit in sierra leone.the ebola virus disease epidemic was devastating to the west african region, particularly for pregnant women. prior to the epidemic, maternal mortality in this region was among the highest in the world. throughout the region, screening of patients with ebola was difficult, as the symptoms of malaria or typhoid mimicked ebola, but even more difficult for pregnant women, because of the large overlap between ebola symptoms and pregnancy-related complications. in november 2014, the world's first mat ...201931241247
meet the ebola workers battling a virus in a war zone. 201931239562
reporting quality of the 2014 ebola outbreak in africa: a systematic analysis.the objective of this study was to conduct a systematic analysis of the reporting quality of the ebola virus disease (evd) outbreak in west africa from 2014-2018 using the modified strobe statement. we included studies on the 2014 evd outbreak alone, limited to those on human patients in africa. we searched the following databases (medline, embase, and web of science) for outbreak reports published between 2014-2018. we assessed factors potentially associated with the quality of reporting. a tot ...201931237909
conceptions within misconceptions: pluralisms in an ebola vaccine trial in west africa.ensuring that biomedical information about research procedures is adequately understood by participants and their communities is key for conducting ethical research. this article explores participants' understanding of trial procedures for an experimental vaccine against ebola virus disease (evd) in a west african context. we found that some trial participants believed there was a chance of contracting ebola and other sicknesses from the vaccine, and others believed both the vaccine and the plac ...202031237180
ensuring on-site ebola patient monitoring and follow-up: development of a laboratory structure embedded in an ebola treatment center.the capacity to rapidly distinguish ebola virus disease from other infectious diseases and to monitor biochemistry and viremia levels is crucial to the clinical management of suspected ebola virus disease cases. this article describes the design and practical considerations of a laboratory straddling the high- and low-risk zones of an ebola treatment center to produce timely diagnostic and clinical results for informed case management of ebola virus disease in real-life conditions. this innovati ...201931232266
operational research: did health systems in sierra leone recover after the 2014-15 ebola outbreak?findings from participants who attended the second post-ebola sort-it course are reported in five short papers on the "legacy of ebola on health systems in sierra-leone". after a decline of health service provision and utilisation during the ebola outbreak, present findings show recovery over time in the post-ebola period. however, important challenges remain, including an important health workforce gap.201931231516
next-generation sequencing study of pathogens in serum from patients with febrile jaundice in sierra leone.people in western africa suffer greatly from febrile jaundice, which is caused by a variety of pathogens. however, yellow fever virus (yfv) is the only pathogen under surveillance in sierra leone owing to the undeveloped medical and public health system there. most of the results of yfv identification are negative. elucidation of the pathogen spectrum is required to reduce the prevalence of febrile jaundice.201931217053
one month follow up of a neonate born to a mother who survived ebola virus disease during pregnancy: a case report in the democratic republic of congo.the authors report a 1 month follow up of a neonate described as "miracle baby" because she was born ebola virus disease-free and survived after her mother was infected with ebola virus during the third trimester of pregnancy.201931215482
trends of and factors associated with cesarean section related surgical site infections in guinea.since the adoption of free obstetric care policy in guinea in 2011, no study has examined the surgical site infections in maternity facilities. the objective of this study was to assess the trends of and factors associated with surgical site infection following cesarean section in guinean maternity facilities from 2013 to 2015. this was a retrospective cohort study using routine medical data from ten facilities. overall, the incidence of surgical site infections following cesarean section showed ...201931214304
world health organization resists declaring ebola emergency - for third time. 201931213685
[bushmeat, human impacts and human health in tropical rainforests: the ebola virus case].at a time when more than 5 million tonnes of bushmeat are harvested annually from tropical forests, and which account for a significant, but unrecorded, share of the gross domestic product of many forest countries, decision makers are encouraged, within conservation and food security policies, to understand the role that wildlife can play in the conservation of ecosystem services. in this article, we present an analysis of the problem, describing the role played by bushmeat in human diets, and t ...201931210471
active monitoring versus direct active monitoring for ebola virus disease in the united states: experiences and perceptions of former persons under monitoring in the district of columbia and indiana.during the 2014-2016 west africa ebola outbreak, the centers for disease control and prevention recommended daily monitoring and surveillance of persons arriving in the united states (us) from impacted areas through either active monitoring (phone calls, online platforms, and so on) or direct active monitoring (in-person or electronic visualization). intensiveness of policies implemented by state/local jurisdictions varied markedly. to study the experiences and perceptions of active monitoring v ...201931207426
centers for disease control and prevention's temporary epidemiology field assignee program: supporting state and local preparedness in the wake of ebola.the centers for disease control and prevention launched the temporary epidemiology field assignee (tefa) program to help state and local jurisdictions respond to the risk of ebola virus importation during the 2014-2016 ebola outbreak in west africa. we describe steps taken to launch the 2-year program, its outcomes and lessons learned.201931205697
