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single dose rvsvδg-junvgp vaccine protects guinea pigs against lethal junin virus challenge.junin virus (junv) is a pathogen of biodefense importance due to its potential for aerosol transmission and mortality rates reaching 30%. currently, there are no junv vaccines licensed by the united states food and drug administration (fda) for at-risk individuals. a vaccine based on recombinant vesicular stomatitis virus (rvsv) has been effectively used to prevent ebola virus disease in humans. here, we evaluated the protective efficacy of a rvsv expressing the junv glycoprotein (rvsvδg-junvgp) ...202134373461
bundibugyo ebolavirus survival is associated with early activation of adaptive immunity and reduced myeloid-derived suppressor cell signaling.ebolaviruses bundibugyo virus (bdbv) and ebola virus (ebov) cause fatal hemorrhagic disease in humans and nonhuman primates. while the host response to ebov is well characterized, less is known about bdbv infection. moreover, immune signatures that mediate natural protection against all ebolaviruses remain poorly defined. to explore these knowledge gaps, we transcriptionally profiled bdbv-infected rhesus macaques, a disease model that results in incomplete lethality. this approach enabled us to ...202134372693
why remdesivir failed: preclinical assumptions overestimate the clinical efficacy of remdesivir for covid-19 and ebola.remdesivir is a nucleoside monophosphoramidate prodrug that has been fda-approved for covid-19. however, the clinical efficacy of remdesivir for covid-19 remains contentious, as several trials have not found statistically significant differences in either time to clinical improvement or mortality between remdesivir-treated and control groups. similarly, the inability for remdesivir to provide a clinically significant benefit above other investigational agents in patients with ebola contrasts wit ...202134252308
natural history of disease in cynomolgus monkeys exposed to ebola virus kikwit strain demonstrates the reliability of this non-human primate model for ebola virus disease.filoviruses (family filoviridae genera ebolavirus and marburgvirus) are negative-stranded rna viruses that cause severe health effects in humans and non-human primates, including death. except in outbreak settings, vaccines and other medical countermeasures against ebola virus (ebov) will require testing under the fda animal rule. multiple vaccine candidates have been evaluated using cynomolgus monkeys (cm) exposed to ebov kikwit strain. to the best of our knowledge, however, animal model develo ...202134214118
serological evidence of filovirus infection in nonhuman primates in zambia.ebolaviruses and marburgviruses are filoviruses that are known to cause severe hemorrhagic fever in humans and nonhuman primates (nhps). while some bat species are suspected to be natural reservoirs of these filoviruses, wild nhps often act as intermediate hosts for viral transmission to humans. using an enzyme-linked immunosorbent assay, we screened two nhp species, wild baboons and vervet monkeys captured in zambia, for their serum igg antibodies specific to the envelope glycoproteins of filov ...202134209295
identification and characterization of defective viral genomes in ebola virus-infected rhesus macaques.ebola virus (ebov), of the family filoviridae, is an rna virus that can cause a hemorrhagic fever with a high mortality rate. defective viral genomes (dvgs) are truncated genomes that have been observed during multiple rna virus infections, including in vitro ebov infection, and have previously been associated with viral persistence and immunostimulatory activity. as dvgs have been detected in cells persistently infected with ebov, we hypothesized that dvgs may also accumulate during viral repli ...202134160256
distinct transcriptional responses to fatal ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses.ebola virus (ebov) is a negative single-stranded rna virus within the filoviridae family and the causative agent of ebola virus disease (evd). nonhuman primates (nhps), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of ebov pathogenesis. however, despite significant genetic similarity (>90%), nhp species display different clinical presentation following ebov infection, notably a ∼1-2 days delay in disease progression. consequentl ...202134112056
the ferret as a model for filovirus pathogenesis and countermeasure evaluation.the domestic ferret (mustela putorius furo) has long been a popular animal model for evaluating viral pathogenesis and transmission as well as the efficacy of candidate countermeasures. without question, the ferret has been most widely implemented for modeling respiratory viruses, particularly influenza viruses; however, in recent years, it has gained attention as a novel animal model for characterizing filovirus infections. although ferrets appear resistant to infection and disease caused by ma ...202133951727
prodrugs of a 1'-cn-4-aza-7,9-dideazaadenosine c-nucleoside leading to the discovery of remdesivir (gs-5734) as a potent inhibitor of respiratory syncytial virus with efficacy in the african green monkey model of rsv.a discovery program targeting respiratory syncytial virus (rsv) identified c-nucleoside 4 (rsv a2 ec50 = 530 nm) as a phenotypic screening lead targeting the rsv rna-dependent rna polymerase (rdrp). prodrug exploration resulted in the discovery of remdesivir (1, gs-5734) that is >30-fold more potent than 4 against rsv in hep-2 and nhbe cells. metabolism studies in vitro confirmed the rapid formation of the active triphosphate metabolite, 1-ntp, and in vivo studies in cynomolgus and african green ...202133835812
transcriptomic analysis reveals host mirnas correlated with immune gene dysregulation during fatal disease progression in the ebola virus cynomolgus macaque disease model.ebola virus is a continuing threat to human populations, causing a virulent hemorrhagic fever disease characterized by dysregulation of both the innate and adaptive host immune responses. severe cases are distinguished by an early, elevated pro-inflammatory response followed by a pronounced lymphopenia with b and t cells unable to mount an effective anti-viral response. the precise mechanisms underlying the dysregulation of the host immune system are poorly understood. in recent years, focus on ...202133806942
mucosal challenge ferret models of ebola virus disease.recent studies have shown the domestic ferret (mustela putorius furo) to be a promising small animal model for the study of ebola virus (ebov) disease and medical countermeasure evaluation. to date, most studies have focused on traditional challenge routes, predominantly intramuscular and intranasal administration. here, we present results from a non-clinical pathogenicity study examining oronasal, oral, and ocular mucosal challenge routes in ferrets. animals were challenged with 1, 10, or 100 p ...202133806375
