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  1. Understanding Ebola Virus Transmission

    PubMed Central

    Judson, Seth; Prescott, Joseph; Munster, Vincent

    2015-01-01

    An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus. PMID:25654239

  2. Ebola (Ebola Virus Disease)

    MedlinePLUS

    ... for Families and Loved Ones of Responders More Communication Resources Radio PSAs Videos Infographics Factsheets Posters More ... in the U.S. Q&A: 2014 Ebola Outbreak Communication Resources for West African Audiences Guinea Guinea-Bissau ...

  3. Ebola Virus Disease

    MedlinePLUS

    ... Zaire species. Transmission It is thought that fruit bats of the Pteropodidae family are natural Ebola virus ... of infected animals such as chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines found ill or ...

  4. Interferon-? Inhibits Ebola Virus Infection

    PubMed Central

    Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID:26562011

  5. Ebola virus disease

    MedlinePLUS

    ... body fluids of infected animals Contact with infected bats Ebola does NOT spread through: Air Water Food ... who has died from Ebola. Avoid contact with bats and nonhuman primates or blood, fluids, and raw ...

  6. EBOLA VIRUS DISEASE INFORMATION FOR NIH CLINICAL CENTER STAFF*

    E-print Network

    Shen, Jun

    1 EBOLA VIRUS DISEASE INFORMATION FOR NIH CLINICAL CENTER STAFF Ebola Virus Disease (EVD) is caused by the Ebola Virus, an RNA virus that was first identified in 1976. Ebola virus has been associated with epidemics in Africa and is capable of causing severe disease

  7. Characteristics of Filoviridae: Marburg and Ebola Viruses

    NASA Astrophysics Data System (ADS)

    Beer, Brigitte; Kurth, Reinhard; Bukreyev, Alexander

    Filoviruses are enveloped, nonsegmented negative-stranded RNA viruses. The two species, Marburg and Ebola virus, are serologically, biochemically, and genetically distinct. Marburg virus was first isolated during an outbreak in Europe in 1967, and Ebola virus emerged in 1976 as the causative agent of two simultaneous outbreaks in southern Sudan and northern Zaire. Although the main route of infection is known to be person-to-person transmission by intimate contact, the natural reservoir for filoviruses still remains a mystery.

  8. Persistence of Ebola Virus in Sterilized Wastewater

    PubMed Central

    2015-01-01

    In the wake of the ongoing 2014/2015 Ebola virus outbreak, significant questions regarding the appropriate handling of Ebola virus-contaminated liquid waste remain, including the persistence of Ebola virus in wastewater. To address these uncertainties, we evaluated the persistence of Ebola virus spiked in sterilized domestic sewage. The viral titer decreased approximately 99% within the first test day from an initial viral titer of 106 TCID50 mL–1; however, it could not be determined if this initial rapid decrease was due to aggregation or inactivation of the viral particles. The subsequent viral titer decrease was less rapid, and infectious Ebola virus particles persisted for all 8 days of the test. The inactivation constant (k) was determined to be ?1.08 (2.1 days for a 90% viral titer decrease). Due to experimental conditions, we believe these results to be an upper bound for Ebola virus persistence in wastewater. Wastewater composition is inherently heterogeneous; subsequently, we caution that interpretation of these results should be made within a holistic assessment, including the effects of wastewater composition, dilution, and potential exposure routes within wastewater infrastructure. While it remains unknown if Ebola virus may be transmitted via wastewater, these data demonstrate a potential exposure route to infectious Ebola virus via wastewater and emphasize the value of a precautionary approach to wastewater handling in an epidemic response. PMID:26523283

  9. Virion nucleic acid of Ebola virus.

    PubMed Central

    Regnery, R L; Johnson, K M; Kiley, M P

    1980-01-01

    The virion nucleic acid of Ebola virus consists of a single-stranded RNA with a molecular weight of approximately 4.0 x 10(6). The virion RNA did not bind to oligodeoxythymidylic acid-cellulose under conditions known to bind RNAs rich in polyadenylic acid and was not infectious under conditions which yielded infectious RNA from Sindbis virus, suggesting that Ebola virus virion nucleic acid is a negative-stranded RNA. PMID:7431486

  10. Ebola Virus Disease.

    PubMed

    Etienne, Nadia Laverne; Burns, Candace; Conlon, Helen Acree

    2015-12-01

    Nurses are the largest group of health care providers and, therefore, are often at the forefront of epidemics: responding, treating, educating, and coordinating care as needed. But what happens when nurses are afraid of contracting an illness and decide to leave the workplace? The fear due to Ebola was in part caused by conflicting information around the proper use of personal protective equipment and need for quarantine. The nursing response to as well as the role occupational health nurses can play in diffusing the fear of contracting contemporary infectious diseases are discussed. PMID:26590092

  11. Ebola Virus Disease in West Africa

    MedlinePLUS

    ... centre Regional Director About us Epidemic and Pandemic Alert and Response Overview Topics Features Outbreak news Situation ... Programmes » Disease Prevention and Control » Epidemic and Pandemic Alert and Response » Features » Ebola virus disease © 2015 WHO | ...

  12. Successful Delivery of RRT in Ebola Virus Disease

    PubMed Central

    Kraft, Colleen; Mehta, Aneesh K.; Varkey, Jay B.; Lyon, G. Marshall; Crozier, Ian; Ströher, Ute; Ribner, Bruce S.

    2015-01-01

    AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease. PMID:25398785

  13. An Ebola virus-centered knowledge base

    PubMed Central

    Kamdar, Maulik R.; Dumontier, Michel

    2015-01-01

    Ebola virus (EBOV), of the family Filoviridae viruses, is a NIAID category A, lethal human pathogen. It is responsible for causing Ebola virus disease (EVD) that is a severe hemorrhagic fever and has a cumulative death rate of 41% in the ongoing epidemic in West Africa. There is an ever-increasing need to consolidate and make available all the knowledge that we possess on EBOV, even if it is conflicting or incomplete. This would enable biomedical researchers to understand the molecular mechanisms underlying this disease and help develop tools for efficient diagnosis and effective treatment. In this article, we present our approach for the development of an Ebola virus-centered Knowledge Base (Ebola-KB) using Linked Data and Semantic Web Technologies. We retrieve and aggregate knowledge from several open data sources, web services and biomedical ontologies. This knowledge is transformed to RDF, linked to the Bio2RDF datasets and made available through a SPARQL 1.1 Endpoint. Ebola-KB can also be explored using an interactive Dashboard visualizing the different perspectives of this integrated knowledge. We showcase how different competency questions, asked by domain users researching the druggability of EBOV, can be formulated as SPARQL Queries or answered using the Ebola-KB Dashboard. Database URL: http://ebola.semanticscience.org. PMID:26055098

  14. Ebola Virus Disease: A Review of Its Past and Present.

    PubMed

    Murray, Michael J

    2015-09-01

    Ebola virus, the virus responsible for Ebola virus disease, has spawned several epidemics during the past 38 years. In 2014, an Ebola epidemic spread from Africa to other continents, becoming a pandemic. The virus's relatively unique structure, its infectivity and lethality, the difficulty in stopping its spread, and the lack of an effective treatment captured the world's attention. This article provides a brief review of the known history of Ebola virus disease, its etiology, epidemiology, and pathophysiology and a review of the limited information on managing patients with Ebola virus disease. PMID:26287303

  15. A STOCHASTIC CELLULAR AUTOMATON MODEL OF EBOLA VIRUS DYNAMICS

    E-print Network

    Hawkins, Jane M.

    A STOCHASTIC CELLULAR AUTOMATON MODEL OF EBOLA VIRUS DYNAMICS E. BURKHEAD AND J. HAWKINS Abstract. We construct a stochastic cellular automaton (SCA) model for the spread of the Ebola virus (EBOV). We. Introduction Ebola virus (EBOV) is a filovirus that causes severe illness in most humans who are exposed to it

  16. An Ebola virus-centered knowledge base.

    PubMed

    Kamdar, Maulik R; Dumontier, Michel

    2015-01-01

    Ebola virus (EBOV), of the family Filoviridae viruses, is a NIAID category A, lethal human pathogen. It is responsible for causing Ebola virus disease (EVD) that is a severe hemorrhagic fever and has a cumulative death rate of 41% in the ongoing epidemic in West Africa. There is an ever-increasing need to consolidate and make available all the knowledge that we possess on EBOV, even if it is conflicting or incomplete. This would enable biomedical researchers to understand the molecular mechanisms underlying this disease and help develop tools for efficient diagnosis and effective treatment. In this article, we present our approach for the development of an Ebola virus-centered Knowledge Base (Ebola-KB) using Linked Data and Semantic Web Technologies. We retrieve and aggregate knowledge from several open data sources, web services and biomedical ontologies. This knowledge is transformed to RDF, linked to the Bio2RDF datasets and made available through a SPARQL 1.1 Endpoint. Ebola-KB can also be explored using an interactive Dashboard visualizing the different perspectives of this integrated knowledge. We showcase how different competency questions, asked by domain users researching the druggability of EBOV, can be formulated as SPARQL Queries or answered using the Ebola-KB Dashboard. PMID:26055098

  17. ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus

    E-print Network

    Waldmann, Uwe

    ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus Journal (without HIV) Subject: Virology #12;#12;ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus v1; ref status: not peer reviewed Peter D. Karp Bonnie Berger Diane Kovats Thomas

  18. ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus

    E-print Network

    Waldmann, Uwe

    ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus Journal for this article. Categories Subject: Message from ISCB Counts Figures: 0 Tables: 0 Pages: 3 #12;#12;ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus Peter D. Karp Bonnie

  19. MODELING THE SPREAD OF EBOLA Ebola is a rare and deadly disease caused by infection with a strain of Ebola virus. The current

    E-print Network

    Morrow, James A.

    MODELING THE SPREAD OF EBOLA 1. Summary Ebola is a rare and deadly disease caused by infection with a strain of Ebola virus. The current 2014 Ebola epidemic outbreak in West Africa (first cases notified in March 2014) is the largest and most complex Ebola outbreak since the Ebola virus was first discovered

  20. Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment.

    PubMed

    Sakurai, Yasuteru; Kolokoltsov, Andrey A; Chen, Cheng-Chang; Tidwell, Michael W; Bauta, William E; Klugbauer, Norbert; Grimm, Christian; Wahl-Schott, Christian; Biel, Martin; Davey, Robert A

    2015-02-27

    Ebola virus causes sporadic outbreaks of lethal hemorrhagic fever in humans, but there is no currently approved therapy. Cells take up Ebola virus by macropinocytosis, followed by trafficking through endosomal vesicles. However, few factors controlling endosomal virus movement are known. Here we find that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small-molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule that we tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. Therefore, TPC proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy. PMID:25722412

  1. Ebola Virus: Sensationalism, Science, and Human Rights.

    PubMed

    Bausch, Daniel G; Clougherty, Marguerite M

    2015-10-01

    Outbreaks of the filoviruses, Ebola and Marburg, usually garner immense public attention, often with a sensationalist bent in the lay press, focused on the apparently mysterious origins of the outbreak and the high mortality rates. The scientific community may present a more objective viewpoint, but usually with a rather technical focus on identifying epidemiological risk factors and experimental therapies and vaccines. Often lost in the discussion are the human rights elements that consistently underlie large outbreaks of these dangerous viruses. PMID:26203057

  2. Possible sexual transmission of Ebola virus - Liberia, 2015.

    PubMed

    Christie, Athalia; Davies-Wayne, Gloria J; Cordier-Lasalle, Thierry; Blackley, David J; Laney, A Scott; Williams, Desmond E; Shinde, Shivam A; Badio, Moses; Lo, Terrence; Mate, Suzanne E; Ladner, Jason T; Wiley, Michael R; Kugelman, Jeffrey R; Palacios, Gustavo; Holbrook, Michael R; Janosko, Krisztina B; de Wit, Emmie; van Doremalen, Neeltje; Munster, Vincent J; Pettitt, James; Schoepp, Randal J; Verhenne, Leen; Evlampidou, Iro; Kollie, Karsor K; Sieh, Sonpon B; Gasasira, Alex; Bolay, Fatorma; Kateh, Francis N; Nyenswah, Tolbert G; De Cock, Kevin M

    2015-05-01

    On March 20, 2015, 30 days after the most recent confirmed Ebola Virus Disease (Ebola) patient in Liberia was isolated, Ebola was laboratory confirmed in a woman in Monrovia. The investigation identified only one epidemiologic link to Ebola: unprotected vaginal intercourse with a survivor. Published reports from previous outbreaks have demonstrated Ebola survivors can continue to harbor virus in immunologically privileged sites for a period of time after convalescence. Ebola virus has been isolated from semen as long as 82 days after symptom onset and viral RNA has been detected in semen up to 101 days after symptom onset. One instance of possible sexual transmission of Ebola has been reported, although the accompanying evidence was inconclusive. In addition, possible sexual transmission of Marburg virus, a filovirus related to Ebola, was documented in 1968. This report describes the investigation by the Government of Liberia and international response partners of the source of Liberia's latest Ebola case and discusses the public health implications of possible sexual transmission of Ebola virus. Based on information gathered in this investigation, CDC now recommends that contact with semen from male Ebola survivors be avoided until more information regarding the duration and infectiousness of viral shedding in body fluids is known. If male survivors have sex (oral, vaginal, or anal), a condom should be used correctly and consistently every time. PMID:25950255

  3. Ebola virus infection modeling and identifiability problems

    PubMed Central

    Nguyen, Van Kinh; Binder, Sebastian C.; Boianelli, Alessandro; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A.

    2015-01-01

    The recent outbreaks of Ebola virus (EBOV) infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4), basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently needed to tackle this lethal disease. Mathematical modeling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modeling approach to unravel the interaction between EBOV and the host cells is still missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells by EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parameters in viral infections kinetics is the key contribution of this work, paving the way for future modeling works on EBOV infection. PMID:25914675

  4. Ebola outbreak in Western Africa 2014: what is going on with Ebola virus?

    PubMed Central

    2015-01-01

    The 2014 outbreak of Ebola virus disease (EVD) in West Africa, caused by Ebola virus (Zaire Ebola virus species), is the largest outbreak of EVD in history. It cause hemorrhagic fever in human and nonhuman primates with high mortality rate up to 90% and can be transmitted by direct contact with blood, body fluids, skin of EVD patients or persons who have died of EVD. As of December 17, 2014, 450 healthcare personnel are known to have been infected with Ebola, of whom 244 died. For development of Ebola vaccine and treatment are highly difficult due to its dangerous and accessibility that requires biosafety level 4 (BSL-4) to conduct experiment. Also there is no specific vaccine and treatment for Ebola virus; however, many candidate vaccines and antiviral-drugs such as ZMapp and TKM-Ebola are being developed for Ebola virus disease. In this review, we focus on the epidemiology of 2014 outbreak of Ebola virus and candidate agent for preventing and curing from Ebola virus. PMID:25648530

  5. Reidentification of Ebola Virus E718 and ME as Ebola Virus/H.sapiens-tc/COD/1976/Yambuku-Ecran

    PubMed Central

    Lofts, Loreen L.; Kugelman, Jeffrey R.; Smither, Sophie J.; Lever, Mark S.; van der Groen, Guido; Johnson, Karl M.; Radoshitzky, Sheli R.; Bavari, Sina; Jahrling, Peter B.; Towner, Jonathan S.; Nichol, Stuart T.; Palacios, Gustavo

    2014-01-01

    Ebola virus (EBOV) was discovered in 1976 around Yambuku, Zaire. A lack of nomenclature standards resulted in a variety of designations for each isolate, leading to confusion in the literature and databases. We sequenced the genome of isolate E718/ME/Ecran and unified the various designations under Ebola virus/H.sapiens-tc/COD/1976/Yambuku-Ecran. PMID:25414499

  6. Elimination of Ebola Virus Transmission in Liberia - September 3, 2015.

    PubMed

    Bawo, Luke; Fallah, Mosoka; Kateh, Francis; Nagbe, Thomas; Clement, Peter; Gasasira, Alex; Mahmoud, Nuha; Musa, Emmanuel; Lo, Terrence Q; Pillai, Satish K; Seeman, Sara; Sunshine, Brittany J; Weidle, Paul J; Nyensweh, Tolbert

    2015-01-01

    Following 42 days since the last Ebola virus disease (Ebola) patient was discharged from a Liberian Ebola treatment unit (ETU), September 3, 2015, marks the second time in a 4-month period that the World Health Organization (WHO) has declared Liberia free of Ebola virus transmission (1). The first confirmed Ebola cases in West Africa were identified in southeastern Guinea on March 23, 2014, and within 1 week, cases were identified and confirmed in Liberia (1). Since then, Liberia has reported 5,036 confirmed and probable Ebola cases and 4,808 Ebola-related deaths. The epidemic in Liberia peaked in late summer and early fall of 2014, when more than 200 confirmed and probable cases were reported each week . PMID:26355323

  7. Ebola Virus Infection: Overview and Update on Prevention and Treatment.

    PubMed

    Martínez, Miguel J; Salim, Abdulbaset M; Hurtado, Juan C; Kilgore, Paul E

    2015-12-01

    In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. The goal of this report is to provide an update on the epidemic and review current progress in the development, evaluation and deployment of prevention and treatment strategies for EVD. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Through 22 July 2015, a total of 27,741 EVD cases and 11,284 deaths were reported from all affected countries. Several therapeutic agents and novel vaccines for EVD have been developed and are now undergoing evaluation. Concurrent with active case investigation, contact tracing, surveillance and supportive care to patients and communities, there has been rapid progress in the development of new therapies and vaccines against EVD. Continued focus on strengthening clinical and public health infrastructure will have direct benefits in controlling the spread of EVD and will provide a strong foundation for deployment of new drugs and vaccines to affected countries when they become available. The unprecedented West Africa Ebola outbreak, response measures, and ensuing drug and vaccine development suggest that new tools for Ebola control may be available in the near future. PMID:26363787

  8. Molecular Dynamics Simulations of Folding and Insertion of the Ebola Virus Fusion Peptide into a

    E-print Network

    Molecular Dynamics Simulations of Folding and Insertion of the Ebola Virus Fusion Peptide- residue Ebola virus fusion peptide into a membrane bilayer. We applied a multi-resolution computational-energy landscape, virus-host interactions 1 Introduction Ebola and Marburg viruses are nonsegmented, negative

  9. Isolation and partial characterisation of a new strain of Ebola We have isolated a new strain of Ebola virus from a non-

    E-print Network

    1271 Isolation and partial characterisation of a new strain of Ebola virus Summary We have isolated a new strain of Ebola virus from a non- fatal human case infected during the autopsy of a wild about the natural reservoir of the Ebola virus. Lancet 1995; 345: 1271-74 Introduction Ebola virus

  10. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

    E-print Network

    Sealfon, Rachel S.

    In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid ...

  11. Experimental inoculation of plants and animals with Ebola virus.

    PubMed Central

    Swanepoel, R.; Leman, P. A.; Burt, F. J.; Zachariades, N. A.; Braack, L. E.; Ksiazek, T. G.; Rollin, P. E.; Zaki, S. R.; Peters, C. J.

    1996-01-01

    Thirty-three varieties of 24 species of plants and 19 species of vertebrates and invertebrates were experimentally inoculated with Ebola Zaire virus. Fruit and insectivorous bats supported replication and circulation of high titers of virus without necessarily becoming ill; deaths occurred only among bats that had not adapted to the diet fed in the laboratory. PMID:8969248

  12. Ebola virus dynamics in mice treated with favipiravir.

    PubMed

    Madelain, Vincent; Oestereich, Lisa; Graw, Frederik; Nguyen, Thi Huyen Tram; de Lamballerie, Xavier; Mentré, France; Günther, Stephan; Guedj, Jeremie

    2015-11-01

    The polymerase inhibitor favipiravir is a candidate for the treatment of Ebola virus disease. Here, we designed a mathematical model to characterize the viral dynamics in 20 mice experimentally infected with Ebola virus, which were either left untreated or treated with favipiravir at 6 or 8days post infection. This approach provided estimates of kinetic parameters of Ebola virus reproduction, such as the half-life of productively infected cells, of about 6h, and the basic reproductive number which indicates that virus produced by a single infected cell productively infects about 9 new cells. Furthermore, the model predicted that favipiravir efficiently blocks viral production, reaching an antiviral effectiveness of 95% and 99.6% at 2 and 6days after initiation of treatment, respectively. The model could be particularly helpful to guide future studies evaluating favipiravir in larger animals. PMID:26343011

  13. ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus.

    PubMed

    Karp, Peter D; Berger, Bonnie; Kovats, Diane; Lengauer, Thomas; Linial, Michal; Sabeti, Pardis; Hide, Winston; Rost, Burkhard

    2015-01-01

    Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to contribute through comparative analysis of the genome sequences of Ebola strains as well as 3-D protein modeling. Other computational approaches to Ebola may include large-scale docking studies of Ebola proteins with human proteins and with small-molecule libraries, computational modeling of the spread of the virus, computational mining of the Ebola literature, and creation of a curated Ebola database. Taken together, such computational efforts could significantly accelerate traditional scientific approaches. In recognition of the need for important and immediate solutions from the field of computational biology against Ebola, the International Society for Computational Biology (ISCB) announces a prize for an important computational advance in fighting the Ebola virus. ISCB will confer the ISCB Fight against Ebola Award, along with a prize of US$2,000, at its July 2016 annual meeting (ISCB Intelligent Systems for Molecular Biology (ISMB) 2016, Orlando, Florida). PMID:26097686

  14. A CELLULAR AUTOMATA MODEL OF EBOLA VIRUS EMILY BURKHEAD AND JANE HAWKINS

    E-print Network

    Hawkins, Jane M.

    A CELLULAR AUTOMATA MODEL OF EBOLA VIRUS DYNAMICS EMILY BURKHEAD AND JANE HAWKINS Abstract. We construct a stochastic cellular automaton (SCA) model for the spread of the Ebola virus (EBOV). We make Ebola virus (EBOV) is a filovirus that causes severe illness in most humans who are exposed to it

  15. Identification of N-glycans from Ebola virus glycoproteins by matrix-assisted laser desorption/

    E-print Network

    Identification of N-glycans from Ebola virus glycoproteins by matrix-assisted laser desorption glycoprotein (GP1) and the soluble glycoprotein (sGP) of Ebola virus were expressed in human embryonic kidney1. These results confirm and expand previous findings on partial characterisation of the Ebola virus

  16. Checklist for Patients Being Evaluated for Ebola Virus Disease (EVD) in the United States

    E-print Network

    Nicholson, Bruce J.

    Checklist for Patients Being Evaluated for Ebola Virus Disease (EVD) in the United States Upon to a country with widespread Ebola transmission* or having contact with an Ebola patient in the 21 days before illness onset Suspect Ebola if fever or compatible Ebola symptoms and an exposure are present See next

  17. Production of novel ebola virus-like particles from cDNAs: an alternative to ebola virus generation by reverse genetics.

    PubMed

    Watanabe, Shinji; Watanabe, Tokiko; Noda, Takeshi; Takada, Ayato; Feldmann, Heinz; Jasenosky, Luke D; Kawaoka, Yoshihiro

    2004-01-01

    We established a plasmid-based system for generating infectious Ebola virus-like particles (VLPs), which contain an Ebola virus-like minigenome consisting of a negative-sense copy of the green fluorescent protein gene. This system produced nearly 10(3) infectious particles per ml of supernatant, equivalent to the titer of Ebola virus generated by a reverse genetics system. Interestingly, infectious Ebola VLPs were generated, even without expression of VP24. Transmission and scanning electron microscopic analyses showed that the morphology of the Ebola VLPs was indistinguishable from that of authentic Ebola virus. Thus, this system allows us to study Ebola virus entry, replication, and assembly without biosafety level 4 containment. Furthermore, it may be useful in vaccine production against this highly pathogenic agent. PMID:14694131

  18. Analysis of Ebola Virus Entry Into Macrophages

    PubMed Central

    Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B.; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A.; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

    2015-01-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. In contrast, expression of Mer, integrin ?V, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin ?V promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

  19. Ebola Virus Disease in Health Care Workers--Guinea, 2014.

    PubMed

    Grinnell, Margaret; Dixon, Meredith G; Patton, Monica; Fitter, David; Bilivogui, Pépé; Johnson, Candice; Dotson, Ellen; Diallo, Boubacar; Rodier, Guenael; Raghunathan, Pratima

    2015-10-01

    An outbreak of Ebola virus disease (Ebola) began in Guinea in December 2013 and has continued through September 2015. Health care workers (HCWs) in West Africa are at high risk for Ebola infection owing to lack of appropriate triage procedures, insufficient equipment, and inadequate infection control practices. To characterize recent epidemiology of Ebola infections among HCWs in Guinea, national Viral Hemorrhagic Fever (VHF) surveillance data were analyzed for HCW cases reported during January 1–December 31, 2014. During 2014, a total of 162 (7.9%) of 2,210 laboratory-confirmed or probable Ebola cases among Guinean adults aged ?15 years occurred among HCWs, resulting in an incidence of Ebola infection among HCWs 42.2 times higher than among non-HCWs. The disproportionate burden of Ebola infection among HCWs taxes an already stressed health infrastructure, underscoring the need for increased understanding of transmission among HCWs and improved infection prevention and control measures to prevent Ebola infection among HCWs. PMID:26421761

  20. Histopathological and Immunohistochemical Studies of Lesions Associated with Ebola Virus in a Naturally Infected Chimpanzee

    E-print Network

    S54 Histopathological and Immunohistochemical Studies of Lesions Associated with Ebola Virus'Ivoire Lesions caused by the Co^te d'Ivoire subtype of Ebola virus in a naturally infected young chimpan- zee, so perti-A new subtype of Ebola (EBO) filovirus designated EBO nent laboratory analyses were done

  1. Paris | 24 juin 2015 Ebola : 3 variants du virus identifis en Guine

    E-print Network

    Wolf, Christian

    Paris | 24 juin 2015 Ebola : 3 variants du virus identifiés en Guinée Le séquençage du génome de souches du virus Ebola circulant en Guinée par des chercheurs de l'Institut Pasteur de Dakar et de Paris développement de traitements et de vaccins efficaces. L'épidémie d'Ebola sévit en Afrique de l'Ouest depuis plus

  2. Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission

    PubMed Central

    Kilianski, Andy; Evans, Nicholas G.

    2015-01-01

    The current Ebola virus outbreak has highlighted the uncertainties surrounding many aspects of Ebola virus virology, including routes of transmission. The scientific community played a leading role during the outbreak—potentially, the largest of its kind—as many of the questions surrounding ebolaviruses have only been interrogated in the laboratory. Scientists provided an invaluable resource for clinicians, public health officials, policy makers, and the lay public in understanding the progress of Ebola virus disease and the continuing outbreak. Not all of the scientific communication, however, was accurate or effective. There were multiple instances of published articles during the height of the outbreak containing potentially misleading scientific language that spurred media overreaction and potentially jeopardized preparedness and policy decisions at critical points. Here, we use articles declaring the potential for airborne transmission of Ebola virus as a case study in the inaccurate reporting of basic science, and we provide recommendations for improving the communication about unknown aspects of disease during public health crises. PMID:26512988

  3. Small molecules with antiviral activity against the Ebola virus.

    PubMed

    Litterman, Nadia; Lipinski, Christopher; Ekins, Sean

    2015-01-01

    The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus. PMID:25713700

  4. Nurses leading the fight against Ebola virus disease.

    PubMed

    Sagar, Priscilla L

    2015-05-01

    The current Ebola crisis has sparked worldwide reaction of panic and disbelief in its wake as it decimated communities in West Africa, particularly in Guinea, Liberia, and Sierra Leone, including its health care workers. This article affirms the crucial role nurses play in maintaining health and preventing diseases, connects the devastating havoc of the Ebola virus disease to another issue of nursing shortage in underdeveloped countries, and asserts the key leadership nurses play in protecting the communities they serve while maintaining their safety and those of other health care workers. Nurses must actively seek a place at the table, as echoed by the American Academy of Nursing and American Nurses Association and the American Nurses Association, when decisions are being made regarding Ebola virus disease: at care settings, in the board room, and at federal, state, and local levels. PMID:25712149

  5. EbolaVirus Disease (EVD) Algorithm for Evaluation of the ReturnedTraveler

    E-print Network

    Kachroo, Pushkin

    EbolaVirus Disease (EVD) Algorithm for Evaluation of the ReturnedTraveler Reportasymptomatic (including during funeral rites) in an Ebola affected area** without appropriate PPE LOW-RISK EXPOSURE after their last exposure to an Ebola patient YES NO ** CDCWebsite to check current affected areas: www.cdc.gov/vhf/ebola

  6. Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus.

    PubMed Central

    Johnson, E.; Jaax, N.; White, J.; Jahrling, P.

    1995-01-01

    The potential of aerogenic infection by Ebola virus was established by using a head-only exposure aerosol system. Virus-containing droplets of 0.8-1.2 microns were generated and administered into the respiratory tract of rhesus monkeys via inhalation. Inhalation of viral doses as low as 400 plaque-forming units of virus caused a rapidly fatal disease in 4-5 days. The illness was clinically identical to that reported for parenteral virus inoculation, except for the occurrence of subcutaneous and venipuncture site bleeding and serosanguineous nasal discharge. Immunocytochemistry revealed cell-associated Ebola virus antigens present in airway epithelium, alveolar pneumocytes, and macrophages in the lung and pulmonary lymph nodes; extracellular antigen was present on mucosal surfaces of the nose, oropharynx and airways. Aggregates of characteristic filamentous virus were present within type I pneumocytes, macrophages, and air spaces of the lung by electron microscopy. Demonstration of fatal aerosol transmission of this virus in monkeys reinforces the importance of taking appropriate precautions to prevent its potential aerosol transmission to humans. Images Figure 3 Figure 4 Figure 5 PMID:7547435

  7. Ebola Virus Disease (The Killer Virus): Another Threat to Humans and Bioterrorism: Brief Review and Recent Updates

    PubMed Central

    Sharma, Sarang; Dutta, Shubha Ranjan; Dudeja, Pooja; Sharma, Vivek

    2015-01-01

    Ebola virus disease (EVD) described as “one of the world’s most virulent diseases” by WHO was popularly known as Ebola haemorrhagic fever in the past. It is usually considered a severe and deadly illness when humans are concerned. EVD outbreaks have shown to have a very high fatality rate ranging from 50 - 90% with a reported occurrence primarily seen near the tropical rainforests of remote villages in Central and West Africa. The virus is transmitted to people from wild animals and within the human community through human-to-human contact. Natural host for Ebola virus is not yet conclusively identified but the most probable host appears to be the fruit bats of the Pteropodidae family. Five subspecies of Ebola virus are recognized till date, with Zaire Ebola virus being the most aggressive of all varieties and recording up to 90% mortality. All Ebola forms are highly contagious and hence have been classed as Category A Priority Pathogens by WHO. Severely ill patients warrant intensive support therapy. Medical workers working in affected areas need to undertake extensive measures to prevent contracting the disease. Till date, no particular anti-viral therapy has demonstrated effectiveness in Ebola virus infection. Also, no vaccine for use in humans is yet approved by the regulatory bodies. If Ebola was actually misused as a biological weapon, it could be a serious threat. Idea behind this article is to briefly review the history and present recent updates on Ebola virus, its pathogenesis and possible hopes for treatment. PMID:26266139

  8. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    SciTech Connect

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-10-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.

  9. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    SciTech Connect

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-10-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/Co gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/Co radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. We found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.

  10. Molecular Evidence of Sexual Transmission of Ebola Virus.

    PubMed

    Mate, Suzanne E; Kugelman, Jeffrey R; Nyenswah, Tolbert G; Ladner, Jason T; Wiley, Michael R; Cordier-Lassalle, Thierry; Christie, Athalia; Schroth, Gary P; Gross, Stephen M; Davies-Wayne, Gloria J; Shinde, Shivam A; Murugan, Ratnesh; Sieh, Sonpon B; Badio, Moses; Fakoli, Lawrence; Taweh, Fahn; de Wit, Emmie; van Doremalen, Neeltje; Munster, Vincent J; Pettitt, James; Prieto, Karla; Humrighouse, Ben W; Ströher, Ute; DiClaro, Joseph W; Hensley, Lisa E; Schoepp, Randal J; Safronetz, David; Fair, Joseph; Kuhn, Jens H; Blackley, David J; Laney, A Scott; Williams, Desmond E; Lo, Terrence; Gasasira, Alex; Nichol, Stuart T; Formenty, Pierre; Kateh, Francis N; De Cock, Kevin M; Bolay, Fatorma; Sanchez-Lockhart, Mariano; Palacios, Gustavo

    2015-12-17

    A suspected case of sexual transmission from a male survivor of Ebola virus disease (EVD) to his female partner (the patient in this report) occurred in Liberia in March 2015. Ebola virus (EBOV) genomes assembled from blood samples from the patient and a semen sample from the survivor were consistent with direct transmission. The genomes shared three substitutions that were absent from all other Western African EBOV sequences and that were distinct from the last documented transmission chain in Liberia before this case. Combined with epidemiologic data, the genomic analysis provides evidence of sexual transmission of EBOV and evidence of the persistence of infective EBOV in semen for 179 days or more after the onset of EVD. (Funded by the Defense Threat Reduction Agency and others.). PMID:26465384

  11. A cellular automata model of Ebola virus dynamics

    NASA Astrophysics Data System (ADS)

    Burkhead, Emily; Hawkins, Jane

    2015-11-01

    We construct a stochastic cellular automaton (SCA) model for the spread of the Ebola virus (EBOV). We make substantial modifications to an existing SCA model used for HIV, introduced by others and studied by the authors. We give a rigorous analysis of the similarities between models due to the spread of virus and the typical immune response to it, and the differences which reflect the drastically different timing of the course of EBOV. We demonstrate output from the model and compare it with clinical data.

  12. Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication.

    PubMed

    Reynard, Olivier; Nguyen, Xuan-Nhi; Alazard-Dany, Nathalie; Barateau, Véronique; Cimarelli, Andrea; Volchkov, Viktor E

    2015-01-01

    The current outbreak of Ebola virus (EBOV) in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue ?-d-N4-hydroxycytidine (NHC) demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV. PMID:26633464

  13. Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication

    PubMed Central

    Reynard, Olivier; Nguyen, Xuan-Nhi; Alazard-Dany, Nathalie; Barateau, Véronique; Cimarelli, Andrea; Volchkov, Viktor E.

    2015-01-01

    The current outbreak of Ebola virus (EBOV) in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue ?-d-N4-hydroxycytidine (NHC) demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV. PMID:26633464

  14. Ebola

    MedlinePLUS

    ... Digestive System How the Body Works Main Page Ebola KidsHealth > Kids > Health Problems > Infections > Ebola Print A ... Kids Need to Do About Ebola? What Is Ebola? Ebola is a dangerous virus that can cause ...

  15. Learning from Ebola Virus: How to Prevent Future Epidemics.

    PubMed

    Kekulé, Alexander S

    2015-07-01

    The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure of the international response and proposes four measures to improve resilience, early detection and response to future outbreaks of infectious diseases. PMID:26184283

  16. Learning from Ebola Virus: How to Prevent Future Epidemics

    PubMed Central

    Kekulé, Alexander S.

    2015-01-01

    The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure of the international response and proposes four measures to improve resilience, early detection and response to future outbreaks of infectious diseases. PMID:26184283

  17. Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996.

    PubMed

    Miranda, M E; Ksiazek, T G; Retuya, T J; Khan, A S; Sanchez, A; Fulhorst, C F; Rollin, P E; Calaor, A B; Manalo, D L; Roces, M C; Dayrit, M M; Peters, C J

    1999-02-01

    Ebola (subtype Reston [EBO-R]) virus infection was detected in macaques imported into the United States from the Philippines in March 1996. Studies were initiated in the Philippines to identify the source of the virus among monkey-breeding and export facilities, to establish surveillance and testing, and to assess the risk and significance of EBO-R infections in humans who work in these facilities. Over a 5-month period, acutely infected animals were found at only one facility, as determined using Ebola antigen detection. Three of 1732 monkeys and 1 of 246 animal handlers tested had detectable antibodies; all were from the same facility, which was the source of infected monkeys imported to the United States. Virus transmission, which was facilitated by poor infection-control practices, continued for several months in one facility and was stopped only when the facility was depopulated. None of the 246 employees of the facilities or 4 contacts of previously antibody-positive individuals reported an Ebola-like illness. This investigation suggests that human EBO-R infection is rare. PMID:9988174

  18. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection.

    PubMed

    Geisbert, Thomas W; Strong, James E; Feldmann, Heinz

    2015-10-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions. PMID:26063223

  19. Diagnosis of Febrile Illnesses Other Than Ebola Virus Disease at an Ebola Treatment Unit in Sierra Leone.

    PubMed

    O'Shea, Matthew K; Clay, Kate A; Craig, Darren G; Matthews, Steven W; Kao, Raymond L C; Fletcher, Thomas E; Bailey, Mark S; Hutley, Emma

    2015-09-01

    Patients with febrile illnesses presenting to an Ebola treatment unit in Sierra Leone had a wide range of diagnoses other than Ebola virus disease. Rapid diagnostic tests were useful in confirming these diagnoses, reducing the length of patient stay with valuable consequences. These alternative diagnoses should assist in future planning. PMID:25991466

  20. Computational elucidation of potential antigenic CTL epitopes in Ebola virus.

    PubMed

    Dikhit, Manas R; Kumar, Santosh; Vijaymahantesh; Sahoo, Bikash R; Mansuri, Rani; Amit, Ajay; Yousuf Ansari, Md; Sahoo, Ganesh C; Bimal, Sanjiva; Das, Pradeep

    2015-12-01

    Cell-mediated immunity is important for the control of Ebola virus infection. We hypothesized that those HLA A0201 and HLA B40 restricted epitopes derived from Ebola virus proteins, would mount a good antigenic response. Here we employed an immunoinformatics approach to identify specific 9mer amino acid which may be capable of inducing a robust cell-mediated immune response in humans. We identified a set of 28 epitopes that had no homologs in humans. Specifically, the epitopes derived from NP, RdRp, GP and VP40 share population coverage of 93.40%, 84.15%, 74.94% and 77.12%, respectively. Based on the other HLA binding specificity and population coverage, seven novel promiscuous epitopes were identified. These 7 promiscuous epitopes from NP, RdRp and GP were found to have world-wide population coverage of more than 95% indicating their potential significance as useful candidates for vaccine design. Epitope conservancy analysis also suggested that most of the peptides are highly conserved (100%) in other virulent Ebola strain (Mayinga-76, Kikwit-95 and Makona-G3816- 2014) and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates. PMID:26462623

  1. Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein

    PubMed Central

    López-Pacheco, Felipe; Pérez-Chavarría, Roberto; González-Vázquez, Juan Carlos; González-González, Everardo; Trujillo-de Santiago, Grissel; Ponce-Ponce de León, César Alejandro; Zhang, Yu Shrike; Dokmeci, Mehmet Remzi; Khademhosseini, Ali; Alvarez, Mario Moisés

    2015-01-01

    Background Current Ebola virus (EBOV) detection methods are costly and impractical for epidemic scenarios. Different immune-based assays have been reported for the detection and quantification of Ebola virus (EBOV) proteins. In particular, several monoclonal antibodies (mAbs) have been described that bind the capsid glycoprotein (GP) of EBOV GP. However, the currently available platforms for the design and production of full-length mAbs are cumbersome and costly. The use of antibody fragments, rather than full-length antibodies, might represent a cost-effective alternative for the development of diagnostic and possibly even therapeutic alternatives for EBOV. Methods/Principal Findings We report the design and expression of three recombinant anti-GP mAb fragments in Escherichia coli cultures. These fragments contained the heavy and light variable portions of the three well-studied anti-GP full-length mAbs 13C6, 13F6, and KZ52, and are consequently named scFv-13C6, scFv-13F6, and Fab-KZ52, respectively. All three fragments exhibited specific anti-GP binding activity in ELISA experiments comparable to that of full-length anti-GP antibodies (i.e., the same order of magnitude) and they are easily and economically produced in bacterial cultures. Conclusion/Significance Antibody fragments might represent a useful, effective, and low cost alternative to full-length antibodies in Ebola related capture and diagnostics applications. PMID:26489048

  2. External Quality Assessment of Molecular Detection of Ebola Virus in China

    PubMed Central

    Wang, Guojing; Sun, Yu; Zhang, Kuo; Jia, Tingting; Hao, Mingju; Zhang, Dong; Chang, Le; Zhang, Lei; Zhang, Rui; Lin, Guigao; Peng, Rongxue; Li, Jinming

    2015-01-01

    In 2014, Ebola hemorrhagic fever broke out in West Africa. As contact between China and West Africa is frequent, the possibility that Ebola virus would enter China was high. Thus, an external assessment of the quality of Ebola virus detection was organized by the National Center for Clinical Laboratories in China. Virus-like particles encapsulating known sequences of epidemic strains of Ebola virus from 2014 were prepared as positive quality controls. The sample panel, which was composed of seven positive and three negative samples, was dispatched to 19 laboratories participating in this assessment of Ebola virus detection. Accurate detection was reported at 14 of the 19 participating laboratories, with a sensitivity of 91.43% and a specificity of 100%. Four participants (21.05%) reported false-negative results and were classified as “acceptable.” One participant (5.26%) did not detect any positive samples and was thus classified as “improvable.” Based on the results returned, the ability to detect weakly positive Ebola specimens should be improved. Furthermore, commercial assays and the standard primers offered by the Chinese Centers for Disease Control and Prevention were found to be most accurate and dependable for Ebola detection. A two-target detection approach is recommended for Ebola screening; this approach could reduce the probability of false-negative results. Additionally, standardization of operations and punctual adjustment of instruments are necessary for the control and prevention of Ebola virus. PMID:26177537

  3. Ebola Virus Disease--Sierra Leone and Guinea, August 2015.

    PubMed

    Hersey, Sara; Martel, Lise D; Jambai, Amara; Keita, Sakoba; Yoti, Zabulon; Meyer, Erika; Seeman, Sara; Bennett, Sarah; Ratto, Jeffrey; Morgan, Oliver; Akyeampong, Mame Afua; Sainvil, Schabbethai; Worrell, Mary Claire; Fitter, David; Arnold, Kathryn E

    2015-01-01

    The Ebola virus disease (Ebola) outbreak in West Africa began in late 2013 in Guinea (1) and spread unchecked during early 2014. By mid-2014, it had become the first Ebola epidemic ever documented. Transmission was occurring in multiple districts of Guinea, Liberia, and Sierra Leone, and for the first time, in capital cities (2). On August 8, 2014, the World Health Organization (WHO) declared the outbreak to be a Public Health Emergency of International Concern (3). Ministries of Health, with assistance from multinational collaborators, have reduced Ebola transmission, and the number of cases is now declining. While Liberia has not reported a case since July 12, 2015, transmission has continued in Guinea and Sierra Leone, although the numbers of cases reported are at the lowest point in a year. In August 2015, Guinea and Sierra Leone reported 10 and four confirmed cases, respectively, compared with a peak of 526 (Guinea) and 1,997 (Sierra Leone) in November 2014. This report details the current situation in Guinea and Sierra Leone, outlines strategies to interrupt transmission, and highlights the need to maintain public health response capacity and vigilance for new cases at this critical time to end the outbreak. PMID:26355422

  4. The Ebola contagion and forecasting virus: evidence from four African countries.

    PubMed

    Nadhem, Selmi; Nejib, Hachicha D

    2015-12-01

    This paper is focused on examining the number of deaths' increases participation in the propagating the Ebola virus during the period ranging from March to October 2014. An application of the MGARCH-DCC model regressions on four countries has led to discover that the finding that human contact play a significant role in transmitting the Ebola virus. Our findings also reveal that Guinea has already suffered from a spread-like virus originating from Sierra Lione and Liberia. Noteworthy also, other countries are now liable to such a risk; for instance, Nigeria is a country vulnerable to the propagation of this virus. Consequently, we undertake to conduct our forecasts for EGARCH model estimates implements; which has estimated a decrease in the Ebola virus incurred number of deadly Ebola virus over the two months following the November and December. PMID:26070395

  5. Molecular mechanisms of Ebola virus pathogenesis: focus on cell death.

    PubMed

    Falasca, L; Agrati, C; Petrosillo, N; Di Caro, A; Capobianchi, M R; Ippolito, G; Piacentini, M

    2015-08-01

    Ebola virus (EBOV) belongs to the Filoviridae family and is responsible for a severe disease characterized by the sudden onset of fever and malaise accompanied by other non-specific signs and symptoms; in 30-50% of cases hemorrhagic symptoms are present. Multiorgan dysfunction occurs in severe forms with a mortality up to 90%. The EBOV first attacks macrophages and dendritic immune cells. The innate immune reaction is characterized by a cytokine storm, with secretion of numerous pro-inflammatory cytokines, which induces a huge number of contradictory signals and hurts the immune cells, as well as other tissues. Other highly pathogenic viruses also trigger cytokine storms, but Filoviruses are thought to be particularly lethal because they affect a wide array of tissues. In addition to the immune system, EBOV attacks the spleen and kidneys, where it kills cells that help the body to regulate its fluid and chemical balance and that make proteins that help the blood to clot. In addition, EBOV causes liver, lungs and kidneys to shut down their functions and the blood vessels to leak fluid into surrounding tissues. In this review, we analyze the molecular mechanisms at the basis of Ebola pathogenesis with a particular focus on the cell death pathways induced by the virus. We also discuss how the treatment of the infection can benefit from the recent experience of blocking/modulating cell death in human degenerative diseases. PMID:26024394

  6. Molecular mechanisms of Ebola virus pathogenesis: focus on cell death

    PubMed Central

    Falasca, L; Agrati, C; Petrosillo, N; Di Caro, A; Capobianchi, M R; Ippolito, G; Piacentini, M

    2015-01-01

    Ebola virus (EBOV) belongs to the Filoviridae family and is responsible for a severe disease characterized by the sudden onset of fever and malaise accompanied by other non-specific signs and symptoms; in 30–50% of cases hemorrhagic symptoms are present. Multiorgan dysfunction occurs in severe forms with a mortality up to 90%. The EBOV first attacks macrophages and dendritic immune cells. The innate immune reaction is characterized by a cytokine storm, with secretion of numerous pro-inflammatory cytokines, which induces a huge number of contradictory signals and hurts the immune cells, as well as other tissues. Other highly pathogenic viruses also trigger cytokine storms, but Filoviruses are thought to be particularly lethal because they affect a wide array of tissues. In addition to the immune system, EBOV attacks the spleen and kidneys, where it kills cells that help the body to regulate its fluid and chemical balance and that make proteins that help the blood to clot. In addition, EBOV causes liver, lungs and kidneys to shut down their functions and the blood vessels to leak fluid into surrounding tissues. In this review, we analyze the molecular mechanisms at the basis of Ebola pathogenesis with a particular focus on the cell death pathways induced by the virus. We also discuss how the treatment of the infection can benefit from the recent experience of blocking/modulating cell death in human degenerative diseases. PMID:26024394

  7. Community Knowledge, Attitudes, and Practices Regarding Ebola Virus Disease - Five Counties, Liberia, September-October, 2014.

    PubMed

    Kobayashi, Miwako; Beer, Karlyn D; Bjork, Adam; Chatham-Stephens, Kevin; Cherry, Cara C; Arzoaquoi, Sampson; Frank, Wilmot; Kumeh, Odell; Sieka, Joseph; Yeiah, Adolphus; Painter, Julia E; Yoder, Jonathan S; Flannery, Brendan; Mahoney, Frank; Nyenswah, Tolbert G

    2015-07-10

    As of July 1, 2015, Guinea, Liberia, and Sierra Leone have reported a total of 27,443 confirmed, probable, and suspected Ebola virus disease (Ebola) cases and 11,220 deaths. Guinea and Sierra Leone have yet to interrupt transmission of Ebola virus. In May, 2015, Liberia successfully achieved Ebola transmission-free status, with no new Ebola cases occurring during a 42-day period; however, new Ebola cases were reported beginning June 29, 2015. Local cultural practices and beliefs have posed challenges to disease control, and therefore, targeted, timely health messages are needed to address practices and misperceptions that might hinder efforts to stop the spread of Ebola. As early as September 2014, Ebola spread to most counties in Liberia. To assess Ebola-related knowledge, attitudes, and practices (KAP) in the community, CDC epidemiologists who were deployed to the counties (field team), carried out a survey conducted by local trained interviewers. The survey was conducted in September and October 2014 in five counties in Liberia with varying cumulative incidence of Ebola cases. Survey results indicated several findings. First, basic awareness of Ebola was high across all surveyed populations (median correct responses = 16 of 17 questions on knowledge of Ebola transmission; range = 2-17). Second, knowledge and understanding of Ebola symptoms were incomplete (e.g., 61% of respondents said they would know if they had Ebola symptoms). Finally, certain fears about the disease were present: >90% of respondents indicated a fear of Ebola patients, >40% a fear of cured patients, and >50% a fear of treatment units (expressions of this last fear were greater in counties with lower Ebola incidence). This survey, which was conducted at a time when case counts were rapidly increasing in Liberia, indicated limited knowledge of Ebola symptoms and widespread fear of Ebola treatment units despite awareness of communication messages. Continued efforts are needed to address cultural practices and beliefs to interrupt Ebola transmission. PMID:26158352

  8. Ebola Virus Disease: A Perspective for the United States.

    PubMed

    Madariaga, Miguel G

    2015-07-01

    Ebola virus caused an epidemic of unprecedented extension in West Africa. There was concern that the outbreak would not be controlled for a prolonged period of time. Two cases of infected returning travelers have been reported in the US. One of the cases has been associated with secondary transmission and other infected subjects have been repatriated for treatment. This article reviews the etiology, pathogenesis, transmission, clinical manifestations, diagnosis, treatment, and prevention of the disease with emphasis on the identification and management in the US. PMID:25731139

  9. Planning and response to Ebola virus disease: An integrated approach.

    PubMed

    Smith, Philip W; Boulter, Kathleen C; Hewlett, Angela L; Kratochvil, Christopher J; Beam, Elizabeth J; Gibbs, Shawn G; Lowe, John-Martin J; Schwedhelm, Michelle M

    2015-05-01

    The care of patients with Ebola virus disease (EVD) requires the application of critical care medicine principles under conditions of stringent infection control precautions. The care of patients with EVD requires a number of elements in terms of physical layout, personal protective apparel, and other equipment. Provision of care is demanding in terms of depth of staff and training. The key to safely providing such care is a system that brings many valuable skills to the table, and allows communication between these individuals. We present our approach to leadership structure and function--a variation of incident command--in providing care to 3 patients with EVD. PMID:25952046

  10. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks.

    PubMed

    Haque, Azizul; Hober, Didier; Blondiaux, Joel

    2015-10-01

    Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. PMID:26248374

  11. Ebola virus disease: societal challenges and new treatments.

    PubMed

    Mirazimi, A

    2015-09-01

    Ebola virus disease (EVD) is a zoonotic disease that causes severe haemorrhagic fever, with high fatality rates of up to 90% in humans. Today, there is no effective treatment available. Person-to-person transmission occurs through exposure to blood or body fluids, which can threaten other household members and first-line healthcare workers. The first cases of EVD in Guinea were identified on 22 March 2014. It was initially believed that this like previous outbreaks would be self-limiting. However, lack of public health infrastructure, delays in virus detection and late implementation of control interventions contributed to widespread transmission of EVD in a region inexperienced in dealing with the disease. Socio-cultural and economic factors probably also played a key role in the spread of the disease, resulting in the current large-scale outbreak. Some promising candidate treatments for this disease are now being developed. PMID:26147380

  12. Against the clock towards new Ebola virus therapies.

    PubMed

    Martínez-Romero, Carles; García-Sastre, Adolfo

    2015-11-01

    Since the end of 2013, West Africa has been suffering the largest Ebola virus (EBOV) outbreak in recorded history. The lack of health care infrastructure in the affected countries, as well as a concentration of infected cases in the most populated areas allowed the virus to spread with no control during the first months of the outbreak. With no specific treatment available to combat EBOV infection and its associated disease, an extraordinary worldwide effort was made to confront the severity of the situation and to establish new therapeutic strategies that would lead to better and faster control and eradicate the outbreak. In the last two years, several candidate therapies and potential vaccines against EBOV have arisen and human clinical trials are ongoing, in hopes of starting their deployment in the affected countries. This article reviews the current candidate therapies against EBOV, their stage of development and future prospects in battling EBOV outbreaks. PMID:26057711

  13. Ebola virus disease control in West Africa: an ecological, one health approach

    PubMed Central

    Meseko, Clement Adebajo; Egbetade, Adeniyi Olugbenga; Fagbo, Shamsudeen

    2015-01-01

    The 2013-2015 Ebola Virus Disease outbreak in West Africa had similar nuances with the 1976 outbreaks in Central Africa; both were caused by the Zaire Ebola Virus strain and originated from rural forested communities. The definitive reservoir host of Ebola virus still remains unknown till date. However, from ecological perspective, it is known that the virus first emerged from forest ecotypes interfacing with human activities. As at March 2015, the outbreak has claimed over 9000 lives, which is unprecedented. Though it remains unproved, the primary sources of infection for past and present outbreaks are forest dwelling, human-hunted fauna. Understanding the ecological factors at play in these forest ecotypes where wild fauna interface with human and causing pathogen spill over is important. A broad based One Health approach incorporating these ecological concepts in the control of Ebola Virus Disease can effectively ameliorate or forestall infection now and in the future. PMID:26401200

  14. Modeling the effect of comprehensive interventions on Ebola virus transmission

    PubMed Central

    Shen, Mingwang; Xiao, Yanni; Rong, Libin

    2015-01-01

    Since the re-emergence of Ebola in West Africa in 2014, comprehensive and stringent interventions have been implemented to decelerate the spread of the disease. The effectiveness of interventions still remains unclear. In this paper, we develop an epidemiological model that includes various controlling measures to systematically evaluate their effects on the disease transmission dynamics. By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. Model analysis shows that there exists a threshold of the effectiveness of isolation, below which increasing the fraction of latent individuals diagnosed prior to symptoms onset or shortening the duration between symptoms onset and isolation may lead to more Ebola infection. This challenges an existing view. Media coverage plays a substantial role in reducing the final epidemic size. The response to reported cumulative infected cases and deaths may have a different effect on the epidemic spread in different countries. Among all the interventions, we find that shortening the duration between death and burial and improving the effectiveness of isolation are two effective interventions for controlling the outbreak of Ebola virus infection. PMID:26515898

  15. Modeling the effect of comprehensive interventions on Ebola virus transmission

    NASA Astrophysics Data System (ADS)

    Shen, Mingwang; Xiao, Yanni; Rong, Libin

    2015-10-01

    Since the re-emergence of Ebola in West Africa in 2014, comprehensive and stringent interventions have been implemented to decelerate the spread of the disease. The effectiveness of interventions still remains unclear. In this paper, we develop an epidemiological model that includes various controlling measures to systematically evaluate their effects on the disease transmission dynamics. By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. Model analysis shows that there exists a threshold of the effectiveness of isolation, below which increasing the fraction of latent individuals diagnosed prior to symptoms onset or shortening the duration between symptoms onset and isolation may lead to more Ebola infection. This challenges an existing view. Media coverage plays a substantial role in reducing the final epidemic size. The response to reported cumulative infected cases and deaths may have a different effect on the epidemic spread in different countries. Among all the interventions, we find that shortening the duration between death and burial and improving the effectiveness of isolation are two effective interventions for controlling the outbreak of Ebola virus infection.