sequencing of mrna from whole blood using nanopore sequencing.sequencing in remote locations and resource-poor settings presents unique challenges. nanopore sequencing can be successfully used under such conditions, and was deployed to west africa during the recent ebola virus epidemic, highlighting this possibility. in addition to its practical advantages (low cost, ease of equipment transport and use), this technology also provides fundamental advantages over second-generation sequencing approaches, particularly the very long read length, ability to dire ...201931205309
logistical challenges in the dr congo ebola virus response. 201931204652
t-705 induces lethal mutagenesis in ebola and marburg populations in macaques.nucleoside analogues (na) disrupt rna viral rna-dependent rna polymerase (rdrp) function and fidelity for multiple viral families. the mechanism of action (moa) of t-705 has been attributed alternatively or concurrently to chain termination and lethal mutagenesis depending on the viral species during in vitro studies. in this study, we evaluated the effect of t-705 on the viral population in non-human primates (nhps) after challenge with ebola virus (ebov) or marburg virus (marv) to identify the ...201931195019
estimating undetected ebola spillovers.the preparedness of health systems to detect, treat, and prevent onward transmission of ebola virus disease (evd) is central to mitigating future outbreaks. early detection of outbreaks is critical to timely response, but estimating detection rates is difficult because unreported spillover events and outbreaks do not generate data. using three independent datasets available on the distributions of secondary infections during evd outbreaks across west africa, in a single district (western area) o ...201931194734
roles of yigl sequence of ebola virus vp40 on genome replication and particle production.ebola virus (ebov) vp40 is a major driving force of nascent virion production and a negative regulator of genome replication/transcription. here, we showed that the yigl sequence at the c-terminus of ebov vp40 is important for virus-like particle (vlp) production and the regulation of genome replication/transcription. accordingly, a mutation in the yigl sequence caused defects in vlp production and genome replication/transcription. the residues i293 and l295 in the yigl sequence were particularl ...201931184566
the 2013-2016 ebola epidemic: evaluating communication strategies between two affected countries in west africa.ebola is a haemorrhagic disease with high fatality rates between 25 and 90%. the 2013-16 ebola outbreak in west africa was the largest to date with >28 000 cases and >11 000 fatalities. this outbreak exposed inadequacies in public health agencies and has spurred health officials to re-evaluate the way ebola virus disease (evd) epidemics are co-ordinated and communicated.202031177274
glucopyranosyl lipid adjuvant enhances immune response to ebola virus-like particle vaccine in mice.the identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to the development of new protein-based vaccines. the ebola virus-like particle (vlp) vaccine expressing ebola virus glycoprotein (gp) and matrix protein (vp40) was used in this study to evaluate the ability of tlr4 agonist glucopyranosyl lipid adjuvant (gla) formulated in a stable emulsion (se) to enhance immunogenicity and promote durable protection against mouse-adapted ebo ...201931174937
the impact of various promotional activities on ebola prevention behaviors and psychosocial factors predicting ebola prevention behaviors in the gambia evaluation of ebola prevention promotions.the outbreak of the ebola virus disease (evd) from 2014 to 2016 is over. however, several outbreaks of contagious diseases have already arisen and will recur. this paper aims to evaluate the effectiveness of evd prevention promotions in the gambia and to assess the psychosocial factors that steer three behaviors: handwashing with soap, calling the ebola hotline, and not touching a person who might be suffering from evd. in 2015, data were gathered from 498 primary care providers. the questionnai ...201931174301
developing a personal protective equipment selection matrix for preventing occupational exposure to ebola virus.in response to the 2014 ebola outbreak in west africa and resulting cases in the united states, the occupational safety and health administration developed a personal protective equipment selection matrix to help employers protect workers from exposure to ebola virus in the event of additional us cases. now, the world's second largest ebola outbreak on record continues to expand in the democratic republic of congo, where more than 70 ebola-infected healthcare workers serve as reminders of the im ...201931173502
ultrasensitive ebola virus antigen sensing via 3d nanoantenna arrays.sensitive detection of pathogens is crucial for early disease diagnosis and quarantine, which is of tremendous need in controlling severe and fatal illness epidemics such as of ebola virus (ebov) disease. serology assays can detect ebov-specific antigens and antibodies cost-effectively without sophisticated equipment; however, they are less sensitive than reverse transcriptase polymerase chain reaction (rt-pcr) tests. herein, a 3d plasmonic nanoantenna assay sensor is developed as an on-chip imm ...201931168856
effect of gamma irradiation on the antibody response measured in human serum from subjects vaccinated with recombinant vesicular stomatitis virus-zaire ebola virus envelope glycoprotein vaccine.rvsvδg-zebov-gp vaccine is a live recombinant (r) vesicular stomatitis virus (vsv), where the vsv g protein is replaced with the zaire ebola virus (zebov) glycoprotein (gp). for vaccine immunogenicity testing, clinical trial sera collected during an active zebov outbreak underwent gamma irradiation (gi) before testing in biosafety level 2 laboratories to inactivate possible wild-type zebov. before irradiating pivotal trial samples, two independent studies evaluated the impact of gi (50 kgy) on b ...201931162004