metagenomic snapshots of viral components in guinean bats.to prevent the emergence of zoonotic infectious diseases and reduce their epidemic potential, we need to understand their origins in nature. bats in the order chiroptera are widely distributed worldwide and are natural reservoirs of prominent zoonotic viruses, including nipah virus, marburg virus, and possibly sars-cov-2. in this study, we applied unbiased metagenomic and metatranscriptomic approaches to decipher the virosphere of frugivorous and insectivorous bat species captured in guéckédou, ...202133803988
development and validation of a triplex assay to study an antibody cocktail against ebola virus in cynomolgus serum.background: to support the rapid development of an antibody cocktail against ebola virus and avoid unnecessary exposure to infectious environments, an automatic and fast turnover triplex assay was developed using simoa® (quanterix corporation, ma, usa). materials & methods: a robust triplex assay was developed and validated for simultaneous quantification of the antibody cocktail against ebola virus in cynomolgus serum. results: the assay had a quantitation range of 78.1-5000 ng/ml. the intra- a ...202133792406
lack of molecular mimicry between nonhuman primates and infectious pathogens: the possible genetic bases.recently, it was found that proteomes from poliovirus, measles virus, dengue virus, and severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) have high molecular mimicry at the heptapeptide level with the human proteome, while heptapeptide commonality is minimal or absent with proteomes from nonhuman primates, that is, gorilla, chimpanzee, and rhesus macaque. to acquire more data on the issue, analyses here have been expanded to ebola virus, francisella tularensis , human immunode ...202133748822
hunting and consumption of rodents by children in the lassa fever endemic area of faranah, guinea.as a consequence of the ebola outbreak, human-animal contact has gained importance for zoonotic transmission surveillance. in faranah (upper guinea), daily life is intertwined with rodents, such as the natal multimammate mouse, mastomys natalensis; a reservoir for lassa virus (lasv). however, this contact is rarely perceived as a health risk by residents, although lassa fever (lf) is known to be endemic to this region. conversely, these observations remain a great concern for global health agend ...202133730025
igy antibodies against ebola virus possess post-exposure protection in a murine pseudovirus challenge model and excellent thermostability.ebola virus (ebov) is one of the most virulent pathogens that causes hemorrhagic fever and displays high mortality rates and low prognosis rates in both humans and nonhuman primates. the post-exposure antibody therapies to prevent ebov infection are considered effective as of yet. however, owing to the poor thermal stability of mammalian antibodies, their application in the tropics has remained limited. therefore, a thermostable therapeutic antibody against ebov was developed modelled on the pou ...202133711011
multivalent dna vaccines as a strategy to combat multiple concurrent epidemics: mosquito-borne and hemorrhagic fever viruses.the emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. outbreaks of ebola, lassa, and marburg viruses in overlapping regions of central and west africa and the co-circulation of zika, dengue, and chikungunya viruses in areas with a. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. the dna vaccine platform stands out as such an applica ...202133673603
development of a well-characterized rhesus macaque model of ebola virus disease for support of product development.ebola virus (ebov) is a negative-sense rna virus that can infect humans and nonhuman primates with severe health consequences. development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. the goal of this study was to further characterize ebov disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. rhesus macaques were intram ...202133652589
rapid protection from covid-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine.the ongoing pandemic of coronavirus disease 2019 (covid-19) continues to exert a significant burden on health care systems worldwide. with limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 (sars-cov-2). recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against sars-cov-2. here, ...202133501447
the ecology of nipah virus in bangladesh: a nexus of land-use change and opportunistic feeding behavior in bats.nipah virus is a bat-borne paramyxovirus that produces yearly outbreaks of fatal encephalitis in bangladesh. understanding the ecological conditions that lead to spillover from bats to humans can assist in designing effective interventions. to investigate the current and historical processes that drive nipah spillover in bangladesh, we analyzed the relationship among spillover events and climatic conditions, the spatial distribution and size of pteropus medius roosts, and patterns of land-use ch ...202133498685
tetravalent rabies-vectored filovirus and lassa fever vaccine induces long-term immunity in nonhuman primates.the objective of this study is to evaluate the immunogenicity of adjuvanted monovalent rabies virus-based vaccine candidates against ebola virus (filorab1), sudan virus (filorab2), marburg virus (filorab3), lassa virus (lassarab1), and combined trivalent vaccine candidate (filorab1-3) and tetravalent vaccine candidate (filorab1-3 and lassarab) in nonhuman primates.202133421072
a descriptive study of zoonotic disease risk at the human-wildlife interface in a biodiversity hot spot in south western uganda.zoonotic diseases pose a significant health challenge at the human-wildlife interface, especially in sub-saharan africa where ecosystem services contribute significantly to local livelihoods and individual well-being. in uganda, the fragmented forests of hoima district, form part of a biodiversity and emerging infectious disease hotspot composed of communities with high dependency on these wildlife protected areas, unaware of the associated health risks. we conducted a cross-sectional mixed meth ...202133406074
icu-like care of nonhuman primates with ebola virus disease.ebola virus disease (evd) supportive care strategies are largely guided by retrospective observational research. this study investigated the effect of evd supportive care algorithms on duration of survival in a controlled nonhuman primate (nhp) model.202033367826
