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Sample records for virus ebola virus

  1. Ebola (Ebola Virus Disease): Prevention

    MedlinePlus

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  2. Ebola (Ebola Virus Disease): Transmission

    MedlinePlus

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  3. Ebola (Ebola Virus Disease): Treatment

    MedlinePlus

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  4. Ebola (Ebola Virus Disease): Diagnosis

    MedlinePlus

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  5. Ebola Virus Disease

    MedlinePlus

    ... 2014 Fact sheets Features Commentaries 2014 Multimedia Contacts Ebola virus disease Fact sheet Updated January 2016 Key ... for survivors of Ebola virus disease Symptoms of Ebola virus disease The incubation period, that is, the ...

  6. Ebola (Ebola Virus Disease): Signs and Symptoms

    MedlinePlus

    ... Virus Disease) About Ebola Questions & Answers 2014 West Africa Outbreak What's New Timeline Case Counts Previous Case ... U.S. Q&A: 2014 Ebola Outbreak 2014 West Africa Ebola Outbreak Communication Resources Guinea Guinea-Bissau Liberia ...

  7. Postmortem stability of Ebola virus.

    PubMed

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

    2015-05-01

    The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus-infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <7 days posteuthanasia; viral RNA was detectable for 10 weeks. PMID:25897646

  8. Postmortem Stability of Ebola Virus

    PubMed Central

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

    2015-01-01

    The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus–infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <7 days posteuthanasia; viral RNA was detectable for 10 weeks. PMID:25897646

  9. [Ebola virus disease: Update].

    PubMed

    de la Calle-Prieto, Fernando; Arsuaga-Vicente, Marta; Mora-Rillo, Marta; Arnalich-Fernandez, Francisco; Arribas, Jose Ramon

    2016-01-01

    The first known Ebola outbreak occurred in 1976. Since then, 24 limited outbreaks had been reported in Central Africa, but never affecting more than 425 persons. The current outbreak in Western Africa is the largest in history with 28,220 reported cases and 11,291 deaths. The magnitude of the epidemic has caused worldwide alarm. For the first time, evacuated patients were treated outside Africa, and secondary cases have occurred in Spain and the United States. Since the start of the current epidemic, our knowledge about the epidemiology, clinical picture, laboratory findings, and virology of Ebola virus disease has considerably expanded. For the first time, experimental treatment has been tried, and there have been spectacular advances in vaccine development. A review is presented of these advances in the knowledge of Ebola virus disease. PMID:26774254

  10. Ebola (Ebola Virus Disease): Q&As on Transmission

    MedlinePlus

    ... Virus Disease) About Ebola Questions & Answers 2014 West Africa Outbreak What's New Timeline Case Counts Previous Case ... U.S. Q&A: 2014 Ebola Outbreak 2014 West Africa Ebola Outbreak Communication Resources Guinea Guinea-Bissau Liberia ...

  11. [Ebola virus disease].

    PubMed

    Karwowska, Kornelia

    2015-01-01

    Ebola virus disease is a zoonosis causing high mortality epidemics in both human and animal populations. The virus belongs to the Filoviride family. It is composed of a single-strand of RNA. Morbidity foci appear in sub-Saharan Africa. The most probable reservoir are fruit bats, which are local delicacy. The most common route of infection is via mucosa or damaged skin. The spread of disease is rapid due to dietary habits, funeral rites and the insufficient supply of disposable equipment in hospitals. The incubation period of the disease ranges from 2 to 21 days. The beginning is abrupt, dominated by influenza-like symptoms. The disease is staggering with the predominant multi-organ failure and shock. Present-day epidemic symptoms from digestive system in the form of vomiting and diarrhoea are dominant. Currently, the research on vaccine and experimental drug is in progress. The virus is damaged by standard disinfectants used in health care units. Epidemic, which broke out in February 2014, caused by the most dangerous type Zaire, is the greatest of the existing. Morbidity and mortality is underestimated due to numerous unreported cases. PMID:25763588

  12. Ebola Virus Persistence in Semen Ex Vivo

    PubMed Central

    Fischer, Robert J.; Judson, Seth; Miazgowicz, Kerri; Bushmaker, Trent

    2016-01-01

    On March 20, 2015, a case of Ebola virus disease was identified in Liberia that most likely was transmitted through sexual contact. We assessed the efficiency of detecting Ebola virus in semen samples by molecular diagnostics and the stability of Ebola virus in ex vivo semen under simulated tropical conditions. PMID:26811984

  13. Ebola, the killer virus.

    PubMed

    Ghazanfar, Haider; Orooj, Fizza; Abdullah, Muhammad Ahmed; Ghazanfar, Ali

    2015-01-01

    Ebola virus disease (EVD) has mostly affected economically deprived countries as limited resources adversely affect a country's infrastructure and administration. Probing into the factors that led to the widespread outbreak, setting forth plans to counter EVD cases in developing countries, and devising definitive measures to limit the spread of the disease are essential steps that must be immediately taken. In this review we summarize the pathogenesis of EVD and the factors that led to its spread. We also highlight interventions employed by certain countries that have successfully limited the epidemic, and add a few preventive measures after studying the current data. According to the available data, barriers to prevent and control the disease in affected countries include irresolute and disorganized health systems, substandard sanitary conditions, poor personal hygiene practices, and false beliefs and stigma related to EVD. The public health sector along with the respective chief authorities in developing countries must devise strategies, keeping the available resources in mind, to deal with the outbreak before it occurs. As a first step, communities should be educated on EVD's symptoms, history, mode of transmission, and methods of protection, including the importance of personal hygiene practices, via seminars, newspapers, and other social media. A popular opinion leader (POL) giving this information would further help to remove the misconception about the nature of the disease and indirectly improve the quality of life of affected patients and their families. PMID:25866626

  14. Ebola virus disease

    MedlinePlus

    ... urine, saliva, sweat, feces, vomit, breast milk, and semen. The virus can enter the body through a ... use condoms for 12 months or until their semen has twice tested negative. Long-term complications can ...

  15. 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.

  16. Ebola virus disease

    MedlinePlus

    ... monkeys, and chimpanzees). The Ebola outbreak in West Africa, which has occurred since March 2014, is the ... Since then, several small outbreaks have occurred in Africa. The 2014 outbreak is the largest. The countries ...

  17. 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

  18. The Ebola virus epidemic: Preparation, not panic.

    PubMed

    Borchardt, Roy A

    2015-02-01

    The largest-ever outbreak and first epidemic of Ebola virus disease is affecting several West African countries. Early symptoms of Ebola can mimic those of other tropical diseases. In a world of rapid global travel, physician assistants need to be capable of identifying patients at greatest risk for developing Ebola. Clinicians also should be familiar with associated symptoms, diagnosis, and treatment considerations. PMID:25565023

  19. Interferon-γ 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

  20. Interferon-γ Inhibits Ebola Virus Infection.

    PubMed

    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; Monick, Martha M; Maury, Wendy

    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

  1. 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

  2. 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

  3. 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

  4. Therapy and prophylaxis of Ebola virus infections.

    PubMed

    Feldmann, Heinz; Jones, Steven M; Schnittler, Hans-Joachim; Geisbert, Thomas

    2005-08-01

    The first cases of Ebola hemorrhagic fever were reported from Sudan and Zaire (now Democratic Republic of the Congo) in 1976, but the virus has only received significant attention since 1995. Until recently, the development of therapeutics or vaccines was not considered a priority. The knowledge gained during the past decade on the biology and pathogenesis of Ebola virus has led to the development of therapeutic strategies that are currently being investigated. Considering the aggressive nature of Ebola infections, in particular the rapid and overwhelming viral burdens, early diagnosis will play a significant role in determining the success of any intervention strategy. Advanced understanding of the immune response has produced several vaccine candidates of which a few can be considered for further evaluation. This review will summarize and discuss the current therapeutic and prophylactic strategies for Ebola hemorrhagic fever. PMID:16121689

  5. Ebola virus-like particles protect from lethal Ebola virus infection

    PubMed Central

    Warfield, Kelly L.; Bosio, Catharine M.; Welcher, Brent C.; Deal, Emily M.; Mohamadzadeh, Mansour; Schmaljohn, Alan; Aman, M. Javad; Bavari, Sina

    2003-01-01

    The filovirus Ebola causes hemorrhagic fever with 70–80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (VP40) in mammalian cells results in spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. VLPs have been tested and found efficacious as vaccines for several viruses, including papillomavirus, HIV, parvovirus, and rotavirus. Herein, we report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLPs matured and activated mouse bone marrow-derived dendritic cells, assessed by increases in cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL-6, IL-10, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor α by the dendritic cells. Further, vaccinating mice with eVLPs activated CD4+ and CD8+ T cells, as well as CD19+ B cells. After vaccination with eVLPs, mice developed high titers of Ebola virus-specific antibodies, including neutralizing antibodies. Importantly, mice vaccinated with eVLPs were 100% protected from an otherwise lethal Ebola virus inoculation. Together, our data suggest that eVLPs represent a promising vaccine candidate for protection against Ebola virus infections and a much needed tool to examine the genesis and nature of immune responses to Ebola virus. PMID:14673108

  6. Neurological Complications of Ebola Virus Infection.

    PubMed

    Billioux, Bridgette Jeanne; Smith, Bryan; Nath, Avindra

    2016-07-01

    Ebola virus disease is one of the deadliest pathogens known to man, with a mortality rate between 25-90% depending on the species and outbreak of Ebola. Typically, it presents with fever, headache, voluminous vomiting and diarrhea, and can progress to a hemorrhagic illness; neurologic symptoms, including meningoencephalitis, seizures, and coma, can also occur. Recently, an outbreak occurred in West Africa, affecting > 28,000 people, and killing > 11,000. Owing to the magnitude of this outbreak, and the large number (>17,000) of Ebola survivors, the medical and scientific communities are learning much more about the acute manifestations and sequelae of Ebola. A number of neurologic complications can occur after Ebola, such as seizures, memory loss, headaches, cranial nerve abnormalities, and tremor. Ebola may also persist in some immunologically privileged sites, including the central nervous system, and can rarely lead to relapse in disease. Owing to these findings, it is important that survivors are evaluated and monitored for neurologic symptoms. Much is unknown about this disease, and treatment remains largely supportive; however, with ongoing clinical and basic science, the mechanisms of how Ebola affects the central nervous system and how it persists after acute disease will hopefully become more clear, and better treatments and clinical practices for Ebola patients will be developed. PMID:27412684

  7. Ebola Virus Disease: Focus on Children.

    PubMed

    Kourtis, Athena P; Appelgren, Kristie; Chevalier, Michelle S; McElroy, Anita

    2015-08-01

    Ebola virus is one of the most deadly pathogens known to infect humans. The current Ebola outbreak in West Africa is unprecedented in magnitude and duration and, as of November 30, 2014, shows no signs of abating. For the first time, cases of Ebola virus disease have been diagnosed in the US, originating from patients who traveled during the incubation period. The outbreak has generated worldwide concern. It is clear that U.S. physicians need to be aware of this disease, know when to consider Ebola and how to care for the patient as well as protect themselves. Children comprise a small percentage of all cases globally, likely because of their lower risk of exposure given social and cultural practices. Limited evidence is available on pediatric disease course and prognosis. In this article, we present an overview of the pathogen, its epidemiology and transmission, clinical and laboratory manifestations, treatment and infection control procedures, with an emphasis on what is known about Ebola virus disease in the pediatric population. PMID:25831417

  8. Effective Chemical Inactivation of Ebola Virus

    PubMed Central

    Haddock, Elaine; Feldmann, Friederike

    2016-01-01

    Reliable inactivation of specimens before removal from high-level biocontainment is crucial for safe operation. To evaluate efficacy of methods of chemical inactivation, we compared in vitro and in vivo approaches using Ebola virus as a surrogate pathogen. Consequently, we have established parameters and protocols leading to reliable and effective inactivation. PMID:27070504

  9. Effective Chemical Inactivation of Ebola Virus.

    PubMed

    Haddock, Elaine; Feldmann, Friederike; Feldmann, Heinz

    2016-07-01

    Reliable inactivation of specimens before removal from high-level biocontainment is crucial for safe operation. To evaluate efficacy of methods of chemical inactivation, we compared in vitro and in vivo approaches using Ebola virus as a surrogate pathogen. Consequently, we have established parameters and protocols leading to reliable and effective inactivation. PMID:27070504

  10. Ebola Virus Persistence in Semen of Male Survivors.

    PubMed

    Uyeki, Timothy M; Erickson, Bobbie Rae; Brown, Shelley; McElroy, Anita K; Cannon, Deborah; Gibbons, Aridth; Sealy, Tara; Kainulainen, Markus H; Schuh, Amy J; Kraft, Colleen S; Mehta, Aneesh K; Lyon, G Marshall; Varkey, Jay B; Ribner, Bruce S; Ellison, Richard T; Carmody, Ellie; Nau, Gerard J; Spiropoulou, Christina; Nichol, Stuart T; Ströher, Ute

    2016-06-15

    We investigated the duration of Ebola virus (EBOV) RNA and infectious EBOV in semen specimens of 5 Ebola virus disease (EVD) survivors. EBOV RNA and infectious EBOV was detected by real-time RT-PCR and virus culture out to 290 days and 70 days, respectively, after EVD onset. PMID:27045122

  11. Development of vaccines for prevention of Ebola virus infection.

    PubMed

    Ye, Ling; Yang, Chinglai

    2015-02-01

    Ebola virus infection causes severe hemorrhagic fevers with high fatality rates up to 90% in humans, for which no effective treatment is currently available. The ongoing Ebola outbreak in West Africa that has caused over 14,000 human infections and over 5000 deaths underscores its serious threat to the public health. While licensed vaccines against Ebola virus infection are still not available, a number of vaccine approaches have been developed and shown to protect against lethal Ebola virus infection in animal models. This review aims to summarize the advancement of different strategies for Ebola vaccine development with a focus on the discussion of their protective efficacies and possible limitations. In addition, the development of animal models for efficacy evaluation of Ebola vaccines and the mechanism of immune protection against Ebola virus infection are also discussed. PMID:25526819

  12. 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

  13. 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

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

    PubMed

    Christie, Athalia; Davies-Wayne, Gloria J; Cordier-Lassalle, Thierry; 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

  15. Antiviral effect of ranpirnase against Ebola virus.

    PubMed

    Hodge, Thomas; Draper, Ken; Brasel, Trevor; Freiberg, Alexander; Squiquera, Luis; Sidransky, David; Sulley, Jamie; Taxman, Debra J

    2016-08-01

    The recent epidemic of Ebola has intensified the need for the development of novel antiviral therapeutics that prolong and improve survival against deadly viral diseases. We sought to determine whether ranpirnase, an endoribonuclease from Rana pipiens with a demonstrated human safety profile in phase III oncology trials, can reduce titers of Ebola virus (EBOV) in infected cells, protect mice against mouse-adapted EBOV challenge, and reduce virus levels in infected mice. Our results demonstrate that 0.50 μg/ml ranpirnase is potently effective at reducing EBOV Zaire Kikwit infection in cultured Vero E6 cells (Selectivity Index 47.8-70.2). In a prophylactic study, a single intravenous dose of 0.1 mg/kg ranpirnase protected 70% of mice from progressive infection. Additionally, in a post-exposure prophylactic study, 100% of female mice survived infection after intraperitoneal administration of 0.1 mg/kg ranpirnase for ten days beginning 1 h post challenge. Most of the male counterparts were sacrificed due to weight loss by Study Day 8 or 9; however, the Clinical Activity/Behavior scores of these mice remained low and no significant microscopic pathologies could be detected in the kidneys, livers or spleens. Furthermore, live virus could not be detected in the sera of ranpirnase-treated mice by Study Day 8 or in the kidneys, livers or spleens by Study Day 12, and viral RNA levels declined exponentially by Study Day 12. Because ranpirnase is exceptionally stable and has a long track record of safe intravenous administration to humans, this drug provides a promising new candidate for clinical consideration in the treatment of Ebola virus disease alone or in combination with other therapeutics. PMID:27350309

  16. 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

  17. New Perspectives on Ebola Virus Evolution.

    PubMed

    Brown, Celeste J; Quates, Caleb J; Mirabzadeh, Christopher A; Miller, Craig R; Wichman, Holly A; Miura, Tanya A; Ytreberg, F Marty

    2016-01-01

    Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. EBOV evolution cannot be understood outside the context of previous outbreaks, however. We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. PMID:27479005

  18. New Perspectives on Ebola Virus Evolution

    PubMed Central

    Brown, Celeste J.; Quates, Caleb J.; Mirabzadeh, Christopher A.; Miller, Craig R.; Wichman, Holly A.; Miura, Tanya A.; Ytreberg, F. Marty

    2016-01-01

    Since the recent devastating outbreak of Ebola virus disease in western Africa, there has been significant effort to understand the evolution of the deadly virus that caused the outbreak. There has been a considerable investment in sequencing Ebola virus (EBOV) isolates, and the results paint an important picture of how the virus has spread in western Africa. EBOV evolution cannot be understood outside the context of previous outbreaks, however. We have focused this study on the evolution of the EBOV glycoprotein gene (GP) because one of its products, the spike glycoprotein (GP1,2), is central to the host immune response and because it contains a large amount of the phylogenetic signal for this virus. We inferred the maximum likelihood phylogeny of 96 nonredundant GP gene sequences representing each of the outbreaks since 1976 up to the end of 2014. We tested for positive selection and considered the placement of adaptive amino acid substitutions along the phylogeny and within the protein structure of GP1,2. We conclude that: 1) the common practice of rooting the phylogeny of EBOV between the first known outbreak in 1976 and the next outbreak in 1995 provides a misleading view of EBOV evolution that ignores the fact that there is a non-human EBOV host between outbreaks; 2) the N-terminus of GP1 may be constrained from evolving in response to the host immune system by the highly expressed, secreted glycoprotein, which is encoded by the same region of the GP gene; 3) although the mucin-like domain of GP1 is essential for EBOV in vivo, it evolves rapidly without losing its twin functions: providing O-linked glycosylation sites and a flexible surface. PMID:27479005

  19. Ebola virus disease in nonendemic countries.

    PubMed

    Wong, Samson Sai-Yin; Wong, Sally Cheuk-Ying

    2015-05-01

    The 2014 West African outbreak of Ebola virus disease was unprecedented in its scale and has resulted in transmissions outside endemic countries. Clinicians in nonendemic countries will most likely face the disease in returning travelers, either among healthcare workers, expatriates, or visiting friends and relatives. Clinical suspicion for the disease must be heightened for travelers or contacts presenting with compatible clinical syndromes, and strict infection control measures must be promptly implemented to minimize the risk of secondary transmission within healthcare settings or in the community. We present a concise review on human filoviral disease with an emphasis on issues that are pertinent to clinicians practicing in nonendemic countries. PMID:25882189

  20. Antibody therapeutics for Ebola virus disease.

    PubMed

    Zeitlin, Larry; Whaley, Kevin J; Olinger, Gene G; Jacobs, Michael; Gopal, Robin; Qiu, Xiangguo; Kobinger, Gary P

    2016-04-01

    With the unprecedented scale of the 2014-2016 West Africa outbreak, the clinical and scientific community scrambled to identify potential therapeutics for Ebola virus disease (EVD). Passive administration of antibodies has a long successful history for prophylaxis and therapy of a variety of infectious diseases, but the importance of antibodies in EVD has been unclear and is the subject of some debate. Recent studies in non-human primates have renewed interest in the potential of antibodies to impact EVD. Currently ongoing clinical evaluation of polyclonal and monoclonal antibody therapy in EVD patients in West Africa may finally offer a definitive answer to this debate. PMID:26826442

  1. 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

  2. Ebola virus disease candidate vaccines under evaluation in clinical trials.

    PubMed

    Martins, Karen A; Jahrling, Peter B; Bavari, Sina; Kuhn, Jens H

    2016-09-01

    Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. PMID:27160784

  3. 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

  4. Statistical considerations for a trial of Ebola virus disease therapeutics.

    PubMed

    Proschan, Michael A; Dodd, Lori E; Price, Dionne

    2016-02-01

    The 2014 West African outbreak of Ebola virus ravaged Liberia, Sierra Leone, and Guinea, causing hemorrhagic fever and death. The need to identify effective therapeutics was acute. The usual drug development paradigm of phase I, followed by phase II, and then phase III trials would take too long. These and other factors led to the design of a clinical trial of Ebola virus disease therapeutics that differs from more conventional clinical trial designs. This article describes the Ebola virus disease medical countermeasures trial design and the thinking behind it. PMID:26768567

  5. Ebola virus disease outbreak: what's going on.

    PubMed

    Giraldi, G; Marsella, L T

    2015-01-01

    The current West African Ebola Virus Disease (EVD) outbreak was confirmed in March, 2014, and after months of slow, fragmented responses, the EVD has been recognized as a public health emergency of international concern. The early diagnosis of the disease is difficult without laboratory testing, because its symptoms can be seen in many other infections. In the wake of international agencies advices, the Italian Ministry of Health, on October 1, 2014, released to the Healthcare Professional Workers (HPWs) the Protocol about the management of cases and contacts within the national territory. Due to the increasing number of humanitarian groups and HPWs involved in the field, the probability to have new cases of contamination is higher than ever. Proven specific treatments against EVD are not yet available, however, a variety of compounds have been under testing. The most effective are select monoclonal antibodies that have a high neutralizing potential against epitopes of Ebola Virus. For facing the matter, it is important a comprehensive approach according to the recommendations proposed by the international agencies because no single institution or country has all the capacities to respond to a new and emerging infectious disease. PMID:25748509

  6. Development of an immunofluorescence focus assay for Ebola virus.

    PubMed Central

    Truant, A L; Regnery, R L; Kiley, M P

    1983-01-01

    A 48-h indirect immunofluorescence focus assay for the quantitation of Ebola virus was developed, utilizing HeLa-229 cell monolayers. The dose dependency and the sensitivity of this assay as compared with conventional assays are reported. This indirect immunofluorescence focus assay can be used as a rapid, quantitative test for the detection of Ebola virus, an agent from Africa known to cause hemorrhagic fever. Images PMID:6352735

  7. Entry of Ebola Virus is an Asynchronous Process.

    PubMed

    Reynard, Olivier; Volchkov, Viktor E

    2015-10-01

    Ebola virus (EBOV) is responsible for a severe fever with a high mortality rate. The diverse nature of the attachment of the virus to the cell surface, the initial step of virus entry, raises questions concerning the kinetics of the virus internalization process. We investigated EBOV entry kinetics using the activity of a particular monoclonal antibody that neutralizes virus infectivity. We demonstrate that inoculation of cells with EBOV results in an asynchronous entry process, as revealed by the ability of the virus to remain in a cell-bound state for an extended period of time before it is internalized. PMID:25941332

  8. Ebola virus disease and critical illness.

    PubMed

    Leligdowicz, Aleksandra; Fischer, William A; Uyeki, Timothy M; Fletcher, Thomas E; Adhikari, Neill K J; Portella, Gina; Lamontagne, Francois; Clement, Christophe; Jacob, Shevin T; Rubinson, Lewis; Vanderschuren, Abel; Hajek, Jan; Murthy, Srinivas; Ferri, Mauricio; Crozier, Ian; Ibrahima, Elhadj; Lamah, Marie-Claire; Schieffelin, John S; Brett-Major, David; Bausch, Daniel G; Shindo, Nikki; Chan, Adrienne K; O'Dempsey, Tim; Mishra, Sharmistha; Jacobs, Michael; Dickson, Stuart; Lyon, G Marshall; Fowler, Robert A

    2016-01-01

    As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa.EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death.Males and females have been equally affected, with children (0-14 years of age) accounting for 19 %, young adults (15-44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40-90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission.While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that

  9. 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

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

    PubMed Central

    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

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

    PubMed Central

    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).

  12. The Merits of Malaria Diagnostics during an Ebola Virus Disease Outbreak

    PubMed Central

    de Wit, Emmie; Falzarano, Darryl; Onyango, Clayton; Rosenke, Kyle; Marzi, Andrea; Ochieng, Melvin; Juma, Bonventure; Fischer, Robert J.; Prescott, Joseph B.; Safronetz, David; Omballa, Victor; Owuor, Collins; Hoenen, Thomas; Groseth, Allison; van Doremalen, Neeltje; Zemtsova, Galina; Self, Joshua; Bushmaker, Trenton; McNally, Kristin; Rowe, Thomas; Emery, Shannon L.; Feldmann, Friederike; Williamson, Brandi; Nyenswah, Tolbert G.; Grolla, Allen; Strong, James E.; Kobinger, Gary; Stroeher, Ute; Rayfield, Mark; Bolay, Fatorma K.; Zoon, Kathryn C.; Stassijns, Jorgen; Tampellini, Livia; de Smet, Martin; Nichol, Stuart T.; Fields, Barry; Sprecher, Armand; Feldmann, Heinz; Massaquoi, Moses

    2016-01-01

    Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection. PMID:26814608

  13. The Merits of Malaria Diagnostics during an Ebola Virus Disease Outbreak.

    PubMed

    de Wit, Emmie; Falzarano, Darryl; Onyango, Clayton; Rosenke, Kyle; Marzi, Andrea; Ochieng, Melvin; Juma, Bonventure; Fischer, Robert J; Prescott, Joseph B; Safronetz, David; Omballa, Victor; Owuor, Collins; Hoenen, Thomas; Groseth, Allison; van Doremalen, Neeltje; Zemtsova, Galina; Self, Joshua; Bushmaker, Trenton; McNally, Kristin; Rowe, Thomas; Emery, Shannon L; Feldmann, Friederike; Williamson, Brandi; Nyenswah, Tolbert G; Grolla, Allen; Strong, James E; Kobinger, Gary; Stroeher, Ute; Rayfield, Mark; Bolay, Fatorma K; Zoon, Kathryn C; Stassijns, Jorgen; Tampellini, Livia; de Smet, Martin; Nichol, Stuart T; Fields, Barry; Sprecher, Armand; Feldmann, Heinz; Massaquoi, Moses; Munster, Vincent J

    2016-02-01

    Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection. PMID:26814608

  14. Potent neutralizing monoclonal antibodies against Ebola virus infection.

    PubMed

    Zhang, Qi; Gui, Miao; Niu, Xuefeng; He, Shihua; Wang, Ruoke; Feng, Yupeng; Kroeker, Andrea; Zuo, Yanan; Wang, Hua; Wang, Ying; Li, Jiade; Li, Chufang; Shi, Yi; Shi, Xuanling; Gao, George F; Xiang, Ye; Qiu, Xiangguo; Chen, Ling; Zhang, Linqi

    2016-01-01

    Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID:27181584

  15. Potent neutralizing monoclonal antibodies against Ebola virus infection

    PubMed Central

    Zhang, Qi; Gui, Miao; Niu, Xuefeng; He, Shihua; Wang, Ruoke; Feng, Yupeng; Kroeker, Andrea; Zuo, Yanan; Wang, Hua; Wang, Ying; Li, Jiade; Li, Chufang; Shi, Yi; Shi, Xuanling; Gao, George F.; Xiang, Ye; Qiu, Xiangguo; Chen, Ling; Zhang, Linqi

    2016-01-01

    Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection. PMID:27181584

  16. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus.