  16. Ebola

    MedlinePLUS

    ... Your Best Self Smart Snacking Losing Weight Safely Ebola KidsHealth > Teens > Infections > Bacterial & Viral Infections > Ebola Print ... Do? How Do People Protect Themselves? What Is Ebola? Ebola is a dangerous virus that can cause ...

  17. Mapping the zoonotic niche of Ebola virus disease in Africa

    PubMed Central

    Pigott, David M; Golding, Nick; Mylne, Adrian; Huang, Zhi; Henry, Andrew J; Weiss, Daniel J; Brady, Oliver J; Kraemer, Moritz UG; Smith, David L; Moyes, Catherine L; Bhatt, Samir; Gething, Peter W; Horby, Peter W; Bogoch, Isaac I; Brownstein, John S; Mekaru, Sumiko R; Tatem, Andrew J; Khan, Kamran; Hay, Simon I

    2014-01-01

    Ebola virus disease (EVD) is a complex zoonosis that is highly virulent in humans. The largest recorded outbreak of EVD is ongoing in West Africa, outside of its previously reported and predicted niche. We assembled location data on all recorded zoonotic transmission to humans and Ebola virus infection in bats and primates (1976–2014). Using species distribution models, these occurrence data were paired with environmental covariates to predict a zoonotic transmission niche covering 22 countries across Central and West Africa. Vegetation, elevation, temperature, evapotranspiration, and suspected reservoir bat distributions define this relationship. At-risk areas are inhabited by 22 million people; however, the rarity of human outbreaks emphasises the very low probability of transmission to humans. Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past. DOI: http://dx.doi.org/10.7554/eLife.04395.001 PMID:25201877

  18. Implications of Ebola virus disease on wildlife conservation in Nigeria

    PubMed Central

    Egbetade, Adeniyi Olugbenga; Sonibare, Adekayode Olanrewaju; Meseko, Clement Adebajo; Jayeola, Omotola Abiola; Otesile, Ebenezer Babatunde

    2015-01-01

    The recent Ebola Virus Disease outbreak in some West African countries spanning from late 2013 and currently on as of 13th March, 2015 is the most widespread and fatal with human mortality that has surpassed all previous outbreaks. The outbreak has had its toll on conservation of endangered species. This portends danger for the wild fauna of the country if proactive measures are not taken to prepare grounds for evidence- based assertions concerning the involvement of wild species. To this end, there is an urgent need for sweeping census of reserves, national parks and wetlands. As well as the creation of a system involving reportage by sectors like the industries (extractive and construction) including persons and organisations involved with wildlife related activities. This documentation of die offs and unusual events to collaborating institutions, will help in monitoring trends which hitherto would have gone unnoticed. The importance of bats and primates in agriculture and public health via consumption of vermin insects and seed dispersal cannot be over-emphasized. There is the need for caution on the tendencies to destroy indicator species which could be silent pointers to emerging or remerging health and environmental issues. Wildlife resources are still reliably useful and caution is advised in the use of blanket destructive policies like fumigation of caves, indiscriminate culling and poisoned baits to destroy supposedly Ebola Disease Virus wildlife reservoirs. This paper highlights the immediate conservation problems and likely future implications of Ebola saga in Nigeria. It tries to identify the gaps in wildlife researches and makes recommendations for probable workable conservation strategies.

  19. Implications of Ebola virus disease on wildlife conservation in Nigeria.

    PubMed

    Egbetade, Adeniyi Olugbenga; Sonibare, Adekayode Olanrewaju; Meseko, Clement Adebajo; Jayeola, Omotola Abiola; Otesile, Ebenezer Babatunde

    2015-01-01

    The recent Ebola Virus Disease outbreak in some West African countries spanning from late 2013 and currently on as of 13th March, 2015 is the most widespread and fatal with human mortality that has surpassed all previous outbreaks. The outbreak has had its toll on conservation of endangered species. This portends danger for the wild fauna of the country if proactive measures are not taken to prepare grounds for evidence- based assertions concerning the involvement of wild species. To this end, there is an urgent need for sweeping census of reserves, national parks and wetlands. As well as the creation of a system involving reportage by sectors like the industries (extractive and construction) including persons and organisations involved with wildlife related activities. This documentation of die offs and unusual events to collaborating institutions, will help in monitoring trends which hitherto would have gone unnoticed. The importance of bats and primates in agriculture and public health via consumption of vermin insects and seed dispersal cannot be over-emphasized. There is the need for caution on the tendencies to destroy indicator species which could be silent pointers to emerging or remerging health and environmental issues. Wildlife resources are still reliably useful and caution is advised in the use of blanket destructive policies like fumigation of caves, indiscriminate culling and poisoned baits to destroy supposedly Ebola Disease Virus wildlife reservoirs. This paper highlights the immediate conservation problems and likely future implications of Ebola saga in Nigeria. It tries to identify the gaps in wildlife researches and makes recommendations for probable workable conservation strategies. PMID:26740844

  20. Surveillance and preparedness for Ebola virus disease -- New York City, 2014.

    PubMed

    Benowitz, Isaac; Ackelsberg, Joel; Balter, Sharon E; Baumgartner, Jennifer C; Dentinger, Catherine; Fine, Anne D; Harper, Scott A; Jones, Lucretia E; Laraque, Fabienne; Lee, Ellen H; Merizalde, Giselle; Yacisin, Kari A; Varma, Jay K; Layton, Marcelle C

    2014-10-17

    In July 2014, as the Ebola virus disease (Ebola) epidemic expanded in Guinea, Liberia, and Sierra Leone, an air traveler brought Ebola to Nigeria and two American health care workers in West Africa were diagnosed with Ebola and later medically evacuated to a U.S. hospital. New York City (NYC) is a frequent port of entry for travelers from West Africa, a home to communities of West African immigrants who travel back to their home countries, and a home to health care workers who travel to West Africa to treat Ebola patients. Ongoing transmission of Ebolavirus in West Africa could result in an infected person arriving in NYC. The announcement on September 30 of an Ebola case diagnosed in Texas in a person who had recently arrived from an Ebola-affected country further reinforced the need in NYC for local preparedness for Ebola. PMID:25321072

  1. EbolaTracks: an automated SMS system for monitoring persons potentially exposed to Ebola virus disease.

    PubMed

    Tracey, L E; Regan, A K; Armstrong, P K; Dowse, G K; Effler, P V

    2015-01-01

    We report development and implementation of a short message service (SMS)-based system to facilitate active monitoring of persons potentially exposed to Ebola virus disease (EVD), whether returning from EVD-affected countries, or contacts of local cases, should they occur. The system solicits information on symptoms and temperature twice daily. We demonstrated proof-of-concept; however this system would likely be even more useful where there are many local contacts to confirmed EVD cases or travellers from EVD-affected countries. PMID:25613652

  2. Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor

    SciTech Connect

    Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

    2015-04-14

    Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 10? PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodology has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.

  3. Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor

    DOE PAGESBeta

    Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

    2015-04-14

    Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 10? PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodologymore »has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.« less

  4. Rapid Detection of Ebola Virus with a Reagent-Free, Point-of-Care Biosensor

    PubMed Central

    Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

    2015-01-01

    Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 104 PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodology has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions. PMID:25875186

  5. Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

    SciTech Connect

    Bukreyev, Alexander Marzi, Andrea; Feldmann, Friederike; Zhang Liqun; Dorward, David W.; Pickles, Raymond J.; Feldmann, Heinz; Collins, Peter L.

    2009-01-20

    We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/{delta}F-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/{delta}F-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/{delta}F-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV.

  6. Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

    PubMed Central

    Bukreyev, Alexander; Marzi, Andrea; Feldmann, Friederike; Zhang, Liqun; Yang, Lijuan; Ward, Jerrold M.; Dorward, David W.; Pickles, Raymond J.; Murphy, Brian R.; Feldmann, Heinz; Collins, Peter L.

    2009-01-01

    We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/?F-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/?F-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/?F-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV. PMID:19010509

  7. In silico analysis suggests repurposing of ibuprofen for prevention and treatment of EBOLA virus disease

    PubMed Central

    Veljkovic, Veljko; Goeijenbier, Marco; Glisic, Sanja; Veljkovic, Nevena; Perovic, Vladimir R.; Sencanski, Milan; Branch, Donald R.; Paessler, Slobodan

    2015-01-01

    The large 2014/2015 Ebola virus outbreak in West Africa points out the urgent need to develop new preventive and therapeutic approaches that are effective against Ebola viruses and  can be rapidly utilized. Recently, a simple theoretical criterion for the virtual screening of molecular libraries for candidate inhibitors of Ebola virus infection was proposed. Using this method the ‘drug space’ was screened and 267 approved and 382 experimental drugs as candidates for treatment of the Ebola virus disease (EVD) have been selected. Detailed analysis of these drugs revealed the non-steroidal anti-inflammatory drug ibuprofen as an inexpensive, widely accessible and minimally toxic candidate for prevention and treatment of EVD. Furthermore, the molecular mechanism underlying this possible protective effect of ibuprofen against EVD is suggested in this article. PMID:26167272

  8. Epidemiological features and trends of Ebola virus disease in West Africa.

    PubMed

    Wang, Ligui; Yang, Guang; Jia, Leili; Li, Zhenjun; Xie, Jing; Li, Peng; Qiu, Shaofu; Hao, Rongzhang; Wu, Zhihao; Ma, Hui; Song, Hongbin

    2015-09-01

    According to a World Health Organization report, the epidemiological features of Ebola virus disease (EVD) have changed significantly in West Africa. In this study, the new epidemiological features and prevalence trends for EVD in Guinea, Liberia, and Sierra Leone are described. It was predicted that the Ebola outbreak would end in June 2015. PMID:26216765

  9. Management of Microbiological Samples in a Confirmed Case of Ebola Virus Disease: Constraints and Limitations.

    PubMed

    Hogardt, Michael; Wolf, Timo; Kann, Gerrit; Brodt, Hans-Reinhard; Brandt, Christian; Keppler, Oliver T; Wicker, Sabine; Zacharowski, Kai; Gottschalk, René; Becker, Stephan; Kempf, Volkhard A J

    2015-11-01

    In light of the recent Ebola virus outbreak, it has to be realized that besides medical treatment, precise algorithms for the management of complicating microbial infections are mandatory for Ebola virus disease (EVD) patients. While the necessity of such diagnostics is apparent, practical details are much less clear. Our approach, established during the treatment of an EVD patient at the University Hospital in Frankfurt am Main, Germany, provides a roadmap for reliable and safe on-site microbiological testing. PMID:26109444

  10. Identify, isolate, inform: Background and considerations for Ebola virus disease preparedness in U.S. ambulatory care settings.

    PubMed

    Chea, Nora; Perz, Joseph F; Srinivasan, Arjun; Laufer, Alison S; Pollack, Lori A

    2015-11-01

    Public health activities to identify and monitor persons at risk for Ebola virus disease in the United States include directing persons at risk to assessment facilities that are prepared to safely evaluate for Ebola virus disease. Although it is unlikely that a person with Ebola virus disease will unexpectedly present to a nonemergency ambulatory care facility, the Centers for Disease Control and Prevention have provided guidance for this setting that can be summarized as identify, isolate, and inform. PMID:26277570

  11. Being Ready to Treat Ebola Virus Disease Patients

    PubMed Central

    Brett-Major, David M.; Jacob, Shevin T.; Jacquerioz, Frederique A.; Risi, George F.; Fischer, William A.; Kato, Yasuyuki; Houlihan, Catherine F.; Crozier, Ian; Bosa, Henry Kyobe; Lawler, James V.; Adachi, Takuya; Hurley, Sara K.; Berry, Louise E.; Carlson, John C.; Button, Thomas. C.; McLellan, Susan L.; Shea, Barbara J.; Kuniyoshi, Gary G.; Ferri, Mauricio; Murthy, Srinivas G.; Petrosillo, Nicola; Lamontagne, Francois; Porembka, David T.; Schieffelin, John S.; Rubinson, Lewis; O'Dempsey, Tim; Donovan, Suzanne M.; Bausch, Daniel G.; Fowler, Robert A.; Fletcher, Thomas E.

    2015-01-01

    As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD. PMID:25510724

  12. Being ready to treat Ebola virus disease patients.

    PubMed

    Brett-Major, David M; Jacob, Shevin T; Jacquerioz, Frederique A; Risi, George F; Fischer, William A; Kato, Yasuyuki; Houlihan, Catherine F; Crozier, Ian; Bosa, Henry Kyobe; Lawler, James V; Adachi, Takuya; Hurley, Sara K; Berry, Louise E; Carlson, John C; Button, Thomas C; McLellan, Susan L; Shea, Barbara J; Kuniyoshi, Gary G; Ferri, Mauricio; Murthy, Srinivas G; Petrosillo, Nicola; Lamontagne, Francois; Porembka, David T; Schieffelin, John S; Rubinson, Lewis; O'Dempsey, Tim; Donovan, Suzanne M; Bausch, Daniel G; Fowler, Robert A; Fletcher, Thomas E

    2015-02-01

    As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD. PMID:25510724

  13. Prognostic Analysis of Patients with Ebola Virus Disease

    PubMed Central

    Liu, Liming; Su, Haibin; Zhang, Jian; Teng, Guangju; Du, Ning; Chen, Haoyang; Fang, Yuan; Zhan, Wei; Kanu, Alex B. J.; Koroma, Sheku M.; Jin, Bo; Xu, Zhe; Song, Haihan

    2015-01-01

    Background The Ebola virus causes an acute, serious illness which is often fatal if untreated. However, factors affecting the survival of the disease remain unclear. Here, we investigated the prognostic factors of Ebola virus disease (EVD) through various statistical models. Methodology/Principal Findings Sixty three laboratory-confirmed EVD patients with relatively complete clinical profiles were included in the study. All the patients were recruited at Jui Government Hospital, Sierra Leone between October 1st, 2014 and January 18th, 2015. We first investigated whether a single clinical presentation would be correlated with the survival of EVD. Log-rank test demonstrated that patients with viral load higher than 106 copies/ml presented significantly shorter survival time than those whose viral load were lower than 106 copies/ml (P = 0.005). Also, using Pearson chi-square test, we identified that chest pain, coma, and viral load (>106 copies/ml) were significantly associated with poor survival of EVD patients. Furthermore, we evaluated the effect of multiple variables on the survival of EVD by Cox proportional hazards model. Interestingly, results revealed that patient’s age, symptom of confusion, and viral load were the significantly associated with the survival of EVD cases (P = 0.017, P = 0.002, and P = 0.027, respectively). Conclusions/Significance These results suggest that age, chest pain, coma, confusion and viral load are associated with the prognosis of EVD, in which viral load could be one of the most important factors for the survival of the disease. PMID:26398207

  14. Radiographic imaging in Ebola Virus Disease: protocol to acquire chest radiographs.

    PubMed

    Busi Rizzi, Elisa; Puro, Vincenzo; Schinina', Vincenzo; Nicastri, Emanuele; Petrosillo, Nicola; Ippolito, Giuseppe

    2015-11-01

    Proper procedures to minimize the risk of contamination in contagious and potentially lethal viral infections are needed; therefore radiology departments should develop appropriate imaging protocols. We describe the imaging protocol used by National Institute for Infectious Diseases Lazzaro Spallanzani to acquire chest radiographs in patients with Ebola virus disease. Key points • Nosocomial transmission to healthcare workers can be prevented using protective equipment. • Chest radiographs can be required in Ebola Virus Disease. • The protocol for performing chest radiographs on patients with Ebola is described. PMID:25903713

  15. Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice.

    PubMed

    Li, Wenfang; Ye, Ling; Carrion, Ricardo; Mohan, Gopi S; Nunneley, Jerritt; Staples, Hilary; Ticer, Anysha; Patterson, Jean L; Compans, Richard W; Yang, Chinglai

    2015-10-01

    In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed "antigenic subversion." To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection. PMID:25877553

  16. Treating the Host Response to Ebola Virus Disease with Generic Statins and Angiotensin Receptor Blockers

    PubMed Central

    Jacobson, Jeffrey R.; Rordam, Ole Martin; Opal, Steven M.

    2015-01-01

    ABSTRACT Treatments targeting the Ebola virus may eventually be shown to work, but they will not have an impact on overall Ebola mortality in West Africa. Endothelial dysfunction is responsible for the fluid and electrolyte imbalances seen in Ebola patients. Because inexpensive generic statins and angiotensin receptor blockers restore endothelial barrier integrity, they can be used to treat the host response in these patients. In Sierra Leone, approximately 100 Ebola patients were treated with this combination, and reports indicate that survival was greatly improved. PMID:26106080

  17. Ebola Virus Stability on Surfaces and in Fluids in Simulated Outbreak Environments

    PubMed Central

    Fischer, Robert; Judson, Seth; Miazgowicz, Kerri; Bushmaker, Trenton; Prescott, Joseph

    2015-01-01

    We evaluated the stability of Ebola virus on surfaces and in fluids under simulated environmental conditions for the climate of West Africa and for climate-controlled hospitals. This virus remains viable for a longer duration on surfaces in hospital conditions than in African conditions and in liquid than in dried blood. PMID:26079114

  18. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    SciTech Connect

    Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.; Cooper, Kurt; Jahrling, Peter B.; Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 ; Schnell, Matthias J.; Blaney, Joseph E.

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  19. Ebola Virus Disease: essential public health principles for clinicians.

    PubMed

    Koenig, Kristi L; Majestic, Cassondra; Burns, Michael J

    2014-11-01

    Ebola Virus Disease (EVD) has become a public health emergency of international concern. The World Health Organization and Centers for Disease Control and Prevention have developed guidance to educate and inform healthcare workers and travelers worldwide. Symptoms of EVD include abrupt onset of fever, myalgias, and headache in the early phase, followed by vomiting, diarrhea and possible progression to hemorrhagic rash, life-threatening bleeding, and multi-organ failure in the later phase. The disease is not transmitted via airborne spread like influenza, but rather from person-to-person, or animal to person, via direct contact with bodily fluids or blood. It is crucial that emergency physicians be educated on disease presentation and how to generate a timely and accurate differential diagnosis that includes exotic diseases in the appropriate patient population. A patient should be evaluated for EVD when both suggestive symptoms, including unexplained hemorrhage, AND risk factors within 3 weeks prior, such as travel to an endemic area, direct handling of animals from outbreak areas, or ingestion of fruit or other uncooked foods contaminated with bat feces containing the virus are present. There are experimental therapies for treatment of EVD virus; however the mainstay of therapy is supportive care. Emergency department personnel on the frontlines must be prepared to rapidly identify and isolate febrile travelers if indicated. All healthcare workers involved in care of EVD patients should wear personal protective equipment. Despite the intense media focus on EVD rather than other threats, emergency physicians must master and follow essential public health principles for management of all infectious diseases. This includes not only identification and treatment of individuals, but also protection of healthcare workers and prevention of spread, keeping in mind the possibility of other more common disease processes. PMID:25493109

  20. Ebola Virus Disease: Essential Public Health Principles for Clinicians

    PubMed Central

    Koenig, Kristi L.; Majestic, Cassondra; Burns, Michael J.

    2014-01-01

    Ebola Virus Disease (EVD) has become a public health emergency of international concern. The World Health Organization and Centers for Disease Control and Prevention have developed guidance to educate and inform healthcare workers and travelers worldwide. Symptoms of EVD include abrupt onset of fever, myalgias, and headache in the early phase, followed by vomiting, diarrhea and possible progression to hemorrhagic rash, life-threatening bleeding, and multi-organ failure in the later phase. The disease is not transmitted via airborne spread like influenza, but rather from person-to-person, or animal to person, via direct contact with bodily fluids or blood. It is crucial that emergency physicians be educated on disease presentation and how to generate a timely and accurate differential diagnosis that includes exotic diseases in the appropriate patient population. A patient should be evaluated for EVD when both suggestive symptoms, including unexplained hemorrhage, AND risk factors within 3 weeks prior, such as travel to an endemic area, direct handling of animals from outbreak areas, or ingestion of fruit or other uncooked foods contaminated with bat feces containing the virus are present. There are experimental therapies for treatment of EVD virus; however the mainstay of therapy is supportive care. Emergency department personnel on the frontlines must be prepared to rapidly identify and isolate febrile travelers if indicated. All healthcare workers involved in care of EVD patients should wear personal protective equipment. Despite the intense media focus on EVD rather than other threats, emergency physicians must master and follow essential public health principles for management of all infectious diseases. This includes not only identification and treatment of individuals, but also protection of healthcare workers and prevention of spread, keeping in mind the possibility of other more common disease processes. PMID:25493109

  1. The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3

    PubMed Central

    Basler, Christopher F.; Mikulasova, Andrea; Martinez-Sobrido, Luis; Paragas, Jason; Mühlberger, Elke; Bray, Mike; Klenk, Hans-Dieter; Palese, Peter; García-Sastre, Adolfo

    2003-01-01

    The Ebola virus VP35 protein was previously found to act as an interferon (IFN) antagonist which could complement growth of influenza delNS1 virus, a mutant influenza virus lacking the influenza virus IFN antagonist protein, NS1. The Ebola virus VP35 could also prevent the virus- or double-stranded RNA-mediated transcriptional activation of both the beta IFN (IFN-?) promoter and the IFN-stimulated ISG54 promoter (C. Basler et al., Proc. Natl. Acad. Sci. USA 97:12289-12294, 2000). We now show that VP35 inhibits virus infection-induced transcriptional activation of IFN regulatory factor 3 (IRF-3)-responsive mammalian promoters and that VP35 does not block signaling from the IFN-?/? receptor. The ability of VP35 to inhibit this virus-induced transcription correlates with its ability to block activation of IRF-3, a cellular transcription factor of central importance in initiating the host cell IFN response. We demonstrate that VP35 blocks the Sendai virus-induced activation of two promoters which can be directly activated by IRF-3, namely, the ISG54 promoter and the ISG56 promoter. Further, expression of VP35 prevents the IRF-3-dependent activation of the IFN-?4 promoter in response to viral infection. The inhibition of IRF-3 appears to occur through an inhibition of IRF-3 phosphorylation. VP35 blocks virus-induced IRF-3 phosphorylation and subsequent IRF-3 dimerization and nuclear translocation. Consistent with these observations, Ebola virus infection of Vero cells activated neither transcription from the ISG54 promoter nor nuclear accumulation of IRF-3. These data suggest that in Ebola virus-infected cells, VP35 inhibits the induction of antiviral genes, including the IFN-? gene, by blocking IRF-3 activation. PMID:12829834

  2. Towards detection and diagnosis of Ebola virus disease at point-of-care.

    PubMed

    Kaushik, Ajeet; Tiwari, Sneham; Dev Jayant, Rahul; Marty, Aileen; Nair, Madhavan

    2016-01-15

    Ebola outbreak-2014 (mainly Zaire strain related Ebola virus) has been declared most widely spread deadly persistent epidemic due to unavailability of rapid diagnostic, detection, and therapeutics. Ebola virus disease (EVD), a severe viral hemorrhagic fever syndrome caused by Ebola virus (EBOV) is transmitted by direct contact with the body fluids of infected person and objects contaminated with virus or infected animals. World Health Organization (WHO) has declared EVD epidemic as public health emergency of international concern with severe global economic burden. At fatal EBOV infection stage, patients usually die before the antibody response. Currently, rapid blood tests to diagnose EBOV infection include the antigen or antibodies capture using ELISA and RNA detection using RT/Q-PCR within 3-10 days after the onset of symptoms. Moreover, few nanotechnology-based colorimetric and paper-based immunoassay methods have been recently reported to detect Ebola virus. Unfortunately, these methods are limited to laboratory only. As state-of-the art (SoA) diagnostics time to confirm Ebola infection, varies from 6h to about 3 days, it causes delay in therapeutic approaches. Thus developing a cost-effective, rapid, sensitive, and selective sensor to detect EVD at point-of-care (POC) is certainly worth exploring to establish rapid diagnostics to decide therapeutics. This review highlights SoA of Ebola diagnostics and also a call to develop rapid, selective and sensitive POC detection of EBOV for global health care. We propose that adopting miniaturized electrochemical EBOV immunosensing can detect virus level at pM concentration within ?40min compared to 3 days of ELISA test at nM levels. PMID:26319169

  3. Management of a pet dog after exposure to a human patient with Ebola virus disease.

    PubMed

    Spengler, Jessica R; Stonecipher, Shelley; McManus, Catherine; Hughes-Garza, Holly; Dow, Max; Zoran, Debra L; Bissett, Wesley; Beckham, Tammy; Alves, Derron A; Wolcott, Mark; Tostenson, Samantha; Dorman, Bill; Jones, Jody; Sidwa, Thomas J; Knust, Barbara; Behravesh, Casey Barton

    2015-09-01

    In October 2014, a health-care worker who had been part of the treatment team for the first laboratory-confirmed case of Ebola virus disease imported to the United States developed symptoms of Ebola virus disease. A presumptive positive reverse transcription PCR assay result for Ebola virus RNA in a blood sample from the worker was confirmed by the CDC, making this the first documented occurrence of domestic transmission of Ebola virus in the United States. The Texas Department of State Health Services commissioner issued a control order requiring disinfection and decontamination of the health-care worker's residence. This process was delayed until the patient's pet dog (which, having been exposed to a human with Ebola virus disease, potentially posed a public health risk) was removed from the residence. This report describes the movement, quarantine, care, testing, and release of the pet dog, highlighting the interdisciplinary, one-health approach and extensive collaboration and communication across local, county, state, and federal agencies involved in the response. PMID:26295560

  4. A No-Notice Drill of Hospital Preparedness in Responding to Ebola Virus Disease in Taiwan.

    PubMed

    Hsu, Shih-Min; Chien, Li-Jung; Tseng, Shu-Hui; Kuo, Steve H S

    2015-01-01

    The Ebola virus was first discovered in 1976, but the outbreak of Ebola virus disease that began in Guinea, West Africa, in December 2013 shocked the world. It is the largest and most severe epidemic of Ebola virus disease to date. The US Centers for Disease Control and Prevention confirmed that inadequate implementation of the policy of acquiring travel history led to a delay in identifying the first imported Ebola virus disease case. The Taiwan Centers for Disease Control developed a no-notice drill that used a simulated patient to assess hospitals' emergency preparedness capacity in responding to Ebola virus disease. Despite the fact that regular inspection shows that more than 90% of regional hospitals and medical centers inquired about patients' travel history, occupation, contact history, and cluster information, the no-notice drill revealed that more than 40% of regional hospitals and medical centers failed to ask emergency room patients about these factors. Therefore, to assist in inquiries about travel history, occupation, contact history, and cluster information in emergency triage and outpatient settings, the Taiwan CDC revised the criteria for hospital infection control inspection. It requested that hospitals issue appropriate reminders and implement process control mechanisms to block diagnostic processes in instances in which healthcare workers do not inquire about travel history, occupation, contact history, and cluster information. Furthermore, the Taiwan CDC will continue no-notice inspections in order to strengthen hospitals' infection control measures and reduce the risk of infectious disease transmission in the healthcare system. PMID:26381373

  5. Next-Generation Sequencing Reveals a Controlled Immune Response to Zaire Ebola Virus Challenge in Cynomolgus Macaques Immunized with Vesicular Stomatitis Virus Expressing Zaire Ebola Virus Glycoprotein (VSV?G/EBOVgp)

    PubMed Central

    Barrenas, Fredrik; Green, Richard R.; Thomas, Matthew J.; Law, G. Lynn; Proll, Sean C.; Engelmann, Flora; Messaoudi, Ilhem; Marzi, Andrea; Feldmann, Heinz

    2015-01-01

    Vesicular stomatitis virus expressing Zaire Ebola virus (EBOV) glycoprotein (VSV?G/EBOVgp) could be used as a vaccine to meet the 2014 Ebola virus outbreak. To characterize the host response to this vaccine, we used mRNA sequencing to analyze peripheral blood mononuclear cells (PBMCs) from cynomolgus macaques after VSV?G/EBOVgp immunization and subsequent EBOV challenge. We found a controlled transcriptional response that transitioned to immune regulation as the EBOV was cleared. This observation supports the safety of the vaccine. PMID:25589554

  6. Next-generation sequencing reveals a controlled immune response to Zaire Ebola virus challenge in cynomolgus macaques immunized with vesicular stomatitis virus expressing Zaire Ebola virus glycoprotein (VSV?G/EBOVgp).

    PubMed

    Barrenas, Fredrik; Green, Richard R; Thomas, Matthew J; Law, G Lynn; Proll, Sean C; Engelmann, Flora; Messaoudi, Ilhem; Marzi, Andrea; Feldmann, Heinz; Katze, Michael G

    2015-03-01

    Vesicular stomatitis virus expressing Zaire Ebola virus (EBOV) glycoprotein (VSV?G/EBOVgp) could be used as a vaccine to meet the 2014 Ebola virus outbreak. To characterize the host response to this vaccine, we used mRNA sequencing to analyze peripheral blood mononuclear cells (PBMCs) from cynomolgus macaques after VSV?G/EBOVgp immunization and subsequent EBOV challenge. We found a controlled transcriptional response that transitioned to immune regulation as the EBOV was cleared. This observation supports the safety of the vaccine. PMID:25589554

  7. The multifunctional Ebola virus VP40 matrix protein is a promising therapeutic target

    PubMed Central

    Madara, Jonathan J; Han, Ziying; Ruthel, Gordon; Freedman, Bruce D; Harty, Ronald N

    2015-01-01

    The highly virulent nature of Ebola virus, evident from the 2014 West African pandemic, highlights the need to develop vaccines or therapeutic agents that limit the pathogenesis and spread of this virus. While vaccines represent an obvious approach, targeting virus interactions with host proteins that critically regulate the virus lifecycle also represent important therapeutic strategies. Among Ebola virus proteins at this critical interface is its matrix protein, VP40, which is abundantly expressed during infection and plays a number of critical roles in the viral lifecycle. In addition to regulating viral transcription, VP40 coordinates virion assembly and budding from infected cells. Details of the molecular mechanisms underpinning these essential functions are currently being elucidated, with a particular emphasis on its interactions with host proteins that control virion assembly and egress. This review focuses on the strategies geared toward developing novel therapeutic agents that target VP40-specific control of host functions critical to virion transcription, assembly and egress. PMID:26120351

  8. Acceptability and Willingness-to-Pay for a Hypothetical Ebola Virus Vaccine in Nigeria

    PubMed Central

    Ughasoro, Maduka Donatus; Esangbedo, Dorothy Omono; Tagbo, Beckie Nnenna; Mejeha, Ijeoma Chigozie

    2015-01-01

    Background Ebola virus disease is a highly virulent and transmissible disease. The largest recorded fatality from Ebola virus disease epidemic is ongoing in a few countries in West Africa, and this poses a health risk to the entire population of the world because arresting the transmission has been challenging. Vaccination is considered a key intervention that is capable of arresting further spread of the disease and preventing future outbreak. However, no vaccine has yet been approved for public use, although various recombinant vaccines are undergoing trials and approval for public use is imminent. Therefore, this study aimed to determine the acceptability of and willingness-to-pay for Ebola virus vaccine by the public. Methods The study was a community-based cross-sectional qualitative and quantitative interventional study conducted in two communities, each in two states in Nigeria. An interviewer-administered questionnaire was used to collect information on respondents’ knowledge of the Ebola virus, the ways to prevent the disease, and their preventive practices, as well as their acceptability of and willingness-to-pay for a hypothetical vaccine against Ebola virus disease. The association between acceptability of the vaccine and other independent variables were evaluated using multivariate regression analysis. Results Ebola virus disease was considered to be a very serious disease by 38.5% of the 582 respondents (224/582), prior to receiving health education on Ebola virus and its vaccine. Eighty percent (80%) accepted to be vaccinated with Ebola vaccine. However, among those that accepted to be vaccinated, most would only accept after observing the outcome on others who have received the vaccine. More than 87.5% was willing to pay for the vaccine, although 55.2% was of the opinion that the vaccine should be provided free of charge. Conclusion The level of acceptability of Ebola virus vaccine among respondents was impressive (though conditional), as well as their willingness to pay for it if the vaccine is not publicly funded. In order to achieve a high uptake of the vaccine, information and education on the vaccine should be extensively shared with the public prior to the introduction of the vaccine, and the vaccine should be provided free of charge by government. PMID:26076007

  9. Modeling the transmission dynamics of Ebola virus disease in Liberia.

    PubMed

    Xia, Zhi-Qiang; Wang, Shi-Fu; Li, Shen-Long; Huang, Liu-Yu; Zhang, Wen-Yi; Sun, Gui-Quan; Gai, Zhong-Tao; Jin, Zhen

    2015-01-01

    Ebola virus disease (EVD) has erupted many times in some zones since it was first found in 1976. The 2014 EVD outbreak in West Africa is the largest ever, which has caused a large number of deaths and the most serious country is Liberia during the outbreak period. Based on the data released by World Health Organization and the actual transmission situations, we investigate the impact of different transmission routes on the EVD outbreak in Liberia and estimate the basic reproduction number R0?=?2.012 in the absence of effective control measures. Through sensitivity and uncertainty analysis, we reveal that the transmission coefficients of suspected and probable cases have stronger correlations on the basic reproduction number. Furthermore, we study the influence of control measures (isolation and safe burial measures) on EVD outbreak. It is found that if combined control measures are taken, the basic reproduction number will be less than one and thus EVD in Liberia may be well contained. The obtained results may provide new guidance to prevent and control the spread of disease. PMID:26347015

  10. Modeling the transmission dynamics of Ebola virus disease in Liberia

    PubMed Central

    Xia, Zhi-Qiang; Wang, Shi-Fu; Li, Shen-Long; Huang, Liu-Yu; Zhang, Wen-Yi; Sun, Gui-Quan; Gai, Zhong-Tao; Jin, Zhen

    2015-01-01

    Ebola virus disease (EVD) has erupted many times in some zones since it was first found in 1976. The 2014 EVD outbreak in West Africa is the largest ever, which has caused a large number of deaths and the most serious country is Liberia during the outbreak period. Based on the data released by World Health Organization and the actual transmission situations, we investigate the impact of different transmission routes on the EVD outbreak in Liberia and estimate the basic reproduction number R0?=?2.012 in the absence of effective control measures. Through sensitivity and uncertainty analysis, we reveal that the transmission coefficients of suspected and probable cases have stronger correlations on the basic reproduction number. Furthermore, we study the influence of control measures (isolation and safe burial measures) on EVD outbreak. It is found that if combined control measures are taken, the basic reproduction number will be less than one and thus EVD in Liberia may be well contained. The obtained results may provide new guidance to prevent and control the spread of disease. PMID:26347015

  11. Characterizing the Transmission Dynamics and Control of Ebola Virus Disease

    PubMed Central

    Chowell, Gerardo; Nishiura, Hiroshi

    2015-01-01

    Carefully calibrated transmission models have the potential to guide public health officials on the nature and scale of the interventions required to control epidemics. In the context of the ongoing Ebola virus disease (EVD) epidemic in Liberia, Drake and colleagues, in this issue of PLOS Biology, employed an elegant modeling approach to capture the distributions of the number of secondary cases that arise in the community and health care settings in the context of changing population behaviors and increasing hospital capacity. Their findings underscore the role of increasing the rate of safe burials and the fractions of infectious individuals who seek hospitalization together with hospital capacity to achieve epidemic control. However, further modeling efforts of EVD transmission and control in West Africa should utilize the spatial-temporal patterns of spread in the region by incorporating spatial heterogeneity in the transmission process. Detailed datasets are urgently needed to characterize temporal changes in population behaviors, contact networks at different spatial scales, population mobility patterns, adherence to infection control measures in hospital settings, and hospitalization and reporting rates. PMID:25607595

  12. Immunology and evolvement of the adenovirus prime, MVA boost Ebola virus vaccine.

    PubMed

    Zhou, Yan; Sullivan, Nancy J

    2015-08-01

    The 2014 Ebola virus outbreak caused an order of magnitude more deaths in a single outbreak than all previous known outbreaks combined, affecting both local and international public health, and threatening the security and economic stability of the countries in West Africa directly confronting the outbreak. The severity of the epidemic lead to a global response to assist with patient care, outbreak control, and deployment of vaccines. The latter was possible due to the long history of basic and clinical research aimed at identifying a safe and effective vaccine to protect against Ebola virus infection. This review highlights the immunology, development, and progress of vaccines based on replication-defective adenovirus vectors, culminating in the successful launch of the first Phase III trial of an Ebola virus vaccine. PMID:26247875

  13. A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.

    PubMed

    Johansen, Lisa M; DeWald, Lisa Evans; Shoemaker, Charles J; Hoffstrom, Benjamin G; Lear-Rooney, Calli M; Stossel, Andrea; Nelson, Elizabeth; Delos, Sue E; Simmons, James A; Grenier, Jill M; Pierce, Laura T; Pajouhesh, Hassan; Lehár, Joseph; Hensley, Lisa E; Glass, Pamela J; White, Judith M; Olinger, Gene G

    2015-06-01

    Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections. PMID:26041706

  14. Analytical Performance Characteristics of the Cepheid GeneXpert Ebola Assay for the Detection of Ebola Virus

    PubMed Central

    Pinsky, Benjamin A.; Sahoo, Malaya K.; Sandlund, Johanna; Kleman, Marika; Kulkarni, Medha; Grufman, Per; Nygren, Malin; Kwiatkowski, Robert; Baron, Ellen Jo; Tenover, Fred; Denison, Blake; Higuchi, Russell; Van Atta, Reuel; Beer, Neil Reginald; Carrillo, Alda Celena; Naraghi-Arani, Pejman; Mire, Chad E.; Ranadheera, Charlene; Grolla, Allen; Lagerqvist, Nina; Persing, David H.

    2015-01-01

    Background The recently developed Xpert® Ebola Assay is a novel nucleic acid amplification test for simplified detection of Ebola virus (EBOV) in whole blood and buccal swab samples. The assay targets sequences in two EBOV genes, lowering the risk for new variants to escape detection in the test. The objective of this report is to present analytical characteristics of the Xpert® Ebola Assay on whole blood samples. Methods and Findings This study evaluated the assay’s analytical sensitivity, analytical specificity, inclusivity and exclusivity performance in whole blood specimens. EBOV RNA, inactivated EBOV, and infectious EBOV were used as targets. The dynamic range of the assay, the inactivation of virus, and specimen stability were also evaluated. The lower limit of detection (LoD) for the assay using inactivated virus was estimated to be 73 copies/mL (95% CI: 51–97 copies/mL). The LoD for infectious virus was estimated to be 1 plaque-forming unit/mL, and for RNA to be 232 copies/mL (95% CI 163–302 copies/mL). The assay correctly identified five different Ebola viruses, Yambuku-Mayinga, Makona-C07, Yambuku-Ecran, Gabon-Ilembe, and Kikwit-956210, and correctly excluded all non-EBOV isolates tested. The conditions used by Xpert® Ebola for inactivation of infectious virus reduced EBOV titer by ?6 logs. Conclusion In summary, we found the Xpert® Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection is critical. PMID:26562786

  15. Biochemical and Functional Characterization of the Ebola Virus VP24 Protein: Implications for a Role in Virus Assembly and Budding

    PubMed Central

    Han, Ziying; Boshra, Hani; Sunyer, J. Oriol; Zwiers, Susan H.; Paragas, Jason; Harty, Ronald N.

    2003-01-01

    The VP24 protein of Ebola virus is believed to be a secondary matrix protein and minor component of virions. In contrast, the VP40 protein of Ebola virus is the primary matrix protein and the most abundant virion component. The structure and function of VP40 have been well characterized; however, virtually nothing is known regarding the structure and function of VP24. Wild-type and mutant forms of VP24 were expressed in mammalian cells to gain a better understanding of the biochemical and functional nature of this viral protein. Results from these experiments demonstrated that (i) VP24 localizes to the plasma membrane and perinuclear region in both transfected and Ebola virus-infected cells, (ii) VP24 associates strongly with lipid membranes, (iii) VP24 does not contain N-linked sugars when expressed alone in mammalian cells, (iv) VP24 can oligomerize when expressed alone in mammalian cells, (v) progressive deletions at the N terminus of VP24 resulted in a decrease in oligomer formation and a concomitant increase in the formation of high-molecular-weight aggregates, and (vi) VP24 was present in trypsin-resistant virus like particles released into the media covering VP24-transfected cells. These data indicate that VP24 possesses structural features commonly associated with viral matrix proteins and that VP24 may have a role in virus assembly and budding. PMID:12525613

  16. The lipid moiety of brincidofovir is required for in vitro antiviral activity against Ebola virus.

    PubMed

    McMullan, Laura K; Flint, Mike; Dyall, Julie; Albariño, César; Olinger, Gene G; Foster, Scott; Sethna, Phiroze; Hensley, Lisa E; Nichol, Stuart T; Lanier, E Randall; Spiropoulou, Christina F

    2016-01-01

    Brincidofovir (BCV) is the 3-hexadecyloxy-1-propanol (HDP) lipid conjugate of the acyclic nucleoside phosphonate cidofovir (CDV). BCV has established broad-spectrum activity against double-stranded DNA (dsDNA) viruses; however, its activity against RNA viruses has been less thoroughly evaluated. Here, we report that BCV inhibited infection of Ebola virus in multiple human cell lines. Unlike the mechanism of action for BCV against cytomegalovirus and other dsDNA viruses, phosphorylation of CDV to the diphosphate form appeared unnecessary. Instead, antiviral activity required the lipid moiety and in vitro activity against EBOV was observed for several HDP-nucleotide conjugates. PMID:26526586

  17. Ocular Manifestations of Ebola Virus Disease: An Ophthalmologist's Guide to Prevent Infection and Panic

    PubMed Central

    Vingolo, Enzo Maria; Messano, Giuseppe Alessio; Fragiotta, Serena; Spadea, Leopoldo; Petti, Stefano

    2015-01-01

    Ebola virus disease (EVD—formerly known as Ebola hemorrhagic fever) is a severe hemorrhagic fever caused by lipid-enveloped, nonsegmented, negative-stranded RNA viruses belonging to the genus Ebolavirus. Case fatality rates may reach up to 76% of infected individuals, making this infection a deadly health problem in the sub-Saharan population. At the moment, there are still no indications on ophthalmological clinical signs and security suggestions for healthcare professionals (doctors and nurses or cooperative persons). This paper provides a short but complete guide to reduce infection risks. PMID:26557674

  18. Viral bioterrorism: Learning the lesson of Ebola virus in West Africa 2013-2015.

    PubMed

    Cenciarelli, Orlando; Gabbarini, Valentina; Pietropaoli, Stefano; Malizia, Andrea; Tamburrini, Annalaura; Ludovici, Gian Marco; Carestia, Mariachiara; Di Giovanni, Daniele; Sassolini, Alessandro; Palombi, Leonardo; Bellecci, Carlo; Gaudio, Pasquale

    2015-12-01

    Among the potential biological agents suitable as a weapon, Ebola virus represents a major concern. Classified by the CDC as a category A biological agent, Ebola virus causes severe hemorrhagic fever, characterized by high case-fatality rate; to date, no vaccine or approved therapy is available. The EVD epidemic, which broke out in West Africa since the late 2013, has got the issue of the possible use of Ebola virus as biological warfare agent (BWA) to come to the fore once again. In fact, due to its high case-fatality rate, population currently associates this pathogen to a real and tangible threat. Therefore, its use as biological agent by terrorist groups with offensive purpose could have serious repercussions from a psychosocial point of view as well as on closely sanitary level. In this paper, after an initial study of the main characteristics of Ebola virus, its potential as a BWA was evaluated. Furthermore, given the spread of the epidemic in West Africa in 2014 and 2015, the potential dissemination of the virus from an urban setting was evaluated. Finally, it was considered the actual possibility to use this agent as BWA in different scenarios, and the potential effects on one or more nation's stability. PMID:26359111

  19. Social Vulnerability and Ebola Virus Disease in Rural Liberia.

    PubMed

    Stanturf, John A; Goodrick, Scott L; Warren, Melvin L; Charnley, Susan; Stegall, Christie M

    2015-01-01

    The Ebola virus disease (EVD) epidemic that has stricken thousands of people in the three West African countries of Liberia, Sierra Leone, and Guinea highlights the lack of adaptive capacity in post-conflict countries. The scarcity of health services in particular renders these populations vulnerable to multiple interacting stressors including food insecurity, climate change, and the cascading effects of disease epidemics such as EVD. However, the spatial distribution of vulnerable rural populations and the individual stressors contributing to their vulnerability are unknown. We developed a Social Vulnerability Classification using census indicators and mapped it at the district scale for Liberia. According to the Classification, we estimate that districts having the highest social vulnerability lie in the north and west of Liberia in Lofa, Bong, Grand Cape Mount, and Bomi Counties. Three of these counties together with the capital Monrovia and surrounding Montserrado and Margibi counties experienced the highest levels of EVD infections in Liberia. Vulnerability has multiple dimensions and a classification developed from multiple variables provides a more holistic view of vulnerability than single indicators such as food insecurity or scarcity of health care facilities. Few rural Liberians are food secure and many cannot reach a medical clinic in <80 minutes. Our results illustrate how census and household survey data, when displayed spatially at a sub-county level, may help highlight the location of the most vulnerable households and populations. Our results can be used to identify vulnerability hotspots where development strategies and allocation of resources to address the underlying causes of vulnerability in Liberia may be warranted. We demonstrate how social vulnerability index approaches can be applied in the context of disease outbreaks, and our methods are relevant elsewhere. PMID:26325519

  20. Social Vulnerability and Ebola Virus Disease in Rural Liberia

    PubMed Central

    2015-01-01

    The Ebola virus disease (EVD) epidemic that has stricken thousands of people in the three West African countries of Liberia, Sierra Leone, and Guinea highlights the lack of adaptive capacity in post-conflict countries. The scarcity of health services in particular renders these populations vulnerable to multiple interacting stressors including food insecurity, climate change, and the cascading effects of disease epidemics such as EVD. However, the spatial distribution of vulnerable rural populations and the individual stressors contributing to their vulnerability are unknown. We developed a Social Vulnerability Classification using census indicators and mapped it at the district scale for Liberia. According to the Classification, we estimate that districts having the highest social vulnerability lie in the north and west of Liberia in Lofa, Bong, Grand Cape Mount, and Bomi Counties. Three of these counties together with the capital Monrovia and surrounding Montserrado and Margibi counties experienced the highest levels of EVD infections in Liberia. Vulnerability has multiple dimensions and a classification developed from multiple variables provides a more holistic view of vulnerability than single indicators such as food insecurity or scarcity of health care facilities. Few rural Liberians are food secure and many cannot reach a medical clinic in <80 minutes. Our results illustrate how census and household survey data, when displayed spatially at a sub-county level, may help highlight the location of the most vulnerable households and populations. Our results can be used to identify vulnerability hotspots where development strategies and allocation of resources to address the underlying causes of vulnerability in Liberia may be warranted. We demonstrate how social vulnerability index approaches can be applied in the context of disease outbreaks, and our methods are relevant elsewhere. PMID:26325519

  1. Ebola virus disease in a humanitarian aid worker - New York City, October 2014.

    PubMed

    Yacisin, Kari; Balter, Sharon; Fine, Annie; Weiss, Don; Ackelsberg, Joel; Prezant, David; Wilson, Ross; Starr, David; Rakeman, Jennifer; Raphael, Marisa; Quinn, Celia; Toprani, Amita; Clark, Nancy; Link, Nathan; Daskalakis, Demetre; Maybank, Aletha; Layton, Marcelle; Varma, Jay K

    2015-04-01

    In late October 2014, Ebola virus disease (Ebola) was diagnosed in a humanitarian aid worker who recently returned from West Africa to New York City (NYC). The NYC Department of Health and Mental Hygiene (DOHMH) actively monitored three close contacts of the patient and 114 health care personnel. No secondary cases of Ebola were detected. In collaboration with local and state partners, DOHMH had developed protocols to respond to such an event beginning in July 2014. These protocols included safely transporting a person at the first report of symptoms to a local hospital prepared to treat a patient with Ebola, laboratory testing for Ebola, and monitoring of contacts. In response to this single case of Ebola, initial health care worker active monitoring protocols needed modification to improve clarity about what types of exposure should be monitored. The response costs were high in both human resources and money: DOHMH alone spent $4.3 million. However, preparedness activities that include planning and practice in effectively monitoring the health of workers involved in Ebola patient care can help prevent transmission of Ebola. PMID:25837242

  2. Recent advances in the development of vaccines for Ebola virus disease.

    PubMed

    Ohimain, Elijah Ige

    2016-01-01

    Ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. Ebola virus (EBOV) is a zoonotic infection, which emerges and re-emerges in human populations. The 2014 outbreak was caused by the Zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. The 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. It is the first time that the virus was sustained in urban centers and spread beyond Africa into Europe and USA. Thus far, over 22,000 cases have been reported with about 50% mortality in one year. There are currently no approved therapeutics and preventive vaccines against Ebola virus disease (EVD). Responding to the devastating effe1cts of the 2014 outbreak and the potential risk of global spread, has spurred research for the development of therapeutics and vaccines. This review is therefore aimed at presenting the progress of vaccine development. Results showed that conventional inactivated vaccines produced from EBOV by heat, formalin or gamma irradiation appear to be ineffective. However, novel vaccines production techniques have emerged leading to the production of candidate vaccines that have been demonstrated to be effective in preclinical trials using small animal and non-human primates (NHP) models. Some of the promising vaccines have undergone phase 1 clinical trials, which demonstrated their safety and immunogenicity. Many of the candidate vaccines are vector based such as Vesicular Stomatitis Virus (VSV), Rabies Virus (RABV), Adenovirus (Ad), Modified Vaccinia Ankara (MVA), Cytomegalovirus (CMV), human parainfluenza virus type 3 (HPIV3) and Venezuelan Equine Encephalitis Virus (VEEV). Other platforms include virus like particle (VLP), DNA and subunit vaccines. PMID:26596227

  3. Administration of Brincidofovir and Convalescent Plasma in a Patient With Ebola Virus Disease.

    PubMed

    Florescu, Diana F; Kalil, Andre C; Hewlett, Angela L; Schuh, Amy J; Stroher, Ute; Uyeki, Timothy M; Smith, Philip W

    2015-09-15

    From 2014 to May 2015, >26 000 Ebola virus disease (EVD) cases were reported from West Africa. We present a patient with EVD who received brincidofovir and convalescent plasma. The relative contributions of supportive care, investigational therapies, and patient's immune-response on survival could not be determined. Randomized trials are needed. PMID:25991468

  4. Effectiveness of Ring Vaccination as Control Strategy for Ebola Virus Disease

    PubMed Central

    Eggo, Rosalind M.; Watson, Conall H.; Camacho, Anton; Funk, Sebastian; Edmunds, W. John

    2016-01-01

    Using an Ebola virus disease transmission model, we found that addition of ring vaccination at the outset of the West Africa epidemic might not have led to containment of this disease. However, in later stages of the epidemic or in outbreaks with less intense transmission or more effective control, this strategy could help eliminate the disease. PMID:26691346

  5. Utility of Oral Swab Sampling for Ebola Virus Detection in Guinea Pig Model

    PubMed Central

    Spengler, Jessica R.; Chakrabarti, Ayan K.; Coleman-McCray, JoAnn D.; Martin, Brock E.; Nichol, Stuart T.; Spiropoulou, Christina F.

    2015-01-01

    To determine the utility of oral swabs for diagnosing infection with Ebola virus, we used a guinea pig model and obtained daily antemortem and postmortem swab samples. According to quantitative reverse transcription PCR analysis, the diagnostic value was poor for antemortem swab samples but excellent for postmortem samples. PMID:26401603

  6. Utility of Oral Swab Sampling for Ebola Virus Detection in Guinea Pig Model.

    PubMed

    Spengler, Jessica R; Chakrabarti, Ayan K; Coleman-McCray, JoAnn D; Martin, Brock E; Nichol, Stuart T; Spiropoulou, Christina F; Bird, Brian H

    2015-10-01

    To determine the utility of oral swabs for diagnosing infection with Ebola virus, we used a guinea pig model and obtained daily antemortem and postmortem swab samples. According to quantitative reverse transcription PCR analysis, the diagnostic value was poor for antemortem swab samples but excellent for postmortem samples. PMID:26401603

  7. Effectiveness of Ring Vaccination as Control Strategy for Ebola Virus Disease.

    PubMed

    Kucharski, Adam J; Eggo, Rosalind M; Watson, Conall H; Camacho, Anton; Funk, Sebastian; Edmunds, W John

    2016-01-01

    Using an Ebola virus disease transmission model, we found that addition of ring vaccination at the outset of the West Africa epidemic might not have led to containment of this disease. However, in later stages of the epidemic or in outbreaks with less intense transmission or more effective control, this strategy could help eliminate the disease. PMID:26691346

  8. Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol.

    PubMed

    Hacke, Moritz; Björkholm, Patrik; Hellwig, Andrea; Himmels, Patricia; de Almodóvar, Carmen Ruiz; Brügger, Britta; Wieland, Felix; Ernst, Andreas M

    2015-01-01

    The high pathogenicity of the Ebola virus reflects multiple concurrent processes on infection. Among other important determinants, Ebola fusogenic glycoprotein (GP) has been associated with the detachment of infected cells and eventually leads to vascular leakage and haemorrhagic fever. Here we report that the membrane-anchored GP is sufficient to induce the detachment of adherent cells. The results show that the detachment induced through either full-length GP1,2 or the subunit GP2 depends on cholesterol and the structure of the transmembrane domain. These data reveal a novel molecular mechanism in which GP regulates Ebola virus assembly and suggest that cholesterol-reducing agents could be useful as therapeutics to counteract GP-mediated cell detachment. PMID:26158910

  9. Ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies

    SciTech Connect

    Ye Ling; Lin Jianguo; Sun Yuliang; Bennouna, Soumaya; Lo, Michael; Wu Qingyang; Bu Zhigao; Pulendran, Bali; Compans, Richard W. . E-mail: compans@microbio.emory.edu; Yang Chinglai . E-mail: chyang@emory.edu

    2006-08-01

    Recombinant baculoviruses (rBV) expressing Ebola virus VP40 (rBV-VP40) or GP (rBV-GP) proteins were generated. Infection of Sf9 insect cells by rBV-VP40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. Ebola virus-like particles (VLPs) were produced by coinfection of Sf9 cells with rBV-VP40 and rBV-GP, and incorporation of Ebola GP into VLPs was demonstrated by SDS-PAGE and Western blot analysis. Recombinant baculovirus infection of insect cells yielded high levels of VLPs, which were shown to stimulate cytokine secretion from human dendritic cells similar to VLPs produced in mammalian cells. The immunogenicity of Ebola VLPs produced in insect cells was evaluated by immunization of mice. Analysis of antibody responses showed that most of the GP-specific antibodies were of the IgG2a subtype, while no significant level of IgG1 subtype antibodies specific for GP was induced, indicating the induction of a Th1-biased immune response. Furthermore, sera from Ebola VLP immunized mice were able to block infection by Ebola GP pseudotyped HIV virus in a single round infection assay, indicating that a neutralizing antibody against the Ebola GP protein was induced. These results show that production of Ebola VLPs in insect cells using recombinant baculoviruses represents a promising approach for vaccine development against Ebola virus infection.