nonhuman primate to human immunobridging to infer the protective effect of an ebola virus vaccine candidate.it has been proven challenging to conduct traditional efficacy trials for ebola virus (ebov) vaccines. in the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model. we here propose to infer the protective effect of the ad26.zebov, mva-bn-filo vaccine regimen with a ...202033335092
spillover of ebolaviruses into people in eastern democratic republic of congo prior to the 2018 ebola virus disease outbreak.the second largest ebola virus disease (evd) outbreak began in the democratic republic of congo in july 2018 in north kivu province. data suggest the outbreak is not epidemiologically linked to the 2018 outbreak in equateur province, and that independent introduction of ebola virus (ebov) into humans occurred. we tested for antibodies to ebolaviruses in febrile patients seeking care in north kivu province prior to the evd outbreak.202033169111
[ocular manifestations of viral diseases].viral infections may involve all ocular tissues and may have short and long-term sight-threatening consequences. among them, ocular infections caused by herpesviruses are the most frequent. hsv-1 keratitis and kerato-uveitis affect approximately are the leading cause of infectious blindness in the western world, mainly because of corneal opacification caused by recurrences. for this reason, they may warrant long-term antiviral prophylaxis. herpes zoster ophthalmicus, accounts for 10 to 20% of al ...202033168354
short communication: expanding the range of services to the survivors of ebola virus disease in the democratic republic of the congo.the objectives of the article are to assess the role of a strategic response in the prevention and control of the disease and the need for extending supports to the survivors of disease.202033163027
single-cell profiling of ebola virus disease in vivo reveals viral and host dynamics.ebola virus (ebov) causes epidemics with high mortality yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. here, we used single-cell transcriptomics and cytof-based single-cell protein quantification to characterize peripheral immune cells during ebov infection in rhesus monkeys. we obtained 100,000 transcriptomes and 15,000,000 protein profiles, finding that immature, proliferative monocyte-lineage cells with reduced antigen-presentation ...202033159858
contemporary understanding of ebola and zika virus in pregnancy.understanding the pathophysiology, management, and prevention of emerging infectious diseases among pregnant women is imperative to achieve a successful response from the medical community. ebola and zika viruses represent infections with profound public health implications. in particular, ebola virus is associated with high case fatality and pregnancy and neonatal loss rates, while zika virus has been associated with multiple congenital anomalies; these features present critical clinical dilemm ...202033153665
a paramyxovirus-like model for ebola virus bipartite promoters.paramyxo- and filovirus nucleocapsids (ncs) have bipartite promoters at their 3' ends to initiate rna synthesis. the 2 elements, promoter element 1 (pe1) and promoter element 2 (pe2), are separated by a spacer region that must be exactly a multiple of 6 nucleotides (nt) long. paramyxovirus ncs have 13 nucleoprotein (np) subunits/turn, such that pe1 and pe2 are juxtaposed on the same face of the nc helix, for concerted recognition by the viral polymerase. ebola virus (ebov) ncs, in contrast, have ...202033152032
[ebola, the first vaccines available].in the recent years, ebola virus has been responsible for several major epidemics. research efforts have allowed the development and evaluation in the field of several vaccine candidates. at present, two of them are already approved and used in the fight against the virus in the democratic republic of congo. this review aims to describe the different candidates, the clinical trials that have been conducted as well as the first results in the field.202033151849
fda approves antibody cocktail for ebola virus. 202033144717
development of an antigen detection assay for early point-of-care diagnosis of zaire ebolavirus.the 2013-2016 ebola virus (ebov) outbreak in west africa and the ongoing cases in the democratic republic of the congo have spurred development of a number of medical countermeasures, including rapid ebola diagnostic tests. the likelihood of transmission increases as the disease progresses due to increasing viral load and potential for contact with others. early diagnosis of ebov is essential for halting spread of the disease. polymerase chain reaction assays are the gold standard for diagnosing ...202033141837
the two-stage interaction of ebola virus vp40 with nucleoprotein results in a switch from viral rna synthesis to virion assembly/budding.ebola virus (ebov) is an enveloped negative-sense rna virus and a member of the filovirus family. nucleoprotein (np) expression alone leads to the formation of inclusion bodies (ibs), which are critical for viral rna synthesis. the matrix protein, vp40, not only plays a critical role in virus assembly/budding, but also can regulate transcription and replication of the viral genome. however, the molecular mechanism by which vp40 regulates viral rna synthesis and virion assembly/budding is unknown ...202033141416
evaluation of novel hiv vaccine candidates using recombinant vesicular stomatitis virus vector produced in serum-free vero cell cultures.acquired immune deficiency syndrome (aids) in humans is a result of the destruction of the immune system caused by human immunodeficiency virus (hiv) infection. this serious epidemic is still progressing world-wide. despite advances in treatment, a safe and effective preventive hiv vaccine is desired to combat this disease, and to save millions of lives. however, such a vaccine is not available yet although extensive amounts of resources in research and development have been invested over three ...202033139138
quantification of ebola virus replication kinetics in vitro.mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. ebola modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. but, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provid ...202033137116
insights of novel coronavirus (sars-cov-2) disease outbreak, management and treatment.emerging and re-emerging viral diseases poses a threat to living organisms, and led to serious concern to humankind and public health. the last two decades, viral epidemics such as the severe acute respiratory syndrome (sars-cov) reported in the years 2002-2003, and h1n1 influenza (swine flu) in 2009, middle east respiratory syndrome (mers-cov) from saudi arabia in 2012, ebola virus in 2014-2016, and zika virus in 2015. the recent outbreak of 2019-cov-2 or severe acute respiratory syndrome-2 (sa ...202033134740