    PubMed

    Messaoudi, Ilhem; Amarasinghe, Gaya K; Basler, Christopher F

    2015-11-01

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirus pathogenesis. PMID:26439085

  17. Analysis of Ebola Virus Entry Into Macrophages.

    PubMed

    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

    2015-10-01

    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 αV, 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 αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

  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 αV, 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 αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

  19. Safety of recombinant VSV-Ebola virus vaccine vector in pigs.

    PubMed

    de Wit, Emmie; Marzi, Andrea; Bushmaker, Trenton; Brining, Doug; Scott, Dana; Richt, Juergen A; Geisbert, Thomas W; Feldmann, Heinz

    2015-04-01

    The ongoing Ebola outbreak in West Africa has resulted in fast-track development of vaccine candidates. We tested a vesicular stomatitis virus vector expressing Ebola virus glycoprotein for safety in pigs. Inoculation did not cause disease and vaccine virus shedding was minimal, which indicated that the vaccine virus does not pose a risk of dissemination in pigs. PMID:25811738

  20. Unique human immune signature of Ebola virus disease in Guinea.

    PubMed

    Ruibal, Paula; Oestereich, Lisa; Lüdtke, Anja; Becker-Ziaja, Beate; Wozniak, David M; Kerber, Romy; Korva, Miša; Cabeza-Cabrerizo, Mar; Bore, Joseph A; Koundouno, Fara Raymond; Duraffour, Sophie; Weller, Romy; Thorenz, Anja; Cimini, Eleonora; Viola, Domenico; Agrati, Chiara; Repits, Johanna; Afrough, Babak; Cowley, Lauren A; Ngabo, Didier; Hinzmann, Julia; Mertens, Marc; Vitoriano, Inês; Logue, Christopher H; Boettcher, Jan Peter; Pallasch, Elisa; Sachse, Andreas; Bah, Amadou; Nitzsche, Katja; Kuisma, Eeva; Michel, Janine; Holm, Tobias; Zekeng, Elsa-Gayle; García-Dorival, Isabel; Wölfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Strecker, Thomas; Di Caro, Antonino; Avšič-Županc, Tatjana; Kurth, Andreas; Meschi, Silvia; Mély, Stephane; Newman, Edmund; Bocquin, Anne; Kis, Zoltan; Kelterbaum, Anne; Molkenthin, Peter; Carletti, Fabrizio; Portmann, Jasmine; Wolff, Svenja; Castilletti, Concetta; Schudt, Gordian; Fizet, Alexandra; Ottowell, Lisa J; Herker, Eva; Jacobs, Thomas; Kretschmer, Birte; Severi, Ettore; Ouedraogo, Nobila; Lago, Mar; Negredo, Anabel; Franco, Leticia; Anda, Pedro; Schmiedel, Stefan; Kreuels, Benno; Wichmann, Dominic; Addo, Marylyn M; Lohse, Ansgar W; De Clerck, Hilde; Nanclares, Carolina; Jonckheere, Sylvie; Van Herp, Michel; Sprecher, Armand; Xiaojiang, Gao; Carrington, Mary; Miranda, Osvaldo; Castro, Carlos M; Gabriel, Martin; Drury, Patrick; Formenty, Pierre; Diallo, Boubacar; Koivogui, Lamine; Magassouba, N'Faly; Carroll, Miles W; Günther, Stephan; Muñoz-Fontela, César

    2016-05-01

    Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology. PMID:27147028

  1. Control of Ebola virus disease - firestone district, liberia, 2014.

    PubMed

    Reaves, Erik J; Mabande, Lyndon G; Thoroughman, Douglas A; Arwady, M Allison; Montgomery, Joel M

    2014-10-24

    On March 30, 2014, the Ministry of Health and Social Welfare (MOHSW) of Liberia alerted health officials at Firestone Liberia, Inc. (Firestone) of the first known case of Ebola virus disease (Ebola) inside the Firestone rubber tree plantation of Liberia. The patient, who was the wife of a Firestone employee, had cared for a family member with confirmed Ebola in Lofa County, the epicenter of the Ebola outbreak in Liberia during March-April 2014. To prevent a large outbreak among Firestone's 8,500 employees, their dependents, and the surrounding population, the company responded by 1) establishing an incident management system, 2) instituting procedures for the early recognition and isolation of Ebola patients, 3) enforcing adherence to standard Ebola infection control guidelines, and 4) providing differing levels of management for contacts depending on their exposure, including options for voluntary quarantine in the home or in dedicated facilities. In addition, Firestone created multidisciplinary teams to oversee the outbreak response, address case detection, manage cases in a dedicated unit, and reintegrate convalescent patients into the community. The company also created a robust risk communication, prevention, and social mobilization campaign to boost community awareness of Ebola and how to prevent transmission. During August 1-September 23, a period of intense Ebola transmission in the surrounding areas, 71 cases of Ebola were diagnosed among the approximately 80,000 Liberians for whom Firestone provides health care (cumulative incidence = 0.09%). Fifty-seven (80%) of the cases were laboratory confirmed; 39 (68%) of these cases were fatal. Aspects of Firestone's response appear to have minimized the spread of Ebola in the local population and might be successfully implemented elsewhere to limit the spread of Ebola and prevent transmission to health care workers (HCWs). PMID:25340914

  2. Role of natural killer cells in innate protection against lethal ebola virus infection.

    PubMed

    Warfield, Kelly L; Perkins, Jeremy G; Swenson, Dana L; Deal, Emily M; Bosio, Catharine M; Aman, M Javad; Yokoyama, Wayne M; Young, Howard A; Bavari, Sina

    2004-07-19

    Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell-mediated protection clearly depended on perforin, but not interferon-gamma secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection. PMID:15249592

  3. Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection

    PubMed Central

    Marzi, Andrea; Murphy, Aisling A.; Feldmann, Friederike; Parkins, Christopher J.; Haddock, Elaine; Hanley, Patrick W.; Emery, Matthew J.; Engelmann, Flora; Messaoudi, Ilhem; Feldmann, Heinz; Jarvis, Michael A.

    2016-01-01

    Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity. PMID:26876974

  4. Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease

    PubMed Central

    Chancellor, John R.; Padmanabhan, Sriranjani P.; Greenough, Thomas C.; Sacra, Richard; Ellison, Richard T.; Madoff, Lawrence C.; Droms, Rebecca J.; Hinkle, David M.; Asdourian, George K.; Finberg, Robert W.; Stroher, Ute; Uyeki, Timothy M.

    2016-01-01

    We report a case of probable Zaire Ebola virus–related ophthalmologic complications in a physician from the United States who contracted Ebola virus disease in Liberia. Uveitis, immune activation, and nonspecific increase in antibody titers developed during convalescence. This case highlights immune phenomena that could complicate management of Ebola virus disease–related uveitis during convalescence. PMID:26812218

  5. Large-Scale Screening and Identification of Novel Ebola Virus and Marburg Virus Entry Inhibitors.

    PubMed

    Anantpadma, Manu; Kouznetsova, Jennifer; Wang, Hang; Huang, Ruili; Kolokoltsov, Andrey; Guha, Rajarshi; Lindstrom, Aaron R; Shtanko, Olena; Simeonov, Anton; Maloney, David J; Maury, Wendy; LaCount, Douglas J; Jadhav, Ajit; Davey, Robert A

    2016-08-01

    Filoviruses are highly infectious, and no FDA-approved drug therapy for filovirus infection is available. Most work to find a treatment has involved only a few strains of Ebola virus and testing of relatively small drug libraries or compounds that have shown efficacy against other virus types. Here we report the findings of a high-throughput screening of 319,855 small molecules from the Molecular Libraries Small Molecule Repository library for their activities against Marburg virus and Ebola virus. Nine of the most potent, novel compounds that blocked infection by both viruses were analyzed in detail for their mechanisms of action. The compounds inhibited known key steps in the Ebola virus infection mechanism by blocking either cell surface attachment, macropinocytosis-mediated uptake, or endosomal trafficking. To date, very few specific inhibitors of macropinocytosis have been reported. The 2 novel macropinocytosis inhibitors are more potent inhibitors of Ebola virus infection and less toxic than ethylisopropylamiloride, one commonly accepted macropinocytosis inhibitor. Each compound blocked infection of primary human macrophages, indicating their potential to be developed as new antifiloviral therapies. PMID:27161622

  6. Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission.

    PubMed

    Kilianski, Andy; Evans, Nicholas G

    2015-10-01

    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

  7. Small molecules with antiviral activity against the Ebola virus

    PubMed Central

    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

  8. 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

  9. 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

  10. Ebola Virus Disease, Democratic Republic of the Congo, 2014.

    PubMed

    Nanclares, Carolina; Kapetshi, Jimmy; Lionetto, Fanshen; de la Rosa, Olimpia; Tamfun, Jean-Jacques Muyembe; Alia, Miriam; Kobinger, Gary; Bernasconi, Andrea

    2016-09-01

    During July-November 2014, the Democratic Republic of the Congo underwent its seventh Ebola virus disease (EVD) outbreak. The etiologic agent was Zaire Ebola virus; 66 cases were reported (overall case-fatality rate 74.2%). Through a retrospective observational study of confirmed EVD in 25 patients admitted to either of 2 Ebola treatment centers, we described clinical features and investigated correlates associated with death. Clinical features were mainly generic. At admission, 76% of patients had >1 gastrointestinal symptom and 28% >1 hemorrhagic symptom. The case-fatality rate in this group was 48% and was higher for female patients (67%). Cox regression analysis correlated death with initial low cycle threshold, indicating high viral load. Cycle threshold was a robust predictor of death, as were fever, hiccups, diarrhea, dyspnea, dehydration, disorientation, hematemesis, bloody feces during hospitalization, and anorexia in recent medical history. Differences from other outbreaks could suggest guidance for optimizing clinical management and disease control. PMID:27533284

  11. 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

  12. Ebola Virus Disease, Democratic Republic of the Congo, 2014

    PubMed Central

    Nanclares, Carolina; Kapetshi, Jimmy; Lionetto, Fanshen; de la Rosa, Olimpia; Tamfun, Jean-Jacques Muyembe; Alia, Miriam; Kobinger, Gary

    2016-01-01

    During July–November 2014, the Democratic Republic of the Congo underwent its seventh Ebola virus disease (EVD) outbreak. The etiologic agent was Zaire Ebola virus; 66 cases were reported (overall case-fatality rate 74.2%). Through a retrospective observational study of confirmed EVD in 25 patients admitted to either of 2 Ebola treatment centers, we described clinical features and investigated correlates associated with death. Clinical features were mainly generic. At admission, 76% of patients had >1 gastrointestinal symptom and 28% >1 hemorrhagic symptom. The case-fatality rate in this group was 48% and was higher for female patients (67%). Cox regression analysis correlated death with initial low cycle threshold, indicating high viral load. Cycle threshold was a robust predictor of death, as were fever, hiccups, diarrhea, dyspnea, dehydration, disorientation, hematemesis, bloody feces during hospitalization, and anorexia in recent medical history. Differences from other outbreaks could suggest guidance for optimizing clinical management and disease control. PMID:27533284

  13. GB virus C coinfections in west African Ebola patients.

    PubMed

    Lauck, Michael; Bailey, Adam L; Andersen, Kristian G; Goldberg, Tony L; Sabeti, Pardis C; O'Connor, David H

    2015-02-01

    In 49 patients with known Ebola virus disease outcomes during the ongoing outbreak in Sierra Leone, 13 were coinfected with the immunomodulatory pegivirus GB virus C (GBV-C). Fifty-three percent of these GBV-C(+) patients survived; in contrast, only 22% of GBV-C(-) patients survived. Both survival and GBV-C status were associated with age, with older patients having lower survival rates and intermediate-age patients (21 to 45 years) having the highest rate of GBV-C infection. Understanding the separate and combined effects of GBV-C and age on Ebola virus survival may lead to new treatment and prevention strategies, perhaps through age-related pathways of immune activation. PMID:25473056

  14. Sequelae of Ebola virus disease: the emergency within the emergency.

    PubMed

    Vetter, Pauline; Kaiser, Laurent; Schibler, Manuel; Ciglenecki, Iza; Bausch, Daniel G

    2016-06-01

    As the massive outbreak of Ebola virus disease (EVD) in west Africa wanes, it has become increasingly clear that thousands of survivors have many sequelae, some of which might be very severe, such as arthritis and vision-threatening uveitis. The mental health effects of EVD on survivors and other family and community members is similarly profound. Furthermore, it is increasingly being recognised that Ebola virus might persist for weeks or months in selected body compartments of survivors, most notably in the semen of men, bringing risk of renewed transmission where it has previously been eliminated. These challenges to EVD survivors constitute a new emergency in terms of addressing individual patient need and to control the disease spread. In this Review, we assess what is known regarding the sequelae of EVD, including possible delayed virus clearance. We discuss some of the key challenges regarding the provision of care to survivors and implementation of necessary future research. PMID:27020309

  15. Modeling the lifecycle of Ebola virus under biosafety level 2 conditions with virus-like particles containing tetracistronic minigenomes.

    PubMed

    Hoenen, Thomas; Watt, Ari; Mora, Anita; Feldmann, Heinz

    2014-01-01

    Ebola viruses cause severe hemorrhagic fevers in humans and non-human primates, with case fatality rates as high as 90%. There are no approved vaccines or specific treatments for the disease caused by these viruses, and work with infectious Ebola viruses is restricted to biosafety level 4 laboratories, significantly limiting the research on these viruses. Lifecycle modeling systems model the virus lifecycle under biosafety level 2 conditions; however, until recently such systems have been limited to either individual aspects of the virus lifecycle, or a single infectious cycle. Tetracistronic minigenomes, which consist of Ebola virus non-coding regions, a reporter gene, and three Ebola virus genes involved in morphogenesis, budding, and entry (VP40, GP1,2, and VP24), can be used to produce replication and transcription-competent virus-like particles (trVLPs) containing these minigenomes. These trVLPs can continuously infect cells expressing the Ebola virus proteins responsible for genome replication and transcription, allowing us to safely model multiple infectious cycles under biosafety level 2 conditions. Importantly, the viral components of this systems are solely derived from Ebola virus and not from other viruses (as is, for example, the case in systems using pseudotyped viruses), and VP40, GP1,2 and VP24 are not overexpressed in this system, making it ideally suited for studying morphogenesis, budding and entry, although other aspects of the virus lifecycle such as genome replication and transcription can also be modeled with this system. Therefore, the tetracistronic trVLP assay represents the most comprehensive lifecycle modeling system available for Ebola viruses, and has tremendous potential for use in investigating the biology of Ebola viruses in future. Here, we provide detailed information on the use of this system, as well as on expected results. PMID:25285674

  16. 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

  17. Ebola virus disease outbreak - Nigeria, July-September 2014.

    PubMed

    Shuaib, Faisal; Gunnala, Rajni; Musa, Emmanuel O; Mahoney, Frank J; Oguntimehin, Olukayode; Nguku, Patrick M; Nyanti, Sara Beysolow; Knight, Nancy; Gwarzo, Nasir Sani; Idigbe, Oni; Nasidi, Abdulsalam; Vertefeuille, John F

    2014-10-01

    On July 20, 2014, an acutely ill traveler from Liberia arrived at the international airport in Lagos, Nigeria, and was confirmed to have Ebola virus disease (Ebola) after being admitted to a private hospital. This index patient potentially exposed 72 persons at the airport and the hospital. The Federal Ministry of Health, with guidance from the Nigeria Centre for Disease Control (NCDC), declared an Ebola emergency. Lagos, (pop. 21 million) is a regional hub for economic, industrial, and travel activities and a setting where communicable diseases can be easily spread and transmission sustained. Therefore, implementing a rapid response using all available public health assets was the highest priority. On July 23, the Federal Ministry of Health, with the Lagos State government and international partners, activated an Ebola Incident Management Center as a precursor to the current Emergency Operations Center (EOC) to rapidly respond to this outbreak. The index patient died on July 25; as of September 24, there were 19 laboratory-confirmed Ebola cases and one probable case in two states, with 894 contacts identified and followed during the response. Eleven patients with laboratory-confirmed Ebola had been discharged, an additional patient was diagnosed at convalescent stage, and eight patients had died (seven with confirmed Ebola; one probable). The isolation wards were empty, and 891 (all but three) contacts had exited follow-up, with the remainder due to exit on October 2. No new cases had occurred since August 31, suggesting that the Ebola outbreak in Nigeria might be contained. The EOC, established quickly and using an Incident Management System (IMS) to coordinate the response and consolidate decision making, is largely credited with helping contain the Nigeria outbreak early. National public health emergency preparedness agencies in the region, including those involved in Ebola responses, should consider including the development of an EOC to improve the ability to

  18. Diagnosis of Ebola Virus Disease: Past, Present, and Future.

    PubMed

    Broadhurst, M Jana; Brooks, Tim J G; Pollock, Nira R

    2016-10-01

    Laboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward. PMID:27413095

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

    PubMed

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

    2015-06-01

    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

  20. Frequently Asked Questions on Ebola Virus Disease

    MedlinePlus

    ... other in a remote area of Sudan. The origin of the virus is unknown, but current evidence ... Sitemap Home Health topics Data Media centre Publications Countries Programmes and projects Governance About WHO Help and ...

  1. Clinical presentation and management of severe Ebola virus disease.

    PubMed

    West, T Eoin; von Saint André-von Arnim, Amélie

    2014-11-01

    Clinicians caring for patients infected with Ebola virus must be familiar not only with screening and infection control measures but also with management of severe disease. By integrating experience from several Ebola epidemics with best practices for managing critical illness, this report focuses on the clinical presentation and management of severely ill infants, children, and adults with Ebola virus disease. Fever, fatigue, vomiting, diarrhea, and anorexia are the most common symptoms of the 2014 West African outbreak. Profound fluid losses from the gastrointestinal tract result in volume depletion, metabolic abnormalities (including hyponatremia, hypokalemia, and hypocalcemia), shock, and organ failure. Overt hemorrhage occurs infrequently. The case fatality rate in West Africa is at least 70%, and individuals with respiratory, neurological, or hemorrhagic symptoms have a higher risk of death. There is no proven antiviral agent to treat Ebola virus disease, although several experimental treatments may be considered. Even in the absence of antiviral therapies, intensive supportive care has the potential to markedly blunt the high case fatality rate reported to date. Optimal treatment requires conscientious correction of fluid and electrolyte losses. Additional management considerations include searching for coinfection or superinfection; treatment of shock (with intravenous fluids and vasoactive agents), acute kidney injury (with renal replacement therapy), and respiratory failure (with invasive mechanical ventilation); provision of nutrition support, pain and anxiety control, and psychosocial support; and the use of strategies to reduce complications of critical illness. Cardiopulmonary resuscitation may be appropriate in certain circumstances, but extracorporeal life support is not advised. Among other ethical issues, patients' medical needs must be carefully weighed against healthcare worker safety and infection control concerns. However, meticulous attention

  2. 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.

  3. 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.

  4. Notes from The Field: Ebola Virus Disease Cluster - Northern Sierra Leone, January 2016.

    PubMed

    Alpren, Charles; Sloan, Michelle; Boegler, Karen A; Martin, Daniel W; Ervin, Elizabeth; Washburn, Faith; Rickert, Regan; Singh, Tushar; Redd, John T

    2016-01-01

    On January 14, 2016, the Sierra Leone Ministry of Health and Sanitation was notified that a buccal swab collected on January 12 from a deceased female aged 22 years (patient A) in Tonkolili District had tested positive for Ebola virus by reverse transcription-polymerase chain reaction (RT-PCR). The most recent case of Ebola virus disease (Ebola) in Sierra Leone had been reported 4 months earlier on September 13, 2015 (1), and the World Health Organization had declared the end of Ebola virus transmission in Sierra Leone on November 7, 2015 (2). The Government of Sierra Leone launched a response to prevent further transmission of Ebola virus by identifying contacts of the decedent and monitoring them for Ebola signs and symptoms, ensuring timely treatment for anyone with Ebola, and conducting an epidemiologic investigation to identify the source of infection. PMID:27388584

  5. [Ocular symptoms and treatment of Ebola virus disease].

    PubMed

    Végh, Mihály; Roth, Hans-Walter; Hári-Kovács, András; Facskó, Andrea

    2015-03-01

    Ocular signs and symptoms of Ebola infection initially suggest banal conjunctivitis, but in advanced cases severe haemorrhagic conjunctivitis appears and, in the final stage of the disease, retinal and chorioidal haemorrhages may occur which can cause even blindness. Although the viral infection accompanied by ocular symptoms of a non-specific conjunctivitis, the high fever present from the onset of the disease should raise the suspicion of Ebola infection. There is no causal therapy know so far, and the only adjunctive treatment may be delivered by an ophthalmologist. Because the virus can be detected in the tear, it can theoretically be the mediator of the infection and, therefore, ophthalmological examinations should be carried out with the highest caution. In case of suspected Ebola infection the nearest competent healthcare authority should be immediately alerted in order to take further actions. PMID:25749536

  6. Pathophysiology of Ebola Virus Infection: Current Challenges and Future Hopes.

    PubMed

    Rivera, Andrea; Messaoudi, Ilhem

    2015-05-01

    The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), are among the deadliest viruses that cause disease in humans, with reported case fatality rates of up to 90% in some outbreaks. The high virulence of EBOV and MARV is largely attributed to the ability of these viruses to interfere with the host immune response. Currently, there are no approved vaccines or postexposure therapeutics, and treatment options for patients infected with EBOV are limited to supportive care. In this review, we discuss mechanisms of EBOV pathogenesis and its ability to subvert host immunity as well as several vaccines and therapeutics with respect to their evaluation in small animal models, nonhuman primates, and human clinical trials. PMID:27622648

  7. Reduced evolutionary rate in reemerged Ebola virus transmission chains

    PubMed Central

    Blackley, David J.; Wiley, Michael R.; Ladner, Jason T.; Fallah, Mosoka; Lo, Terrence; Gilbert, Merle L.; Gregory, Christopher; D’ambrozio, Jonathan; Coulter, Stewart; Mate, Suzanne; Balogun, Zephaniah; Kugelman, Jeffrey; Nwachukwu, William; Prieto, Karla; Yeiah, Adolphus; Amegashie, Fred; Kearney, Brian; Wisniewski, Meagan; Saindon, John; Schroth, Gary; Fakoli, Lawrence; Diclaro, Joseph W.; Kuhn, Jens H.; Hensley, Lisa E.; Jahrling, Peter B.; Ströher, Ute; Nichol, Stuart T.; Massaquoi, Moses; Kateh, Francis; Clement, Peter; Gasasira, Alex; Bolay, Fatorma; Monroe, Stephan S.; Rambaut, Andrew; Sanchez-Lockhart, Mariano; Scott Laney, A.; Nyenswah, Tolbert; Christie, Athalia; Palacios, Gustavo

    2016-01-01

    On 29 June 2015, Liberia’s respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak (“flare-up”) of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over. PMID:27386513

  8. Molecular Evidence of Sexual Transmission of Ebola Virus

    PubMed Central

    Mate, S.E.; Kugelman, J.R.; Nyenswah, T.G.; Ladner, J.T.; Wiley, M.R.; Cordier-Lassalle, T.; Christie, A; Schroth, G.P.; Gross, S.M.; Davies-Wayne, G.J.; Shinde, S.A.; Murugan, R.; Sieh, S.B.; Badio, M.; Fakoli, L.; Taweh, F.; de Wit, E.; van Doremalen, N.; Munster, V.J.; Pettitt, J.; Prieto, K.; Humrighouse, B.W.; Ströher, U.; DiClaro, J.W.; Hensley, L.E.; Schoepp, R.J.; Safronetz, D.; Fair, J.; Kuhn, J.H.; Blackley, D.J.; Laney, A.S.; Williams, D.E.; Lo, T.; Gasasira, A.; Nichol, S.T.; Formenty, P.; Kateh, F.N.; De Cock, K.M.; Bolay, F.; Sanchez-Lockhart, M.; Palacios, G.

    2016-01-01

    Summary 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

  9. Reduced evolutionary rate in reemerged Ebola virus transmission chains.

    PubMed

    Blackley, David J; Wiley, Michael R; Ladner, Jason T; Fallah, Mosoka; Lo, Terrence; Gilbert, Merle L; Gregory, Christopher; D'ambrozio, Jonathan; Coulter, Stewart; Mate, Suzanne; Balogun, Zephaniah; Kugelman, Jeffrey; Nwachukwu, William; Prieto, Karla; Yeiah, Adolphus; Amegashie, Fred; Kearney, Brian; Wisniewski, Meagan; Saindon, John; Schroth, Gary; Fakoli, Lawrence; Diclaro, Joseph W; Kuhn, Jens H; Hensley, Lisa E; Jahrling, Peter B; Ströher, Ute; Nichol, Stuart T; Massaquoi, Moses; Kateh, Francis; Clement, Peter; Gasasira, Alex; Bolay, Fatorma; Monroe, Stephan S; Rambaut, Andrew; Sanchez-Lockhart, Mariano; Scott Laney, A; Nyenswah, Tolbert; Christie, Athalia; Palacios, Gustavo

    2016-04-01

    On 29 June 2015, Liberia's respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak ("flare-up") of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over. PMID:27386513

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

    PubMed

    Pigott, David M; Golding, Nick; Mylne, Adrian; Huang, Zhi; Henry, Andrew J; Weiss, Daniel J; Brady, Oliver J; Kraemer, Moritz U G; 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. PMID:25201877

  11. 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

  12. 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 β-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. 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.

  14. 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

  15. Persistence of Ebola Virus in Ocular Fluid during Convalescence.

    PubMed

    Varkey, Jay B; Shantha, Jessica G; Crozier, Ian; Kraft, Colleen S; Lyon, G Marshall; Mehta, Aneesh K; Kumar, Gokul; Smith, Justine R; Kainulainen, Markus H; Whitmer, Shannon; Ströher, Ute; Uyeki, Timothy M; Ribner, Bruce S; Yeh, Steven

    2015-06-18

    Among the survivors of Ebola virus disease (EVD), complications that include uveitis can develop during convalescence, although the incidence and pathogenesis of EVD-associated uveitis are unknown. We describe a patient who recovered from EVD and was subsequently found to have severe unilateral uveitis during convalescence. Viable Zaire ebolavirus (EBOV) was detected in aqueous humor 14 weeks after the onset of EVD and 9 weeks after the clearance of viremia. PMID:25950269

  16. Persistent Infection with Ebola Virus under Conditions of Partial Immunity

    PubMed Central

    Gupta, Manisha; Mahanty, Siddhartha; Greer, Patricia; Towner, Jonathan S.; Shieh, Wun-Ju; Zaki, Sherif R.; Ahmed, Rafi; Rollin, Pierre E.