  10. Genotypic anomaly in Ebola virus strains circulating in Magazine Wharf area, Freetown, Sierra Leone, 2015.

    PubMed

    Smits, Saskia L; Pas, Suzan D; Reusken, Chantal B; Haagmans, Bart L; Pertile, Peirro; Cancedda, Corrado; Dierberg, Kerry; Wurie, Isata; Kamara, Abdul; Kargbo, David; Caddy, Sarah L; Arias, Armando; Thorne, Lucy; Lu, Jia; Jah, Umaru; Goodfellow, Ian; Koopmans, Marion P

    2015-10-01

    The Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, similar to the Ebolavirus/H.sapiens-wt/SLE/2014/Makona-J0169 strain (J0169) detected in the same town in November 2014. This suggests that recently circulating viruses from Freetown descend from a J0169-like virus. PMID:26539753

  11. Evolution and Spread of Ebola Virus in Liberia, 2014-2015.

    PubMed

    Ladner, Jason T; Wiley, Michael R; Mate, Suzanne; Dudas, Gytis; Prieto, Karla; Lovett, Sean; Nagle, Elyse R; Beitzel, Brett; Gilbert, Merle L; Fakoli, Lawrence; Diclaro, Joseph W; Schoepp, Randal J; Fair, Joseph; Kuhn, Jens H; Hensley, Lisa E; Park, Daniel J; Sabeti, Pardis C; Rambaut, Andrew; Sanchez-Lockhart, Mariano; Bolay, Fatorma K; Kugelman, Jeffrey R; Palacios, Gustavo

    2015-12-01

    The 2013-present Western African Ebola virus disease (EVD) outbreak is the largest ever recorded with >28,000 reported cases. Ebola virus (EBOV) genome sequencing has played an important role throughout this outbreak; however, relatively few sequences have been determined from patients in Liberia, the second worst-affected country. Here, we report 140 EBOV genome sequences from the second wave of the Liberian outbreak and analyze them in combination with 782 previously published sequences from throughout the Western African outbreak. While multiple early introductions of EBOV to Liberia are evident, the majority of Liberian EVD cases are consistent with a single introduction, followed by spread and diversification within the country. Movement of the virus within Liberia was widespread, and reintroductions from Liberia served as an important source for the continuation of the already ongoing EVD outbreak in Guinea. Overall, little evidence was found for incremental adaptation of EBOV to the human host. PMID:26651942

  12. Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics

    E-print Network

    Kugelman, Jeffrey R.

    Until recently, Ebola virus (EBOV) was a rarely encountered human pathogen that caused disease among small populations with extraordinarily high lethality. At the end of 2013, EBOV initiated an unprecedented disease outbreak ...

  13. Emerging Targets and Novel Approaches to Ebola Virus Prophylaxis and Treatment

    PubMed Central

    Choi, Jin Huk; Croyle, Maria A.

    2013-01-01

    Ebola is a highly virulent pathogen causing severe hemorrhagic fever with a high case fatality rate in humans and non-human primates (NHPs). Although safe and effective vaccines or other medicinal agents to block Ebola infection are currently unavailable, a significant effort has been put forth to identify several promising candidates for the treatment and prevention of Ebola hemorrhagic fever. Among these, recombinant-virus based vectors have been identified as potent vaccine candidates with some affording both pre- and post-exposure protection from the virus. Recently, Investigational New Drug (IND) applications have been approved by the United States (U.S.) Food and Drug Administration (FDA) and Phase I clinical trials initiated for two small molecule therapeutics, 1) anti-sense phosphorodiamidate morphino oligomers (PMOs: AVI-6002, AVI-6003), and 2) lipid-nanoparticle/small interfering RNA (LNP/siRNA: TKM-Ebola). These potential alternatives to vector-based vaccines require multiple doses to achieve therapeutic efficacy which is not ideal with regard to patient compliance and outbreak scenarios. These concerns have fueled a quest for even better vaccination and treatment strategies. Here, we summarize recent advances in vaccines or post-exposure therapeutics for prevention of Ebola hemorrhagic fever. The utility of novel pharmaceutical approaches to refine and overcome barriers associated with the most promising therapeutic platforms will also be discussed. PMID:23813435

  14. Use of an ultraviolet tracer in simulation training for the clinical management of Ebola virus disease.

    PubMed

    Clay, K A; O'Shea, M K; Fletcher, T; Moore, A J; Burns, D S; Craig, D; Adam, M; Johnston, A M; Bailey, M S; Gibson, C

    2015-11-01

    In October 2014 the UK military deployed to Sierra Leone to provide care for healthcare workers affected by Ebola virus disease. A training package designed by the Army Medical Services Training Centre prepared the deploying personnel in the required infection prevention and control measures. The training used ultraviolet tracer to provide validation of the skills required when treating patients with Ebola and to confirm subsequent decontamination. This training construct provided useful feedback to clinicians on their infection control measures and would be useful in the context of any infection spread by droplets and fomites. PMID:26319591

  15. FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection

    PubMed Central

    Johansen, Lisa M.; Brannan, Jennifer M.; Delos, Sue E.; Shoemaker, Charles J.; Stossel, Andrea; Lear, Calli; Hoffstrom, Benjamin G.; DeWald, Lisa Evans; Schornberg, Kathryn L.; Scully, Corinne; Lehár, Joseph; Hensley, Lisa E.; White, Judith M.; Olinger, Gene G.

    2014-01-01

    Ebola viruses remain a substantial threat to both civilian and military populations as bioweapons, during sporadic outbreaks, and from the possibility of accidental importation from endemic regions by infected individuals. Currently, no approved therapeutics exist to treat or prevent infection by Ebola viruses. Therefore, we performed an in vitro screen of Food and Drug Administration (FDA)– and ex–US-approved drugs and selected molecular probes to identify drugs with antiviral activity against the type species Zaire ebolavirus (EBOV). From this screen, we identified a set of selective estrogen receptor modulators (SERMs), including clomiphene and toremifene, which act as potent inhibitors of EBOV infection. Anti-EBOV activity was confirmed for both of these SERMs in an in vivo mouse infection model. This anti-EBOV activity occurred even in the absence of detectable estrogen receptor expression, and both SERMs inhibited virus entry after internalization, suggesting that clomiphene and toremifene are not working through classical pathways associated with the estrogen receptor. Instead, the response appeared to be an off-target effect where the compounds interfere with a step late in viral entry and likely affect the triggering of fusion. These data support the screening of readily available approved drugs to identify therapeutics for the Ebola viruses and other infectious diseases. The SERM compounds described in this report are an immediately actionable class of approved drugs that can be repurposed for treatment of filovirus infections. PMID:23785035

  16. Transmission of Ebola Viruses: What We Know and What We Do Not Know

    PubMed Central

    Moore, Kristine A.; Kelley, Nicholas S.; Brosseau, Lisa M.; Wong, Gary; Murphy, Frederick A.; Peters, Clarence J.; LeDuc, James W.; Russell, Phillip K.; Van Herp, Michel; Kapetshi, Jimmy; Muyembe, Jean-Jacques T.; Ilunga, Benoit Kebela; Strong, James E.; Grolla, Allen; Wolz, Anja; Kargbo, Brima; Kargbo, David K.; Formenty, Pierre; Sanders, David Avram; Kobinger, Gary P.

    2015-01-01

    ABSTRACT Available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission, but this is based on a limited number of studies. Key areas requiring further study include (i) the role of aerosol transmission (either via large droplets or small particles in the vicinity of source patients), (ii) the role of environmental contamination and fomite transmission, (iii) the degree to which minimally or mildly ill persons transmit infection, (iv) how long clinically relevant infectiousness persists, (v) the role that “superspreading events” may play in driving transmission dynamics, (vi) whether strain differences or repeated serial passage in outbreak settings can impact virus transmission, and (vii) what role sylvatic or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013–2015 West Africa situation. In this review, we address what we know and what we do not know about Ebola virus transmission. We also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread. PMID:25698835

  17. Ebola Virus Disease: Essential Public Health Principles for Clinicians

    E-print Network

    Koenig, Kristi L.; Majestic, Cassondra; Burns, Michael J.

    2014-01-01

    for Disease Control and Prevention. 2014 Ebola Outbreak inControl and Prevention. Questions and Evaluation of US Patients Suspected of Having EbolaPrevention and Control Recommendations for Hospitalized Patients with Known Koenig and Schultz’s Disaster Medicine: Comprehensive Principles or Suspected Ebola

  18. Cluster of Ebola Virus Disease, Bong and Montserrado Counties, Liberia.

    PubMed

    Nyenswah, Tolbert G; Fallah, Mosaka; Calvert, Geoffrey M; Duwor, Stanley; Hamilton, E Dutch; Mokashi, Vishwesh; Arzoaquoi, Sampson; Dweh, Emmanuel; Burbach, Ryan; Dlouhy, Diane; Oeltmann, John E; Moonan, Patrick K

    2015-07-01

    Lack of trust in government-supported services after the death of a health care worker with symptoms of Ebola resulted in ongoing Ebola transmission in 2 Liberia counties. Ebola transmission was facilitated by attempts to avoid cremation of the deceased patient and delays in identifying and monitoring contacts. PMID:26079309

  19. Cluster of Ebola Virus Disease, Bong and Montserrado Counties, Liberia

    PubMed Central

    Nyenswah, Tolbert G.; Fallah, Mosaka; Calvert, Geoffrey M.; Duwor, Stanley; Hamilton, E. Dutch; Mokashi, Vishwesh; Arzoaquoi, Sampson; Dweh, Emmanuel; Burbach, Ryan; Dlouhy, Diane; Oeltmann, John E.

    2015-01-01

    Lack of trust in government-supported services after the death of a health care worker with symptoms of Ebola resulted in ongoing Ebola transmission in 2 Liberia counties. Ebola transmission was facilitated by attempts to avoid cremation of the deceased patient and delays in identifying and monitoring contacts. PMID:26079309

  20. Infectious Disease Physician Assessment of Hospital Preparedness for Ebola Virus Disease.

    PubMed

    Polgreen, Philip M; Santibanez, Scott; Koonin, Lisa M; Rupp, Mark E; Beekmann, Susan E; Del Rio, Carlos

    2015-09-01

    Background. ?The first case of Ebola diagnosed in the United States and subsequent cases among 2 healthcare workers caring for that patient highlighted the importance of hospital preparedness in caring for Ebola patients. Methods. ?From October 21, 2014 to November 11, 2014, infectious disease physicians who are part of the Emerging Infections Network (EIN) were surveyed about current Ebola preparedness at their institutions. Results. ?Of 1566 EIN physician members, 869 (55.5%) responded to this survey. Almost all institutions represented in this survey showed a substantial degree of preparation for the management of patients with suspected and confirmed Ebola virus disease. Despite concerns regarding shortages of personal protective equipment, approximately two thirds of all respondents reported that their facilities had sufficient and ready availability of hoods, full body coveralls, and fluid-resistant or impermeable aprons. The majority of respondents indicated preference for transfer of Ebola patients to specialized treatment centers rather than caring for them locally. In general, we found that larger hospitals and teaching hospitals reported higher levels of preparedness. Conclusions. ?Prior to the Centers for Disease Control and Prevention's plan for a tiered approach that identified specific roles for frontline, assessment, and designated treatment facilities, our query of infectious disease physicians suggested that healthcare facilities across the United States were making preparations for screening, diagnosis, and treatment of Ebola patients. Nevertheless, respondents from some hospitals indicated that they were relatively unprepared. PMID:26180836

  1. Infectious Disease Physician Assessment of Hospital Preparedness for Ebola Virus Disease

    PubMed Central

    Polgreen, Philip M.; Santibanez, Scott; Koonin, Lisa M.; Rupp, Mark E.; Beekmann, Susan E.; del Rio, Carlos

    2015-01-01

    Background.?The first case of Ebola diagnosed in the United States and subsequent cases among 2 healthcare workers caring for that patient highlighted the importance of hospital preparedness in caring for Ebola patients. Methods.?From October 21, 2014 to November 11, 2014, infectious disease physicians who are part of the Emerging Infections Network (EIN) were surveyed about current Ebola preparedness at their institutions. Results.?Of 1566 EIN physician members, 869 (55.5%) responded to this survey. Almost all institutions represented in this survey showed a substantial degree of preparation for the management of patients with suspected and confirmed Ebola virus disease. Despite concerns regarding shortages of personal protective equipment, approximately two thirds of all respondents reported that their facilities had sufficient and ready availability of hoods, full body coveralls, and fluid-resistant or impermeable aprons. The majority of respondents indicated preference for transfer of Ebola patients to specialized treatment centers rather than caring for them locally. In general, we found that larger hospitals and teaching hospitals reported higher levels of preparedness. Conclusions.?Prior to the Centers for Disease Control and Prevention's plan for a tiered approach that identified specific roles for frontline, assessment, and designated treatment facilities, our query of infectious disease physicians suggested that healthcare facilities across the United States were making preparations for screening, diagnosis, and treatment of Ebola patients. Nevertheless, respondents from some hospitals indicated that they were relatively unprepared. PMID:26180836

  2. Responding to the Potential of Ebola Virus Disease (EVD) Importation into Malaysia

    PubMed Central

    WAN MOHAMED NOOR, Wan Noraini; SANDHU, Sukhvinder Singh; AHMAD MAHIR, Husna Maizura; KURUP, Devan; RUSLI, Norhayati; SAAT, Zainah; CHONG, Chee Kheong; SULAIMAN, Lokman Hakim; ABDULLAH, Noor Hisham

    2014-01-01

    The current Ebola outbreak, which is the first to affect West African countries, has been declared to have met the conditions for a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO). Thus, the Ministry of Health (MOH) of Malaysia has taken steps to strengthen and enhanced the five core components of preparedness and response to mitigate the outbreak. The National Crisis Preparedness and Response Centre (CPRC) commands, controls and coordinates the preparedness and response plans for disasters, outbreaks, crises and emergencies (DOCE) related to health in a centralised way. Through standardised case definition and mandatory notification of Ebola by public and private practitioners, surveillance of Ebola is made possible. Government hospitals and laboratories have been identified to manage and diagnose Ebola virus infections, and medical staff members have been trained to handle an Ebola outbreak, with emphasis on strict infection prevention and control practices. Monitoring of the points of entry, focusing on travellers and students visiting or coming from West African countries is made possible by interagency collaborations. To alleviate the public’s anxiety, effective risk communications are being delivered through various channels. With experience in past outbreak control, the MOH’s preparedness and response plans are in place to abate an Ebola outbreak. PMID:25897276

  3. EBOLA VACCINE. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain.

    PubMed

    Marzi, Andrea; Robertson, Shelly J; Haddock, Elaine; Feldmann, Friederike; Hanley, Patrick W; Scott, Dana P; Strong, James E; Kobinger, Gary; Best, Sonja M; Feldmann, Heinz

    2015-08-14

    The latest Ebola virus (EBOV) epidemic spread rapidly through Guinea, Sierra Leone, and Liberia, creating a global public health crisis and accelerating the assessment of experimental therapeutics and vaccines in clinical trials. One of those vaccines is based on recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (VSV-EBOV), a live-attenuated vector with marked preclinical efficacy. Here, we provide the preclinical proof that VSV-EBOV completely protects macaques against lethal challenge with the West African EBOV-Makona strain. Complete and partial protection was achieved with a single dose given as late as 7 and 3 days before challenge, respectively. This indicates that VSV-EBOV may protect humans against EBOV infections in West Africa with relatively short time to immunity, promoting its use for immediate public health responses. PMID:26249231

  4. Prevalence and Current Approaches of Ebola Virus Disease in ASEAN Countries

    PubMed Central

    San, Kok Pui; Jiun, Ting Wei; May, Tam Ai; Neng, Yap Chan; Seng, Hee Kah; Soon, Lim Jing; Pazooki, Nazanin

    2015-01-01

    As indicated by the World Health Organization as of year 2014, around 10,000 people have been influenced with Ebola infection. The episode of Ebola in African locale is courged with a high death rate. Notwithstanding, in the United States, people influenced by Ebola have been given brilliant wellbeing offices, as the U.S. is one of the highest nations that have taken sterner wellbeing measures and principles against Ebola. Aside from the U.S., individuals in Asia, where billions live in indigence and general wellbeing frameworks are frequently extremely powerless, are under more serious danger of the Ebola infection. Despite the fact that nations like Singapore, Malaysia, South Korea and Japan can take stretched out measures to battle against the infection, nations like Philippines and Indonesia have unfathomable quantities of poor who may be incredibly influenced by a conceivable episode. At this moment, the chances that Asia will take a critical hit from the Ebola infection appear to be genuinely little. Yet, while it is far-fetched that Asia will encounter a real flare-up, genuine concerns stay about the infection coming to urban communities like Hong Kong, Beijing, Shanghai and Singapore through their worldwide airplane terminals. Wellbeing priests from the Association of Southeast Asian Nations (ASEAN) reported key measures not long ago to keep the Ebola plague from coming to the locale and to backing influenced nations. This article accordingly will concentrate on the prevalence and current approaches of Ebola Virus Disease in ASEAN nations which is the need of the hour. PMID:26500929

  5. Prevalence and Current Approaches of Ebola Virus Disease in ASEAN Countries.

    PubMed

    Rajiah, Kingston; San, Kok Pui; Jiun, Ting Wei; May, Tam Ai; Neng, Yap Chan; Seng, Hee Kah; Soon, Lim Jing; Pazooki, Nazanin

    2015-09-01

    As indicated by the World Health Organization as of year 2014, around 10,000 people have been influenced with Ebola infection. The episode of Ebola in African locale is courged with a high death rate. Notwithstanding, in the United States, people influenced by Ebola have been given brilliant wellbeing offices, as the U.S. is one of the highest nations that have taken sterner wellbeing measures and principles against Ebola. Aside from the U.S., individuals in Asia, where billions live in indigence and general wellbeing frameworks are frequently extremely powerless, are under more serious danger of the Ebola infection. Despite the fact that nations like Singapore, Malaysia, South Korea and Japan can take stretched out measures to battle against the infection, nations like Philippines and Indonesia have unfathomable quantities of poor who may be incredibly influenced by a conceivable episode. At this moment, the chances that Asia will take a critical hit from the Ebola infection appear to be genuinely little. Yet, while it is far-fetched that Asia will encounter a real flare-up, genuine concerns stay about the infection coming to urban communities like Hong Kong, Beijing, Shanghai and Singapore through their worldwide airplane terminals. Wellbeing priests from the Association of Southeast Asian Nations (ASEAN) reported key measures not long ago to keep the Ebola plague from coming to the locale and to backing influenced nations. This article accordingly will concentrate on the prevalence and current approaches of Ebola Virus Disease in ASEAN nations which is the need of the hour. PMID:26500929

  6. Physicochemical inactivation of Lassa, Ebola, and Marburg viruses and effect on clinical laboratory analyses

    SciTech Connect

    Mitchell, S.W.; McCormick, J.B.

    1984-09-01

    Clinical specimens from patients infected with Lassa, Ebola, or Marburg virus may present a serious biohazard to laboratory workers. The authors have examined the effects of heat, alteration of pH, and gamma radiation on these viruses in human blood and on the electrolytes, enzymes, and coagulation factors measured in laboratory tests that are important in the care of an infected patient. Heating serum at 60 degrees C for 1 h reduced high titers of these viruses to noninfectious levels without altering the serum levels of glucose, blood urea nitrogen, and electrolytes. Dilution of blood in 3% acetic acid, diluent for a leukocyte count, inactivated all of these viruses. All of the methods tested for viral inactivation markedly altered certain serum proteins, making these methods unsuitable for samples that are to be tested for certain enzyme levels and coagulation factors.

  7. Soluble Glycoprotein Is Not Required for Ebola Virus Virulence in Guinea Pigs.

    PubMed

    Hoenen, Thomas; Marzi, Andrea; Scott, Dana P; Feldmann, Friederike; Callison, Julie; Safronetz, David; Ebihara, Hideki; Feldmann, Heinz

    2015-10-01

    Ebola virus (EBOV) uses transcriptional editing to express several glycoproteins (GPs), including secreted soluble GP (sGP) and structural GP1,2, from a single gene. Recombinant viruses predominantly expressing GP1,2 are known to rapidly mutate and acquire an editing site predominantly expressing sGP in vivo, suggesting an important role of this protein during infection. Therefore, we generated a recombinant virus that is no longer able to express sGP and assessed its virulence in the EBOV guinea pig model. Surprisingly, although this virus remained genetically stable, it did not show any significant attenuation in vivo, showing that sGP is not required for virulence in this model. PMID:25957965

  8. Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain

    PubMed Central

    Marzi, Andrea; Feldmann, Friederike; Hanley, Patrick W.; Scott, Dana P.; Günther, Stephan

    2015-01-01

    In late 2013, the largest documented outbreak of Ebola hemorrhagic fever started in Guinea and has since spread to neighboring countries, resulting in almost 27,000 cases and >11,000 deaths in humans. In March 2014, Ebola virus (EBOV) was identified as the causative agent. This study compares the pathogenesis of a new EBOV strain, Makona, which was isolated in Guinea in 2014 with the prototype strain from the 1976 EBOV outbreak in the former Zaire. Both strains cause lethal disease in cynomolgus macaques with similar pathologic changes and hallmark features of Ebola hemorrhagic fever. However, disease progression was delayed in EBOV-Makona–infected animals, suggesting decreased rather than increased virulence of this most recent EBOV strain. PMID:26402165

  9. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak.

    PubMed

    Gire, Stephen K; Goba, Augustine; Andersen, Kristian G; Sealfon, Rachel S G; Park, Daniel J; Kanneh, Lansana; Jalloh, Simbirie; Momoh, Mambu; Fullah, Mohamed; Dudas, Gytis; Wohl, Shirlee; Moses, Lina M; Yozwiak, Nathan L; Winnicki, Sarah; Matranga, Christian B; Malboeuf, Christine M; Qu, James; Gladden, Adrianne D; Schaffner, Stephen F; Yang, Xiao; Jiang, Pan-Pan; Nekoui, Mahan; Colubri, Andres; Coomber, Moinya Ruth; Fonnie, Mbalu; Moigboi, Alex; Gbakie, Michael; Kamara, Fatima K; Tucker, Veronica; Konuwa, Edwin; Saffa, Sidiki; Sellu, Josephine; Jalloh, Abdul Azziz; Kovoma, Alice; Koninga, James; Mustapha, Ibrahim; Kargbo, Kandeh; Foday, Momoh; Yillah, Mohamed; Kanneh, Franklyn; Robert, Willie; Massally, James L B; Chapman, Sinéad B; Bochicchio, James; Murphy, Cheryl; Nusbaum, Chad; Young, Sarah; Birren, Bruce W; Grant, Donald S; Scheiffelin, John S; Lander, Eric S; Happi, Christian; Gevao, Sahr M; Gnirke, Andreas; Rambaut, Andrew; Garry, Robert F; Khan, S Humarr; Sabeti, Pardis C

    2014-09-12

    In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response. PMID:25214632

  10. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

    PubMed Central

    Gire, Stephen K.; Goba, Augustine; Andersen, Kristian G.; Sealfon, Rachel S. G.; Park, Daniel J.; Kanneh, Lansana; Jalloh, Simbirie; Momoh, Mambu; Fullah, Mohamed; Dudas, Gytis; Wohl, Shirlee; Moses, Lina M.; Yozwiak, Nathan L.; Winnicki, Sarah; Matranga, Christian B.; Malboeuf, Christine M.; Qu, James; Gladden, Adrianne D.; Schaffner, Stephen F.; Yang, Xiao; Jiang, Pan-Pan; Nekoui, Mahan; Colubri, Andres; Coomber, Moinya Ruth; Fonnie, Mbalu; Moigboi, Alex; Gbakie, Michael; Kamara, Fatima K.; Tucker, Veronica; Konuwa, Edwin; Saffa, Sidiki; Sellu, Josephine; Jalloh, Abdul Azziz; Kovoma, Alice; Koninga, James; Mustapha, Ibrahim; Kargbo, Kandeh; Foday, Momoh; Yillah, Mohamed; Kanneh, Franklyn; Robert, Willie; Massally, James L. B.; Chapman, Sinéad B.; Bochicchio, James; Murphy, Cheryl; Nusbaum, Chad; Young, Sarah; Birren, Bruce W.; Grant, Donald S.; Scheiffelin, John S.; Lander, Eric S.; Happi, Christian; Gevao, Sahr M.; Gnirke, Andreas; Rambaut, Andrew; Garry, Robert F.; Khan, S. Humarr; Sabeti, Pardis C.

    2015-01-01

    In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ?2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response. PMID:25214632

  11. Ebola virus vaccine: benefit and risks of adenovirus-based vectors.

    PubMed

    Mennechet, Franck Jd; Tran, Thi Thu Phuong; Eichholz, Karsten; van de Perre, Philippe; Kremer, Eric J

    2015-11-01

    In 2014, an outbreak of Ebola virus spread rapidly in West Africa. The epidemic killed more than 10,000 people and resulted in transmissions outside the endemic countries. WHO hopes for effective vaccines by the end of 2015. Numerous vaccine candidates have been proposed, and several are currently being evaluated in humans. Among the vaccine candidates are vectors derived from adenovirus (Ad). Despite previous encouraging preclinical and Phase I/II trials, Ad vectors used in three Phase II trials targeting HIV were prematurely interrupted because of the lack of demonstrated efficacy. The vaccine was not only ineffective but also led to a higher rate of HIV acquisition. In this context, the authors discuss the potential benefits, risks and impact of using Ad-derived vaccines to control Ebola virus disease. PMID:26325242

  12. Considerations for safe EMS transport of patients infected with Ebola virus.

    PubMed

    Lowe, John J; Jelden, Katelyn C; Schenarts, Paul J; Rupp, Lloyd E; Hawes, Kingdon J; Tysor, Benjamin M; Swansiger, Raymond G; Schwedhelm, Shelly S; Smith, Philip W; Gibbs, Shawn G

    2015-01-01

    The Nebraska Biocontainment Unit through the Nebraska Medical Center in Omaha, Nebraska, recently received patients with confirmed Ebola virus from West Africa. The Nebraska Biocontainment Unit and Omaha Fire Department's emergency medical services (EMS) coordinated patient transportation from airport to the high-level isolation unit. Transportation of these highly infectious patients capitalized on over 8 years of meticulous planning and rigorous infection control training to ensure the safety of transport personnel as well as the community during transport. Although these transports occurred with advanced notice and after confirmed Ebola virus disease (EVD) diagnosis, approaches and key lessons acquired through this effort will advance the ability of any EMS provider to safely transport a confirmed or suspected patient with EVD. Three critical areas have been identified from our experience: ambulance preparation, appropriate selection and use of personal protective equipment, and environmental decontamination. PMID:25380073

  13. Adenovirus-Vectored Vaccine Provides Postexposure Protection to Ebola Virus-Infected Nonhuman Primates.

    PubMed

    Wong, Gary; Richardson, Jason S; Pillet, Stéphane; Racine, Trina; Patel, Ami; Soule, Geoff; Ennis, Jane; Turner, Jeffrey; Qiu, Xiangguo; Kobinger, Gary P

    2015-10-01

    Ebola virus (EBOV) causes lethal disease in up to 90% of EBOV-infected humans. Among vaccines, only the vesicular stomatitis virus platform has been successful in providing postexposure protection in nonhuman primates. Here, we show that an adjuvanted human adenovirus serotype 5 (Ad5)-vectored vaccine (Ad5-Zaire EBOV glycoprotein) protected 67% (6 of 9) and 25% (1 of 4) of cynomolgus macaques when administered 30 minutes and 24 hours following EBOV challenge, respectively. The treatment also protected 33% of rhesus macaques (1 of 3) when given at 24 hours. The results highlight the utility of adjuvanted Ad5 vaccines for rapid immunization against EBOV. PMID:25957963

  14. Ebola

    MedlinePLUS

    ... virus. It is a severe and often fatal disease. It can affect humans and other primates. Researchers ... of Ebola are similar to other, more common, diseases. This makes it difficult to diagnose Ebola in ...

  15. Duration of Ebola virus RNA persistence in semen of survivors: population-level estimates and projections.

    PubMed

    Eggo, Rosalind M; Watson, Conall H; Camacho, Anton; Kucharski, Adam J; Funk, Sebastian; Edmunds, W John

    2015-12-01

    Ebola virus can persist in semen after recovery, potentially for months, which may impact the duration of enhanced surveillance required after interruption of transmission. We combined recent data on viral RNA persistence with weekly disease incidence to estimate the current number of semen-positive men in affected West African countries. We find the number is low, and since few reported sexual transmission events have occurred, the future risk is also likely low, although sexual health promotion remains critical. PMID:26676163

  16. Modeling of the Ebola Virus Delta Peptide Reveals a Potential Lytic Sequence Motif

    PubMed Central

    Gallaher, William R.; Garry, Robert F.

    2015-01-01

    Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with 2014 Ebola virus (EBOV) sequences, a differential level of conservation was noted between the soluble form of glycoprotein (sGP) and the full length glycoprotein (GP), which are both encoded by the GP gene via RNA editing. In the region of the proteins encoded after the RNA editing site sGP was more conserved than the overlapping region of GP when compared to a distant outlier species, Tai Forest ebolavirus. Half of the amino acids comprising the “delta peptide”, a 40 amino acid carboxy-terminal fragment of sGP, were identical between otherwise widely divergent species. A lysine-rich amphipathic peptide motif was noted at the carboxyl terminus of delta peptide with high structural relatedness to the cytolytic peptide of the non-structural protein 4 (NSP4) of rotavirus. EBOV delta peptide is a candidate viroporin, a cationic pore-forming peptide, and may contribute to EBOV pathogenesis. PMID:25609303

  17. Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining

    PubMed Central

    Wang, Bo; Kluwe, Christien A.; Lungu, Oana I.; DeKosky, Brandon J.; Kerr, Scott A.; Johnson, Erik L.; Jung, Jiwon; Rezigh, Alec B.; Carroll, Sean M.; Reyes, Ann N.; Bentz, Janelle R.; Villanueva, Itamar; Altman, Amy L.; Davey, Robert A.; Ellington, Andrew D.; Georgiou, George

    2015-01-01

    The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different Ebolaviruses. We developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the VH:VL paired antibody repertoire encoded by highly expanded B cells in the draining popliteal lymph node (PLN). This approach requires neither screening nor selection for antigen-binding. Specifically we show that mouse immunization with Ebola VLPs gives rise to a highly polarized antibody repertoire in CD138+ antibody-secreting cells within the PLN. All highly expanded antibody clones (7/7 distinct clones/animal) were expressed recombinantly, and shown to recognize the VLPs used for immunization. Using this approach we obtained diverse panels of antibodies including: (i) antibodies with high affinity towards GP; (ii) antibodies which bound Ebola VLP Kissidougou-C15, the strain circulating in the recent West African outbreak; (iii) non-GP binding antibodies that recognize wild type Sudan or Bundibugyo viruses that have 39% and 37% sequence divergence from Ebola virus, respectively and (iv) antibodies to the Reston virus GP for which no antibodies have been reported. PMID:26355042

  18. Development of Lentivirus-Based Reference Materials for Ebola Virus Nucleic Acid Amplification Technology-Based Assays

    PubMed Central

    Mattiuzzo, Giada; Ashall, James; Doris, Kathryn S.; MacLellan-Gibson, Kirsty; Nicolson, Carolyn; Wilkinson, Dianna E.; Harvey, Ruth; Almond, Neil; Anderson, Robert; Efstathiou, Stacey; Minor, Philip D.; Page, Mark

    2015-01-01

    The 2013-present Ebola virus outbreak in Western Africa has prompted the production of many diagnostic assays, mostly based on nucleic acid amplification technologies (NAT). The calibration and performance assessment of established assays and those under evaluation requires reference materials that can be used in parallel with the clinical sample to standardise or control for every step of the procedure, from extraction to the final qualitative/quantitative result. We have developed safe and stable Ebola virus RNA reference materials by encapsidating anti sense viral RNA into HIV-1-like particles. The lentiviral particles are replication-deficient and non-infectious due to the lack of HIV-1 genes and Envelope protein. Ebola virus genes were subcloned for encapsidation into two lentiviral preparations, one containing NP-VP35-GP and the other VP40 and L RNA. Each reference material was formulated as a high-titre standard for use as a calibrator for secondary or internal standards, and a 10,000-fold lower titre preparation to serve as an in-run control. The preparations have been freeze-dried to maximise stability. These HIV-Ebola virus RNA reference materials were suitable for use with in-house and commercial quantitative RT-PCR assays and with digital RT-PCR. The HIV-Ebola virus RNA reference materials are stable at up to 37°C for two weeks, allowing the shipment of the material worldwide at ambient temperature. These results support further evaluation of the HIV-Ebola virus RNA reference materials as part of an International collaborative study for the establishment of the 1st International Standard for Ebola virus RNA. PMID:26562415

  19. ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus

    E-print Network

    Karp, Peter D.

    Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to ...

  20. A Novel Life Cycle Modeling System for Ebola Virus Shows a Genome Length-Dependent Role of VP24 in Virus Infectivity

    PubMed Central

    Watt, Ari; Moukambi, Felicien; Banadyga, Logan; Groseth, Allison; Callison, Julie; Herwig, Astrid; Ebihara, Hideki

    2014-01-01

    ABSTRACT Work with infectious Ebola viruses is restricted to biosafety level 4 (BSL4) laboratories, presenting a significant barrier for studying these viruses. Life cycle modeling systems, including minigenome systems and transcription- and replication-competent virus-like particle (trVLP) systems, allow modeling of the virus life cycle under BSL2 conditions; however, all current systems model only certain aspects of the virus life cycle, rely on plasmid-based viral protein expression, and have been used to model only single infectious cycles. We have developed a novel life cycle modeling system allowing continuous passaging of infectious trVLPs containing a tetracistronic minigenome that encodes a reporter and the viral proteins VP40, VP24, and GP1,2. This system is ideally suited for studying morphogenesis, budding, and entry, in addition to genome replication and transcription. Importantly, the specific infectivity of trVLPs in this system was ?500-fold higher than that in previous systems. Using this system for functional studies of VP24, we showed that, contrary to previous reports, VP24 only very modestly inhibits genome replication and transcription when expressed in a regulated fashion, which we confirmed using infectious Ebola viruses. Interestingly, we also discovered a genome length-dependent effect of VP24 on particle infectivity, which was previously undetected due to the short length of monocistronic minigenomes and which is due at least partially to a previously unknown function of VP24 in RNA packaging. Based on our findings, we propose a model for the function of VP24 that reconciles all currently available data regarding the role of VP24 in nucleocapsid assembly as well as genome replication and transcription. IMPORTANCE Ebola viruses cause severe hemorrhagic fevers in humans, with no countermeasures currently being available, and must be studied in maximum-containment laboratories. Only a few of these laboratories exist worldwide, limiting our ability to study Ebola viruses and develop countermeasures. Here we report the development of a novel reverse genetics-based system that allows the study of Ebola viruses without maximum-containment laboratories. We used this system to investigate the Ebola virus protein VP24, showing that, contrary to previous reports, it only modestly inhibits virus genome replication and transcription but is important for packaging of genomes into virus particles, which constitutes a previously unknown function of VP24 and a potential antiviral target. We further propose a comprehensive model for the function of VP24 in nucleocapsid assembly. Importantly, on the basis of this approach, it should easily be possible to develop similar experimental systems for other viruses that are currently restricted to maximum-containment laboratories. PMID:24965473

  1. Ebola Hemorrhagic Fever: Diagnosis

    MedlinePLUS

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  2. Ebola Hemorrhagic Fever: Prevention

    MedlinePLUS

    ... Search The CDC Cancel Submit Search The CDC Ebola (Ebola Virus Disease) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Ebola (Ebola Virus Disease) About Ebola Questions & Answers 2014 ...

  3. Ebola Hemorrhagic Fever: Treatment

    MedlinePLUS

    ... Search The CDC Cancel Submit Search The CDC Ebola (Ebola Virus Disease) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Ebola (Ebola Virus Disease) About Ebola Questions & Answers 2014 ...

  4. Understanding the Emergence of Ebola Virus Disease in Sierra Leone: Stalking the Virus in the Threatening Wake of Emergence

    PubMed Central

    Wauquier, Nadia; Bangura, James; Moses, Lina; Humarr Khan, Sheik; Coomber, Moinya; Lungay, Victor; Gbakie, Michael; Sesay, Mohammed S.K.; Gassama, Ibrahim A.K.; Massally, James L.B.; Gbakima, Aiah; Squire, James; Lamin, Mohamed; Kanneh, Lansana; Yillah, Mohammed; Kargbo, Kandeh; Roberts, Willie; Vandi, Mohammed; Kargbo, David; Vincent, Tom; Jambai, Amara; Guttieri, Mary; Fair, Joseph; Souris, Marc; Gonzalez, Jean Paul

    2015-01-01

    Since Ebola Virus Disease (EVD) was first identified in 1976 in what is now the Democratic Republic of Congo, and despite the numerous outbreaks recorded to date, rarely has an epidemic origin been identified. Indeed, among the twenty-one most documented EVD outbreaks in Africa, an index case has been identified four times, and hypothesized in only two other instances. The initial steps of emergence and spread of a virus are critical in the development of a potential outbreak and need to be thoroughly dissected and understood in order to improve on preventative strategies. In the current West African outbreak of EVD, a unique index case has been identified, pinpointing the geographical origin of the epidemic in Guinea. Herein, we provide an accounting of events that serve as the footprint of EVD emergence in Sierra Leone and a road map for risk mitigation fueled by lessons learned. PMID:25969797

  5. A Kunjin Replicon Virus-like Particle Vaccine Provides Protection Against Ebola Virus Infection in Nonhuman Primates.

    PubMed

    Pyankov, Oleg V; Bodnev, Sergey A; Pyankova, Olga G; Solodkyi, Vladislav V; Pyankov, Stepan A; Setoh, Yin Xiang; Volchkova, Valentina A; Suhrbier, Andreas; Volchkov, Viktor V; Agafonov, Alexander A; Khromykh, Alexander A

    2015-10-01

    The current unprecedented outbreak of Ebola virus (EBOV) disease in West Africa has demonstrated the urgent need for a vaccine. Here, we describe the evaluation of an EBOV vaccine candidate based on Kunjin replicon virus-like particles (KUN VLPs) encoding EBOV glycoprotein with a D637L mutation (GP/D637L) in nonhuman primates. Four African green monkeys (Cercopithecus aethiops) were injected subcutaneously with a dose of 10(9) KUN VLPs per animal twice with an interval of 4 weeks, and animals were challenged 3 weeks later intramuscularly with 600 plaque-forming units of Zaire EBOV. Three animals were completely protected against EBOV challenge, while one vaccinated animal and the control animal died from infection. We suggest that KUN VLPs encoding GP/D637L represent a viable EBOV vaccine candidate. PMID:25732811

  6. Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs

    PubMed Central

    Kouznetsova, Jennifer; Sun, Wei; Martínez-Romero, Carles; Tawa, Gregory; Shinn, Paul; Chen, Catherine Z; Schimmer, Aaron; Sanderson, Philip; McKew, John C; Zheng, Wei; García-Sastre, Adolfo

    2014-01-01

    In light of the current outbreak of Ebola virus disease, there is an urgent need to develop effective therapeutics to treat Ebola infection, and drug repurposing screening is a potentially rapid approach for identifying such therapeutics. We developed a biosafety level 2 (BSL-2) 1536-well plate assay to screen for entry inhibitors of Ebola virus-like particles (VLPs) containing the glycoprotein (GP) and the matrix VP40 protein fused to a beta-lactamase reporter protein and applied this assay for a rapid drug repurposing screen of Food and Drug Administration (FDA)-approved drugs. We report here the identification of 53 drugs with activity of blocking Ebola VLP entry into cells. These 53 active compounds can be divided into categories including microtubule inhibitors, estrogen receptor modulators, antihistamines, antipsychotics, pump/channel antagonists, and anticancer/antibiotics. Several of these compounds, including microtubule inhibitors and estrogen receptor modulators, had previously been reported to be active in BSL-4 infectious Ebola virus replication assays and in animal model studies. Our assay represents a robust, effective and rapid high-throughput screen for the identification of lead compounds in drug development for the treatment of Ebola virus infection. PMID:26038505

  7. Lauren Smith Discuss the factors leading to the present Ebola virus epidemic in West Africa and how to stop its spread.

    E-print Network

    Lasenby, Joan

    areas14 . However, border controls can have negative impacts rather than positive by preventingLauren Smith 1 Discuss the factors leading to the present Ebola virus epidemic in West Africa and how to stop its spread. The Ebola virus (EVD) was first identified in 1976, in Zaire and has since

  8. Mission critical: mobilization of essential animal models for Ebola, Nipah, and Machupo virus infections.

    PubMed

    Zumbrun, E E

    2015-01-01

    The reports for Ebola virus Zaire (EBOV), Nipah virus, and Machupo virus (MACV) pathogenesis, in this issue of Veterinary Pathology, are timely considering recent events, both nationally and internationally. EBOV, Nipah virus, and MACV cause highly lethal infections for which no Food and Drug Administration (FDA) licensed vaccines or therapies exist. Not only are there concerns that these agents could be used by those with malicious intent, but shifts in ecological distribution of viral reservoirs due to climate change or globalization could lead to more frequent infections within remote regions than previously seen as well as outbreaks in more populous areas. The current EBOV epidemic shows no sign of abating across 3 West African nations (as of October 2014), including densely populated areas, far outpacing infection rates of previous outbreaks. A limited number of cases have also arisen in the United States and Europe. With few treatment options for these deadly viruses, development of animal models reflective of human disease is paramount to combat these diseases. As an example of this potential, a new treatment compound, ZMapp, that had demonstrated efficacy against EBOV infection in nonhuman primates (NHPs) received an emergency compassionate use exception from the FDA for the treatment of 2 American medical workers infected with EBOV, and they are currently virus free and recovering. PMID:25352204

  9. Structural and Functional Characterization of Reston Ebola Virus VP35 Interferon Inhibitory Domain

    SciTech Connect

    Leung, Daisy W.; Shabman, Reed S.; Farahbakhsh, Mina; Prins, Kathleen C.; Borek, Dominika M.; Wang, Tianjiao; Mühlberger, Elke; Basler, Christopher F.; Amarasinghe, Gaya K.

    2010-09-21

    Ebolaviruses are causative agents of lethal hemorrhagic fever in humans and nonhuman primates. Among the filoviruses characterized thus far, Reston Ebola virus (REBOV) is the only Ebola virus that is nonpathogenic to humans despite the fact that REBOV can cause lethal disease in nonhuman primates. Previous studies also suggest that REBOV is less effective at inhibiting host innate immune responses than Zaire Ebola virus (ZEBOV) or Marburg virus. Virally encoded VP35 protein is critical for immune suppression, but an understanding of the relative contributions of VP35 proteins from REBOV and other filoviruses is currently lacking. In order to address this question, we characterized the REBOV VP35 interferon inhibitory domain (IID) using structural, biochemical, and virological studies. These studies reveal differences in double-stranded RNA binding and interferon inhibition between the two species. These observed differences are likely due to increased stability and loss of flexibility in REBOV VP35 IID, as demonstrated by thermal shift stability assays. Consistent with this finding, the 1.71-{angstrom} crystal structure of REBOV VP35 IID reveals that it is highly similar to that of ZEBOV VP35 IID, with an overall backbone r.m.s.d. of 0.64 {angstrom}, but contains an additional helical element at the linker between the two subdomains of VP35 IID. Mutations near the linker, including swapping sequences between REBOV and ZEBOV, reveal that the linker sequence has limited tolerance for variability. Together with the previously solved ligand-free and double-stranded-RNA-bound forms of ZEBOV VP35 IID structures, our current studies on REBOV VP35 IID reinforce the importance of VP35 in immune suppression. Functional differences observed between REBOV and ZEBOV VP35 proteins may contribute to observed differences in pathogenicity, but these are unlikely to be the major determinant. However, the high level of similarity in structure and the low tolerance for sequence variability, coupled with the multiple critical roles played by Ebola virus VP35 proteins, highlight the viability of VP35 as a potential target for therapeutic development.

  10. Regional Spread of Ebola Virus, West Africa, 2014

    PubMed Central

    Shankar, Manjunath; Wellman, Michael; Merlin, Toby; Meltzer, Martin I.

    2015-01-01

    To explain the spread of the 2014 Ebola epidemic in West Africa, and thus help with response planning, we analyzed publicly available data. We found that the risk for infection in an area can be predicted by case counts, population data, and distances between affected and nonaffected areas. PMID:25693782

  11. Clinical predictors of mortality in patients with Ebola virus disease.

    PubMed

    Barry, Moumié; Touré, Abdoulaye; Traoré, Fodé Amara; Sako, Fodé-Bangaly; Sylla, Djibril; Kpamy, Dimai Ouo; Bah, Elhadj Ibrahima; Bangoura, M'Mah; Poncin, Marc; Keita, Sakoba; Tounkara, Thierno Mamadou; Cisse, Mohamed; Vanhems, Philippe

    2015-06-15

    In an observational cohort study including 89 Ebola patients, predictive factors of death were analyzed. The crude mortality rate was 43.8%. Myalgia (adjusted odds ratio [OR], 4.04; P = .02), hemorrrhage (adjusted OR, 3.5; P = .02), and difficulty breathing (adjusted OR, 5.75; P = .01) were independently associated with death. PMID:25770172

  12. Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone

    PubMed Central

    Park, Daniel J.; Dudas, Gytis; Wohl, Shirlee; Goba, Augustine; Whitmer, Shannon L.M.; Andersen, Kristian G.; Sealfon, Rachel S.; Ladner, Jason T.; Kugelman, Jeffrey R.; Matranga, Christian B.; Winnicki, Sarah M.; Qu, James; Gire, Stephen K.; Gladden-Young, Adrianne; Jalloh, Simbirie; Nosamiefan, Dolo; Yozwiak, Nathan L.; Moses, Lina M.; Jiang, Pan-Pan; Lin, Aaron E.; Schaffner, Stephen F.; Bird, Brian; Towner, Jonathan; Mamoh, Mambu; Gbakie, Michael; Kanneh, Lansana; Kargbo, David; Massally, James L.B.; Kamara, Fatima K.; Konuwa, Edwin; Sellu, Josephine; Jalloh, Abdul A.; Mustapha, Ibrahim; Foday, Momoh; Yillah, Mohamed; Erickson, Bobbie R.; Sealy, Tara; Blau, Dianna; Paddock, Christopher; Brault, Aaron; Amman, Brian; Basile, Jane; Bearden, Scott; Belser, Jessica; Bergeron, Eric; Campbell, Shelley; Chakrabarti, Ayan; Dodd, Kimberly; Flint, Mike; Gibbons, Aridth; Goodman, Christin; Klena, John; McMullan, Laura; Morgan, Laura; Russell, Brandy; Salzer, Johanna; Sanchez, Angela; Wang, David; Jungreis, Irwin; Tomkins-Tinch, Christopher; Kislyuk, Andrey; Lin, Michael F.; Chapman, Sinead; MacInnis, Bronwyn; Matthews, Ashley; Bochicchio, James; Hensley, Lisa E.; Kuhn, Jens H.; Nusbaum, Chad; Schieffelin, John S.; Birren, Bruce W.; Forget, Marc; Nichol, Stuart T.; Palacios, Gustavo F.; Ndiaye, Daouda; Happi, Christian; Gevao, Sahr M.; Vandi, Mohamed A.; Kargbo, Brima; Holmes, Edward C.; Bedford, Trevor; Gnirke, Andreas; Ströher, Ute; Rambaut, Andrew; Garry, Robert F.; Sabeti, Pardis C.

    2015-01-01

    Summary The 2013–2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. PMID:26091036

  13. Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.

    PubMed

    Park, Daniel J; Dudas, Gytis; Wohl, Shirlee; Goba, Augustine; Whitmer, Shannon L M; Andersen, Kristian G; Sealfon, Rachel S; Ladner, Jason T; Kugelman, Jeffrey R; Matranga, Christian B; Winnicki, Sarah M; Qu, James; Gire, Stephen K; Gladden-Young, Adrianne; Jalloh, Simbirie; Nosamiefan, Dolo; Yozwiak, Nathan L; Moses, Lina M; Jiang, Pan-Pan; Lin, Aaron E; Schaffner, Stephen F; Bird, Brian; Towner, Jonathan; Mamoh, Mambu; Gbakie, Michael; Kanneh, Lansana; Kargbo, David; Massally, James L B; Kamara, Fatima K; Konuwa, Edwin; Sellu, Josephine; Jalloh, Abdul A; Mustapha, Ibrahim; Foday, Momoh; Yillah, Mohamed; Erickson, Bobbie R; Sealy, Tara; Blau, Dianna; Paddock, Christopher; Brault, Aaron; Amman, Brian; Basile, Jane; Bearden, Scott; Belser, Jessica; Bergeron, Eric; Campbell, Shelley; Chakrabarti, Ayan; Dodd, Kimberly; Flint, Mike; Gibbons, Aridth; Goodman, Christin; Klena, John; McMullan, Laura; Morgan, Laura; Russell, Brandy; Salzer, Johanna; Sanchez, Angela; Wang, David; Jungreis, Irwin; Tomkins-Tinch, Christopher; Kislyuk, Andrey; Lin, Michael F; Chapman, Sinead; MacInnis, Bronwyn; Matthews, Ashley; Bochicchio, James; Hensley, Lisa E; Kuhn, Jens H; Nusbaum, Chad; Schieffelin, John S; Birren, Bruce W; Forget, Marc; Nichol, Stuart T; Palacios, Gustavo F; Ndiaye, Daouda; Happi, Christian; Gevao, Sahr M; Vandi, Mohamed A; Kargbo, Brima; Holmes, Edward C; Bedford, Trevor; Gnirke, Andreas; Ströher, Ute; Rambaut, Andrew; Garry, Robert F; Sabeti, Pardis C

    2015-06-18

    The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. PMID:26091036

  14. Evolution of ebola virus disease from exotic infection to global health priority, Liberia, mid-2014.

    PubMed

    Arwady, M Allison; Bawo, Luke; Hunter, Jennifer C; Massaquoi, Moses; Matanock, Almea; Dahn, Bernice; Ayscue, Patrick; Nyenswah, Tolbert; Forrester, Joseph D; Hensley, Lisa E; Monroe, Benjamin; Schoepp, Randal J; Chen, Tai-Ho; Schaecher, Kurt E; George, Thomas; Rouse, Edward; Schafer, Ilana J; Pillai, Satish K; De Cock, Kevin M

    2015-04-01

    Over the span of a few weeks during July and August 2014, events in West Africa changed perceptions of Ebola virus disease (EVD) from an exotic tropical disease to a priority for global health security. We describe observations during that time of a field team from the Centers for Disease Control and Prevention and personnel of the Liberian Ministry of Health and Social Welfare. We outline the early epidemiology of EVD within Liberia, including the practical limitations on surveillance and the effect on the country's health care system, such as infections among health care workers. During this time, priorities included strengthening EVD surveillance; establishing safe settings for EVD patient care (and considering alternative isolation and care models when Ebola Treatment Units were overwhelmed); improving infection control practices; establishing an incident management system; and working with Liberian airport authorities to implement EVD screening of departing passengers. PMID:25811176

  15. Evolution of Ebola Virus Disease from Exotic Infection to Global Health Priority, Liberia, Mid-2014

    PubMed Central

    Bawo, Luke; Hunter, Jennifer C.; Massaquoi, Moses; Matanock, Almea; Dahn, Bernice; Ayscue, Patrick; Nyenswah, Tolbert; Forrester, Joseph D.; Hensley, Lisa E.; Monroe, Benjamin; Schoepp, Randal J.; Chen, Tai-Ho; Schaecher, Kurt E.; George, Thomas; Rouse, Edward; Schafer, Ilana J.; Pillai, Satish K.; De Cock, Kevin M.

    2015-01-01

    Over the span of a few weeks during July and August 2014, events in West Africa changed perceptions of Ebola virus disease (EVD) from an exotic tropical disease to a priority for global health security. We describe observations during that time of a field team from the Centers for Disease Control and Prevention and personnel of the Liberian Ministry of Health and Social Welfare. We outline the early epidemiology of EVD within Liberia, including the practical limitations on surveillance and the effect on the country’s health care system, such as infections among health care workers. During this time, priorities included strengthening EVD surveillance; establishing safe settings for EVD patient care (and considering alternative isolation and care models when Ebola Treatment Units were overwhelmed); improving infection control practices; establishing an incident management system; and working with Liberian airport authorities to implement EVD screening of departing passengers. PMID:25811176

  16. Distinct lineages of Ebola virus in Guinea during the 2014 West African epidemic.

    PubMed

    Simon-Loriere, Etienne; Faye, Ousmane; Faye, Oumar; Koivogui, Lamine; Magassouba, Nfaly; Keita, Sakoba; Thiberge, Jean-Michel; Diancourt, Laure; Bouchier, Christiane; Vandenbogaert, Matthias; Caro, Valérie; Fall, Gamou; Buchmann, Jan P; Matranga, Christan B; Sabeti, Pardis C; Manuguerra, Jean-Claude; Holmes, Edward C; Sall, Amadou A

    2015-08-01

    An epidemic of Ebola virus disease of unprecedented scale has been ongoing for more than a year in West Africa. As of 29 April 2015, there have been 26,277 reported total cases (of which 14,895 have been laboratory confirmed) resulting in 10,899 deaths. The source of the outbreak was traced to the prefecture of Guéckédou in the forested region of southeastern Guinea. The virus later spread to the capital, Conakry, and to the neighbouring countries of Sierra Leone, Liberia, Nigeria, Senegal and Mali. In March 2014, when the first cases were detected in Conakry, the Institut Pasteur of Dakar, Senegal, deployed a mobile laboratory in Donka hospital to provide diagnostic services to the greater Conakry urban area and other regions of Guinea. Through this process we sampled 85 Ebola viruses (EBOV) from patients infected from July to November 2014, and report their full genome sequences here. Phylogenetic analysis reveals the sustained transmission of three distinct viral lineages co-circulating in Guinea, including the urban setting of Conakry and its surroundings. One lineage is unique to Guinea and closely related to the earliest sampled viruses of the epidemic. A second lineage contains viruses probably reintroduced from neighbouring Sierra Leone on multiple occasions, while a third lineage later spread from Guinea to Mali. Each lineage is defined by multiple mutations, including non-synonymous changes in the virion protein 35 (VP35), glycoprotein (GP) and RNA-dependent RNA polymerase (L) proteins. The viral GP is characterized by a glycosylation site modification and mutations in the mucin-like domain that could modify the outer shape of the virion. These data illustrate the ongoing ability of EBOV to develop lineage-specific and potentially phenotypically important variation. PMID:26106863

  17. [Development of SYBR Green I real-time RT-PCR for the detection of Ebola virus].

