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nutritional care for patients with ebola virus disease.during the ebola virus disease (evd) outbreak of 2014-2016 in west africa, practitioners faced challenges providing nutritional care for patients in ebola treatment units (etus). the current evd outbreak in the democratic republic of the congo demonstrates the need to understand lessons learned from previous outbreaks and to update nutritional guidelines. we conducted a literature review to identify articles that included nutrition as an integral part of supportive care. we found little informat ...202031845848
uncrewed aircraft systems versus motorcycles to deliver laboratory samples in west africa: a comparative economic study.transportation of laboratory samples in low-income and middle-income countries is often constrained by poor road conditions, difficult geographical terrain, and insecurity. these constraints can lead to long turnaround times for laboratory diagnostic tests and hamper epidemic control or patient treatment efforts. although uncrewed aircraft systems (uas)-ie, drones-can mitigate some of these transportation constraints, their cost-effectiveness compared with land-based transportation systems is un ...202031839129
digital rolling circle amplification-based detection of ebola and other tropical viruses.emerging tropical viruses have caused serious outbreaks during the recent years, such as ebola virus (ebov) in 2014 and the most recent in 2018 to 2019 in congo. thus, immediate diagnostic attention is demanded at the point of care in resource-limited settings, because the performance and the operational parameters of conventional ebov testing are limited. especially, their sensitivity, specificity, and coverage of other tropical disease viruses make them unsuitable for diagnostic at the point o ...202031837428
exposure to ebola virus and risk for infection with malaria parasites, rural gabon.an association between malaria and risk for death among patients with ebola virus disease has suggested within-host interactions between plasmodium falciparum parasites and ebola virus. to determine whether such an interaction might also influence the probability of acquiring either infection, we used a large snapshot surveillance study from rural gabon to test if past exposure to ebola virus is associated with current infection with plasmodium spp. during nonepidemic conditions. we found a stro ...202031829919
performance of the public health system during a full-scale yellow fever simulation exercise in lagos state, nigeria, in 2018: how prepared are we for the next outbreak?recurring outbreaks of infectious diseases have characterized the west african region in the past 4 decades. there is a moderate to high risk of yellow fever in countries in the region, and the disease has reemerged in nigeria after 21 years. a full-scale simulation exercise of the outbreak of yellow fever was conducted to assess preparedness and response in the event of a full-scale outbreak. the exercise was a multi-agency exercise conducted in lagos, and it involved health facilities, points ...202031859573
analyzing targeted violence against medical workers and evd incidence in the 2018-19 democratic republic of the congo outbreak using vector autoregression and granger causality.the purpose of this study was to evaluate the relationship between violent events targeted against aid workers and the incidence of ebola virus disease (evd) during the 2018-19 democratic republic of the congo (drc) outbreak in the north kivu and ituri provinces. time series models using vector autoregression were constructed using violent event data confined to the outbreak region from the armed conflict location and event dataset (acled), in combination with evd incidence reporting from the wo ...202031859571
ebola patient virus cycle threshold and risk of household transmission of ebola virus.identifying risk factors for household transmission of ebola virus (ebov) is important to guide preventive measures during ebola outbreaks.202031858125
association between treatment with oral third-generation cephalosporin antibiotics and mortality outcomes in ebola virus disease: a multinational retrospective cohort study.to evaluate the association between oral third-generation cephalosporin antibiotic treatment and mortality in ebola virus disease (evd).202031912627
case definitions used during the first 6 months of the 10th ebola virus disease outbreak in the democratic republic of the congo - four neighboring countries, august 2018-february 2019.on august 1, 2018, the democratic republic of the congo (drc) declared its 10th ebola virus disease (ebola) outbreak in an area with a high volume of cross-border population movement to and from neighboring countries. the world health organization (who) designated rwanda, south sudan, and uganda as the highest priority countries for ebola preparedness because of the high risk for cross-border spread from drc (1). countries might base their disease case definitions on global standards; however, h ...202031917783