    2004-01-01

    Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective immunity are not well defined. Using a mouse model, we determined the role of the immune system in clearance of and protection against Ebola virus. All CD8 T-cell-deficient mice succumbed to subcutaneous infection and had high viral antigen titers in tissues, whereas mice deficient in B cells or CD4 T cells cleared infection and survived, suggesting that CD8 T cells, independent of CD4 T cells and antibodies, are critical to protection against subcutaneous Ebola virus infection. B-cell-deficient mice that survived the primary subcutaneous infection (vaccinated mice) transiently depleted or not depleted of CD4 T cells also survived lethal intraperitoneal rechallenge for ≥25 days. However, all vaccinated B-cell-deficient mice depleted of CD8 T cells had high viral antigen titers in tissues following intraperitoneal rechallenge and died within 6 days, suggesting that memory CD8 T cells by themselves can protect mice from early death. Surprisingly, vaccinated B-cell-deficient mice, after initially clearing the infection, were found to have viral antigens in tissues later (day 120 to 150 post-intraperitoneal infection). Furthermore, following intraperitoneal rechallenge, vaccinated B-cell-deficient mice that were transiently depleted of CD4 T cells had high levels of viral antigen in tissues earlier (days 50 to 70) than vaccinated undepleted mice. This demonstrates that under certain immunodeficiency conditions, Ebola virus can persist and that loss of primed CD4 T cells accelerates the course of persistent infections. These data show that CD8 T cells play an important role in protection against acute disease, while both CD4 T cells and antibodies are required for long-term protection, and they provide evidence of persistent infection by Ebola virus suggesting that under

  17. Potential for large outbreaks of Ebola virus disease.

    PubMed

    Camacho, A; Kucharski, A J; Funk, S; Breman, J; Piot, P; Edmunds, W J

    2014-12-01

    Outbreaks of Ebola virus can cause substantial morbidity and mortality in affected regions. The largest outbreak of Ebola to date is currently underway in West Africa, with 3944 cases reported as of 5th September 2014. To develop a better understanding of Ebola transmission dynamics, we revisited data from the first known Ebola outbreak, which occurred in 1976 in Zaire (now Democratic Republic of Congo). By fitting a mathematical model to time series stratified by disease onset, outcome and source of infection, we were able to estimate several epidemiological quantities that have previously proved challenging to measure, including the contribution of hospital and community infection to transmission. We found evidence that transmission decreased considerably before the closure of the hospital, suggesting that the decline of the outbreak was most likely the result of changes in host behaviour. Our analysis suggests that the person-to-person reproduction number was 1.34 (95% CI: 0.92-2.11) in the early part of the outbreak. Using stochastic simulations we demonstrate that the same epidemiological conditions that were present in 1976 could have generated a large outbreak purely by chance. At the same time, the relatively high person-to-person basic reproduction number suggests that Ebola would have been difficult to control through hospital-based infection control measures alone. PMID:25480136

  18. Laboratory diagnosis of Ebola virus disease and corresponding biosafety considerations in the China Ebola Treatment Center.

    PubMed

    Huang, Qing; Fu, Wei-Ling; You, Jian-Ping; Mao, Qing

    2016-10-01

    Ebola virus disease (EVD), caused by Ebola virus (EBOV), is a potent acute infectious disease with a high case-fatality rate. Etiological and serological EBOV detection methods, including techniques that involve the detection of the viral genome, virus-specific antigens and anti-virus antibodies, are standard laboratory diagnostic tests that facilitate confirmation or exclusion of EBOV infection. In addition, routine blood tests, liver and kidney function tests, electrolytes and coagulation tests and other diagnostic examinations are important for the clinical diagnosis and treatment of EVD. Because of the viral load in body fluids and secretions from EVD patients, all body fluids are highly contagious. As a result, biosafety control measures during the collection, transport and testing of clinical specimens obtained from individuals scheduled to undergo EBOV infection testing (including suspected, probable and confirmed cases) are crucial. This report has been generated following extensive work experience in the China Ebola Treatment Center (ETC) in Liberia and incorporates important information pertaining to relevant diagnostic standards, clinical significance, operational procedures, safety controls and other issues related to laboratory testing of EVD. Relevant opinions and suggestions are presented in this report to provide contextual awareness associated with the development of standards and/or guidelines related to EVD laboratory testing. PMID:26952811

  19. Ebola virus outbreak, updates on current therapeutic strategies.

    PubMed

    Elshabrawy, Hatem A; Erickson, Timothy B; Prabhakar, Bellur S

    2015-07-01

    Filoviruses are enveloped negative-sense single-stranded RNA viruses, which include Ebola and Marburg viruses, known to cause hemorrhagic fever in humans with a case fatality of up to 90%. There have been several Ebola virus outbreaks since the first outbreak in the Democratic Republic of Congo in 1976 of which, the recent 2013-2015 epidemic in Guinea, Liberia, and Sierra Leone is the largest in recorded history. Within a few months of the start of the outbreak in December 2013, thousands of infected cases were reported with a significant number of deaths. As of March 2015, according to the Centers for Disease Control and Prevention, there have been nearly 25,000 suspected cases, with 15,000 confirmed by laboratory testing, and over 10,000 deaths. The large number of cases and the high mortality rate, combined with the lack of effective Food and Drug Administration-approved treatments, necessitate the development of potent and safe therapeutic measures to combat the current and future outbreaks. Since the beginning of the outbreak, there have been considerable efforts to develop and characterize protective measures including vaccines and antiviral small molecules, and some have proven effective in vitro and in animal models. Most recently, a cocktail of monoclonal antibodies has been shown to be highly effective in protecting non-human primates from Ebola virus infection. In this review, we will discuss what is known about the nature of the virus, phylogenetic classification, genomic organization and replication, disease transmission, and viral entry and highlight the current approaches and efforts, in the development of therapeutics, to control the outbreak. PMID:25962887

  20. 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

  1. Secondary Infections with Ebola Virus in Rural Communities, Liberia and Guinea, 2014-2015.

    PubMed

    Lindblade, Kim A; Nyenswah, Tolbert; Keita, Sakoba; Diallo, Boubakar; Kateh, Francis; Amoah, Aurora; Nagbe, Thomas K; Raghunathan, Pratima; Neatherlin, John C; Kinzer, Mike; Pillai, Satish K; Attfield, Kathleen R; Hajjeh, Rana; Dweh, Emmanuel; Painter, John; Barradas, Danielle T; Williams, Seymour G; Blackley, David J; Kirking, Hannah L; Patel, Monita R; Dea, Monica; Massoudi, Mehran S; Barskey, Albert E; Zarecki, Shauna L Mettee; Fomba, Moses; Grube, Steven; Belcher, Lisa; Broyles, Laura N; Maxwell, T Nikki; Hagan, Jose E; Yeoman, Kristin; Westercamp, Matthew; Mott, Joshua; Mahoney, Frank; Slutsker, Laurence; DeCock, Kevin M; Marston, Barbara; Dahl, Benjamin

    2016-09-01

    Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities. PMID:27268508

  2. Secondary Infections with Ebola Virus in Rural Communities, Liberia and Guinea, 2014–2015

    PubMed Central

    Nyenswah, Tolbert; Keita, Sakoba; Diallo, Boubakar; Kateh, Francis; Amoah, Aurora; Nagbe, Thomas K.; Raghunathan, Pratima; Neatherlin, John C.; Kinzer, Mike; Pillai, Satish K.; Attfield, Kathleen R.; Hajjeh, Rana; Dweh, Emmanuel; Painter, John; Barradas, Danielle T.; Williams, Seymour G.; Blackley, David J.; Kirking, Hannah L.; Patel, Monita R.; Dea, Monica; Massoudi, Mehran S.; Barskey, Albert E.; Zarecki, Shauna L. Mettee; Fomba, Moses; Grube, Steven; Belcher, Lisa; Broyles, Laura N.; Maxwell, T. Nikki; Hagan, Jose E.; Yeoman, Kristin; Westercamp, Matthew; Mott, Joshua; Mahoney, Frank; Slutsker, Laurence; DeCock, Kevin M.; Marston, Barbara; Dahl, Benjamin

    2016-01-01

    Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities. PMID:27268508

  3. Ebola virus outbreaks in Africa: past and present.

    PubMed

    Muyembe-Tamfum, J J; Mulangu, S; Masumu, Justin; Kayembe, J M; Kemp, A; Paweska, Janusz T

    2012-01-01

    Ebola haemorrhagic fever (EHF) is a zoonosis affecting both human and non-human primates (NHP). Outbreaks in Africa occur mainly in the Congo and Nile basins. The first outbreaks of EHF occurred nearly simultaneously in 1976 in the Democratic Republic of the Congo (DRC, former Zaire) and Sudan with very high case fatality rates of 88% and 53%, respectively. The two outbreaks were caused by two distinct species of Ebola virus named Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SEBOV). The source of transmission remains unknown. After a long period of silence (1980-1993), EHF outbreaks in Africa caused by the two species erupted with increased frequency and new species were discovered, namely Côte d'Ivoire ebolavirus (CIEBOV) in 1994 in the Ivory Coast and Bundibugyo ebolavirus (BEBOV) in 2007 in Uganda. The re-emergence of EHF outbreaks in Gabon and Republic of the Congo were concomitant with an increase in mortality amongst gorillas and chimpanzees infected with ZEBOV. The human outbreaks were related to multiple, unrelated index cases who had contact with dead gorillas or chimpanzees. However, in areas where NHP were rare or absent, as in Kikwit (DRC) in 1995, Mweka (DRC) in 2007, Gulu (Uganda) in 2000 and Yambio (Sudan) in 2004, the hunting and eating of fruit bats may have resulted in the primary transmission of Ebola virus to humans. Human-to-human transmission is associated with direct contact with body fluids or tissues from an infected subject or contaminated objects. Despite several, often heroic field studies, the epidemiology and ecology of Ebola virus, including identification of its natural reservoir hosts, remains a formidable challenge for public health and scientific communities. PMID:23327370

  4. Ebola virus disease: What clinicians in the United States need to know

    PubMed Central

    Fischer, William A.; Uyeki, Timothy M.; Tauxe, Robert V.

    2015-01-01

    In March 2014 the World Health Organization was notified of an outbreak of Ebola virus disease (EVD) in the forest region of Guinea. Over the subsequent 8 months, this outbreak has become the most devastating Ebola epidemic in history with 21,296 infections and 8,429 deaths. The recent introduction of Ebola into noncontiguous countries including the United States from infected travelers highlights the importance of preparedness of all healthcare providers. Early identification and rapid isolation of patients suspected of being infected with Ebola virus is critical to limiting the spread of this virus. Additionally, enhanced understanding of Ebola case definitions, clinical presentation, treatment and infection control strategies will improve the ability of healthcare providers to safe care for patients with Ebola virus disease. PMID:26116335

  5. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody.

    PubMed

    Corti, Davide; Misasi, John; Mulangu, Sabue; Stanley, Daphne A; Kanekiyo, Masaru; Wollen, Suzanne; Ploquin, Aurélie; Doria-Rose, Nicole A; Staupe, Ryan P; Bailey, Michael; Shi, Wei; Choe, Misook; Marcus, Hadar; Thompson, Emily A; Cagigi, Alberto; Silacci, Chiara; Fernandez-Rodriguez, Blanca; Perez, Laurent; Sallusto, Federica; Vanzetta, Fabrizia; Agatic, Gloria; Cameroni, Elisabetta; Kisalu, Neville; Gordon, Ingelise; Ledgerwood, Julie E; Mascola, John R; Graham, Barney S; Muyembe-Tamfun, Jean-Jacques; Trefry, John C; Lanzavecchia, Antonio; Sullivan, Nancy J

    2016-03-18

    Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible. PMID:26917593

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Possible FDA-approved drugs to treat Ebola virus infection.

    PubMed

    Yuan, Shu

    2015-01-01

    There is currently no effective treatment for the Ebola virus (EBOV) thus far. Most drugs and vaccines developed to date have not yet been approved for human trials. Two FDA-approved c-AbI1 tyrosine kinase inhibitors Gleevec and Tasigna block the release of viral particles; however, their clinical dosages are much lower than the dosages required for effective EBOV suppression. An α-1,2-glucosidase inhibitor Miglustat has been shown to inhibit EBOV particle assembly and secretion. Additionally, the estrogen receptor modulators Clomiphene and Toremifene prevent membrane fusion of EBOV and 50-90% of treated mice survived after Clomiphene/Toremifene treatments. However, the uptake efficiency of Clomiphene by oral administration is very low. Thus, I propose a hypothetical treatment protocol to treat Ebola virus infection with a cumulative use of both Miglustat and Toremifene to inhibit the virus effectively and synergistically. EBOV infection induces massive apoptosis of peripheral lymphocytes. Also, cytolysis of endothelial cells triggers disseminated intravascular coagulation (DIC) and subsequent multiple organ failures. Therefore, blood transfusions and active treatments with FDA-approved drugs to treat DIC are also recommended. PMID:25984303

  12. Epidemiological situation of Ebola virus disease in West Africa.

    PubMed

    Arima, Yuzo; Shimada, Tomoe

    2015-01-01

    After Guinea reported an outbreak of Ebola virus disease (EVD) in March 2014, EVD spread to neighboring Sierra Leone and Liberia in West Africa. Since then, the EVD outbreak spread over a wide geographic area among these three countries, and became the largest EVD epidemic ever with unprecedented numbers of confirmed cases and fatalities. As of April 2015, one year past the start of the outbreak, transmission is still ongoing. And, while six other countries, including those outside of the African continent (the United Kingdom, Spain, and the United States), have reported EVD cases, the source of the infection all originated from Guinea, Sierra Leone, or Liberia. As for the pathogen, Ebola virus, the route of transmission and associated prevention measures are well known, and change in the virulence or transmissibility of the virus has not been confirmed. However, there are specific factors that likely contributed to the unprecedented magnitude of the current EVD outbreak. In addition to the limited and poor medical and public health infrastructure in the affected countries, implementing appropriate responses rapidly was challenging for these countries, whose medical community, the general public, and governments had never experienced EVD before. PMID:26923957

  13. Association of ebola virus matrix protein VP40 with microtubules.

    PubMed

    Ruthel, Gordon; Demmin, Gretchen L; Kallstrom, George; Javid, Melodi P; Badie, Shirin S; Will, Amy B; Nelle, Timothy; Schokman, Rowena; Nguyen, Tam L; Carra, John H; Bavari, Sina; Aman, M Javad

    2005-04-01

    Viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear that use of host cell microtubules is a vital part of the infection process for many viruses. A variety of viral proteins have been identified that interact with microtubules, either directly or via a microtubule-associated motor protein. Here, we report that Ebola virus associates with microtubules via the matrix protein VP40. When transfected into mammalian cells, a fraction of VP40 colocalized with microtubule bundles and VP40 coimmunoprecipitated with tubulin. The degree of colocalization and microtubule bundling in cells was markedly intensified by truncation of the C terminus to a length of 317 amino acids. Further truncation to 308 or fewer amino acids abolished the association with microtubules. Both the full-length and the 317-amino-acid truncation mutant stabilized microtubules against depolymerization with nocodazole. Direct physical interaction between purified VP40 and tubulin proteins was demonstrated in vitro. A region of moderate homology to the tubulin binding motif of the microtubule-associated protein MAP2 was identified in VP40. Deleting this region resulted in loss of microtubule stabilization against drug-induced depolymerization. The presence of VP40-associated microtubules in cells continuously treated with nocodazole suggested that VP40 promotes tubulin polymerization. Using an in vitro polymerization assay, we demonstrated that VP40 directly enhances tubulin polymerization without any cellular mediators. These results suggest that microtubules may play an important role in the Ebola virus life cycle and potentially provide a novel target for therapeutic intervention against this highly pathogenic virus. PMID:15795257

  14. 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

  15. 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

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

    PubMed Central

    Hober, Didier; Blondiaux, Joel

    2015-01-01

    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

  17. The Ebola Virus and Human Rights Concerns in Africa.

    PubMed

    Durojaye, Ebenezer T; Mirugi-Mukundi, Gladys

    2015-09-01

    In the wake of the Ebola virus disease (EVD) that is ravaging parts of Africa certain measures are being taken by governments to prevent the spread of the epidemic within their borders. Some of these measures are drastic and may likely have implications for the fundamental rights of individuals. The EVD outbreaks have brought to the fore again the tension between public health and human rights. This article discusses the origin and mode of transmission of the EVD and then considers the human rights challenges that may arise as a result of states' responses to the disease in Africa. PMID:26897909

  18. 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

  19. Critical Care for Multiple Organ Failure Secondary to Ebola Virus Disease in the United States

    PubMed Central

    Sueblinvong, Viranuj; Johnson, Daniel W.; Weinstein, Gary L.; Connor, Michael J.; Crozier, Ian; Liddell, Allison M.; Franch, Harold A.; Wall, Bruce R.; Kalil, Andre C.; Feldman, Mark; Lisco, Steven J.; Sevransky, Jonathan E.

    2016-01-01

    Objective This report describes three patients with Ebola virus disease who were treated in the United States and developed for severe critical illness and multiple organ failure secondary to Ebola virus infection. The patients received mechanical ventilation, renal replacement therapy, invasive monitoring, vasopressor support, and investigational therapies for Ebola virus disease. Data Sources Patient medical records from three tertiary care centers (Emory University Hospital, University of Nebraska Medical Center, and Texas Health Presbyterian Dallas Hospital). Study Selection Not applicable. Data Extraction Not applicable. Data Synthesis Not applicable. Conclusion In the severe form, patients with Ebola virus disease may require life-sustaining therapy, including mechanical ventilation and renal replacement therapy. In conjunction with other reported cases, this series suggests that respiratory and renal failure may occur in severe Ebola virus disease, especially in patients burdened with high viral loads. Ebola virus disease complicated by multiple organ failure can be survivable with the application of advanced life support measures. This collective, multicenter experience is presented with the hope that it may inform future treatment of patients with Ebola virus disease requiring critical care treatment. PMID:26196353

  20. 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

  1. Use of Existing Diagnostic Reverse-Transcription Polymerase Chain Reaction Assays for Detection of Ebola Virus RNA in Semen.

    PubMed

    Pettitt, James; Higgs, Elizabeth S; Adams, Rick D; Jahrling, Peter B; Hensley, Lisa E

    2016-04-15

    Sexual transmission of Ebola virus in Liberia has now been documented and associated with new clusters in regions previously declared Ebola free. Assays that have Emergency Use Authorization (EUA) and are routinely used to detect Ebola virus RNA in whole blood and plasma specimens at the Liberian Institute for Biomedical Research were tested for their suitability in detecting the presence of Ebola virus RNA in semen. Qiagen AVL extraction protocols, as well as the Ebola Zaire Target 1 and major groove binder quantitative reverse-transcription polymerase chain reaction assays, were demonstrably suitable for this purpose and should facilitate epidemiologic investigations, including those involving long-term survivors of Ebola. PMID:26374912

  2. 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

  3. Sequencing ebola and marburg viruses genomes using microarrays.

    PubMed

    Hardick, Justin; Woelfel, Roman; Gardner, Warren; Ibrahim, Sofi

    2016-08-01

    Periodic outbreaks of Ebola and Marburg hemorrhagic fevers have occurred in Africa over the past four decades with case fatality rates reaching as high as 90%. The latest Ebola outbreak in West Africa in 2014 raised concerns that these infections can spread across continents and pose serious health risks. Early and accurate identification of the causative agents is necessary to contain outbreaks. In this report, we describe sequencing-by-hybridization (SBH) technique using high density microarrays to identify Ebola and Marburg viruses. The microarrays were designed to interrogate the sequences of entire viral genomes, and were evaluated with three species of Ebolavirus (Reston, Sudan, and Zaire), and three strains of Marburgvirus (Angola, Musoke, and Ravn). The results showed that the consensus sequences generated with four or more hybridizations had 92.1-98.9% accuracy over 95-99% of the genomes. Additionally, with SBH microarrays it was possible to distinguish between different strains of the Lake Victoria Marburgvirus. J. Med. Virol. 88:1303-1308, 2016. © 2016 Wiley Periodicals, Inc. PMID:26822839

  4. 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.

  5. 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

  6. Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection

    PubMed Central

    Veljkovic, Veljko; Loiseau, Philippe M.; Figadere, Bruno; Glisic, Sanja; Veljkovic, Nevena; Perovic, Vladimir R.; Cavanaugh, David P.; Branch, Donald R.

    2015-01-01

    The ongoing Ebola virus epidemic has presented numerous challenges with respect to control and treatment because there are no approved drugs or vaccines for the Ebola virus disease (EVD). Herein is proposed simple theoretical criterion for fast virtual screening of molecular libraries for candidate inhibitors of Ebola virus infection. We performed a repurposing screen of 6438 drugs from DrugBank using this criterion and selected 267 approved and 382 experimental drugs as candidates for treatment of EVD including 15 anti-malarial drugs and 32 antibiotics. An open source Web server allowing screening of molecular libraries for candidate drugs for treatment of EVD was also established. PMID:25717373

  7. Euthanasia assessment in ebola virus infected nonhuman primates.

    PubMed

    Warren, Travis K; Trefry, John C; Marko, Shannon T; Chance, Taylor B; Wells, Jay B; Pratt, William D; Johnson, Joshua C; Mucker, Eric M; Norris, Sarah L; Chappell, Mark; Dye, John M; Honko, Anna N

    2014-11-01

    Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy assessment will be survival following challenge; however, there exists no standardized approach for assessing the health or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria is important to (a) ensure test subjects are euthanized without unnecessary distress; (b) enhance the likelihood that animals exhibiting mild or moderate signs of disease are not prematurely euthanized; (c) minimize the occurrence of spontaneous deaths and loss of end-stage samples; (d) enhance the reproducibility of experiments between different researchers; and (e) provide a defensible rationale for euthanasia decisions that withstands regulatory scrutiny. Historic records were compiled for 58 surviving and non-surviving monkeys exposed to Ebola virus at the US Army Medical Research Institute of Infectious Diseases. Clinical pathology parameters were statistically analyzed and those exhibiting predicative value for survival are reported. These findings may be useful for standardization of objective euthanasia assessments in rhesus monkeys exposed to Ebola virus and may serve as a useful approach for other standardization efforts. PMID:25421892

  8. 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

  9. 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. PMID:26740844

  10. 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 re-emerging 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

  11. Ebola virus VP40 late domains are not essential for viral replication in cell culture.

    PubMed

    Neumann, Gabriele; Ebihara, Hideki; Takada, Ayato; Noda, Takeshi; Kobasa, Darwyn; Jasenosky, Luke D; Watanabe, Shinji; Kim, Jin H; Feldmann, Heinz; Kawaoka, Yoshihiro

    2005-08-01

    Ebola virus particle formation and budding are mediated by the VP40 protein, which possesses overlapping PTAP and PPXY late domain motifs (7-PTAPPXY-13). These late domain motifs have also been found in the Gag proteins of retroviruses and the matrix proteins of rhabdo- and arenaviruses. While in vitro studies suggest a critical role for late domain motifs in the budding of these viruses, including Ebola virus, it remains unclear as to whether the VP40 late domains play a role in Ebola virus replication. Alteration of both late domain motifs drastically reduced VP40 particle formation in vitro. However, using reverse genetics, we were able to generate recombinant Ebola virus containing mutations in either or both of the late domains. Viruses containing mutations in one or both of their late domain motifs were attenuated by one log unit. Transmission and scanning electron microscopy did not reveal appreciable differences between the mutant and wild-type viruses released from infected cells. These findings indicate that the Ebola VP40 late domain motifs enhance virus replication but are not absolutely required for virus replication in cell culture. PMID:16051823

  12. 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 × 10⁴ 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

  13. 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 × 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.

  14. 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

  15. Ebola virus disease: any risk for oral and maxillo-facial surgery? An overview.

    PubMed

    Reichart, Peter A; Gelderblom, Hans R; Khongkhunthian, Pathawee; Schmidt-Westhausen, Andrea

    2016-06-01

    The 2014-2015 outbreak of the Ebola virus disease (EVD) in West Africa has been considered a major global health emergency by the WHO. Implications for health care providers including oral and maxillo-facial surgeons have been published by the WHO, the Centers for Disease Control and Prevention (USA), and other medical societies and public health organizations. While the risk of infection with the Ebola virus seems to be rather small in Europe, maxillo-facial and plastic surgeons often travel to Africa to treat patients with facial burns, cleft-lip and palate, and noma. The likelihood of an encounter with patients infected by Ebola virus in subsaharan and West Africa, therefore, has increased during the last 2 years. The purpose of this short overview was to summarize the virology of the Ebola virus, transmission, epidemiology, clinical features, oral manifestations, treatment, and possible implications for maxillo-facial surgeons of EDV. PMID:26781718

  16. 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/ΔF-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/ΔF-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/ΔF-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

  17. 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.