    PubMed

    Liu, Yang; Shi, Zi-Xue; Ma, Yu-Kun; Wang, Hao-Ting; Wang, Zong-Yao; Shao, Dong-Hua; Wei, Jian-Chao; Wang, Shao-Hui; Li, Bei-Bei; Wang, Shui-Ming; Liu, Xue-Hui; Ma, Zhi-Yong

    2012-09-01

    In order to establish a rapid and accurate method for the detection of Ebola virus (EBOV), the primers used in SYBR Green I real-time RT-PCR were designed based on the EBOV NP gene sequences published in GenBank. The SYBR Green I real-time RT-PCR was established and optimized for the detection of EBOV. The EBOV RNA that was transcribed in vitro was used as a template. The sensitivity of this method was found to reach 1.0 x 10(2) copies/microL and the detection range was 10(2) - 10(10). No cross reaction with RNA samples from Marburg virus, Dengue virus, Xinjiang hemorrhagic fever virus, Japanese encephalitis virus, Influenza virus (H1N1 and H3N2) and Porcine reproductive and respiratory syndrome virus E genomic RNA was found. The method would be useful for the detection and monitoring of EBOV in China. PMID:23233935

  18. Functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal Ebola virus infection.

    PubMed

    Cilloniz, Cristian; Ebihara, Hideki; Ni, Chester; Neumann, Gabriele; Korth, Marcus J; Kelly, Sara M; Kawaoka, Yoshihiro; Feldmann, Heinz; Katze, Michael G

    2011-09-01

    Ebola virus is the etiologic agent of a lethal hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Previous studies with Zaire Ebola virus (ZEBOV), mouse-adapted virus (MA-ZEBOV), and mutant viruses (ZEBOV-NP(ma), ZEBOV-VP24(ma), and ZEBOV-NP/VP24(ma)) allowed us to identify the mutations in viral protein 24 (VP24) and nucleoprotein (NP) responsible for acquisition of high virulence in mice. To elucidate specific molecular signatures associated with lethality, we compared global gene expression profiles in spleen samples from mice infected with these viruses and performed an extensive functional analysis. Our analysis showed that the lethal viruses (MA-ZEBOV and ZEBOV-NP/VP24(ma)) elicited a strong expression of genes 72 h after infection. In addition, we found that although the host transcriptional response to ZEBOV-VP24(ma) was nearly the same as that to ZEBOV-NP/VP24(ma), the contribution of a mutation in the NP gene was required for a lethal phenotype. Further analysis indicated that one of the most relevant biological functions differentially regulated by the lethal viruses was the inflammatory response, as was the induction of specific metalloproteinases, which were present in our newly identify functional network that was associated with Ebola virus lethality. Our results suggest that this dysregulated proinflammatory response increased the severity of disease. Consequently, the newly discovered molecular signature could be used as the starting point for the development of new drugs and therapeutics. To our knowledge, this is the first study that clearly defines unique molecular signatures associated with Ebola virus lethality. PMID:21734050

  19. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses

    PubMed Central

    Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

    2015-01-01

    Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared. PMID:26575624

  20. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses.

    PubMed

    Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

    2015-11-24

    Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared. PMID:26575624

  1. Interferon ?/? Receptor-Deficient Mice as a Model for Ebola Virus Disease.

    PubMed

    Brannan, Jennifer M; Froude, Jeffery W; Prugar, Laura I; Bakken, Russell R; Zak, Samantha E; Daye, Sharon P; Wilhelmsen, Catherine E; Dye, John M

    2015-10-01

    A major obstacle in ebolavirus research is the lack of a small-animal model for Sudan virus (SUDV), as well as other wild-type (WT) ebolaviruses. Here, we expand on research by Bray and by Lever et al suggesting that WT ebolaviruses are pathogenic in mice deficient for the type 1 interferon (IFN) ?/? receptor (IFN?/?R-/-). We examined the disease course of several WT ebolaviruses: Boneface (SUDV/Bon) and Gulu variants of SUDV, Ebola virus (EBOV), Bundibugyo virus (BDBV), Taï Forest virus, and Reston virus (RESTV). We determined that exposure to WT SUDV or EBOV results in reproducible signs of disease in IFN?/?R-/- mice, as measured by weight loss and partial lethality. Vaccination with the SUDV or EBOV glycoprotein (GP)-expressing Venezuelan equine encephalitis viral replicon particle vaccine protected these mice from SUDV/Bon and EBOV challenge, respectively. Treatment with SUDV- or EBOV-specific anti-GP antibodies protected mice from challenge when delivered 1-3 days after infection. Serial sampling experiments revealed evidence of disseminated intravascular coagulation in the livers of mice infected with the Boneface variant of SUDV, EBOV, and BDBV. Taken together, these data solidify the IFN?/?R-/- mouse as an important and useful model for the study of WT EBOV disease. PMID:25943199

  2. Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus.

    PubMed

    Matassov, Demetrius; Marzi, Andrea; Latham, Terri; Xu, Rong; Ota-Setlik, Ayuko; Feldmann, Friederike; Geisbert, Joan B; Mire, Chad E; Hamm, Stefan; Nowak, Becky; Egan, Michael A; Geisbert, Thomas W; Eldridge, John H; Feldmann, Heinz; Clarke, David K

    2015-10-01

    Previously, recombinant vesicular stomatitis virus (rVSV) pseudotypes expressing Ebolavirus glycoproteins (GPs) in place of the VSV G protein demonstrated protection of nonhuman primates from lethal homologous Ebolavirus challenge. Those pseudotype vectors contained no additional attenuating mutations in the rVSV genome. Here we describe rVSV vectors containing a full complement of VSV genes and expressing the Ebola virus (EBOV) GP from an additional transcription unit. These rVSV vectors contain the same combination of attenuating mutations used previously in the clinical development pathway of an rVSV/human immunodeficiency virus type 1 vaccine. One of these rVSV vectors (N4CT1-EBOVGP1), which expresses membrane-anchored EBOV GP from the first position in the genome (GP1), elicited a balanced cellular and humoral GP-specific immune response in mice. Guinea pigs immunized with a single dose of this vector were protected from any signs of disease following lethal EBOV challenge, while control animals died in 7-9 days. Subsequently, N4CT1-EBOVGP1 demonstrated complete, single-dose protection of 2 macaques following lethal EBOV challenge. A single sham-vaccinated macaque died from disease due to EBOV infection. These results demonstrate that highly attenuated rVSV vectors expressing EBOV GP may provide safer alternatives to current EBOV vaccines. PMID:26109675

  3. First Italian Ebola virus disease case: management of hospital internal and external communication.

    PubMed

    Salce, Lorella; Barbato, Simona; Renna, Daniela; Bianchini, Francesco; Vaccaro, Paola; Mazzeo, Fabio; Gasparini, Annunziatina; Rizza, Claudio; Lanfranchi, Emanuele; Petrosillo, Nicola; Nicastri, Emanuele; Di Caro, Antonino; Capobianchi, Maria R; Puro, Vincenzo; Ippolito, Giuseppe

    2015-11-01

    On November 25, 2014, an Italian physician infected by Ebola virus in Sierra Leone was admitted to the "Lazzaro Spallanzani" National Institute for Infectious Diseases in Rome, Italy. He was the first Italian case and was successfully cured in 38 days. The staff responsible for communication had a critical role ensuring that this challenging mission went smoothly. The Institutional Press Office working together with the press offices of the Ministry of Health was able to provide the high level of expertise necessary within both medical and communication contexts. Communication strategy, tools and procedures adopted before and after the arrival of the patient are summarized. PMID:26485015

  4. Balancing the Duty to Treat Patients with Ebola Virus Disease with the Risks to Dialysis Personnel.

    PubMed

    Evans, Nicholas G

    2015-12-01

    In 2014, the author was invited to present at the American Society for Nephrology's annual conference in Philadelphia on the ethics of treating patients with Ebola virus disease. The argument was made that the status of health care workers, including nephrologists, was the dominant ethical standard that generated both the duty to treat and the conflicts between this commitment and other ethical commitments that arise in public health emergencies. Conflicts between duty to treat and personal safety, duty to community, and duty to colleagues were illustrated, and suggestions for designing ethics into medical practice were given. This article is a summary of that presentation. PMID:26251324

  5. Ebola Virus VP35 Interaction with Dynein LC8 Regulates Viral RNA Synthesis

    PubMed Central

    Luthra, Priya; Jordan, David S.; Leung, Daisy W.; Amarasinghe, Gaya K.

    2015-01-01

    Ebola virus VP35 inhibits alpha/beta interferon production and functions as a viral polymerase cofactor. Previously, the 8-kDa cytoplasmic dynein light chain (LC8) was demonstrated to interact with VP35, but the functional consequences were unclear. Here we demonstrate that the interaction is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Mutational analysis demonstrates that VP35 interaction is required for the functional effects of LC8. PMID:25741013

  6. Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976

    PubMed Central

    Hofmann-Winkler, Heike; Gnirß, Kerstin; Wrensch, Florian; Pöhlmann, Stefan

    2015-01-01

    The ongoing Ebola virus (EBOV) disease (EVD) epidemic in Western Africa is the largest EVD outbreak recorded to date and requires the rapid development and deployment of antiviral measures. The viral glycoprotein (GP) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention. However, it is unknown whether the GPs of the currently and previously circulating EBOVs use the same mechanisms for cellular entry and are thus susceptible to inhibition by the same antivirals and cellular defenses. Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. Thus, the viruses responsible for the ongoing EVD epidemic should be fully susceptible to established antiviral strategies targeting GP and cellular entry factors. PMID:25840443

  7. Ebola virus disease in the Democratic Republic of the Congo, 1976-2014.

    PubMed

    Rosello, Alicia; Mossoko, Mathias; Flasche, Stefan; Van Hoek, Albert Jan; Mbala, Placide; Camacho, Anton; Funk, Sebastian; Kucharski, Adam; Ilunga, Benoit Kebela; Edmunds, W John; Piot, Peter; Baguelin, Marc; Muyembe Tamfum, Jean-Jacques

    2015-01-01

    The Democratic Republic of the Congo has experienced the most outbreaks of Ebola virus disease since the virus' discovery in 1976. This article provides for the first time a description and a line list for all outbreaks in this country, comprising 996 cases. Compared to patients over 15 years old, the odds of dying were significantly lower in patients aged 5 to 15 and higher in children under five (with 100% mortality in those under 2 years old). The odds of dying increased by 11% per day that a patient was not hospitalised. Outbreaks with an initially high reproduction number, R (>3), were rapidly brought under control, whilst outbreaks with a lower initial R caused longer and generally larger outbreaks. These findings can inform the choice of target age groups for interventions and highlight the importance of both reducing the delay between symptom onset and hospitalisation and rapid national and international response. PMID:26525597

  8. The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway

    SciTech Connect

    Mulherkar, Nirupama; Raaben, Matthijs; Torre, Juan Carlos de la; Whelan, Sean P.; Chandran, Kartik

    2011-10-25

    Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. The route(s) of productive EBOV internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. Here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, GP, induces macropinocytic uptake of viral particles into cells. GP's highly-glycosylated mucin domain is dispensable for virus-induced macropinocytosis, arguing that interactions between other sequences in GP and the host cell surface are responsible. Unexpectedly, we also found a requirement for the large GTPase dynamin-2, which is proposed to be dispensable for several types of macropinocytosis. Our results provide evidence that EBOV uses an atypical dynamin-dependent macropinocytosis-like entry pathway to enter Vero cells, adherent human peripheral blood-derived monocytes, and a mouse dendritic cell line.

  9. Coverage of the Ebola Virus Disease Epidemic in Three Widely Circulated United States Newspapers: Implications for Preparedness and Prevention

    PubMed Central

    Basch, Corey H; Basch, Charles E; Redlener, Irwin

    2014-01-01

    Background:Widespread media attention about Ebola influences public awareness and interest, yet there is limited research on what aspects of Ebola have and have not been communicated through the media. Methods:We examined the nature and extent of coverage about Ebola in the three most widely circulated United States (U.S.) daily newspapers. Between September 17, 2014 and October 17, 2014, 301 articles about Ebola in The New York Times, USA Today, and The Wall Street Journal were identified and coded. Results:The most common topic was coverage of cases in the United States (39%), followed by the outbreak in Africa (33.6%). Conclusion:This is the first study to describe coverage of the Ebola epidemic in widely circulated U.S. newspapers. A substantial portion of the American public is concerned about being infected with Ebola virus disease (EVD). In this study, a large emphasis was placed on death tolls and the cases in the United States. Much more can be done to educate readers about relevant aspects of the Ebola epidemic, including how Ebola is and is not transmitted. PMID:25649411

  10. Clinical characteristics of 154 patients suspected of having Ebola virus disease in the Ebola holding center of Jui Government Hospital in Sierra Leone during the 2014 Ebola outbreak.

    PubMed

    Yan, T; Mu, J; Qin, E; Wang, Y; Liu, L; Wu, D; Jia, H; Li, Z; Guo, T; Wang, X; Qin, Y; Li, Y; Chen, S; Zhang, Y; Zhang, J; Wu, Y; Wang, S; Li, J

    2015-10-01

    This article sought to analyze the clinical features of 154 patients suspected of having Ebola virus disease (EVD) in an Ebola holding center in Sierra Leone from October 1 through November 9, 2014. We found that 108 of the 154 patients were confirmed with EVD. Eighty-five had known outcomes. Forty-nine of the 85 patients had been exposed to EVD. The average mortality rate was 60%. The mean interval between the onset of symptoms and hospitalization was 5.8 ± 3.3 days. The mean incubation period was 9.2 ± 6.7 days. Common symptoms of the EVD patients on admission were fatigue (85.2%), anorexia (84.3%), fever (75.9%), and headache (72.2%). Our data showed that the total symptoms of confirmed EVD patients were significantly higher than those of non-EVD patients (9 vs. 5.5; p < 0.001). The likelihood of EVD was 87.6% when a patient presented more than 6 out of 21 symptoms on admission. The survivors were significantly younger than non-survivors (24.0 ± 10.0 years vs. 31.3 ± 15.3 years; p = 0.016). The real-time polymerase chain reaction (PCR) analysis showed that, in the survivors, the virus load was significantly lower (Ct value: 25.2 ± 4.1 vs. 28.7 ± 5.7; p = 0.002). Multivariate analysis showed that age, fever, and viral load were independent predictors of mortality. Taken together, our data suggested that a cutoff of six symptoms could be used to predict patients with high or low risk of EVD. It seemed that age, fever, and viral load were the main risk factors associated with EVD mortality. PMID:26223324

  11. An Upstream Open Reading Frame Modulates Ebola Virus Polymerase Translation and Virus Replication

    PubMed Central

    Shabman, Reed S.; Hoenen, Thomas; Groseth, Allison; Jabado, Omar; Binning, Jennifer M.; Amarasinghe, Gaya K.; Feldmann, Heinz; Basler, Christopher F.

    2013-01-01

    Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5? and 3? untranslated regions (UTRs) present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV) 5?-UTRs lack internal ribosomal entry site function. However, the 5?-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5?-UTR derived from the viral polymerase (L) mRNA strongly suppressed translation of GFP compared to a ?-actin 5?-UTR. The L 5?-UTR is one of four viral genes to possess upstream AUGs (uAUGs), and ablation of each uAUG enhanced translation of the primary ORF (pORF), most dramatically in the case of the L 5?-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a “weak” Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2? was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10–100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target. PMID:23382680

  12. RNA Editing of the GP Gene of Ebola Virus is an Important Pathogenicity Factor.

    PubMed

    Volchkova, Valentina A; Dolnik, Olga; Martinez, Mikel J; Reynard, Olivier; Volchkov, Viktor E

    2015-10-01

    Synthesis of the surface glycoprotein GP of Ebola virus (EBOV) is dependent on transcriptional RNA editing, whereas direct expression of the GP gene results in synthesis of nonstructural secreted glycoprotein sGP. In this study, we investigate the role of RNA editing in the pathogenicity of EBOV using a guinea pig model and recombinant guinea pig-adapted EBOV containing mutations at the editing site, allowing expression of surface GP without the need for RNA editing, and also preventing synthesis of sGP. We demonstrate that the elimination of the editing site leads to EBOV attenuation in vivo, explained by lower virus spread caused by the higher virus cytotoxicity and, most likely, by an increased ability of the host defense systems to recognize and eliminate virus-infected cells. We also demonstrate that expression of sGP does not affect pathogenicity of EBOV in guinea pigs. In conclusion, data obtained indicate that downregulation of the level of surface GP expression through a mechanism of GP gene RNA editing plays an important role in the high pathogenicity of EBOV. PMID:26138826

  13. Ebola Virus Diseases in Africa: a commentary on its history, local and global context

    PubMed Central

    Awah, Paschal Kum; Boock, Alphonse Um; Kum, Kaiseuh Awah

    2015-01-01

    Ebola Virus Disease (EVD) started as a minor infection in Uganda in 1974 and has been frequent in Central Africa Region for the past 40 years. For over 40 years, Ebola was treated as an African disease, called a fever and known by other names where occurrences have been frequent. EVD has become a global public health threat following the most recent outbreak in West Africa. By December 31, 2014, Ebola has infected more than 23,500 people in West Africa and killed over 9,500, nearly all in the three worst-affected countries of Guinea, Liberia and Sierra Leone. It is transmitted through blood, vomit, diarrhea and other bodily fluids but cultural attributes associate its etiology to man-made and supernatural causes, hence stemming public health approaches to contain EVD difficult. Distrust and conflict between two healing systems are rife necessitating an African Model of EVD care and prevention. The African model remains indispensable to understand EVD and developing appropriate EVD containing approaches.

  14. The Role of Social Mobilization in Controlling Ebola Virus in Lofa County, Liberia

    PubMed Central

    Fast, Shannon M.; Mekaru, Sumiko; Brownstein, John S.; Postlethwaite, Timothy A.; Markuzon, Natasha

    2015-01-01

    The West Africa Ebola virus epidemic now appears to be coming to an end. In the proposed model, we simulate changes in population behavior that help to explain the observed transmission dynamics. We introduce an EVD transmission model accompanied by a model of social mobilization. The model was fit to Lofa County, Liberia through October 2014, using weekly counts of new cases reported by the US CDC. In simulation studies, we analyze the dynamics of the disease transmission with and without population behavior change, given the availability of beds in Ebola treatment units (ETUs) estimated from observed data. Only the model scenario that included individuals' behavioral change achieved a good fit to the observed case counts. Although the capacity of the Lofa County ETUs greatly increased in mid-August, our simulations show that the expansion was insufficient to alone control the outbreak. Modeling the entire outbreak without considering behavior change fit the data poorly, and extrapolating from early data without taking behavioral changes into account led to a prediction of exponential outbreak growth, contrary to the observed decline.  Education and awareness-induced behavior change in the population was instrumental in curtailing the Ebola outbreak in Lofa County and is likely playing an important role in stopping the West Africa epidemic altogether. PMID:26075140

  15. Transport and Management of Patients With Confirmed or Suspected Ebola Virus Disease.

    PubMed

    Isakov, Alexander; Miles, Wade; Gibbs, Shawn; Lowe, John; Jamison, Aaron; Swansiger, Raymond

    2015-09-01

    The foundation of safe care for patients with confirmed or suspected Ebola virus disease is effective infection control practice, which requires implementation of appropriate administrative policies, work practices, and environmental controls, accompanied by focused education, training, and supervision. In 2002, Emory University partnered with the Centers for Disease Control and Prevention to develop a capability for the evaluation and management of individuals with serious communicable disease. In 2005, the University of Nebraska developed a similar isolation capability. In each case, the hospitals partnered with emergency medical services (EMS) professionals to ensure safe out-of-hospital transport and management of their patients. The objectives of these hospital and out-of-hospital collaborations were to close education, training, and practice gaps to best facilitate the care for patients with serious communicable disease while ensuring the safety of the medics and the general public through meticulous implementation of infection control practices as recommended by Centers for Disease Control and Prevention. The description of practices implemented by EMS teams in these communities for the transport of patients with confirmed Ebola virus disease is shared so that others might more readily implement these practices, policies, and procedures as applicable to their mission requirements and system design. Transport of patients with relevant travel history and development of illness (persons under investigation) is also included. PMID:26003000

  16. In silico analysis suggests interaction between Ebola virus and the extracellular matrix

    PubMed Central

    Veljkovic, Veljko; Glisic, Sanja; Muller, Claude P.; Scotch, Matthew; Branch, Donald R.; Perovic, Vladimir R.; Sencanski, Milan; Veljkovic, Nevena; Colombatti, Alfonso

    2015-01-01

    The worst Ebola virus (EV) outbreak in history has hit Liberia, Sierra Leone and Guinea hardest and the trend lines in this crisis are grave, and now represents a global public health threat concern. Limited therapeutic and/or prophylactic options are available for people suffering from Ebola virus disease (EVD) and further complicate the situation. Previous studies suggested that the EV glycoprotein (GP) is the main determinant causing structural damage of endothelial cells that triggers the hemorrhagic diathesis, but molecular mechanisms underlying this phenomenon remains elusive. Using the informational spectrum method (ISM), a virtual spectroscopy method for analysis of the protein-protein interactions, the interaction of GP with endothelial extracellular matrix (ECM) was investigated. Presented results of this in silico study suggest that Elastin Microfibril Interface Located Proteins (EMILINs) are involved in interaction between GP and ECM. This finding could contribute to a better understanding of EV/endothelium interaction and its role in pathogenesis, prevention and therapy of EVD. PMID:25745423

  17. Ebola virus mediated infectivity is restricted in canine and feline cells.

    PubMed

    Han, Ziying; Bart, Stephen M; Ruthel, Gordon; Vande Burgt, Nathan H; Haines, Kathleen M; Volk, Susan W; Vite, Charles H; Freedman, Bruce D; Bates, Paul; Harty, Ronald N

    2016-01-15

    Ebolaviruses and marburgviruses belong to the Filoviridae family and often cause severe, fatal hemorrhagic fever in humans and non-human primates. The magnitude of the 2014 outbreak in West Africa and the unprecedented emergence of Ebola virus disease (EVD) in the United States underscore the urgency to better understand the dynamics of Ebola virus infection, transmission and spread. To date, the susceptibility and possible role of domestic animals and pets in the transmission cycle and spread of EVD remains unclear. We utilized infectious VSV recombinants and lentivirus pseudotypes expressing the EBOV surface glycoprotein (GP) to assess the permissiveness of canine and feline cells to EBOV GP-mediated entry. We observed a general restriction in EBOV-mediated infection of primary canine and feline cells. To address the entry mechanism, we used cells deficient in NPC1, a host protein implicated in EBOV entry, and a pharmacological blockade of cholesterol transport, to show that an NPC1-dependent mechanism of EBOV entry is conserved in canine and feline cells. These data demonstrate that cells of canine and feline origin are susceptible to EBOV GP mediated infection; however, infectivity of these cells is reduced significantly compared to controls. Moreover, these data provide new insights into the mechanism of EBOV GP mediated entry into cells of canine and feline origin. PMID:26711035

  18. Ebola Virus Diagnostics: The US Centers for Disease Control and Prevention Laboratory in Sierra Leone, August 2014 to March 2015.

    PubMed

    Flint, Mike; Goodman, Christin H; Bearden, Scott; Blau, Dianna M; Amman, Brian R; Basile, Alison J; Belser, Jessica A; Bergeron, Éric; Bowen, Michael D; Brault, Aaron C; Campbell, Shelley; Chakrabarti, Ayan K; Dodd, Kimberly A; Erickson, Bobbie R; Freeman, Molly M; Gibbons, Aridth; Guerrero, Lisa W; Klena, John D; Lash, R Ryan; Lo, Michael K; McMullan, Laura K; Momoh, Gbetuwa; Massally, James L; Goba, Augustine; Paddock, Christopher D; Priestley, Rachael A; Pyle, Meredith; Rayfield, Mark; Russell, Brandy J; Salzer, Johanna S; Sanchez, Angela J; Schuh, Amy J; Sealy, Tara K; Steinau, Martin; Stoddard, Robyn A; Taboy, Céline; Turnsek, Maryann; Wang, David; Zemtsova, Galina E; Zivcec, Marko; Spiropoulou, Christina F; Ströher, Ute; Towner, Jonathan S; Nichol, Stuart T; Bird, Brian H

    2015-10-01

    In August 2014, the Viral Special Pathogens Branch of the US Centers for Disease Control and Prevention established a field laboratory in Sierra Leone in response to the ongoing Ebola virus outbreak. Through March 2015, this laboratory tested >12 000 specimens from throughout Sierra Leone. We describe the organization and procedures of the laboratory located in Bo, Sierra Leone. PMID:26232439

  19. Airway Delivery of an Adenovirus-Based Ebola Virus Vaccine Bypasses Existing Immunity to Homologous Adenovirus in Nonhuman Primates

    PubMed Central

    Richardson, Jason S.; Pillet, Stéphane; Bello, Alexander J.

    2013-01-01

    Anti-adenovirus serotype 5 antibodies are capable of neutralizing adenovirus serotype 5-based vaccines. In mice and guinea pigs, intranasal delivery of adenovirus serotype 5-based vaccine bypasses induced adenovirus serotype 5 preexisting immunity, resulting in protection against species-adapted Ebola virus challenge. In this study, nonhuman primates were vaccinated with adenovirus serotype 5-based vaccine either intramuscularly or via the airway route (intranasally/intratracheally) in the presence or absence of adenovirus serotype 5 preexisting immunity. Immune responses were evaluated to determine the effect of both the vaccine delivery route and preexisting immunity before and after a lethal Ebola virus (Zaïre strain Kikwit 95) challenge. Intramuscular vaccination fully protected nonhuman primates in the absence of preexisting immunity, whereas the presence of preexisting immunity abrogated vaccine efficacy and resulted in complete mortality. In contrast, the presence of preexisting immunity to adenovirus serotype 5 did not alter the survival rate of nonhuman primates receiving the adenovirus serotype 5-based Ebola virus vaccine in the airway. This study shows that airway vaccination with adenovirus serotype 5-based Ebola virus vaccine can efficiently bypass preexisting immunity to adenovirus serotype 5 and induce protective immune responses, albeit at lower efficacy than that using an intramuscular vaccine delivery route. PMID:23302894

  20. Molecular Signature of the Ebola Virus Associated with the Fishermen Community Outbreak in Aberdeen, Sierra Leone, in February 2015.

    PubMed

    Capobianchi, Maria R; Gruber, Cesare E M; Carletti, Fabrizio; Meschi, Silvia; Castilletti, Concetta; Vairo, Francesco; Biava, Mirella; Minosse, Claudia; Strada, Gino; Portella, Gina; Miccio, Rossella; Minardi, Valeria; Rolla, Luca; Kamara, Abdul; Chillemi, Giovanni; Desideri, Alessandro; Di Caro, Antonino; Ippolito, Giuseppe

    2015-01-01

    We report the complete genome sequence of Ebola virus from a health worker linked to a cluster of cases occurring in the fishing community of Aberdeen, Sierra Leone (February 2015), which were characterized by unusually severe presentation. The sequence, clustering in the SL subclade 3.2.4, harbors mutations potentially relevant for pathogenesis. PMID:26404609

  1. The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field.

    PubMed

    van Griensven, Johan; De Weiggheleire, Anja; Delamou, Alexandre; Smith, Peter G; Edwards, Tansy; Vandekerckhove, Philippe; Bah, Elhadj Ibrahima; Colebunders, Robert; Herve, Isola; Lazaygues, Catherine; Haba, Nyankoye; Lynen, Lutgarde

    2016-01-01

    The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation. PMID:26261205

  2. The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field

    PubMed Central

    van Griensven, Johan; De Weiggheleire, Anja; Delamou, Alexandre; Smith, Peter G.; Edwards, Tansy; Vandekerckhove, Philippe; Bah, Elhadj Ibrahima; Colebunders, Robert; Herve, Isola; Lazaygues, Catherine; Haba, Nyankoye; Lynen, Lutgarde

    2016-01-01

    The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation. PMID:26261205

  3. Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection

    PubMed Central

    Ayithan, Natarajan; Bradfute, Steven B.; Anthony, Scott M.; Stuthman, Kelly S.; Bavari, Sina; Bray, Mike; Ozato, Keiko

    2015-01-01

    Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar-/- mice. Accordingly, EBOV infected Ifnar-/- mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar-/- mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host. PMID:25719445

  4. Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus.

    PubMed

    Barrientos, Laura G; O'Keefe, Barry R; Bray, Mike; Sanchez, Anthony; Gronenborn, Angela M; Boyd, Michael R

    2003-03-01

    Ebola virus (Ebo) causes severe hemorrhagic fever and high mortality in humans. There are currently no effective therapies. Here, we have explored potential anti-Ebo activity of the human immunodeficiency virus (HIV)-inactivating protein cyanovirin-N (CV-N). CV-N is known to potently inhibit the infectivity of a broad spectrum of HIV strains at the level of viral entry. This involves CV-N binding to N-linked high-mannose oligossacharides on the viral glycoprotein gp120. The Ebola envelope contains somewhat similar oligosaccharide constituents, suggesting possible susceptibility to inhibition by CV-N. Our initial results revealed that CV-N had both in vitro and in vivo antiviral activity against the Zaire strain of the Ebola virus (Ebo-Z). Addition of CV-N to the cell culture medium at the time of Ebo-Z infection inhibited the development of viral cytopathic effects (CPEs). CV-N also delayed the death of Ebo-Z-infected mice, both when given as a series of daily subcutaneous injections and when the virus was incubated ex vivo together with CV-N before inoculation into the mice. Furthermore, similar to earlier results with HIV gp120, CV-N bound with considerable affinity to the Ebola surface envelope glycoprotein, GP(1,2). Competition experiments with free oligosaccharides were consistent with the view that carbohydrate-mediated CV-N/GP(1,2) interactions involve oligosaccharides residing on the Ebola viral envelope. Overall, these studies broaden the range of viruses known to be inhibited by CV-N, and further implicate carbohydrate moieties on viral surface proteins as common viral molecular targets for this novel protein. PMID:12719006

  5. Public health response to commercial airline travel of a person with Ebola virus infection - United States, 2014.

    PubMed

    Regan, Joanna J; Jungerman, Robynne; Montiel, Sonia H; Newsome, Kimberly; Objio, Tina; Washburn, Faith; Roland, Efrosini; Petersen, Emily; Twentyman, Evelyn; Olaiya, Oluwatosin; Naughton, Mary; Alvarado-Ramy, Francisco; Lippold, Susan A; Tabony, Laura; McCarty, Carolyn L; Kinsey, Cara Bicking; Barnes, Meghan; Black, Stephanie; Azzam, Ihsan; Stanek, Danielle; Sweitzer, John; Valiani, Anita; Kohl, Katrin S; Brown, Clive; Pesik, Nicki

    2015-01-30

    Before the current Ebola epidemic in West Africa, there were few documented cases of symptomatic Ebola patients traveling by commercial airline, and no evidence of transmission to passengers or crew members during airline travel. In July 2014 two persons with confirmed Ebola virus infection who were infected early in the Nigeria outbreak traveled by commercial airline while symptomatic, involving a total of four flights (two international flights and two Nigeria domestic flights). It is not clear what symptoms either of these two passengers experienced during flight; however, one collapsed in the airport shortly after landing, and the other was documented to have fever, vomiting, and diarrhea on the day the flight arrived. Neither infected passenger transmitted Ebola to other passengers or crew on these flights. In October 2014, another airline passenger, a U.S. health care worker who had traveled domestically on two commercial flights, was confirmed to have Ebola virus infection. Given that the time of onset of symptoms was uncertain, an Ebola airline contact investigation in the United States was conducted. In total, follow-up was conducted for 268 contacts in nine states, including all 247 passengers from both flights, 12 flight crew members, eight cleaning crew members, and one federal airport worker (81 of these contacts were documented in a report published previously). All contacts were accounted for by state and local jurisdictions and followed until completion of their 21-day incubation periods. No secondary cases of Ebola were identified in this investigation, confirming that transmission of Ebola during commercial air travel did not occur. PMID:25632954

  6. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa.

    PubMed

    Carroll, Miles W; Matthews, David A; Hiscox, Julian A; Elmore, Michael J; Pollakis, Georgios; Rambaut, Andrew; Hewson, Roger; García-Dorival, Isabel; Bore, Joseph Akoi; Koundouno, Raymond; Abdellati, Saïd; Afrough, Babak; Aiyepada, John; Akhilomen, Patience; Asogun, Danny; Atkinson, Barry; Badusche, Marlis; Bah, Amadou; Bate, Simon; Baumann, Jan; Becker, Dirk; Becker-Ziaja, Beate; Bocquin, Anne; Borremans, Benny; Bosworth, Andrew; Boettcher, Jan Peter; Cannas, Angela; Carletti, Fabrizio; Castilletti, Concetta; Clark, Simon; Colavita, Francesca; Diederich, Sandra; Donatus, Adomeh; Duraffour, Sophie; Ehichioya, Deborah; Ellerbrok, Heinz; Fernandez-Garcia, Maria Dolores; Fizet, Alexandra; Fleischmann, Erna; Gryseels, Sophie; Hermelink, Antje; Hinzmann, Julia; Hopf-Guevara, Ute; Ighodalo, Yemisi; Jameson, Lisa; Kelterbaum, Anne; Kis, Zoltan; Kloth, Stefan; Kohl, Claudia; Korva, Miša; Kraus, Annette; Kuisma, Eeva; Kurth, Andreas; Liedigk, Britta; Logue, Christopher H; Lüdtke, Anja; Maes, Piet; McCowen, James; Mély, Stéphane; Mertens, Marc; Meschi, Silvia; Meyer, Benjamin; Michel, Janine; Molkenthin, Peter; Muñoz-Fontela, César; Muth, Doreen; Newman, Edmund N C; Ngabo, Didier; Oestereich, Lisa; Okosun, Jennifer; Olokor, Thomas; Omiunu, Racheal; Omomoh, Emmanuel; Pallasch, Elisa; Pályi, Bernadett; Portmann, Jasmine; Pottage, Thomas; Pratt, Catherine; Priesnitz, Simone; Quartu, Serena; Rappe, Julie; Repits, Johanna; Richter, Martin; Rudolf, Martin; Sachse, Andreas; Schmidt, Kristina Maria; Schudt, Gordian; Strecker, Thomas; Thom, Ruth; Thomas, Stephen; Tobin, Ekaete; Tolley, Howard; Trautner, Jochen; Vermoesen, Tine; Vitoriano, Inês; Wagner, Matthias; Wolff, Svenja; Yue, Constanze; Capobianchi, Maria Rosaria; Kretschmer, Birte; Hall, Yper; Kenny, John G; Rickett, Natasha Y; Dudas, Gytis; Coltart, Cordelia E M; Kerber, Romy; Steer, Damien; Wright, Callum; Senyah, Francis; Keita, Sakoba; Drury, Patrick; Diallo, Boubacar; de Clerck, Hilde; Van Herp, Michel; Sprecher, Armand; Traore, Alexis; Diakite, Mandiou; Konde, Mandy Kader; Koivogui, Lamine; Magassouba, N'Faly; Avši?-Županc, Tatjana; Nitsche, Andreas; Strasser, Marc; Ippolito, Giuseppe; Becker, Stephan; Stoecker, Kilian; Gabriel, Martin; Raoul, Hervé; Di Caro, Antonino; Wölfel, Roman; Formenty, Pierre; Günther, Stephan

    2015-08-01

    West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak. PMID:26083749

  7. Ebola Virus Outbreak Investigation, Sierra Leone, September 28–November 11, 2014

    PubMed Central

    Lu, Hui-Jun; Qian, Jun; Kargbo, David; Zhang, Xiao-Guang; Yang, Fan; Hu, Yi; Sun, Yang; Cao, Yu-Xi; Deng, Yong-Qiang; Su, Hao-Xiang; Dafae, Foday; Sun, Yu; Wang, Cheng-Yu; Nie, Wei-Min; Bai, Chang-Qing; Xia, Zhi-Ping; Liu, Kun; Kargbo, Brima; Gao, George F.

    2015-01-01

    During 2014–2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. The China Mobile Laboratory Testing Team was dispatched to support response efforts; during September 28–November 11, 2014, they conducted PCR testing on samples from 1,635 suspected EVD patients. Of those patients, 50.4% were positive, of whom 84.6% lived within a 3-km zone along main roads connecting rural towns and densely populated cities. The median time from symptom onset to testing was 5 days. At testing, 75.7% of the confirmed patients had fever, and 94.1% reported at least 1 gastrointestinal symptom; all symptoms, except rash and hemorrhage, were more frequent in confirmed than nonconfirmed patients. Virus loads were significantly higher in EVD patients with fever, diarrhea, fatigue, or headache. The case-fatality rate was lower among patients 15–44 years of age and with virus loads of <100,000 RNA copies/mL. These findings are key for optimizing EVD control and treatment measures. PMID:26485317

  8. Natural Immunity to Ebola Virus in the Syrian Hamster Requires Antibody Responses.

    PubMed

    Prescott, Joseph; Falzarano, Darryl; Feldmann, Heinz

    2015-10-01

    Most ebolaviruses can cause severe disease in humans and other primates, with high case fatality rates during human outbreaks. Although these viruses have been studied for almost 4 decades, little is know regarding the mechanisms by which they cause disease and what is important for protection or treatment after infection. Because of the sporadic nature of the outbreaks and difficulties accessing the populations affected by ebolaviruses, little is also known about what constitutes an appropriate immune response to infection in humans that survive infection. Such knowledge would allow a targeted approach to therapies. In contrast to humans, rodents are protected from disease on infection with ebolaviruses, although adapted versions of some of the viruses are lethal in mice, hamsters and guinea pigs. Using the recently described hamster model, along with T-cell depletion strategies, we show that CD4(+) T cells are required for natural immunity to Ebola virus infection and that CD4-dependent antibody responses are required for immunity in this model. PMID:25948862

  9. Experimental Respiratory Infection of Marmosets (Callithrix jacchus) With Ebola Virus Kikwit.

    PubMed

    Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Nunez, Alejandro; Salguero, Francisco J; Lever, Mark S

    2015-10-01

    Ebola virus (EBOV) causes a highly infectious and lethal hemorrhagic fever in primates with high fatality rates during outbreaks and EBOV may be exploited as a potential biothreat pathogen. There is therefore a need to develop and license appropriate medical countermeasures against this virus. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess vaccines or therapies against EBOV disease (EVD), initial susceptibility, lethality and pathogenesis studies were performed. Low doses of EBOV-Kikwit, between 4 and 27 times the 50% tissue culture infectious dose, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to EVD between 6 and 8 days after challenge. Typical signs of EVD were observed. Pathogenesis studies revealed that virus was isolated from the lungs of animals beginning on day 3 after challenge and from the liver, spleen and blood beginning on day 5. The most striking features were observed in animals that succumbed to infection, including high viral titers in all organs, increased levels of liver function enzymes and blood clotting times, decreased levels of platelets, multifocal moderate to severe hepatitis, and perivascular edema. PMID:26209682

  10. Ebola Virus Outbreak Investigation, Sierra Leone, September 28-November 11, 2014.

    PubMed

    Lu, Hui-Jun; Qian, Jun; Kargbo, David; Zhang, Xiao-Guang; Yang, Fan; Hu, Yi; Sun, Yang; Cao, Yu-Xi; Deng, Yong-Qiang; Su, Hao-Xiang; Dafae, Foday; Sun, Yu; Wang, Cheng-Yu; Nie, Wei-Min; Bai, Chang-Qing; Xia, Zhi-Ping; Liu, Kun; Kargbo, Brima; Gao, George F; Jiang, Jia-Fu

    2015-11-01

    During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. The China Mobile Laboratory Testing Team was dispatched to support response efforts; during September 28-November 11, 2014, they conducted PCR testing on samples from 1,635 suspected EVD patients. Of those patients, 50.4% were positive, of whom 84.6% lived within a 3-km zone along main roads connecting rural towns and densely populated cities. The median time from symptom onset to testing was 5 days. At testing, 75.7% of the confirmed patients had fever, and 94.1% reported at least 1 gastrointestinal symptom; all symptoms, except rash and hemorrhage, were more frequent in confirmed than nonconfirmed patients. Virus loads were significantly higher in EVD patients with fever, diarrhea, fatigue, or headache. The case-fatality rate was lower among patients 15-44 years of age and with virus loads of <100,000 RNA copies/mL. These findings are key for optimizing EVD control and treatment measures. PMID:26485317

  11. Small molecule inhibitors of ER a-glucosidases are active against multiple hemorrhagic fever viruses

    E-print Network

    : ER a-glucosidase Imino sugar Hemorrhagic fever virus Ebola virus Marburg virus a b s t r a c t Host of two of the most pathogenic hemorrhagic fever viruses, Marburg virus and Ebola virus, in mice. Our), Bunyaviridae member Rift Val- ley fever virus (RVFV), Filoviridae members Ebola virus (EBOV) and Marburg virus

  12. Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4+ T Cells

    PubMed Central

    Rao, Mangala; Bray, Mike; Alving, Carl R.; Jahrling, Peter; Matyas, Gary R.

    2002-01-01

    Ebola Zaire virus (EBO-Z) causes severe hemorrhagic fever in humans, with a high mortality rate. It is thought that a vaccine against EBO-Z may have to induce both humoral and cell-mediated immune responses to successfully confer protection. Because it is known that liposome-encapsulated antigens induce both antibody and cellular responses, we evaluated the protective efficacy of liposome-encapsulated irradiated EBO-Z [L(EV)], which contains all of the native EBO-Z proteins. In a series of experiments, mice immunized intravenously with L(EV) were completely protected (94/94 mice) against illness and death when they were challenged with a uniformly lethal mouse-adapted variant of EBO-Z. In contrast, only 55% of mice immunized intravenously with nonencapsulated irradiated virus (EV) survived challenge, and all became ill. Treatment with anti-CD4 antibodies before or during immunization with L(EV) eliminated protection, while treatment with anti-CD8 antibodies had no effect, thus indicating a requirement for CD4+ T lymphocytes for successful immunization. On the other hand, treatment with either anti-CD4 or anti-CD8 antibodies after immunization did not abolish the protection. After immunization with L(EV), antigen-specific gamma interferon (IFN?)-secreting CD4+ T lymphocytes were induced as analyzed by enzyme-linked immunospot assay. Anti-CD4 monoclonal antibody treatment abolished IFN? production (80 to 90% inhibition compared to that for untreated mice). Mice immunized with L(EV), but not EV, developed cytotoxic T lymphocytes specific to two peptides (amino acids [aa] 161 to 169 and aa 231 to 239) present in the amino-terminal end of the EBO-Z surface glycoprotein. Because of the highly successful results in the mouse model, L(EV) was also tested in three cynomolgus monkeys. Although immunization of the monkeys with L(EV)-induced virus-neutralizing antibodies against EBO-Z caused a slight delay in the onset of illness, it did not prevent death. PMID:12186901

  13. Digital Sensing and Sizing of Vesicular Stomatitis Virus Pseudotypes in Complex Media; A Model for Ebola and Marburg Detection

    PubMed Central

    Chinnala, Jyothsna; Goldberg, Bennett B.; Connor, John H.; Ünlü, M. Selim

    2015-01-01

    Rapid, sensitive, and direct label-free capture and characterization of nanoparticles from complex media such as blood or serum will broadly impact medicine and the life sciences. We demonstrate identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (VSV), defective VSV, and Ebola- and Marburg-pseudotyped VSV with high sensitivity and specificity. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of non-specifically bound particles to achieve a limit-of-detection (LOD) of 5×103 pfu/mL for the Ebola and Marburg VSV pseudotypes. We demonstrate the simultaneous detection of multiple viruses in a single sample (composed of serum or whole blood) for screening applications and uncompromised detection capabilities in samples contaminated with high levels of bacteria. By employing affinity-based capture, size discrimination, and a “digital” detection scheme to count single virus particles, we show that a robust and sensitive virus/nanoparticle sensing assay can been established for targets in complex samples. The nanoparticle microscopy system is termed the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) and is capable of high-throughput and rapid sizing of large numbers of biological nanoparticles on an antibody microarray for research and diagnostic applications. PMID:24840765

  14. Detection of Zaire Ebola virus by real-time reverse transcription-polymerase chain reaction, Sierra Leone, 2014.

    PubMed

    Liu, Licheng; Sun, Yang; Kargbo, Brima; Zhang, Chuntao; Feng, Huahua; Lu, Huijun; Liu, Wenseng; Wang, Chengyu; Hu, Yi; Deng, Yongqiang; Jiang, Jiafu; Kang, Xiaoping; Yang, Honglei; Jiang, Yongqiang; Yang, Yinhui; Kargbo, David; Qian, Jun; Chen, Weijun

    2015-09-15

    During the 2014 Ebola virus disease (EVD) outbreak, a real-time quantitative polymerase chain reaction was established to detect and identify the Zaire Ebola virus. We describe the use of this assay to screen 315 clinical samples from EVD suspected person in Sierra Leone. The detection rate in blood samples was 77.81% (207/266), and there were relatively higher detection rate (79.32% and 81.42%, respectively) during the first two weeks after onset of symptoms. In the two weeks that followed, the detection rate declined to 66.67% and 25.00%, respectively. There was the highest virus load at the first week and then decreased. The detection rate in swab samples was 89.79% (44/49). This may be benefit from the included patients. 46 of 49 swab samples were collected from died patients. Taken together, the results presented here indicate that the assay specifically and sensitively detects Zaire Ebola virus. PMID:26025458

  15. Translating Professional Obligations to Care for Patients With Ebola Virus Disease Into Practice in Nonepidemic Settings.

    PubMed

    Sugarman, Jeremy; Kass, Nancy; Rushton, Cynda H; Hughes, Mark T; Kirsch, Thomas D

    2015-10-01

    Determining how clinicians should meet their professional obligations to treat patients with Ebola virus disease in nonepidemic settings necessitates considering measures to minimize risks to clinicians, the context of care, and fairness. Minimizing risks includes providing appropriate equipment and training, implementing strategies for reducing exposure to infectious material, identifying a small number of centers to provide care, and determining which risky procedures should be used when they pose minimal likelihood of appreciable clinical benefit. Factors associated with the clinical environment, such as the local prevalence of the disease, the nature of the setting, and the availability of effective treatment, are also relevant to obligations to treat. Fairness demands that the best possible medical care be provided for health care professionals who become infected and that the rights and interests of relevant stakeholders be addressed through policy-making processes. Going forward it will be essential to learn from current approaches and to modify them based on data. PMID:25919348

  16. Experience on the management of the first imported Ebola virus disease case in Senegal

    PubMed Central

    Abdoulaye, Bousso; Moussa, Seydi; Daye, Ka; Boubakar, Badiane Seydou; Cor, Sarr Samba; Idrissa, Talla; Mamadou, Ndiaye El Hadj; Oumar, Ba Ibrahima; Tidiane, Ndour Cheikh; Selly, Ly Mamadou; Tacko, Diop Cheikh; Amadou, Diack Papa; Mandiaye, Loume; Mbaye, Diouf; Marie, Coll-Seck Awa

    2015-01-01

    The Ebola virus disease, as a first epidemic in West Africa, stands as the most deadly one throughout history. Guinea, the source of the epidemic, Sierra Leone and Liberia remain the most strongly affected. That epidemic thoroughly destabilized the health system of those countries. Following Nigeria, Senegal received its first imported case from the neighboring Republic of Guinea. In that sub regional psychotic context, such a situation has been handled and managed starting from the potential of a health system that is already suitably structured. The organization of the response, the management of the communication system and the rigorous monitoring of contacts have been decisive in the control of the epidemic. Our countries have to be prepared in order to face health threats, and that is the reason why the need to empower our health systems is important.

  17. [Ocular manifestations of Ebola virus disease: What we learned from the last epidemic].

    PubMed

    Rousseau, A; Labetoulle, M

    2015-10-01

    The Ebola virus disease (EVD) outbreak, which was declared as such in West Africa in March 2014, has become the largest EVD epidemic to date. It is the first time that EVD has been responsible for cases imported to the US as well as locally-acquired cases in Europe. Research on pathophysiology and treatment has been considerably accelerated, and more precise descriptions of various forms of ocular involvement have been obtained. Conjunctival hyperemia is often present during the acute phase, and it may contribute to the diagnosis of EVD in an epidemic context. During convalescence, ocular inflammatory manifestations may develop and can be caused by viral persistence in ocular tissue. Eye care providers need to be aware of the ophthalmic manifestations of EVD, sometimes several weeks after the acute infection, in order to recognize them and take appropriate safety precautions. PMID:26341021

  18. Virology. Mutation rate and genotype variation of Ebola virus from Mali case sequences.

    PubMed

    Hoenen, T; Safronetz, D; Groseth, A; Wollenberg, K R; Koita, O A; Diarra, B; Fall, I S; Haidara, F C; Diallo, F; Sanogo, M; Sarro, Y S; Kone, A; Togo, A C G; Traore, A; Kodio, M; Dosseh, A; Rosenke, K; de Wit, E; Feldmann, F; Ebihara, H; Munster, V J; Zoon, K C; Feldmann, H; Sow, S

    2015-04-01

    The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 × 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns. PMID:25814067

  19. Ebola virus disease and Marburg disease in pregnancy: a review and management considerations for filovirus infection.

    PubMed

    Bebell, Lisa M; Riley, Laura E

    2015-06-01

    The largest-ever recorded outbreak of viral hemorrhagic fever is ongoing. As a result of the epidemic and rural nature of outbreaks, little is published about the Filovirus infections Ebola virus disease and Marburg disease in pregnancy. This review of viral hemorrhagic fever focusing on Marburg and Ebola uses knowledge of disease in nonpregnant individuals and pregnancy-specific data to inform management for pregnant women. Filovirus infection presentation is similar between pregnant and nonpregnant patients, although infections may be more severe in pregnancy. Although labeled as hemorrhagic fevers, Marburg and Ebola do not commonly cause gross bleeding and should be conceptualized as diseases of high gastrointestinal losses. Early, aggressive supportive care is the mainstay of Filovirus infection management with massive fluid resuscitation as the key management principle. Patients often require 5-10 L or more per day of intravenous or oral fluid to maintain circulating blood volume in the setting of ongoing gastrointestinal loss. Fluid shifts warrant aggressive monitoring and correction of potassium levels and acid-base disturbances to prevent life-threatening arrhythmias and metabolic complications. Regardless of maternal survival, fetal loss rates are nearly 100% in Filovirus infection, likely resulting from unchecked transplacental and hematogenous viral spread. High fetal loss rates support the placenta as a difficult-to-eradicate Filovirus infection reservoir. In conclusion, the management of Filovirus infection in pregnancy should focus on stabilizing the mother with intensive monitoring and aggressive fluid and electrolyte repletion as well as maintaining strict infection control to minimize transmission to others. PMID:26000499

  20. Social pathways for Ebola virus disease in rural Sierra Leone, and some implications for containment.

    PubMed

    Richards, Paul; Amara, Joseph; Ferme, Mariane C; Kamara, Prince; Mokuwa, Esther; Sheriff, Amara Idara; Suluku, Roland; Voors, Maarten

    2015-04-01

    The current outbreak of Ebola Virus Disease in Upper West Africa is the largest ever recorded. Molecular evidence suggests spread has been almost exclusively through human-to-human contact. Social factors are thus clearly important to understand the epidemic and ways in which it might be stopped, but these factors have so far been little analyzed. The present paper focuses on Sierra Leone, and provides cross sectional data on the least understood part of the epidemic-the largely undocumented spread of Ebola in rural areas. Various forms of social networking in rural communities and their relevance for understanding pathways of transmission are described. Particular attention is paid to the relationship between marriage, funerals and land tenure. Funerals are known to be a high-risk factor for infection. It is suggested that more than a shift in awareness of risks will be needed to change local patterns of behavior, especially in regard to funerals, since these are central to the consolidation of community ties. A concluding discussion relates the information presented to plans for halting the disease. Local consultation and access are seen as major challenges to be addressed. PMID:25886400

  1. Hospital preparedness for Ebola virus disease: a training course in the Philippines

    PubMed Central

    Carlos, Celia; Capistrano, Rowena; Tobora, Charissa Fay; delos Reyes, Mari Rose; Lupisan, Socorro; Corpuz, Aura; Aumentado, Charito; Suy, Lyndon Lee; Hall, Julie; Donald, Julian; Counahan, Megan; Curless, Melanie S; Rhymer, Wendy; Gavin, Melanie; Lynch, Chelsea; Black, Meredith A; Anduyon, Albert D; Buttner, Petra

    2015-01-01

    Objective To develop, teach and evaluate a training workshop that could rapidly prepare large numbers of health professionals working in hospitals in the Philippines to detect and safely manage Ebola virus disease (EVD). The strategy was to train teams (each usually with five members) of key health professionals from public, private and local government hospitals across the Philippines who could then guide Ebola preparedness in their hospitals. Methods The workshop was developed collaboratively by the Philippine Department of Health and the country office of the World Health Organization. It was evaluated using a pre- and post-workshop test and two evaluation forms. ?2 tests and linear regression analyses were conducted comparing pre- and post-workshop test results. Results A three-day workshop was developed and used to train 364 doctors, nurses and medical technologists from 78 hospitals across the Philippines in three initial batches. Knowledge about EVD increased significantly (P < 0.009) although knowledge on transmission remained suboptimal. Confidence in managing EVD increased significantly (P = 0.018) with 96% of participants feeling more prepared to safely manage EVD cases. Discussion: The three-day workshop to prepare hospital staff for EVD was effective at increasing the level of knowledge about EVD and the level of confidence in managing EVD safely. This workshop could be adapted for use as baseline training in EVD in other developing countries to prepare large numbers of hospital staff to rapidly detect, isolate and safely manage EVD cases. PMID:25960920

  2. Learning from the challenges of Ebola Virus Disease contact tracers in Sierra Leone, February, 2015

    PubMed Central

    Ilesanmi, Olayinka Stephen

    2015-01-01

    Introduction Sierra Leone was in the process of strengthening tracing of Ebola Virus Disease (EVD) contact with training of contact tracers, continuous mentoring and monitoring, supervision and continuous support. This was through various national and international organizations. This study aimed at identifying the challenges of contact tracers with a view of improving contact tracing activities in Tonkolili District, Sierra Leone. Methods In-depth interview was conducted among contact tracers who were actively involved in contact tracing within the 4 weeks preceding the interview. In-depth interview guide was used to interview the contact tracers. Questions were asked about the state of EVD outbreak, challenges of contact tracing, ways to improving contact tracers activities and ways to ensure community participation and follow up action. Results A total of 12 Contact tracers were interviewed. Most of the contact tracers saw the lifting of ban by the Government on movement as a delay to stopping the outbreak. Some of them were being threatened by their communities and insulted. Some communities with EVD cases felt it was no longer in Sierra Leone and that the contact tracers were the ones infecting the people with Ebola. More than 80% of the participants indicated that retraining of contact tracers and re-orientation of community members would help in putting a stop to the outbreak. Conclusion All participants indicated interest in improving their activities and performance. They suggested that more social mobilization is needed to ensure the cooperation of their communities.

  3. Social Pathways for Ebola Virus Disease in Rural Sierra Leone, and Some Implications for Containment

    PubMed Central

    Richards, Paul; Amara, Joseph; Ferme, Mariane C.; Kamara, Prince; Mokuwa, Esther; Sheriff, Amara Idara; Suluku, Roland; Voors, Maarten

    2015-01-01

    The current outbreak of Ebola Virus Disease in Upper West Africa is the largest ever recorded. Molecular evidence suggests spread has been almost exclusively through human-to-human contact. Social factors are thus clearly important to understand the epidemic and ways in which it might be stopped, but these factors have so far been little analyzed. The present paper focuses on Sierra Leone, and provides cross sectional data on the least understood part of the epidemic—the largely undocumented spread of Ebola in rural areas. Various forms of social networking in rural communities and their relevance for understanding pathways of transmission are described. Particular attention is paid to the relationship between marriage, funerals and land tenure. Funerals are known to be a high-risk factor for infection. It is suggested that more than a shift in awareness of risks will be needed to change local patterns of behavior, especially in regard to funerals, since these are central to the consolidation of community ties. A concluding discussion relates the information presented to plans for halting the disease. Local consultation and access are seen as major challenges to be addressed. PMID:25886400

  4. Global health security: the wider lessons from the west African Ebola virus disease epidemic.

    PubMed

    Heymann, David L; Chen, Lincoln; Takemi, Keizo; Fidler, David P; Tappero, Jordan W; Thomas, Mathew J; Kenyon, Thomas A; Frieden, Thomas R; Yach, Derek; Nishtar, Sania; Kalache, Alex; Olliaro, Piero L; Horby, Peter; Torreele, Els; Gostin, Lawrence O; Ndomondo-Sigonda, Margareth; Carpenter, Daniel; Rushton, Simon; Lillywhite, Louis; Devkota, Bhimsen; Koser, Khalid; Yates, Rob; Dhillon, Ranu S; Rannan-Eliya, Ravi P

    2015-05-01

    The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security--its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing. PMID:25987157

  5. Interpretation of Negative Molecular Test Results in Patients With Suspected or Confirmed Ebola Virus Disease: Report of Two Cases

    PubMed Central

    Edwards, Jeffrey K.; Kleine, Christian; Munster, Vincent; Giuliani, Ruggero; Massaquoi, Moses; Sprecher, Armand; Chertow, Daniel S.