population movement patterns among the democratic republic of the congo, rwanda, and uganda during an outbreak of ebola virus disease: results from community engagement in two districts - uganda, march 2019.tailoring communicable disease preparedness and response strategies to unique population movement patterns between an outbreak area and neighboring countries can help limit the international spread of disease. global recognition of the value of addressing community connectivity in preparedness and response, through field work and visualizing the identified movement patterns, is reflected in the world health organization's declaration on july 17, 2019, that the 10th ebola virus disease (ebola) ou ...202031917781
niemann-pick c1 heterogeneity of bat cells controls filovirus tropism.fruit bats are suspected to be natural hosts of filoviruses, including ebola virus (ebov) and marburg virus (marv). interestingly, however, previous studies suggest that these viruses have different tropisms depending on the bat species. here, we show a molecular basis underlying the host-range restriction of filoviruses. we find that bat-derived cell lines fbkt1 and zfbk13-76e show preferential susceptibility to ebov and marv, respectively, whereas the other bat cell lines tested are similarly ...202031940478
the use of antimalarial drugs against viral infection.in recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. in particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., hiv, dengue virus, chikungunya virus, ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). here, we reviewed the in vitro/in vivo and clinical studies conducted ...202031936284
hexamer phasing governs transcription initiation in the 3'-leader of ebola virus.the genomic, bipartite replication promoter of ebola virus (ebov) consists of elements 1 (pe1) and 2 (pe2). pe1 (55 nt at the 3'-terminus) is separated from pe2 (harboring eight 3'-un5 hexamers) by the transcription start sequence (tss) of the first nucleoprotein (np) gene plus a spacer sequence. insertions or deletions in the spacer were reported to support genome replication if comprising 6 or 12, but not 1/2/3/5/9 nt. this gave rise to the formulation of the "rule of 6" for the ebov replicati ...202031924730
broad spectrum antiviral agent niclosamide and its therapeutic potential.the recent outbreak of coronavirus disease 2019 (covid-19) highlights an urgent need for therapeutics. through a series of drug repurposing screening campaigns, niclosamide, an fda-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as sars-cov, mers-cov, zikv, hcv, and human adenovirus, indicating its potential as an antiviral agent. in this brief review, we summarize the broad antiviral activity of niclosamide and hi ...202032125140
viruses go modular.the ww domain is a modular protein structure that recognizes the proline-rich pro-pro-x-tyr (ppxy) motif contained in specific target proteins. the compact modular nature of the ww domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the hippo pathway). as a result, ww domains play key roles in a plethora of both normal and disease processes. intriguingly, rna and dna viruses have evolved strategies to hijack cellular ww d ...202032111739
the integrity of the yxxl motif of ebola virus vp24 is important for the transport of nucleocapsid-like structures and for the regulation of viral rna synthesis.while it is well appreciated that late domains in the viral matrix proteins are crucial to mediate efficient virus budding, little is known about roles of late domains in the viral nucleocapsid proteins. here, we characterized the functional relevance of a yxxl motif with potential late-domain function in the ebola virus nucleocapsid protein vp24. mutations in the yxxl motif had two opposing effects on the functions of vp24. on the one hand, the mutation affected the regulatory function of vp24 ...202032102881
online bayesian phylodynamic inference in beast with application to epidemic reconstruction.reconstructing pathogen dynamics from genetic data as they become available during an outbreak or epidemic represents an important statistical scenario in which observations arrive sequentially in time and one is interested in performing inference in an "online" fashion. widely used bayesian phylogenetic inference packages are not set up for this purpose, generally requiring one to recompute trees and evolutionary model parameters de novo when new data arrive. to accommodate increasing data flow ...202032101295
serine-arginine protein kinase 1 regulates ebola virus transcription.ebola virus (ebov) causes a severe and often fatal disease for which no approved vaccines or antivirals are currently available. ebov vp30 has been described as a viral phosphoprotein, and nonphosphorylated vp30 is essential and sufficient to support secondary transcription in an ebov-specific minigenome system; however, phosphorylatable serine residues near the n terminus of vp30 are required to support primary viral transcription as well as the reinitiation of vp30-mediated transcription at in ...202032098814