  18. Ebola virus disease cluster in the United States--Dallas County, Texas, 2014.

    PubMed

    Chevalier, Michelle S; Chung, Wendy; Smith, Jessica; Weil, Lauren M; Hughes, Sonya M; Joyner, Sibeso N; Hall, Emily; Srinath, Divya; Ritch, Julia; Thathiah, Prea; Threadgill, Heidi; Cervantes, Diana; Lakey, David L

    2014-11-21

    Since March 10, 2014, Guinea, Liberia, and Sierra Leone have experienced the largest known Ebola virus disease (Ebola) epidemic with approximately 13,000 persons infected as of October 28, 2014. Before September 25, 2014, only four patients with Ebola had been treated in the United States; all of these patients had been diagnosed in West Africa and medically evacuated to the United States for care. PMID:25412069

  19. A Health Care Worker with Ebola Virus Disease and Adverse Prognostic Factors Treated in Sierra Leone.

    PubMed

    O'Shea, Matthew K; Clay, Katherine A; Craig, Darren G; Moore, Alastair J; Lewis, Stephen; Espina, Melanie; Praught, Jeff; Horne, Simon; Kao, Raymond; Johnston, Andrew M

    2016-04-01

    We describe the management of a Sierra Leonean health care worker with severe Ebola virus disease complicated by diarrhea, significant electrolyte disturbances, and falciparum malaria coinfection. With additional resources and staffing, high quality care can be provided to patients with Ebola infection and adverse prognostic factors in west Africa. PMID:26903609

  20. 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

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

    PubMed Central

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

    2015-01-01

    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

  2. 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

  3. Ebola virus disease in mice with transplanted human hematopoietic stem cells.

    PubMed

    Lüdtke, Anja; Oestereich, Lisa; Ruibal, Paula; Wurr, Stephanie; Pallasch, Elisa; Bockholt, Sabrina; Ip, Wing Hang; Rieger, Toni; Gómez-Medina, Sergio; Stocking, Carol; Rodríguez, Estefanía; Günther, Stephan; Muñoz-Fontela, César

    2015-04-01

    The development of treatments for Ebola virus disease (EVD) has been hampered by the lack of small-animal models that mimick human disease. Here we show that mice with transplanted human hematopoetic stem cells reproduce features typical of EVD. Infection with Ebola virus was associated with viremia, cell damage, liver steatosis, signs of hemorrhage, and high lethality. Our study provides a small-animal model with human components for the development of EVD therapies. PMID:25673711

  4. The etiology of Ebola virus disease-like illnesses in Ebola virusnegative patients from Sierra Leone.

    PubMed

    Li, Wen-Gang; Chen, Wei-Wei; Li, Lei; Ji, Dong; Ji, Ying-Jie; Li, Chen; Gao, Xu-Dong; Wang, Li-Fu; Zhao, Min; Duan, Xue-Zhang; Duan, Hui-Juan

    2016-05-10

    During the 2014 Ebola virus disease (EVD) outbreak, less than half of EVD-suspected cases were laboratory tested as Ebola virus (EBOV)-negative, but disease identity remained unknown. In this study we investigated the etiology of EVD-like illnesses in EBOV-negative cases. From November 13, 2014 to March 16, 2015, EVD-suspected patients were admitted to Jui Government Hospital and assessed for EBOV infection by real-time PCR. Of 278 EBOV negative patients, 223 (80.21%), 142 (51.08%), 123 (44.24%), 114 (41.01%), 59 (21.22%), 35 (12.59%), and 12 (4.32%) reported fever, headache, joint pain, fatigue, nausea/vomiting, diarrhea, hemorrhage, respectively. Furthermore, 121 (43.52%), 44 (15.83%), 36 (12.95%), 33 (11.87%), 23 (8.27%), 10 (3.60%) patients were diagnosed as infection with malaria, HIV, Lassa fever, tuberculosis, yellow fever, and pneumonia, respectively. No significant differences in clinical features and symptoms were found between non-EVD and EVD patients. To the best of our knowledge, the present study is the first to explore the etiology of EVD-like illnesses in uninfected patients in Sierra Leone, highlighting the importance of accurate diagnosis to EVD confirmation. PMID:27058894

  5. Stability of a Vesicular Stomatitis Virus-Vectored Ebola Vaccine.

    PubMed

    Arnemo, Marianne; Viksmoen Watle, Sara Sofie; Schoultz, Kristin Merete; Vainio, Kirsti; Norheim, Gunnstein; Moorthy, Vasee; Fast, Patricia; Røttingen, John-Arne; Gjøen, Tor

    2016-03-15

    The live attenuated vesicular stomatitis virus-vectored Ebola vaccine rVSV-ZEBOV is currently undergoing clinical trials in West Africa. The vaccine is to be stored at -70°C or less. Since maintaining the cold chain is challenging in rural areas, the rVSV-ZEBOV vaccine's short-term and long-term stability at different temperatures was examined. Different dilutions were tested since the optimal vaccine dosage had not yet been determined at the start of this experiment. The results demonstrate that the original vaccine formulation was stable for 1 week at 4°C and for 24 hours at 25°C. The stability of the vaccine was compromised by both high temperatures and dilution. PMID:26563239

  6. Effectiveness of Four Disinfectants against Ebola Virus on Different Materials

    PubMed Central

    Smither, Sophie; Phelps, Amanda; Eastaugh, Lin; Ngugi, Sarah; O’Brien, Lyn; Dutch, Andrew; Lever, Mark Stephen

    2016-01-01

    The West Africa Ebola virus (EBOV) outbreak has highlighted the need for effective disinfectants capable of reducing viral load in a range of sample types, equipment and settings. Although chlorine-based products are widely used, they can also be damaging to equipment or apparatus that needs continuous use such as aircraft use for transportation of infected people. Two aircraft cleaning solutions were assessed alongside two common laboratory disinfectants in a contact kill assay with EBOV on two aircraft relevant materials representative of a porous and non-porous surface. A decimal log reduction of viral titre of 4 is required for a disinfectant to be deemed effective and two of the disinfectants fulfilled this criteria under the conditions tested. One product, Ardrox 6092, was found to perform similarly to sodium hypochlorite, but as it does not have the corrosive properties of sodium hypochlorite, it could be an alternative disinfectant solution to be used for decontamination of EBOV on sensitive apparatus. PMID:27399759

  7. 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

  8. 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

  9. Ebola virus disease: the UK critical care perspective.

    PubMed

    Martin, D; Howard, J; Agarwal, B; Rajalingam, Y; Athan, B; Bhagani, S; Cropley, I; Hopkins, S; Mepham, S; Rodger, A; Warren, S; Jacobs, M

    2016-05-01

    The recent outbreak of Ebola virus disease (EVD) has required the treatment of affected patients in the NHS system within the UK. Managing patients with a confirmed viral haemorrhagic fever requires a thorough understanding of treatment options within the confines of an effective biocontainment setting. The Royal Free Hospital High Level Isolation Unit (HLIU) in London, is a purpose built facility that allows healthcare workers to safely treat patients with highly contagious diseases. This HLIU uses Trexler isolator tents to prevent the spread of infection from patients to healthcare workers. Provision of invasive organ support can be provided in this environment, if considered appropriate, and is achievable without posing additional risk to staff. We report our recent experiences of managing patients with EVD, with particular focus on those aspects of care pertinent to anaesthesia and critical care medicine. PMID:27106962

  10. Effectiveness of Four Disinfectants against Ebola Virus on Different Materials.

    PubMed

    Smither, Sophie; Phelps, Amanda; Eastaugh, Lin; Ngugi, Sarah; O'Brien, Lyn; Dutch, Andrew; Lever, Mark Stephen

    2016-01-01

    The West Africa Ebola virus (EBOV) outbreak has highlighted the need for effective disinfectants capable of reducing viral load in a range of sample types, equipment and settings. Although chlorine-based products are widely used, they can also be damaging to equipment or apparatus that needs continuous use such as aircraft use for transportation of infected people. Two aircraft cleaning solutions were assessed alongside two common laboratory disinfectants in a contact kill assay with EBOV on two aircraft relevant materials representative of a porous and non-porous surface. A decimal log reduction of viral titre of 4 is required for a disinfectant to be deemed effective and two of the disinfectants fulfilled this criteria under the conditions tested. One product, Ardrox 6092, was found to perform similarly to sodium hypochlorite, but as it does not have the corrosive properties of sodium hypochlorite, it could be an alternative disinfectant solution to be used for decontamination of EBOV on sensitive apparatus. PMID:27399759

  11. Ebola virus disease surveillance and response preparedness in northern Ghana

    PubMed Central

    Adokiya, Martin N.; Awoonor-Williams, John K.

    2016-01-01

    Background The recent Ebola virus disease (EVD) outbreak has been described as unprecedented in terms of morbidity, mortality, and geographical extension. It also revealed many weaknesses and inadequacies for disease surveillance and response systems in Africa due to underqualified staff, cultural beliefs, and lack of trust for the formal health care sector. In 2014, Ghana had high risk of importation of EVD cases. Objective The objective of this study was to assess the EVD surveillance and response system in northern Ghana. Design This was an observational study conducted among 47 health workers (district directors, medical, disease control, and laboratory officers) in all 13 districts of the Upper East Region representing public, mission, and private health services. A semi-structured questionnaire with focus on core and support functions (e.g. detection, confirmation) was administered to the informants. Their responses were recorded according to specific themes. In addition, 34 weekly Integrated Disease Surveillance and Response reports (August 2014 to March 2015) were collated from each district. Results In 2014 and 2015, a total of 10 suspected Ebola cases were clinically diagnosed from four districts. Out of the suspected cases, eight died and the cause of death was unexplained. All the 10 suspected cases were reported, none was confirmed. The informants had knowledge on EVD surveillance and data reporting. However, there were gaps such as delayed reporting, low quality protective equipment (e.g. gloves, aprons), inadequate staff, and lack of laboratory capacity. The majority (38/47) of the respondents were not satisfied with EVD surveillance system and response preparedness due to lack of infrared thermometers, ineffective screening, and lack of isolation centres. Conclusion EVD surveillance and response preparedness is insufficient and the epidemic is a wake-up call for early detection and response preparedness. Ebola surveillance remains a neglected public

  12. Intra-host dynamics of Ebola virus during 2014.

    PubMed

    Ni, Ming; Chen, Chen; Qian, Jun; Xiao, Hai-Xia; Shi, Wei-Feng; Luo, Yang; Wang, Hai-Yin; Li, Zhen; Wu, Jun; Xu, Pei-Song; Chen, Su-Hong; Wong, Gary; Bi, Yuhai; Xia, Zhi-Ping; Li, Wei; Lu, Hui-Jun; Ma, Juncai; Tong, Yi-Gang; Zeng, Hui; Wang, Sheng-Qi; Gao, George F; Bo, Xiao-Chen; Liu, Di

    2016-01-01

    Since 2013, West Africa has encountered the largest Ebola virus (EBOV) disease outbreak on record, and Sierra Leone is the worst-affected country, with nearly half of the infections. By means of next-generation sequencing and phylogeographic analysis, the epidemiology and transmission of EBOV have been well elucidated. However, the intra-host dynamics that mainly reflect viral-host interactions still need to be studied. Here, we show a total of 710 intra-host single nucleotide variations (iSNVs) from deep-sequenced samples from EBOV-infected patients, through a well-tailored bioinformatics pipeline. We present a comprehensive distribution of iSNVs during this outbreak and along the EBOV genome. Analyses of iSNV and its allele frequency reveal that VP40 is the most conserved gene during this outbreak, and thus it would be an ideal therapeutic target. In the co-occurring iSNV network, varied iSNV sites present different selection features. Intriguingly, the T-to-C substitutions at the 3'-UTR of the nucleoprotein (NP; positions 3008 and 3011), observed in many patients, result in the upregulation of the transcription of NP through an Ebola mini-genome reporting system. Additionally, no iSNV enrichment within B-cell epitopes of GP has been observed. PMID:27595345

  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. Initiating a watch list for Ebola virus antibody escape mutations.

    PubMed

    Miller, Craig R; Johnson, Erin L; Burke, Aran Z; Martin, Kyle P; Miura, Tanya A; Wichman, Holly A; Brown, Celeste J; Ytreberg, F Marty

    2016-01-01

    The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens. PMID:26925318

  15. Initiating a watch list for Ebola virus antibody escape mutations

    PubMed Central

    Johnson, Erin L.; Burke, Aran Z.; Martin, Kyle P.; Miura, Tanya A.; Wichman, Holly A.; Brown, Celeste J.

    2016-01-01

    The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens. PMID:26925318

  16. Virus fitness differences observed between two naturally occurring isolates of Ebola virus Makona variant using a reverse genetics approach.

    PubMed

    Albariño, César G; Guerrero, Lisa Wiggleton; Chakrabarti, Ayan K; Kainulainen, Markus H; Whitmer, Shannon L M; Welch, Stephen R; Nichol, Stuart T

    2016-09-01

    During the large outbreak of Ebola virus disease that occurred in Western Africa from late 2013 to early 2016, several hundred Ebola virus (EBOV) genomes have been sequenced and the virus genetic drift analyzed. In a previous report, we described an efficient reverse genetics system designed to generate recombinant EBOV based on a Makona variant isolate obtained in 2014. Using this system, we characterized the replication and fitness of 2 isolates of the Makona variant. These virus isolates are nearly identical at the genetic level, but have single amino acid differences in the VP30 and L proteins. The potential effects of these differences were tested using minigenomes and recombinant viruses. The results obtained with this approach are consistent with the role of VP30 and L as components of the EBOV RNA replication machinery. Moreover, the 2 isolates exhibited clear fitness differences in competitive growth assays. PMID:27366976

  17. The West African ebola virus disease epidemic 2014-2015: A commissioned review.

    PubMed

    Omilabu, S A; Salu, O B; Oke, B O; James, A B

    2016-01-01

    The first epidemic of Ebola haemorrhagic disease in West Africa is the largest and longest Ebola epidemic till date, where the outbreak notably involved three countries with distant spread to other countries. It has caused significant mortality, with reported case fatality rates of up to 70%. Data and relevant information were extracted from the review of majorly relevant publications/papers about the Ebola epidemic in West Africa and other previous outbreaks of Ebola virus (EBOV). As of 2016, with the epidemic under control, the World Health Organization has warned that flare-ups of the disease are likely to continue for some time as recently occurred in Sierra Leone and the on-going in Guinea. As this may not be the last outbreak of Ebola virus disease (EVD) in West Africa, there is a need to focus on diagnostic and research capacity required to curtail EVD with adequate measures for emergency preparedness and policies for innovative treatment strategies. PMID:27424613

  18. Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates.

    PubMed

    Sullivan, Nancy J; Geisbert, Thomas W; Geisbert, Joan B; Xu, Ling; Yang, Zhi-Yong; Roederer, Mario; Koup, Richard A; Jahrling, Peter B; Nabel, Gary J

    2003-08-01

    Containment of highly lethal Ebola virus outbreaks poses a serious public health challenge. Although an experimental vaccine has successfully protected non-human primates against disease, more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. Here, we report the development of accelerated vaccination against Ebola virus in non-human primates. The antibody response to immunization with an adenoviral (ADV) vector encoding the Ebola glycoprotein (GP) was induced more rapidly than with DNA priming and ADV boosting, but it was of lower magnitude. To determine whether this earlier immune response could nonetheless protect against disease, cynomolgus macaques were challenged with Ebola virus after vaccination with ADV-GP and nucleoprotein (NP) vectors. Protection was highly effective and correlated with the generation of Ebola-specific CD8(+) T-cell and antibody responses. Even when animals were immunized once with ADV-GP/NP and challenged 28 days later, they remained resistant to challenge with either low or high doses of virus. This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola, and is applicable to other viruses. PMID:12904795

  19. 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

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

    PubMed

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

    2015-07-01

    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

  1. Implementation of an Ebola virus disease vaccine clinical trial during the Ebola epidemic in Liberia: Design, procedures, and challenges.

    PubMed

    Kennedy, Stephen B; Neaton, James D; Lane, H Clifford; Kieh, Mark W S; Massaquoi, Moses B F; Touchette, Nancy A; Nason, Martha C; Follmann, Dean A; Boley, Fatorma K; Johnson, Melvin P; Larson, Gregg; Kateh, Francis N; Nyenswah, Tolbert G

    2016-02-01

    The index case of the Ebola virus disease epidemic in West Africa is believed to have originated in Guinea. By June 2014, Guinea, Liberia, and Sierra Leone were in the midst of a full-blown and complex global health emergency. The devastating effects of this Ebola epidemic in West Africa put the global health response in acute focus for urgent international interventions. Accordingly, in October 2014, a World Health Organization high-level meeting endorsed the concept of a phase 2/3 clinical trial in Liberia to study Ebola vaccines. As a follow-up to the global response, in November 2014, the Government of Liberia and the US Government signed an agreement to form a research partnership to investigate Ebola and to assess intervention strategies for treating, controlling, and preventing the disease in Liberia. This agreement led to the establishment of the Joint Liberia-US Partnership for Research on Ebola Virus in Liberia as the beginning of a long-term collaborative partnership in clinical research between the two countries. In this article, we discuss the methodology and related challenges associated with the implementation of the Ebola vaccines clinical trial, based on a double-blinded randomized controlled trial, in Liberia. PMID:26768572

  2. Ebola virus encodes a miR-155 analog to regulate importin-α5 expression.

    PubMed

    Liu, Yuanwu; Sun, Jing; Zhang, Hongwen; Wang, Mingming; Gao, George Fu; Li, Xiangdong

    2016-10-01

    The 2014 outbreak of Ebola virus caused more than 10,000 human deaths. Current knowledge of suitable drugs, clinical diagnostic biomarkers and molecular mechanisms of Ebola virus infection is either absent or insufficient. By screening stem-loop structures from the viral genomes of four virulence species, we identified a novel, putative viral microRNA precursor that is specifically expressed by the Ebola virus. The sequence of the microRNA precursor was further confirmed by mining the existing RNA-Seq database. Two putative mature microRNAs were predicted and subsequently validated in human cell lines. Combined with this prediction of the microRNA target, we identified importin-α5, which is a key regulator of interferon signaling following Ebola virus infection, as one putative target. We speculate that this microRNA could facilitate the evasion of the host immune system by the virus. Moreover, this microRNA might be a potential clinical therapeutic target or a diagnostic biomarker for Ebola virus. PMID:27094387

  3. Mechanisms of immunity in post-exposure vaccination against Ebola virus infection.

    PubMed

    Bradfute, Steven B; Anthony, Scott M; Stuthman, Kelly S; Ayithan, Natarajan; Tailor, Prafullakumar; Shaia, Carl I; Bray, Mike; Ozato, Keiko; Bavari, Sina

    2015-01-01

    Ebolaviruses can cause severe hemorrhagic fever that is characterized by rapid viral replication, coagulopathy, inflammation, and high lethality rates. Although there is no clinically proven vaccine or treatment for Ebola virus infection, a virus-like particle (VLP) vaccine is effective in mice, guinea pigs, and non-human primates when given pre-infection. In this work, we report that VLPs protect Ebola virus-infected mice when given 24 hours post-infection. Analysis of cytokine expression in serum revealed a decrease in pro-inflammatory cytokine and chemokine levels in mice given VLPs post-exposure compared to infected, untreated mice. Using knockout mice, we show that VLP-mediated post-exposure protection requires perforin, B cells, macrophages, conventional dendritic cells (cDCs), and either CD4+ or CD8+ T cells. Protection was Ebola virus-specific, as marburgvirus VLPs did not protect Ebola virus-infected mice. Increased antibody production in VLP-treated mice correlated with protection, and macrophages were required for this increased production. However, NK cells, IFN-gamma, and TNF-alpha were not required for post-exposure-mediated protection. These data suggest that a non-replicating Ebola virus vaccine can provide post-exposure protection and that the mechanisms of immune protection in this setting require both increased antibody production and generation of cytotoxic T cells. PMID:25785602

  4. Mechanisms of Immunity in Post-Exposure Vaccination against Ebola Virus Infection

    PubMed Central

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

    2015-01-01

    Ebolaviruses can cause severe hemorrhagic fever that is characterized by rapid viral replication, coagulopathy, inflammation, and high lethality rates. Although there is no clinically proven vaccine or treatment for Ebola virus infection, a virus-like particle (VLP) vaccine is effective in mice, guinea pigs, and non-human primates when given pre-infection. In this work, we report that VLPs protect Ebola virus-infected mice when given 24 hours post-infection. Analysis of cytokine expression in serum revealed a decrease in pro-inflammatory cytokine and chemokine levels in mice given VLPs post-exposure compared to infected, untreated mice. Using knockout mice, we show that VLP-mediated post-exposure protection requires perforin, B cells, macrophages, conventional dendritic cells (cDCs), and either CD4+ or CD8+ T cells. Protection was Ebola virus-specific, as marburgvirus VLPs did not protect Ebola virus-infected mice. Increased antibody production in VLP-treated mice correlated with protection, and macrophages were required for this increased production. However, NK cells, IFN-gamma, and TNF-alpha were not required for post-exposure-mediated protection. These data suggest that a non-replicating Ebola virus vaccine can provide post-exposure protection and that the mechanisms of immune protection in this setting require both increased antibody production and generation of cytotoxic T cells. PMID:25785602

  5. 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.; 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.

  6. 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

  7. 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

  8. Animal models for Ebola and Marburg virus infections.

    PubMed

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

  9. [Real-time PCR Detection Method for the Reston Subtype of the Ebola Virus].

    PubMed

    Xu, Lili; Bao, Linlin; Gu, Songzhi; Qin, Chuan

    2015-05-01

    We aimed to develop a real-time polymerase chain reaction (PCR) detection method for the Reston subtype of the Ebola virus. The NP gene of the Reston subtype of the Ebola virus was selected as the detection object. Sequences of different subtypes of Ebola viruses were aligned using Clustal W software. The most unique and conserved regions of the Reston subtype of the Ebola virus were recruited as candidate sequences for specific primers. Primer Express and Primer Premier 5. 0 software were used to filter the optimal pair of primers for detection. Real-time PCR was carried out using optimized parameters and positive DNA prepared by serial (tenfold) dilution of a recombinant plasmid and by plotting a standard curve. In addition, the reproducibility, accuracy, and specificity of the assay were tested. Results showed that the sensitivity of detection of the Reston subtype of the Ebola virus by real-time PCR could reached 10(2) copies/microL. The linear relationship (R2) reached 0.997, the slope of the standard curve was -0.3101, and amplification efficiency was 110.145%. A sharp and narrow melting peak appeared at 79.94 degrees C for all standards in different dilutions. In conclusion, a fast and sensitive real-time PCR detection system for the Reston subtype of the Ebola virus was developed. This system could be used as a supplementary diagnostic and monitoring approach for basic and clinical studies on the Reston subtype of the Ebola virus. The detection system does not require expensive technology or specialist operators. PMID:26470534

  10. Structural and molecular basis for Ebola virus neutralization by protective human antibodies.

    PubMed

    Misasi, John; Gilman, Morgan S A; Kanekiyo, Masaru; Gui, Miao; Cagigi, Alberto; Mulangu, Sabue; Corti, Davide; Ledgerwood, Julie E; Lanzavecchia, Antonio; Cunningham, James; Muyembe-Tamfun, Jean Jacques; Baxa, Ulrich; Graham, Barney S; Xiang, Ye; Sullivan, Nancy J; McLellan, Jason S

    2016-03-18

    Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines. PMID:26917592

  11. 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-β) 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-α/β 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-α4 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-β gene, by blocking IRF-3 activation. PMID:12829834

  12. RNA binding specificity of Ebola virus transcription factor VP30.

    PubMed

    Schlereth, Julia; Grünweller, Arnold; Biedenkopf, Nadine; Becker, Stephan; Hartmann, Roland K

    2016-09-01

    The transcription factor VP30 of the non-segmented RNA negative strand Ebola virus balances viral transcription and replication. Here, we comprehensively studied RNA binding by VP30. Using a novel VP30:RNA electrophoretic mobility shift assay, we tested truncated variants of 2 potential natural RNA substrates of VP30 - the genomic Ebola viral 3'-leader region and its complementary antigenomic counterpart (each ∼155 nt in length) - and a series of other non-viral RNAs. Based on oligonucleotide interference, the major VP30 binding region on the genomic 3'-leader substrate was assigned to the internal expanded single-stranded region (∼ nt 125-80). Best binding to VP30 was obtained with ssRNAs of optimally ∼ 40 nt and mixed base composition; underrepresentation of purines or pyrimidines was tolerated, but homopolymeric sequences impaired binding. A stem-loop structure, particularly at the 3'-end or positioned internally, supports stable binding to VP30. In contrast, dsRNA or RNAs exposing large internal loops flanked by entirely helical arms on both sides are not bound. Introduction of a 5´-Cap(0) structure impaired VP30 binding. Also, ssDNAs bind substantially weaker than isosequential ssRNAs and heparin competes with RNA for binding to VP30, indicating that ribose 2'-hydroxyls and electrostatic contacts of the phosphate groups contribute to the formation of VP30:RNA complexes. Our results indicate a rather relaxed RNA binding specificity of filoviral VP30, which largely differs from that of the functionally related transcription factor of the Paramyxoviridae which binds to ssRNAs as short as 13 nt with a preference for oligo(A) sequences. PMID:27315567

  13. Positive evolution of the glycoprotein (GP) gene is related to transmission of the Ebola virus.

    PubMed

    Jing, Y X; Wang, L N; Wu, X M; Song, C X

    2016-01-01

    Ebola hemorrhagic fever is a fatal disease caused by the negative-strand RNA of the Ebola virus. A high-intensity outbreak of this fever was reported in West Africa last year; however, there is currently no definitive treatment strategy available for this disease. In this study, we analyzed the molecular evolutionary history and attempted to determine the positive selection sites in the Ebola genes using multiple-genomic sequences of the various Ebola virus subtypes, in order to gain greater clarity into the evolution of the virus and its various subtypes. Only the glycoprotein (GP) gene was positively selected among the 8 Ebola genes, with the other genes remaining in the purification stage. The positive selection sites in the GP gene were identified by a random-site model; these sites were found to be located in the mucin-like region, which is associated with transmembrane protein binding. Additionally, different branches of the phylogenetic tree displayed different positive sites, which in turn was responsible for differences in the cell adhesion ability of the virus. In conclusion, the pattern of positive sites in the GP gene is associated with the epidemiology and prevalence of Ebola in different areas. PMID:27051001

  14. 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

  15. Media coverage of the Ebola virus disease in four widely circulated Nigerian newspapers: lessons from Nigeria

    PubMed Central

    Smith, Sam; Smith, Stella

    2016-01-01

    Background: The importance of the media in the coverage of Ebola virus disease (EVD) in Nigeria and its implications (negative or positive) amongst the populace cannot be overemphasized.This study was conducted to assess the role of media in the Ebola reportage and its implication in creating awareness and stopping the spread amongst the populace. Methods: The nature and extent of media coverage about Ebola in four major national newspapers were examined. The four major national newspapers were The Sun, The Vanguard, The Nation and The Punch newspapers. The period of study ranged from 20 July (when the index case came to Nigeria) to 20 October 2014. Analysis of the newspaper article was according to content. Results: A total of 1625 articles were published between July 2014 to October 2014 and these were divided into news (1127; 69.4%), features (267; 16.4%), opinion (76; 4.7%), editorials (149; 9.2%) and interviews (6; 0.4%). The most common topic was Ebola cases in Nigeria (17.5%) followed by discrimination due to Ebola (10.8%) and least of all the use of salt and or Kola for the cure of Ebola (5.2%). Conclusion: Although the World Health Organization (WHO) declared Nigeria Ebola free on the 20th October 2014, continual reportage of the Ebola disease for effective awareness, prevention and control of the virus is recommended. PMID:27386424

  16. 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

  17. 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

  18. Toremifene interacts with and destabilizes the Ebola virus glycoprotein.

    PubMed

    Zhao, Yuguang; Ren, Jingshan; Harlos, Karl; Jones, Daniel M; Zeltina, Antra; Bowden, Thomas A; Padilla-Parra, Sergi; Fry, Elizabeth E; Stuart, David I

    2016-07-01

    Ebola viruses (EBOVs) are responsible for repeated outbreaks of fatal infections, including the recent deadly epidemic in West Africa. There are currently no approved therapeutic drugs or vaccines for the disease. EBOV has a membrane envelope decorated by trimers of a glycoprotein (GP, cleaved by furin to form GP1 and GP2 subunits), which is solely responsible for host cell attachment, endosomal entry and membrane fusion. GP is thus a primary target for the development of antiviral drugs. Here we report the first, to our knowledge, unliganded structure of EBOV GP, and high-resolution complexes of GP with the anticancer drug toremifene and the painkiller ibuprofen. The high-resolution apo structure gives a more complete and accurate picture of the molecule, and allows conformational changes introduced by antibody and receptor binding to be deciphered. Unexpectedly, both toremifene and ibuprofen bind in a cavity between the attachment (GP1) and fusion (GP2) subunits at the entrance to a large tunnel that links with equivalent tunnels from the other monomers of the trimer at the three-fold axis. Protein–drug interactions with both GP1 and GP2 are predominately hydrophobic. Residues lining the binding site are highly conserved among filoviruses except Marburg virus (MARV), suggesting that MARV may not bind these drugs. Thermal shift assays show up to a 14 °C decrease in the protein melting temperature after toremifene binding, while ibuprofen has only a marginal effect and is a less potent inhibitor. These results suggest that inhibitor binding destabilizes GP and triggers premature release of GP2, thereby preventing fusion between the viral and endosome membranes. Thus, these complex structures reveal the mechanism of inhibition and may guide the development of more powerful anti-EBOV drugs. PMID:27362232

  19. 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

  20. Misconceptions about Ebola virus disease among lay people in Guinea: Lessons for community education.

    PubMed

    Kpanake, Lonzozou; Gossou, Komlantsè; Sorum, Paul Clay; Mullet, Etienne

    2016-05-01

    To characterize the perception of Ebola virus disease (EVD) in Guinea, we administered, from November 2014 to February 2015, a questionnaire to a convenience sample of 200 lay people in Conakry and a group of 8 physicians. We found widespread misconceptions among lay people, including that praying to God can protect against EVD, that traditional healers are more competent than physicians in treating EVD, that people get infected through physical proximity without contact, that the Ebola epidemic is the result of Western bioterrorism experiments, that Western medical staff disseminated the virus, and that the purpose of quarantine measures is to hasten the death of Ebola patients. Major educational interventions, sensitive to local cultural beliefs, are needed to overcome the misconceptions about Ebola in Guinea. PMID:26865320

  1. Circulating microRNA profiles of Ebola virus infection.

    PubMed

    Duy, Janice; Koehler, Jeffrey W; Honko, Anna N; Schoepp, Randal J; Wauquier, Nadia; Gonzalez, Jean-Paul; Pitt, M Louise; Mucker, Eric M; Johnson, Joshua C; O'Hearn, Aileen; Bangura, James; Coomber, Moinya; Minogue, Timothy D

    2016-01-01

    Early detection of Ebola virus (EBOV) infection is essential to halting transmission and adjudicating appropriate treatment. However, current methods rely on viral identification, and this approach can misdiagnose presymptomatic and asymptomatic individuals. In contrast, disease-driven alterations in the host transcriptome can be exploited for pathogen-specific diagnostic biomarkers. Here, we present for the first time EBOV-induced changes in circulating miRNA populations of nonhuman primates (NHPs) and humans. We retrospectively profiled longitudinally-collected plasma samples from rhesus macaques challenged via intramuscular and aerosol routes and found 36 miRNAs differentially present in both groups. Comparison of miRNA abundances to viral loads uncovered 15 highly correlated miRNAs common to EBOV-infected NHPs and humans. As proof of principle, we developed an eight-miRNA classifier that correctly categorized infection status in 64/74 (86%) human and NHP samples. The classifier identified acute infections in 27/29 (93.1%) samples and in 6/12 (50%) presymptomatic NHPs. These findings showed applicability of NHP-derived miRNAs to a human cohort, and with additional research the resulting classifiers could impact the current capability to diagnose presymptomatic and asymptomatic EBOV infections. PMID:27098369

  2. 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

  3. Circulating microRNA profiles of Ebola virus infection

    PubMed Central

    Duy, Janice; Koehler, Jeffrey W.; Honko, Anna N.; Schoepp, Randal J.; Wauquier, Nadia; Gonzalez, Jean-Paul; Pitt, M. Louise; Mucker, Eric M.; Johnson, Joshua C.; O’Hearn, Aileen; Bangura, James; Coomber, Moinya; Minogue, Timothy D.