    2015-01-01

    Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) is the most sensitive quantitative diagnostic assay for detection of Ebola virus in multiple body fluids. Despite the strengths of this assay, we present 2 cases of Ebola virus disease (EVD) and highlight the potential for false-negative results during the early and late stages of EVD. The first case emphasizes the low negative-predictive value of qRT-PCR during incubation and the early febrile stage of EVD, and the second case emphasizes the potential for false-negative results during recovery and late neurologic complications of EVD. Careful interpretation of test results are needed to guide difficult admission and discharge decisions in suspected or confirmed EVD. PMID:26512358

  6. Interpretation of Negative Molecular Test Results in Patients With Suspected or Confirmed Ebola Virus Disease: Report of Two Cases.

    PubMed

    Edwards, Jeffrey K; Kleine, Christian; Munster, Vincent; Giuliani, Ruggero; Massaquoi, Moses; Sprecher, Armand; Chertow, Daniel S

    2015-12-01

    Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) is the most sensitive quantitative diagnostic assay for detection of Ebola virus in multiple body fluids. Despite the strengths of this assay, we present 2 cases of Ebola virus disease (EVD) and highlight the potential for false-negative results during the early and late stages of EVD. The first case emphasizes the low negative-predictive value of qRT-PCR during incubation and the early febrile stage of EVD, and the second case emphasizes the potential for false-negative results during recovery and late neurologic complications of EVD. Careful interpretation of test results are needed to guide difficult admission and discharge decisions in suspected or confirmed EVD. PMID:26512358

  7. Contact Tracing Activities during the Ebola Virus Disease Epidemic in Kindia and Faranah, Guinea, 2014

    PubMed Central

    Taylor, Melanie M.; Dee, Jacob; Hakim, Avi; Cantey, Paul; Lim, Travis; Bah, Hawa; Camara, Sékou Mohamed; Ndongmo, Clement B.; Togba, Mory; Touré, Leonie Yvonne; Bilivogui, Pepe; Sylla, Mohammed; Kinzer, Michael; Coronado, Fátima; Tongren, Jon Eric; Swaminathan, Mahesh; Mandigny, Lise; Diallo, Boubacar; Seyler, Thomas; Rondy, Marc; Rodier, Guénaël; Perea, William A.; Dahl, Benjamin

    2015-01-01

    The largest recorded Ebola virus disease epidemic began in March 2014; as of July 2015, it continued in 3 principally affected countries: Guinea, Liberia, and Sierra Leone. Control efforts include contact tracing to expedite identification of the virus in suspect case-patients. We examined contact tracing activities during September 20–December 31, 2014, in 2 prefectures of Guinea using national and local data about case-patients and their contacts. Results show less than one third of case-patients (28.3% and 31.1%) were registered as contacts before case identification; approximately two thirds (61.1% and 67.7%) had no registered contacts. Time to isolation of suspected case-patients was not immediate (median 5 and 3 days for Kindia and Faranah, respectively), and secondary attack rates varied by relationships of persons who had contact with the source case-patient and the type of case-patient to which a contact was exposed. More complete contact tracing efforts are needed to augment control of this epidemic. PMID:26488116

  8. Buffer AVL Alone Does Not Inactivate Ebola Virus in a Representative Clinical Sample Type.

    PubMed

    Smither, Sophie J; Weller, Simon A; Phelps, Amanda; Eastaugh, Lin; Ngugi, Sarah; O'Brien, Lyn M; Steward, Jackie; Lonsdale, Steve G; Lever, Mark S

    2015-10-01

    Rapid inactivation of Ebola virus (EBOV) is crucial for high-throughput testing of clinical samples in low-resource, outbreak scenarios. The EBOV inactivation efficacy of Buffer AVL (Qiagen) was tested against marmoset serum (EBOV concentration of 1 × 10(8) 50% tissue culture infective dose per milliliter [TCID50 · ml(-1)]) and murine blood (EBOV concentration of 1 × 10(7) TCID50 · ml(-1)) at 4:1 vol/vol buffer/sample ratios. Posttreatment cell culture and enzyme-linked immunosorbent assay (ELISA) analysis indicated that treatment with Buffer AVL did not inactivate EBOV in 67% of samples, indicating that Buffer AVL, which is designed for RNA extraction and not virus inactivation, cannot be guaranteed to inactivate EBOV in diagnostic samples. Murine blood samples treated with ethanol (4:1 [vol/vol] ethanol/sample) or heat (60°C for 15 min) also showed no viral inactivation in 67% or 100% of samples, respectively. However, combined Buffer AVL and ethanol or Buffer AVL and heat treatments showed total viral inactivation in 100% of samples tested. The Buffer AVL plus ethanol and Buffer AVL plus heat treatments were also shown not to affect the extraction of PCR quality RNA from EBOV-spiked murine blood samples. PMID:26179307

  9. Contact Tracing Activities during the Ebola Virus Disease Epidemic in Kindia and Faranah, Guinea, 2014.

    PubMed

    Dixon, Meredith G; Taylor, Melanie M; Dee, Jacob; Hakim, Avi; Cantey, Paul; Lim, Travis; Bah, Hawa; Camara, Sékou Mohamed; Ndongmo, Clement B; Togba, Mory; Touré, Leonie Yvonne; Bilivogui, Pepe; Sylla, Mohammed; Kinzer, Michael; Coronado, Fátima; Tongren, Jon Eric; Swaminathan, Mahesh; Mandigny, Lise; Diallo, Boubacar; Seyler, Thomas; Rondy, Marc; Rodier, Guénaël; Perea, William A; Dahl, Benjamin

    2015-11-01

    The largest recorded Ebola virus disease epidemic began in March 2014; as of July 2015, it continued in 3 principally affected countries: Guinea, Liberia, and Sierra Leone. Control efforts include contact tracing to expedite identification of the virus in suspect case-patients. We examined contact tracing activities during September 20-December 31, 2014, in 2 prefectures of Guinea using national and local data about case-patients and their contacts. Results show less than one third of case-patients (28.3% and 31.1%) were registered as contacts before case identification; approximately two thirds (61.1% and 67.7%) had no registered contacts. Time to isolation of suspected case-patients was not immediate (median 5 and 3 days for Kindia and Faranah, respectively), and secondary attack rates varied by relationships of persons who had contact with the source case-patient and the type of case-patient to which a contact was exposed. More complete contact tracing efforts are needed to augment control of this epidemic. PMID:26488116

  10. Taking the bull by the horns: Ethical considerations in the design and implementation of an Ebola virus therapy trial.

    PubMed

    Kombe, Francis; Folayan, Morenike O; Ambe, Jennyfer; Igonoh, Adaora; Abayomi, Akin

    2016-01-01

    Ebola virus is categorized as one of the most dangerous pathogens in the world. Although there is no known cure for Ebola virus, there is some evidence that the severity of the disease can be curtailed using plasma from survivors. Although there is a general consensus on the importance of research, methodological and ethical challenges for conducting research in an emergency situation have been identified. Performing clinical trials is important, especially for health conditions that are of public health significance (including rare epidemics) to develop new therapies as well as to test the efficacy and effectiveness of new interventions. However, routine clinical trial procedures can be difficult to apply in emergency public health crises hence require a consideration of alternative approaches on how therapies in these situations are tested and brought to the market. This paper examines some of the ethical issues that arise when conducting clinical trials during a highly dangerous pathogen outbreak, with a special focus on the Ebola virus outbreak in West Africa. The issues presented here come from a review of a protocol that was submitted to the Global Emerging Pathogens Treatment Consortium (GET). In reviewing the proposal, which was about conducting a clinical trial to evaluate the safety and efficacy of using convalescent plasma in the management of Ebola virus disease, the authors deliberated on various issues, which were documented as minutes and later used as a basis for this paper. The experiences and reflections shared by the authors, who came from different regions and disciplines across Africa, present wide-ranging perspectives on the conduct of clinical trials during a dangerous disease outbreak in a resource-poor setting. PMID:26653137

  11. Ebola from emergence to epidemic: the virus and the disease, global preparedness and perspectives.

    PubMed

    Dhama, Kuldeep; Malik, Yashpal Singh; Malik, Satya Veer Singh; Singh, Raj Kumar

    2015-05-01

    Humans constantly encounter threats from many infectious, zoonotic, and devastating pathogens. Outbreaks of severe acute respiratory syndrome (SARS), bird flu, and swine flu posing pandemic threats have compelled health agencies to follow global preparedness for combating the emerging deadly pathogens. The outbreak in West Africa of highly contagious Ebola viral disease (EVD) that started in Guinea in December 2013, assumed global proportions to become the largest outbreak of EVD and the most prominent international health concern. With fatality rates of nearly 50%-90%, it has claimed, as of 11 April 2015, 10,619 human lives out of a total of 25,626 cases reported worldwide. Ebola virus (EBOV), a member of Filoviridae family, is associated with severe, often lethal, hemorrhagic fever disease in humans and animals. The animal hosts, including non-human primates and reservoir hosts (fruit bats), play a significant role in transmission and maintenance of EBOV in nature. Although no approved vaccine for the prevention of EVD currently exists, disease control can be greatly enhanced by timely laboratory confirmation through blood tests using enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Adherence to strict sanitary and hygienic measures, monitoring and surveillance of EBOV, as well as quarantine checks on international trade, transport, and visitors from affected countries are mandatory to prevent and control the spread of EVD. This review describes the salient properties of EBOV and the development of novel diagnostics, vaccines, and control strategies for this emerging disease of high public health concern and international emergency. PMID:25989163

  12. Ebola Virus Outbreak among Wild Chimpanzees Living in a Rain Forest of Co^te Pierre Formenty, Christophe Boesch, Monique Wyers, World Health Organization (WHO), TaiF Forest Project, and Centre

    E-print Network

    S120 Ebola Virus Outbreak among Wild Chimpanzees Living in a Rain Forest of Co^te d'Ivoire Pierre, Paris, France An outbreak of Ebola in nature is described for the first time. During a few weeks. Laboratory procedures included histology, immunohistochemistry, bacteriology, and serology. Ebola

  13. A Multi-Site Knowledge Attitude and Practice Survey of Ebola Virus Disease in Nigeria

    PubMed Central

    Iliyasu, Garba; Ogoina, Dimie; Otu, Akan A.; Dayyab, Farouq M.; Ebenso, Bassey; Otokpa, Daniel; Rotifa, Stella; Olomo, Wisdom T.; Habib, Abdulrazaq G.

    2015-01-01

    Background The 2014 Ebola Virus Disease (EVD) outbreak was characterised by fear, misconceptions and irrational behaviours. We conducted a knowledge attitude and practice survey of EVD in Nigeria to inform implementation of effective control measures. Methods Between July 30th and September 30th 2014, we undertook a cross sectional study on knowledge, attitude and practice (KAP) of Ebola Virus Disease (EVD) among adults of the general population and healthcare workers (HCW) in three states of Nigeria, namely Bayelsa, Cross River and Kano states. Demographic information and data on KAP were obtained using a self-administered standardized questionnaire. The percentage KAP scores were categorised as good and poor. Independent predictors of good knowledge of EVD were ascertained using a binary logistic regression model. Results Out of 1035 study participants with median age of 32 years, 648 (62.6%) were males, 846 (81.7%) had tertiary education and 441 (42.6%) were HCW. There were 218, 239 and 578 respondents from Bayelsa, Cross River and Kano states respectively. The overall median percentage KAP scores and interquartile ranges (IQR) were 79.46% (15.07%), 95.0% (33.33%) and 49.95% (37.50%) respectively. Out of the 1035 respondents, 470 (45.4%), 544(52.56%) and 252 (24.35%) had good KAP of EVD defined using 80%, 90% and 70% score cut-offs respectively. Independent predictors of good knowledge of EVD were being a HCW (Odds Ratio-OR-2.89, 95% Confidence interval-CI of 1.41–5.90), reporting ‘moderate to high fear of EVD’ (OR-2.15, 95% CI-(1.47–3.13) and ‘willingness to modify habit’ (OR-1.68, 95% CI-1.23–2.30). Conclusion Our results reveal suboptimal EVD-related knowledge, attitude and practice among adults in Nigeria. To effectively control future outbreaks of EVD in Nigeria, there is a need to implement public sensitization programmes that improve understanding of EVD and address EVD-related myths and misconceptions, especially among the general population. PMID:26317535

  14. Evaluating Clinical Trial Designs for Investigational Treatments of Ebola Virus Disease

    PubMed Central

    Cooper, Ben S.; Boni, Maciej F.; Pan-ngum, Wirichada; Day, Nicholas P. J.; Horby, Peter W.; Olliaro, Piero; Lang, Trudie; White, Nicholas J.; White, Lisa J.; Whitehead, John

    2015-01-01

    Background Experimental treatments for Ebola virus disease (EVD) might reduce EVD mortality. There is uncertainty about the ability of different clinical trial designs to identify effective treatments, and about the feasibility of implementing individually randomised controlled trials during an Ebola epidemic. Methods and Findings A treatment evaluation programme for use in EVD was devised using a multi-stage approach (MSA) with two or three stages, including both non-randomised and randomised elements. The probabilities of rightly or wrongly recommending the experimental treatment, the required sample size, and the consequences for epidemic outcomes over 100 d under two epidemic scenarios were compared for the MSA, a sequential randomised controlled trial (SRCT) with up to 20 interim analyses, and, as a reference case, a conventional randomised controlled trial (RCT) without interim analyses. Assuming 50% 14-d survival in the population treated with the current standard of supportive care, all designs had similar probabilities of identifying effective treatments correctly, while the MSA was less likely to recommend treatments that were ineffective. The MSA led to a smaller number of cases receiving ineffective treatments and faster roll-out of highly effective treatments. For less effective treatments, the MSA had a high probability of including an RCT component, leading to a somewhat longer time to roll-out or rejection. Assuming 100 new EVD cases per day, the MSA led to between 6% and 15% greater reductions in epidemic mortality over the first 100 d for highly effective treatments compared to the SRCT. Both the MSA and SRCT led to substantially fewer deaths than a conventional RCT if the tested interventions were either highly effective or harmful. In the proposed MSA, the major threat to the validity of the results of the non-randomised components is that referral patterns, standard of care, or the virus itself may change during the study period in ways that affect mortality. Adverse events are also harder to quantify without a concurrent control group. Conclusions The MSA discards ineffective treatments quickly, while reliably providing evidence concerning effective treatments. The MSA is appropriate for the clinical evaluation of EVD treatments. PMID:25874579

  15. Evaluating Environmental Persistence and Disinfection of the Ebola Virus Makona Variant

    PubMed Central

    Cook, Bradley W. M.; Cutts, Todd A.; Nikiforuk, Aidan M.; Poliquin, Philip Guillaume; Court, Deborah A.; Strong, James E.; Theriault, Steven S.

    2015-01-01

    Background: The current disease outbreak caused by the Ebola virus Makona variant (EBOV/Mak) has led to unprecedented morbidity and lethality given its geographic reach and sustained transmission. Sodium hypochlorite and ethanol are well-accepted decontamination agents, however little published evidence supports the selection of appropriate concentrations and contact times. The present study addresses the environmental robustness of EBOV/Mak and evaluates the effectiveness of sodium hypochlorite and ethanol as disinfectants. Methods: EBOV/Mak was suspended in a simulated organic soil load and dried onto surfaces. Viability was measured at 1 hour, 24 hours, 72 hours, and 192 hours. For the evaluation of disinfectants, EBOV/Mak in a simulated organic soil was dried onto stainless steel carriers and disinfected with 0.01% (v/v), 0.1% (v/v), 0.5% (v/v) and 1% (v/v) sodium hypochlorite solutions or 67% (v/v) ethanol at contact times of 1, 5 or 10 minutes. Results: EBOV/Mak persisted longer on steel and plastic surfaces (192 hours) than cotton (<24 hours). Dilute sodium hypochlorite (0.01% and 0.1%) showed little antiviral action, whereas 0.5% and 1% sodium hypochlorite solutions demonstrated recoverable virus at one minute but sterilized surfaces in five minutes. Disinfection with 67% ethanol did not fully clear infectious virions from 3/9 carriers at 1 minute but sterilized all carriers at 5 and 10 minutes. Conclusions: Sodium hypochlorite and ethanol effectively decontaminate EBOV/Mak suspended in a simulated organic load; however, selection of concentration and contact time proves critical. PMID:25875372

  16. Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone.

    PubMed

    Tong, Yi-Gang; Shi, Wei-Feng; Liu, Di; Qian, Jun; Liang, Long; Bo, Xiao-Chen; Liu, Jun; Ren, Hong-Guang; Fan, Hang; Ni, Ming; Sun, Yang; Jin, Yuan; Teng, Yue; Li, Zhen; Kargbo, David; Dafae, Foday; Kanu, Alex; Chen, Cheng-Chao; Lan, Zhi-Heng; Jiang, Hui; Luo, Yang; Lu, Hui-Jun; Zhang, Xiao-Guang; Yang, Fan; Hu, Yi; Cao, Yu-Xi; Deng, Yong-Qiang; Su, Hao-Xiang; Sun, Yu; Liu, Wen-Sen; Wang, Zhuang; Wang, Cheng-Yu; Bu, Zhao-Yang; Guo, Zhen-Dong; Zhang, Liu-Bo; Nie, Wei-Min; Bai, Chang-Qing; Sun, Chun-Hua; An, Xiao-Ping; Xu, Pei-Song; Zhang, Xiang-Li-Lan; Huang, Yong; Mi, Zhi-Qiang; Yu, Dong; Yao, Hong-Wu; Feng, Yong; Xia, Zhi-Ping; Zheng, Xue-Xing; Yang, Song-Tao; Lu, Bing; Jiang, Jia-Fu; Kargbo, Brima; He, Fu-Chu; Gao, George F; Cao, Wu-Chun

    2015-08-01

    A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics. PMID:25970247

  17. ALIX Rescues Budding of a Double PTAP/PPEY L-Domain Deletion Mutant of Ebola VP40: A Role for ALIX in Ebola Virus Egress.

    PubMed

    Han, Ziying; Madara, Jonathan J; Liu, Yuliang; Liu, Wenbo; Ruthel, Gordon; Freedman, Bruce D; Harty, Ronald N

    2015-10-01

    Ebola (EBOV) is an enveloped, negative-sense RNA virus belonging to the family Filoviridae that causes hemorrhagic fever syndromes with high-mortality rates. To date, there are no licensed vaccines or therapeutics to control EBOV infection and prevent transmission. Consequently, the need to better understand the mechanisms that regulate virus transmission is critical to developing countermeasures. The EBOV VP40 matrix protein plays a central role in late stages of virion assembly and egress, and independent expression of VP40 leads to the production of virus-like particles (VLPs) by a mechanism that accurately mimics budding of live virus. VP40 late (L) budding domains mediate efficient virus-cell separation by recruiting host ESCRT and ESCRT-associated proteins to complete the membrane fission process. L-domains consist of core consensus amino acid motifs including PPxY, P(T/S)AP, and YPx(n)L/I, and EBOV VP40 contains overlapping PPxY and PTAP motifs whose interactions with Nedd4 and Tsg101, respectively, have been characterized extensively. Here, we present data demonstrating for the first time that EBOV VP40 possesses a third L-domain YPx(n)L/I consensus motif that interacts with the ESCRT-III protein Alix. We show that the YPx(n)L/I motif mapping to amino acids 18-26 of EBOV VP40 interacts with the Alix Bro1-V fragment, and that siRNA knockdown of endogenous Alix expression inhibits EBOV VP40 VLP egress. Furthermore, overexpression of Alix Bro1-V rescues VLP production of the budding deficient EBOV VP40 double PTAP/PPEY L-domain deletion mutant to wild-type levels. Together, these findings demonstrate that EBOV VP40 recruits host Alix via a YPx(n)L/I motif that can function as an alternative L-domain to promote virus egress. PMID:25786915

  18. Clinical Inquiries Received by CDC Regarding Suspected Ebola Virus Disease in Children--United States, July 9, 2014-January 4, 2015.

    PubMed

    Goodman, Alyson B; Meites, Elissa; Anstey, Erica H; Fullerton, Kathleen E; Jayatilleke, Achala; Ruben, Wendy; Koumans, Emily; Oster, Alexandra M; Karwowski, Mateusz P; Dziuban, Eric; Kirkcaldy, Robert D; Glover, Maleeka; Lowe, Luis; Peacock, Georgina; Mahon, Barbara; Griese, Stephanie E

    2015-09-18

    The 2014–2015 Ebola virus disease (Ebola) epidemic is the largest in history and represents the first time Ebola has been diagnosed in the United States. On July 9, 2014, CDC activated its Emergency Operations Center and established an Ebola clinical consultation service to assist U.S. state and local public health officials and health care providers with the evaluation of suspected cases. CDC reviewed all 89 inquiries received by the consultation service during July 9, 2014– January 4, 2015, about children (persons aged ?18 years). Most (56 [63%]) children had no identifiable epidemiologic risk factors for Ebola; among the 33 (37%) who did have an epidemiologic risk factor, in every case this was travel from an Ebola-affected country. Thirty-two of these children met criteria for a person under investigation (PUI) because of clinical signs or symptoms. Fifteen PUIs had blood samples tested for Ebola virus RNA by reverse transcription–polymerase chain reaction; all tested negative. Febrile children who have recently traveled from an Ebola-affected country can be expected to have other common diagnoses, such as malaria and influenza, and in the absence of epidemiologic risk factors for Ebola, the likelihood of Ebola is extremely low. Delaying evaluation and treatment for these other more common illnesses might lead to poorer clinical outcomes. Additionally, many health care providers expressed concerns about whether and how parents should be allowed in the isolation room. While maintaining an appropriate level of vigilance for Ebola, public health officials and health care providers should ensure that pediatric PUIs receive timely triage, diagnosis, and treatment of other more common illnesses, and care reflecting best practices in supporting children’s psychosocial needs. PMID:26390343

  19. State-of-the-Art Workshops on Medical Countermeasures Potentially Available for Human Use Following Accidental Exposures to Ebola Virus.

    PubMed

    Jahrling, Peter B; Hensley, Lisa E; Barrett, Kevin; Lane, Henry Clifford; Davey, Richard T

    2015-10-01

    The ongoing outbreak of Ebola in West Africa has raised a general awareness that at present there are no Ebola-specific medical countermeasures (MCMs) with proven effectiveness. This paper recapitulates discussions held at the 6th International Filovirus Symposium in March 2014 as well as the subsequent design of a randomized clinical trial design for treating Ebola virus-infected patients evacuated from West Africa to the United States. A number of different drugs or biologics were critically reviewed and 3 different postexposure strategies were identified as being farthest along in development; passive immunotherapy with monoclonal antibodies, postexposure vaccination with constructs involving viral vectors (such as vesicular stomatitis virus), and antisense compounds directly targeting the viral genome such as modified phosphorodiamidate morpholino oligomer-based compounds and small interfering RNA products. At the time of the meetings, there were no investigational new drugs (INDs) in place for the candidate MCMs. Developers and sponsors of these candidate products were strongly encouraged to prepare pre-IND packets and submit pre-IND meeting requests to the Food and Drug Administration. Some of these investigational products have already been used under emergency authorizations to treat patients in Africa as well as patients evacuated to the United States or Western Europe. PMID:25957962

  20. Lipid nanoparticle siRNA treatment of Ebola virus Makona infected nonhuman primates

    PubMed Central

    Thi, Emily P.; Mire, Chad E.; Lee, Amy C.H.; Geisbert, Joan B.; Zhou, Joy Z.; Agans, Krystle N.; Snead, Nicholas M.; Deer, Daniel J.; Barnard, Trisha R.; Fenton, Karla A.; MacLachlan, Ian; Geisbert, Thomas W.

    2015-01-01

    The current outbreak of Ebola virus (EBOV) in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled1. Several postexposure interventions have been employed under compassionate use to treat a number of patients repatriated to Europe and the United States2. However, the in vivo efficacy of these interventions against the new outbreak strain of EBOV is unknown. Here, we show that lipid nanoparticle (LNP)-encapsulated siRNAs rapidly adapted to target the Makona outbreak strain of EBOV are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days postexposure while animals were viremic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal hematology, blood chemistry, and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered while the untreated control animals succumbed. These results represent the first successful demonstration of therapeutic anti-EBOV efficacy against the new outbreak strain in nonhuman primates (NHPs) and highlight the rapid development of LNP-delivered siRNA as a countermeasure against this highly lethal human disease. PMID:25901685

  1. Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms

    SciTech Connect

    Shedlock, Devon J.; Bailey, Michael A.; Popernack, Paul M.; Cunningham, James M.; Burton, Dennis R.; Sullivan, Nancy J.

    2010-06-05

    Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.

  2. Epidemiological profile of the Ebola virus disease outbreak in Nigeria, July-September 2014

    PubMed Central

    Musa, Emmanuel Onunche; Adedire, Elizabeth; Adeoye, Olawunmi; Adewuyi, Peter; Waziri, Ndadilnasiya; Nguku, Patrick; Nanjuya, Miriam; Adebayo, Bisola; Fatiregun, Akinola; Enya, Bassey; Ohuabunwo, Chima; Sabitu, Kabiru; Shuaib, Faisal; Okoh, Alex; Oguntimehin, Olukayode; Onyekwere, Nnanna; Nasidi, Abdulsalami; Olayinka, Adebola

    2015-01-01

    Introduction In July 2014, Nigeria experienced an outbreak of Ebola virus disease following the introduction of the disease by an ill Liberian Traveler. The Government of Nigeria with the support of Technical and Development Partners responded quickly and effectively to contain the outbreak. The epidemiological profile of the outbreak that majorly affected two States in the country in terms of person, place and time characteristics of the cases identified is hereby described. Methods Using field investigation technique, all confirmed and probable cases were identified, line-listed and analysed using Microsoft Excel 2007 by persons, time and place. Results A total of 20 confirmed and probable cases; 16 in Lagos (including the index case from Liberia) and 4 in Port Harcourt were identified. The mean age was 39.5 ± 12.4 years with over 40% within the age group 30-39 years. The most frequent exposure type was direct physical contact in 70% of all cases and 73% among health care workers. The total case-fatality was 40%; higher among healthcare workers (46%) compared with non-healthcare workers (22%). The epidemic curve initially shows a typical common source outbreak, followed by a propagated pattern. Conclusion Investigation revealed the size and spread of the outbreak and provided information on the characteristics of persons, time and place. Enhanced surveillance measures, including contact tracing and follow- up proved very useful in early case detection and containment of the outbreak. PMID:26587177

  3. Structure of the Ebola Virus Glycoprotein Bound to An Antibody From a Human Survivor

    SciTech Connect

    Lee, J.E.; Fusco, M.L.; Hessell, A.J.; Oswald, W.B.; Burton, D.R.; Saphire, E.O.

    2009-05-20

    Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the amino terminus of GP1. This structure provides a template for unraveling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development.

  4. [Epidemiology of Ebola virus disease and of other highly contagious, life-threatening diseases with low incidence in Germany].

    PubMed

    Ehlkes, L; Kreuels, B; Schwarz, N G; May, Jürgen

    2015-07-01

    Apart from sporadic exported cases, the occurrence of Ebola, Marburg and Lassa virus diseases is limited to the African continent. Crimean-Congo Hemorrhagic Fever occurs in Southeastern Europe but, so far, not in Germany. Other hemorrhagic fever disease-viruses occur in distinct regions in South America. Pulmonary plague is the bacterial infectious disease with the most contagious and lethal course and it is endemic to Madagascar and East Africa, but also occurs in other countries (e.g. India, USA). Monkey pox epidemics have occurred in remote areas of the Congo Basin. Such outbreaks could potentially become more common with the discontinuation of the cross-protective smallpox vaccination. The Severe Acute Respiratory Syndrome (SARS) that emerged in 2002/2003 is another pathogen with significant epidemic potential. Typical for these diseases is a natural circulation between reservoir animals in remote areas. Sporadic transmission to humans can occur through contact with an infected animal. Subsequent human-to-human transmission can lead to epidemics, such as the current outbreak of Ebola virus disease in West Africa. PMID:25997608

  5. Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates.

    PubMed

    Marzi, Andrea; Engelmann, Flora; Feldmann, Friederike; Haberthur, Kristen; Shupert, W Lesley; Brining, Douglas; Scott, Dana P; Geisbert, Thomas W; Kawaoka, Yoshihiro; Katze, Michael G; Feldmann, Heinz; Messaoudi, Ilhem

    2013-01-29

    Ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. These viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. Although not licensed for human use, recombinant vesicular stomatitis virus (rVSV) expressing the filovirus glycoprotein (GP) has been shown to protect macaques from Ebola virus and Marburg virus infections, both prophylactically and postexposure in a homologous challenge setting. However, the immune mechanisms of protection conferred by this vaccine platform remain poorly understood. In this study, we set out to investigate the role of humoral versus cellular immunity in rVSV vaccine-mediated protection against lethal Zaire ebolavirus (ZEBOV) challenge. Groups of cynomolgus macaques were depleted of CD4+ T, CD8+ T, or CD20+ B cells before and during vaccination with rVSV/ZEBOV-GP. Unfortunately, CD20-depleted animals generated a robust IgG response. Therefore, an additional group of vaccinated animals were depleted of CD4+ T cells during challenge. All animals were subsequently challenged with a lethal dose of ZEBOV. Animals depleted of CD8+ T cells survived, suggesting a minimal role for CD8+ T cells in vaccine-mediated protection. Depletion of CD4+ T cells during vaccination caused a complete loss of glycoprotein-specific antibodies and abrogated vaccine protection. In contrast, depletion of CD4+ T cells during challenge resulted in survival of the animals, indicating a minimal role for CD4+ T-cell immunity in rVSV-mediated protection. Our results suggest that antibodies play a critical role in rVSV-mediated protection against ZEBOV. PMID:23319647

  6. Epidemiological and Surveillance Response to Ebola Virus Disease Outbreak in Lofa County, Liberia (March-September, 2014); Lessons Learned

    PubMed Central

    Kouadio, Koffi Isidore; Clement, Peter; Bolongei, Josephus; Tamba, Alpha; Gasasira, Alex Ntale; Warsame, Abdihamid; Okeibunor, Joseph Chukwudi; Ota, Martin Okechukwu; Tamba, Boima; Gumede, Nicksy; Shaba, Keith; Poy, Alain; Salla, Mbaye; Mihigo, Richard; Nshimirimana, Deo

    2015-01-01

    Ebola Virus Disease (EVD) outbreak was confirmed in Liberia on March 31st 2014. A response comprising of diverse expertise was mobilized and deployed to the country to contain transmission of Ebola and give relief to a people already impoverished from protracted civil war. This paper describes the epidemiological and surveillance response to the EVD outbreak in Lofa County in Liberia from March to September 2014. Five of the 6 districts of Lofa were affected. The most affected districts were Voinjama/Guardu Gbondi and Foya. By 26th September, 2014, a total of 619 cases, including 19.4% probable cases, 20.3% suspected cases and 44.2% confirmed cases were recorded by the Ebola Emergency Response Team (EERT) of Lofa County. Adults (20-50 years) were the most affected. Overall fatality rate was 53.3%.  Twenty two (22) cases were reported among the Health Care Workers with a fatality rate of 81.8%. Seventy eight percent (78%) of the contacts successfully completed 21 days follow-up while 134 (6.15%) that developed signs and symptoms of EVD were referred to the ETU in Foya. The contributions of the weak health systems as well as socio-cultural factors in fueling the epidemic are highlighted. Importantly, the lessons learnt including the positive impact of multi-sectorial and multidisciplinary and coordinated response led by the government and community.  Again, given that the spread of infectious disease can be considered a security threat every effort has to put in place to strengthen the health systems in developing countries including the International Health Regulation (IHR)’s core capacities. Key words:  Ebola virus disease, outbreak, epidemiology and surveillance, socio-cultural factors, health system, West Africa.  PMID:26064783

  7. Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs

    SciTech Connect

    Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.; Reynard, Olivier; Volchkova, Valentina A.; Reid, St. Patrick; Ramanan, Parameshwaran; Cárdenas, Washington B.; Amarasinghe, Gaya K.; Volchkov, Viktor E.; Basler, Christopher F.

    2010-10-11

    Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-{alpha}/{beta} responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-{alpha}/{beta} production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that loss of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.

  8. Ebola Virus Disease in West Africa — The First 9 Months of the Epidemic and Forward Projections

    PubMed Central

    2014-01-01

    BACKGROUND On March 23, 2014, the World Health Organization (WHO) was notified of an out-break of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a “public health emergency of international concern.” METHODS By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa — Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14. RESULTS The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R0) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total. CONCLUSIONS These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months. PMID:25244186

  9. Ebola Virus Modulates Transforming Growth Factor ? Signaling and Cellular Markers of Mesenchyme-Like Transition in Hepatocytes

    PubMed Central

    Wahl-Jensen, Victoria; Safronetz, David; Trost, Brett; Hoenen, Thomas; Arsenault, Ryan; Feldmann, Friederike; Traynor, Dawn; Postnikova, Elena; Kusalik, Anthony; Napper, Scott; Blaney, Joseph E.; Feldmann, Heinz; Jahrling, Peter B.

    2014-01-01

    ABSTRACT Ebola virus (EBOV) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. Although EBOV is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. We employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes. Pathway overrepresentation analysis and functional network analysis of kinome data revealed that transforming growth factor (TGF-?)-mediated signaling responses were temporally modulated in response to EBOV infection. Upregulation of TGF-? signaling in the kinome data sets correlated with the upregulation of TGF-? secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-? signaling, or additional cell receptors and downstream signaling pathway intermediates identified from our kinome analysis, also inhibited EBOV replication. Further, the inhibition of select cell signaling intermediates identified from our kinome analysis provided partial protection in a lethal model of EBOV infection. To gain perspective on the cellular consequence of TGF-? signaling modulation during EBOV infection, we assessed cellular markers associated with upregulation of TGF-? signaling. We observed upregulation of matrix metalloproteinase 9, N-cadherin, and fibronectin expression with concomitant reductions in the expression of E-cadherin and claudin-1, responses that are standard characteristics of an epithelium-to-mesenchyme-like transition. Additionally, we identified phosphorylation events downstream of TGF-? that may contribute to this process. From these observations, we propose a model for a broader role of TGF-?-mediated signaling responses in the pathogenesis of Ebola virus disease. IMPORTANCE Ebola virus (EBOV), formerly Zaire ebolavirus, causes a severe hemorrhagic disease in humans and nonhuman primates and is the most lethal Ebola virus species, with case fatality rates of up to 90%. Although EBOV is considered a worldwide concern, many questions remain regarding EBOV molecular pathogenesis. As it is appreciated that many cellular processes are regulated through kinase-mediated phosphorylation events, we employed temporal kinome analysis to investigate the functional responses of human hepatocytes to EBOV infection. Administration of kinase inhibitors targeting signaling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and reduced EBOV pathogenesis in vivo. Further analysis of our data also demonstrated that EBOV infection modulated TGF-?-mediated signaling responses and promoted “mesenchyme-like” phenotypic changes. Taken together, these results demonstrated that EBOV infection specifically modulates TGF-?-mediated signaling responses in epithelial cells and may have broader implications in EBOV pathogenesis. PMID:24942569

  10. Development of a reverse genetics system to generate a recombinant Ebola virus Makona expressing a green fluorescent protein.

    PubMed

    Albariño, César G; Wiggleton Guerrero, Lisa; Lo, Michael K; Nichol, Stuart T; Towner, Jonathan S

    2015-10-01

    Previous studies have demonstrated the potential application of reverse genetics technology in studying a broad range of aspects of viral biology, including gene regulation, protein function, cell entry, and pathogenesis. Here, we describe a highly efficient reverse genetics system used to generate recombinant Ebola virus (EBOV) based on a recent isolate from a human patient infected during the 2014-2015 outbreak in Western Africa. We also rescued a recombinant EBOV expressing a fluorescent reporter protein from a cleaved VP40 protein fusion. Using this virus and an inexpensive method to quantitate the expression of the foreign gene, we demonstrate its potential usefulness as a tool for screening antiviral compounds and measuring neutralizing antibodies. PMID:26122472

  11. Public Knowledge, Perception and Source of Information on Ebola Virus Disease – Lagos, Nigeria; September, 2014

    PubMed Central

    Gidado, Saheed; Oladimeji, Abisola M.; Roberts, Alero Ann; Nguku, Patrick; Nwangwu, Iruoma Genevieve; Waziri, Ndadilnasiya Endie; Shuaib, Faisal; Oguntimehin, Olukayode; Musa, Emmanuel; Nzuki, Charles; Nasidi, Abdulsalami; Adewuyi, Peter; Daniel, Tom-Aba; Olayinka, Adebola; Odubanjo, Oladoyin; Poggensee, Gabriele

    2015-01-01

    Background: The first ever outbreak of Ebola virus disease (EVD) in Nigeria was declared in July, 2014. Level of public knowledge, perception and adequacy of information on EVD were unknown. We assessed the public preparedness level to adopt disease preventive behavior which is premised on appropriate knowledge, perception and adequate information. Methods: We enrolled 5,322 respondents in a community-based cross-sectional study. We used interviewer-administered questionnaire to collect data on socio-demographic characteristics, EVD–related knowledge, perception and source of information. We performed univariate and bivariate data analysis using Epi-Info software setting p-value of 0.05 as cut-off for statistical significance. Results: Mean age of respondents was 34 years (± 11.4 years), 52.3% were males. Forty one percent possessed satisfactory general knowledge; 44% and 43.1% possessed satisfactory knowledge on mode of spread and preventive measures, respectively. Residing in EVD cases districts, male respondents and possessing at least secondary education were positively associated with satisfactory general knowledge (p-value: 0.01, 0.001 and 0.000004, respectively). Seventy one percent perceived EVD as a public health problem while 61% believed they cannot contract the disease. Sixty two percent and 64% of respondents will not shake hands and hug a successfully treated EVD patient respectively. Only 2.2% of respondents practice good hand-washing practice. Television (68.8%) and radio (55.0%) are the most common sources of information on EVD. Conclusions: Gaps in EVD-related knowledge and perception exist. Targeted public health messages to raise knowledge level, correct misconception and discourage stigmatization should be widely disseminated, with television and radio as media of choice. PMID:25914860

  12. Influences of Glycosylation on Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines?

    PubMed Central

    Dowling, William; Thompson, Elizabeth; Badger, Catherine; Mellquist, Jenny L.; Garrison, Aura R.; Smith, Jeffery M.; Paragas, Jason; Hogan, Robert J.; Schmaljohn, Connie

    2007-01-01

    The Ebola virus (EBOV) envelope glycoprotein (GP) is the primary target of protective immunity. Mature GP consists of two disulfide-linked subunits, GP1 and membrane-bound GP2. GP is highly glycosylated with both N- and O-linked carbohydrates. We measured the influences of GP glycosylation on antigenicity, immunogenicity, and protection by testing DNA vaccines comprised of GP genes with deleted N-linked glycosylation sites or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP. Our data indicate that this is likely due to the inability of GP2 and GP1 to dimerize at the cell surface and suggest that glycosylation at this site is required for achieving the conformational integrity of GP2 and GP1. In contrast, mutation of two N-linked sites on GP1, which flank previously defined protective antibody epitopes on GP, may enhance immunogenicity, possibly by unmasking epitopes. We further showed that although deleting the mucin region apparently had no effect on antigenicity in vitro, it negatively impacted the elicitation of protective immunity in mice. In addition, we confirmed the presence of previously identified B-cell and T-cell epitopes in GP but show that when analyzed individually none of them were neither absolutely required nor sufficient for protective immunity to EBOV. Finally, we identified other potential regions of GP that may contain relevant antibody or T-cell epitopes. PMID:17151111

  13. Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays.

    PubMed

    Sozhamannan, Shanmuga; Holland, Mitchell Y; Hall, Adrienne T; Negrón, Daniel A; Ivancich, Mychal; Koehler, Jeffrey W; Minogue, Timothy D; Campbell, Catherine E; Berger, Walter J; Christopher, George W; Goodwin, Bruce G; Smith, Michael A

    2015-06-01

    Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

  14. Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays

    PubMed Central

    Sozhamannan, Shanmuga; Holland, Mitchell Y.; Hall, Adrienne T.; Negrón, Daniel A.; Ivancich, Mychal; Koehler, Jeffrey W.; Minogue, Timothy D.; Campbell, Catherine E.; Berger, Walter J.; Christopher, George W.; Goodwin, Bruce G.; Smith, Michael A.

    2015-01-01

    Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

  15. Public health challenges and legacies of Japan's response to the Ebola virus disease outbreak in West Africa 2014 to 2015.

    PubMed

    Saito, Tomoya

    2015-11-01

    The largest outbreak of Ebola virus disease occurred in West Africa in 2014 and resulted in unprecedented transmission even in distant countries. In Japan, only nine individuals were screened for Ebola and there was no confirmed case. However, the government promoted the reinforcement of response measures and interagency collaboration, with training and simulation exercises conducted country-wide. The legacies included: publication of a communication policy on case disclosure, a protocol for collaboration between public health and other agencies, and establishing an expert committee to assemble the limited available expertise. There were challenges in taking proportionate and flexible measures in the management of people identified to be at high risk at entry points to Japan, in the decentralised medical response strategy, and in the medical countermeasures preparedness. The Ebola outbreak in West Africa provided a crucial opportunity to reveal the challenges and improve the preparedness for rare but high impact emerging diseases that are prone to be neglected. Efforts to uphold the lessons learnt and maintain public health preparedness should help prepare for future emerging diseases, including bioterrorist acts and pandemics. PMID:26559148

  16. [Health Communication: Preventing the Spread of Ebola Virus Disease in the Portuguese Spoken African Countries--Methodology KISS & KEYWORDS].

    PubMed

    Santiago, Isabel De; Miguel, José Pereira; Antunes, Francisco

    2015-01-01

    In this work, Health Communication is considered as an important discipline in medicine and health sciences for his role as true determinant of health. We highlight their contribution to health promotion and disease prevention. Thus, the Health Communication Plan (PCS): Preventing the spread of Ebola virus disease in the Portuguese Speaking African Countries - KISS & KEYWORDS methodology is a tool that aims to minimize the risk of infection by Ebola virus in the Portuguese Speaking African Countries and also train for a general improvement of health conditions of the local populations. In the PCS design are especially considered the social and cultural contexts of the target populations, especially the customs, traditions and religion. Health Communication is considered as an Essential Function of Public Health and its main is to provide a population-based approach. The target of communication actions are population groups in addition to the individual communication, target-audiences are people without access to the media, in Guinea Bissau, Cape Verde and Sao Tome and Principe. Under the communication plan uses the methodology, models and practices both by media professionals as health. A proximity approach and cultural mediation, previously identified key facts, are defined objectives; outlines to the Plan in concrete and its implementation methodology (target-audience and following intervention, materials to be used and key-messages and partners to mobilize) following the World Health Organisation standards. PMID:26061502

  17. Ebola Virus Disease: Rapid Diagnosis and Timely Case Reporting are Critical to the Early Response for Outbreak Control.

    PubMed

    Stamm, Lola V

    2015-09-01

    Ebola virus disease (EVD) is a life-threatening zoonosis caused by infection with the Ebola virus. Since the first reported EVD outbreak in the Democratic Republic of the Congo, several small outbreaks have been reported in central Africa with about 2,400 cases occurring between 1976 and 2013. The 2013-2015 EVD outbreak in west Africa is the first documented outbreak in this region and the largest ever with over 27,000 cases and more than 11,000 deaths. Although EVD transmission rates have recently decreased in west Africa, this crisis continues to threaten global health and security, particularly since infected travelers could spread EVD to other resource-limited areas of the world. Because vaccines and drugs are not yet licensed for EVD, outbreak control is dependent on the use of non-pharmaceutical interventions (e.g., infection control practices, isolation of EVD cases, contact tracing with follow-up and quarantine, sanitary burial, health education). However, delays in diagnosing and reporting EVD cases in less accessible rural areas continue to hamper control efforts. New advances in rapid diagnostics for identifying presumptive EVD cases and in mobile-based technologies for communicating critical health-related information should facilitate deployment of an early response to prevent the amplification of sporadic EVD cases into large-scale outbreaks. PMID:26175026

  18. Development and deployment of a rapid recombinase polymerase amplification Ebola virus detection assay in Guinea in 2015.

    PubMed

    Faye, Oumar; Faye, Ousmane; Soropogui, Barré; Patel, Pranav; El Wahed, Ahmed Abd; Loucoubar, Cheikh; Fall, Gamou; Kiory, Davy; Magassouba, N'Faly; Keita, Sakoba; Kondé, Mandy Kader; Diallo, Alpha Amadou; Koivogui, Lamine; Karlberg, Helen; Mirazimi, Ali; Nentwich, Oliver; Piepenburg, Olaf; Niedrig, Matthias; Weidmann, Manfred; Sall, Amadou Alpha

    2015-11-01

    In the absence of a vaccine or specific treatments for Ebola virus disease (EVD), early identification of cases is crucial for the control of EVD epidemics. We evaluated a new extraction kit (SpeedXtract (SE), Qiagen) on sera and swabs in combination with an improved diagnostic reverse transcription recombinase polymerase amplification assay for the detection of Ebola virus (EBOV-RT-RPA). The performance of combined extraction and detection was best for swabs. Sensitivity and specificity of the combined SE and EBOV-RT-RPA were tested in a mobile laboratory consisting of a mobile glovebox and a Diagnostics-in-a-Suitcase powered by a battery and solar panel, deployed to Matoto Conakry, Guinea as part of the reinforced surveillance strategy in April 2015 to reach the goal of zero cases. The EBOV-RT-RPA was evaluated in comparison to two real-time PCR assays. Of 928 post-mortem swabs, 120 tested positive, and the combined SE and EBOV-RT-RPA yielded a sensitivity and specificity of 100% in reference to one real-time RT-PCR assay. Another widely used real-time RT-PCR was much less sensitive than expected. Results were provided very fast within 30 to 60 min, and the field deployment of the mobile laboratory helped improve burial management and community engagement. PMID:26558690

  19. Development of a TaqMan Array Card for Acute-Febrile-Illness Outbreak Investigation and Surveillance of Emerging Pathogens, Including Ebola Virus.

    PubMed

    Liu, Jie; Ochieng, Caroline; Wiersma, Steve; Ströher, Ute; Towner, Jonathan S; Whitmer, Shannon; Nichol, Stuart T; Moore, Christopher C; Kersh, Gilbert J; Kato, Cecilia; Sexton, Christopher; Petersen, Jeannine; Massung, Robert; Hercik, Christine; Crump, John A; Kibiki, Gibson; Maro, Athanasia; Mujaga, Buliga; Gratz, Jean; Jacob, Shevin T; Banura, Patrick; Scheld, W Michael; Juma, Bonventure; Onyango, Clayton O; Montgomery, Joel M; Houpt, Eric; Fields, Barry

    2016-01-01

    Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. Convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR-based TaqMan array card (TAC) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 AFI-associated organisms, including 15 viruses (chikungunya, Crimean-Congo hemorrhagic fever [CCHF] virus, dengue, Ebola virus, Bundibugyo virus, Sudan virus, hantaviruses [Hantaan and Seoul], hepatitis E, Marburg, Nipah virus, o'nyong-nyong virus, Rift Valley fever virus, West Nile virus, and yellow fever virus), 8 bacteria (Bartonella spp., Brucella spp., Coxiella burnetii, Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, and Yersinia pestis), and 3 protozoa (Leishmania spp., Plasmodium spp., and Trypanosoma brucei). Two extrinsic controls (phocine herpesvirus 1 and bacteriophage MS2) were included to ensure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, interassay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and the TAC exhibited an overall 88% (278/315; 95% confidence interval [CI], 84% to 92%) sensitivity and a 99% (5,261/5,326, 98% to 99%) specificity. This TaqMan array card can be used in field settings as a rapid screen for outbreak investigation or for the surveillance of pathogens, including Ebola virus. PMID:26491176

  20. Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

    PubMed Central

    Lear, Calli; Chen, Li; Yantosca, L. Michael; Scully, Corinne; Sarraju, Ashish; Sokolovska, Anna; Zariffard, M. Reza; Eisen, Damon P.; Mungall, Bruce A.; Kotton, Darrell N.; Omari, Amel; Huang, I-Chueh; Farzan, Michael; Takahashi, Kazue; Stuart, Lynda; Stahl, Gregory L.; Ezekowitz, Alan B.; Spear, Gregory T.; Olinger, Gene G.; Schmidt, Emmett V.; Michelow, Ian C.

    2013-01-01

    Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes. PMID:23573288

  1. Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo

    PubMed Central

    Moyen, Nanikaly; Thirion, Laurence; Emmerich, Petra; Dzia-Lepfoundzou, Amelia; Richet, Hervé; Boehmann, Yannik; Dimi, Yannick; Gallian, Pierre; Gould, Ernest A.; Günther, Stephan; de Lamballerie, Xavier

    2015-01-01

    Background Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV. Methodology and Findings In 2011, we conducted a MARV and EBOV seroprevalence study amongst 809 blood donors recruited in rural (75; 9.3%) and urban (734; 90.7%) areas of the Republic of Congo. Serum titres of IgG antibodies to MARV and EBOV were assessed by indirect double-immunofluorescence microscopy. MARV seroprevalence was 0.5% (4 in 809) without any identified risk factors. Prevalence of IgG to EBOV was 2.5%, peaking at 4% in rural areas and in Pointe Noire. Independent risk factors identified by multivariate analysis were contact with bats and exposure to birds. Conclusions/Significance This MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors. PMID:26047124

  2. Relationship Between Ebola Virus Real-Time Quantitative Polymerase Chain Reaction-Based Threshold Cycle Value and Virus Isolation From Human Plasma.

    PubMed

    Spengler, Jessica R; McElroy, Anita K; Harmon, Jessica R; Ströher, Ute; Nichol, Stuart T; Spiropoulou, Christina F

    2015-10-01

    We performed a longitudinal analysis of plasma samples obtained from 4 patients with Ebola virus (EBOV) disease (EVD) to determine the relationship between the real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based threshold cycle (Ct) value and the presence of infectious EBOV. EBOV was not isolated from plasma samples with a Ct value of >35.5 or >12 days after onset of symptoms. EBOV was not isolated from plasma samples in which anti-EBOV nucleoprotein immunoglobulin G was detected. These data demonstrate the utility of interpreting qRT-PCR results in the context of the course of EBOV infection and associated serological responses for patient-management decisions. PMID:25941333

  3. Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

    SciTech Connect

    Usami, Katsuaki; Matsuno, Keita; Igarashi, Manabu; Denda-Nagai, Kaori; Takada, Ayato; Irimura, Tatsuro

    2011-04-01

    Highlights: {yields} Ebola virus infection is mediated by binding to and fusion with the target cells. {yields} Structural feature of the viral glycoprotein determines the infectivity. {yields} Surface C-type lectin, MGL, of macrophages and dendritic cells mediate the infection. {yields} GP2, one of glycoprotein subunits, plays an essential role in MGL-mediated infection. {yields} There is a critical amino acid residue involved in high infectivity. -- Abstract: Ebola virus (EBOV) infection is initiated by the interaction of the viral surface envelope glycoprotein (GP) with the binding sites on target cells. Differences in the mortality among different species of the Ebola viruses, i.e., Zaire ebolavirus (ZEBOV) and Reston ebolavirus (REBOV), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the GPs in cells expressing macrophage galactose-type calcium-type lectin (MGL/CD301). Through mutagenesis of GP2, the transmembrane-anchored subunit of GP, we found that residues 502-527 of the GP2 sequence determined the different infectivity between VSV-ZEBOV GP and -REBOV GP in MGL/CD301-expressing cells and a histidine residue at position 516 of ZEBOV GP2 appeared essential in the differential infectivity. These findings may provide a clue to clarify a molecular basis of different pathogenicity among EBOV species.

  4. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    DOE PAGESBeta

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; et al

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/?NPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludesmore »a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.« less

  5. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    SciTech Connect

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; Shabman, Reed  S.; Chiu, Wah; Davey, Robert  A.; Otwinowski, Zbyszek; Basler, Christopher  F.; Amarasinghe, Gaya  K.

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/?NPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.

  6. Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies

    PubMed Central

    Iversen, Patrick L.; Saoud, Jay B.; Sazani, Peter; Charleston, Jay S.; Axtelle, Tim; Wong, Michael; Smith, William B.; Vutikullird, Apinya; Kaye, Edward

    2014-01-01

    Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMOplus) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates in previous studies. AVI-6002 (a combination of AVI-7537 and AVI-7539) or AVI-6003 (a combination of AVI-7287 and AVI-7288) were administered as sequential intravenous (i.v.) infusions of a 1:1 fixed dose ratio of the two subcomponents. In each study, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in six-dose escalation cohorts of five subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg/kg per component) or placebo in a 4:1 ratio. Both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied. A maximum tolerated dose was not observed in either study. The four chemically similar PMOplus components exhibited generally similar PK profiles. The mean peak plasma concentration and area under the concentration-time curve values of the four components exhibited dose-proportional PK. The estimated plasma half-life of all four components was 2 to 5 h. The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence. PMID:25155593

  7. Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy

    E-print Network

    Harrison, Stephen C.

    .g., Ebola virus, RSV) Authors Bo Liang, Zongli Li, Simon Jenni, ..., Nikolaus Grigorieff, Stephen C viruses, a group that includes Ebola and rabies viruses, catalyze RNA-dependent RNA poly- merization of the most lethal human and animal pathogens, including Ebola virus and rabies virus. Their multifunctional

  8. Be-CoDiS: An epidemiological model to predict the risk of human diseases spread worldwide. Application to the 2014 Ebola Virus Disease epidemic

    E-print Network

    Benjamin, Ivorra; Diène, Ngom

    2014-01-01

    Ebola virus disease is a lethal human and primate disease that currently requires a particular attention from the national and international health authorities due to important outbreaks concurring in some Western African countries and possible spread to other continents, which has already occurred in the USA and Spain. Regarding the emergency of this situation, there is a need of development of decision tools to help the authorities to focus their efforts in important factors that can help to eradicate Ebola. Mathematical modeling and, more precisely, epidemiological modeling can help to predict the possible evolution of the Ebola outbreaks and to give some recommendations in the region to be prioritized for surveillance. In this work, we present a first formulation of a new spatial-temporal epidemiological model, called Be-CoDiS (Between-COuntries Disease Spread), based on the combination of a deterministic Individual-Based model (modelling the interaction between countries, considered as individual) for be...