favipiravir, an anti-influenza drug against life-threatening rna virus infections.favipiravir has been developed as an anti-influenza drug and licensed as an anti-influenza drug in japan. additionally, favipiravir is being stockpiled for 2 million people as a countermeasure for novel influenza strains. this drug functions as a chain terminator at the site of incorporation of the viral rna and reduces the viral load. favipiravir cures all mice in a lethal influenza infection model, while oseltamivir fails to cure the animals. thus, favipiravir contributes to curing animals wit ...202032097670
update on ebola treatment center costs and sustainability, united states, 2019.we surveyed 56 ebola treatment centers (etcs) in the united states and identified costs incurred since 2014 ($1.76 million/etc) and sustainability strategies. etcs reported heavy reliance on federal funding. it is uncertain if, or for how long, etcs can maintain capabilities should federal funding expire in 2020.202032097110
crystal structure of the měnglà virus vp30 c-terminal domain.the family filoviridae contains many important human viruses, including marburg virus (marv) and ebola virus (ebov). měnglà virus (mlav), a newly discovered filovirus, is considered a potential human pathogen. the vp30 c-terminal domain (ctd) of these filoviruses plays an essential role in virion assembly. in common with other filoviruses, mlav vp30 ctd mainly exists as a dimer in solution. in this work, we determined the crystal structure of recombinant mlav vp30 ctd monomer, verifying that c-t ...202032093889
a systematic review of mental health programs among populations affected by the ebola virus disease.the ebola virus disease (evd) is associated with major mental health consequences (e.g., depression, anxiety, ptsd). studies have shown a need for relevant and effective programs to address mental health consequences associated to evd. this systematic review aimed to describe programs implemented following evd outbreaks and to evaluate their effectiveness and relevance in order to provide evidence-based data to improve mental health services.202032087433
the bat meat chain and perceptions of the risk of contracting ebola in the mount cameroon region.local people's interaction with bats render them vulnerable to ebola virus disease (evd). this paper examines perceptions of risk involved in the hunting, handling, processing and consumption of bat meat in the mount cameroon region of southwest cameroon. it focuses on the myriad cultural beliefs, gendered patterns of activity and institutional arrangements in which the bat meat production chain is embedded.202032354371
the surveillance outbreak response management and analysis system (sormas): digital health global goods maturity assessment.digital health is a dynamic field that has been generating a large number of tools; many of these tools do not have the level of maturity required to function in a sustainable model. it is in this context that the concept of global goods maturity is gaining importance. digital square developed a global good maturity model (ggmm) for digital health tools, which engages the digital health community to identify areas of investment for global goods. the surveillance outbreak response management and ...202032347809
mutation of hydrophobic residues in the c-terminal domain of the marburg virus matrix protein vp40 disrupts trafficking to the plasma membrane.marburg virus (marv) is a lipid-enveloped negative sense single stranded rna virus, which can cause a deadly hemorrhagic fever. marv encodes seven proteins, including vp40 (mvp40), a matrix protein that interacts with the cytoplasmic leaflet of the host cell plasma membrane. vp40 traffics to the plasma membrane inner leaflet, where it assembles to facilitate the budding of viral particles. vp40 is a multifunctional protein that interacts with several host proteins and lipids to complete the vira ...202032344654
the new scope of virus taxonomy: partitioning the virosphere into 15 hierarchical ranks.virus taxonomy emerged as a discipline in the middle of the twentieth century. traditionally, classification by virus taxonomists has been focussed on the grouping of relatively closely related viruses. however, during the past few years, the international committee on taxonomy of viruses (ictv) has recognized that the taxonomy it develops can be usefully extended to include the basal evolutionary relationships among distantly related viruses. consequently, the ictv has changed its code to allow ...202032341570
can you catch it? lessons learned and modification of ed triage symptom- and travel-screening strategy.efficient identification and isolation of patients with communicable diseases limits exposure to health care workers, other patients, and visitors. in august 2014, our team developed and implemented an algorithm to triage suspected cases of ebola virus disease in a midwestern united states emergency department and outpatient clinics based on patient travel history and symptoms. here, we present the lessons learned and modifications to update the tool.202032340737