addressing obstacles to the inclusion of palliative care in humanitarian health projects: a qualitative study of humanitarian health professionals' and policy makers' perceptions.humanitarian non-governmental organizations provide assistance to communities affected by war, disaster and epidemic. a primary focus of healthcare provision by these organizations is saving lives; however, curative care will not be sufficient, appropriate, or available for some patients. in these instances, palliative care approaches to ease suffering and promote dignity are needed. though several recent initiatives have increased the probability of palliative care being included in humanitaria ...202033133234
screening for anti-influenza actives of prefractionated traditional chinese medicines.traditional chinese medicines (tcms) have proven to possess advantages in counteracting virus infections according to clinical practices. it's therefore of great value to discover novel antivirals from tcms. in this paper, one hundred medicinal plants which have been included in tcm prescriptions for antiviral treatment were selected and prefractionated into 5 fractions each by sequentially using cyclohexane, dichloromethane, ethyl acetate, n-butanol, and water. 500 tcm-simplified extracts were ...202033123207
update on biosafety and emerging infections for the clinical microbiology laboratory.biosafety risks are prevalent in all areas of the clinical laboratories. clinical laboratorians have become accustomed to accepting these risks. when an emerging pathogen appears, the concerns become elevated. since the appearance of ebola virus in the united states in 2014, biosafety practices have made progress. a recent association of public health laboratories survey shows that clinical laboratories are unprepared for current and emerging biosafety challenges. this article focuses on the bio ...202033121616
method feasibility for cross-species testing, qualification, and validation of the filovirus animal nonclinical group anti-ebola virus glycoprotein immunoglobulin g enzyme-linked immunosorbent assay for non-human primate serum samples.an anti-zaire ebola virus (ebov) glycoprotein (gp) immunoglobulin g (igg) enzyme linked immunosorbent assay (elisa) was developed to quantify the serum levels of anti-ebov igg in human and non-human primate (nhp) serum following vaccination and/or exposure to ebov. this method was validated for testing human serum samples as previously reported. however, for direct immunobridging comparability between humans and nhps, additional testing was warranted. first, method feasibility experiments were p ...202033119638
ebola, quarantine, and the need for a new ethical framework.quarantine is a broad public health strategy used to control infectious diseases outbreaks. an arguably most aggressive public health intervention, quarantine limits the asymptomatic individuals' liberty and can result in significant harm. quarantine was used in an attempt to control several ebola outbreaks during the ebola epidemic in west africa in 2014. the most concerning quarantine intervention occurred at west point, a slum of 75,000 people in the capital liberian capital, monrovia. this w ...202033117502
the use of near-infrared light-emitting fluorescent nanodiamond particles to detect ebola virus glycoprotein: technology development and proof of principle.there is a dire need for rapid diagnostic tests of high sensitivity, efficiency, and point-of-test reporting capability to mitigate lethal viral epidemic outbreaks.202033116489
presence of ebola virus in breast milk and risk of mother-to-child transmission: synthesis of evidence.to help inform global guidelines on infant feeding, this systematic review synthesizes evidence related to the presence of the ebola virus (ebov) in breast milk and its potential risk of viral transmission to the infant when breastfeeding. we relied on a comprehensive search strategy to identify studies including women with suspected, probable, or confirmed ebov infection, intending to breastfeed or give breast milk to an infant. our search identified 10,454 records, and after deduplication and ...202033113592
nurses' experiences of their decision-making process when participating in clinical trials during the 2014-2016 west african ebola crisis.due to the absence of a licenced vaccine or drug for treatment of ebola patients during the 2014-2016 west africa outbreak, frontline nurses were at increased risk of exposure. hence, they were prioritized to participate in clinical trials to receive experimental therapeutics. to our knowledge no study has explored the nurses' experiences of their decision-making process when volunteering in clinical trials using unproven agents, which is the purpose of this qualitative study.202033111332
role of platelet cytokines in dengue virus infection.platelets are anucleated blood cells derived from bone marrow megakaryocytes and play a crucial role in hemostasis and thrombosis. platelets contain specialized storage organelles, called alpha-granules, contents of which are rich in cytokines such as c-x-c motif chemokine ligand (cxcl) 1/4/7, (c-c motif) ligand (ccl) 5/3, cxcl8 (also called as interleukin 8, il-8), and transforming growth factor β (tgf-β). activation of platelets lead to degranulation and release of contents into the plasma. pl ...202033102253
innate immune responses to acute viral infection during pregnancy.immunological adaptations in pregnancy allow maternal tolerance of the semi-allogeneic fetus but also increase maternal susceptibility to infection. at implantation, the endometrial stroma, glands, arteries and immune cells undergo anatomical and functional transformation to create the decidua, the specialized secretory endometrium of pregnancy. the maternal decidua and the invading fetal trophoblast constitute a dynamic junction that facilitates a complex immunological dialogue between the two. ...202033101294
meta-analysis of predictive symptoms for ebola virus disease.one of the leading challenges in the 2013-2016 west african ebola virus disease (evd) outbreak was how best to quickly identify patients with evd, separating them from those without the disease, in order to maximise limited isolation bed capacity and keep health systems functioning.202033095771
development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples.surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. however, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as we ...202033095766
molecular determinants of ebola nucleocapsid stability from molecular dynamics simulations.ebola virus (ebov) is a human pathogen with the ability to cause hemorrhagic fever and bleeding diathesis in hosts. the life cycle of ebov depends on its nucleocapsid. the ebola nucleocapsid consists of a helical assembly of nucleoproteins (nps) encapsidating single-stranded viral rna (ssrna). knowledge of the molecular determinants of ebola nucleocapsid stability is essential for the development of therapeutics against ebov. however, large degrees of freedom associated with the ebola nucleocaps ...202033092380