  9. Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

    PubMed Central

    Kuhn, Jens H.; Andersen, Kristian G.; Baize, Sylvain; Bào, Y?míng; Bavari, Sina; Berthet, Nicolas; Blinkova, Olga; Brister, J. Rodney; Clawson, Anna N.; Fair, Joseph; Gabriel, Martin; Garry, Robert F.; Gire, Stephen K.; Goba, Augustine; Gonzalez, Jean-Paul; Günther, Stephan; Happi, Christian T.; Jahrling, Peter B.; Kapetshi, Jimmy; Kobinger, Gary; Kugelman, Jeffrey R.; Leroy, Eric M.; Maganga, Gael Darren; Mbala, Placide K.; Moses, Lina M.; Muyembe-Tamfum, Jean-Jacques; N’Faly, Magassouba; Nichol, Stuart T.; Omilabu, Sunday A.; Palacios, Gustavo; Park, Daniel J.; Paweska, Janusz T.; Radoshitzky, Sheli R.; Rossi, Cynthia A.; Sabeti, Pardis C.; Schieffelin, John S.; Schoepp, Randal J.; Sealfon, Rachel; Swanepoel, Robert; Towner, Jonathan S.; Wada, Jiro; Wauquier, Nadia; Yozwiak, Nathan L.; Formenty, Pierre

    2014-01-01

    In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures. PMID:25421896

  10. Ebola Virus Disease 2013-2014 Outbreak in West Africa: An Analysis of the Epidemic Spread and Response

    PubMed Central

    Cenciarelli, Orlando; Pietropaoli, Stefano; Carestia, Mariachiara; D'Amico, Fabrizio; Sassolini, Alessandro; Di Giovanni, Daniele; Rea, Silvia; Gabbarini, Valentina; Tamburrini, Annalaura; Palombi, Leonardo; Bellecci, Carlo; Gaudio, Pasquale

    2015-01-01

    The Ebola virus epidemic burst in West Africa in late 2013, started in Guinea, reached in a few months an alarming diffusion, actually involving several countries (Liberia, Sierra Leone, Nigeria, Senegal, and Mali). Guinea and Liberia, the first nations affected by the outbreak, have put in place measures to contain the spread, supported by international organizations; then they were followed by the other nations affected. In the present EVD outbreak, the geographical spread of the virus has followed a new route: the achievement of large urban areas at an early stage of the epidemic has led to an unprecedented diffusion, featuring the largest outbreak of EVD of all time. This has caused significant concerns all over the world: the potential reaching of far countries from endemic areas, mainly through fast transports, induced several countries to issue information documents and health supervision for individuals going to or coming from the areas at risk. In this paper the geographical spread of the epidemic was analyzed, assessing the sequential appearance of cases by geographic area, considering the increase in cases and mortality according to affected nations. The measures implemented by each government and international organizations to contain the outbreak, and their effectiveness, were also evaluated. PMID:25852754

  11. Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material

    PubMed Central

    Trefry, John C.; Wollen, Suzanne E.; Nasar, Farooq; Shamblin, Joshua D.; Kern, Steven J.; Bearss, Jeremy J.; Jefferson, Michelle A.; Chance, Taylor B.; Kugelman, Jeffery R.; Ladner, Jason T.; Honko, Anna N.; Kobs, Dean J.; Wending, Morgan Q.S.; Sabourin, Carol L.; Pratt, William D.; Palacios, Gustavo F.; Pitt, M. Louise M.

    2015-01-01

    Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein’s poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations. PMID:26703716

  12. Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material.

    PubMed

    Trefry, John C; Wollen, Suzanne E; Nasar, Farooq; Shamblin, Joshua D; Kern, Steven J; Bearss, Jeremy J; Jefferson, Michelle A; Chance, Taylor B; Kugelman, Jeffery R; Ladner, Jason T; Honko, Anna N; Kobs, Dean J; Wending, Morgan Q S; Sabourin, Carol L; Pratt, William D; Palacios, Gustavo F; Pitt, M Louise M

    2015-01-01

    Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein's poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations. PMID:26703716

  13. Innovative Technological Approach to Ebola Virus Disease Outbreak Response in Nigeria Using the Open Data Kit and Form Hub Technology

    PubMed Central

    Nguku, Patrick; Waziri, Ndadilnasiya; Adewuyi, Peter; Adeoye, Olawunmi; Adeseye, Aderonke; Oguntimehin, Olukayode; Shuaib, Faisal

    2015-01-01

    The recent outbreak of Ebola Virus Disease (EVD) in West Africa has ravaged many lives. Effective containment of this outbreak relies on prompt and effective coordination and communication across various interventions; early detection and response being critical to successful control. The use of information and communications technology (ICT) in active surveillance has proved to be effective but its use in Ebola outbreak response has been limited. Due to the need for timeliness in reporting and communication for early discovery of new EVD cases and promptness in response; it became imperative to empower the response team members with technologies and solutions which would enable smooth and rapid data flow. The Open Data Kit and Form Hub technology were used in combination with the Dashboard technology and ArcGIS mapping for follow up of contacts, identification of cases, case investigation and management and also for strategic planning during the response. A remarkable improvement was recorded in the reporting of daily follow-up of contacts after the deployment of the integrated real time technology. The turnaround time between identification of symptomatic contacts and evacuation to the isolation facility and also for receipt of laboratory results was reduced and informed decisions could be taken by all concerned. Accountability in contact tracing was ensured by the use of a GPS enabled device. The use of innovative technologies in the response of the EVD outbreak in Nigeria contributed significantly to the prompt control of the outbreak and containment of the disease by providing a valuable platform for early warning and guiding early actions. PMID:26115402

  14. Innovative Technological Approach to Ebola Virus Disease Outbreak Response in Nigeria Using the Open Data Kit and Form Hub Technology.

    PubMed

    Tom-Aba, Daniel; Olaleye, Adeniyi; Olayinka, Adebola Tolulope; Nguku, Patrick; Waziri, Ndadilnasiya; Adewuyi, Peter; Adeoye, Olawunmi; Oladele, Saliu; Adeseye, Aderonke; Oguntimehin, Olukayode; Shuaib, Faisal

    2015-01-01

    The recent outbreak of Ebola Virus Disease (EVD) in West Africa has ravaged many lives. Effective containment of this outbreak relies on prompt and effective coordination and communication across various interventions; early detection and response being critical to successful control. The use of information and communications technology (ICT) in active surveillance has proved to be effective but its use in Ebola outbreak response has been limited. Due to the need for timeliness in reporting and communication for early discovery of new EVD cases and promptness in response; it became imperative to empower the response team members with technologies and solutions which would enable smooth and rapid data flow. The Open Data Kit and Form Hub technology were used in combination with the Dashboard technology and ArcGIS mapping for follow up of contacts, identification of cases, case investigation and management and also for strategic planning during the response. A remarkable improvement was recorded in the reporting of daily follow-up of contacts after the deployment of the integrated real time technology. The turnaround time between identification of symptomatic contacts and evacuation to the isolation facility and also for receipt of laboratory results was reduced and informed decisions could be taken by all concerned. Accountability in contact tracing was ensured by the use of a GPS enabled device. The use of innovative technologies in the response of the EVD outbreak in Nigeria contributed significantly to the prompt control of the outbreak and containment of the disease by providing a valuable platform for early warning and guiding early actions. PMID:26115402

  15. Ebola Virus Disease Outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and Outcomes

    PubMed Central

    Kratz, Thomas; Roddy, Paul; Tshomba Oloma, Antoine; Jeffs, Benjamin; Pou Ciruelo, Diana; de la Rosa, Olimpia; Borchert, Matthias

    2015-01-01

    Data collected during the 2012 Ebola virus disease (EVD) epidemic in the Democratic Republic of the Congo were analysed for clinical signs, symptoms and case fatality of EVD caused by Bundibugyo virus (BDBV), establishment of differential diagnoses, description of medical treatment and evaluation of the quality of clinical documentation. In a quantitative observational prospective study, global epidemiological data from 52 patients (34 patients within the community, 18 patients treated in the Ebola Treatment Centre) were entered anonymously into a database, subsequently matched and analysed. Relevant findings include an over-representation of females among community EVD cases (85.3%) and of community EVD cases in the age group of 15-54 years (82.4%). All ETC patients had fever (55.6% of all 18 ETC patients during their hospital stay) or self-reported fever (88.2% upon admission) at some point of time during their illness. Major symptoms of ETC patients during hospital stay included asthenia (82.4%), anorexia (82.4%), myalgia (70.6%), sore throat/difficulty swallowing (70.6%), arthralgia (76.5%) and nausea (70.6%). Gastrointestinal signs and symptoms (nausea, diarrhoea, vomiting) (76.4%) as well as general pain (94.1%) were frequent in ETC patients. The median duration of EVD was 18 days, while the mean incubation period was 11.3 days. Differential diagnosis of EVD included malaria (28.3%), intestinal parasitosis (10.9%), and infectious syndrome (10.9%). There was also an important variation in clinical evolvement. Quality of documentation was adversely affected by the way patient file contents were transferred from inside to outside the high-risk zone, entailing a mean mismatch value of 27.3% between patient file contents inside vs. outside the high-risk zone. This study adds further description of EVD (frequently non-specific signs and symptoms, non frequent bleeding, a long incubation period, long duration of disease) and emphasizes the need for improving clinical monitoring and documentation in EVD outbreak settings. PMID:26107529

  16. The effect of Ebola Virus Disease outbreak on hand washing among secondary school students in Ondo State Nigeria, October, 2014

    PubMed Central

    Ilesanmi, Olayinka Stephen; Alele, Faith Osaretin

    2015-01-01

    Introduction Hand washing with soap and water is one of the cheapest, most effective ways of limiting the spread of Ebola Virus Disease (EVD). Despite its importance the prevalence of hand washing was low before the EVD outbreak in Nigeria. This study aimed at determining the factors associated with improved hand washing practices following the EVD outbreak. Methods A descriptive cross sectional study of 440 students from a secondary school in Owo, Ondo State was done. Data was collected in October 2014 when Nigeria was yet to be declared EVD free. Systematic random sampling was used. A semi-structured, interviewer administered questionnaire was used. Data was analysed with epi info version 7, descriptive statistics were done, Chi square test was used for the assessment of significant associations between proportions. Determinants of good hand washing practices was identified using logistics regression analysis at 5% level of significance. Results Of 440 respondents, mean age was 13.7±1.9 years. Females were 48.2%. Only 4.6% have never heard of Ebola Virus Disease.Level of hand washing with soap and water improved by62.6%. Significant improvement in hand washing was in 75.8% of those who heard through social media (p < 0.001), 70.5% of Newspaper readers(p < 0.001), 65.6% of radio listeners (p = 0.001), 75.4% of family members p < 0.001, 76.3% talk in church p < 0.001, 77.6% peers p = 0.02, 72.4% TV p < 0.001.Change in hand washing practices was associated with watching television (AOR: 2.2; CI 95%: 1.1-4.3) and listening to health education in church (AOR: 2.4; CI 95%: 1.2-4.7).Major reason for change in hand washing practices was because of EVD deadly nature, 170(40.5%). Conclusion Watching health education messages on television and listening to it in church are the determinants of change in hand washing practices. Promotion of hand washing with soap and water needs to be sustained to prevent other diseases. Training of students on prevention of EVD was conducted in selected schools.

  17. Multiple Cationic Amphiphiles Induce a Niemann-Pick C Phenotype and Inhibit Ebola Virus Entry and Infection

    PubMed Central

    Shoemaker, Charles J.; Schornberg, Kathryn L.; Delos, Sue E.; Scully, Corinne; Pajouhesh, Hassan; Olinger, Gene G.; Johansen, Lisa M.; White, Judith M.

    2013-01-01

    Ebola virus (EBOV) is an enveloped RNA virus that causes hemorrhagic fever in humans and non-human primates. Infection requires internalization from the cell surface and trafficking to a late endocytic compartment, where viral fusion occurs, providing a conduit for the viral genome to enter the cytoplasm and initiate replication. In a concurrent study, we identified clomiphene as a potent inhibitor of EBOV entry. Here, we screened eleven inhibitors that target the same biosynthetic pathway as clomiphene. From this screen we identified six compounds, including U18666A, that block EBOV infection (IC50 1.6 to 8.0 µM) at a late stage of entry. Intriguingly, all six are cationic amphiphiles that share additional chemical features. U18666A induces phenotypes, including cholesterol accumulation in endosomes, associated with defects in Niemann–Pick C1 protein (NPC1), a late endosomal and lysosomal protein required for EBOV entry. We tested and found that all six EBOV entry inhibitors from our screen induced cholesterol accumulation. We further showed that higher concentrations of cationic amphiphiles are required to inhibit EBOV entry into cells that overexpress NPC1 than parental cells, supporting the contention that they inhibit EBOV entry in an NPC1-dependent manner. A previously reported inhibitor, compound 3.47, inhibits EBOV entry by blocking binding of the EBOV glycoprotein to NPC1. None of the cationic amphiphiles tested had this effect. Hence, multiple cationic amphiphiles (including several FDA approved agents) inhibit EBOV entry in an NPC1-dependent fashion, but by a mechanism distinct from that of compound 3.47. Our findings suggest that there are minimally two ways of perturbing NPC1-dependent pathways that can block EBOV entry, increasing the attractiveness of NPC1 as an anti-filoviral therapeutic target. PMID:23441171

  18. Viruses 2014, 6, 3837-3854; doi:10.3390/v6103837 ISSN 1999-4915

    E-print Network

    Loudon, Catherine

    .mdpi.com/journal/viruses Article A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding 2014 / Published: 17 October 2014 Abstract: Ebola virus (EBOV) causes viral hemorrhagic fever in humans seven proteins including viral protein 40 (VP40). VP40 is the major Ebola virus matrix protein

  19. Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics

    PubMed Central

    Sanchez-Lockhart, Mariano; Andersen, Kristian G.; Gire, Stephen; Park, Daniel J.; Sealfon, Rachel; Lin, Aaron E.; Wohl, Shirlee; Sabeti, Pardis C.

    2015-01-01

    ABSTRACT? Until recently, Ebola virus (EBOV) was a rarely encountered human pathogen that caused disease among small populations with extraordinarily high lethality. At the end of 2013, EBOV initiated an unprecedented disease outbreak in West Africa that is still ongoing and has already caused thousands of deaths. Recent studies revealed the genomic changes this particular EBOV variant undergoes over time during human-to-human transmission. Here we highlight the genomic changes that might negatively impact the efficacy of currently available EBOV sequence-based candidate therapeutics, such as small interfering RNAs (siRNAs), phosphorodiamidate morpholino oligomers (PMOs), and antibodies. Ten of the observed mutations modify the sequence of the binding sites of monoclonal antibody (MAb) 13F6, MAb 1H3, MAb 6D8, MAb 13C6, and siRNA EK-1, VP24, and VP35 targets and might influence the binding efficacy of the sequence-based therapeutics, suggesting that their efficacy should be reevaluated against the currently circulating strain. PMID:25604787

  20. Preparation of an intensive care unit in France for the reception of a confirmed case of Ebola virus infection.

    PubMed

    Dubost, Clément; Pasquier, Pierre; Kearns, Kévin; Ficko, Cécile; Rapp, Christophe; Wolff, Michel; Richard, Jean-Christophe; Diehl, Jean-Luc; Le Tulzo, Yves; Mérat, Stéphane

    2015-12-01

    The current Ebola Virus Disease (EVD) outbreak in West Africa is a major challenge for the worldwide medical community. On April 29th 2015, the World Health Organization (WHO) declared 26,277 infected cases; among them, 10,884 have deceased. The epidemic is still ongoing, particularly in Sierra Leone. It is now clear that northern countries will be implicated in the care of EVD patients, both in the field and back at home. Because of the severity of EVD, a fair amount of patients may require intensive care. It is highly probable that intensive care would be able to significantly reduce the mortality linked with EVD. The preparation of a modern Intensive Care Unit (ICU) to treat an EVD patient in good conditions requires time and specific equipment. The cornerstone of this preparation includes two main goals: treating the patient and protecting healthcare providers. Staff training is time consuming and must be performed far in advance of patient arrival. To be efficient, preparation should be planned at a national level with help from public authorities, as was the case in France during the summer of 2014. Due to the severity of the disease, the high risk of transmission and scarce knowledge on EVD treatment, our propositions are necessarily original and innovative. Our review includes four topics: a brief report on the actual outbreak, where to receive and hospitalize the patients, the specific organization of the ICU and finally ethical aspects. PMID:26620545

  1. Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease

    PubMed Central

    Misasi, John; Sullivan, Nancy J.

    2014-01-01

    Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and non-human primates. Ebola protein interactions with host cellular proteins disrupt Type I and Type II interferon responses, RNAi anti-viral responses, antigen presentation, T-cell mediated antibody responses, humoral antibodies and cell mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and “cytokine storm” that is characteristic of fatal ebolavirus infection. Here we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade anti-viral defenses. PMID:25417101

  2. Single dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus

    PubMed Central

    Geisbert, Joan B.; Latham, Theresa E.; Agans, Krystle N.; Xu, Rong; Ota-Setlik, Ayuko; Egan, Michael A.; Fenton, Karla A.; Clarke, David K.; Eldridge, John H.; Geisbert, Thomas W.

    2015-01-01

    The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus1. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal hemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in nearly 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primate (NHPs) against ZEBOV2. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately ten-fold lower vaccine-associated viremia compared to the first generation vaccine and both provided complete, single dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV. PMID:25853476

  3. Ethical considerations in the conduct of research on therapies for the prevention and treatment of Ebola virus disease in developing countries

    PubMed Central

    Folayan, Morenike Oluwatoyin; Haire, Bridget Gabrielle

    2015-01-01

    The devastating toll of the Ebola epidemic in West Africa necessitates considerations of new approaches to research into new prevention technologies and treatments for Ebola Virus Disease (EVD). Research must be planned and delivered in consultation with civil society from the epicentre to prevent mistrust and misunderstanding. Ethical considerations include development of local research and regulatory capacity; negotiating the standard of prevention packages for research participants, including healthcare workers; and strengthening health systems in developing countries to ensure effective response to future EVD outbreaks in the region. Also, strategic consultation with local communities is an ethical imperative for EVD research, particularly where there is potential for differential access to prevention and care packages between trial staff and local hospital staff.

  4. The Laboratory Medicine and the care of patients infected by the Ebola virus. Experience in a reference hospital of Madrid, Spain.

    PubMed

    Fernandez-Puntero, Belen; Gomez-Rioja, Ruben; Alcaide, Maria Jose; Oliver, Paloma; Fernandez-Calle, Pilar; Iturzaeta, Jose Manuel; Buno, Antonio

    2015-11-01

    The ongoing Ebola virus outbreak in several countries in West Africa was considered by the World Health Organisation (WHO) as a public health emergency of international concern. Healthcare providers must be prepared by organising specific procedures in our hospitals based on recommendations from national and international healthcare organisations. Two aims should be considered: appropriate medical care for patients with suspected or confirmed disease must be ensured, as must measures to prevent transmission to healthcare workers. The clinical laboratory plays an important role and must define and establish its own procedures in accordance with clinicians and integrated into those of the institution, starting with the definition of the organisation model in the laboratory to achieve those goals. In this review we present our experience based on the care of three patients with confirmed cases. We hope it will help other colleagues to plan for Ebola. PMID:26053009

  5. Necrotizing Scleritis, Conjunctivitis, and Other Pathologic Findings in the Left Eye and Brain of an Ebola Virus-Infected Rhesus Macaque (Macaca mulatta) With Apparent Recovery and a Delayed Time of Death.

    PubMed

    Alves, Derron A; Honko, Anna N; Kortepeter, Mark G; Sun, Mei; Johnson, Joshua C; Lugo-Roman, Luis A; Hensley, Lisa E

    2016-01-01

    A 3.5-year-old adult female rhesus macaque (Macaca mulatta) manifested swelling of the left upper eyelid and conjunctiva and a decline in clinical condition 18 days following intramuscular challenge with Ebola virus (EBOV; Kikwit-1995), after apparent clinical recovery. Histologic lesions with strong EBOV antigen staining were noted in the left eye (scleritis, conjunctivitis, and peri-optic neuritis), brain (choriomeningoencephalitis), stomach, proximal duodenum, and pancreas. Spleen, liver, and adrenal glands, common targets for acute infection, appeared histologically normal with no evidence of EBOV immunoreactivity. These findings may provide important insight for understanding sequelae seen in West African survivors of Ebola virus disease. PMID:26153408

  6. A Single Intranasal Inoculation with a Paramyxovirus-Vectored Vaccine Protects Guinea Pigs against a Lethal-Dose Ebola Virus Challenge

    PubMed Central

    Bukreyev, Alexander; Yang, Lijuan; Zaki, Sherif R.; Shieh, Wun-Ju; Rollin, Pierre E.; Murphy, Brian R.; Collins, Peter L.; Sanchez, Anthony

    2006-01-01

    To determine whether intranasal inoculation with a paramyxovirus-vectored vaccine can induce protective immunity against Ebola virus (EV), recombinant human parainfluenza virus type 3 (HPIV3) was modified to express either the EV structural glycoprotein (GP) by itself (HPIV3/EboGP) or together with the EV nucleoprotein (NP) (HPIV3/EboGP-NP). Expression of EV GP by these recombinant viruses resulted in its efficient incorporation into virus particles and increased cytopathic effect in Vero cells. HPIV3/EboGP was 100-fold more efficiently neutralized by antibodies to EV than by antibodies to HPIV3. Guinea pigs infected with a single intranasal inoculation of 105.3 PFU of HPIV3/EboGP or HPIV3/EboGP-NP showed no apparent signs of disease yet developed a strong humoral response specific to the EV proteins. When these animals were challenged with an intraperitoneal injection of 103 PFU of EV, there were no outward signs of disease, no viremia or detectable EV antigen in the blood, and no evidence of infection in the spleen, liver, and lungs. In contrast, all of the control animals died or developed severe EV disease following challenge. The highly effective immunity achieved with a single vaccine dose suggests that intranasal immunization with live vectored vaccines based on recombinant respiratory viruses may be an advantageous approach to inducing protective responses against severe systemic infections, such as those caused by hemorrhagic fever agents. PMID:16474134

  7. Modeling the 2014 Ebola Virus Epidemic - Agent-Based Simulations, Temporal Analysis and Future Predictions for Liberia and Sierra Leone.

    PubMed

    Siettos, Constantinos; Anastassopoulou, Cleo; Russo, Lucia; Grigoras, Christos; Mylonakis, Eleftherios

    2015-01-01

    We developed an agent-based model to investigate the epidemic dynamics of Ebola virus disease (EVD) in Liberia and Sierra Leone from May 27 to December 21, 2014. The dynamics of the agent-based simulator evolve on small-world transmission networks of sizes equal to the population of each country, with adjustable densities to account for the effects of public health intervention policies and individual behavioral responses to the evolving epidemic. Based on time series of the official case counts from the World Health Organization (WHO), we provide estimates for key epidemiological variables by employing the so-called Equation-Free approach. The underlying transmission networks were characterized by rather random structures in the two countries with densities decreasing by ~19% from the early (May 27-early August) to the last period (mid October-December 21). Our estimates for the values of key epidemiological variables, such as the mean time to death, recovery and the case fatality rate, are very close to the ones reported by the WHO Ebola response team during the early period of the epidemic (until September 14) that were calculated based on clinical data. Specifically, regarding the effective reproductive number Re, our analysis suggests that until mid October, Re was above 2.3 in both countries; from mid October to December 21, Re dropped well below unity in Liberia, indicating a saturation of the epidemic, while in Sierra Leone it was around 1.9, indicating an ongoing epidemic. Accordingly, a ten-week projection from December 21 estimated that the epidemic will fade out in Liberia in early March; in contrast, our results flashed a note of caution for Sierra Leone since the cumulative number of cases could reach as high as 18,000, and the number of deaths might exceed 5,000, by early March 2015. However, by processing the reported data of the very last period (December 21, 2014-January 18, 2015), we obtained more optimistic estimates indicative of a remission of the epidemic in Sierra Leone, as reflected by the derived Re (~0.82, 95% CI: 0.81-0.83). PMID:26064785

  8. Ebola Virus and Severe Acute Respiratory Syndrome Coronavirus Display Late Cell Entry Kinetics: Evidence that Transport to NPC1+ Endolysosomes Is a Rate-Defining Step

    PubMed Central

    Mingo, Rebecca M.; Simmons, James A.; Shoemaker, Charles J.; Nelson, Elizabeth A.; Schornberg, Kathryn L.; D'Souza, Ryan S.; Casanova, James E.

    2014-01-01

    ABSTRACT Ebola virus (EBOV) causes hemorrhagic fevers with high mortality rates. During cellular entry, the virus is internalized by macropinocytosis and trafficked through endosomes until fusion between the viral and an endosomal membrane is triggered, releasing the RNA genome into the cytoplasm. We found that while macropinocytotic uptake of filamentous EBOV viruslike particles (VLPs) expressing the EBOV glycoprotein (GP) occurs relatively quickly, VLPs only begin to enter the cytoplasm after a 30-min lag, considerably later than particles bearing the influenza hemagglutinin or GP from lymphocytic choriomeningitis virus, which enter through late endosomes (LE). For EBOV, the long lag is not due to the large size or unusual shape of EBOV filaments, the need to prime EBOV GP to the 19-kDa receptor-binding species, or a need for unusually low endosomal pH. In contrast, since we observed that EBOV entry occurs upon arrival in Niemann-Pick C1 (NPC1)-positive endolysosomes (LE/Lys), we propose that trafficking to LE/Lys is a key rate-defining step. Additional experiments revealed, unexpectedly, that severe acute respiratory syndrome (SARS) S-mediated entry also begins only after a 30-min lag. Furthermore, although SARS does not require NPC1 for entry, SARS entry also begins after colocalization with NPC1. Since the only endosomal requirement for SARS entry is cathepsin L activity, we tested and provide evidence that NPC1+ LE/Lys have higher cathepsin L activity than LE, with no detectable activity in earlier endosomes. Our findings suggest that both EBOV and SARS traffic deep into the endocytic pathway for entry and that they do so to access higher cathepsin activity. IMPORTANCE Ebola virus is a hemorrhagic fever virus that causes high fatality rates when it spreads from zoonotic vectors into the human population. Infection by severe acute respiratory syndrome coronavirus (SARS-CoV) causes severe respiratory distress in infected patients. A devastating outbreak of EBOV occurred in West Africa in 2014, and there was a significant outbreak of SARS in 2003. No effective vaccine or treatment has yet been approved for either virus. We present evidence that both viruses traffic late into the endocytic pathway, to NPC1+ LE/Lys, in order to enter host cells, and that they do so to access high levels of cathepsin activity, which both viruses use in their fusion-triggering mechanisms. This unexpected similarity suggests an unexplored vulnerability, trafficking to NPC1+ LE/Lys, as a therapeutic target for SARS and EBOV. PMID:25552710

  9. Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe

    PubMed Central

    2012-01-01

    A high-throughput screen identified adamantane dipeptide 1 as an inhibitor of Ebola virus (EboV) infection. Hit-to-lead optimization to determine the structure–activity relationship (SAR) identified the more potent EboV inhibitor 2 and a photoaffinity labeling agent 3. These antiviral compounds were employed to identify the target as Niemann-Pick C1 (NPC1), a host protein that binds the EboV glycoprotein and is essential for infection. These studies establish NPC1 as a promising target for antiviral therapy. PMID:23526644

  10. Development and use of mobile containment units for the evaluation and treatment of potential Ebola virus disease patients in a United States hospital.

    PubMed

    Sugalski, Gregory; Murano, Tiffany; Fox, Adam; Rosania, Anthony

    2015-05-01

    Ebola virus disease (EVD) has been the subject of recent attention due to the current outbreak in West Africa, as well as the appearance of a number of cases within the United States. The presence of EVD patients in the United States required health care systems to prepare for the identification and management of both patients under investigation and patients with confirmed EVD infection. This article discusses the development and use of a mobile containment unit in an extended treatment area as a novel approach to isolation and screening of potential EVD patients. PMID:25900204

  11. Meeting the Challenge of Ebola Virus Disease in a Holistic Manner by Taking into Account Socioeconomic and Cultural Factors: The Experience of West Africa

    PubMed Central

    Phua, Kai-Lit

    2015-01-01

    Even if an effective vaccine against Ebola virus disease (EVD) becomes available, the challenges posed by this disease are complex. Certain socioeconomic and cultural factors have been linked to recent outbreaks of EVD in West Africa. The outbreaks revealed widespread ignorance by laypersons of EVD etiology, mode of transmission, and personal protective measures that can be taken. Lack of trust in the authorities, virus infection during the preparation of “bushmeat” for human consumption, traditional funerary practices, and relatively free flow of goods and people between regions and across international borders may have facilitated the spread of EVD and hindered outbreak control efforts. Inadequacy in health systems of the most seriously affected countries, such as Guinea, Sierra Leone, and Liberia, is also an important factor. The objectives of this article are to argue that EVD should be evaluated in a systematic and holistic manner and that this can be done through the use of the modified Haddon Matrix. PMID:26604778

  12. Preventive and social cost implications of Ebola Virus Disease (EVD) outbreak on selected organizations in Lagos state, Nigeria

    PubMed Central

    Olugasa, Babasola Oluseyi; Oshinowo, Oluwafunmilola Yemisi; Odigie, Eugene Amienwanlen

    2015-01-01

    Introduction As Ebola virus disease (EVD) continues to pose public health challenge in West Africa, with attending fears and socio-economic implications in the current epidemic challenges. It is compelling to estimate the social and preventive costs of EVD containment in a Nigerian city. Hence, this study was to determine the social and preventive cost implications of EVD among selected public institutions in Lagos, Nigeria, from July to December, 2014. Methods Questionnaires and key-informants interview were administered to respondents and administrators of selected hospitals, hotels and schools in Eti-Osa Local Government Area of Lagos State. Knowledge of disease transmission, mortality and protocols for prevention, including cost of specific preventive measures adopted against EVD were elicited from respondents. Descriptive statistics and categorical analysis were used to summarize and estimate social and preventive costs incurred by respective institutions. Results An estimated five million, nineteen thousand, three hundred and seventy-nine Naira and eighty kobo (N5,019,379.80) only was observed as direct and social cost implication of EVD prevention. This amount translated into a conservative estimate of one billion, twenty-seven million, ninety-four thousand, seven hundred and fifty-six Naira (N1,027,094,756.10) for a total of four thousand schools, two hundred and fifty-three hospitals and one thousand, four hundred and fifty one hotels in Lagos during the period (July 20-November 20, 2014). Conclusion The high cost of prevention of EVD within the short time-frame indicated high importance attached to a preventive policy against highly pathogenic zoonotic disease in Nigeria.

  13. Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger.

    PubMed

    Markosyan, Ruben M; Miao, Chunhui; Zheng, Yi-Min; Melikyan, Gregory B; Liu, Shan-Lu; Cohen, Fredric S

    2016-01-01

    Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the transfer of both cytoplasmic and membrane dyes. A small molecule fusion inhibitor, a neutralizing antibody, as well as mutations in EBOV GP known to reduce viral infection, all greatly reduce fusion. By monitoring redistribution of small aqueous dyes between cells and by electrical capacitance measurements, we discovered that EBOV GP-mediated fusion pores do not readily enlarge-a marked difference from the behavior of other viral fusion proteins. EBOV GP must be cleaved by late endosome-resident cathepsins B or L in order to become fusion-competent. Cleavage of cell surface-expressed GP appears to occur in endosomes, as evidenced by the fusion block imposed by cathepsin inhibitors, agents that raise endosomal pH, or an inhibitor of anterograde trafficking. Treating effector cells with a recombinant soluble cathepsin B or thermolysin, which cleaves GP into an active form, increases the extent of fusion, suggesting that a fraction of surface-expressed GP is not cleaved. Whereas the rate of fusion is increased by a brief exposure to acidic pH, fusion does occur at neutral pH. Importantly, the extent of fusion is independent of external pH in experiments in which cathepsin activity is blocked and EBOV GP is cleaved by thermolysin. These results imply that low pH promotes fusion through the well-known pH-dependent activity of cathepsins; fusion induced by cleaved EBOV GP is a process that is fundamentally independent of pH. The cell-cell fusion system has revealed some previously unappreciated features of EBOV entry, which could not be readily elucidated in the context of endosomal entry. PMID:26730950

  14. Emergency Medical Services Public Health Implications and Interim Guidance for the Ebola Virus in the United States

    E-print Network

    McCoy, Christopher E.; Lotfipour, Shahram; Chakravarthy, Bharath; Schultz, Carl; Barton, Erik

    2014-01-01

    www.cdc.gov/vhf/ebola/hcp/infection-prevention-and-control-Ebola Outbreak in West Africa. Centers for Disease Control and Prevention.Ebola Diagnosed in the United States. Centers for Disease Control and Prevention.

  15. Extracting transmission networks from phylogeographic data for epidemic and endemic diseases: Ebola virus in Sierra Leone, 2009 H1N1 pandemic influenza and polio in Nigeria

    PubMed Central

    Famulare, Michael; Hu, Hao

    2015-01-01

    Background Phylogeography improves our understanding of spatial epidemiology. However, application to practical problems requires choices among computational tools to balance statistical rigor, computational complexity, sensitivity to sampling strategy and interpretability. Methods We introduce a fast, heuristic algorithm to reconstruct partially-observed transmission networks (POTN) that combines features of phylogenetic and transmission tree approaches. We compare the transmission network generated by POTN with existing algorithms (BEAST and SeqTrack), and discuss the benefits and challenges of phylogeographic analysis on examples of epidemic and endemic diseases: Ebola virus, H1N1 pandemic influenza and polio. Results For the 2014 Sierra Leone Ebola virus outbreak and the 2009 H1N1 outbreak, all three methods provide similarly plausible transmission histories but differ in detail. For polio in northern Nigeria, we discuss performance trade-offs between the POTN and discrete phylogeography in BEAST and conclude that spatial history reconstruction is limited by under-sampling. Conclusions POTN is complementary to available tools on densely-sampled data, fails gracefully on under-sampled data and is scalable to accommodate larger datasets. We provide further evidence for the utility of phylogeography for understanding transmission networks of rapidly evolving epidemics. We propose simple heuristic criteria to identify how sampling rates and disease dynamics interact to determine fundamental limitations of phylogeographic inference. PMID:25733563

  16. IFITMs restrict the replication of multiple pathogenic viruses

    PubMed Central

    Perreira, Jill M.; Chin, Christopher R.; Feeley, Eric M.; Brass, Abraham L.

    2014-01-01

    The IFITM family of proteins inhibit a growing number of pathogenic viruses, among them influenza A virus, dengue virus, hepatitis C virus, and Ebola virus. This review covers recent developments in our understanding of the IFITM’s molecular determinants, potential mechanisms of action, and impact on pathogenesis. PMID:24076421

  17. Middletown, Connecticut 06459 Ebola Travel Advisory

    E-print Network

    Thomas, Ellen

    Middletown, Connecticut 06459 Ebola Travel Advisory The devastating outbreak of the Ebola virus in West Africa has caused pain and suffering on an almost that region. Even though this topic has receded from the headlines, Ebola remains

  18. Simulating familial Ebola transmission in urban environments

    E-print Network

    Morrow, James A.

    Simulating familial Ebola transmission in urban environments Team # 38723 February 10, 2015, specifically considering the best way to distribute a hypothetical cure for Ebola virus disease (EVD) in an ur to Ebola . . . . . . . . . . . . . . . . . . . . . . 3 1.2 Assumptions and Simplifications

  19. Radiology preparedness in ebola virus disease: guidelines and challenges for disinfection of medical imaging equipment for the protection of staff and patients.

    PubMed

    Mollura, Daniel J; Palmore, Tara N; Folio, Les R; Bluemke, David A

    2015-05-01

    The overlap of early Ebola virus disease (EVD) symptoms (eg, fever, headache, abdominal pain, diarrhea, emesis, and fatigue) with symptoms of other more common travel-related diseases (eg, malaria, typhoid fever, pneumonia, and meningococcemia) may result in delayed diagnosis of EVD before isolation of infected patients. Radiology departments should consider policies for and approaches to decontamination of expensive and potentially easily damaged radiology equipment. In addition, the protection of radiology personnel must be considered during the work-up phase of undiagnosed EVD patients presenting to emergency departments. The purpose of this article is to consider the effect of EVD on radiology departments and imaging equipment, with particular consideration of guidelines currently available from the Centers for Disease Control and Prevention that may be applicable to radiology. PMID:25654616

  20. Radiology Preparedness in Ebola Virus Disease: Guidelines and Challenges for Disinfection of Medical Imaging Equipment for the Protection of Staff and Patients

    PubMed Central

    Palmore, Tara N.; Folio, Les R.; Bluemke, David A.

    2015-01-01

    The overlap of early Ebola virus disease (EVD) symptoms (eg, fever, headache, abdominal pain, diarrhea, emesis, and fatigue) with symptoms of other more common travel-related diseases (eg, malaria, typhoid fever, pneumonia, and meningococcemia) may result in delayed diagnosis of EVD before isolation of infected patients. Radiology departments should consider policies for and approaches to decontamination of expensive and potentially easily damaged radiology equipment. In addition, the protection of radiology personnel must be considered during the work-up phase of undiagnosed EVD patients presenting to emergency departments. The purpose of this article is to consider the effect of EVD on radiology departments and imaging equipment, with particular consideration of guidelines currently available from the Centers for Disease Control and Prevention that may be applicable to radiology. © RSNA, 2015 PMID:25654616

  1. Community Care Centre (CCC) as adjunct in the management of Ebola Virus Disease (EVD) cases during outbreaks: experience from Sierra Leone

    PubMed Central

    Olu, Olushayo; Cormican, Martin; Kamara, Kande-Bure; Butt, Waqar

    2015-01-01

    Community Care Centres (CCCs) represent an innovative response to the containment of infection and the care of those infected in the context of an an Ebola Virus Disease (EVD) outbreak of unprecedented scale. This paper describes the implementation of this response in the Port Loko district of Sierra Leone in the last quarter of 2014. CCCs were effective in encouraging EVD patients to come forward, thus removing risk of transmission to their families and communities however there is significant scope for improvement in care for patients in the centres if the model is applied in future outbreaks of infectious disease. Changes in lay out of the centres, in staff training and support, in logistics and patient education are recommended.

  2. The L–VP35 and L–L interaction domains reside in the amino terminus of the Ebola virus L protein and are potential targets for antivirals

    PubMed Central

    Trunschke, Martina; Conrad, Dominik; Enterlein, Sven; Olejnik, Judith; Brauburger, Kristina; Mühlberger, Elke

    2013-01-01

    The Ebola virus (EBOV) RNA-dependent RNA polymerase (RdRp) complex consists of the catalytic subunit of the polymerase, L, and its cofactor VP35. Using immunofluorescence analysis and coimmunoprecipitation assays, we mapped the VP35 binding site on L. A core binding domain spanning amino acids 280– 370 of L was sufficient to mediate weak interaction with VP35, while the entire N-terminus up to amino acid 380 was required for strong VP35–L binding. Interestingly, the VP35 binding site overlaps with an N-terminal L homo-oligomerization domain in a non-competitive manner. N-terminal L deletion mutants containing the VP35 binding site were able to efficiently block EBOV replication and transcription in a minigenome system suggesting the VP35 binding site on L as a potential target for the development of antivirals. PMID:23582637

  3. Ebola/Marburg Research

    MedlinePLUS

    ... It is now being tested in the NIH-led PREVAIL II (Partnership for Research on Ebola Virus ... the 2014–2015 Ebola outbreak in West Africa. Led by the Broad Institute's Dr. Pardis Sabeti, researchers ...

  4. A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of Ebola hemorrhagic fever. Commission de Lutte contre les Epidémies à Kikwit.

    PubMed

    Zaki, S R; Shieh, W J; Greer, P W; Goldsmith, C S; Ferebee, T; Katshitshi, J; Tshioko, F K; Bwaka, M A; Swanepoel, R; Calain, P; Khan, A S; Lloyd, E; Rollin, P E; Ksiazek, T G; Peters, C J

    1999-02-01

    Laboratory diagnosis of Ebola hemorrhagic fever (EHF) is currently performed by virus isolation and serology and can be done only in a few high-containment laboratories worldwide. In 1995, during the EHF outbreak in the Democratic Republic of Congo, the possibility of using immunohistochemistry (IHC) testing of formalin-fixed postmortem skin specimens was investigated as an alternative diagnostic method for EHF. Fourteen of 19 cases of suspected EHF met the surveillance definition for EHF and were positive by IHC. IHC, serologic, and virus isolation results were concordant for all EHF and non-EHF cases. IHC and electron microscopic examination showed that endothelial cells, mononuclear phagocytes, and hepatocytes are main targets of infection, and IHC showed an association of cellular damage with viral infection. The finding of abundant viral antigens and particles in the skin of EHF patients suggests an epidemiologic role for contact transmission. IHC testing of formalin-fixed skin specimens is a safe, sensitive, and specific method for laboratory diagnosis of EHF and should be useful for EHF surveillance and prevention. PMID:9988163

  5. Foodborne viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Testing for human pathogenic viruses in foods represents a formidable task requiring the extraction, concentration, and assay of a host of viruses from a wide range of food matrices. The enteric viruses, particularly genogroup I and II (GI and GII) noroviruses and hepatitis A virus, are the princip...

  6. Temporal Course of 2014 Ebola Virus Disease (EVD) Outbreak in West Africa Elucidated through Morbidity and Mortality Data: A Tale of Three Countries

    PubMed Central

    Hsieh, Ying-Hen

    2015-01-01

    The explosive outbreak of Ebola virus disease (EVD) in West Africa in 2014 appeared to have lessened in 2015, but potentially continues be a global public health threat. A simple mathematical model, the Richards model, is utilized to gauge the temporal variability in the spread of the Ebola virus disease (EVD) in West Africa in terms of its reproduction number R and its temporal changes via detection of epidemic waves and turning points during the 2014 outbreaks in the three most severely affected countries; namely, Guinea, Liberia, and Sierra Leone. The results reveal multiple waves of infection in each of these three countries, of varying lengths from a little more than one week to more than one month. All three countries exhibit marginally fluctuating reproduction numbers during June-October before gradually declining. Although high mobility continues between neighboring populations of these countries across the borders, outbreak in these three countries exhibits decidedly different temporal patterns. Guinea had the most waves but maintained consistently low transmissibility and hence has the smallest number of reported cases. Liberia had highest level of transmission before October, but has remained low since, with no detectable wave after the New Year. Sierra Leone has gradually declining waves since October, but still generated detectable waves up to mid-March 2015, and hence has cumulated the largest number of cases—exceeding that of Guinea and Liberia combined. Analysis indicates that, despite massive amount of international relief and intervention efforts, the outbreak is persisting in these regions in waves, albeit more sparsely and at a much lower level since the beginning of 2015. PMID:26559945

  7. Phylogenetic assessment of filoviruses: how many lineages of Marburg virus?

    E-print Network

    Peterson, A. Townsend; Holder, Mark T.

    2012-07-01

    Filoviruses have to date been considered as consisting of one diverse genus (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider this idea by means of detailed phylogenetic analyses of sequence data available...

  8. Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease

    PubMed Central

    Ker, Katharine; Tansley, Gavin; Beecher, Deirdre; Perner, Anders; Shakur, Haleema; Harris, Tim; Roberts, Ian

    2015-01-01

    Background Dehydration is an important cause of death in patients with Ebola virus disease (EVD). Parenteral fluids are often required in patients with fluid requirements in excess of their oral intake. The peripheral intravenous route is the most commonly used method of parenteral access, but inserting and maintaining an intravenous line can be challenging in the context of EVD. Therefore it is important to consider the advantages and disadvantages of different routes for achieving parenteral access (e.g. intravenous, intraosseous, subcutaneous and intraperitoneal). Objectives To compare the reliability, ease of use and speed of insertion of different parenteral access methods. Search methods We ran the search on 17 November 2014. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid MEDLINE(R) and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), CINAHL (EBSCOhost), clinicaltrials.gov and screened reference lists. Selection criteria Randomised controlled trials comparing different parenteral routes for the infusion of fluids or medication. Data collection and analysis Two review authors examined the titles and abstracts of records obtained by searching the electronic databases to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. Outcome measures of interest were success of insertion; time required for insertion; number of insertion attempts; number of dislodgements; time period with functional access; local site reactions; clinicians' perception of ease of administration; needlestick injury to healthcare workers; patients' discomfort; and mortality. For trials involving the administration of fluids we also collected data on the volume of fluid infused, changes in serum electrolytes and markers of renal function. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the following outcomes: success of insertion, time required for insertion, number of dislodgements, volume of fluid infused and needlestick injuries. Main results We included 17 trials involving 885 participants. Parenteral access was used to infuse fluids in 11 trials and medications in six trials. None of the trials involved patients with EVD. Intravenous and intraosseous access was compared in four trials; intravenous and subcutaneous access in 11; peripheral intravenous and intraperitoneal access in one; saphenous vein cutdown and intraosseous access in one; and intraperitoneal with subcutaneous access in one. All of the trials assessing the intravenous method involved peripheral intravenous access. We judged few trials to be at low risk of bias for any of the assessed domains. Compared to the intraosseous group, patients in the intravenous group were more likely to experience an insertion failure (risk ratio (RR) 3.89, 95% confidence interval (CI) 2.39 to 6.33; n = 242; GRADE rating: low). We did not pool data for time to insertion but estimates from the trials suggest that inserting intravenous access takes longer (GRADE rating: moderate). Clinicians judged the intravenous route to be easier to insert (RR 0.15, 95% CI 0.04 to 0.61; n = 182). A larger volume of fluids was infused via the intravenous route (GRADE rating: moderate). There was no evidence of a difference between the two routes for any other outcomes, including adverse events. Compared to the subcutaneous group, patients in the intravenous group were more likely to experience an insertion failure (RR 14.79, 95% CI 2.87 to 76.08; n = 238; GRADE rating: moderate) and dislodgement of the device (RR 3.78, 95% CI 1.16 to 12.34; n = 67; GRADE rating: low). Clinicians also judged the intravenous route as being more difficult to insert and patients were more likely to be agitated in the intravenous group. Patients in the intravenous group were more likely to develop a local infection and phlebitis,

  9. Ebola and next gen. sequencing Maisie Steinbrink

    E-print Network

    Skop, Ahna

    Ebola and next gen. sequencing Maisie Steinbrink Mikayla Simons #12;Road map 1. What is Ebola? Why does it matter? 2.Next Generation Sequencing 3. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. #12;What is Ebola? #12;Types of Ebolavirus Ebola Zaire Tai Forest

  10. Bat Flight and Zoonotic Viruses

    PubMed Central

    Cryan, Paul M.; Cunningham, Andrew A.; Fooks, Anthony R.; Hayman, David T.S.; Luis, Angela D.; Peel, Alison J.; Plowright, Raina K.; Wood, James L.N.

    2014-01-01

    Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in bats are the subject of speculation. We hypothesize that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this host–virus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant of the fever response and less virulent to their natural hosts. PMID:24750692

  11. Bat flight and zoonotic viruses

    USGS Publications Warehouse

    O'Shea, Thomas; Cryan, Paul M.; Cunningham, Andrew A.; Fooks, Anthony R.; Hayman, David T.S.; Luis, Angela D.; Peel, Alison J.; Plowright, Raina K.; Wood, James L.N.

    2014-01-01

    Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in bats are the subject of speculation. We hypothesize that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this host–virus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant of the fever response and less virulent to their natural hosts.

  12. Hepadna viruses

    SciTech Connect

    Robinson, W.; Koike, K.; Will, H.

    1987-01-01

    This book examines the molecular biology, disease pathogenesis, epidemiology, and clinical features of hepadna and other viruses with hepatic tropism and outlines future directions and approaches for their management. The volume's six sections provide a review of the various features, mechanisms, and functions of these viruses, ranging from hepadna virus replication and regulation of gene expression to the structure and function of hepadna-virus gene products.

  13. Ebola: Hidden reservoirs

    E-print Network

    Heeney, Jonathan L.

    2015-11-25

    West Africa's Ebola epidemic continues to reveal surprises. Although the animal species that originally passed the virus to people remains a mystery, a virus reservoir and persistent disease have been identified in some human survivors....

  14. Assessment of the MSF triage system, separating patients into different wards pending Ebola virus laboratory confirmation, Kailahun, Sierra Leone, July to September 2014.

    PubMed

    Vogt, Florian; Fitzpatrick, Gabriel; Patten, Gabriela; van den Bergh, Rafael; Stinson, Kathryn; Pandolfi, Luigi; Squire, James; Decroo, Tom; Declerck, Hilde; Van Herp, Michel

    2015-12-17

    Prevention of nosocomial Ebola virus (EBOV) infection among patients admitted to an Ebola management centre (EMC) is paramount. Current Médecins Sans Frontières (MSF) guidelines recommend classifying admitted patients at triage into suspect and highly-suspect categories pending laboratory confirmation. We investigated the performance of the MSF triage system to separate patients with subsequent EBOV-positive laboratory test (true-positive admissions) from patients who were initially admitted on clinical grounds but subsequently tested EBOV-negative (false-positive admissions). We calculated standard diagnostic test statistics for triage allocation into suspect or highly-suspect wards (index test) and subsequent positive or negative laboratory results (reference test) among 433 patients admitted into the MSF EMC Kailahun, Sierra Leone, between 1 July and 30 September 2014. 254 (59%) of admissions were classified as highly-suspect, the remaining 179 (41%) as suspect. 276 (64%) were true-positive admissions, leaving 157 (36.3%) false-positive admissions exposed to the risk of nosocomial EBOV infection. The positive predictive value for receiving a positive laboratory result after being allocated to the highly-suspect ward was 76%. The corresponding negative predictive value was 54%. Sensitivity and specificity were 70% and 61%, respectively. Results for accurate patient classification were unconvincing. The current triage system should be changed. Whenever possible, patients should be accommodated in single compartments pending laboratory confirmation. Furthermore, the initial triage step on whether or not to admit a patient in the first place must be improved. What is ultimately needed is a point-of-care EBOV diagnostic test that is reliable, accurate, robust, mobile, affordable, easy to use outside strict biosafety protocols, providing results with quick turnaround time. PMID:26727011

  15. The landscape configuration of zoonotic transmission of Ebola virus disease in West and Central Africa: interaction between population density and vegetation cover

    PubMed Central

    Haseeb, MA

    2015-01-01

    Ebola virus disease (EVD) is an emerging infectious disease of zoonotic origin that has been responsible for high mortality and significant social disruption in West and Central Africa. Zoonotic transmission of EVD requires contact between susceptible human hosts and the reservoir species for Ebolaviruses, which are believed to be fruit bats. Nevertheless, features of the landscape that may facilitate such points of contact have not yet been adequately identified. Nor have spatial dependencies between zoonotic EVD transmission and landscape structures been delineated. This investigation sought to describe the spatial relationship between zoonotic EVD transmission events, or spillovers, and population density and vegetation cover. An inhomogeneous Poisson process model was fitted to all precisely geolocated zoonotic transmissions of EVD in West and Central Africa. Population density was strongly associated with spillover; however, there was significant interaction between population density and green vegetation cover. In areas of very low population density, increasing vegetation cover was associated with a decrease in risk of zoonotic transmission, but as population density increased in a given area, increasing vegetation cover was associated with increased risk of zoonotic transmission. This study showed that the spatial dependencies of Ebolavirus spillover were associated with the distribution of population density and vegetation cover in the landscape, even after controlling for climate and altitude. While this is an observational study, and thus precludes direct causal inference, the findings do highlight areas that may be at risk for zoonotic EVD transmission based on the spatial configuration of important features of the landscape. PMID:25648654

  16. Dealing with Ebola virus disease in Spain: epidemiological inquiries received by the Department of Public Health Alerts, April to December 2014.

    PubMed

    Blaya-Nováková, Vendula; Lópaz-Pérez, María Ángeles; Méndez-Navas, Isabel; Domínguez-Berjón, María Felicitas; Astray-Mochales, Jenaro

    2015-11-01

    We describe the inquiries regarding Ebola virus disease (EVD) received by the Department of Public Health Alerts of the Community of Madrid between April and December 2014. A total of 242 inquiries were received. Consultations were initiated most frequently by hospital clinicians (59 inquiries, 24%), private citizens (57 inquiries, 24%) and primary care physicians (53 inquiries, 22%). The most frequent topic of inquiry was possible EVD in a patient (215 inquiries, 89%). Among these, 31 persons (14%) presented both EVD-compatible symptoms and epidemiological risk factors, and 11 persons (5%) fulfilled the criteria for a person under investigation. Recent travel abroad was reported in 96 persons (45%), but only 32 (15%) had travelled to an EVD-affected area. Two high-risk and one low-risk contact were identified through these inquiries. Low specificity of the EVD symptoms led to many difficulties in protocol application. Ineffective communication with healthcare professionals and unfamiliarity with the EVD protocols caused many case classification errors. A rapid consultation service by telephone is essential for providing qualified advice during emergencies. Our experience may help other countries dimension their activities and resources for managing similar exceptional outbreaks in the future. PMID:26554574

  17. Live Virus Smallpox Vaccine

    MedlinePLUS

    ... Index SMALLPOX FACT SHEET The Live Virus Smallpox Vaccine The vaccinia virus is the "live virus" used ... cannot cause smallpox. What is a "live virus" vaccine? A "live virus" vaccine is a vaccine that ...

  18. Diseases Caused by Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The symptoms, causal agents, epidemiology and management of important virus diseases in chickpea and lentil crops were reviewed in depth. The virus diseases include.Alflafa mosaic virus, Cucumber mosaiv virus, Faba bean necrotic yellows virus, Pea enation mosaic virus, Pea seed-borne mosaci virus,...

  19. Datasets: Phylogenetic assessment of filoviruses: how many lineages of Marburg virus?

    E-print Network

    Peterson, A. Townsend; Holder, Mark T.

    2012-06-08

    Filoviruses have to date been considered as consisting of one diverse genus (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider this idea by means of detailed phylogenetic analyses of sequence ...

  20. Computer viruses

    NASA Technical Reports Server (NTRS)

    Denning, Peter J.

    1988-01-01

    The worm, Trojan horse, bacterium, and virus are destructive programs that attack information stored in a computer's memory. Virus programs, which propagate by incorporating copies of themselves into other programs, are a growing menace in the late-1980s world of unprotected, networked workstations and personal computers. Limited immunity is offered by memory protection hardware, digitally authenticated object programs,and antibody programs that kill specific viruses. Additional immunity can be gained from the practice of digital hygiene, primarily the refusal to use software from untrusted sources. Full immunity requires attention in a social dimension, the accountability of programmers.

  1. Heartland Virus

    MedlinePLUS

    ... through the bite of a mosquito, tick, or sandfly. How do people get infected with Heartland virus? ... in the same genus as Rift Valley fever, Sandfly fever, Toscana, and Severe fever with thrombocytopenia syndrome ( ...

  2. West Nile Virus

    MedlinePLUS

    ... virus is a virus that can infect humans, birds, horses and mosquitoes. Infection from this virus is ... spread by mosquitoes. Mosquitoes become infected by biting birds that carry the virus. People can get West ...

  3. Computer Viruses. Technology Update.

    ERIC Educational Resources Information Center

    Ponder, Tim, Comp.; Ropog, Marty, Comp.; Keating, Joseph, Comp.