anti-siglec-1 antibodies block ebola viral uptake and decrease cytoplasmic viral entry.several ebola viruses cause outbreaks of lethal haemorrhagic fever in humans, but developing therapies tackle only zaire ebola virus. dendritic cells (dcs) are targets of this infection in vivo. here, we found that ebola virus entry into activated dcs requires the sialic acid-binding ig-like lectin 1 (siglec-1/cd169), which recognizes sialylated gangliosides anchored to viral membranes. blockage of the siglec-1 receptor by anti-siglec-1 monoclonal antibodies halted ebola viral uptake and cytopla ...201931160823
addressing disease-related stigma during infectious disease outbreaks.outbreaks of emerging infectious disease are a constant threat. in the last 10 years, there have been outbreaks of 2009 influenza a (h1n1), ebola virus disease, and zika virus. stigma associated with infectious disease can be a barrier to adopting healthy behaviors, leading to more severe health problems, ongoing disease transmission, and difficulty controlling infectious disease outbreaks. much has been learned about infectious disease and stigma in the context of nearly 4 decades of the human ...201931156079
geographic charisma and the potential energy of ebola.the ebola virus is unparalleled in its charismatic ability to ignite fear, anxiety and disgust at a scale grossly disproportionate to the number of lives it claims. as an archetypal 'emerging infectious disease' (eid), this designation and the politics that have encircled it have provided ebola with a conceptual space in which epidemiology and geography to splice together in the genesis and maintenance of its charismatic valence. even before the west african outbreak of 2013-2016, ebola was an ' ...201931155737
ebola virus replication stands out.a recent study by deflubé et al. (proc. natl. acad. sci. u. s. a. 2019;116:8535-8543) reported that ebola virus genomes have variable 3' terminal nucleotides. this finding is a departure from other nonsegmented, negative-strand rna viruses (nnsvs) that have been studied to date and has broad implications for filoviral replication and innate immune evasion.201931155428
responding to the ebola virus disease outbreak in dr congo: when will we learn from sierra leone? 201931153643
a qualitative study assessing the feasibility of implementing a group cognitive-behavioural therapy-based intervention in sierra leone.mental health support in sierra leone is sparse, and qualitative research into the feasibility of implementing psychological interventions is equally underdeveloped. following the 2014 ebola virus disease outbreak, south london and maudsley nhs trust were commissioned to develop a psychological intervention that uk clinicians could train national staff with minimal psychological experience to deliver to their peers. following the completion of the stepped care, group-based cognitive-behavioural ...201931144684
can tracking people through phone-call data improve lives? 201931142864
the mental health professional at the feet of the ebola virus: individual treatment and global mental challenges.summarymental health professionals form an important component of the response teams currently working in the democratic republic of the congo to treat what is historically the second-largest ebola outbreak. they provide psychological treatment to patients under extraordinary conditions, helping them cope with anxiety and the daily death of other patients.declaration of interestnone.201931142389
evaluating temperature sensitivity of vesicular stomatitis virus-based vaccines.use of the vesicular stomatitis virus (vsv)-based ebola virus vaccine during outbreaks and the potential use of a similar vsv-based lassa virus vaccine has raised questions about the vaccines' stability should the cold chain fail. we demonstrated that current cold chain conditions might tolerate significant variances without affecting efficacy.201931141474
antiviral innate responses induced by vsv-ebov vaccination contribute to rapid protection.ebola virus (ebov) is a single-stranded rna virus that causes ebola virus disease (evd), characterized by excessive inflammation, lymphocyte apoptosis, hemorrhage, and coagulation defects leading to multiorgan failure and shock. recombinant vesicular stomatitis virus expressing the ebov glycoprotein (vsv-ebov), which is highly efficacious against lethal challenge in nonhuman primates, is the only vaccine that successfully completed a phase iii clinical trial. additional studies showed vsv-ebov p ...201931138743
exploring the human-animal interface of ebola virus disease outbreaks.whereas the prevention and treatment of ebola virus disease (evd) have been well studied after the 2013-16 outbreak in west africa, the emergence of human outbreaks and their mechanisms have yet to be explored in detail. in particular, it has yet to be clarified whether the emergence records offer any theoretical insight into the changing interface between humans and animal reservoirs. here we explore the epidemiological record of emergence, investigating predominant causes of the introduction t ...201931137254
synthesis and structure-activity relationships of 3,5-disubstituted-pyrrolo[2,3- b]pyridines as inhibitors of adaptor-associated kinase 1 with antiviral activity.there are currently no approved drugs for the treatment of emerging viral infections, such as dengue and ebola. adaptor-associated kinase 1 (aak1) is a cellular serine-threonine protein kinase that functions as a key regulator of the clathrin-associated host adaptor proteins and regulates the intracellular trafficking of multiple unrelated rna viruses. moreover, aak1 is overexpressed specifically in dengue virus-infected but not bystander cells. because aak1 is a promising antiviral drug target, ...201931136173