local perspectives on ebola during its tenth outbreak in dr congo: a nationwide qualitative study.the democratic republic of congo (dr congo) struggled to end the tenth outbreak of ebola virus disease (ebola), which appeared in north kivu in 2018. it was reported that rumors were hampering the response effort. we sought to identify any rumors that could have influenced outbreak containment and affected prevention in unaffected areas of dr congo.202033091054
bayesian reconstruction of transmission trees from genetic sequences and uncertain infection times.genetic sequence data of pathogens are increasingly used to investigate transmission dynamics in both endemic diseases and disease outbreaks. such research can aid in the development of appropriate interventions and in the design of studies to evaluate them. several computational methods have been proposed to infer transmission chains from sequence data; however, existing methods do not generally reliably reconstruct transmission trees because genetic sequence data or inferred phylogenetic trees ...202033085643
mental models of infectious diseases and public understanding of covid-19 prevention.the emergence of viral diseases such as ebola virus disease, zika virus disease, and the coronavirus disease (covid-19) has posed considerable challenges to health care systems around the world. public health strategy to address emerging infectious diseases has depended in part on human behavior change and yet the perceptions and knowledge motivating that behavior have been at times inconsistent with the latest consensus of peer-reviewed science. part of that disjuncture likely involves the exis ...202033081500
immunological perspective for ebola virus infection and various treatment measures taken to fight the disease.ebolaviruses, discovered in 1976, belongs to the filoviridae family, which also includes marburg and lloviu viruses. they are negative-stranded rna viruses with six known species identified to date. ebola virus (ebov) is a member of zaire ebolavirus species and can cause the ebola virus disease (evd), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. there are three ebov outbreaks documented in the last six years resulting in significant morbidity (> 32, ...202033080902
modelling the daily risk of ebola in the presence and absence of a potential vaccine.ebola virus - one of the deadliest viral diseases, with a mortality rate around 90% - damages the immune system and organs, with symptoms including episodic fever, chills, malaise and myalgia. the recombinant vesicular stomatitis virus-based candidate vaccine (rvsv-zebov) has demonstrated clinical efficacy against ebola in ring-vaccination clinical trials. in order to evaluate the potential effect of this candidate vaccine, we developed risk equations for the daily risk of ebola infection both c ...202033078134
the ebola outbreak is finally slowing down. 201933077971
the brighton collaboration standardized template for collection of key information for risk/benefit assessment of a modified vaccinia ankara (mva) vaccine platform.the brighton collaboration viral vector vaccines safety working group (v3swg) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. the modified vaccinia ankara (mva) vector system is being explored as a platform for development of multiple vaccines. this paper reviews the molecular and biological features specifically of the mva-bn vector system, followed by a template with details on the safety and characteristics of an mva-bn based vaccine against z ...202033077299
implementation of accelerated research: strategies for implementation as applied in a phase 1 ad26.zebov, mva-bn-filo two-dose ebola vaccine clinical trial in uganda.the 2013-2016 ebola epidemic in west africa is the worst ever caused by ebolaviruses with over 28,000 human cases and 11,325 deaths. the world health organisation (who) declared the epidemic a public health crisis that required accelerated development of novel interventions including vaccines. the medical research council/uganda virus research institute and london school of hygiene and tropical medicine uganda research unit (mrc/uvri & lshtm uganda research unit) was among the african research s ...202033073737
knowledge, (mis-)conceptions, risk perception, and behavior change during pandemics: a scoping review of 149 studies.the severe acute respiratory syndrome-coronavirus-2 pandemic has spread rapidly and has a growing impact on individuals, communities, and healthcare systems worldwide. at the core of any pandemic response is the ability of authorities and other stakeholders to react appropriately by promoting hygiene and social distancing behaviors. successfully reaching this goal requires both individual and collective efforts to drastically modify daily routines and activities. there is a need to clarify how k ...202033073717
reflecting on knowledge translation strategies from global health research projects in tunisia and the republic of côte d'ivoire.we describe the knowledge translation strategies in two projects and share lessons learned about knowledge sharing and uptake.202033068122
immunity to ebola virus: the full picture is being revealed. 202033065040
longitudinal antibody and t cell responses in ebola virus disease survivors and contacts: an observational cohort study.the 2013-16 ebola virus disease epidemic in west africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. the large number of cases provided an opportunity to study the long-term kinetics of zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus.202033065039
her2-mediated enhancement of ebola virus entry.multiple cell surface molecules including tam receptors (tyro3, axl, and mertk), a family of tyrosine kinase receptors, can serve as attachment receptors for ebola virus (ebov) entry into cells. the interaction of these receptors with ebov particles is believed to trigger the initial internalization events that lead to macropinocytosis. however, the details of how these interactions lead to ebov internalization have yet to be elucidated. here, we screened receptor tyrosine kinase (rtk) inhibitor ...202033052961
emergency management at the health and security interface.the world has recently witnessed the global impact of natural disease outbreaks, such as those caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), ebola virus and middle east respiratory syndrome coronavirus, and the lasting impact of the accidental spread of foot and mouth disease in the united kingdom. natural outbreaks, of both emerging and re-emerging diseases, can have significant impacts on local, national and regional communities. an effective response to these outbrea ...202033046925