impact of prophylactic vaccination strategies on ebola virus transmission: a modeling analysis.ebola epidemics constitute serious public health emergencies. multiple vaccines are under development to prevent these epidemics and avoid the associated morbidity and mortality. assessing the potential impact of these vaccines on morbidity and mortality of ebola is essential for devising prevention strategies. a mean-field compartmental stochastic model was developed for this purpose and validated by simulating the 2014 sierra leone epidemic. we assessed the impacts of prophylactic vaccination ...202032339195
dynamics of conflict during the ebola outbreak in the democratic republic of the congo 2018-2019.the 2018-2019 ebola virus disease (evd) outbreak in north kivu and ituri provinces in the democratic republic of the congo (drc) is the largest ever recorded in the drc. it has been declared a public health emergency of international concern. the outbreak emerged in a region of chronic conflict and insecurity, and directed attacks against health care workers may have interfered with disease response activities. our study characterizes and quantifies the broader conflict dynamics over the course ...202032336281
evaluating the impact of intravenous fluid resuscitation on survival for the management of patients with ebola virus disease. 202031055594
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
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
machine-learning prognostic models from the 2014-16 ebola outbreak: data-harmonization challenges, validation strategies, and mhealth applications.ebola virus disease (evd) plagues low-resource and difficult-to-access settings. machine learning prognostic models and mhealth tools could improve the understanding and use of evidence-based care guidelines in such settings. however, data incompleteness and lack of interoperability limit model generalizability. this study harmonizes diverse datasets from the 2014-16 evd epidemic and generates several prognostic models incorporated into the novel ebola care guidelines app that provides informed ...202031312805
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
utilization of maternity waiting homes: before, during, and after the ebola virus disease outbreak in bong county, liberia.maternity waiting homes (mwhs) are used to increase the number of women delivering at health care facilities. the first mwhs in liberia were opened in 2012, prior to the ebola virus disease (evd) outbreak.202031294786
survivors of ebola virus disease develop polyfunctional antibody responses.monoclonal antibodies can mediate protection against ebola virus (ebov) infection through direct neutralization as well as through the recruitment of innate immune effector functions. however, the antibody functional response following survival of acute ebov disease has not been well characterized. in this study, serum antibodies from ebola virus disease (evd) survivors from sierra leone were profiled to capture variation in overall subclass/isotype abundance, neutralizing activity, and innate i ...202031301137
global phosphoproteomic analysis of ebola virions reveals a novel role for vp35 phosphorylation-dependent regulation of genome transcription.ebola virus (ebov) causes severe human disease with a high case fatality rate. the balance of evidence implies that the virus circulates in bats. the molecular basis for host-viral interactions, including the role for phosphorylation during infections, is largely undescribed. to address this, and to better understand the biology of ebov, the phosphorylation of ebov proteins was analyzed in virions purified from infected monkey vero-e6 cells and bat eponi/22.1 cells using high-resolution mass spe ...202031562565
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
health care workers' awareness and infection control practices about ebola virus disease in hajj 2015.saudi arabia being a major pilgrimage center with an annual turnover of millions of pilgrims from all over the world has a high risk for transmission of infections; ebola virus disease (evd) being one of them. health care workers (hcws) are particularly vulnerable to these infections. the objectives of this research were to assess the overall knowledge and infection control practices of hcws about evd, and to evaluate and compare the role of pre deployment hajj training of hcws assigned hajj dut ...202030981653
2017 outbreak of ebola virus disease in northern democratic republic of congo.in 2017, the democratic republic of the congo (drc) recorded its eighth ebola virus disease (evd) outbreak, approximately 3 years after the previous outbreak.202030942884
caring for infectious disease in the prehospital setting: a qualitative analysis of ems providers experiences and suggestions for improvement.objective: the purpose of this study was to examine the attitudes and behaviors of emergency medical technicians (emts) and paramedics when faced with the decision to care for patients with suspected ebola virus disease (evd) and to illicit suggestions for improvement of infectious disease (id) preparedness. methods: a convenience sample of 22 emt/paramedics were recruited from an emergency department at one of the designated ebola centers. each provider participated in one of three on-site focu ...202030917729
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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