improving health information systems during an emergency: lessons and recommendations from an ebola treatment centre in sierra leone.the 2014-2016 west africa ebola epidemic highlighted the difficulty of collecting patient information during emergencies, especially in highly infectious environments. health information systems (hiss) appropriate for such settings were lacking prior to this outbreak. here we describe our development and implementation of paper and electronic hiss at the sierra leone kerry town ebola treatment centre (etc) from 2014 to 2015. we share our approach, experiences, and recommendations for future heal ...201931133075
recent advances in marburgvirus research.marburgviruses are closely related to ebolaviruses and cause a devastating disease in humans. in 2012, we published a comprehensive review of the first 45 years of research on marburgviruses and the disease they cause, ranging from molecular biology to ecology. spurred in part by the deadly ebola virus outbreak in west africa in 2013-2016, research on all filoviruses has intensified. not meant as an introduction to marburgviruses, this article instead provides a synopsis of recent progress in ma ...201931131088
anti-niemann pick c1 single-stranded oligonucleotides with locked nucleic acids potently reduce ebola virus infection in vitro.ebola virus is the causative agent of ebola virus disease, a severe, often fatal illness in humans. so far, there are no us food and drug administration (fda)-approved therapeutics directed against ebola virus. here, we selected the host factor niemann-pick c1 (npc1), which has been shown to be essential for ebola virus entry into host cytoplasm, as a therapeutic target for suppression by locked nucleic acid-modified antisense oligonucleotides. screening of antisense oligonucleotides in human an ...201931125846
exploitation of glycosylation in enveloped virus pathobiology.glycosylation is a ubiquitous post-translational modification responsible for a multitude of crucial biological roles. as obligate parasites, viruses exploit host-cell machinery to glycosylate their own proteins during replication. viral envelope proteins from a variety of human pathogens including hiv-1, influenza virus, lassa virus, sars, zika virus, dengue virus, and ebola virus have evolved to be extensively glycosylated. these host-cell derived glycans facilitate diverse structural and func ...201931121217
quality improvement of health systems in an epidemic context: a framework based on lessons from the ebola virus disease outbreak in west africa.quality improvement (qi) in health generally focuses on the provision of health services with the aim of improving service delivery. yet qi can be applied not only to health services but also to health systems overall. this is of growing relevance considering that due to deficiencies in health systems, the main countries affected by ebola virus disease (evd) outbreak in west africa (2014-2016) were insufficiently prepared for the epidemic, and according to the who, epidemics are increasingly bec ...202031120603
inhibition of marburg virus rna synthesis by a synthetic anti-vp35 antibody.marburg virus causes sporadic outbreaks of severe hemorrhagic fever with high case fatality rates. approved, effective, and safe therapeutic or prophylactic countermeasures are lacking. to address this, we used phage display to engineer a synthetic antibody, sfab h3, which binds the marburg virus vp35 protein (mvp35). mvp35 is a critical cofactor of the viral replication complex and a viral immune antagonist. sfab h3 displayed high specificity for mvp35 and not for the closely related ebola viru ...201931120240
characterization of novel splice variants of zinc finger antiviral protein (zap).given the unprecedented scale of the recent ebola and zika viral epidemics, it is crucial to understand the biology of host factors with broad antiviral action in order to develop novel therapeutic approaches. here, we look into one such factor: zinc finger antiviral protein (zap) inhibits a variety of rna and dna viruses. alternative splicing results in two isoforms that differ at their c termini: zapl (long) encodes a poly(adp-ribose) polymerase (parp)-like domain that is missing in zaps (shor ...201931118263
creating a national specimen referral system in guinea: lessons from initial development and implementation.in the wake of the 2014-2016, west africa ebola virus disease (evd) outbreak, the government of guinea recognized an opportunity to strengthen its national laboratory system, incorporating capacity and investments developed during the response. the ministry of health (moh) identified creation of a holistic, safe, secure, and timely national specimen referral system as a priority for improved detection and confirmation of priority diseases, in line with national integrated disease surveillance an ...201931111025
[functional analysis of host proteins involved in rna virus replication].since rna virus genome encodes only a limited number of viral proteins, replication of rna virus mostly relies on host cells. elucidation of host proteins that play important roles in the virus replication cycles contributes not only to fundamental virology research but also to applied research such as development of antiviral drugs. we revealed that ebola virus matrix protein vp40 utilized host copii transport machinery for its intracellular transport to the plasma membrane. second, we demonstr ...201831105137
longitudinal analysis of the human b cell response to ebola virus infection.ebola virus (ebov) remains a public health threat. we performed a longitudinal study of b cell responses to ebov in four survivors of the 2014 west african outbreak. infection induced lasting ebov-specific immunoglobulin g (igg) antibodies, but their subclass composition changed over time, with igg1 persisting, igg3 rapidly declining, and igg4 appearing late. striking changes occurred in the immunoglobulin repertoire, with massive recruitment of naive b cells that subsequently underwent hypermut ...201931104840
rigorous surveillance is necessary for high confidence in end-of-outbreak declarations for ebola and other infectious diseases.the world health organization considers an ebola outbreak to have ended once 42 days have passed since the last possible exposure to a confirmed case. benefits of a quick end-of-outbreak declaration, such as reductions in trade/travel restrictions, must be balanced against the chance of flare-ups from undetected residual cases. we show how epidemiological modelling can be used to estimate the surveillance level required for decision-makers to be confident that an outbreak is over. results from a ...201931104606