    This document provides general information on computer viruses, how to help protect a computer network from them, measures to take if a computer becomes infected. Highlights include the origins of computer viruses; virus contraction; a description of some common virus types (File Virus, Boot Sector/Partition Table Viruses, Trojan Horses, and…

  4. Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study

    PubMed Central

    Boëlle, Pierre-Yves; Magassouba, N’Faly; Bah, Elhadj Ibrahima; Koivogui, Lamine; Diallo, Boubacar; Diallo, Alpha Amadou; Keita, Sakoba; Konde, Mandy Kader; Fowler, Robert; Fall, Gamou; Cauchemez, Simon; Sall, Amadou Alpha

    2015-01-01

    Background The case fatality ratio (CFR) of Ebola virus disease (EVD) can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investigate whether viremia in EVD patients may be used to evaluate baseline EVD CFRs. Methods and Findings We analyzed the laboratory and epidemiological records of patients with EVD confirmed by reverse transcription PCR hospitalized in the Conakry area, Guinea, between 1 March 2014 and 28 February 2015. We used viremia and other variables to model the CFR. Data for 699 EVD patients were analyzed. In the week following symptom onset, mean viremia remained stable, and the CFR increased with viremia, V, from 21% (95% CI 16%–27%) for low viremia (V < 104.4 copies/ml) to 53% (95% CI 44%–61%) for intermediate viremia (104.4 ? V < 105.2 copies/ml) and 81% (95% CI 75%–87%) for high viremia (V ? 105.2 copies/ml). Compared to adults (15–44 y old [y.o.]), the CFR was larger in young children (0–4 y.o.) (odds ratio [OR]: 2.44; 95% CI 1.02–5.86) and older adults (?45 y.o.) (OR: 2.84; 95% CI 1.81–4.46) but lower in children (5–14 y.o.) (OR: 0.46; 95% CI 0.24–0.86). An order of magnitude increase in mean viremia in cases after July 2014 compared to those before coincided with a 14% increase in the CFR. Our findings come from a large hospital-based study in Conakry and may not be generalizable to settings with different case profiles, such as with individuals who never sought care. Conclusions Viremia in EVD patients was a strong predictor of death that partly explained variations in CFR in the study population. This study provides baseline CFRs by viremia group, which allow appropriate adjustment when estimating efficacy in treatment studies. In randomized controlled trials, stratifying analysis on viremia groups could reduce sample size requirements by 25%. We hypothesize that monitoring the viremia of hospitalized patients may inform the ability of surveillance systems to detect EVD patients from the different severity strata. PMID:26625118

  5. Parainfluenza Viruses

    PubMed Central

    Henrickson, Kelly J.

    2003-01-01

    Human parainfluenza viruses (HPIV) were first discovered in the late 1950s. Over the last decade, considerable knowledge about their molecular structure and function has been accumulated. This has led to significant changes in both the nomenclature and taxonomic relationships of these viruses. HPIV is genetically and antigenically divided into types 1 to 4. Further major subtypes of HPIV-4 (A and B) and subgroups/genotypes of HPIV-1 and HPIV-3 have been described. HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly. Each subtype can cause somewhat unique clinical diseases in different hosts. HPIV are enveloped and of medium size (150 to 250 nm), and their RNA genome is in the negative sense. These viruses belong to the Paramyxoviridae family, one of the largest and most rapidly growing groups of viruses causing significant human and veterinary disease. HPIV are closely related to recently discovered megamyxoviruses (Hendra and Nipah viruses) and metapneumovirus. PMID:12692097

  6. Investigating the zoonotic origin of the West African Ebola epidemic

    E-print Network

    Report Investigating the zoonotic origin of the West African Ebola epidemic Almudena Marí Saéz1,6,14, , Sébastien Calvignac-Spencer2, & Fabian H Leendertz2,* Abstract The severe Ebola virus disease epidemic). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks

  7. Ecological dynamics of emerging bat virus spillover.

    PubMed

    Plowright, Raina K; Eby, Peggy; Hudson, Peter J; Smith, Ina L; Westcott, David; Bryden, Wayne L; Middleton, Deborah; Reid, Peter A; McFarlane, Rosemary A; Martin, Gerardo; Tabor, Gary M; Skerratt, Lee F; Anderson, Dale L; Crameri, Gary; Quammen, David; Jordan, David; Freeman, Paul; Wang, Lin-Fa; Epstein, Jonathan H; Marsh, Glenn A; Kung, Nina Y; McCallum, Hamish

    2015-01-01

    Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility. PMID:25392474

  8. Ecological dynamics of emerging bat virus spillover

    PubMed Central

    Plowright, Raina K.; Eby, Peggy; Hudson, Peter J.; Smith, Ina L.; Westcott, David; Bryden, Wayne L.; Middleton, Deborah; Reid, Peter A.; McFarlane, Rosemary A.; Martin, Gerardo; Tabor, Gary M.; Skerratt, Lee F.; Anderson, Dale L.; Crameri, Gary; Quammen, David; Jordan, David; Freeman, Paul; Wang, Lin-Fa; Epstein, Jonathan H.; Marsh, Glenn A.; Kung, Nina Y.; McCallum, Hamish

    2015-01-01

    Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility. PMID:25392474

  9. Be-CoDiS: A Mathematical Model to Predict the Risk of Human Diseases Spread Between Countries-Validation and Application to the 2014-2015 Ebola Virus Disease Epidemic.

    PubMed

    Ivorra, Benjamin; Ngom, Diène; Ramos, Ángel M

    2015-09-01

    Ebola virus disease is a lethal human and primate disease that currently requires a particular attention from the international health authorities due to important outbreaks in some Western African countries and isolated cases in the UK, the USA and Spain. Regarding the emergency of this situation, there is a need for the development of decision tools, such as mathematical models, to assist the authorities to focus their efforts in important factors to eradicate Ebola. In this work, we propose a novel deterministic spatial-temporal model, called Between-Countries Disease Spread (Be-CoDiS), to study the evolution of human diseases within and between countries. The main interesting characteristics of Be-CoDiS are the consideration of the movement of people between countries, the control measure effects and the use of time-dependent coefficients adapted to each country. First, we focus on the mathematical formulation of each component of the model and explain how its parameters and inputs are obtained. Then, in order to validate our approach, we consider two numerical experiments regarding the 2014-2015 Ebola epidemic. The first one studies the ability of the model in predicting the EVD evolution between countries starting from the index cases in Guinea in December 2013. The second one consists of forecasting the evolution of the epidemic by using some recent data. The results obtained with Be-CoDiS are compared to real data and other model outputs found in the literature. Finally, a brief parameter sensitivity analysis is done. A free MATLAB version of Be-CoDiS is available at: http://www.mat.ucm.es/momat/software.htm . PMID:26449916

  10. Antiviral Drug May Prevent Ebola, Small Study Suggests

    MedlinePLUS

    ... news/fullstory_154290.html Antiviral Drug May Prevent Ebola, Small Study Suggests Health care workers deemed at ... Antiviral drugs may help protect people from developing Ebola after exposure to the deadly virus, a new ...

  11. SAMPLING VIRUSES FROM SOIL

    EPA Science Inventory

    This chapter describes in detail methods for detecting viruses of bacteria and humans in soil. Methods also are presented for the assay of these viruses. Reference sources are provided for information on viruses of plants.

  12. Virus Movement Maintains Local Virus Population Diversity

    SciTech Connect

    J. Snyder; B. Wiedenheft; M. Lavin; F. Roberto; J. Spuhler; A. Ortmann; T. Douglas; M. Young

    2007-11-01

    Viruses are the largest reservoir of genetic material on the planet, yet little is known about the population dynamics of any virus within its natural environment. Over a 2-year period, we monitored the diversity of two archaeal viruses found in hot springs within Yellowstone National Park (YNP). Both temporal phylogeny and neutral biodiversity models reveal that virus diversity in these local environments is not being maintained by mutation but rather by high rates of immigration from a globally distributed metacommunity. These results indicate that geographically isolated hot springs are readily able to exchange viruses. The importance of virus movement is supported by the detection of virus particles in air samples collected over YNP hot springs and by their detection in metacommunity sequencing projects conducted in the Sargasso Sea. Rapid rates of virus movement are not expected to be unique to these archaeal viruses but rather a common feature among virus metacommunities. The finding that virus immigration rather than mutation can dominate community structure has significant implications for understanding virus circulation and the role that viruses play in ecology and evolution by providing a reservoir of mobile genetic material.

  13. Predicting and controlling the Ebola infection

    E-print Network

    Rachah, Amira

    2015-01-01

    We present a comparison between two different mathematical models used in the description of the Ebola virus propagation currently occurring in West Africa. In order to improve the prediction and the control of the propagation of the virus, numerical simulations and optimal control of the two models for Ebola are investigated. In particular, we study when the two models generate similar results.

  14. Teicoplanin inhibits Ebola pseudovirus infection in cell culture.

    PubMed

    Wang, Yizhuo; Cui, Rui; Li, Guiming; Gao, Qianqian; Yuan, Shilin; Altmeyer, Ralf; Zou, Gang

    2016-01-01

    There is currently no approved antiviral therapy for treatment of Ebola virus disease. To discover readily available approved drugs that can be rapidly repurposed for treatment of Ebola virus infections, we screened 1280 FDA-approved drugs and identified glycopeptide antibiotic teicoplanin inhibiting Ebola pseudovirus infection by blocking virus entry in the low micromolar range. Teicoplanin could be evaluated further and incorporated into ongoing clinical studies. PMID:26585243

  15. Ebola: Implications and Perspectives

    PubMed Central

    Del Rio, Carlos; Guarner, Jeannette

    2015-01-01

    The 2014 Ebola virus disease outbreak in West Africa has been the largest in recorded history. During this Ebola epidemic, the media has focused much attention to the magnitude of the problem in West Africa but has also overplayed the potential for an Ebola virus pandemic as patients have been transported for treatment to the United States and Europe causing panic and paranoia in the population. Knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and prevention of this infection will allow a better understanding of the disease and decrease irrational fear of spread. PMID:26330663

  16. Development of Small-Molecule Antivirals for Ebola.

    PubMed

    Janeba, Zlatko

    2015-11-01

    Ebola hemorrhagic fever is a deadly disease caused by infection with one of the Ebola virus species. Although a significant progress has recently been made in understanding of Ebola virus biology and pathogenesis, development of effective anti-Ebola treatments has not been very productive, compared to other areas of antiviral research (e.g., HIV and HCV infections). No approved vaccine or medicine is available for Ebola but several are currently under development. This review summarises attempts in identification, evaluation, and development of small-molecule candidates for treatment of Ebola viral disease, including the most promising experimental drugs brincidofovir (CMX001), BCX4430, and favipiravir (T-705). PMID:26172225

  17. A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

    E-print Network

    Bird, Centers for Disease Control and Prevention, United States of America Received April 17, 2013, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion

  18. Virophages or satellite viruses?

    PubMed

    Krupovic, Mart; Cvirkaite-Krupovic, Virginija

    2011-11-01

    It has been argued that the smaller viruses associated with giant DNA viruses are a new biological entity. However, Mart Krupovic and Virginija Cvirkaite-Krupovic argue here that these smaller viruses should be classified with the satellite viruses. PMID:22016897

  19. The Tobacco Mosaic Virus.

    ERIC Educational Resources Information Center

    Sulzinski, Michael A.

    1992-01-01

    Explains how the tobacco mosaic virus can be used to study virology. Presents facts about the virus, procedures to handle the virus in the laboratory, and four laboratory exercises involving the viruses' survival under inactivating conditions, dilution end point, filterability, and microscopy. (MDH)

  20. Evaluation of the Biofire FilmArray BioThreat-E Test (v2.5) for Rapid Identification of Ebola Virus Disease in Heat-Treated Blood Samples Obtained in Sierra Leone and the United Kingdom.

    PubMed

    Weller, Simon A; Bailey, Daniel; Matthews, Steven; Lumley, Sarah; Sweed, Angela; Ready, Derren; Eltringham, Gary; Richards, Jade; Vipond, Richard; Lukaszewski, Roman; Payne, Phillippa M; Aarons, Emma; Simpson, Andrew J; Hutley, Emma J; Brooks, Tim

    2016-01-01

    Rapid Ebola virus (EBOV) detection is crucial for appropriate patient management and care. The performance of the FilmArray BioThreat-E test (v2.5) using whole-blood samples was evaluated in Sierra Leone and the United Kingdom and was compared with results generated by a real-time Ebola Zaire PCR reference method. Samples were tested in diagnostic laboratories upon availability, included successive samples from individual patients, and were heat treated to facilitate EBOV inactivation prior to PCR. The BioThreat-E test had a sensitivity of 84% (confidence interval [CI], 64% to 95%) and a specificity of 89% (CI, 73% to 97%) in Sierra Leone (n = 60; 44 patients) and a sensitivity of 75% (CI, 19% to 99%) and a specificity of 100% (CI, 97% to 100%) in the United Kingdom (n = 108; 70 patients) compared to the reference real-time PCR. Statistical analysis (Fisher's exact test) indicated there was no significant difference between the methods at the 99% confidence level in either country. In 9 discrepant results (5 real-time PCR positives and BioThreat-E test negatives and 4 real-time PCR negatives and BioThreat-E test positives), the majority (n = 8) were obtained from samples with an observed or probable low viral load. The FilmArray BioThreat-E test (v2.5) therefore provides an attractive option for laboratories (either in austere field settings or in countries with an advanced technological infrastructure) which do not routinely offer an EBOV diagnostic capability. PMID:26537445

  1. Virus-Vectored Influenza Virus Vaccines

    PubMed Central

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

    Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

  2. Clinical development of Ebola vaccines

    PubMed Central

    Sridhar, Saranya

    2015-01-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines.

  3. Clinical development of Ebola vaccines.

    PubMed

    Sridhar, Saranya

    2015-09-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  4. Viruses of the family Filoviridae --which consists of the genera Marburgvirus and

    E-print Network

    Dever, Jennifer A.

    of Ebolavirus and one of Marburgvirus. Among these, Ebola virus (EBOV; formerly known as Zaire ebolavirus . These concerns are compounded by the fact that there are no approved vaccines or drugs to combat any filovirus

  5. Viruses in sweetpotato.

    PubMed

    Loebenstein, Gad

    2012-01-01

    Sweetpotato in the Mediterranean is mainly grown in Egypt, Spain, Portugal, and Israel. Yields vary from 34 tons/ha in Israel to 7.8 tons/ha in Portugal. As sweetpotatoes are vegetatively propagated, the differences in yields are probably due to the quality in the propagation material, mainly infection by various viruses. The main viruses affecting sweetpotato in Mediterranean countries are Sweet potato feathery mottle virus potyvirus, Sweet potato sunken vein virus (Sweet potato chlorotic stunt virus) crinivirus, and their combined infection, causing the sweetpotato disease. Eleven other viruses sporadically reported from Mediterranean countries are also reviewed, as well as possible methods for control. PMID:22682172

  6. Assessing Community Reactions to Ebola Virus Disease and Other Disasters: Using Social Psychological Research to Enhance Public Health and Disaster Communications

    PubMed Central

    Boscarino, Joseph A.; Adams, Richard E.

    2015-01-01

    Drawing on the lessons learned from previous disaster and disease outbreak studies over the past two decades, in the following article we review research related to social psychological assessment of community attitudes, knowledge, and beliefs associated with the recent Ebola outbreak and other public health threats, and discuss the use of this information to assist in future disaster planning and crisis communications. Psychologists, physicians, and others in the healthcare field need to be aware of these developments and involved with preparations related to mitigating the psychological impact of Ebola disease outbreaks among different populations, as well as other potential public health threats in the future. PMID:25844070

  7. Arthropods as a source of new RNA viruses.

    PubMed

    Bichaud, L; de Lamballerie, X; Alkan, C; Izri, A; Gould, E A; Charrel, R N

    2014-12-01

    The discovery and development of methods for isolation, characterisation and taxonomy of viruses represents an important milestone in the study, treatment and control of virus diseases during the 20th century. Indeed, by the late-1950s, it was becoming common belief that most human and veterinary pathogenic viruses had been discovered. However, at that time, knowledge of the impact of improved commercial transportation, urbanisation and deforestation, on disease emergence, was in its infancy. From the late 1960s onwards viruses, such as hepatitis virus (A, B and C) hantavirus, HIV, Marburg virus, Ebola virus and many others began to emerge and it became apparent that the world was changing, at least in terms of virus epidemiology, largely due to the influence of anthropological activities. Subsequently, with the improvement of molecular biotechnologies, for amplification of viral RNA, genome sequencing and proteomic analysis the arsenal of available tools for virus discovery and genetic characterization opened up new and exciting possibilities for virological discovery. Many recently identified but "unclassified" viruses are now being allocated to existing genera or families based on whole genome sequencing, bioinformatic and phylogenetic analysis. New species, genera and families are also being created following the guidelines of the International Committee for the Taxonomy of Viruses. Many of these newly discovered viruses are vectored by arthropods (arboviruses) and possess an RNA genome. This brief review will focus largely on the discovery of new arthropod-borne viruses. PMID:25239874

  8. Virus Assembly and Maturation

    NASA Astrophysics Data System (ADS)

    Johnson, John E.

    2004-03-01

    We use two techniques to look at three-dimensional virus structure: electron cryomicroscopy (cryoEM) and X-ray crystallography. Figure 1 is a gallery of virus particles whose structures Timothy Baker, one of my former colleagues at Purdue University, used cryoEM to determine. It illustrates the variety of sizes of icosahedral virus particles. The largest virus particle on this slide is the Herpes simplex virus, around 1200Å in diameter; the smallest we examined was around 250Å in diameter. Viruses bear their genomic information either as positive-sense DNA and RNA, double-strand DNA, double-strand RNA, or negative-strand RNA. Viruses utilize the various structure and function "tactics" seen throughout cell biology to replicate at high levels. Many of the biological principles that we consider general were in fact discovered in the context of viruses ...

  9. SOLENOPSIS INVICTA VIRUSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unique Solenopsis invicta viruses (SINV) have been identified and their genome sequenced. Oligonucleotide primers have been developed using the isolated nucleic acid sequences of the SINV. The viruses are used as a biocontrol agent for control of fire ants....

  10. Viruses and human cancer

    SciTech Connect

    Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

    1987-01-01

    This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

  11. Viruses and Breast Cancer

    PubMed Central

    Lawson, James S.; Heng, Benjamin

    2010-01-01

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix. PMID:24281093

  12. Tumorigenic DNA viruses

    SciTech Connect

    Klein, G.

    1989-01-01

    The eighth volume of Advances in Viral Oncology focuses on the three major DNA virus groups with a postulated or proven tumorigenic potential: papillomaviruses, animal hepatitis viruses, and the Epstein-Bar virus. In the opening chapters, the contributors analyze the evidence that papillomaviruses and animal hepatitis viruses are involved in tumorigenesis and describe the mechanisms that trigger virus-host cell interactions. A detailed section on the Epstein-Barr virus (EBV) - comprising more than half the book - examines the transcription and mRNA processing patterns of the virus genome; the mechanisms by which EBV infects lymphoid and epithelial cells; the immunological aspects of the virus; the actions of EBV in hosts with Acquired Immune Deficiency Syndrome; and the involvement of EBV in the etiology of Burkitt's lymphoma.

  13. West Nile Virus

    MedlinePLUS

    West Nile virus (WNV) is an infectious disease that first appeared in the United States in 1999. Infected mosquitoes ... and usually go away on their own. If West Nile virus enters the brain, however, it can be life- ...

  14. Advances in virus research

    SciTech Connect

    Maramorosch, K. ); Murphy, F.A. ); Shatkin, A.J. )

    1988-01-01

    This book contains eight chapters. Some of the titles are: Initiation of viral DNA replication; Vaccinia: virus, vector, vaccine; The pre-S region of hepadnavirus envelope proteins; and Archaebacterial viruses.

  15. West Nile Virus

    MedlinePLUS

    ... West Nile virus has been found in animals, birds, and humans in all continental states in the ... picked up the virus after feeding on infected birds. Pets and other animals can also become infected ...

  16. Human Parainfluenza Viruses

    MedlinePLUS

    ... Search The CDC Cancel Submit Search The CDC Human Parainfluenza Viruses (HPIVs) Note: Javascript is disabled or ... CDC.gov . Recommend on Facebook Tweet Share Compartir Human parainfluenza viruses (HPIVs) commonly cause respiratory illnesses in ...

  17. Hepatitis D Virus Replication.

    PubMed

    Taylor, John M

    2015-01-01

    This work reviews specific related aspects of hepatitis delta virus (HDV) reproduction, including virion structure, the RNA genome, the mode of genome replication, the delta antigens, and the assembly of HDV using the envelope proteins of its helper virus, hepatitis B virus (HBV). These topics are considered with perspectives ranging from a history of discovery through to still-unsolved problems. HDV evolution, virus entry, and associated pathogenic potential and treatment of infections are considered in other articles in this collection. PMID:26525452

  18. Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.

    PubMed

    Andersen, Kristian G; Shapiro, B Jesse; Matranga, Christian B; Sealfon, Rachel; Lin, Aaron E; Moses, Lina M; Folarin, Onikepe A; Goba, Augustine; Odia, Ikponmwonsa; Ehiane, Philomena E; Momoh, Mambu; England, Eleina M; Winnicki, Sarah; Branco, Luis M; Gire, Stephen K; Phelan, Eric; Tariyal, Ridhi; Tewhey, Ryan; Omoniwa, Omowunmi; Fullah, Mohammed; Fonnie, Richard; Fonnie, Mbalu; Kanneh, Lansana; Jalloh, Simbirie; Gbakie, Michael; Saffa, Sidiki; Karbo, Kandeh; Gladden, Adrianne D; Qu, James; Stremlau, Matthew; Nekoui, Mahan; Finucane, Hilary K; Tabrizi, Shervin; Vitti, Joseph J; Birren, Bruce; Fitzgerald, Michael; McCowan, Caryn; Ireland, Andrea; Berlin, Aaron M; Bochicchio, James; Tazon-Vega, Barbara; Lennon, Niall J; Ryan, Elizabeth M; Bjornson, Zach; Milner, Danny A; Lukens, Amanda K; Broodie, Nisha; Rowland, Megan; Heinrich, Megan; Akdag, Marjan; Schieffelin, John S; Levy, Danielle; Akpan, Henry; Bausch, Daniel G; Rubins, Kathleen; McCormick, Joseph B; Lander, Eric S; Günther, Stephan; Hensley, Lisa; Okogbenin, Sylvanus; Schaffner, Stephen F; Okokhere, Peter O; Khan, S Humarr; Grant, Donald S; Akpede, George O; Asogun, Danny A; Gnirke, Andreas; Levin, Joshua Z; Happi, Christian T; Garry, Robert F; Sabeti, Pardis C

    2015-08-13

    The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT. PMID:26276630

  19. Avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) is type A influenza, which is adapted to an avian host. Although avian influenza has been isolated from numerous avian species, the primary natural hosts for the virus are dabbling ducks, shorebirds, and gulls. The virus can be found world-wide in these species and in o...

  20. Encephalitis Virus, Kyrgyzstan

    E-print Network

    Baker, Robert J.

    Tick-Borne Encephalitis Virus, Kyrgyzstan Benjamin J. Briggs, Barry Atkinson, Donna M. Czechowski-borne encephalitis virus (TBEV) is an emerging pathogen in Europe and Asia. We investigated TBEV in Kyrgyzstan reported. Tick-borne encephalitis virus (TBEV) is a flavivirus in the family Flaviviridae. The TBEV

  1. Computer Virus Protection

    ERIC Educational Resources Information Center

    Rajala, Judith B.

    2004-01-01

    A computer virus is a program--a piece of executable code--that has the unique ability to replicate. Like biological viruses, computer viruses can spread quickly and are often difficult to eradicate. They can attach themselves to just about any type of file, and are spread by replicating and being sent from one individual to another. Simply having…

  2. Understanding West Nile Virus

    MedlinePLUS

    ... Content Marketing Share this: Main Content Area Understanding West Nile Virus The West Nile Virus first emerged in the Western Hemisphere in 1999 ... of the brain and spinal cord. What Is West Nile Virus? Transmission Symptoms Diagnosis Prevention Last Updated April 02, ...

  3. Avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) is caused by type A influenza virus, a member of the Orthomyxoviridae family. AI viruses are serologically categorized into 16 hemagglutinin (H1-H16) and 9 neuraminidase (N1-N9) subtypes. All subtypes have been identified in birds. Infections by AI viruses have been reported in ...

  4. Meeting the Challenge of Developing Drugs for Ebola

    E-print Network

    Gleeson, Joseph G.

    Meeting the Challenge of Developing Drugs for Ebola and Other Neglected Tropical Diseases James Mc million dollars) 5 years5 years #12;Ebola Virus: Major Outbreaks New York Times, October 13, 2013 (Data Deaths Total 8031 Cases 3865 Deaths ew York Times, Updated October 8, 2014 #12;Ebola Cases as of October

  5. Analysis of Ebola Glycoprotein Sequences from Strains of Varying Lethality

    E-print Network

    Analysis of Ebola Glycoprotein Sequences from Strains of Varying Lethality Biochem 218 Spring 2002 Tammy Doukas tdoukas@stanford.edu I. Background and Significance Ebola hemorrhagic fever is a disease in humans, chimpanzees, and monkeys, caused by infection with Ebola virus, and associated with high

  6. Avian influenza virus and Newcastle disease virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) severely impact poultry egg production. Decreased egg yield and hatchability, as well as misshapen eggs, are often observed during infection with AIV and NDV, even with low-virulence strains or in vaccinated flocks. Data suggest that in...

  7. Haloarchaeal virus morphotypes.

    PubMed

    Atanasova, Nina S; Bamford, Dennis H; Oksanen, Hanna M

    2015-11-01

    Hypersaline waters and salt crystals are known to contain high numbers of haloarchaeal cells and their viruses. Both culture-dependent and culture-independent studies indicate that these viruses represent a world-wide distributed reservoir of orphan genes and possibly novel virion morphotypes. To date, 90 viruses have been described for halophilic archaeal hosts, all belonging to the Halobacteriaceae family. This number is higher than that described for the members of any other archaeal family, but still very low compared to the viruses of bacteria and eukaryotes. The known haloarchaeal viruses represent icosahedral tailed, icosahedral internal membrane-containing, pleomorphic, and spindle-shaped virion morphotypes. This morphotype distribution is low, especially when compared to the astronomical number (>10(31)) of viruses on Earth. This strongly suggests that only certain protein folds are capable of making a functional virion. Viruses infecting cells belonging to any of the three domains of life are known to share similar major capsid protein folds which can be used to classify viruses into structure-based lineages. The latest observation supporting this proposal comes from the studies of icosahedral tailed haloarchaeal viruses which are the most abundant virus isolates from hypersaline environments. These viruses were shown to have the same major capsid protein fold (HK97-fold) with tailed bacteriophages belonging to the order Caudovirales and with eukaryotic herpes viruses. This proposes that these viruses have a common origin dating back to ancient times. Here we summarize the current knowledge of haloarchaeal viruses from the perspective of virus morphotypes. PMID:26151345

  8. [Bats and Viruses: complex relationships].

    PubMed

    Rodhain, E

    2015-10-01

    With more than 1 200 species, bats and flying foxes (Order Chiroptera) constitute the most important and diverse order of Mammals after Rodents. Many species of bats are insectivorous while others are frugivorous and few of them are hematophagous. Some of these animals fly during the night, others are crepuscular or diurnal. Some fly long distances during seasonal migrations. Many species are colonial cave-dwelling, living in a rather small home range while others are relatively solitary. However, in spite of the importance of bats for terrestrial biotic communities and ecosystem ecology, the diversity in their biology and lifestyles remain poorly known and underappreciated. More than sixty viruses have been detected or isolated in bats; these animals are therefore involved in the natural cycles of many of them. This is the case, for instance, of rabies virus and other Lyssavirus (Family Rhabdoviridae), Nipah and Hendra viruses (Paramyxoviridae), Ebola and Marburg viruses (Filoviridae), SARS-CoV and MERS-CoV (Coronaviridae). For these zoonotic viruses, a number of bat species are considered as important reservoir hosts, efficient disseminators or even directly responsible of the transmission. Some of these bat-borne viruses cause highly pathogenic diseases while others are of potential significance for humans and domestic or wild animals; so, bats are an important risk in human and animal public health. Moreover, some groups of viruses developed through different phylogenetic mechanisms of coevolution between viruses and bats. The fact that most of these viral infections are asymptomatic in bats has been observed since a long time but the mechanisms of the viral persistence are not clearly understood. The various bioecology of the different bat populations allows exchange of virus between migrating and non-migrating conspecific species. For a better understanding of the role of bats in the circulation of these viral zoonoses, epidemiologists must pay attention to some of their biologic properties which are not fully documented, like their extreme longevity, their diet, the population size and the particular densities observed in species with crowded roosting behavior, the population structure and migrations, the hibernation permitting overwintering of viruses, their particular innate and acquired immune response, probably related at least partially to their ability to fly, allowing persistent virus infections and preventing immunopathological consequences, etc. It is also necessary to get a better knowledge of the interactions between bats and ecologic changes induced by man and to attentively follow bat populations and their viruses through surveillance networks involving human and veterinary physicians, specialists of wild fauna, ecologists, etc. in order to understand the mechanisms of disease emergence, to try to foresee and, perhaps, to prevent viral emergences beforehand. Finally, a more fundamental research about immune mechanisms developed in viral infections is essential to reveal the reasons why Chiroptera are so efficient reservoir hosts. Clearly, a great deal of additional work is needed to document the roles of bats in the natural history of viruses. PMID:26330152

  9. Equine influenza virus.

    PubMed

    Landolt, Gabriele A

    2014-12-01

    For decades the horse has been viewed as an isolated or "dead-end" host for influenza A viruses, with equine influenza virus being considered as relatively stable genetically. Although equine influenza viruses are genetically more stable than those of human lineage, they are by no means in evolutionary stasis. Moreover, recent transmission of equine-lineage influenza viruses to dogs also challenges the horse's status as a dead-end host. This article reviews recent developments in the epidemiology and evolution of equine influenza virus. In addition, the clinical presentation of equine influenza infection, diagnostic techniques, and vaccine recommendations are briefly summarized. PMID:25282321

  10. The use of pseudotypes to study viruses, virus sero-epidemiology and vaccination.

    PubMed

    Bentley, Emma M; Mather, Stuart T; Temperton, Nigel J

    2015-06-12

    The globalization of the world's economies, accompanied by increasing international travel, changing climates, altered human behaviour and demographics is leading to the emergence of different viral diseases, many of which are highly pathogenic and hence are considered of great public and animal health importance. To undertake basic research and therapeutic development, many of these viruses require handling by highly trained staff in BSL-3/4 facilities not readily available to the majority of the global R&D community. In order to circumvent the enhanced biosafety requirement, the development of non-pathogenic, replication-defective pseudotyped viruses is an effective and established solution to permit the study of many aspects of virus biology in a low containment biosafety level (BSL)-1/2 laboratory. Under the spectre of the unfolding Ebola crisis, this timely conference (the second to be organised by the Viral Pseudotype Unit, www.viralpseudotypeunit.info*) discusses the recent advances in pseudotype technology and how it is revolutionizing the study of important human and animal pathogens (human and avian influenza viruses, rabies/lyssaviruses, HIV, Marburg and Ebola viruses). Key topics addressed in this conference include the exploitation of pseudotypes for serology and serosurveillance, immunogenicity testing of current and next-generation vaccines and new pseudotype assay formats (multiplexing, kit development). The first pseudotype-focused Euroscicon conference organised by the Viral Pseudotype Unit was recently reviewed [1]. PMID:25936665

  11. Nano-optofluidic Detection of Single Viruses and Nanoparticles

    E-print Network

    Novotny, Lukas

    Nano-optofluidic Detection of Single Viruses and Nanoparticles Anirban Mitra, Bradley Deutsch is of critical importance for early detection of threats and preventive measures. There is also a strong need- amples are SARS, Ebola, AIDS, and the avian flu. There is also evidence that viral agents cause some

  12. Other Viruses and Viruslike Agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The diseases reported under 'Virus and Virus-like Agents' in the first volume of this compendium, with the exception of Cherry rasp leaf virus and Rubus chinese seed-borne virus, should be considered oddities since there are no known type isolates available for these reported viruses. Without a po...

  13. Lifestyles of plant viruses

    PubMed Central

    Roossinck, Marilyn J.

    2010-01-01

    The vast majority of well-characterized eukaryotic viruses are those that cause acute or chronic infections in humans and domestic plants and animals. However, asymptomatic persistent viruses have been described in animals, and are thought to be sources for emerging acute viruses. Although not previously described in these terms, there are also many viruses of plants that maintain a persistent lifestyle. They have been largely ignored because they do not generally cause disease. The persistent viruses in plants belong to the family Partitiviridae or the genus Endornavirus. These groups also have members that infect fungi. Phylogenetic analysis of the partitivirus RNA-dependent RNA polymerase genes suggests that these viruses have been transmitted between plants and fungi. Additional families of viruses traditionally thought to be fungal viruses are also found frequently in plants, and may represent a similar scenario of persistent lifestyles, and some acute or chronic viruses of crop plants may maintain a persistent lifestyle in wild plants. Persistent, chronic and acute lifestyles of plant viruses are contrasted from both a functional and evolutionary perspective, and the potential role of these lifestyles in host evolution is discussed. PMID:20478885

  14. Water system virus detection

    NASA Technical Reports Server (NTRS)

    Fraser, A. S.; Wells, A. F.; Tenoso, H. J. (inventors)

    1978-01-01

    The performance of a waste water reclamation system is monitored by introducing a non-pathogenic marker virus, bacteriophage F2, into the waste-water prior to treatment and, thereafter, testing the reclaimed water for the presence of the marker virus. A test sample is first concentrated by absorbing any marker virus onto a cellulose acetate filter in the presence of a trivalent cation at low pH and then flushing the filter with a limited quantity of a glycine buffer solution to desorb any marker virus present on the filter. Photo-optical detection of indirect passive immune agglutination by polystyrene beads indicates the performance of the water reclamation system in removing the marker virus. A closed system provides for concentrating any marker virus, initiating and monitoring the passive immune agglutination reaction, and then flushing the system to prepare for another sample.

  15. Viruses in Antarctic lakes

    NASA Technical Reports Server (NTRS)

    Kepner, R. L. Jr; Wharton, R. A. Jr; Suttle, C. A.; Wharton RA, J. r. (Principal Investigator)

    1998-01-01

    Water samples collected from four perennially ice-covered Antarctic lakes during the austral summer of 1996-1997 contained high densities of extracellular viruses. Many of these viruses were found to be morphologically similar to double-stranded DNA viruses that are known to infect algae and protozoa. These constitute the first observations of viruses in perennially ice-covered polar lakes. The abundance of planktonic viruses and data suggesting substantial production potential (relative to bacteria] secondary and photosynthetic primary production) indicate that viral lysis may be a major factor in the regulation of microbial populations in these extreme environments. Furthermore, we suggest that Antarctic lakes may be a reservoir of previously undescribed viruses that possess novel biological and biochemical characteristics.

  16. The human oncogenic viruses

    SciTech Connect

    Luderer, A.A.; Weetall, H.H

    1986-01-01

    This book contains eight selections. The titles are: Cytogenetics of the Leukemias and Lymphomas; Cytogenetics of Solid Tumors: Renal Cell Carcinoma, Malignant Melanoma, Retinoblastoma, and Wilms' Tumor; Elucidation of a Normal Function for a Human Proto-Oncogene; Detection of HSV-2 Genes and Gene Products in Cervical Neoplasia; Papillomaviruses in Anogennital Neoplasms; Human Epstein-Barr Virus and Cancer; Hepatitis B Virus and Hepatocellular Carcinoma; and Kaposi's Sarcoma: Acquired Immunodeficiency Syndrome (AIDS) and Associated Viruses.

  17. Viruses for Tumor Therapy

    PubMed Central

    Bell, John; McFadden, Grant

    2014-01-01

    Oncolytic virotherapy exploits live viruses with selective tropism for cancerous cells and tissues to treat cancer. As discussed here, the field has progressed considerably as a result of both the successes and failures of previous and on-going clinical trials for various cancers. These studies indicate that oncolytic viruses are remarkably safe and more efficacious when virus replication stimulates sustained antitumor immune responses. In the future, virotherapy should be combined with immunomodulatory reagents that target immune tolerance to established cancers. PMID:24629333

  18. Water system virus detection

    NASA Technical Reports Server (NTRS)

    Fraser, A. S.; Wells, A. F.; Tenoso, H. J.

    1975-01-01

    A monitoring system developed to test the capability of a water recovery system to reject the passage of viruses into the recovered water is described. A nonpathogenic marker virus, bacteriophage F2, is fed into the process stream before the recovery unit and the reclaimed water is assayed for its presence. Detection of the marker virus consists of two major components, concentration and isolation of the marker virus, and detection of the marker virus. The concentration system involves adsorption of virus to cellulose acetate filters in the presence of trivalent cations and low pH with subsequent desorption of the virus using volumes of high pH buffer. The detection of the virus is performed by a passive immune agglutination test utilizing specially prepared polystyrene particles. An engineering preliminary design was performed as a parallel effort to the laboratory development of the marker virus test system. Engineering schematics and drawings of a fully functional laboratory prototype capable of zero-G operation are presented. The instrument consists of reagent pump/metering system, reagent storage containers, a filter concentrator, an incubation/detector system, and an electronic readout and control system.

  19. Viruses in artichoke.

    PubMed

    Gallitelli, Donato; Mascia, Tiziana; Martelli, Giovanni P

    2012-01-01

    Most of the 25 viruses found in globe artichoke (Cynara scolymus L.) and cardoon (Cynara cardunculus L.) were recorded from Europe and the Mediterranean basin, where they decrease both the productivity and the quality of the crop. Although, sometimes, these viruses are agents of diseases of different severity, most often their infections are symptomless. These conditions have contributed to spread virus-infected material since farmers multiply traditional artichoke types vegetatively with no effective selection of virus-free plants. This review reports the main properties of these viruses and the techniques used for their detection and identification. ELISA kits are commercially available for most of the viruses addressed in this review but have seldom been used for their detection in artichoke. Conversely, nucleic acid-based diagnostic reagents, some of which are commercially available, have successfully been employed to identify some viruses in artichoke sap. Control measures mainly use virus-free stocks for new plantations. A combined procedure of meristem-tip culture and thermotherapy proved useful for producing virus-free regenerants of the reflowering southern Italian cultivar Brindisino, which kept earliness and typical heads shape. PMID:22682171

  20. Ebola: Where Are the Facts? | Poster

    Cancer.gov

    Since the first outbreak of Ebola in western Africa and the subsequent cases in the United States, a lot of information has been circulating about the virus. To keep NCI at Frederick employees informed, the Poster staff has compiled the following list of reputable websites that provide accurate and up-to-date information about Ebola: Global

  1. Chikungunya Virus, Southeastern France

    PubMed Central

    Caro, Valérie; Plumet, Sébastien; Thiberge, Jean-Michel; Souarès, Yvan; Failloux, Anna-Bella; Tolou, Hugues J.; Budelot, Michel; Cosserat, Didier; Leparc-Goffart, Isabelle; Desprès, Philippe

    2011-01-01

    In September 2010, autochthonous transmission of chikungunya virus was recorded in southeastern France, where the Aedes albopictus mosquito vector is present. Sequence analysis of the viral genomes of imported and autochthonous isolates indicated new features for the potential emergence and spread of the virus in Europe. PMID:21529410

  2. Chikungunya virus, southeastern France.

    PubMed

    Grandadam, Marc; Caro, Valérie; Plumet, Sébastien; Thiberge, Jean Michel; Souarès, Yvan; Failloux, Anna-Bella; Tolou, Hugues J; Budelot, Michel; Cosserat, Didier; Leparc-Goffart, Isabelle; Desprès, Philippe

    2011-05-01

    In September 2010, autochthonous transmission of chikungunya virus was recorded in southeastern France, where the Aedes albopictus mosquito vector is present. Sequence analysis of the viral genomes of imported and autochthonous isolates indicated new features for the potential emergence and spread of the virus in Europe. PMID:21529410

  3. Papaya Ringspot Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The term papaya ringspot virus (PRSV) was coined by Jensen in 1949, to describe a papaya disease in Hawaii. Later work showed that diseases such as papaya mosaic and watermelon mosaic virus-1 were caused by PRSV. The primary host range of PRSV is papaya and cucurbits, with Chenopium amaranticolor ...

  4. Cutthroat Trout Virus

    USGS Multimedia Gallery

    Electron micrograph of the cutthroat trout virus (CTV) showing the small, round virions of approximately 30 nanometers in diameter containing a single-stranded RNA genome. CTV, whose genome was first characterized by USGS researchers, is being used in research into the human virus Hepatitis E....

  5. Bovine viral diarrhea viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with bovine viral diarrhea viruses (BVDV) result in significant economic losses for beef and dairy producers worldwide. BVDV is actually an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. While denoted as a bovine pathogen...

  6. INFLUENZA VIRUS IN POULTRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) is normally found in wild birds, particularly in ducks and shorebirds, where it does not cause any perceptible clinical disease. However, poultry, including chickens and turkeys, are not normal hosts for avian influenza, but if the virus is introduced it can result in mi...

  7. Barley Yellow Dwarf Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Barley yellow dwarf (BYD) is the most widespread and economically important virus disease of cereals. The viruses causing BYD were initially grouped based on common biological properties, including persistent and often strain-specific transmission by aphids and induction of yellowing symptoms. The...

  8. Newcastle disease virus (velogens)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Newcastle disease virus (NDV) is also known as avian paramyxovirus serotype-1 (APMV-1). While all NDV are referred to as APMV-1 and are of one serotype, only infections with virulent NDV (vNDV) cause Newcastle disease (ND). Newcastle disease virus strains are defined as virulent if they 1) have th...

  9. EPIDEMIOLOGY OF RETICULOENDOTHELIOSIS VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reticuloendotheliosis virus (REV) is an avian retrovirus unrelated to the leukosis/sarcoma group of viruses. REV infects chickens, turkeys, ducks, geese, pheasants, quail, and probably many other avian species . The most common clinical diseases induced by REV are chronic lymphomas and an immunosupp...

  10. RYEGRASS MOSAIC VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A brief technical description of Ryegrass mosaic virus (RGMV) is presented. Described are biological properties, genome organization, and phylogenetic relationships among RGMV and other potyvirus species. RGMV is designated as a the type species of the genus Rymovirus within the plant virus family ...

  11. Mayaro virus proteins.

    PubMed

    Mezencio, J M; Rebello, M A

    1993-01-01

    Mayaro virus was grown in BHK-21 cells and purified by centrifugation in a potassium-tartrate gradient (5-50%). The electron microscopy analyses of the purified virus showed an homogeneous population of enveloped particles with 69 +/- 2.3 nm in diameter. Three structural virus proteins were identified and designated p1, p2 and p3. Their average molecular weight were p1, 54 KDa; p2, 50 KDa and p3, 34 KDa. In Mayaro virus infected Aedes albopictus cells and in BHK-21 infected cells we detected six viral proteins, in which three of them are the structural virus proteins and the other three were products from processing of precursors of viral proteins, whose molecular weights are 62 KDa, 64 KDa and 110 KDa. The 34 KDa protein was the first viral protein synthesized at 5 hours post-infection in both cell lines studied. PMID:8107591

  12. Role of Protein Phosphatase 1 in Dephosphorylation of Ebola Virus VP30 Protein and Its Targeting for the Inhibition of Viral Transcription*

    PubMed Central

    Ilinykh, Philipp A.; Tigabu, Bersabeh; Ivanov, Andrey; Ammosova, Tatiana; Obukhov, Yuri; Garron, Tania; Kumari, Namita; Kovalskyy, Dmytro; Platonov, Maxim O.; Naumchik, Vasiliy S.; Freiberg, Alexander N.; Nekhai, Sergei; Bukreyev, Alexander

    2014-01-01

    The filovirus Ebola (EBOV) causes the most severe hemorrhagic fever known. The EBOV RNA-dependent polymerase complex includes a filovirus-specific VP30, which is critical for the transcriptional but not replication activity of EBOV polymerase; to support transcription, VP30 must be in a dephosphorylated form. Here we show that EBOV VP30 is phosphorylated not only at the N-terminal serine clusters identified previously but also at the threonine residues at positions 143 and 146. We also show that host cell protein phosphatase 1 (PP1) controls VP30 dephosphorylation because expression of a PP1-binding peptide cdNIPP1 increased VP30 phosphorylation. Moreover, targeting PP1 mRNA by shRNA resulted in the overexpression of SIPP1, a cytoplasm-shuttling regulatory subunit of PP1, and increased EBOV transcription, suggesting that cytoplasmic accumulation of PP1 induces EBOV transcription. Furthermore, we developed a small molecule compound, 1E7-03, that targeted a non-catalytic site of PP1 and increased VP30 dephosphorylation. The compound inhibited the transcription but increased replication of the viral genome and completely suppressed replication of EBOV in cultured cells. Finally, mutations of Thr143 and Thr146 of VP30 significantly inhibited EBOV transcription and strongly induced VP30 phosphorylation in the N-terminal Ser residues 29–46, suggesting a novel mechanism of regulation of VP30 phosphorylation. Our findings suggest that targeting PP1 with small molecules is a feasible approach to achieve dysregulation of the EBOV polymerase activity. This novel approach may be used for the development of antivirals against EBOV and other filovirus species. PMID:24936058

  13. Realms of the Viruses Online

    ERIC Educational Resources Information Center

    Liu, Dennis

    2007-01-01

    Viruses have evolved strategies for infecting all taxa, but most viruses are highly specific about their cellular host. In humans, viruses cause diverse diseases, from chronic but benign warts, to acute and deadly hemorrhagic fever. Viruses have entertaining names like Zucchini Yellow Mosaic, Semliki Forest, Coxsackie, and the original terminator,…

  14. Computer Viruses: Pathology and Detection.

    ERIC Educational Resources Information Center

    Maxwell, John R.; Lamon, William E.

    1992-01-01

    Explains how computer viruses were originally created, how a computer can become infected by a virus, how viruses operate, symptoms that indicate a computer is infected, how to detect and remove viruses, and how to prevent a reinfection. A sidebar lists eight antivirus resources. (four references) (LRW)

  15. A Virus in Turbo Pascal.

    ERIC Educational Resources Information Center

    Teleky, Heidi Ann; And Others

    1993-01-01

    Addresses why the authors feel it is not inappropriate to teach about viruses in the how-to, hands-on fashion. Identifies the special features of Turbo Pascal that have to be used for the creation of an effective virus. Defines virus, derives its structure, and from this structure is derived the implemented virus. (PR)

  16. Ocular Tropism of Respiratory Viruses

    PubMed Central

    Rota, Paul A.; Tumpey, Terrence M.

    2013-01-01

    SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620

  17. Avian influenza A viruses

    PubMed Central

    Pereira, H. G.; T?mová, B.; Law, V. G.

    1965-01-01

    The antigenic structure of eight strains of influenza A viruses of avian origin was investigated by haemagglutination inhibition, virus neutralization and strain-specific complement fixation. All strains could be distinguished from each other, but certain cross-reactions were observed allowing the establishment of four antigenic groupings, as follows: (1) classic fowl plague virus (“Dutch” strain), Turkey/England/63 (“Langham” strain) and virus N; (2) two strains isolated from ducks, one in Czechoslovakia in 1956 and one in England in 1962; (3) a third strain isolated from ducks in England in 1956; (4) the “Smith” strain (Chicken/Scotland/59) and the tern virus (Tern/South Africa/61). This article also reports the results of tests to determine the capacity of the above-mentioned viruses to infect monkey-kidney cultures and to produce plaques in chick-embryo fibroblasts. It concludes with a discussion of problems connected with the classification and nomenclature of these viruses. Imagesp858-1-a PMID:5294310

  18. Virus entry: open sesame.

    PubMed

    Marsh, Mark; Helenius, Ari

    2006-02-24

    Detailed information about the replication cycle of viruses and their interactions with host organisms is required to develop strategies to stop them. Cell biology studies, live-cell imaging, and systems biology have started to illuminate the multiple and subtly different pathways that animal viruses use to enter host cells. These insights are revolutionizing our understanding of endocytosis and the movement of vesicles within cells. In addition, such insights reveal new targets for attacking viruses before they can usurp the host-cell machinery for replication. PMID:16497584

  19. West Nile virus.

    PubMed

    McVey, D S; Wilson, W C; Gay, C G

    2015-08-01

    This review covers the basic biology of the West Nile virus and the host-vector-pathogen interactions that result in significant disease in wild birds, horses and humans. The review describes the basic properties of the virus, cellular infection and the pathogenesis of the disease, and the ecology of virus maintenance, amplification and transmission. Disease epidemiology and risk estimation strategies that are currently in use are also examined, and host immune responses and vaccination practices described. The principles of vector control, exposure control and long-term risks caused by climatic and habitat factors are also included. PMID:26601446

  20. Viruses in reptiles

    PubMed Central

    2011-01-01

    The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself. 1. Introduction 2. Methods for working with reptilian viruses 3. Reptilian viruses described by virus families 3.1. Herpesviridae 3.2. Iridoviridae 3.2.1 Ranavirus 3.2.2 Erythrocytic virus 3.2.3 Iridovirus 3.3. Poxviridae 3.4. Adenoviridae 3.5. Papillomaviridae 3.6. Parvoviridae 3.7. Reoviridae 3.8. Retroviridae and inclusion body disease of Boid snakes 3.9. Arboviruses 3.9.1. Flaviviridae 3.9.2. Togaviridae 3.10. Caliciviridae 3.11. Picornaviridae 3.12. Paramyxoviridae 4. Summary 5. Acknowledgements 6. Competing interests 7. References PMID:21933449

  1. Respiratory syncytial virus (RSV)

    MedlinePLUS

    ... RSV often spreads quickly in crowded households and day care centers. The virus can live for a half ... The following increase the risk for RSV: Attending day care Being near tobacco smoke Having school-aged brothers ...

  2. What's West Nile Virus?

    MedlinePLUS

    ... is caused by a bite from an infected mosquito that's already carrying the virus, but it's important ... the risk of being bitten by an infected mosquito is greatest from July to early September. But ...

  3. Hepatitis B virus (image)

    MedlinePLUS

    Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

  4. Hepatitis virus panel

    MedlinePLUS

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... Blood (serology) tests are used to check for antibodies to each of the hepatitis viruses.

  5. A primer on Ebola for clinicians.

    PubMed

    Toner, Eric; Adalja, Amesh; Inglesby, Thomas

    2015-02-01

    The size of the world's largest Ebola outbreak now ongoing in West Africa makes clear that further exportation of Ebola virus disease to other parts of the world will remain a real possibility for the indefinite future. Clinicians outside of West Africa, particularly those who work in emergency medicine, critical care, infectious diseases, and infection control, should be familiar with the fundamentals of Ebola virus disease, including its diagnosis, treatment, and control. In this article we provide basic information on the Ebola virus and its epidemiology and microbiology. We also describe previous outbreaks and draw comparisons to the current outbreak with a focus on the public health measures that have controlled past outbreaks. We review the pathophysiology and clinical features of the disease, highlighting diagnosis, treatment, and hospital infection control issues that are relevant to practicing clinicians. We reference official guidance and point out where important uncertainty or controversy exists. PMID:25325294

  6. Ebola Hemorrhagic Fever and the Current State of Vaccine Development

    PubMed Central

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-il

    2014-01-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine. PMID:25562048

  7. Proteins of Norwalk virus.

    PubMed

    Greenberg, H B; Valdesuso, J R; Kalica, A R; Wyatt, R G; McAuliffe, V J; Kapikian, A Z; Chanock, R M

    1981-03-01

    The proteins of the Norwalk virus were studied by polyacrylamide gel electrophoresis. Highly purified specifically immunoprecipitated virions appeared to contain a single primary structural protein with a molecular weight of 59,000. In addition, a soluble Norwalk viral protein with a molecular weight of 30,000 was identified in fecal specimens containing Norwalk virus. The protein structure of the virion is similar to that of the Calciviridae family. PMID:6785451

  8. Proteins of Norwalk virus.

    PubMed Central

    Greenberg, H B; Valdesuso, J R; Kalica, A R; Wyatt, R G; McAuliffe, V J; Kapikian, A Z; Chanock, R M

    1981-01-01

    The proteins of the Norwalk virus were studied by polyacrylamide gel electrophoresis. Highly purified specifically immunoprecipitated virions appeared to contain a single primary structural protein with a molecular weight of 59,000. In addition, a soluble Norwalk viral protein with a molecular weight of 30,000 was identified in fecal specimens containing Norwalk virus. The protein structure of the virion is similar to that of the Calciviridae family. Images PMID:6785451

  9. Smaller Fleas: Viruses of Microorganisms

    PubMed Central

    Hyman, Paul; Abedon, Stephen T.

    2012-01-01

    Life forms can be roughly differentiated into those that are microscopic versus those that are not as well as those that are multicellular and those that, instead, are unicellular. Cellular organisms seem generally able to host viruses, and this propensity carries over to those that are both microscopic and less than truly multicellular. These viruses of microorganisms, or VoMs, in fact exist as the world's most abundant somewhat autonomous genetic entities and include the viruses of domain Bacteria (bacteriophages), the viruses of domain Archaea (archaeal viruses), the viruses of protists, the viruses of microscopic fungi such as yeasts (mycoviruses), and even the viruses of other viruses (satellite viruses). In this paper we provide an introduction to the concept of viruses of microorganisms, a.k.a., viruses of microbes. We provide broad discussion particularly of VoM diversity. VoM diversity currently spans, in total, at least three-dozen virus families. This is roughly ten families per category—bacterial, archaeal, fungal, and protist—with some virus families infecting more than one of these microorganism major taxa. Such estimations, however, will vary with further discovery and taxon assignment and also are dependent upon what forms of life one includes among microorganisms. PMID:24278736

  10. The outbreak of Ebola in western Africa has certainly been a major news story and has resulted in concerns about this virus spreading to the US due to the recent cases involving people who had direct

    E-print Network

    Thomas, Ellen

    The outbreak of Ebola in western Africa has certainly been a major news story and has resulted contact with Ebola in Africa and health care workers who cared for them in the US. In order to contract Ebola you would need to be exposed to a person who has symptoms and be exposed to their bodily fluids so

  11. Control of cucurbit viruses.

    PubMed

    Lecoq, Hervé; Katis, Nikolaos

    2014-01-01

    More than 70 well-characterized virus species transmitted by a diversity of vectors may infect cucurbit crops worldwide. Twenty of those cause severe epidemics in major production areas, occasionally leading to complete crop failures. Cucurbit viruses' control is based on three major axes: (i) planting healthy seeds or seedlings in a clean environment, (ii) interfering with vectors activity, and (iii) using resistant cultivars. Seed disinfection and seed or seedling quality controls guarantee growers on the sanitary status of their planting material. Removal of virus or vector sources in the crop environment can significantly delay the onset of viral epidemics. Insecticide or oil application may reduce virus spread in some situations. Diverse cultural practices interfere with or prevent vector reaching the crop. Resistance can be obtained by grafting for soil-borne viruses, by cross-protection, or generally by conventional breeding or genetic engineering. The diversity of the actions that may be taken to limit virus spread in cucurbit crops and their limits will be discussed. The ultimate goal is to provide farmers with technical packages that combine these methods within an integrated disease management program and are adapted to different countries and cropping systems. PMID:25410104

  12. Virus templated metallic nanoparticles

    NASA Astrophysics Data System (ADS)

    Aljabali, Alaa A. A.; Barclay, J. Elaine; Lomonossoff, George P.; Evans, David J.