risk perception during the 2014-2015 ebola outbreak in sierra leone.perceived susceptibility to a disease threat (risk perception) can influence protective behaviour. this study aims to determine how exposure to information sources, knowledge and behaviours potentially influenced risk perceptions during the 2014-2015 ebola virus disease outbreak in sierra leone.202033046052
estimating effective population size changes from preferentially sampled genetic sequences.coalescent theory combined with statistical modeling allows us to estimate effective population size fluctuations from molecular sequences of individuals sampled from a population of interest. when sequences are sampled serially through time and the distribution of the sampling times depends on the effective population size, explicit statistical modeling of sampling times improves population size estimation. previous work assumed that the genealogy relating sampled sequences is known and modeled ...202033044955
development of an enzyme-linked immunosorbent assay to determine the expression dynamics of ebola virus soluble glycoprotein during infection.ebola virus (ebov) is a highly pathogenic virus with human case fatality rates of up to 90%. ebov uses transcriptional editing to express three different glycoproteins (gps) from its gp gene: soluble gp (sgp), gp, and small sgp (ssgp). the molecular ratio of unedited to edited mrna is about 70% (sgp): 25% (gp): 5% (ssgp), indicating that sgp is produced more abundantly than gp. while the presence of sgp has been confirmed in the blood during human ebov infection, there is no report about its exp ...202033036194
prepare for the future: dissecting the spike to seek broadly neutralizing antibodies and universal vaccine for pandemic coronaviruses.learning from the lengthy fight against hiv-1, influenza, and ebola virus infection, broadly neutralizing antibodies (bnabs), directed at conserved regions of surface proteins crucial to virus entry (env, hemagglutinin, and gp, respectively), are an essential resource for passive as well as active immunization. rare in their emergence and antigen recognition mode, bnabs are active toward a large set of different viral strains. isolation, characterization and production of bnabs lead to their pos ...202033033717
inhibiting ebola virus and sars-cov-2 entry. 202033033203
remdesivir targets a structurally analogous region of the ebola virus and sars-cov-2 polymerases.remdesivir is a broad-spectrum antiviral nucleotide prodrug that has been clinically evaluated in ebola virus patients and recently received emergency use authorization (eua) for treatment of covid-19. with approvals from the federal select agent program and the centers for disease control and prevention's institutional biosecurity board, we characterized the resistance profile of remdesivir by serially passaging ebola virus under remdesivir selection; we generated lineages with low-level reduce ...202033028676
receptor-mediated host cell preference of a bat-derived filovirus, lloviu virus.lloviu virus (llov), a bat-derived filovirus that is phylogenetically distinct from human pathogenic filoviruses such as ebola virus (ebov) and marburg virus (marv), was discovered in europe. however, since infectious llov has never been isolated, the biological properties of this virus remain poorly understood. we found that vesicular stomatitis virus (vsv) pseudotyped with the glycoprotein (gp) of llov (vsv-llov) showed higher infectivity in one bat (miniopterus sp.)-derived cell line than in ...202033027954
possible transmission of viruses from contaminated human feces and sewage: implications for sars-cov-2.humanity has experienced outbreaks by viruses such as severe acute respiratory syndrome coronavirus 1 (sars-cov-1) in 2003, eastern respiratory syndrome coronavirus (mers-cov) in 2012, ebola virus in 2014 and nowadays sars-cov-2. while clinicians seek for a vaccine to reduce the epidemic outbreak, environmental engineers need to understand consequence of virus entity in sewage given the reported persistency of viruses in human feces and sewage environments for more than days. herein, we discuss ...202033022459
the mental health of frontline health care providers during pandemics: a rapid review of the literature.this rapid review addresses two key questions posed by the covid-19 pandemic: what are the anticipated mental health sequelae for frontline health workers? and what are best practices during health emergencies to address the mental health needs of these workers?202033019857
ebola and marburg virus matrix layers are locally ordered assemblies of vp40 dimers.filoviruses such as ebola and marburg virus bud from the host membrane as enveloped virions. this process is achieved by the matrix protein vp40. when expressed alone, vp40 induces budding of filamentous virus-like particles, suggesting that localization to the plasma membrane, oligomerization into a matrix layer, and generation of membrane curvature are intrinsic properties of vp40. there has been no direct information on the structure of vp40 matrix layers within viruses or virus-like particle ...202033016878
a case for girl-child education to prevent and curb the impact of emerging infectious diseases epidemics.not only do epidemics such as hiv/aids, ebola virus disease (evd), and the current coronavirus disease (covid-19) cause the loss of millions of lives, but they also cost the global economy billions of dollars. consequently, there is an urgent need to formulate interventions that will help control their spread and impact when they emerge. the education of young girls and women is one such historical approach. they are usually the vulnerable targets of disease outbreaks - they are most likely to b ...202033005122
potential for virus endogenization in humans through testicular germ cell infection: the case of hiv.viruses have colonized the germ line of our ancestors at several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few non-retroviruses. among the recently emerged viruses infecting humans, several target the testis (eg hiv, zika and ebola viruses). here we aimed to investigate whether human testicular germ cells (tgcs) can support integration by hiv, a contemporary retrovirus that started to spread in the human pop ...202032999017
historical epidemiology and global health history.the subdiscipline of historical epidemiology holds the promise of creating a more robust and more nuanced foundation for global public health decision-making by deepening the empirical record from which we draw lessons about past interventions. this essay draws upon historical epidemiological research on three global public health campaigns to illustrate this promise: the rockefeller foundation's efforts to control hookworm disease (1909-c.1930), the world health organization's pilot projects fo ...202032997055