the natural product eugenol is an inhibitor of the ebola virus in vitro.since the 2014 ebola virus (ebov) outbreak in west africa there has been considerable effort towards developing drugs to treat ebola virus disease and yet to date there is no fda approved treatment. this is important as at the time of writing this manuscript there is an ongoing outbreak in the democratic republic of the congo which has killed over 1000.201931101988
incorporation of ebola glycoprotein into hiv particles facilitates dendritic cell and macrophage targeting and enhances hiv-specific immune responses.the development of an effective vaccine against hiv infection remains a global priority. dendritic cell (dc)-based hiv immunotherapeutic vaccine is a promising approach which aims at optimizing the hiv-specific immune response using primed dcs to promote and enhance both the cellular and humoral arms of immunity. since the ebola virus envelope glycoprotein (ebogp) has strong dc-targeting ability, we investigated whether ebogp is able to direct hiv particles towards dcs efficiently and promote po ...201931100082
malaria surveillance - united states, 2016.malaria in humans is caused by intraerythrocytic protozoa of the genus plasmodium. these parasites are transmitted by the bite of an infective female anopheles species mosquito. the majority of malaria infections in the united states occur among persons who have traveled to regions with ongoing malaria transmission. however, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposur ...201931099769
complete genome sequence of a new ebola virus strain isolated during the 2017 likati outbreak in the democratic republic of the congo.genomic sequencing for early identification of ebola virus remains a big challenge in low-income countries. here, we report the complete genome sequence of an ebola virus strain obtained during the 2017 likati outbreak in the democratic republic of the congo (drc) by using the oxford nanopore technologies (ont) minion sequencer.201931097506
association of ebola virus infection with hearing loss in regions where ebola virus infection is endemic: a systematic review.many survivors of ebola virus infection describe new-onset hearing loss after infection. the prevalence, severity, and pathophysiologic features of hearing loss in this population have not been well characterized.201931095264
identification of ebola virus inhibitors targeting gp2 using principles of molecular mimicry.a key step in the ebola virus (ebov) replication cycle involves conformational changes in viral glycoprotein 2 (gp2) which facilitate host-viral membrane fusion and subsequent release of the viral genome. ebola gp2 plays a critical role in virus entry and has similarities in mechanism and structure to the hiv gp41 protein for which inhibitors have been successfully developed. in this work, a putative binding pocket for the c-terminal heptad repeat in the n-terminal heptad repeat trimer was targe ...201931092576
utilizing the focused conversation method in qualitative public health research: a team-based approach.qualitative research studies are becoming increasingly necessary to understand the complex challenges in the healthcare setting. successfully integrating interdisciplinary teams of investigators can be challenging, as investigators inherently view data through their disciplinary lens. thus, new methods, such as focused conservation, are needed to facilitate qualitative data analysis by interdisciplinary teams. the purpose of this manuscript is to provide a clear description of how we implemented ...201931088551
in silico selection of amplification targets for rapid polymorphism screening in ebola virus outbreaks.to achieve maximum transmission chain tracking in the current ebola outbreak, whole genome sequencing (wgs) has been proposed to provide optimal information. however, wgs remains a costly and time-intensive procedure that is poorly suited for the large numbers of samples being generated, especially under severe time and work-environment constraints as in the present drc outbreak. to better prepare for future outbreaks, where an apparent single outbreak may actually represent overlapping outbreak ...201931080442
analyzing and forecasting the ebola incidence in north kivu, the democratic republic of the congo from 2018-19 in real time.during an ebola virus disease (evd) outbreak, the analysis and forecasting of the incidence in real time is challenged by reporting of cases, especially the reporting delay. it should be remembered that the latest count of cases is likely underestimated in real time, and moreover, the effective reproduction number, i.e. the average number of secondary cases generated by a single primary case at a given point in time, is also underestimated without proper adjustment. the present study aimed to ad ...201931080016
backbone resonance assignments and secondary structure of ebola nucleoprotein 600-739 construct.ebola viral infections have resulted in several deadly epidemics in recent years in west and central africa. because only one of the seven proteins encoded by the viral genome possesses enzymatic activity, disruption of protein-protein interactions is a promising route for antiviral drug development. we carried out a screening campaign to identify small, drug-like compounds that bind to the c-terminal region of the multifunctional ebola nucleoprotein (enp) with the objective of discovering ones ...201931076990
intranasal immunization with recombinant vaccinia virus tiantan harboring zaire ebola virus gp elicited systemic and mucosal neutralizing antibody in mice.accumulating literature revealed that human mucosa was likely one of the important routes for ebov attachment and further infection. therefore inducing effective mucosal immune responses play key role in preventing the virus infection. vaccinia virus tiantan strain (vv) was a remarkably attenuated poxvirus, which has been broadly exploited as a multifunctional vector during the development of genetically recombinant vaccine and cancer therapeutic agent. in this study, we generated a recombinant ...201931076161