    2016-01-01

    Early detection of Ebola virus (EBOV) infection is essential to halting transmission and adjudicating appropriate treatment. However, current methods rely on viral identification, and this approach can misdiagnose presymptomatic and asymptomatic individuals. In contrast, disease-driven alterations in the host transcriptome can be exploited for pathogen-specific diagnostic biomarkers. Here, we present for the first time EBOV-induced changes in circulating miRNA populations of nonhuman primates (NHPs) and humans. We retrospectively profiled longitudinally-collected plasma samples from rhesus macaques challenged via intramuscular and aerosol routes and found 36 miRNAs differentially present in both groups. Comparison of miRNA abundances to viral loads uncovered 15 highly correlated miRNAs common to EBOV-infected NHPs and humans. As proof of principle, we developed an eight-miRNA classifier that correctly categorized infection status in 64/74 (86%) human and NHP samples. The classifier identified acute infections in 27/29 (93.1%) samples and in 6/12 (50%) presymptomatic NHPs. These findings showed applicability of NHP-derived miRNAs to a human cohort, and with additional research the resulting classifiers could impact the current capability to diagnose presymptomatic and asymptomatic EBOV infections. PMID:27098369

  4. Evaluation of Ebola Virus Inhibitors for Drug Repurposing.

    PubMed

    Madrid, Peter B; Panchal, Rekha G; Warren, Travis K; Shurtleff, Amy C; Endsley, Aaron N; Green, Carol E; Kolokoltsov, Andrey; Davey, Robert; Manger, Ian D; Gilfillan, Lynne; Bavari, Sina; Tanga, Mary J

    2015-07-10

    A systematic screen of FDA-approved drugs was performed to identify compounds with in vitro antiviral activities against Ebola virus (EBOV). Compounds active (>50% viral inhibition and <30% cellular toxicity) at a single concentration were tested in dose-response assays to quantitate the antiviral activities in replication and viral entry assays as well as cytotoxicity in the Vero cell line used to conduct these assays. On the basis of the approved human dosing, toxicity/tolerability, and pharmacokinetic data, seven of these in vitro hits from different pharmacological classes (chloroquine (CQ), amiodarone, prochlorperazine, benztropine, azithromycin, chlortetracycline, and clomiphene) were evaluated for their in vivo efficacy at a single dose and were administered via either intraperitoneal (ip) or oral route. Initially, azithromycin (100 mg/kg, twice daily, ip), CQ (90 mg/kg, twice daily, ip), and amiodarone (60 mg/kg, twice daily, ip) demonstrated significant increases in survival in the mouse model. After repeat evaluation, only CQ was found to reproducibly give significant efficacy in the mouse model with this dosing regimen. Azithromycin and CQ were also tested in a guinea pig model of EBOV infection over a range of doses, but none of the doses increased survival, and drug-related toxicity was observed at lower doses than in the mouse. These results show the benefits and specific challenges associated with drug repurposing and highlight the need for careful evaluation of approved drugs as rapidly deployable countermeasures against future pandemics. PMID:27622822

  5. Characterizing the transmission dynamics and control of ebola virus disease.

    PubMed

    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

  6. Identification of entry inhibitors of Ebola virus pseudotyped vectors from a myxobacterial compound library.

    PubMed

    Beck, Simon; Henß, Lisa; Weidner, Tatjana; Herrmann, Jennifer; Müller, Rolf; Chao, Yu-Kai; Grimm, Christian; Weber, Christopher; Sliva, Katja; Schnierle, Barbara S

    2016-08-01

    Myxobacteria produce secondary metabolites many of which were described to have various biological effects including anti-fungal, anti-bacterial and anti-viral activity. The majority of these metabolites are novel scaffolds with unique modes-of-action and hence might be potential leads for drug discovery. Here, we tested a myxobacterial natural product library for compounds with inhibitory activity against Ebola virus (EBOV). The assay was performed with a surrogate system using Ebola envelope glycoprotein (GP) pseudotyped lentiviral vectors. EBOV specificity was proven by counter-screening with vesicular stomatitis virus G protein pseudotyped vectors. Two compounds were identified that preferentially inhibited EBOV GP mediated cell entry: Chondramides that act on the actin skeleton but might be too toxic and noricumazole A, a potassium channel inhibitor, which might constitute a novel pathway to inhibit Ebola virus cell entry. PMID:27241689

  7. Ebola Virus Disease Epidemic: What Can the World Learn and Not Learn from West Africa?

    PubMed Central

    Azuine, Romuladus E.; Ekejiuba, Sussan E.; Singh, Gopal K.; Azuine, Magnus A.

    2015-01-01

    With over 4,500 deaths and counting, and new cases identified in two developed countries that are struggling and faltering in their handling of the epidemic, the 2014 Ebola Virus Disease (EVD) epidemic is unlike any of its kind ever encountered. The ability of some poor, resource-limited, developing countries in sub-Saharan Africa to efficiently handle the epidemic within their shores provides some lessons learned for the global health community. Among others, the 2014 EVD epidemic teaches us that it is time to put the “P” back in public and population health around the world. The global health community must support a sustainable strategy to mitigate Ebola virus and other epidemics both within and outside their shores, even after the cameras are gone. Ebola virus must not be called the disease of the poor and developing world.

  8. 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

  9. 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

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

    SciTech Connect

    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.

    2015-11-12

    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. Our 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. In conclusion, 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.

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

    DOE PAGESBeta

    Pinsky, Benjamin A.; Sahoo, Malaya K.; Sandlund, Johanna; Kleman, Marika; Kulkarni, Medha; Grufman, Per; Nygren, Malin; Kwiatkowski, Robert; Baron, Ellen Jo; Tenover, Fred; et al

    2015-11-12

    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. Our 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,more » 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. In conclusion, 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.« less

  12. Prophylactic Efficacy of Quercetin 3-β-O-d-Glucoside against Ebola Virus Infection.

    PubMed

    Qiu, Xiangguo; Kroeker, Andrea; He, Shihua; Kozak, Robert; Audet, Jonathan; Mbikay, Majambu; Chrétien, Michel

    2016-09-01

    Ebola outbreaks occur on a frequent basis, with the 2014-2015 outbreak in West Africa being the largest one ever recorded. This outbreak has resulted in over 11,000 deaths in four African countries and has received international attention and intervention. Although there are currently no approved therapies or vaccines, many promising candidates are undergoing clinical trials, and several have had success in promoting recovery from Ebola. However, these prophylactics and therapeutics have been designed and tested only against the same species of Ebola virus as the one causing the current outbreak. Future outbreaks involving other species would require reformulation and possibly redevelopment. Therefore, a broad-spectrum alternative is highly desirable. We have found that a flavonoid derivative called quercetin 3-β-O-d-glucoside (Q3G) has the ability to protect mice from Ebola even when given as little as 30 min prior to infection. Furthermore, we have demonstrated that this compound targets the early steps of viral entry. Most promisingly, antiviral activity against two distinct species of Ebola virus was seen. This study serves as a proof of principle that Q3G has potential as a prophylactic against Ebola virus infection. PMID:27297486

  13. Systems for rapidly detecting and treating persons with ebola virus disease--United States.

    PubMed

    Koonin, Lisa M; Jamieson, Denise J; Jernigan, John A; Van Beneden, Chris A; Kosmos, Christine; Harvey, Melissa Cole; Pietz, Harald; Bertolli, Jeanne; Perz, Joseph F; Whitney, Cynthia G; Halpin, Alison Sheehan-Laufer; Daley, W Randolph; Pesik, Nicki; Margolis, Gregg S; Tumpey, Abbigail; Tappero, Jordan; Damon, Inger

    2015-03-01

    The U.S. Department of Health and Human Services (HHS), CDC, other U.S. government agencies, the World Health Organization (WHO), and international partners are taking multiple steps to respond to the current Ebola virus disease (Ebola) outbreak in West Africa to reduce its toll there and to reduce the chances of international spread. At the same time, CDC and HHS are working to ensure that persons who have a risk factor for exposure to Ebola and who develop symptoms while in the United States are rapidly identified and isolated, and safely receive treatment. HHS and CDC have actively worked with state and local public health authorities and other partners to accelerate health care preparedness to care for persons under investigation (PUI) for Ebola or with confirmed Ebola. This report describes some of these efforts and their impact. PMID:25742383

  14. Cluster of Ebola Virus Disease Linked to a Single Funeral - Moyamba District, Sierra Leone, 2014.

    PubMed

    Curran, Kathryn G; Gibson, James J; Marke, Dennis; Caulker, Victor; Bomeh, John; Redd, John T; Bunga, Sudhir; Brunkard, Joan; Kilmarx, Peter H

    2016-03-01

    As of February 17, 2016, a total of 14,122 cases (62% confirmed) of Ebola Virus Disease (Ebola) and 3,955 Ebola-related deaths had been reported in Sierra Leone since the epidemic in West Africa began in 2014. A key focus of the Ebola response in Sierra Leone was the promotion and implementation of safe, dignified burials to prevent Ebola transmission by limiting contact with potentially infectious corpses. Traditional funeral practices pose a substantial risk for Ebola transmission through contact with infected bodies, body fluids, contaminated clothing, and other personal items at a time when viral load is high; however, the role of funeral practices in the Sierra Leone epidemic and ongoing Ebola transmission has not been fully characterized. In September 2014, a sudden increase in the number of reported Ebola cases occurred in Moyamba, a rural and previously low-incidence district with a population of approximately 260,000. The Sierra Leone Ministry of Health and Sanitation and CDC investigated and implemented public health interventions to control this cluster of Ebola cases, including community engagement, active surveillance, and close follow-up of contacts. A retrospective analysis of cases that occurred during July 11-October 31, 2014, revealed that 28 persons with confirmed Ebola had attended the funeral of a prominent pharmacist during September 5-7, 2014. Among the 28 attendees with Ebola, 21 (75%) reported touching the man's corpse, and 16 (57%) reported having direct contact with the pharmacist before he died. Immediate, safe, dignified burials by trained teams with appropriate protective equipment are critical to interrupt transmission and control Ebola during times of active community transmission; these measures remain important during the current response phase. PMID:26938950

  15. 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

  16. Blood kinetics of Ebola virus in survivors and nonsurvivors

    PubMed Central

    Lanini, Simone; Portella, Gina; Vairo, Francesco; Kobinger, Gary P.; Pesenti, Antonio; Langer, Martin; Kabia, Soccoh; Brogiato, Giorgio; Amone, Jackson; Castilletti, Concetta; Miccio, Rossella; Zumla, Alimuddin; Capobianchi, Maria Rosaria; Di Caro, Antonino; Strada, Gino; Ippolito, Giuseppe

    2015-01-01

    BACKGROUND. Infection with Ebola virus (EBOV) results in a life-threatening disease, with reported mortality rates between 50%–70%. The factors that determine patient survival are poorly understood; however, clinical observations indicate that EBOV viremia may be associated with fatal outcome. We conducted a study of the kinetics of Zaire EBOV viremia in patients with EBOV disease (EVD) who were managed at an Ebola Treatment Centre in Sierra Leone during the recent West African outbreak. METHODS. Data from 84 EVD patients (38 survivors, 46 nonsurvivors) were analyzed, and EBOV viremia was quantified between 2 and 13 days after symptom onset. Time since symptom onset and clinical outcome were used as independent variables to compare EBOV viral kinetics in survivors and nonsurvivors. RESULTS. In all patients, EBOV viremia kinetics was a quadratic function of time; however, EBOV viremia was 0.94 logarithm (log) copies per ml (cp/ml) (P = 0.011) higher in nonsurvivors than in survivors from day 2 after the onset of symptoms. Survivors reached peak viremia levels at an earlier time after symptom onset than nonsurvivors (day 5 versus day 7) and had lower mean peak viremia levels compared with nonsurvivors (7.46 log cp/ml; 95% CI, 7.17–7.76 vs. 8.60 log cp/ml; 95% CI, 8.27–8.93). Before reaching peak values, EBOV viremia similarly increased both in survivors and nonsurvivors; however, the decay of viremia after the peak was much stronger in survivors than in nonsurvivors. CONCLUSION. Our results demonstrate that plasma concentrations of EBOV are markedly different between survivors and nonsurvivors at very early time points after symptom onset and may be predicative of outcome. Further studies focused on the early phase of the disease will be required to identify the causal and prognostic factors that determine patient outcome. FUNDING. Italian Ministry of Health; Italian Ministry of Foreign Affairs; EMERGENCY’s private donations; and Royal Engineers for DFID

  17. Development of a preventive vaccine for Ebola virus infection in primates.

    PubMed

    Sullivan, N J; Sanchez, A; Rollin, P E; Yang, Z Y; Nabel, G J

    2000-11-30

    Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype, one of four strains identified to date. Its rapid progression allows little opportunity to develop natural immunity, and there is currently no effective anti-viral therapy. Therefore, vaccination offers a promising intervention to prevent infection and limit spread. Here we describe a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of DNA immunization and boosting with adenoviral vectors that encode viral proteins generated cellular and humoral immunity in cynomolgus macaques. Challenge with a lethal dose of the highly pathogenic, wild-type, 1976 Mayinga strain of Ebola Zaire virus resulted in uniform infection in controls, who progressed to a moribund state and death in less than one week. In contrast, all vaccinated animals were asymptomatic for more than six months, with no detectable virus after the initial challenge. These findings demonstrate that it is possible to develop a preventive vaccine against Ebola virus infection in primates. PMID:11117750

  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. Ultrasensitive Detection of Ebola Virus Oligonucleotide Based on Upconversion Nanoprobe/Nanoporous Membrane System.

    PubMed

    Tsang, Ming-Kiu; Ye, WeiWei; Wang, Guojing; Li, Jingming; Yang, Mo; Hao, Jianhua

    2016-01-26

    Ebola outbreaks are currently of great concern, and therefore, development of effective diagnosis methods is urgently needed. The key for lethal virus detection is high sensitivity, since early-stage detection of virus may increase the probability of survival. Here, we propose a luminescence scheme of assay consisting of BaGdF5:Yb/Er upconversion nanoparticles (UCNPs) conjugated with oligonucleotide probe and gold nanoparticles (AuNPs) linked with target Ebola virus oligonucleotide. As a proof of concept, a homogeneous assay was fabricated and tested, yielding a detection limit at picomolar level. The luminescence resonance energy transfer is ascribed to the spectral overlapping of upconversion luminescence and the absorption characteristics of AuNPs. Moreover, we anchored the UCNPs and AuNPs on a nanoporous alumina (NAAO) membrane to form a heterogeneous assay. Importantly, the detection limit was greatly improved, exhibiting a remarkable value at the femtomolar level. The enhancement is attributed to the increased light-matter interaction throughout the nanopore walls of the NAAO membrane. The specificity test suggested that the nanoprobes were specific to Ebola virus oligonucleotides. The strategy combining UCNPs, AuNPs, and NAAO membrane provides new insight into low-cost, rapid, and ultrasensitive detection of different diseases. Furthermore, we explored the feasibility of clinical application by using inactivated Ebola virus samples. The detection results showed great potential of our heterogeneous design for practical application. PMID:26720408

  20. [Research of Human-mouse Chimeric Antibodies Against Ebola Virus Nucleoprotein].

    PubMed

    Zhou, Rongping; Sun, Lina; Liu, Yang; Wu, Wei; Li, Chuan; Liang, Mifang; Qiu, Peihong

    2016-01-01

    The Ebola virus is highly infectious and can result in death in ≤ 90% of infected subjects. Detection of the Ebola virus and diagnosis of infection are extremely important for epidemic control. Presently, Chinese laboratories detect the nucleic acids of the Ebola virus by real-time reverse transcription-polymerase chain reaction (RT-PCR). However, such detection takes a relatively long time and necessitates skilled personnel and expensive equipment. Enzyme-linked immunosorbent assay (ELISA) of serum is simple, easy to operate, and can be used to ascertain if a patient is infected with the Ebola virus as well as the degree of infection. Hence, ELISA can be used in epidemiological investigations and is a strong complement to detection of nucleic acids. Cases of Ebola hemorrhagic fever have not been documented in China, so quality-control material for positive serology is needed. Construction and expression of human-mouse chimeric antibodies against the nucleoprotein of the Ebola virus was carried out. Genes encoding variable heavy (VH) and variable light (VL) chains were extracted and amplified from murine hybridoma cells. Genes encoding the VH and VL chains of monoclonal antibodies were amplified by RT-PCR. According to sequence analyses, a primer was designed to amplify functional sequences relative to VH and VL chain. The eukaryotic expression vector HL51-14 carrying some human antibody heavy chain- and light chain-constant regions was used. IgG antibodies were obtained by transient transfection of 293T cells. Subsequently, immunological detection and immunological identification were identified by ELISA, immunofluorescence assay, and western blotting. These results showed that we constructed and purified two human- mouse chimeric antibodies. PMID:27295878

  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. Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses

    PubMed Central

    Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Howell, Katie A.; Patel, Sonal J.; Gunn, Bronwyn; Karim, Marcus; Lai, Jonathan R.; Frei, Julia C.; Nyakatura, Elisabeth K.; Zeitlin, Larry; Douglas, Robin; Fusco, Marnie L.; Froude, Jeffrey W.; Saphire, Erica Ollmann; Herbert, Andrew S.; Wirchnianski, Ariel S.; Lear-Rooney, Calli M.; Alter, Galit; Dye, John M.; Glass, Pamela J.; Warfield, Kelly L.

    2015-01-01

    ABSTRACT The unprecedented 2014-2015 Ebola virus disease (EVD) outbreak in West Africa has highlighted the need for effective therapeutics against filoviruses. Monoclonal antibody (MAb) cocktails have shown great potential as EVD therapeutics; however, the existing protective MAbs are virus species specific. Here we report the development of pan-ebolavirus and pan-filovirus antibodies generated by repeated immunization of mice with filovirus glycoproteins engineered to drive the B cell responses toward conserved epitopes. Multiple pan-ebolavirus antibodies were identified that react to the Ebola, Sudan, Bundibugyo, and Reston viruses. A pan-filovirus antibody that was reactive to the receptor binding regions of all filovirus glycoproteins was also identified. Significant postexposure efficacy of several MAbs, including a novel antibody cocktail, was demonstrated. For the first time, we report cross-neutralization and in vivo protection against two highly divergent filovirus species, i.e., Ebola virus and Sudan virus, with a single antibody. Competition studies indicate that this antibody targets a previously unrecognized conserved neutralizing epitope that involves the glycan cap. Mechanistic studies indicated that, besides neutralization, innate immune cell effector functions may play a role in the antiviral activity of the antibodies. Our findings further suggest critical novel epitopes that can be utilized to design effective cocktails for broad protection against multiple filovirus species. IMPORTANCE Filoviruses represent a major public health threat in Africa and an emerging global concern. Largely driven by the U.S. biodefense funding programs and reinforced by the 2014 outbreaks, current immunotherapeutics are primarily focused on a single filovirus species called Ebola virus (EBOV) (formerly Zaire Ebola virus). However, other filoviruses including Sudan, Bundibugyo, and Marburg viruses have caused human outbreaks with mortality rates as high as 90%. Thus

  3. Inflammatory responses in Ebola virus-infected patients

    PubMed Central

    BAIZE, S; LEROY, E M; GEORGES, A J; GEORGES-COURBOT, M-C; CAPRON, M; BEDJABAGA, I; LANSOUD-SOUKATE, J; MAVOUNGOU, E

    2002-01-01

    Ebola virus subtype Zaire (Ebo-Z) induces acute haemorrhagic fever and a 60–80% mortality rate in humans. Inflammatory responses were monitored in victims and survivors of Ebo-Z haemorrhagic fever during two recent outbreaks in Gabon. Survivors were characterized by a transient release in plasma of interleukin-1β (IL-1β), IL-6, tumour necrosis factor-α (TNFα), macrophage inflammatory protein-1α (MIP-1α) and MIP-1β early in the disease, followed by circulation of IL-1 receptor antagonist (IL-1RA) and soluble receptors for TNFα (sTNF-R) and IL-6 (sIL-6R) towards the end of the symptomatic phase and after recovery. Fatal infection was associated with moderate levels of TNFα and IL-6, and high levels of IL-10, IL-1RA and sTNF-R, in the days before death, while IL-1β was not detected and MIP-1α and MIP-1β concentrations were similar to those of endemic controls. Simultaneous massive activation of monocytes/macrophages, the main target of Ebo-Z, was suggested in fatal infection by elevated neopterin levels. Thus, presence of IL-1β and of elevated concentrations of IL-6 in plasma during the symptomatic phase can be used as markers of non-fatal infection, while release of IL-10 and of high levels of neopterin and IL-1RA in plasma as soon as a few days after the disease onset is indicative of a fatal outcome. In conclusion, recovery from Ebo-Z infection is associated with early and well-regulated inflammatory responses, which may be crucial in controlling viral replication and inducing specific immunity. In contrast, defective inflammatory responses and massive monocyte/macrophage activation were associated with fatal outcome. PMID:11982604

  4. 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

  5. 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

  6. Ebola Virus Disease: Ethics and Emergency Medical Response Policy.

    PubMed

    Jecker, Nancy S; Dudzinski, Denise M; Diekema, Douglas S; Tonelli, Mark

    2015-09-01

    Caring for patients affected with Ebola virus disease (EVD) while simultaneously preventing EVD transmission represents a central ethical challenge of the EVD epidemic. To address this challenge, we propose a model policy for resuscitation and emergent procedure policy of patients with EVD and set forth ethical principles that lend support to this policy. The policy and principles we propose bear relevance beyond the EVD epidemic, offering guidance for the care of patients with other highly contagious, virulent, and lethal diseases. The policy establishes (1) a limited code status for patients with confirmed or suspected EVD. Limited code status means that a code blue will not be called for patients with confirmed or suspected EVD at any stage of the disease; however, properly protected providers (those already in full protective equipment) may initiate resuscitative efforts if, in their clinical assessment, these efforts are likely to benefit the patient. The policy also requires that (2) resuscitation not be attempted for patients with advanced EVD, as resuscitation would be medically futile; (3) providers caring for or having contact with patients with confirmed or suspected EVD be properly protected and trained; (4) the treating team identify and treat in advance likely causes of cardiac and respiratory arrest to minimize the need for emergency response; (5) patients with EVD and their proxies be involved in care discussions; and (6) care team and provider discretion guide the care of patients with EVD. We discuss ethical issues involving medical futility and the duty to avoid harm and propose a utilitarian-based principle of triage to address resource scarcity in the emergency setting. PMID:25855946

  7. 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

  8. Ebola Virus RNA Stability in Human Blood and Urine in West Africa’s Environmental Conditions

    PubMed Central

    Delaune, Deborah; Poyot, Thomas; Valade, Eric; Mérens, Audrey; Rollin, Pierre E.; Foissaud, Vincent

    2016-01-01

    We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa’s environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly. PMID:26812135

  9. Thromboelastography in the Management of Coagulopathy Associated With Ebola Virus Disease.

    PubMed

    Wilson, Andrew J; Martin, Daniel S; Maddox, Victoria; Rattenbury, Simon; Bland, Davis; Bhagani, Sanjay; Cropley, Ian; Hopkins, Susan; Mepham, Stephen; Rodger, Alison; Warren, Simon; Chowdary, Pratima; Jacobs, Michael

    2016-03-01

    Here, we describe the first use of thromboelastography (TEG) in the management of 2 cases of Ebola virus disease. Early in their illness, both patients had evidence of a consumptive coagulopathy. As this resolved, TEG demonstrated that both developed a marked hypercoagulable state, which was treated with low-molecular-weight heparin. PMID:26611775

  10. 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

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

    PubMed

    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

    2015-05-21

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

  12. Perspectives on West Africa Ebola Virus Disease Outbreak, 2013-2016

    DOE PAGESBeta

    Spengler, Jessica R.; Ervin, Elizabeth D.; Towner, Jonathan S.; Rollin, Pierre E.; Nichol, Stuart T.

    2016-06-01

    The variety of factors that contributed to the initial undetected spread of Ebola virus disease in West Africa during 2013-2016 and the difficulty controlling the outbreak once the etiology was identified highlight priorities for disease prevention, detection, and response. These factors include occurrence in a region recovering from civil instability and lacking experience with Ebola response; inadequate surveillance, recognition of suspected cases, and Ebola diagnosis; mobile populations and extensive urban transmission; and the community's insufficient general understanding about the disease. The magnitude of the outbreak was not attributable to a substantial change of the virus. Finally, continued efforts during themore » outbreak and in preparation for future outbreak response should involve identifying the reservoir, improving in-country detection and response capacity, conducting survivor studies and supporting survivors, engaging in culturally appropriate public education and risk communication, building productive interagency relationships, and continuing support for basic research.« less

  13. Perspectives on West Africa Ebola Virus Disease Outbreak, 2013–2016

    PubMed Central

    Spengler, Jessica R.; Ervin, Elizabeth D.; Towner, Jonathan S.; Rollin, Pierre E.