to b or not to b: mechanisms of protection conferred by rvsv-ebov-gp and the roles of innate and adaptive immunity.zaire ebola virus (ebov) is a member of the filoviridae family of negative sense, single-stranded rna viruses. ebov infection causes ebola virus disease (evd), characterized by coagulopathy, lymphopenia, and multi-organ failure, which can culminate in death. in 2019, the fda approved the first vaccine against ebov, a recombinant live-attenuated viral vector wherein the g protein of vesicular stomatitis virus is replaced with the glycoprotein (gp) of ebov (rvsv-ebov-gp, ervebo® by merck). this va ...202032992829
programmable low-cost dna-based platform for viral rna detection.detection of viruses is critical for controlling disease spread. recent emerging viral threats, including zika virus, ebola virus, and sars-cov-2 responsible for coronavirus disease 2019 (covid-19) highlight the cost and difficulty in responding rapidly. to address these challenges, we develop a platform for low-cost and rapid detection of viral rna with dna nanoswitches that mechanically reconfigure in response to specific viruses. using zika virus as a model system, we show nonenzymatic detect ...202032978154
expression of a large single-chain 13f6 antibody with binding activity against ebola virus-like particles in a plant system.pathogenic animal and human viruses present a growing and persistent threat to humans worldwide. ebola virus (ebov) causes zoonosis in humans. here, two structurally different anti-ebola 13f6 antibodies, recognizing the heavily glycosylated mucin-like domain (mld) of the glycoprotein (gp), were expressed in transgenic nicotiana tabacum plants and designed as inexpensive and effective diagnostic antibodies against ebola virus disease (evd). the first was anti-ebov 13f6 full size antibody with hea ...202032977599
the allocation of usdollar;105 billion in global funding from g20 countries for infectious disease research between 2000 and 2017: a content analysis of investments.each year, billions of us$ are spent globally on infectious disease research and development. however, there is little systematic tracking of global research and development. we present research on investments into infectious diseases research from funders in the g20 countries across an 18-year time period spanning 2000-17, comparing amounts invested for different conditions and considering the global burden of disease to identify potential areas of relative underfunding.202032971052
north american big brown bats (eptesicus fuscus) harbor an exogenous deltaretrovirus.bats are the reservoir for a large number of zoonotic viruses, including members of coronaviridae (severe acute respiratory syndrome coronavirus [sars-cov] and sars-cov-2), paramyxoviridae (hendra and nipah viruses), rhabdoviridae (rabies virus), and filoviridae (ebola virus) as exemplars. many retroviruses, such as human immunodeficiency virus, are similarly zoonotic; however, only infectious exogenous gammaretroviruses have recently been identified in bats. here, viral metagenomic sequencing o ...202032968009
aframomum melegueta secondary metabolites exhibit polypharmacology against sars-cov-2 drug targets: in vitro validation of furin inhibition.covid-19 pandemic is currently decimating the world's most advanced technologies and largest economies and making its way to the continent of africa. weak medical infrastructure and over-reliance on medical aids may eventually predict worse outcomes in africa. to reverse this trend, africa must re-evaluate the only area with strategic advantage; phytotherapy. one of the many plants with previous antiviral potency is against rna viruses is aframomum melegueta. in this study, one hundred (100) a. ...202032964551
bibliometric analysis of ebola research indexed in web of science and scopus (2010-2020).within the past decade, africa has faced several recurrent outbreaks of ebola virus disease (evd), including the 2014-2016 outbreak in west africa and the recent 2018-2020 kivu outbreak in the democratic republic of congo. the study thus aimed at quantifying and mapping the scientific output of evd research published within 2010-2020 though a bibliometric perspective.202032964036
past, present, and future of remdesivir: an overview of the antiviral in recent times.in the current covid-19 pandemic, evidence to justify the use of any specific antiviral drug with proven efficacy is not yet available. antiviral drug development always remains a challenge to the scientists. remdesivir has emerged as a promising molecule, based on results of clinical trials and observational studies and has receieved marketing approval for covid-19 treatment under "emergency use authorization" in countries such as united states. remdesivir is a newer antiviral drug that acts as ...202032963442
understanding the activated form of a class-i fusion protein: modeling the interaction of the ebola virus glycoprotein 2 with a lipid bilayer.the fusion of the viral and target cell membranes is a key step in the life cycle of all enveloped viruses. here, a range of structural data is used to generate an evidence-based model of the active conformation of an archetypical type-i fusion protein, the ebola glycoprotein 2 (gp2). the stability of the trimeric complex is demonstrated using molecular dynamics and validated by simulating the interaction of the complex with a lipid bilayer. in this model, the fusion peptides project away from t ...202032960042
methanol fixation, but not giemsa staining, inactivates ebola and lassa viruses in peripheral blood smears made on plastic microscope slides.diseases caused by many highly pathogenic viruses, including ebola virus (ebov) and lassa virus (lasv), present with nonspecific signs and symptoms that overlap with common tropical diseases such as malaria. initial diagnostic tests performed on patients under investigation for viral hemorrhagic fevers routinely include analysis of peripheral blood smears to detect and quantify plasmodium species. in light of recent and ongoing ebola virus disease and lassa fever epidemics, clinical laboratories ...202032959767
first prototype of the infectious diseases seeker (ids) software for prompt identification of infectious diseases.the rapid detection of ongoing outbreak - and the identification of causative pathogen - is pivotal for the early recognition of public health threats. the emergence and re-emergence of infectious diseases are linked to several determinants, both human factors - such as population density, travel, and trade - and ecological factors - like climate change and agricultural practices. several technologies are available for the rapid molecular identification of pathogens [e.g. real-time polymerase ch ...202032959625