conserved b and t cell epitopes prediction of ebola virus glycoprotein for vaccine development: an immuno-informatics approach.ebola virus (ebov), a non-segmented single-stranded rna virus, is often-most transmitted through body fluids like sweat, tears, saliva, and nasal secretions. till date, there is no licensed vaccine of ebov is available in the market; however, the world is increasingly vulnerable to this emerging threat. hence, it is the need of time to develop a vaccine for ebov to hinder its dissemination. the current study has been designed for identification and characterization of the potential b and t-cell ...201931075428
reproductive health sequelae among women who survived ebola virus disease in liberia.to estimate the incidence of failed pregnancy and menstrual irregularities among liberian women who had survived ebola virus disease (evd) and to identify host-specific and disease-specific factors associated with these outcomes.201931074837
evaluation of the sick returned traveler.infections are common during travel, and frontline physicians frequently must evaluate sick returned travelers. sick travelers can be clinically challenging due to the wide range of endemic diseases in different geographic regions. to guide the diagnostic and treatment plan, consideration of endemic and emerging infections in the region of travel, as well as careful review of the travelers' exposures and preventative measures are necessary. routine laboratory tests and cultures cannot confirm ma ...201931072653
ebola virus vp35 has novel ntpase and helicase-like activities.ebola virus (ebov) is a non-segmented, negative-sense rna virus (nnsv) in the family filoviridae, and is recognized as one of the most lethal pathogens in the planet. for rna viruses, cellular or virus-encoded rna helicases play pivotal roles in viral life cycles by remodelling viral rna structures and/or unwinding viral dsrna produced during replication. however, no helicase or helicase-like activity has ever been found to associate with any nnsv-encoded proteins, and it is unknown whether the ...201931066445
author correction: infection with the makona variant results in a delayed and distinct host immune response compared to previous ebola virus variants.a correction to this article has been published and is linked from the html and pdf versions of this paper. the error has not been fixed in the paper.201931065012
evaluating the impact of intravenous fluid resuscitation on survival for the management of patients with ebola virus disease. 202031055594
extracellular vesicles and ebola virus: a new mechanism of immune evasion.ebola virus (ebov) disease can result in a range of symptoms anywhere from virtually asymptomatic to severe hemorrhagic fever during acute infection. additionally, spans of asymptomatic persistence in recovering survivors is possible, during which transmission of the virus may occur. in acute infection, substantial cytokine storm and bystander lymphocyte apoptosis take place, resulting in uncontrolled, systemic inflammation in affected individuals. recently, studies have demonstrated the presenc ...201931052499
impact of intravenous fluid therapy on survival among patients with ebola virus disease: an international multisite retrospective cohort study.intravenous fluid (ivf) is a frequently recommended intervention in ebola virus disease (evd), yet its impact on patient outcomes remains unclear.202031050703
toward an alignment-free method for feature extraction and accurate classification of viral sequences.the classification of pathogens in emerging and re-emerging viruses represents major interests in taxonomic studies, functional genomics, host-pathogen interplay, prevention, and disease treatments. it consists of assigning a given sequence to its related group of known sequences sharing similar characteristics and traits. the challenges to such classification could be associated with several virus properties including recombination, mutation rate, multiplicity of motifs, and diversity. in domai ...201931050550
assessing health systems in guinea for prevention and control of priority zoonotic diseases: a one health approach.to guide one health capacity building efforts in the republic of guinea in the wake of the 2014-2016 ebola virus disease (evd) outbreak, we sought to identify and assess the existing systems and structures for zoonotic disease detection and control. we partnered with the government ministries responsible for human, animal, and environmental health to identify a list of zoonotic diseases - rabies, anthrax, brucellosis, viral hemorrhagic fevers, trypanosomiasis and highly pathogenic avian influenz ...201931049389
anti-ebola therapy for patients with ebola virus disease: a systematic review.management of ebola virus disease (evd) has historically focused on infection prevention, case detection and supportive care. several specific anti-ebola therapies have been investigated, including during the 2014-2016 west african outbreak. our objective was to conduct a systematic review of the effect of anti-ebola virus therapies on clinical outcomes to guide their potential use and future evaluation.201931046707
cryo-em structure of the ebola virus nucleoprotein-rna complex.ebola virus is an emerging virus that is capable of causing a deadly disease in humans. replication, transcription and packaging of the viral genome are carried out by the viral nucleocapsid. the nucleocapsid is a complex of the viral nucleoprotein, rna and several other viral proteins. the nucleoprotein forms large, rna-bound, helical filaments and acts as a scaffold for additional viral proteins. the 3.1 å resolution single-particle cryo-electron microscopy structure of the nucleoprotein-rna h ...201931045563