    2016-01-01

    The variety of factors that contributed to the initial undetected spread of Ebola virus disease in West Africa during 2013–2016 and the difficulty controlling the outbreak once the etiology was identified highlight priorities for disease prevention, detection, and response. These factors include occurrence in a region recovering from civil instability and lacking experience with Ebola response; inadequate surveillance, recognition of suspected cases, and Ebola diagnosis; mobile populations and extensive urban transmission; and the community’s insufficient general understanding about the disease. The magnitude of the outbreak was not attributable to a substantial change of the virus. Continued efforts during the outbreak and in preparation for future outbreak response should involve identifying the reservoir, improving in-country detection and response capacity, conducting survivor studies and supporting survivors, engaging in culturally appropriate public education and risk communication, building productive interagency relationships, and continuing support for basic research. PMID:27070842

  14. Perspectives on West Africa Ebola Virus Disease Outbreak, 2013-2016.

    PubMed

    Spengler, Jessica R; Ervin, Elizabeth D; Towner, Jonathan S; Rollin, Pierre E; Nichol, Stuart T

    2016-06-01

    The variety of factors that contributed to the initial undetected spread of Ebola virus disease in West Africa during 2013-2016 and the difficulty controlling the outbreak once the etiology was identified highlight priorities for disease prevention, detection, and response. These factors include occurrence in a region recovering from civil instability and lacking experience with Ebola response; inadequate surveillance, recognition of suspected cases, and Ebola diagnosis; mobile populations and extensive urban transmission; and the community's insufficient general understanding about the disease. The magnitude of the outbreak was not attributable to a substantial change of the virus. Continued efforts during the outbreak and in preparation for future outbreak response should involve identifying the reservoir, improving in-country detection and response capacity, conducting survivor studies and supporting survivors, engaging in culturally appropriate public education and risk communication, building productive interagency relationships, and continuing support for basic research. PMID:27070842

  15. 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.

  16. Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

    PubMed Central

    Iversen, Patrick L.; Warren, Travis K.; Wells, Jay B.; Garza, Nicole L.; Mourich, Dan V.; Welch, Lisa S.; Panchal, Rekha G.; Bavari, Sina

    2012-01-01

    There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates. PMID:23202506

  17. An "Urban legend" of global proportion: an analysis of nonfiction accounts of the Ebola virus.

    PubMed

    Weldon, R A

    2001-01-01

    Using Brunvald's (1981) six criteria of successful urban legends, this study explores nonfiction accounts of the Ebola virus. Focusing particularly on Richard Preston's book The Hot Zone (1994), this study addresses the social construction of the predatorial virus, demonstrating how events are constructed as social problems via media representations, and reality is transformed into legend. The implications of these depictions of the predatorial virus are discussed, along with exploring the effects of mass media reports on health care beliefs and practices. Likewise, implications regarding these stories, cultural beliefs and values are discussed. PMID:11550594

  18. United States FDA's emergency use authorization of Ebola virus diagnostics: current impact and lessons for the future.

    PubMed

    Whitehouse, Chris A; Bavari, Sina; Perkins, Mark D

    2015-01-01

    The Ebola outbreak that took hold in West Africa in 2014 outran the epidemic response capacity of many organizations. Five months after the epidemic was first declared, there were still only two laboratories in West Africa with the capacity to confirm Ebola virus infection. In the summer of 2014, before the first case of imported Ebola occurred in the USA, the US FDA announced it would issue Emergency Use Authorizations for Ebola virus in vitro diagnostics to speed their availability. Between October 2014 and March 2015, the FDA issued Emergency Use Authorizations for nine diagnostic products. The actions of the FDA not only allowed nationwide deployment of Ebola virus testing capacity in the USA but also established an attractive regulatory goalpost for companies developing assays for use in West Africa. Here, we comment on the diagnostic assays for which the FDA has issued emergency authorizations and their fitness for purpose. PMID:26394699

  19. Vaccine To Confer to Nonhuman Primates Complete Protection against Multistrain Ebola and Marburg Virus Infections▿

    PubMed Central

    Swenson, Dana L.; Wang, Danher; Luo, Min; Warfield, Kelly L.; Woraratanadharm, Jan; Holman, David H.; Dong, John Y.; Pratt, William D.

    2008-01-01

    Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack. PMID:18216185

  20. Improving burial practices and cemetery management during an Ebola virus disease epidemic - Sierra Leone, 2014.

    PubMed

    Nielsen, Carrie F; Kidd, Sarah; Sillah, Ansumana R M; Davis, Edward; Mermin, Jonathan; Kilmarx, Peter H

    2015-01-16

    As of January 3, 2015, Ebola virus disease (Ebola) has killed more than 2,500 persons in Sierra Leone since the epidemic began there in May 2014. Ebola virus is transmitted principally by direct physical contact with an infected person or their body fluids during the later stages of illness or after death. Contact with the bodies and fluids of persons who have died of Ebola is especially common in West Africa, where family and community members often touch and wash the body of the deceased in preparation for funerals. These cultural practices have been a route of Ebola transmission. In September 2014, CDC, in collaboration with the Sierra Leone Ministry of Health and Sanitation (MOH), assessed burial practices, cemetery management, and adherence to practices recommended to reduce the risk for Ebola virus transmission. The assessment was conducted by directly observing burials and cemetery operations in three high-incidence districts. In addition, a community assessment was conducted to assess the acceptability to the population of safe, nontraditional burial practices and cemetery management intended to reduce the risk for Ebola virus transmission. This report summarizes the results of these assessments, which found that 1) there were not enough burial teams to manage the number of reported deaths, 2) Ebola surveillance, swab collection, and burial team responses to a dead body alert were not coordinated, 3) systematic procedures for testing and reporting of Ebola laboratory results for dead bodies were lacking, 4) cemetery space and management were inadequate, and 5) safe burial practices, as initially implemented, were not well accepted by communities. These findings were used to inform the development of a national standard operating procedure (SOP) for safe, dignified medical burials, released on October 1. A second, national-level, assessment was conducted during October 10-15 to assess burial team practices and training and resource needs for SOP

  1. 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

  2. Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice

    PubMed Central

    Konduru, Krishnamurthy; Bradfute, Steven B.; Jacques, Jerome; Manangeeswaran, Mohanraj; Nakamura, Siham; Morshed, Sufi; Wood, Steven C.; Bavari, Sina

    2011-01-01

    Ebola virus is a Filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. Filoviruses are classified as "Category A bioterrorism agents", and currently there are no licensed therapeutics or vaccines to treat and prevent infection. The Filovirus glycoprotein (GP) is sufficient to protect individuals against infection, and several vaccines based on GP are under development including recombinant adenovirus, parainfluenza virus, Venezuelan equine encephalitis virus, vesicular stomatitis virus (VSV) and virus-like particles. Here we describe the development of a GP Fc fusion protein as a vaccine candidate. We expressed the extracellular domain of the Zaire Ebola virus (ZEBOV) GP fused to the Fc fragment of human IgG1 (ZEBOVGP-Fc) in mammalian cells and showed that GP undergoes the complex furin cleavage and processing observed in the native membrane-bound GP. Mice immunized with ZEBOVGP-Fc developed T-cell immunity against ZEBOV GP and neutralizing antibodies against replication-competent VSV-G deleted recombinant VSV containing ZEBOV GP. The ZEBOVGP-Fc vaccinated mice were protected against challenge with a lethal dose of ZEBOV. These results show that vaccination with the ZEBOVGP-Fc fusion protein alone without the need of a viral vector or assembly into virus-like particles is sufficient to induce protective immunity against ZEBOV in mice. Our data suggested that Filovirus GP Fc fusion proteins could be developed as a simple, safe, efficacious, and cost effective vaccine against Filovirus infection for human use. PMID:21329775

  3. A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose

    PubMed Central

    Tsuda, Yoshimi; Parkins, Christopher J.; Caposio, Patrizia; Feldmann, Friederike; Botto, Sara; Ball, Susan; Messaoudi, Ilhem; Cicin-Sain, Luka; Feldmann, Heinz; Jarvis, Michael A.

    2015-01-01

    Ebola virus (Zaire ebolavirus; EBOV) is a highly lethal hemorrhagic disease virus that most recently was responsible for two independent 2014 outbreaks in multiple countries in Western Africa, and the Democratic Republic of the Congo, respectively. Herein, we show that a cytomegalovirus (CMV)-based vaccine provides durable protective immunity from Ebola virus following a single vaccine dose. This study has implications for human vaccination against ebolaviruses, as well as for development of a ‘disseminating’ vaccine to target these viruses in wild African great apes. PMID:25820063

  4. Community quarantine to interrupt Ebola virus transmission - Mawah Village, Bong County, Liberia, August-October, 2014.

    PubMed

    Nyenswah, Tolbert; Blackley, David J; Freeman, Tabeh; Lindblade, Kim A; Arzoaquoi, Samson K; Mott, Joshua A; Williams, Justin N; Halldin, Cara N; Kollie, Francis; Laney, A Scott

    2015-02-27

    On September 30, 2014, the Bong County health officer notified the county Ebola task force of a growing outbreak of Ebola virus disease (Ebola) in Mawah, a village of approximately 800 residents. During September 9-16, household quarantine had been used by the community in response to a new Ebola infection. Because the infection led to a local outbreak that grew during September 17-20, county authorities suggested community quarantine be considered, and beginning on approximately September 20, the Fuamah District Ebola Task Force (Task Force) engaged Mawah leaders to provide education about Ebola and to secure cooperation for the proposed measures. On September 30, Bong County requested technical assistance to develop strategies to limit transmission in the village and to prevent spread to other areas. The county health team, with support from the Task Force and CDC, traveled to Mawah on October 1 and identified approximately two dozen residents reporting symptoms consistent with Ebola. Because of an ambulance shortage, 2 days were required, beginning October 1, to transport the patients to an Ebola treatment unit in Monrovia. Community quarantine measures, consisting of restrictions on entering or leaving Mawah, regulated river crossings, and market closures, were implemented on October 1. Local leaders raised concerns about availability of medical care and food. The local clinic was reopened on October 11, and food was distributed on October 12. The Task Force reported a total of 22 cases of Ebola in Mawah during September 9-October 2, of which 19 were fatal. During October 3-November 21, no new cases were reported in the village. Involving community members during planning and implementation helped support a safe and effective community quarantine in Mawah. PMID:25719679

  5. 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

  6. Requirements for Cell Rounding and Surface Protein Down-Regulation by Ebola Virus Glycoprotein

    PubMed Central

    Francica, Joseph R.; Matukonis, Meghan K.; Bates, Paul

    2009-01-01

    Ebola virus causes an acute hemorrhagic fever that is associated with high morbidity and mortality. The viral glycoprotein is thought to contribute to pathogenesis, though precise mechanisms are unknown. Cellular pathogenesis can be modeled in vitro by expression of the Ebola viral glycoprotein (GP) in cells, which causes dramatic morphological changes, including cell rounding and surface protein down-regulation. These effects are known to be dependent on the presence of a highly glycosylated region of the glycoprotein, the mucin domain. Here we show that the mucin domain from the highly pathogenic Zaire subtype of Ebola virus is sufficient to cause characteristic cytopathology when expressed in the context of a foreign glycoprotein. Similarly to full length Ebola GP, expression of the mucin domain causes rounding, detachment from the extracellular matrix, and the down-regulation of cell surface levels of β1 integrin and major histocompatibility complex class 1. These effects were not seen when the mucin domain was expressed in the context of a glycophosphatidylinositol-anchored isoform of the foreign glycoprotein. In contrast to earlier analysis of full length Ebola glycoproteins, chimeras carrying the mucin domains from the Zaire and Reston strains appear to cause similar levels of down-modulation and cell detachment. Cytopathology associated with Ebola glycoprotein expression does not occur when GP expression is restricted to the endoplasmic reticulum. In contrast to a previously published report, our results demonstrate that GP-induced surface protein down-regulation is not mediated through a dynamin-dependent pathway. Overall, these results support a model in which the mucin domain of Ebola GP acts at the cell surface to induce protein down modulation and cytopathic effects. PMID:19013626

  7. An Improved Ward Architecture for Treatment of Patients with Ebola Virus Disease in Liberia.

    PubMed

    You, Jianping; Mao, Qing

    2016-04-01

    During the recent outbreak of Ebola virus disease (EVD) in west Africa, we established an Ebola treatment center (ETC) with improved ward architecture. The ETC was built with movable prefabricated boards according to infectious disease unit standard requirements. The clinical staff ensured their own security while providing patients with effective treatment. Of the 180 admissions to the ETC, 10 cases were confirmed with EVD of which six patients survived. None of the clinical staff was infected. We hope that our experience will enable others to avoid unnecessary risks while delivering EVD care. PMID:26755568

  8. In Silico Study of Plant Polyphenols' Interactions with VP24-Ebola Virus Membrane-associated Protein.

    PubMed

    Pleško, Sebastian; Volk, Helena; Lukšič, Miha; Podlipnik, Črtomir

    2015-01-01

    The Zaire Ebola viral protein VP24 selectively inhibits nuclear import of STAT1 and as such blocks interferon-induced antiviral responses vital for cell's emergency. Inhibition of VP24 with small molecule inhibitor may neutralize the threatening action of Ebola virus. We performed molecular docking of compounds from a selected small library of plant polyphenols on to VP24. Our research shows that 1,2,3,6-tetragalloyl glucose, epigallocatechin gallate, chlorogenic acic, oleuropein and miquelianin represent promising leads for further studies. PMID:26454589

  9. Ethical challenges posed by the Ebola virus epidemic in West Africa.

    PubMed

    Omonzejele, Peter F

    2014-12-01

    This paper examines how people in West Africa are reacting to the Ebola virus disease, an epidemic presently prevalent in the region. Certain lifestyle changes are suggested. Additionally, the heart of the paper focuses on the request by governments to be allowed access to experimental drugs, such as Zmapp and TKM-Ebola, for their infected populations. The author argues that granting such a request would circumvent research ethics procedures, which could potentially constitute significant risk to users of the drugs. The Pfizer Kano meningitis trial of 1996 is cited as an example to buttress how unapproved drugs could prove fatal. PMID:25387576

  10. Assessment of the potential for international dissemination of Ebola virus via commercial air travel during the 2014 west African outbreak

    PubMed Central

    Bogoch, Isaac I; Creatore, Maria I; Cetron, Martin S; Brownstein, John S; Pesik, Nicki; Miniota, Jennifer; Tam, Theresa; Hu, Wei; Nicolucci, Adriano; Ahmed, Saad; Yoon, James W; Berry, Isha; Hay, Simon I; Anema, Aranka; Tatem, Andrew J; MacFadden, Derek; German, Matthew; Khan, Kamran

    2015-01-01

    Summary Background The WHO declared the 2014 west African Ebola epidemic a public health emergency of international concern in view of its potential for further international spread. Decision makers worldwide are in need of empirical data to inform and implement emergency response measures. Our aim was to assess the potential for Ebola virus to spread across international borders via commercial air travel and assess the relative efficiency of exit versus entry screening of travellers at commercial airports. Methods We analysed International Air Transport Association data for worldwide flight schedules between Sept 1, 2014, and Dec 31, 2014, and historic traveller flight itinerary data from 2013 to describe expected global population movements via commercial air travel out of Guinea, Liberia, and Sierra Leone. Coupled with Ebola virus surveillance data, we modelled the expected number of internationally exported Ebola virus infections, the potential effect of air travel restrictions, and the efficiency of airport-based traveller screening at international ports of entry and exit. We deemed individuals initiating travel from any domestic or international airport within these three countries to have possible exposure to Ebola virus. We deemed all other travellers to have no significant risk of exposure to Ebola virus. Findings Based on epidemic conditions and international flight restrictions to and from Guinea, Liberia, and Sierra Leone as of Sept 1, 2014 (reductions in passenger seats by 51% for Liberia, 66% for Guinea, and 85% for Sierra Leone), our model projects 2·8 travellers infected with Ebola virus departing the above three countries via commercial flights, on average, every month. 91 547 (64%) of all air travellers departing Guinea, Liberia, and Sierra Leone had expected destinations in low-income and lower-middle-income countries. Screening international travellers departing three airports would enable health assessments of all travellers at highest risk

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Clinical inquiries regarding Ebola virus disease received by CDC--United States, July 9-November 15, 2014.

    PubMed

    Karwowski, Mateusz P; Meites, Elissa; Fullerton, Kathleen E; Ströher, Ute; Lowe, Luis; Rayfield, Mark; Blau, Dianna M; Knust, Barbara; Gindler, Jacqueline; Van Beneden, Chris; Bialek, Stephanie R; Mead, Paul; Oster, Alexandra M

    2014-12-12

    Since early 2014, there have been more than 6,000 reported deaths from Ebola virus disease (Ebola), mostly in Guinea, Liberia, and Sierra Leone. On July 9, 2014, CDC activated its Emergency Operations Center for the Ebola outbreak response and formalized the consultation service it had been providing to assist state and local public health officials and health care providers evaluate persons in the United States thought to be at risk for Ebola. During July 9-November 15, CDC responded to clinical inquiries from public health officials and health care providers from 49 states and the District of Columbia regarding 650 persons thought to be at risk. Among these, 118 (18%) had initial signs or symptoms consistent with Ebola and epidemiologic risk factors placing them at risk for infection, thereby meeting the definition of persons under investigation (PUIs). Testing was not always performed for PUIs because alternative diagnoses were made or symptoms resolved. In total, 61 (9%) persons were tested for Ebola virus, and four, all of whom met PUI criteria, had laboratory-confirmed Ebola. Overall, 490 (75%) inquiries concerned persons who had neither traveled to an Ebola-affected country nor had contact with an Ebola patient. Appropriate medical evaluation and treatment for other conditions were noted in some instances to have been delayed while a person was undergoing evaluation for Ebola. Evaluating and managing persons who might have Ebola is one component of the overall approach to domestic surveillance, the goal of which is to rapidly identify and isolate Ebola patients so that they receive appropriate medical care and secondary transmission is prevented. Health care providers should remain vigilant and consult their local and state health departments and CDC when assessing ill travelers from Ebola-affected countries. Most of these persons do not have Ebola; prompt diagnostic assessments, laboratory testing, and provision of appropriate care for other conditions are

  17. 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

  18. 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

  19. Bioengineering of Tobacco Mosaic Virus to Create a Non-Infectious Positive Control for Ebola Diagnostic Assays

    NASA Astrophysics Data System (ADS)

    Lam, Patricia; Gulati, Neetu M.; Stewart, Phoebe L.; Keri, Ruth A.; Steinmetz, Nicole F.

    2016-03-01

    The 2014 Ebola epidemic is the largest to date. There is no cure or treatment for this deadly disease; therefore there is an urgent need to develop new diagnostics to accurately detect Ebola. Current RT-PCR assays lack sensitive and reliable positive controls. To address this critical need, we devised a bio-inspired positive control for use in RT-PCR diagnostics: we encapsulated scrambled Ebola RNA sequences inside of tobacco mosaic virus to create a biomimicry that is non-infectious, but stable, and could therefore serve as a positive control in Ebola diagnostic assays. Here, we report the bioengineering and validation of this probe.

  20. Bioengineering of Tobacco Mosaic Virus to Create a Non-Infectious Positive Control for Ebola Diagnostic Assays

    PubMed Central

    Lam, Patricia; Gulati, Neetu M.; Stewart, Phoebe L.; Keri, Ruth A.; Steinmetz, Nicole F.

    2016-01-01

    The 2014 Ebola epidemic is the largest to date. There is no cure or treatment for this deadly disease; therefore there is an urgent need to develop new diagnostics to accurately detect Ebola. Current RT-PCR assays lack sensitive and reliable positive controls. To address this critical need, we devised a bio-inspired positive control for use in RT-PCR diagnostics: we encapsulated scrambled Ebola RNA sequences inside of tobacco mosaic virus to create a biomimicry that is non-infectious, but stable, and could therefore serve as a positive control in Ebola diagnostic assays. Here, we report the bioengineering and validation of this probe. PMID:27030058

  1. Bioengineering of Tobacco Mosaic Virus to Create a Non-Infectious Positive Control for Ebola Diagnostic Assays.

    PubMed

    Lam, Patricia; Gulati, Neetu M; Stewart, Phoebe L; Keri, Ruth A; Steinmetz, Nicole F

    2016-01-01

    The 2014 Ebola epidemic is the largest to date. There is no cure or treatment for this deadly disease; therefore there is an urgent need to develop new diagnostics to accurately detect Ebola. Current RT-PCR assays lack sensitive and reliable positive controls. To address this critical need, we devised a bio-inspired positive control for use in RT-PCR diagnostics: we encapsulated scrambled Ebola RNA sequences inside of tobacco mosaic virus to create a biomimicry that is non-infectious, but stable, and could therefore serve as a positive control in Ebola diagnostic assays. Here, we report the bioengineering and validation of this probe. PMID:27030058

  2. 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.

  3. 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

  4. Transmission Dynamics and Final Epidemic Size of Ebola Virus Disease Outbreaks with Varying Interventions.

    PubMed

    Barbarossa, Maria Vittoria; Dénes, Attila; Kiss, Gábor; Nakata, Yukihiko; Röst, Gergely; Vizi, Zsolt

    2015-01-01

    The 2014 Ebola Virus Disease (EVD) outbreak in West Africa was the largest and longest ever reported since the first identification of this disease. We propose a compartmental model for EVD dynamics, including virus transmission in the community, at hospitals, and at funerals. Using time-dependent parameters, we incorporate the increasing intensity of intervention efforts. Fitting the system to the early phase of the 2014 West Africa Ebola outbreak, we estimate the basic reproduction number as 1.44. We derive a final size relation which allows us to forecast the total number of cases during the outbreak when effective interventions are in place. Our model predictions show that, as long as cases are reported in any country, intervention strategies cannot be dismissed. Since the main driver in the current slowdown of the epidemic is not the depletion of susceptibles, future waves of infection might be possible, if control measures or population behavior are relaxed. PMID:26197242

  5. Transmission Dynamics and Final Epidemic Size of Ebola Virus Disease Outbreaks with Varying Interventions

    PubMed Central

    Barbarossa, Maria Vittoria; Dénes, Attila; Kiss, Gábor; Nakata, Yukihiko; Röst, Gergely; Vizi, Zsolt

    2015-01-01

    The 2014 Ebola Virus Disease (EVD) outbreak in West Africa was the largest and longest ever reported since the first identification of this disease. We propose a compartmental model for EVD dynamics, including virus transmission in the community, at hospitals, and at funerals. Using time-dependent parameters, we incorporate the increasing intensity of intervention efforts. Fitting the system to the early phase of the 2014 West Africa Ebola outbreak, we estimate the basic reproduction number as 1.44. We derive a final size relation which allows us to forecast the total number of cases during the outbreak when effective interventions are in place. Our model predictions show that, as long as cases are reported in any country, intervention strategies cannot be dismissed. Since the main driver in the current slowdown of the epidemic is not the depletion of susceptibles, future waves of infection might be possible, if control measures or population behavior are relaxed. PMID:26197242

  6. Clinical care of two patients with Ebola virus disease in the United States.

    PubMed

    Lyon, G Marshall; Mehta, Aneesh K; Varkey, Jay B; Brantly, Kent; Plyler, Lance; McElroy, Anita K; Kraft, Colleen S; Towner, Jonathan S; Spiropoulou, Christina; Ströher, Ute; Uyeki, Timothy M; Ribner, Bruce S

    2014-12-18

    West Africa is currently experiencing the largest outbreak of Ebola virus disease (EVD) in history. Two patients with EVD were transferred from Liberia to our hospital in the United States for ongoing care. Malaria had also been diagnosed in one patient, who was treated for it early in the course of EVD. The two patients had substantial intravascular volume depletion and marked electrolyte abnormalities. We undertook aggressive supportive measures of hydration (typically, 3 to 5 liters of intravenous fluids per day early in the course of care) and electrolyte correction. As the patients' condition improved clinically, there was a concomitant decline in the amount of virus detected in plasma. PMID:25390460

  7. Inactivated or live-attenuated bivalent vaccines that confer protection against rabies and Ebola viruses.

    PubMed

    Blaney, Joseph E; Wirblich, Christoph; Papaneri, Amy B; Johnson, Reed F; Myers, Carey J; Juelich, Terry L; Holbrook, Michael R; Freiberg, Alexander N; Bernbaum, John G; Jahrling, Peter B; Paragas, Jason; Schnell, Matthias J

    2011-10-01

    The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas. PMID:21849459

  8. Inactivated or Live-Attenuated Bivalent Vaccines That Confer Protection against Rabies and Ebola Viruses

    PubMed Central

    Blaney, Joseph E.; Wirblich, Christoph; Papaneri, Amy B.; Johnson, Reed F.; Myers, Carey J.; Juelich, Terry L.; Holbrook, Michael R.; Freiberg, Alexander N.; Bernbaum, John G.; Jahrling, Peter B.; Paragas, Jason; Schnell, Matthias J.

    2011-01-01

    The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas. PMID:21849459

  9. Live neonates born to mothers with Ebola virus disease: a review of the literature.

    PubMed

    Nelson, J M; Griese, S E; Goodman, A B; Peacock, G

    2016-06-01

    Ebola virus disease (EVD) is associated with a high mortality, especially among neonates. There is a paucity of literature on live neonates born to pregnant women with EVD, and therefore, our understanding of their clinical illness and outcomes is extremely limited. A literature search was conducted to identify descriptions of live neonates born to pregnant women with EVD. To date, five known reports have provided limited information about 15 live neonates born to pregnant women with EVD. All 15 neonates died, and of those with information, death was within 19 days of birth. Of the 12 neonates with information on signs and symptoms, 8 (67%) were reported to have fever; no other signs or symptoms were reported. There are no published data describing the clinical course or treatments provided for these neonates. Potential modes of Ebola virus transmission from mother to neonate are through in utero transmission, during delivery, direct contact or through breast milk. There is an urgent need for more information about neonates with EVD, including clinical course (for example, onset and presentation of illness, symptomatology and course of illness) and treatments provided as well as information on Ebola viral load in breast milk from Ebola-positive and convalescing mothers. PMID:26658125

  10. 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 ...