aid group says ebola vaccine is not reaching enough people. 201932958941
distribution of household disinfection kits during the 2014-2015 ebola virus outbreak in monrovia, liberia: the msf experience.during the initial phase of the 2014-2016 ebola virus disease (evd) outbreak in monrovia, liberia, all hospitals' isolation capacities were overwhelmed by the sheer caseload. as a stop-gap measure to halt transmission, medecins sans frontieres (msf) distributed household disinfection kits to those who were at high risk of evd contamination. the kit contained chlorine and personal protective materials to be used for the care of a sick person or the handling of a dead body. this intervention was n ...202032956374
unrecognized ebola virus infection in guinea: complexity of surveillance in a health crisis situation: case report.the ebola epidemic that raged in west africa between 2013 and 2016 was the largest since the discovery of the virus in 1976. during this epidemic, more than 11,000 cases were notified with a lethality of over 67%. several means of transmission have been described. the great difficulty noted during the epidemic was the estimation of the number of asymptomatic and pauci symptomatic cases, however there is evidence that this population has been in contact with the virus for some time. thus, they co ...202032952845
characterization of rvsvδg-zebov-gp glycoproteins using automated capillary western blotting.ebolavirus (ebov) entry to host cells requires membrane-associated glycoprotein (gp). a recombinant vesicular stomatitis virus vector carrying zaire ebola virus glycoprotein (rvsv-zebov) was developed as a vaccine against ebolaviruses. the vsv glycoprotein gene was deleted (rvsvδg) and zebov glycoprotein (gp) was inserted into the deleted vsv glycoprotein open reading frame (orf) resulting in a live, replication-competent vector (rvsvδg-zebov-gp). automated capillary westerns were used to charac ...202032951937
non-malarial febrile illness: a systematic review of published aetiological studies and case reports from africa, 1980-2015.the availability of reliable point-of-care tests for malaria has heralded a paradigm shift in the management of febrile illnesses away from presumptive antimalarial therapy. in the absence of a definitive diagnosis, health care providers are more likely to prescribe empirical antimicrobials to those who test negative for malaria. to improve management and guide further test development, better understanding is needed of the true causative agents and their geographic variability.202032951596
a biaryl sulfonamide derivative as a novel inhibitor of filovirus infection.ebolaviruses and marburgviruses, members of the family filoviridae, are known to cause fatal diseases often associated with hemorrhagic fever. recent outbreaks of ebola virus disease in west african countries and the democratic republic of the congo have made clear the urgent need for the development of therapeutics and vaccines against filoviruses. using replication-incompetent vesicular stomatitis virus (vsv) pseudotyped with the ebola virus (ebov) envelope glycoprotein (gp), we screened a che ...202032946918
short k-mer abundance profiles yield robust machine learning features and accurate classifiers for rna viruses.high-throughput sequencing technologies have greatly enabled the study of genomics, transcriptomics and metagenomics. automated annotation and classification of the vast amounts of generated sequence data has become paramount for facilitating biological sciences. genomes of viruses can be radically different from all life, both in terms of molecular structure and primary sequence. alignment-based and profile-based searches are commonly employed for characterization of assembled viral contigs fro ...202032946529
efficacy of microbicides for inactivation of ebola-makona virus on a non-porous surface: a targeted hygiene intervention for reducing virus spread.microbicides play critical roles in infection prevention and control of ebola virus by decontaminating high-touch environmental surfaces (hites), interrupting the virus-hites-hands nexus. we evaluated the efficacy of formulations containing different microbicidal actives for inactivating ebola virus-makona strain (ebov/mak) on stainless-steel carriers per astm e2197-11. formulations of sodium hypochlorite (naocl) (0.05-1%), ethanol (70%), chloroxylenol (pcmx) (0.12-0.48% by weight) in hard water ...202032943689
glycan-gold nanoparticles as multifunctional probes for multivalent lectin-carbohydrate binding: implications for blocking virus infection and nanoparticle assembly.multivalent lectin-glycan interactions are widespread in biology and are often exploited by pathogens to bind and infect host cells. glycoconjugates can block such interactions and thereby prevent infection. the inhibition potency strongly depends on matching the spatial arrangement between the multivalent binding partners. however, the structural details of some key lectins remain unknown and different lectins may exhibit overlapping glycan specificity. this makes it difficult to design a glyco ...202032935985
march8 inhibits ebola virus glycoprotein, human immunodeficiency virus type 1 envelope glycoprotein, and avian influenza virus h5n1 hemagglutinin maturation.membrane-associated ring-ch-type 8 (march8) strongly blocks human immunodeficiency virus type 1 (hiv-1) envelope glycoprotein (env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. we now report that march8 also blocks the ebola virus (ebov) glycoprotein (gp) incorporation via surface downregulation. to understand how these viral fusion proteins are downregulated, we investigated the effects of march8 on ebov gp maturation and external ...202032934085
a potent postentry restriction to primate lentiviruses in a yinpterochiropteran bat.bats are primary reservoirs for multiple lethal human viruses, such as ebola, nipah, hendra, rabies, severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome-related coronavirus (mers-cov), and, most recently, sars-cov-2. the innate immune systems of these immensely abundant, anciently diverged mammals remain insufficiently characterized. while bat genomes contain many endogenous retroviral elements indicative of past exogenous infections, little is known about ...202032934084
serosurvey on healthcare personnel caring for patients with ebola virus disease and lassa virus in the united states.healthcare personnel (hcp) were recruited to provide serum samples, which were tested for antibodies against ebola or lassa virus to evaluate for asymptomatic seroconversion.202032933606
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