implementing infection prevention and control capacity building strategies within the context of ebola outbreak in a "hard-to-reach" area of liberia.in august 2014, who declared that ebola outbreak ravaging west africa including liberia had become a public health emergency of international concern (pheic). infection prevention and control (ipc) among healthcare workers was pivotal in reducing healthcare worker infection and containing the recent evd outbreak. hard to reach areas (htra) presents peculiar challenges in public health emergencies. we present the result of ipc capacity building strategies deployed in gbarpolu county: an htra of l ...201831037168
understanding long-term effects of ebola virus disease. 201931036880
effectiveness of dettol antiseptic liquid for inactivation of ebola virus in suspension.the efficacy of dettol antiseptic liquid (dal) for inactivating ebola virus (makona c07 variant) (ebov/mak) within an organic load in suspension was evaluated per astm e1052-11. three dal lots were evaluated at dilutions of 1:10, 1:20, and 1:40, with contact times of 0.5, 1, 5, and 10 min. approximately 7 log10 tissue culture infectious dose50 (tcid50) of ebov/mak was exposed to dal at ambient temperature. each dilution tested reduced the infectious ebov/mak titer by ~5 log10 within one min. det ...201931036865
ebola virus disease in women and children. 201931033589
expanding research capacity in sub-saharan africa through informatics, bioinformatics, and data science training programs in mali.bioinformatics and data science research have boundless potential across africa due to its high levels of genetic diversity and disproportionate burden of infectious diseases, including malaria, tuberculosis, hiv and aids, ebola virus disease, and lassa fever. this work lays out an incremental approach for reaching underserved countries in bioinformatics and data science research through a progression of capacity building, training, and research efforts. two global health informatics training pr ...201931031807
ebola virus disease: clinical challenges, recognition, and management.the 2014 to 2016 ebola outbreak response resulted in many lessons learned about biocontainment patient care, leading to enhanced domestic capabilities for highly infectious and hazardous communicable diseases. however, additional opportunities for improvement remain. the article identifies and describes key considerations and challenges for laboratory analysis, clinical management, transportation, and personnel management during the care of patients infected with ebola or other special pathogens ...201931027659
ictv virus taxonomy profile: filoviridae.members of the family filoviridae produce variously shaped, often filamentous, enveloped virions containing linear non-segmented, negative-sense rna genomes of 15-19 kb. several filoviruses (e.g., ebola virus) are pathogenic for humans and are highly virulent. several filoviruses infect bats (e.g., marburg virus), whereas the hosts of most other filoviruses are unknown. this is a summary of the international committee on taxonomy of viruses (ictv) report on filoviridae, which is available at www ...201931021739
inflammatory and humoral immune response during ebola virus infection in survivor and fatal cases occurred in sierra leone during the 2014⁻2016 outbreak in west africa.ebola virus (ebov) infection is characterized by an excessive inflammatory response, a loss of lymphocytes and a general paralysis of the immune system, however pathophysiological mechanisms are not fully understood. in a cohort of 23 fatal and 21 survivors of ebola virus disease (evd) cases admitted to the emergency ebola-treatment-center in goderich (freetown, sierra leone) during the 2014 to 2016 ebov epidemic in western africa, we analyzed the pathway-focused gene expression profile of secre ...201931018522
identification of ruvbl1 and ruvbl2 as novel cellular interactors of the ebola virus nucleoprotein.ebola virus (ebov) is a filovirus that has become a global public health threat in recent years. ebov is the causative agent of a severe, often fatal hemorrhagic fever. a productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. to date, several investigations have discovered specific host-pathogen interactions for various ebov proteins. however, relatively little is known about the ebov nucleoprotein (np) with regard to host inte ...201931018511
assessment of the function and intergenus-compatibility of ebola and lloviu virus proteins.sequences for lloviu virus (llov), a putative novel filovirus, were first identified in miniopterus schreibersii bats in spain following a massive bat die-off in 2002, and also recently found in bats in hungary. however, until now it is unclear if these sequences correspond to a fully functional, infectious virus, and whether it will show a pathogenic phenotype like african filoviruses, such as ebola- and marburgviruses, or be apathogenic for humans, like the asian filovirus reston virus. since ...201931017565
pre-clinical development of a vaccine against lassa fever.lassa virus (lasv) is a persistent global health threat that causes about half a million cases of lassa fever each year in western africa. although most cases are mild, the disease can cause significant morbidity and results in as many as 5,000 deaths per year. since 2015, nigeria has been experiencing a severe and extended outbreak of lassa fever, raising concerns that it could spill over into other countries and reach a magnitude similar to the west african ebola outbreak of 2013-2016. despite ...201831015807
towards high quality real-time whole genome sequencing during outbreaks using usutu virus as example.recently, protocols for amplicon based whole genome sequencing using nanopore technology have been described for ebola virus, zika virus, yellow fever virus and west nile virus. however, there is some debate regarding reliability of sequencing using this technology, which is important for applications beyond diagnosis such as linking lineages to outbreaks, tracking transmission pathways and pockets of circulation, or mapping specific markers. to our knowledge, no in depth analyses of the require ...201931014969