    2010-12-01

    Plant viruses are considered as nanobuilding blocks that can be used as synthons or templates for novel materials. Cowpea mosaic virus (CPMV) particles have been shown to template the fabrication of metallic nanoparticles by an electroless deposition metallization process. Palladium ions were electrostatically bound to the virus capsid and, when reduced, acted as nucleation sites for the subsequent metal deposition from solution. The method, although simple, produced highly monodisperse metallic nanoparticles with a diameter of ca. <=35 nm. CPMV-templated particles were prepared with cobalt, nickel, iron, platinum, cobalt-platinum and nickel-iron.Plant viruses are considered as nanobuilding blocks that can be used as synthons or templates for novel materials. Cowpea mosaic virus (CPMV) particles have been shown to template the fabrication of metallic nanoparticles by an electroless deposition metallization process. Palladium ions were electrostatically bound to the virus capsid and, when reduced, acted as nucleation sites for the subsequent metal deposition from solution. The method, although simple, produced highly monodisperse metallic nanoparticles with a diameter of ca. <=35 nm. CPMV-templated particles were prepared with cobalt, nickel, iron, platinum, cobalt-platinum and nickel-iron. Electronic supplementary information (ESI) available: Additional experimental detail, agarose gel electrophoresis results, energy dispersive X-ray spectra, ?-potential measurements, dynamic light scattering data, nanoparticle tracking analysis and an atomic force microscopy image of Ni-CPMV. See DOI: 10.1039/c0nr00525h

  13. Readability of Ebola Information on Websites of Public Health Agencies, United States, United Kingdom, Canada, Australia, and Europe

    PubMed Central

    Spanoudakis, Elpiniki; Holmes, Alison H.

    2015-01-01

    Public involvement in efforts to control the current Ebola virus disease epidemic requires understandable information. We reviewed the readability of Ebola information from public health agencies in non–Ebola-affected areas. A substantial proportion of citizens would have difficulty understanding existing information, which would potentially hinder effective health-seeking behaviors. PMID:26079313

  14. Readability of Ebola Information on Websites of Public Health Agencies, United States, United Kingdom, Canada, Australia, and Europe.

    PubMed

    Castro-Sánchez, Enrique; Spanoudakis, Elpiniki; Holmes, Alison H

    2015-07-01

    Public involvement in efforts to control the current Ebola virus disease epidemic requires understandable information. We reviewed the readability of Ebola information from public health agencies in non-Ebola-affected areas. A substantial proportion of citizens would have difficulty understanding existing information, which would potentially hinder effective health-seeking behaviors. PMID:26079313

  15. 9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  16. 9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  17. 9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  18. Investigating the zoonotic origin of the West African Ebola epidemic.

    PubMed

    Marí Saéz, Almudena; Weiss, Sabrina; Nowak, Kathrin; Lapeyre, Vincent; Zimmermann, Fee; Düx, Ariane; Kühl, Hjalmar S; Kaba, Moussa; Regnaut, Sebastien; Merkel, Kevin; Sachse, Andreas; Thiesen, Ulla; Villányi, Lili; Boesch, Christophe; Dabrowski, Piotr W; Radoni?, Aleksandar; Nitsche, Andreas; Leendertz, Siv Aina J; Petterson, Stefan; Becker, Stephan; Krähling, Verena; Couacy-Hymann, Emmanuel; Akoua-Koffi, Chantal; Weber, Natalie; Schaade, Lars; Fahr, Jakob; Borchert, Matthias; Gogarten, Jan F; Calvignac-Spencer, Sébastien; Leendertz, Fabian H

    2015-01-01

    The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2-year-old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free-tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology. PMID:25550396

  19. Investigating the zoonotic origin of the West African Ebola epidemic

    PubMed Central

    Marí Saéz, Almudena; Weiss, Sabrina; Nowak, Kathrin; Lapeyre, Vincent; Zimmermann, Fee; Düx, Ariane; Kühl, Hjalmar S; Kaba, Moussa; Regnaut, Sebastien; Merkel, Kevin; Sachse, Andreas; Thiesen, Ulla; Villányi, Lili; Boesch, Christophe; Dabrowski, Piotr W; Radoni?, Aleksandar; Nitsche, Andreas; Leendertz, Siv Aina J; Petterson, Stefan; Becker, Stephan; Krähling, Verena; Couacy-Hymann, Emmanuel; Akoua-Koffi, Chantal; Weber, Natalie; Schaade, Lars; Fahr, Jakob; Borchert, Matthias; Gogarten, Jan F; Calvignac-Spencer, Sébastien; Leendertz, Fabian H

    2015-01-01

    The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2-year-old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free-tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology. PMID:25550396

  20. Testing for Human Immunodeficiency Virus

    MedlinePLUS

    ... incisions made in the mother’s abdomen and uterus. Human Immunodeficiency Virus (HIV): A virus that attacks certain cells of the body’s immune system and causes acquired immunodeficiency syndrome (AIDS). Immune System: ...

  1. Herpes Simplex Virus (Cold Sores)

    MedlinePLUS

    ... involve the brain and its lining to cause encephalitis and meningitis. In the newborn, herpes viruses cause ... or even death. Herpes simplex viruses also cause encephalitis, an infection of the brain. Children with encephalitis ...

  2. Special Issue: Honey Bee Viruses

    PubMed Central

    Gisder, Sebastian; Genersch, Elke

    2015-01-01

    Pollination of flowering plants is an important ecosystem service provided by wild insect pollinators and managed honey bees. Hence, losses and declines of pollinating insect species threaten human food security and are of major concern not only for apiculture or agriculture but for human society in general. Honey bee colony losses and bumblebee declines have attracted intensive research interest over the last decade and although the problem is far from being solved we now know that viruses are among the key players of many of these bee losses and bumblebee declines. With this special issue on bee viruses we, therefore, aimed to collect high quality original papers reflecting the current state of bee virus research. To this end, we focused on newly discovered viruses (Lake Sinai viruses, bee macula-like virus), or a so far neglected virus species (Apis mellifera filamentous virus), and cutting edge technologies (mass spectrometry, RNAi approach) applied in the field. PMID:26702462

  3. Production of virus resistant plants

    DOEpatents

    Dougherty, W.G.; Lindbo, J.A.

    1996-12-10

    A method of suppressing virus gene expression in plants using untranslatable plus sense RNA is disclosed. The method is useful for the production of plants that are resistant to virus infection. 9 figs.

  4. TT viruses in animals.

    PubMed

    Okamoto, H

    2009-01-01

    Infection with TT virus (Torque teno virus, TTV), a small, nonenveloped virus with a circular, single-stranded DNA genome classified in the floating genus Anellovirus, is not restricted to humans. Using highly conserved primers derived from the untranslated region of the human TTV genome, a variety of TTV-like viruses have been found circulating in nonhuman primates such as chimpanzees, macaques, and tamarins. TTV variants in nonhuman primates are species-specific, although some genetic groups of human and chimpanzee TTVs cluster to make human/chimpanzee clades. TTVs from macaques and tamarins are increasingly divergent from TTV variants infecting humans and chimpanzees. TTV-like mini virus (TTMV) infections have also been detected in chimpanzees, with genotypes distinct but interspersed with human TTMV genotypes. Pets are also naturally infected with species-specific TTVs, and several isolates have been found in cats and dogs. In addition, other mammals such as tupaias and pigs have species-specific TTVs: swine TTVs are found among pigs worldwide. The genomic organization and proposed transcriptional profiles of TTVs infecting nonhuman primate and other mammalian species are similar to those of human TTVs, and co-evolution of TTVs with their hosts has been suggested. To date, TTVs infecting nonhuman primates and other mammalian species have been under-examined. It is likely that essentially all animals are naturally infected with species-specific TTVs. PMID:19230556

  5. Frequently Asked Questions on Ebola Virus Disease

    MedlinePLUS

    ... personal protective equipment (PPE) or are not applying infection prevention and control (IPC) measures when caring for patients. All health-care providers working at all levels of the health system – hospitals, clinics and health posts – should be fully informed ...

  6. Raspberry latent virus in Rubus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Raspberry latent virus (RpLV) is a recently characterized virus reported from the Pacific Northwest, including Oregon and Washington in the United States and British Columbia in Canada. The virus appears to spread rapidly in the Fraser River Valley (northwest Washington and southwest British Columb...

  7. Ipomoviruses: Squash vein yellowing virus, Cucumber vein yellowing virus, Cassava brown streak virus, and Ugandan cassava brown streak virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ipomoviruses including Squash vein yellowing virus, Cucumber vein yellowing virus and Cassava brown streak virus are currently causing significant economic impact on crop production in several regions of the world. Only recently have results of detailed characterization of their whitefly transmissi...

  8. Protecting Your Computer from Viruses

    ERIC Educational Resources Information Center

    Descy, Don E.

    2006-01-01

    A computer virus is defined as a software program capable of reproducing itself and usually capable of causing great harm to files or other programs on the same computer. The existence of computer viruses--or the necessity of avoiding viruses--is part of using a computer. With the advent of the Internet, the door was opened wide for these…

  9. Pathobiology of avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus causes serious disease in a wide variety of birds and mammals. Its natural hosts are wild aquatic birds, in which most infections are unapparent. Avian Influenza (AI) viruses are classified into 16 hemagglutinin (H1-16) and nine neuraminidase (N1-9) subtypes. Each virus has on...

  10. Avian influenza virus RNA extraction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficient extraction and purification of viral RNA is critical for down-stream molecular applications whether it is the sensitive and specific detection of virus in clinical samples, virus gene cloning and expression, or quantification of avian influenza (AI) virus by molecular methods from expe...

  11. An introduction to computer viruses

    SciTech Connect

    Brown, D.R.

    1992-03-01

    This report on computer viruses is based upon a thesis written for the Master of Science degree in Computer Science from the University of Tennessee in December 1989 by David R. Brown. This thesis is entitled An Analysis of Computer Virus Construction, Proliferation, and Control and is available through the University of Tennessee Library. This paper contains an overview of the computer virus arena that can help the reader to evaluate the threat that computer viruses pose. The extent of this threat can only be determined by evaluating many different factors. These factors include the relative ease with which a computer virus can be written, the motivation involved in writing a computer virus, the damage and overhead incurred by infected systems, and the legal implications of computer viruses, among others. Based upon the research, the development of a computer virus seems to require more persistence than technical expertise. This is a frightening proclamation to the computing community. The education of computer professionals to the dangers that viruses pose to the welfare of the computing industry as a whole is stressed as a means of inhibiting the current proliferation of computer virus programs. Recommendations are made to assist computer users in preventing infection by computer viruses. These recommendations support solid general computer security practices as a means of combating computer viruses.

  12. Research on computer virus database management system

    NASA Astrophysics Data System (ADS)

    Qi, Guoquan

    2011-12-01

    The growing proliferation of computer viruses becomes the lethal threat and research focus of the security of network information. While new virus is emerging, the number of viruses is growing, virus classification increasing complex. Virus naming because of agencies' capture time differences can not be unified. Although each agency has its own virus database, the communication between each other lacks, or virus information is incomplete, or a small number of sample information. This paper introduces the current construction status of the virus database at home and abroad, analyzes how to standardize and complete description of virus characteristics, and then gives the information integrity, storage security and manageable computer virus database design scheme.

  13. Simian Varicella Virus Pathogenesis

    PubMed Central

    Mahalingam, Ravi; Messaoudi, Ilhem; Gilden, Don

    2010-01-01

    Because varicella zoster virus (VZV) is an exclusively human pathogen, the development of an animal model is necessary to study pathogenesis, latency, and reactivation. The pathological, virological, and immunological features of simian varicella virus (SVV) infection in nonhuman primates are similar to those of VZV infection in humans. Both natural infection of cynomolgus and African green monkeys as well as intrabronchial inoculation of rhesus macaques with SVV provide the most useful models to study viral and immunological aspects of latency and the host immune response. Experimental immunosuppression of monkeys latently infected with SVV results in zoster, thus providing a new model system to study how the loss of adaptive immunity modulates virus reactivation. PMID:20186611

  14. Zika virus outside Africa.

    PubMed

    Hayes, Edward B

    2009-09-01

    Zika virus (ZIKV) is a flavivirus related to yellow fever, dengue, West Nile, and Japanese encephalitis viruses. In 2007 ZIKV caused an outbreak of relatively mild disease characterized by rash, arthralgia, and conjunctivitis on Yap Island in the southwestern Pacific Ocean. This was the first time that ZIKV was detected outside of Africa and Asia. The history, transmission dynamics, virology, and clinical manifestations of ZIKV disease are discussed, along with the possibility for diagnostic confusion between ZIKV illness and dengue.The emergence of ZIKV outside of its previously known geographic range should prompt awareness of the potential for ZIKV to spread to other Pacific islands and the Americas. PMID:19788800

  15. Zika Virus Outside Africa

    PubMed Central

    2009-01-01

    Zika virus (ZIKV) is a flavivirus related to yellow fever, dengue, West Nile, and Japanese encephalitis viruses. In 2007 ZIKV caused an outbreak of relatively mild disease characterized by rash, arthralgia, and conjunctivitis on Yap Island in the southwestern Pacific Ocean. This was the first time that ZIKV was detected outside of Africa and Asia. The history, transmission dynamics, virology, and clinical manifestations of ZIKV disease are discussed, along with the possibility for diagnostic confusion between ZIKV illness and dengue.The emergence of ZIKV outside of its previously known geographic range should prompt awareness of the potential for ZIKV to spread to other Pacific islands and the Americas. PMID:19788800

  16. Viruses and viral proteins

    PubMed Central

    Verdaguer, Nuria; Ferrero, Diego; Murthy, Mathur R. N.

    2014-01-01

    For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes. PMID:25485129

  17. Virus Chapter: Dicistrovidae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Dicistroviridae family comprises viruses infecting both beneficial arthropods such as honey bees and shrimp and insect pests of medical and agricultural importance. During the last five years, advances in sequencing and phylogenetic analysis have led to the discovery and identification of sever...

  18. Viruses of Haloarchaea

    PubMed Central

    Luk, Alison W. S.; Williams, Timothy J.; Erdmann, Susanne; Papke, R. Thane; Cavicchioli, Ricardo

    2014-01-01

    In hypersaline environments, haloarchaea (halophilic members of the Archaea) are the dominant organisms, and the viruses that infect them, haloarchaeoviruses are at least ten times more abundant. Since their discovery in 1974, described haloarchaeoviruses include head-tailed, pleomorphic, spherical and spindle-shaped morphologies, representing Myoviridae, Siphoviridae, Podoviridae, Pleolipoviridae, Sphaerolipoviridae and Fuselloviridae families. This review overviews current knowledge of haloarchaeoviruses, providing information about classification, morphotypes, macromolecules, life cycles, genetic manipulation and gene regulation, and host-virus responses. In so doing, the review incorporates knowledge from laboratory studies of isolated viruses, field-based studies of environmental samples, and both genomic and metagenomic analyses of haloarchaeoviruses. What emerges is that some haloarchaeoviruses possess unique morphological and life cycle properties, while others share features with other viruses (e.g., bacteriophages). Their interactions with hosts influence community structure and evolution of populations that exist in hypersaline environments as diverse as seawater evaporation ponds, to hot desert or Antarctic lakes. The discoveries of their wide-ranging and important roles in the ecology and evolution of hypersaline communities serves as a strong motivator for future investigations of both laboratory-model and environmental systems. PMID:25402735

  19. Wineberry latent virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wineberry latent virus (WLV) was discovered in a single symptomless plant of wineberry, Rubus phoenicolasius, which was growing in an experimental planting in Scotland. The plant originated in the United States, where wineberry is established in the wild in the Northeast. Experimentally, WLV can be ...

  20. GENOME OF HORSEPOX VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we present the genomic sequence of horsepox virus (HSPV) isolate MNR-76, an orthopoxvirus (OPV) isolated in 1976 from diseased Mongolian horses. The 212 kbp genome contained 7.5 kbp inverted terminal repeats (ITR) and lacked extensive terminal tandem repetition. HSPV contained 236 ORFs with sim...

  1. Tomato ringspot virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tomato ringspot virus (ToRSV) causes a nematode-vectored disease of highbush blueberry in New York, Oregon, Pennsylvania and Washington in the United States but has not been reported elsewhere in the world on this crop or on other Vaccinium spp. The occurrence and intensity of symptoms vary among b...

  2. From Shakespeare to Viruses

    SciTech Connect

    Sung-Hou Kim

    2009-02-09

    Berkeley Lab scientists have created a unique new tool for analyzing and comparing long sets of data, be it the genomes of mammals or viruses, or the works of Shakespeare. The results of the Shakespeare analysis surprised scholars with their accuracy

  3. Honey Bee Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Viruses are significant threats to the health and well-being of the honey bee, Apis mellifera. To alleviate the threats posed by these invasive organisms, a better understanding of bee viral infections will be of crucial importance in developing effective and environmentally-benign disease control ...

  4. Apple mosaic virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Apple mosaic virus (ApMV), a member of the ilarvirus group, naturally infects Betula, Aesculus, Humulus, and several crop genera in the family Rosaceae (Malus, Prunus, Rosa and Rubus). ApMV was first reported in Rubus in several blackberry and raspberry cultivars in the United States and subsequentl...

  5. Blueberry shock virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberry shock disease first observed in Washington state in 1987 and initially confused with blueberry scorch caused by Blueberry scorch virus (BlScV). However, shock affected plants produced a second flush of leaves after flowering and the plants appeared normal by late summer except for the lac...

  6. Newcastle disease virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Newcastle disease virus (NDV), a member of the Avulavirus genus in the Paramyxoviridae family, has a ribonucleic acid (RNA) genome that is negative sense, non-segmented, and single-stranded. The genome codes for six structural proteins: nucleocapsid, phosphoprotein, matrix, fusion, hemagglutinin-neu...

  7. Varicella zoster virus latency

    PubMed Central

    Eshleman, Emily; Shahzad, Aamir; Cohrs, Randall J

    2011-01-01

    Primary infection by varicella zoster virus (VZV) typically results in childhood chickenpox, at which time latency is established in the neurons of the cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. During latency, the histone-associated virus genome assumes a circular episomal configuration from which transcription is epigenetically regulated. The lack of an animal model in which VZV latency and reactivation can be studied, along with the difficulty in obtaining high-titer cell-free virus, has limited much of our understanding of VZV latency to descriptive studies of ganglia removed at autopsy and analogy to HSV-1, the prototype alphaherpesvirus. However, the lack of miRNA, detectable latency-associated transcript and T-cell surveillance during VZV latency highlight basic differences between the two neurotropic herpesviruses. This article focuses on VZV latency: establishment, maintenance and reactivation. Comparisons are made with HSV-1, with specific attention to differences that make these viruses unique human pathogens. PMID:21695042

  8. Raspberry leaf curl virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Raspberry leaf curl virus (RLCV) is limited to hosts in the genus Rubus and is transmitted persistently by the small raspberry aphid, Aphis rubicola Oestlund. It is found only in North America, principally in the northeastern United States and southeastern Canada and in the Rocky Mountain regions of...

  9. From Shakespeare to Viruses

    ScienceCinema

    Kim, Sung-Hou

    2013-05-29

    Berkeley Lab scientists have created a unique new tool for analyzing and comparing long sets of data, be it the genomes of mammals or viruses, or the works of Shakespeare. The results of the Shakespeare analysis surprised scholars with their accuracy.

  10. Human Viruses and Cancer

    PubMed Central

    Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M.

    2014-01-01

    The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt’s lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers. PMID:25341666

  11. Viruses--a conundrum.

    PubMed

    Pandit, H M

    1996-01-01

    To understand the pathophysiology of a disease, it is important to know the origin, causes and effects. This also helps to control and to treat the disease. In virus infections, it is difficult and confusing when the origin is sought. In this article it is hypothesized that the viruses, which are nucleoproteins, arise as fragments or broken segments of DNA or RNA. Various factors, such as radiation, toxic chemicals, pollution, are listed as possible causes of such fragmentations. It is logical that these DNA or RNA fragments must come from the genomes or the genes essential for the proliferation or cell division. The symbiotic and parasitic interrelationships of bacteria, plants and animals make the problem more complex and confusing, because all of them thrive and grow in each other cells, thus producing more nucleoproteins of each. Virions contain a small quantum of energy as the initial source of bioenergy to ignite and initiate the complex chemical reactions needed to use the potential energy reservoirs from the host. In this respect viruses can be considered as borderline between the living and the non-living. If one has to develop an effective drug or method for treating virus infections or cancers, the drug must have an antimitotic activity without affecting other normal functions. Such seems to be the case of globin derivatives of sickle cell and thalassemia red blood cells. PMID:8875804

  12. Cell injury with viruses.

    PubMed Central

    Tamm, I.

    1975-01-01

    The inhibitions of cellular protein and RNA synthesis in picornavirus-infected cells are early events which require only limited synthesis of virus-specific proteins. The inhibition of cellular protein synthesis appears to be due to blocking of the association of ribosomes with host messenger RNA. Inhibition of cellular RNA synthesis involves inactivation of the template-enzyme complex and affects ribosomal RNA synthesis before messenger RNA synthesis. Inhibition of cellular DNA synthesis also occurs early and may be secondary to inhibition of cellular protein synthesis. Early chromatid breaks may be related to inhibitions of cellular protein and nucleic acid synthesis. Stimulation of phospholipid synthesis in picornavirus-infected cells also requires only limited synthesis of virus-specific proteins. In contrast, release of lysosomal enzymes, proliferation of smooth cytoplasmic membranes, cellular vacuolization, retraction, and rounding, and diffuse chromosomal changes related to karyorrhexis and pyknosis are all dependent on considerable synthesis of virus-specific proteins during the middle part of the picornavirus growth cycle. The early virus-induced alterations in cellular biosynthetic processes are not the direct or sole cause of the subsequent marked pathologic changes in the membranes and chromosomes of the cell. Images Figure 1 PMID:1180330

  13. Turnip Yellow Mosaic Virus

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The bumpy exterior of the turnip yellow mosaic virus (TYMV) protein coat, or capsid, was defined in detail by Dr. Alexander McPherson of the University of California, Irvin using proteins crystallized in space for analysis on Earth. TYMV is an icosahedral virus constructed from 180 copies of the same protein arranged into 12 clusters of five proteins (pentamers), and 20 clusters of six proteins (hexamers). The final TYMV structure led to the unexpected hypothesis that the virus releases its RNA by essentially chemical-mechanical means. Most viruses have fairly flat coats, but in TYNV, the fold in each protein, called the jellyroll, is clustered at the points where the protein pentamers and hexamers join. The jellyrolls are almost standing on end, producing a bumpy surface with knobs at all of the pentamers and hexamers. At the inside surface of the pentamers is a void that is not present at the hexamers. The coating had been seen in early stuties of TYMV, but McPherson's atomic structure shows much more detail. The inside surface is strikingly, and unexpectedly, different than the outside. While the pentamers contain a central void on the inside, the hexameric units contain peptides linked to each other, forming a ring or, more accurately, rings to fill the void. Credit: Dr. Alexander McPherson, University of California, Irvine

  14. Using viruses as nanomedicines

    PubMed Central

    van Kan-Davelaar, H E; van Hest, J C M; Cornelissen, J J L M; Koay, M S T

    2014-01-01

    The field of nanomedicine involves the design and fabrication of novel nanocarriers for the intracellular delivery of therapeutic cargo or for use in molecular diagnostics. Although traditionally recognized for their ability to invade and infect host cells, viruses and bacteriophages have been engineered over the past decade as highly promising molecular platforms for the targeted delivery and treatment of many human diseases. Inherently biodegradable, the outer capsids of viruses are composed entirely of protein building blocks, which can be genetically or chemically engineered with molecular imaging reagents, targeting ligands and therapeutic molecules. While there are several examples of viruses as in vitro molecular cargo carriers, their potential for applications in nanomedicine has only recently emerged. Here we highlight recent developments towards the design and engineering of viruses for the treatment of cancer, bacterial infections and immune system-related diseases. Linked Articles This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-17 PMID:24571489

  15. VIRUS PERSISTENCE IN GROUNDWATER

    EPA Science Inventory

    The purpose of the study was to determine whether measurable chemical and physical factors correlate with virus survival in groundwater. Groundwater samples were obtained from 11 sites throughout the United States. Water temperature was measured at the time of collection. Several...

  16. Is there a way out for the 2014 Ebola outbreak in Western Africa?

    PubMed

    Andreas, Angelo; Binoun A Egom, Christian; Kruzliak, Peter; Egom, Emmanuel E

    2015-10-01

    The 2014 Ebola outbreak in West Africa, primarily affecting Guinea, Sierra Leone, and Liberia, has exceeded all previous Ebola outbreaks in the number of cases and in international response. Although infections only occur frequently in Western Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. This review aims (i) to discuss the latest data to aid our current recommendations for the prevention and control of the Ebola virus infection, (ii) to review its pathophysiology as well as offering insights on the most current data available about Ebola vaccine progress and potential use. PMID:26522290

  17. Genome of deerpox virus.

    PubMed

    Afonso, C L; Delhon, G; Tulman, E R; Lu, Z; Zsak, A; Becerra, V M; Zsak, L; Kutish, G F; Rock, D L

    2005-01-01

    Deerpox virus (DPV), an uncharacterized and unclassified member of the Poxviridae, has been isolated from North American free-ranging mule deer (Odocoileus hemionus) exhibiting mucocutaneous disease. Here we report the genomic sequence and comparative analysis of two pathogenic DPV isolates, W-848-83 (W83) and W-1170-84 (W84). The W83 and W84 genomes are 166 and 170 kbp, containing 169 and 170 putative genes, respectively. Nucleotide identity between DPVs is 95% over the central 157 kbp. W83 and W84 share similar gene orders and code for similar replicative, structural, virulence, and host range functions. DPV open reading frames (ORFs) with putative virulence and host range functions include those similar to cytokine receptors (R), including gamma interferon receptor (IFN-gammaR), interleukin 1 receptor (IL-1R), and type 8 CC-chemokine receptors; cytokine binding proteins (BP), including IL-18BP, IFN-alpha/betaBP, and tumor necrosis factor binding protein (TNFBP); serpins; and homologues of vaccinia virus (VACV) E3L, K3L, and A52R proteins. DPVs also encode distinct forms of major histocompatibility complex class I, C-type lectin-like protein, and transforming growth factor beta1 (TGF-beta1), a protein not previously described in a mammalian chordopoxvirus. Notably, DPV encodes homologues of cellular endothelin 2 and IL-1R antagonist, novel poxviral genes also likely involved in the manipulation of host responses. W83 and W84 differ from each other by the presence or absence of five ORFs. Specifically, homologues of a CD30 TNFR family protein, swinepox virus SPV019, and VACV E11L core protein are absent in W83, and homologues of TGF-beta1 and lumpy skin disease virus LSDV023 are absent in W84. Phylogenetic analysis indicates that DPVs are genetically distinct from viruses of other characterized poxviral genera and that they likely comprise a new genus within the subfamily Chordopoxvirinae. PMID:15613325

  18. Mechanism of human antibody-mediated neutralization of Marburg virus.

    PubMed

    Flyak, Andrew I; Ilinykh, Philipp A; Murin, Charles D; Garron, Tania; Shen, Xiaoli; Fusco, Marnie L; Hashiguchi, Takao; Bornholdt, Zachary A; Slaughter, James C; Sapparapu, Gopal; Klages, Curtis; Ksiazek, Thomas G; Ward, Andrew B; Saphire, Erica Ollmann; Bukreyev, Alexander; Crowe, James E

    2015-02-26

    The mechanisms by which neutralizing antibodies inhibit Marburg virus (MARV) are not known. We isolated a panel of neutralizing antibodies from a human MARV survivor that bind to MARV glycoprotein (GP) and compete for binding to a single major antigenic site. Remarkably, several of the antibodies also bind to Ebola virus (EBOV) GP. Single-particle EM structures of antibody-GP complexes reveal that all of the neutralizing antibodies bind to MARV GP at or near the predicted region of the receptor-binding site. The presence of the glycan cap or mucin-like domain blocks binding of neutralizing antibodies to EBOV GP, but not to MARV GP. The data suggest that MARV-neutralizing antibodies inhibit virus by binding to infectious virions at the exposed MARV receptor-binding site, revealing a mechanism of filovirus inhibition. PMID:25723164

  19. Detection of sweet potato viruses in Yunnan and genetic diversity analysis of the common viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two hundred seventy-nine samples with virus-like symptoms collected from 16 regions in Yunnan Province were tested by RT-PCR/PCR using virus-specific primers for 8 sweet potato viruses. Six viruses, Sweet potato chlorotic fleck virus (SPCFV), Sweet Potato feathery mottle virus (SPFMV), Sweet potato ...

  20. Reservoir host immune responses to emerging zoonotic viruses.

    PubMed

    Mandl, Judith N; Ahmed, Rafi; Barreiro, Luis B; Daszak, Peter; Epstein, Jonathan H; Virgin, Herbert W; Feinberg, Mark B

    2015-01-15

    Zoonotic viruses, such as HIV, Ebola virus, coronaviruses, influenza A viruses, hantaviruses, or henipaviruses, can result in profound pathology in humans. In contrast, populations of the reservoir hosts of zoonotic pathogens often appear to tolerate these infections with little evidence of disease. Why are viruses more dangerous in one species than another? Immunological studies investigating quantitative and qualitative differences in the host-virus equilibrium in animal reservoirs will be key to answering this question, informing new approaches for treating and preventing zoonotic diseases. Integrating an understanding of host immune responses with epidemiological, ecological, and evolutionary insights into viral emergence will shed light on mechanisms that minimize fitness costs associated with viral infection, facilitate transmission to other hosts, and underlie the association of specific reservoir hosts with multiple emerging viruses. Reservoir host studies provide a rich opportunity for elucidating fundamental immunological processes and their underlying genetic basis, in the context of distinct physiological and metabolic constraints that contribute to host resistance and disease tolerance. PMID:25533784

  1. Discrete virus infection model of hepatitis B virus.

    PubMed

    Zhang, Pengfei; Min, Lequan; Pian, Jianwei

    2015-08-17

    In 1996 Nowak and his colleagues proposed a differential equation virus infection model, which has been widely applied in the study for the dynamics of hepatitis B virus (HBV) infection. Biological dynamics may be described more practically by discrete events rather than continuous ones. Using discrete systems to describe biological dynamics should be reasonable. Based on one revised Nowak et al's virus infection model, this study introduces a discrete virus infection model (DVIM). Two equilibriums of this model, E1 and E2, represents infection free and infection persistent, respectively. Similar to the case of the basic virus infection model, this study deduces a basic virus reproductive number R0 independing on the number of total cells of an infected target organ. A proposed theorem proves that if the basic virus reproductive number R0<1 then the virus free equilibrium E1 is locally stable. The DVIM is more reasonable than an abstract discrete susceptible-infected-recovered model (SIRS) whose basic virus reproductive number R0 is relevant to the number of total cells of the infected target organ. As an application, this study models the clinic HBV DNA data of a patient who was accepted via anti-HBV infection therapy with drug lamivudine. The results show that the numerical simulation is good in agreement with the clinic data. PMID:26405998

  2. Phage Displayed Peptides to Avian H5N1 Virus Distinguished the Virus from Other Viruses

    PubMed Central

    Qin, Chengfeng; Ren, Xiaofeng

    2011-01-01

    The purpose of the current study was to identify potential ligands and develop a novel diagnostic test to highly pathogenic avian influenza A virus (HPAI), subtype H5N1 viruses using phage display technology. The H5N1 viruses were used as an immobilized target in a biopanning process using a 12-mer phage display random peptide library. After five rounds of panning, three phages expressing peptides HAWDPIPARDPF, AAWHLIVALAPN or ATSHLHVRLPSK had a specific binding activity to H5N1 viruses were isolated. Putative binding motifs to H5N1 viruses were identified by DNA sequencing. In terms of the minimum quantity of viruses, the phage-based ELISA was better than antiserum-based ELISA and a manual, semi-quantitative endpoint RT-PCR for detecting H5N1 viruses. More importantly, the selected phages bearing the specific peptides to H5N1 viruses were capable of differentiating this virus from other avian viruses in enzyme-linked immunosorbent assays. PMID:21887228

  3. Assessment of Environmental Contamination and Environmental Decontamination Practices within an Ebola Holding Unit, Freetown, Sierra Leone

    PubMed Central

    Youkee, Daniel; Brown, Colin S.; Lilburn, Paul; Shetty, Nandini; Brooks, Tim; Simpson, Andrew; Bentley, Neil; Lado, Marta; Kamara, Thaim B.; Walker, Naomi F.; Johnson, Oliver

    2015-01-01

    Evidence to inform decontamination practices at Ebola holding units (EHUs) and treatment centres is lacking. We conducted an audit of decontamination procedures inside Connaught Hospital EHU in Freetown, Sierra Leone, by assessing environmental swab specimens for evidence of contamination with Ebola virus by RT-PCR. Swabs were collected following discharge of Ebola Virus Disease (EVD) patients before and after routine decontamination. Prior to decontamination, Ebola virus RNA was detected within a limited area at all bedside sites tested, but not at any sites distant to the bedside. Following decontamination, few areas contained detectable Ebola virus RNA. In areas beneath the bed there was evidence of transfer of Ebola virus material during cleaning. Retraining of cleaning staff reduced evidence of environmental contamination after decontamination. Current decontamination procedures appear to be effective in eradicating persistence of viral RNA. This study supports the use of viral swabs to assess Ebola viral contamination within the clinical setting. We recommend that regular refresher training of cleaning staff and audit of environmental contamination become standard practice at all Ebola care facilities during EVD outbreaks. PMID:26692018

  4. Principles of Virus Structural Organization

    PubMed Central

    Prasad, B.V. Venkataram; Schmid, Michael F

    2013-01-01

    Viruses, the molecular nanomachines infecting hosts ranging from prokaryotes to eukaryotes, come in different sizes, shapes and symmetries. Questions such as what principles govern their structural organization, what factors guide their assembly, how these viruses integrate multifarious functions into one unique structure have enamored researchers for years. In the last five decades, following Caspar and Klug's elegant conceptualization of how viruses are constructed, high resolution structural studies using X-ray crystallography and more recently cryo-EM techniques have provided a wealth of information on structures of variety of viruses. These studies have significantly furthered our understanding of the principles that underlie structural organization in viruses. Such an understanding has practical impact in providing a rational basis for the design and development of antiviral strategies. In this chapter, we review principles underlying capsid formation in a variety of viruses, emphasizing the recent developments along with some historical perspective. PMID:22297509

  5. Mechanisms of Virus Assembly

    NASA Astrophysics Data System (ADS)

    Perlmutter, Jason D.; Hagan, Michael F.

    2015-04-01

    Viruses are nanoscale entities containing a nucleic acid genome encased in a protein shell called a capsid and in some cases are surrounded by a lipid bilayer membrane. This review summarizes the physics that govern the processes by which capsids assemble within their host cells and in vitro. We describe the thermodynamics and kinetics for the assembly of protein subunits into icosahedral capsid shells and how these are modified in cases in which the capsid assembles around a nucleic acid or on a lipid bilayer. We present experimental and theoretical techniques used to characterize capsid assembly, and we highlight aspects of virus assembly that are likely to receive significant attention in the near future.

  6. Mechanisms of virus assembly

    E-print Network

    Jason D Perlmutter; Michael F Hagan

    2014-07-15

    Viruses are nanoscale entities containing a nucleic acid genome encased in a protein shell called a capsid, and in some cases surrounded by a lipid bilayer membrane. This review summarizes the physics that govern the processes by which capsids assembles within their host cells and in vitro. We describe the thermodynamics and kinetics for assembly of protein subunits into icosahedral capsid shells, and how these are modified in cases where the capsid assembles around a nucleic acid or on a lipid bilayer. We present experimental and theoretical techniques that have been used to characterize capsid assembly, and we highlight aspects of virus assembly which are likely to receive significant attention in the near future.

  7. Introducing Virological Concepts Using an Insect Virus.

    ERIC Educational Resources Information Center

    Sheppard, Roger F.

    1980-01-01

    A technique is presented which utilizes wax moth larvae in a laboratory investigation of an insect virus. Describes how an insect virus can be used to introduce undergraduate biology students to laboratory work on viruses and several virological concepts. (SA)

  8. Influenza Type A Viruses and Subtypes

    MedlinePLUS

    ... influenza A viruses are known to infect both birds and people. Influenza A H5 There are nine ... H5N9). Most H5 viruses identified worldwide in wild birds and poultry are low pathogenic viruses, but occasionally ...

  9. Variant (Swine Origin) Influenza Viruses in Humans

    MedlinePLUS

    ... Past Newsletters Variant (Swine Origin) Influenza Viruses in Humans Language: English Español Recommend on Facebook Tweet ... Page Background Reporting Additional Information Key Facts about Human Infections with Variant Viruses (Swine Origin Influenza Viruses ...

  10. NATIONAL RESPIRATORY AND ENTERIC VIRUS SURVEILLANCE SYSTEM

    EPA Science Inventory

    The National Respiratory and Enteric Virus Surveillance System is a lab based system which monitors temporal and geographic patterns associated with the detection of respiratory syncytial virus (RSV), human parainfluenza viruses (HPIV), respiratory and enteric adenoviruses, and r...

  11. Viruses manipulate the marine environment.

    PubMed

    Rohwer, Forest; Thurber, Rebecca Vega

    2009-05-14

    Marine viruses affect Bacteria, Archaea and eukaryotic organisms and are major components of the marine food web. Most studies have focused on their role as predators and parasites, but many of the interactions between marine viruses and their hosts are much more complicated. A series of recent studies has shown that viruses have the ability to manipulate the life histories and evolution of their hosts in remarkable ways, challenging our understanding of this almost invisible world. PMID:19444207

  12. Interferon production and virus replication in lymphoblastoid cells infected with different viruses.

    PubMed

    Heremans, H; de Ley, M; Volckaert-Vervliet, G; Billiau, A

    1980-01-01

    A semicontinuous infection system was used to test viral replication and interferon induction in lymphoblastoid cells: measles virus, Newcastle disease virus (NDV), Sendai virus, human parainfluenza virus (type II and III), Semliki forest virus (SFV) and Vesicular stomatitis virus (VSV). With the exception of Sendai virus, all viruses replicated in the Namalva cell line. Only measles virus was able to induce high levels of interferon. Three other cell lines, NC37, Raji (TK+-variant) and Raji (TK--variant) were tested using measles virus as inducer. The interferon yields from these cells were inferior to those obtained from Namalva cells. PMID:6243928

  13. Reemergence of chikungunya virus.

    PubMed

    Morrison, Thomas E

    2014-10-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes acute fever and acute and chronic musculoskeletal pain in humans. Since 2004, CHIKV has caused millions of cases of disease in the Indian Ocean region and has emerged in new areas, including Europe, the Middle East, and the Pacific region. The mosquito vectors for this virus are globally distributed in tropical and temperate zones, providing the opportunity for CHIKV to continue to expand into new geographic regions. In October 2013, locally acquired cases of CHIKV infection were identified on the Caribbean island of Saint Martin, signaling the arrival of the virus in the Western Hemisphere. In just 9 months, CHIKV has spread to 22 countries in the Caribbean and Central and South America, resulting in hundreds of thousands of cases. CHIKV disease can be highly debilitating, and large epidemics have severe economic consequences. Thus, there is an urgent need for continued research into the epidemiology, pathogenesis, prevention, and treatment of these infections. PMID:25078691

  14. Nuclear entry of DNA viruses

    PubMed Central

    Fay, Nikta; Panté, Nelly

    2015-01-01

    DNA viruses undertake their replication within the cell nucleus, and therefore they must first deliver their genome into the nucleus of their host cells. Thus, trafficking across the nuclear envelope is at the basis of DNA virus infections. Nuclear transport of molecules with diameters up to 39 nm is a tightly regulated process that occurs through the nuclear pore complex (NPC). Due to the enormous diversity of virus size and structure, each virus has developed its own strategy for entering the nucleus of their host cells, with no two strategies alike. For example, baculoviruses target their DNA-containing capsid to the NPC and subsequently enter the nucleus intact, while the hepatitis B virus capsid crosses the NPC but disassembles at the nuclear side of the NPC. For other viruses such as herpes simplex virus and adenovirus, although both dock at the NPC, they have each developed a distinct mechanism for the subsequent delivery of their genome into the nucleus. Remarkably, other DNA viruses, such as parvoviruses and human papillomaviruses, access the nucleus through an NPC-independent mechanism. This review discusses our current understanding of the mechanisms used by DNA viruses to deliver their genome into the nucleus, and further presents the experimental evidence for such mechanisms. PMID:26029198

  15. RECOVIR Software for Identifying Viruses

    NASA Technical Reports Server (NTRS)

    Chakravarty, Sugoto; Fox, George E.; Zhu, Dianhui

    2013-01-01

    Most single-stranded RNA (ssRNA) viruses mutate rapidly to generate a large number of strains with highly divergent capsid sequences. Determining the capsid residues or nucleotides that uniquely characterize these strains is critical in understanding the strain diversity of these viruses. RECOVIR (an acronym for "recognize viruses") software predicts the strains of some ssRNA viruses from their limited sequence data. Novel phylogenetic-tree-based databases of protein or nucleic acid residues that uniquely characterize these virus strains are created. Strains of input virus sequences (partial or complete) are predicted through residue-wise comparisons with the databases. RECOVIR uses unique characterizing residues to identify automatically strains of partial or complete capsid sequences of picorna and caliciviruses, two of the most highly diverse ssRNA virus families. Partition-wise comparisons of the database residues with the corresponding residues of more than 300 complete and partial sequences of these viruses resulted in correct strain identification for all of these sequences. This study shows the feasibility of creating databases of hitherto unknown residues uniquely characterizing the capsid sequences of two of the most highly divergent ssRNA virus families. These databases enable automated strain identification from partial or complete capsid sequences of these human and animal pathogens.

  16. Computer virus information update CIAC-2301

    SciTech Connect

    Orvis, W.J.

    1994-01-15

    While CIAC periodically issues bulletins about specific computer viruses, these bulletins do not cover all the computer viruses that affect desktop computers. The purpose of this document is to identify most of the known viruses for the MS-DOS and Macintosh platforms and give an overview of the effects of each virus. The authors also include information on some windows, Atari, and Amiga viruses. This document is revised periodically as new virus information becomes available. This document replaces all earlier versions of the CIAC Computer virus Information Update. The date on the front cover indicates date on which the information in this document was extracted from CIAC`s Virus database.

  17. Structure of Flexible Filamentous Plant Viruses

    SciTech Connect

    Kendall, Amy; McDonald, Michele; Bian, Wen; Bowles, Timothy; Baumgarten, Sarah C.; Shi, Jian; Stewart, Phoebe L.; Bullitt, Esther; Gore, David; Irving, Thomas C.; Havens, Wendy M.; Ghabrial, Said A.; Wall, Joseph S.; Stubbs, Gerald

    2008-10-23

    Flexible filamentous viruses make up a large fraction of the known plant viruses, but in comparison with those of other viruses, very little is known about their structures. We have used fiber diffraction, cryo-electron microscopy, and scanning transmission electron microscopy to determine the symmetry of a potyvirus, soybean mosaic virus; to confirm the symmetry of a potexvirus, potato virus X; and to determine the low-resolution structures of both viruses. We conclude that these viruses and, by implication, most or all flexible filamentous plant viruses share a common coat protein fold and helical symmetry, with slightly less than 9 subunits per helical turn.

  18. Evolutionary Origins of Human Herpes Simplex Viruses 1 and 2

    PubMed Central

    Wertheim, Joel O.; Smith, Martin D.; Smith, Davey M.; Scheffler, Konrad; Kosakovsky Pond, Sergei L.

    2014-01-01

    Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus–host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two-thirds of the human population infected by at least one virus. Here, we investigated whether the additional human simplex virus is the result of ancient viral lineage duplication or cross-species transmission. We found that standard phylogenetic models of nucleotide substitution are inadequate for distinguishing among these competing hypotheses; the extent of synonymous substitutions causes a substantial underestimation of the lengths of some of the branches in the phylogeny, consistent with observations in other viruses (e.g., avian influenza, Ebola, and coronaviruses). To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment. This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct Homo precursor of modern humans, around 1.6 Ma. These results provide a new framework for understanding human herpes simplex virus evolution and demonstrate the importance of using selection-informed models of sequence evolution when investigating viral origin hypotheses. PMID:24916030

  19. Formation of reticuloendotheliosis virus pseudotypes of Rous sarcoma virus.

    PubMed

    Sawyer, R C; Hanafusa, H

    1977-06-01

    Superinfection of chicken embryo fibroblasts transformed by the defective Bryan strain of Rous sarcoma virus (BH-RSV) with two different reticuloendotheliosis viruses (REVs), REV strain T (REV-T) or spleen necrosis virus (SNV), resulted in the production of infectious sarcoma virus pseudotypes. These pseudotypes were neutralized by antiserum prepared against SNV and were unable to infect chicken cells preinfected with either REV-T or SNV. These results suggest that defective BH-RSV is able to use the glycoprotein from REV to form infectious pseudotypes. On the other hand, neither REV-T nor SNV was able to supply a functional reverse transcriptase to the polymerase-negative mutant BH-RSValpha, nor was REV-T or SNV able to complement the defect in the internal protein gene of the temperature-sensitive avian sarcoma virus mutant NY45. PMID:195082

  20. Detection of Nipah virus RNA in fruit bat (Pteropus giganteus) from India.

    PubMed

    Yadav, Pragya D; Raut, Chandrashekhar G; Shete, Anita M; Mishra, Akhilesh C; Towner, Jonathan S; Nichol, Stuart T; Mourya, Devendra T

    2012-09-01

    The study deals with the survey of different bat populations (Pteropus giganteus, Cynopterus sphinx, and Megaderma lyra) in India for highly pathogenic Nipah virus (NiV), Reston Ebola virus, and Marburg virus. Bats (n = 140) from two states in India (Maharashtra and West Bengal) were tested for IgG (serum samples) against these viruses and for virus RNAs. Only NiV RNA was detected in a liver homogenate of P. giganteus captured in Myanaguri, West Bengal. Partial sequence analysis of nucleocapsid, glycoprotein, fusion, and phosphoprotein genes showed similarity with the NiV sequences from earlier outbreaks in India. A serum sample of this bat was also positive by enzyme-linked immunosorbent assay for NiV-specific IgG. This is the first report on confirmation of Nipah viral RNA in Pteropus bat from India and suggests the possible role of this species in transmission of NiV in India. PMID:22802440

  1. The Global Virus Network: Challenging chikungunya.

    PubMed

    McSweegan, Edward; Weaver, Scott C; Lecuit, Marc; Frieman, Matthew; Morrison, Thomas E; Hrynkow, Sharon

    2015-08-01

    The recent spread of chikungunya virus to the Western Hemisphere, together with the ongoing Ebola epidemic in West Africa, have highlighted the importance of international collaboration in the detection and management of disease outbreaks. In response to this need, the Global Virus Network (GVN) was formed in 2011. The GVN is a coalition of leading medical virologists in 34 affiliated laboratories in 24 countries, who collaborate to share their resources and expertise. The GVN supports research, promotes training for young scientists, serves as a technical resource for governments, businesses and international organizations, facilitates international scientific cooperation, and advocates for funding and evidence-based public policies. In response to the spread of chikungunya, the GVN formed a task force to identify research gaps and opportunities, including models of infection and disease, candidate vaccines and antivirals, epidemiology and vector control measures. Its members also serve as authoritative sources of information for the public, press, and policy-makers. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World". PMID:26071007

  2. Groundnut Ringspot Virus in Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tospoviruses in vegetable crops are difficult to manage due to a shortage of basic information about the viruses and their vectors. This is especially true for the recently detected Groundnut ringspot virus (GRSV). This publication presents all current knowledge of GRSV in Florida....

  3. TOTAL CULTURABLE VIRUS QUANTAL ASSAY

    EPA Science Inventory

    This chapter describes a quantal method for assaying culturable human enteric viruses from water matrices. The assay differs from the plaque assay described in Chapter 10 (December 1987 Revision) in that it is based upon the direct microscopic viewing of cells for virus-induced ...

  4. Antiviral immunity and virus vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As obligate intracellular organisms, viruses have co-evolved with their respective host species, which in turn have evolved diverse and sophisticated capabilities to protect themselves against viral infections and their associated diseases. Viruses have also evolved a remarkable variety of strategie...

  5. Soy isoflavones and virus infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Isoflavones and their related flavonoid compounds exert antiviral properties in vitro and in vivo against a wide range of viruses. Genistein is, by far, the most studied soy isoflavone in this regard, and it has been shown to inhibit the infectivity of enveloped or nonenveloped viruses, as well as s...

  6. Swine Influenza Virus: Emerging Understandings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: In March-April 2009, a novel pandemic H1N1 emerged in the human population in North America [1]. The gene constellation of the emerging virus was demonstrated to be a combination of genes from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before...

  7. INFECTIOUS DOSE OF NORWALK VIRUS

    EPA Science Inventory

    The Norwalk virus and related viruses (caliciviruses) have been identified as a common cause of waterborne disease. Moreover, there are many outbreaks of waterborne disease every year where the causative agent was never identified, and it is thought that many of these are due to ...

  8. Tobacco ringspot virus in Rubus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tobacco ringspot virus (TRSV) has a broad host range among woody and perennial plants and has been reported from blackberry but not from red or black raspberry. The virus has been detected in blackberry in the southeastern United States with a single report from blackberry in British Columbia, Cana...

  9. Tomato ringspot virus in Rubus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tomato ringspot virus (ToRSV) is the most widespread and important of the nematode-transmitted viruses affecting cultivated Rubus in North and South America but is not known to occur outside of the Western Hemisphere. A recent report from Turkey on ToRSV in blackberry in borders of stone fruit orcha...

  10. Virus Detection and Field Management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are two primary pathogens of Oat – Crown Rust and the Luteoviruses Barley and Cereal Yellow Dwarf Virus (BYDV and CYDV). These viruses can only be transmitted by aphids, are limited to the vascular system in infected plants and can lead to severe stunting and a concomitant yield loss. In 200...

  11. Marine Viruses: Truth or Dare

    NASA Astrophysics Data System (ADS)

    Breitbart, Mya

    2012-01-01

    Over the past two decades, marine virology has progressed from a curiosity to an intensely studied topic of critical importance to oceanography. At concentrations of approximately 10 million viruses per milliliter of surface seawater, viruses are the most abundant biological entities in the oceans. The majority of these viruses are phages (viruses that infect bacteria). Through lysing their bacterial hosts, marine phages control bacterial abundance, affect community composition, and impact global biogeochemical cycles. In addition, phages influence their hosts through selection for resistance, horizontal gene transfer, and manipulation of bacterial metabolism. Recent work has also demonstrated that marine phages are extremely diverse and can carry a variety of auxiliary metabolic genes encoding critical ecological functions. This review is structured as a scientific "truth or dare," revealing several well-established "truths" about marine viruses and presenting a few "dares" for the research community to undertake in future studies.

  12. Optimal control strategies for the spread of Ebola in West Africa

    E-print Network

    Rachah, Amira

    2015-01-01

    The spread of Ebola virus in 2014 is unprecedented. The epidemic is still affecting West Africa, exacerbated by extraordinary socioeconomic disadvantages and health system inadequacies. With the aim of understanding, predicting, and control the propagation of the virus in the populations of affected countries, it is crucial to model the dynamics of the virus and study several strategies to control it. In this paper, we present a very simple mathematical model that describes quite well the spread of Ebola. Then, we discuss several strategies for the control of the propagation of this lethal virus into populations, in order to predict the impact of vaccine programmes, treatment, and the impact of educational campaigns.

  13. Genome Sequence of Bivens Arm Virus, a Tibrovirus Belonging to the Species Tibrogargan virus (Mononegavirales: Rhabdoviridae)

    PubMed Central

    Hensley, Lisa E.

    2015-01-01

    The new rhabdoviral genus Tibrovirus currently has two members, Coastal Plains virus and Tibrogargan virus. Here, we report the coding-complete genome sequence of a putative member of this genus, Bivens Arm virus. A genomic comparison reveals Bivens Arm virus to be closely related to, but distinct from, Tibrogargan virus. PMID:25792044

  14. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. While investigating virus-invertebrate host interactions we found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), were unable to infect certain Lepido...

  15. Comparison of Immunohistochemistry and Virus Isolation for Diagnosis of West Nile Virus

    PubMed Central

    Ellis, Angela E.; Mead, Daniel G.; Allison, Andrew B.; Gibbs, Samantha E. J.; Gottdenker, Nicole L.; Stallknecht, David E.; Howerth, Elizabeth W.

    2005-01-01

    Immunohistochemistry and virus isolation were performed on 1,057 birds. Immunohistochemistry, virus isolation, or both found 325 birds to be West Nile virus positive. Of these, 271 were positive by both methods. These results indicate that virus isolation and immunohistochemistry are approximately equal in their ability to detect West Nile virus. PMID:15956415

  16. Live-attenuated influenza A virus vaccines using a B virus backbone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The currently FDA-licensed live attenuated influenza virus vaccine contains a trivalent mixture of types A (H1N1 and H3N2) and B vaccine viruses. The two A virus vaccines have the backbone of a cold-adapted influenza A virus and the B virus vaccine has the six backbone segments derived from a cold-...

  17. How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus

    E-print Network

    Hulshof, Joost

    How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus Maria Xiridou1 *, Barbara Borkent Medical Centre Utrecht, Utrecht, The Netherlands Abstract Background: Hepatitis D (or hepatitis delta) virus is a defective virus that relies on hepatitis B virus (HBV) for transmission; infection

  18. The Acute bee paralysis virus-Kashmir bee virus-Israeli acute paralysis virus complex.

    PubMed

    de Miranda, Joachim R; Cordoni, Guido; Budge, Giles

    2010-01-01

    Acute bee paralysis virus (ABPV), Kashmir bee virus (KBV) and Israeli acute paralysis virus (IAPV) are part of a complex of closely related viruses from the Family Dicistroviridae. These viruses have a widespread prevalence in honey bee (Apis mellifera) colonies and a predominantly sub-clinical etiology that contrasts sharply with the extremely virulent pathology encountered at elevated titres, either artificially induced or encountered naturally. These viruses are frequently implicated in honey bee colony losses, especially when the colonies are infested with the parasitic mite Varroa destructor. Here we review the historical and recent literature of this virus complex, covering history and origins; the geographic, host and tissue distribution; pathology and transmission; genetics and variation; diagnostics, and discuss these within the context of the molecular and biological similarities and differences between the viruses. We also briefly discuss three recent developments relating specifically to IAPV, concerning its association with Colony Collapse Disorder, treatment of IAPV infection with siRNA and possible honey bee resistance to IAPV. PMID:19909972

  19. O'nyong-nyong Virus, Chad

    PubMed Central

    Bessaud, Maël; Peyrefitte, Christophe N.; Pastorino, Boris A.M.; Gravier, Patrick; Tock, Fabienne; Boete, Fabrice; Tolou, Hugues J.

    2006-01-01

    We report the first laboratory-confirmed human infection with O'nyong-nyong virus in Chad. This virus was isolated from peripheral blood mononuclear cells of a patient with evidence of a seroconversion to a virus related to Chikungunya virus. Genome sequence was partly determined, and phylogenetic studies were conducted. PMID:16965706

  20. Getah Virus Infection among Racehorses, Japan, 2014

    PubMed Central

    Bannai, Hiroshi; Tsujimura, Koji; Kobayashi, Minoru; Kikuchi, Takuya; Yamanaka, Takashi; Kondo, Takashi

    2015-01-01

    An outbreak of Getah virus infection occurred among racehorses in Japan during September and October 2014. Of 49 febrile horses tested by reverse transcription PCR, 25 were positive for Getah virus. Viruses detected in 2014 were phylogenetically different from the virus isolated in Japan in 1978. PMID:25898181