  11. Response to Comment on "Mutation rate and genotype variation of Ebola virus from Mali case sequences".

    PubMed

    Hoenen, Thomas; Groseth, Allison; Safronetz, David; Wollenberg, Kurt; Feldmann, Heinz

    2016-08-12

    Rambaut et al show that the erratum to our report on Ebola virus Makona evolution not only corrected sample dates modified by others in GenBank but also corrected an additional transcriptional error in our original analysis. We agree with their observation that both factors contributed to our revised evolutionary rate estimate but continue to stand by our revised estimate and conclusions. PMID:27516593

  12. Comment on "Mutation rate and genotype variation of Ebola virus from Mali case sequences".

    PubMed

    Rambaut, Andrew; Dudas, Gytis; de Carvalho, Luiz Max; Park, Daniel J; Yozwiak, Nathan L; Holmes, Edward C; Andersen, Kristian G

    2016-08-12

    Hoenen et al (Reports, 3 April 2015, p. 117; published online 26 March) suggested that the Ebola virus Makona responsible for the West African epidemic evolved more slowly than previously reported. We show that this was based on corrupted data. An erratum provided a rate compatible with the initial and later, more precise, estimates but did not correctly state the nature of the error. PMID:27516592

  13. Role of Ebola Virus vp24 Protein in Inhibition of Interferonogenesis.

    PubMed

    Shelemba, A A; Lushnikova, E L; Kolesnikov, S I; Nepomnyashchikh, L M; Chepurnov, A A

    2016-01-01

    The effects of recombinant analog of natural Ebola virus protein vp24 in configurations virulent (vp24-ad) and avirulent (vp24-w) for guinea pigs on interferonogenesis were studied in vivo and in vitro. Amino acid differences were determined by His186 substitution in avirulent (nonlethal) configuration for Tyr in the virulent (lethal) one. Recombinant analogs vp24-w and vp24-ad inhibited interferonogenesis in vivo and in vitro. Inhibition by the two protein configurations was virtually the same. PMID:26750927

  14. Mannosyl Glycodendritic Structure Inhibits DC-SIGN-Mediated Ebola Virus Infection in cis and in trans

    PubMed Central

    Lasala, Fátima; Arce, Eva; Otero, Joaquín R.; Rojo, Javier; Delgado, Rafael

    2003-01-01

    We have designed a glycodendritic structure, BH30sucMan, that blocks the interaction between dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and Ebola virus (EBOV) envelope. BH30sucMan inhibits DC-SIGN-mediated EBOV infection at nanomolar concentrations. BH30sucMan may counteract important steps of the infective process of EBOV and, potentially, of microorganisms shown to exploit DC-SIGN for cell entry and infection. PMID:14638512

  15. [Ebola virus disease: clinical and diagnostic aspects and organization of treatment-and-prophylactic measures].

    PubMed

    Fisun, A Ia; Zhdanov, K V; Zakharenko, S M; Kovalenko, A N

    2014-11-01

    The article presents data about world spread of Ebola virus disease, biological characteristics of the pathogen, the laws of the epidemic process in this disease, its pathogenesis, clinical manifestations and diagnosis. Pointed out that the current anti-viral agents, effective for the Ebola virus, have not been developed. Timely performed pathogenetic therapy improves the prognosis of the disease. The basis of this therapy is infusion-detoxification activities and replenishment of losses, of electrolytes, as well as anti-inflammatory and anti-emetic drugs. The Armed Forces of the Russian Federation received the guidelines for preventive measure that can reduce Ebola virus disease transmission. Recommendations for emergency anti-epidemic commission consisted of representatives of the command, specialists and medical services and logistics, are given. Fundamentally important condition for the effective anti-epidemic measures is not only the constant readiness of medical personnel in the detection of disease EVD, but also the appropriate level of equipment of medical institutions of medical supplies and equipment. PMID:25816675

  16. Modeling of the Ebola virus delta peptide reveals a potential lytic sequence motif.

    PubMed

    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. Molecular docking based screening of predicted potential inhibitors for VP40 from Ebola virus

    PubMed Central

    Abazari, Danya; Moghtadaei, Mehrad; Behvarmanesh, Ali; Ghannadi, Bahareh; Aghaei, Monireh; Behruznia, Mahboobeh; Rigi, Garshasb

    2015-01-01

    Ebola virus is a member of Filoviridae and cause severe human disease with 90 percent mortality. The life cycle of Ebola contains an assembly stage which is mediated by VP40 proteins. VP40 subunits oligomerize and form ring-structures which are either octamers or hexamers. Prevention of VP40 matrix protein assembly prevents virus particle formation as well as virus budding. In the present study we simulated the biological condition for a single VP40 subunit. Then a library containing 120.000 drugs like chemicals was used as the virtual screening database. Top 10 successive hits were then analyzed regarding absorption, distribution, metabolism, and excretion properties. Moreover probable accessorial human protein targets and toxicity properties of successive hits were analyzed by in silico tools. We found 4 chemicals that could bind VP40 subunits in a manner that by making an interfering steric condense prevents matrix protein oligomerization. The pharmacokinetic and toxicity studies also validated the potential of 4 finlay successive hits to be considered as a new anti-Ebola drugs. PMID:26124568

  18. Molecular docking based screening of predicted potential inhibitors for VP40 from Ebola virus.

    PubMed

    Abazari, Danya; Moghtadaei, Mehrad; Behvarmanesh, Ali; Ghannadi, Bahareh; Aghaei, Monireh; Behruznia, Mahboobeh; Rigi, Garshasb

    2015-01-01

    Ebola virus is a member of Filoviridae and cause severe human disease with 90 percent mortality. The life cycle of Ebola contains an assembly stage which is mediated by VP40 proteins. VP40 subunits oligomerize and form ring-structures which are either octamers or hexamers. Prevention of VP40 matrix protein assembly prevents virus particle formation as well as virus budding. In the present study we simulated the biological condition for a single VP40 subunit. Then a library containing 120.000 drugs like chemicals was used as the virtual screening database. Top 10 successive hits were then analyzed regarding absorption, distribution, metabolism, and excretion properties. Moreover probable accessorial human protein targets and toxicity properties of successive hits were analyzed by in silico tools. We found 4 chemicals that could bind VP40 subunits in a manner that by making an interfering steric condense prevents matrix protein oligomerization. The pharmacokinetic and toxicity studies also validated the potential of 4 finlay successive hits to be considered as a new anti-Ebola drugs. PMID:26124568

  19. 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

  20. Factors Underlying Ebola Virus Infection Among Health Workers, Kenema, Sierra Leone, 2014–2015

    PubMed Central

    Senga, Mikiko; Pringle, Kimberly; Ramsay, Andrew; Brett-Major, David M.; Fowler, Robert A.; French, Issa; Vandi, Mohamed; Sellu, Josephine; Pratt, Christian; Saidu, Josephine; Shindo, Nahoko; Bausch, Daniel G.

    2016-01-01

    Background. Ebola virus disease (EVD) in health workers (HWs) has been a major challenge during the 2014–2015 outbreak. We examined factors associated with Ebola virus exposure and mortality in HWs in Kenema District, Sierra Leone. Methods. We analyzed data from the Sierra Leone National Viral Hemorrhagic Fever Database, contact tracing records, Kenema Government Hospital (KGH) staff and Ebola Treatment Unit (ETU) rosters, and burial logs. Results. From May 2014 through January 2015, 600 cases of EVD originated in Kenema District, including 92 (15%) HWs, 66 (72%) of whom worked at KGH. Among KGH medical staff and international volunteers, 18 of 62 (29%) who worked in the ETU developed EVD, compared with 48 of 83 (58%) who worked elsewhere in the hospital. Thirteen percent of HWs with EVD reported contact with EVD patients, while 27% reported contact with other infected HWs. The number of HW EVD cases at KGH declined roughly 1 month after implementation of a new triage system at KGH and the opening of a second ETU within the district. The case fatality ratio for HWs and non-HWs with EVD was 69% and 74%, respectively. Conclusions. The cluster of HW EVD cases in Kenema District is one of the largest ever reported. Most HWs with EVD had potential virus exposure both inside and outside of hospitals. Prevention measures for HWs must address a spectrum of infection risks in both formal and informal care settings as well as in the community. PMID:27193749

  1. 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

  2. The Ebola Virus VP35 Protein Is a Suppressor of RNA Silencing

    PubMed Central

    Geutjes, Ernst-Jan; Prins, Marcel; de Haan, Peter; Berkhout, Ben

    2007-01-01

    RNA silencing or interference (RNAi) is a gene regulation mechanism in eukaryotes that controls cell differentiation and developmental processes via expression of microRNAs. RNAi also serves as an innate antiviral defence response in plants, nematodes, and insects. This antiviral response is triggered by virus-specific double-stranded RNA molecules (dsRNAs) that are produced during infection. To overcome antiviral RNAi responses, many plant and insect viruses encode RNA silencing suppressors (RSSs) that enable them to replicate at higher titers. Recently, several human viruses were shown to encode RSSs, suggesting that RNAi also serves as an innate defence response in mammals. Here, we demonstrate that the Ebola virus VP35 protein is a suppressor of RNAi in mammalian cells and that its RSS activity is functionally equivalent to that of the HIV-1 Tat protein. We show that VP35 can replace HIV-1 Tat and thereby support the replication of a Tat-minus HIV-1 variant. The VP35 dsRNA-binding domain is required for this RSS activity. Vaccinia virus E3L protein and influenza A virus NS1 protein are also capable of replacing the HIV-1 Tat RSS function. These findings support the hypothesis that RNAi is part of the innate antiviral response in mammalian cells. Moreover, the results indicate that RSSs play a critical role in mammalian virus replication. PMID:17590081

  3. Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.

    PubMed

    Warfield, Kelly L; Dye, John M; Wells, Jay B; Unfer, Robert C; Holtsberg, Frederick W; Shulenin, Sergey; Vu, Hong; Swenson, Dana L; Bavari, Sina; Aman, M Javad

    2015-01-01

    Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components. PMID:25793502

  4. Homologous and Heterologous Protection of Nonhuman Primates by Ebola and Sudan Virus-Like Particles

    PubMed Central

    Warfield, Kelly L.; Dye, John M.; Wells, Jay B.; Unfer, Robert C.; Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Swenson, Dana L.; Bavari, Sina; Aman, M. Javad

    2015-01-01

    Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components. PMID:25793502

  5. Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lytic bacteriophages, viruses which infect and lyse bacterial cells, can provide a natural method to reduce bacterial pathogens on produce commodities. The use of multi-phage cocktails is most likely to be effective against bacterial pathogens on produce commodities, and minimize the development of...

  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. 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

  8. 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

  9. Deaths, late deaths, and role of infecting dose in Ebola virus disease in Sierra Leone: retrospective cohort study

    PubMed Central

    Bower, Hilary; Smout, Elizabeth; Bangura, Mohamed S; Kamara, Osman; Turay, Cecilia; Johnson, Sembia; Oza, Shefali; Checchi, Francesco

    2016-01-01

    Objectives To assess the frequency of fatal recrudescence from Ebola virus disease after discharge from treatment centres, and explore the influence of infecting dose on case fatality rates. Design Retrospective cohort study. Setting Western Area, Sierra Leone. Participants 151 survivors treated for Ebola virus disease at the Kerry Town treatment centre and discharged. Survivors were followed up for a vital status check at four to nine months after discharge, and again at six to 13 months after discharge. Verbal autopsies were conducted for four survivors who had died since discharge (that is, late deaths). Survivors still living in Western Area were interviewed together with their household members. Exposure level to Ebola virus disease was ascertained as a proxy of infecting dose, including for those who died. Main outcome measures Risks and causes of late death; case fatality rates; odds ratios of death from Ebola virus disease by age, sex, exposure level, date, occupation, and household risk factors. Results Follow-up information was obtained on all 151 survivors of Ebola virus disease, a mean of 10 months after discharge. Four deaths occurred after discharge, all within six weeks: two probably due to late complications, one to prior tuberculosis, and only one after apparent full recovery, giving a maximum estimate of recrudescence leading to death of 0.7%. In these households, 395 people were reported to have had Ebola virus disease, of whom 227 died. A further 53 people fulfilled the case definition for probable disease, of whom 11 died. Therefore, the case fatality rate was 57.5% (227/395) for reported Ebola virus disease, or 53.1% (238/448) including probable disease. Case fatality rates were higher in children aged under 2 years and adults older than 30 years, in larger households, and in infections occurring earlier in the epidemic in Sierra Leone. There was no consistent trend of case fatality rate with exposure level, although increasing exposure

  10. Ebola virus outbreak 2014: clinical review for emergency physicians.

    PubMed

    Meyers, Linda; Frawley, Thomas; Goss, Sarah; Kang, Christopher

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest in history. Ebola viral disease is a severe and fatal illness characterized by a nonspecific viral syndrome followed by fulminant septic shock and coagulopathy. Despite ongoing efforts directed at experimental treatments and vaccine development, current medical management of Ebola viral disease is largely limited to supportive therapy, thus making early case identification and immediate implementation of appropriate control measures critical. Because a case of Ebola viral disease was confirmed in the United States on September 30, 2014, emergency medicine providers should be knowledgeable about it for a number of reasons: we are being called on to answer questions about Ebola and allay public fears, we are likely to be first to encounter an infected patient, and there are increasing numbers of US emergency physicians working in Africa who risk coming in direct contact with the disease. This article seeks to provide emergency physicians with the essential and up-to-date information required to identify, evaluate, and manage Ebola viral disease and to join global efforts to contain the current outbreak. PMID:25455908

  11. Assessing the contribution of interferon antagonism to the virulence of West African Ebola viruses

    PubMed Central

    Dunham, Eric C.; Banadyga, Logan; Groseth, Allison; Chiramel, Abhilash I.; Best, Sonja M.; Ebihara, Hideki; Feldmann, Heinz; Hoenen, Thomas

    2015-01-01

    The current Ebola virus (EBOV) outbreak in West Africa is unprecedented in terms of both its size and duration, and there has been speculation and concern regarding the potential for EBOV to increase in virulence as a result of its prolonged circulation in humans. Here we investigate the relative potency of the interferon (IFN) inhibitors encoded by EBOVs from West Africa, since an important EBOV virulence factor is inhibition of the antiviral IFN response. Based on this work we show that, in terms of IFN antagonism, the West African viruses display no discernible differences from the prototype Mayinga isolate, which corroborates epidemiological data suggesting these viruses show no increased virulence compared with those from previous outbreaks. This finding has important implications for public health decisions, since it does not provide experimental support for theoretical claims that EBOV might gain increased virulence due to the extensive human-to-human transmission in the on-going outbreak. PMID:26242723

  12. Assessing the contribution of interferon antagonism to the virulence of West African Ebola viruses.

    PubMed

    Dunham, Eric C; Banadyga, Logan; Groseth, Allison; Chiramel, Abhilash I; Best, Sonja M; Ebihara, Hideki; Feldmann, Heinz; Hoenen, Thomas

    2015-01-01

    The current Ebola virus (EBOV) outbreak in West Africa is unprecedented in terms of both its size and duration, and there has been speculation and concern regarding the potential for EBOV to increase in virulence as a result of its prolonged circulation in humans. Here we investigate the relative potency of the interferon (IFN) inhibitors encoded by EBOVs from West Africa, since an important EBOV virulence factor is inhibition of the antiviral IFN response. Based on this work we show that, in terms of IFN antagonism, the West African viruses display no discernible differences from the prototype Mayinga isolate, which corroborates epidemiological data suggesting these viruses show no increased virulence compared with those from previous outbreaks. This finding has important implications for public health decisions, since it does not provide experimental support for theoretical claims that EBOV might gain increased virulence due to the extensive human-to-human transmission in the on-going outbreak. PMID:26242723

  13. Rapid Detection and Quantification of RNA of Ebola and Marburg Viruses, Lassa Virus, Crimean-Congo Hemorrhagic Fever Virus, Rift Valley Fever Virus, Dengue Virus, and Yellow Fever Virus by Real-Time Reverse Transcription-PCR

    PubMed Central

    Drosten, Christian; Göttig, Stephan; Schilling, Stefan; Asper, Marcel; Panning, Marcus; Schmitz, Herbert; Günther, Stephan

    2002-01-01

    Viral hemorrhagic fevers (VHFs) are acute infections with high case fatality rates. Important VHF agents are Ebola and Marburg viruses (MBGV/EBOV), Lassa virus (LASV), Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), dengue virus (DENV), and yellow fever virus (YFV). VHFs are clinically difficult to diagnose and to distinguish; a rapid and reliable laboratory diagnosis is required in suspected cases. We have established six one-step, real-time reverse transcription-PCR assays for these pathogens based on the Superscript reverse transcriptase-Platinum Taq polymerase enzyme mixture. Novel primers and/or 5′-nuclease detection probes were designed for RVFV, DENV, YFV, and CCHFV by using the latest DNA database entries. PCR products were detected in real time on a LightCycler instrument by using 5′-nuclease technology (RVFV, DENV, and YFV) or SybrGreen dye intercalation (MBGV/EBOV, LASV, and CCHFV). The inhibitory effect of SybrGreen on reverse transcription was overcome by initial immobilization of the dye in the reaction capillaries. Universal cycling conditions for SybrGreen and 5′-nuclease probe detection were established. Thus, up to three assays could be performed in parallel, facilitating rapid testing for several pathogens. All assays were thoroughly optimized and validated in terms of analytical sensitivity by using in vitro-transcribed RNA. The ≥95% detection limits as determined by probit regression analysis ranged from 1,545 to 2,835 viral genome equivalents/ml of serum (8.6 to 16 RNA copies per assay). The suitability of the assays was exemplified by detection and quantification of viral RNA in serum samples of VHF patients. PMID:12089242

  14. 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

  15. Clinical Management of Ebola Virus Disease in the United States and Europe

    PubMed Central

    Uyeki, Timothy M.; Mehta, Aneesh K.; Davey, Richard T.; Liddell, Allison M.; Wolf, Timo; Vetter, Pauline; Schmiedel, Stefan; Grünewald, Thomas; Jacobs, Michael; Arribas, Jose R.; Evans, Laura; Hewlett, Angela L.; Brantsaeter, Arne B.; Ippolito, Giuseppe; Rapp, Christophe; Hoepelman, Andy I.M.; Gutman, Julie

    2016-01-01

    Background Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited. Methods We reviewed available clinical, laboratory, and virologic data from all patients with laboratory-confirmed Ebola virus infection who received care in U.S. and European hospitals from August 2014 through December 2015. Results A total of 27 patients (median age, 36 years [range, 25 to 75]) with EVD received care; 19 patients (70%) were male, 9 of 26 patients (35%) had coexisting conditions, and 22 (81%) were health care personnel. Of the 27 patients, 24 (89%) were medically evacuated from West Africa or were exposed to and infected with Ebola virus in West Africa and had onset of illness and laboratory confirmation of Ebola virus infection in Europe or the United States, and 3 (11%) acquired EVD in the United States or Europe. At the onset of illness, the most common signs and symptoms were fatigue (20 patients [80%]) and fever or feverishness (17 patients [68%]). During the clinical course, the predominant findings included diarrhea, hypoalbuminemia, hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia; 14 patients (52%) had hypoxemia, and 9 (33%) had oliguria, of whom 5 had anuria. Aminotransferase levels peaked at a median of 9 days after the onset of illness. Nearly all the patients received intravenous fluids and electrolyte supplementation; 9 (33%) received noninvasive or invasive mechanical ventilation; 5 (19%) received continuous renal-replacement therapy; 22 (81%) received empirical antibiotics; and 23 (85%) received investigational therapies (19 [70%] received at least two experimental interventions). Ebola viral RNA levels in blood peaked at a median of 7 days after the onset of illness, and the median time from the onset of symptoms to clearance of viremia was 17.5 days. A total of 5 patients died, including 3 who had

  16. Identification of novel cellular targets for therapeutic intervention against Ebola virus infection by siRNA screening.

    PubMed

    Kolokoltsov, Andrey A; Saeed, Mohammad F; Freiberg, Alexander N; Holbrook, Michael R; Davey, Robert A

    2009-06-01

    While much progress has been made in developing drugs against a few prominent viruses such as HIV, few examples exist for emerging infectious agents. In some cases broad spectrum anti-viral drugs, such as ribavirin, are effective, but for some groups of viruses, these show little efficacy in animal models. Traditional methods focus on screening small molecule libraries to identify drugs that target virus factors, with the intention that side-effects to the host can be minimized. However, this greatly limits potential drug targets and virus genes can rapidly mutate to avoid drug action. Recent advances in siRNA gene targeting technologies have provided a powerful tool to specifically target and suppress the expression of cell genes. Since viruses are completely dependent upon host cell proteins for propagation, siRNA screening promises to reveal novel cell proteins and signaling pathways that may be viable targets for drug therapy regimens. Here we used an siRNA screening approach to identify gene products that play critical roles in Ebola virus infection. By gene cluster analysis, proteins in phosphatidylinositol-3-kinase and calcium/calmodulin kinase related networks were identified as important for Zaire Ebola virus infection and prioritized for further evaluation. Key roles of each were confirmed by testing available drugs specific for members of each pathway. Interestingly, both sets of proteins are also important in cancer and subject to intense investigation. Thus development of new drugs against these cancer targets may also prove useful in combating Ebola virus. PMID:20930947

  17. Structures of protective antibodies reveal sites of vulnerability on Ebola virus

    PubMed Central

    Murin, Charles D.; Fusco, Marnie L.; Bornholdt, Zachary A.; Qiu, Xiangguo; Olinger, Gene G.; Zeitlin, Larry; Kobinger, Gary P.; Ward, Andrew B.; Saphire, Erica Ollmann

    2014-01-01

    Ebola virus (EBOV) and related filoviruses cause severe hemorrhagic fever, with up to 90% lethality, and no treatments are approved for human use. Multiple recent outbreaks of EBOV and the likelihood of future human exposure highlight the need for pre- and postexposure treatments. Monoclonal antibody (mAb) cocktails are particularly attractive candidates due to their proven postexposure efficacy in nonhuman primate models of EBOV infection. Two candidate cocktails, MB-003 and ZMAb, have been extensively evaluated in both in vitro and in vivo studies. Recently, these two therapeutics have been combined into a new cocktail named ZMapp, which showed increased efficacy and has been given compassionately to some human patients. Epitope information and mechanism of action are currently unknown for most of the component mAbs. Here we provide single-particle EM reconstructions of every mAb in the ZMapp cocktail, as well as additional antibodies from MB-003 and ZMAb. Our results illuminate key and recurring sites of vulnerability on the EBOV glycoprotein and provide a structural rationale for the efficacy of ZMapp. Interestingly, two of its components recognize overlapping epitopes and compete with each other for binding. Going forward, this work now provides a basis for strategic selection of next-generation antibody cocktails against Ebola and related viruses and a model for predicting the impact of ZMapp on potential escape mutations in ongoing or future Ebola outbreaks. PMID:25404321

  18. Perceptions of Ebola virus disease in Nigeria: Understanding the influence of imagination on health orientation.

    PubMed

    Oduyemi, Rachael O; Ayegboyin, Matthew; Salami, Kabiru K

    2016-06-01

    The 2014 Ebola virus disease (EVD) outbreak was officially declared in the West Africa region by the World Health Organization (WHO) on 23 March 2014. This first episode of EVD in Nigeria on 20 July 2014 raised more intense panic globally than the seven occurrences of the disease in Zaire. Although Nigeria was declared Ebola free by the WHO within 3 months, it is imperative to understand people's perceptions of the disease in the country. A discussion of peoples' perception of EVD in Nigeria is the aim of this article. This discussion paper complements secondary data with grey literature to explore how peoples' imagination and personification of thoughts influence their health orientation. Data are sourced from secondary information compiled from 'The Nation Newspaper, 2014'; 'Nairaland online forum, 2014' and 'Giftedgreen online magazine, 2014'. Ebola virus disease was perceived as a spiritual manipulation of witchcraft activities and described as biological terrorism and a means of creating a drug market, among other issues, in the country. Public health professionals should consider the sociocultural milieu to understand and offer health-care services in epidemics. Public health orientation work is urgently required in Nigeria to forestall future occurrence of EVD and other highly infectious diseases. PMID:27080239

  19. A Mathematical Model with Quarantine States for the Dynamics of Ebola Virus Disease in Human Populations

    PubMed Central

    Ngwa, Gideon A.

    2016-01-01

    A deterministic ordinary differential equation model for the dynamics and spread of Ebola Virus Disease is derived and studied. The model contains quarantine and nonquarantine states and can be used to evaluate transmission both in treatment centres and in the community. Possible sources of exposure to infection, including cadavers of Ebola Virus victims, are included in the model derivation and analysis. Our model's results show that there exists a threshold parameter, R 0, with the property that when its value is above unity, an endemic equilibrium exists whose value and size are determined by the size of this threshold parameter, and when its value is less than unity, the infection does not spread into the community. The equilibrium state, when it exists, is locally and asymptotically stable with oscillatory returns to the equilibrium point. The basic reproduction number, R 0, is shown to be strongly dependent on the initial response of the emergency services to suspected cases of Ebola infection. When intervention measures such as quarantining are instituted fully at the beginning, the value of the reproduction number reduces and any further infections can only occur at the treatment centres. Effective control measures, to reduce R 0 to values below unity, are discussed. PMID:27579053

  20. A Mathematical Model with Quarantine States for the Dynamics of Ebola Virus Disease in Human Populations.

    PubMed

    Ngwa, Gideon A; Teboh-Ewungkem, Miranda I

    2016-01-01

    A deterministic ordinary differential equation model for the dynamics and spread of Ebola Virus Disease is derived and studied. The model contains quarantine and nonquarantine states and can be used to evaluate transmission both in treatment centres and in the community. Possible sources of exposure to infection, including cadavers of Ebola Virus victims, are included in the model derivation and analysis. Our model's results show that there exists a threshold parameter, R 0, with the property that when its value is above unity, an endemic equilibrium exists whose value and size are determined by the size of this threshold parameter, and when its value is less than unity, the infection does not spread into the community. The equilibrium state, when it exists, is locally and asymptotically stable with oscillatory returns to the equilibrium point. The basic reproduction number, R 0, is shown to be strongly dependent on the initial response of the emergency services to suspected cases of Ebola infection. When intervention measures such as quarantining are instituted fully at the beginning, the value of the reproduction number reduces and any further infections can only occur at the treatment centres. Effective control measures, to reduce R 0 to values below unity, are discussed. PMID:27579053

  1. Ebola

    MedlinePlus

    ... pick up the virus from contact with infected animals. Tropical animals in Africa believed to carry the virus include ... for Ebola have been effective when tested on animals, but are not officially approved for use in ...

  2. Ebola

    MedlinePlus

    Ebola hemorrhagic fever is caused by a virus. It is a severe and often fatal disease. It can affect humans and ... after exposure to the virus. Symptoms usually include Fever Headache Joint and muscle aches Weakness Diarrhea Vomiting ...

  3. 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

  4. 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

  5. The potential for sexual transmission to compromise control of Ebola virus outbreaks.

    PubMed

    Vinson, John E; Drake, John M; Rohani, Pejman; Park, Andrew W

    2016-06-01

    Recent evidence suggests that sexual contact may give rise to transmission of Ebola virus long after infection has been cleared from blood. We develop a simple mathematical model that incorporates contact transmission and sexual transmission parametrized from data relating to the 2013-2015 West African Ebola epidemic. The model explores scenarios where contact transmission is reduced following infection events, capturing behaviour change, and quantifies how these actions reducing transmission may be compromised by sexual transmission in terms of increasing likelihood, size and duration of outbreaks. We characterize the extent to which sexual transmission operates in terms of the probability of initial infection resolving to sexual infectiousness and the sexual transmission rate, and relate these parameters to the overall case burden. We find that sexual transmission can have large effects on epidemic dynamics (increasing attack ratios from 25% in scenarios without sexual transmission but with contact-transmission-reducing behaviour, up to 80% in equivalent scenarios with sexual transmission). PMID:27277951

  6. Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle.