caring for patients with ebola virus disease: are u.s. biocontainment centers ready for the next outbreak?the 2014 west african ebola virus disease (evd) outbreak is the largest and deadliest evd epidemic to date, resulting in fivefold more cases than all other outbreaks combined. this outbreak was particularly devastating to healthcare workers in west africa and resulted in several evd patients being medically evacuated for treatment in the u.s. and europe. governmental agencies provide recommendations for triaging and testing patients with evd, however best laboratory practices are still unknown a ...201931010606
identifying gaps in frontline healthcare facility high-consequence infectious disease preparedness.hospital infection disease preparedness gaps were brought to the forefront during the 2013-2016 ebola virus disease (evd) outbreak. the ability of us hospitals to rapidly identify, isolate, and manage patients with potentially high-consequence pathogens is a critical component to health security. since the evd cases in dallas, texas, the continuity of hospital preparedness has been questionable. while certain hospitals were designated as evd treatment facilities, the readiness of most american h ...201931009258
fifteen years post-sars: key milestones in canada's public health emergency response.this year marks the 15th anniversary of severe acute respiratory syndrome (sars) in canada and the 100th anniversary of the 1918 spanish influenza pandemic. these, and other recent public health events, provide an opportunity for us to review and reflect on the evolution of canada's public health emergency response over the past 15 years-from sars, to the 2009 h1n1 pandemic influenza, to ebola virus and zika virus disease. key lessons have been learned and milestones achieved that have shaped an ...201831007618
emerging infectious diseases and antimicrobial resistance (eidar).the infectious disease clinical research program's (idcrp) emerging infectious diseases and antimicrobial resistance (eidar) research area is a department of defense (dod) clinical research capability that is responsive and adaptive to emerging infectious disease (eid) threats to us military readiness. among active-duty and other military health system (mhs) beneficiaries, eidar research is largely focused on evaluating the incidence, risk factors, and acute- and long-term health effects of mili ...201931004432
current status of small molecule drug development for ebola virus and other filoviruses.the filovirus family includes some of the deadliest viruses known, including ebola virus and marburg virus. these viruses cause periodic outbreaks of severe disease that can be spread from person to person, making the filoviruses important public health threats. there remains a need for approved drugs that target all or most members of this virus family. small molecule inhibitors that target conserved functions hold promise as pan-filovirus therapeutics. to date, compounds that effectively targe ...201931003196
the world after ebola: an overview of ebola complications, vaccine development, lessons learned, financial losses, and disease preparedness.the 2014-2016 ebola outbreak in west africa was the largest of its kind with 11,000 deaths and approximately 28,637 affected cases. the aim of the study was to analyze the global situation after the ebola outbreak including ebola complications, vaccine development, lessons learned, financial losses, and disease preparedness. we searched in pubmed, google, and google scholar by using keywords ebola virus, ebola vaccine development and ebola virus transmission, the world after ebola, financial los ...201931002597
bombali virus in mops condylurus bat, kenya.bombali virus (genus ebolavirus) was identified in organs and excreta of an angolan free-tailed bat (mops condylurus) in kenya. complete genome analysis revealed 98% nucleotide sequence similarity to the prototype virus from sierra leone. no ebola virus-specific rna or antibodies were detected from febrile humans in the area who reported contact with bats.201931002301
serologic prevalence of ebola virus in equatorial africa.we conducted a serologic survey of 2,430 serum samples collected during 1997-2012 for various studies to determine the prevalence of the hemorrhagic fever virus ebola virus (ebov) in equatorial africa. we screened serum samples for neutralizing antibodies by using a pseudotype microneutralization assay and a newly developed luciferase immunoprecipitation system assay. specimens seroreactive for ebov were confirmed by using an elisa. our results suggest a serologic prevalence of 2%-3.5% in the re ...201931002071
retrospective versus real-time ebola virus sequencing. 201931000466
2018 ebola virus disease outbreak in équateur province, democratic republic of the congo: a retrospective genomic characterisation.the 2018 ebola virus disease (evd) outbreak in équateur province, democratic republic of the congo, began on may 8, and was declared over on july 24; it resulted in 54 documented cases and 33 deaths. we did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures).201931000465
medical countermeasures during the 2018 ebola virus disease outbreak in the north kivu and ituri provinces of the democratic republic of the congo: a rapid genomic assessment.the real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. in response to the recently established genomic capacity in the democratic republic of the congo, we explored the real-time generation of genomic information at the start of the 2018 ebola virus disease (evd) outbreak in north kivu province.201931000464
calu-3 cells are largely resistant to entry driven by filovirus glycoproteins and the entry defect can be rescued by directed expression of dc-sign or cathepsin l.priming of the viral glycoprotein (gp) by the cellular proteases cathepsin b and l (catb, catl) is believed to be essential for cell entry of filoviruses. however, pseudotyping systems that predominantly produce non-filamentous particles have frequently been used to prove this concept. here, we report that gp-mediated entry of retroviral-, rhabdoviral and filoviral particles depends on catb/catl activity and that this effect is cell line-independent. moreover, we show that the human cell line ca ...201930999160
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