    PubMed

    Dye, John M; Wu, Hua; Hooper, Jay W; Khurana, Surender; Kuehne, Ana I; Coyle, Elizabeth M; Ortiz, Ramon A; Fuentes, Sandra; Herbert, Andrew S; Golding, Hana; Bakken, Russell A; Brannan, Jennifer M; Kwilas, Steve A; Sullivan, Eddie J; Luke, Thomas C; Smith, Gale; Glenn, Gregory; Li, Wenfang; Ye, Ling; Yang, Chinglai; Compans, Richard W; Tripp, Ralph A; Jiao, Jin-An

    2016-01-01

    Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities. PMID:27109916

  7. Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

    PubMed Central

    Dye, John M.; Wu, Hua; Hooper, Jay W.; Khurana, Surender; Kuehne, Ana I.; Coyle, Elizabeth M.; Ortiz, Ramon A.; Fuentes, Sandra; Herbert, Andrew S.; Golding, Hana; Bakken, Russell A.; Brannan, Jennifer M.; Kwilas, Steve A.; Sullivan, Eddie J.; Luke, Thomas C.; Smith, Gale; Glenn, Gregory; Li, Wenfang; Ye, Ling; Yang, Chinglai; Compans, Richard W.; Tripp, Ralph A.; Jiao, Jin-an

    2016-01-01

    Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities. PMID:27109916

  8. 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

  9. 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

  10. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

    PubMed

    Warren, Travis K; Jordan, Robert; Lo, Michael K; Ray, Adrian S; Mackman, Richard L; Soloveva, Veronica; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C; Larson, Nate; Strickley, Robert; Wells, Jay; Stuthman, Kelly S; Van Tongeren, Sean A; Garza, Nicole L; Donnelly, Ginger; Shurtleff, Amy C; Retterer, Cary J; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P; Grimes, Elizabeth; Welch, Lisa S; Gomba, Laura; Wilhelmsen, Catherine L; Nichols, Donald K; Nuss, Jonathan E; Nagle, Elyse R; Kugelman, Jeffrey R; Palacios, Gustavo; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M; Trancheva, Iva; Feng, Joy Y; Barauskas, Ona; Xu, Yili; Wong, Pamela; Braun, Molly R; Flint, Mike; McMullan, Laura K; Chen, Shan-Shan; Fearns, Rachel; Swaminathan, Swami; Mayers, Douglas L; Spiropoulou, Christina F; Lee, William A; Nichol, Stuart T; Cihlar, Tomas; Bavari, Sina

    2016-03-17

    The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the

  11. Potential Impact of Sexual Transmission on Ebola Virus Epidemiology: Sierra Leone as a Case Study

    PubMed Central

    Richner, Heinz; Althaus, Christian L.

    2016-01-01

    Background Sexual transmission of Ebola virus disease (EVD) 6 months after onset of symptoms has been recently documented, and Ebola virus RNA has been detected in semen of survivors up to 9 months after onset of symptoms. As countries affected by the 2013–2015 epidemic in West Africa, by far the largest to date, are declared free of Ebola virus disease (EVD), it remains unclear what threat is posed by rare sexual transmission events that could arise from survivors. Methodology/Principal Findings We devised a compartmental mathematical model that includes sexual transmission from convalescent survivors: a SEICR (susceptible-exposed-infectious-convalescent-recovered) transmission model. We fitted the model to weekly incidence of EVD cases from the 2014–2015 epidemic in Sierra Leone. Sensitivity analyses and Monte Carlo simulations showed that a 0.1% per sex act transmission probability and a 3-month convalescent period (the two key unknown parameters of sexual transmission) create very few additional cases, but would extend the epidemic by 83 days [95% CI: 68–98 days] (p < 0.0001) on average. Strikingly, a 6-month convalescent period extended the average epidemic by 540 days (95% CI: 508–572 days), doubling the current length, despite an insignificant rise in the number of new cases generated. Conclusions/Significance Our results show that reductions in the per sex act transmission probability via abstinence and condom use should reduce the number of sporadic sexual transmission events, but will not significantly reduce the epidemic size and may only minimally shorten the length of time the public health community must maintain response preparedness. While the number of infectious survivors is expected to greatly decline over the coming months, our results show that transmission events may still be expected for quite some time as each event results in a new potential cluster of non-sexual transmission. Precise measurement of the convalescent period is thus

  12. Dynamical Analysis of an SEIT Epidemic Model with Application to Ebola Virus Transmission in Guinea

    PubMed Central

    Li, Zhiming; Teng, Zhidong; Feng, Xiaomei; Li, Yingke; Zhang, Huiguo

    2015-01-01

    In order to investigate the transmission mechanism of the infectious individual with Ebola virus, we establish an SEIT (susceptible, exposed in the latent period, infectious, and treated/recovery) epidemic model. The basic reproduction number is defined. The mathematical analysis on the existence and stability of the disease-free equilibrium and endemic equilibrium is given. As the applications of the model, we use the recognized infectious and death cases in Guinea to estimate parameters of the model by the least square method. With suitable parameter values, we obtain the estimated value of the basic reproduction number and analyze the sensitivity and uncertainty property by partial rank correlation coefficients. PMID:26246849

  13. 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

    2015-10-01

    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

  14. Dynamical Analysis of an SEIT Epidemic Model with Application to Ebola Virus Transmission in Guinea.

    PubMed

    Li, Zhiming; Teng, Zhidong; Feng, Xiaomei; Li, Yingke; Zhang, Huiguo

    2015-01-01

    In order to investigate the transmission mechanism of the infectious individual with Ebola virus, we establish an SEIT (susceptible, exposed in the latent period, infectious, and treated/recovery) epidemic model. The basic reproduction number is defined. The mathematical analysis on the existence and stability of the disease-free equilibrium and endemic equilibrium is given. As the applications of the model, we use the recognized infectious and death cases in Guinea to estimate parameters of the model by the least square method. With suitable parameter values, we obtain the estimated value of the basic reproduction number and analyze the sensitivity and uncertainty property by partial rank correlation coefficients. PMID:26246849

  15. Hanta virus (image)

    MedlinePlus

    Hanta virus is a distant cousin of Ebola virus, but is found worldwide. The virus is spread by human contact with rodent waste. Dangerous respiratory illness develops. Effective treatment is not yet ...

  16. [New promising treatments of Ebola virus disease are underway].

    PubMed

    Jespersen, Sanne; Thomsen, Cecilie Norup; Wejse, Christian; Storgaard, Merete

    2016-01-25

    The largest Ebola epidemic ever is about to end. No major breakthrough in terms of specific treatment has been seen, but a number of valuable lessons have been learned, including the potential of intensive supportive care. New products are under development, but clinical trials were initiated late in the epidemic leading to inability to include sufficient numbers. Several large vaccine trials are underway with one vaccine so far showing 100 per cent efficacy. A paradigm shift in accelerated testing of drugs and vaccines during an ongoing epidemic is emerging. PMID:26815716

  17. Impact of spatial dispersion, evolution, and selection on Ebola Zaire Virus epidemic waves

    PubMed Central

    Azarian, Taj; Lo Presti, Alessandra; Giovanetti, Marta; Cella, Eleonora; Rife, Brittany; Lai, Alessia; Zehender, Gianguglielmo; Ciccozzi, Massimo; Salemi, Marco

    2015-01-01

    Ebola virus Zaire (EBOV) has reemerged in Africa, emphasizing the global importance of this pathogen. Amidst the response to the current epidemic, several gaps in our knowledge of EBOV evolution are evident. Specifically, uncertainty has been raised regarding the potential emergence of more virulent viral variants through amino acid substitutions. Glycoprotein (GP), an essential component of the EBOV genome, is highly variable and a potential site for the occurrence of advantageous mutations. For this study, we reconstructed the evolutionary history of EBOV by analyzing 65 GP sequences from humans and great apes over diverse locations across epidemic waves between 1976 and 2014. We show that, although patterns of spatial dispersion throughout Africa varied, the evolution of the virus has largely been characterized by neutral genetic drift. Therefore, the radical emergence of more transmissible variants is unlikely, a positive finding, which is increasingly important on the verge of vaccine deployment. PMID:25973685

  18. Impact of spatial dispersion, evolution, and selection on Ebola Zaire Virus epidemic waves.

    PubMed

    Azarian, Taj; Lo Presti, Alessandra; Giovanetti, Marta; Cella, Eleonora; Rife, Brittany; Lai, Alessia; Zehender, Gianguglielmo; Ciccozzi, Massimo; Salemi, Marco

    2015-01-01

    Ebola virus Zaire (EBOV) has reemerged in Africa, emphasizing the global importance of this pathogen. Amidst the response to the current epidemic, several gaps in our knowledge of EBOV evolution are evident. Specifically, uncertainty has been raised regarding the potential emergence of more virulent viral variants through amino acid substitutions. Glycoprotein (GP), an essential component of the EBOV genome, is highly variable and a potential site for the occurrence of advantageous mutations. For this study, we reconstructed the evolutionary history of EBOV by analyzing 65 GP sequences from humans and great apes over diverse locations across epidemic waves between 1976 and 2014. We show that, although patterns of spatial dispersion throughout Africa varied, the evolution of the virus has largely been characterized by neutral genetic drift. Therefore, the radical emergence of more transmissible variants is unlikely, a positive finding, which is increasingly important on the verge of vaccine deployment. PMID:25973685

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

    PubMed

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

    2015-10-01

    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

  20. Geographic potential of disease caused by Ebola and Marburg viruses in Africa.

    PubMed

    Peterson, A Townsend; Samy, Abdallah M

    2016-10-01

    Filoviruses represent a significant public health threat worldwide. West Africa recently experienced the largest-scale and most complex filovirus outbreak yet known, which underlines the need for a predictive understanding of the geographic distribution and potential for transmission to humans of these viruses. Here, we used ecological niche modeling techniques to understand the relationship between known filovirus occurrences and environmental characteristics. Our study derived a picture of the potential transmission geography of Ebola virus species and Marburg, paired with views of the spatial uncertainty associated with model-to-model variation in our predictions. We found that filovirus species have diverged ecologically, but only three species are sufficiently well known that models could be developed with significant predictive power. We quantified uncertainty in predictions, assessed potential for outbreaks outside of known transmission areas, and highlighted the Ethiopian Highlands and scattered areas across East Africa as additional potentially unrecognized transmission areas. PMID:27311387

  1. Monitoring of Ebola Virus Makona Evolution through Establishment of Advanced Genomic Capability in Liberia.

    PubMed

    Kugelman, Jeffrey R; Wiley, Michael R; Mate, Suzanne; Ladner, Jason T; Beitzel, Brett; Fakoli, Lawrence; Taweh, Fahn; Prieto, Karla; Diclaro, Joseph W; Minogue, Timothy; Schoepp, Randal J; Schaecher, Kurt E; Pettitt, James; Bateman, Stacey; Fair, Joseph; Kuhn, Jens H; Hensley, Lisa; Park, Daniel J; Sabeti, Pardis C; Sanchez-Lockhart, Mariano; Bolay, Fatorma K; Palacios, Gustavo

    2015-07-01

    To support Liberia's response to the ongoing Ebola virus (EBOV) disease epidemic in Western Africa, we established in-country advanced genomic capabilities to monitor EBOV evolution. Twenty-five EBOV genomes were sequenced at the Liberian Institute for Biomedical Research, which provided an in-depth view of EBOV diversity in Liberia during September 2014-February 2015. These sequences were consistent with a single virus introduction to Liberia; however, shared ancestry with isolates from Mali indicated at least 1 additional instance of movement into or out of Liberia. The pace of change is generally consistent with previous estimates of mutation rate. We observed 23 nonsynonymous mutations and 1 nonsense mutation. Six of these changes are within known binding sites for sequence-based EBOV medical countermeasures; however, the diagnostic and therapeutic impact of EBOV evolution within Liberia appears to be low. PMID:26079255

  2. Monitoring of Ebola Virus Makona Evolution through Establishment of Advanced Genomic Capability in Liberia

    PubMed Central

    Kugelman, Jeffrey R.; Wiley, Michael R.; Mate, Suzanne; Ladner, Jason T.; Beitzel, Brett; Fakoli, Lawrence; Taweh, Fahn; Prieto, Karla; Diclaro, Joseph W.; Minogue, Timothy; Schoepp, Randal J.; Schaecher, Kurt E.; Pettitt, James; Bateman, Stacey; Fair, Joseph; Kuhn, Jens H.; Hensley, Lisa; Park, Daniel J.; Sabeti, Pardis C.; Sanchez-Lockhart, Mariano; Bolay, Fatorma K.

    2015-01-01

    To support Liberia’s response to the ongoing Ebola virus (EBOV) disease epidemic in Western Africa, we established in-country advanced genomic capabilities to monitor EBOV evolution. Twenty-five EBOV genomes were sequenced at the Liberian Institute for Biomedical Research, which provided an in-depth view of EBOV diversity in Liberia during September 2014–February 2015. These sequences were consistent with a single virus introduction to Liberia; however, shared ancestry with isolates from Mali indicated at least 1 additional instance of movement into or out of Liberia. The pace of change is generally consistent with previous estimates of mutation rate. We observed 23 nonsynonymous mutations and 1 nonsense mutation. Six of these changes are within known binding sites for sequence-based EBOV medical countermeasures; however, the diagnostic and therapeutic impact of EBOV evolution within Liberia appears to be low. PMID:26079255

  3. The Baboon (Papio spp.) as a Model of Human Ebola Virus Infection

    PubMed Central

    Perry, Donna L.; Bollinger, Laura; L.White, Gary

    2012-01-01

    Baboons are susceptible to natural Ebola virus (EBOV) infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV) infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited. PMID:23202470

  4. 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.

  5. Occupational safety and health protections against Ebola virus disease.

    PubMed

    Ringen, Knut; Landrigan, Philip J; Stull, Jeffrey O; Duffy, Richard; Melius, James; McDiarmid, Melissa A

    2015-07-01

    Even as the Ebola epidemic is finally showing signs of remitting, controversy continues regarding the modes of disease transmission, the understanding of which necessarily dictates methods of prevention. The initial public health response to the epidemic was based on assumptions formed during previous outbreaks, and in the belief that transmission was restricted to direct "contact" with other infected patients. However, the current Ebola outbreak differed from previous experiences in its intensity of transmission, speed of spread, and fatality rate and was also particularly unforgiving on health workers occupationally infected. Even with these differences, however, other modes of transmission were not considered by public health authorities, thus denying both the hard-hit health worker populations and the wider public more protective guidance. International Labor Conventions require employers to provide a comprehensive safety program that anticipates work-related risks and specifies strategies for protection against them. Such a precautionary approach is recommended in future epidemic planning, especially where evidence regarding transmission is incomplete. PMID:25950864

  6. 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

  7. 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

  8. A web-based resource for designing therapeutics against Ebola Virus.

    PubMed

    Dhanda, Sandeep Kumar; Chaudhary, Kumardeep; Gupta, Sudheer; Brahmachari, Samir Kumar; Raghava, Gajendra P S

    2016-01-01

    In this study, we describe a web-based resource, developed for assisting the scientific community in designing an effective therapeutics against the Ebola virus. Firstly, we predicted and identified experimentally validated epitopes in each of the antigens/proteins of the five known ebolaviruses. Secondly, we generated all the possible overlapping 9mer peptides from the proteins of ebolaviruses. Thirdly, conserved peptides across all the five ebolaviruses (four human pathogenic species) with no identical sequence in the human proteome, based on 1000 Genomes project, were identified. Finally, we identified peptide or epitope-based vaccine candidates that could activate both the B- and T-cell arms of the immune system. In addition, we also identified efficacious siRNAs against the mRNA transcriptome (absent in human transcriptome) of all the five ebolaviruses. It was observed that three species can potentially be targeted by a single siRNA (19mer) and 75 siRNAs can potentially target at least two species. A web server, EbolaVCR, has been developed that incorporates all the above information and useful computational tools (http://crdd.osdd.net/oscadd/ebola/). PMID:27113850

  9. A web-based resource for designing therapeutics against Ebola Virus

    PubMed Central

    Dhanda, Sandeep Kumar; Chaudhary, Kumardeep; Gupta, Sudheer; Brahmachari, Samir Kumar; Raghava, Gajendra P. S.

    2016-01-01

    In this study, we describe a web-based resource, developed for assisting the scientific community in designing an effective therapeutics against the Ebola virus. Firstly, we predicted and identified experimentally validated epitopes in each of the antigens/proteins of the five known ebolaviruses. Secondly, we generated all the possible overlapping 9mer peptides from the proteins of ebolaviruses. Thirdly, conserved peptides across all the five ebolaviruses (four human pathogenic species) with no identical sequence in the human proteome, based on 1000 Genomes project, were identified. Finally, we identified peptide or epitope-based vaccine candidates that could activate both the B- and T-cell arms of the immune system. In addition, we also identified efficacious siRNAs against the mRNA transcriptome (absent in human transcriptome) of all the five ebolaviruses. It was observed that three species can potentially be targeted by a single siRNA (19mer) and 75 siRNAs can potentially target at least two species. A web server, EbolaVCR, has been developed that incorporates all the above information and useful computational tools (http://crdd.osdd.net/oscadd/ebola/). PMID:27113850

  10. 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. PMID:26740846

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

    PubMed

    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. PMID:26740846

  12. 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

  13. 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

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

    PubMed

    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

  15. New monoclonal antibodies to the Ebola virus glycoprotein: Identification and analysis of the amino acid sequence of the variable domains.

    PubMed

    Panina, A A; Aliev, T K; Shemchukova, O B; Dement'yeva, I G; Varlamov, N E; Pozdnyakova, L P; Bokov, M N; Dolgikh, D A; Sveshnikov, P G; Kirpichnikov, M P

    2016-03-01

    We determined the nucleotide and amino acid sequences of variable domains of three new monoclonal antibodies to the glycoprotein of Ebola virus capsid. The framework and hypervariable regions of immunoglobulin heavy and light chains were identified. The primary structures were confirmed using massspectrometry analysis. Immunoglobulin database search showed the uniqueness of the sequences obtained. PMID:27193713

  16. Molecular Characterization of the First Ebola Virus Isolated in Italy, from a Health Care Worker Repatriated from Sierra Leone

    PubMed Central

    Castilletti, Concetta; Carletti, Fabrizio; Gruber, Cesare E. M.; Bordi, Licia; Lalle, Eleonora; Quartu, Serena; Meschi, Silvia; Lapa, Daniele; Colavita, Francesca; Chiappini, Roberta; Mazzarelli, Antonio; Marsella, Patrizia; Petrosillo, Nicola; Nicastri, Emanuele; Chillemi, Giovanni; Valentini, Alessio; Desideri, Alessandro; Di Caro, Antonino; Ippolito, Giuseppe

    2015-01-01

    Here, we report the complete genome sequence of an Ebola virus (EBOV) isolated from a health worker repatriated from Sierra Leone to Italy in November 2014. The sequence, clustering in clade 3 of the Sierra Leone sequences, was analyzed with respect to mutations possibly affecting diagnostic and therapeutic targets as well as virulence. PMID:26089420

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

    PubMed Central

    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

  18. Recommendations for dealing with waste contaminated with Ebola virus: a Hazard Analysis of Critical Control Points approach

    PubMed Central

    Edmunds, Kelly L; Elrahman, Samira Abd; Bell, Diana J; Brainard, Julii; Dervisevic, Samir; Fedha, Tsimbiri P; Few, Roger; Howard, Guy; Lake, Iain; Maes, Peter; Matofari, Joseph; Minnigh, Harvey; Mohamedani, Ahmed A; Montgomery, Maggie; Morter, Sarah; Muchiri, Edward; Mudau, Lutendo S; Mutua, Benedict M; Ndambuki, Julius M; Pond, Katherine; Sobsey, Mark D; van der Es, Mike; Zeitoun, Mark

    2016-01-01

    Abstract Objective To assess, within communities experiencing Ebola virus outbreaks, the risks associated with the disposal of human waste and to generate recommendations for mitigating such risks. Methods A team with expertise in the Hazard Analysis of Critical Control Points framework identified waste products from the care of individuals with Ebola virus disease and constructed, tested and confirmed flow diagrams showing the creation of such products. After listing potential hazards associated with each step in each flow diagram, the team conducted a hazard analysis, determined critical control points and made recommendations to mitigate the transmission risks at each control point. Findings The collection, transportation, cleaning and shared use of blood-soiled fomites and the shared use of latrines contaminated with blood or bloodied faeces appeared to be associated with particularly high levels of risk of Ebola virus transmission. More moderate levels of risk were associated with the collection and transportation of material contaminated with bodily fluids other than blood, shared use of latrines soiled with such fluids, the cleaning and shared use of fomites soiled with such fluids, and the contamination of the environment during the collection and transportation of blood-contaminated waste. Conclusion The risk of the waste-related transmission of Ebola virus could be reduced by the use of full personal protective equipment, appropriate hand hygiene and an appropriate disinfectant after careful cleaning. Use of the Hazard Analysis of Critical Control Points framework could facilitate rapid responses to outbreaks of emerging infectious disease. PMID:27274594

  19. Clinical Features of and Risk Factors for Fatal Ebola Virus Disease, Moyamba District, Sierra Leone, December 2014-February 2015.

    PubMed

    Haaskjold, Yngvar Lunde; Bolkan, Håkon Angell; Krogh, Kurt Østhuus; Jongopi, James; Lundeby, Karen Marie; Mellesmo, Sindre; Garcés, Pedro San José; Jøsendal, Ola; Øpstad, Åsmund; Svensen, Erling; Fuentes, Luis Matias Zabala; Kamara, Alfred Sandy; Riera, Melchor; Arranz, Javier; Roberts, David P; Stamper, Paul D; Austin, Paula; Moosa, Alfredo J; Marke, Dennis; Hassan, Shoaib; Eide, Geir Egil; Berg, Åse; Blomberg, Bjørn

    2016-09-01

    The 2013-2016 outbreak of Ebola virus disease (EVD) in West Africa infected >28,000 people, including >11,000 who died, and disrupted social life in the region. We retrospectively studied clinical signs and symptoms and risk factors for fatal outcome among 31 Ebola virus-positive patients admitted to the Ebola Treatment Center in Moyamba District, Sierra Leone. We found a higher rate of bleeding manifestations than reported elsewhere during the outbreak. Significant predictors for death were shorter time from symptom onset to admission, male sex, high viral load on initial laboratory testing, severe pain, diarrhea, bloody feces, and development of other bleeding manifestations during hospitalization. These risk factors for death could be used to identify patients in need of more intensive medical support. The lack of fever in as many as one third of EVD cases may have implications for temperature-screening practices and case definitions. PMID:27268303

  20. 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

  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. Beyond Knowledge and Awareness: Addressing Misconceptions in Ghana’s Preparation towards an Outbreak of Ebola Virus Disease

    PubMed Central

    Adongo, Philip Baba; Tabong, Philip Teg-Nefaah; Asampong, Emmanuel; Ansong, Joana; Robalo, Magda; Adanu, Richard M.

    2016-01-01

    Background Ebola Virus Disease (EVD) is not new to the world. However, the West African EVD epidemic which started in 2014 evolved into the largest, most severe and most complex outbreak in the history of the disease. The three most-affected countries faced enormous challenges in stopping the transmission and providing care for all patients. Although Ghana had not recorded any confirmed Ebola case, social factors have been reported to hinder efforts to control the outbreak in the three most affected countries. This qualitative study was designed to explore community knowledge and attitudes about Ebola and its transmission. Methods This study was carried out in five of the ten regions in Ghana. Twenty-five focus group discussions (N = 235) and 40 in-depth interviews were conducted across the five regions with community members, stakeholders and opinion leaders. The interviews were recorded digitally and transcribed verbatim. Framework analysis was adopted in the analysis of the data using Nvivo 10. Results The results showed a high level of awareness and knowledge about Ebola. The study further showed that knowledge on how to identify suspected cases of Ebola was also high among respondents. However, there was a firm belief that Ebola was a spiritual condition and could also be transmitted through air, mosquito bites and houseflies. These misconceptions resulted in perceptions of stigma and discrimination towards people who may get Ebola or work with Ebola patients. Conclusion We conclude that although knowledge and awareness about Ebola is high among Ghanaians who participated in the study, there are still misconceptions about the disease. The study recommends that health education on Ebola disease should move beyond creating awareness to targeting the identified misconceptions to improve future containment efforts. PMID:26889683

  3. Particle-to-PFU Ratio of Ebola Virus Influences Disease Course and Survival in Cynomolgus Macaques

    PubMed Central

    Alfson, Kendra J.; Avena, Laura E.; Beadles, Michael W.; Staples, Hilary; Nunneley, Jerritt W.; Ticer, Anysha; Dick, Edward J.; Owston, Michael A.; Reed, Christopher; Patterson, Jean L.; Carrion, Ricardo

    2015-01-01

    ABSTRACT This study addresses the role of Ebola virus (EBOV) specific infectivity in virulence. Filoviruses are highly lethal, enveloped, single-stranded negative-sense RNA viruses that can cause hemorrhagic fever. No approved vaccines or therapies exist for filovirus infections, and infectious virus must be handled in maximum containment. Efficacy testing of countermeasures, in addition to investigations of pathogenicity and immune response, often requires a well-characterized animal model. For EBOV, an obstacle in performing accurate disease modeling is a poor understanding of what constitutes an infectious dose in animal models. One well-recognized consequence of viral passage in cell culture is a change in specific infectivity, often measured as a particle-to-PFU ratio. Here, we report that serial passages of EBOV in cell culture resulted in a decrease in particle-to-PFU ratio. Notably, this correlated with decreased potency in a lethal cynomolgus macaque (Macaca fascicularis) model of infection; animals were infected with the same viral dose as determined by plaque assay, but animals that received more virus particles exhibited increased disease. This suggests that some particles are unable to form a plaque in a cell culture assay but are able to result in lethal disease in vivo. These results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures. IMPORTANCE Ebola virus (EBOV) can cause severe hemorrhagic disease with a high case-fatality rate, and there are no approved vaccines or therapies. Specific infectivity can be considered the total number of viral particles per PFU, and its impact on disease is poorly understood. In stocks of most mammalian viruses, there are particles that are unable to complete an infectious cycle or unable to cause cell pathology in cultured cells. We asked if these particles cause disease in nonhuman primates by infecting monkeys with equal infectious doses of genetically

  4. Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists

    PubMed Central

    Cheng, Han; Lear-Rooney, Calli M.; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W.; Olinger, Gene G.

    2015-01-01

    ABSTRACT Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. IMPORTANCE Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of

  5. Mechanism of Binding to Ebola Virus Glycoprotein by the ZMapp, ZMAb, and MB-003 Cocktail Antibodies

    PubMed Central

    Davidson, Edgar; Bryan, Christopher; Fong, Rachel H.; Barnes, Trevor; Pfaff, Jennifer M.; Mabila, Manu; Rucker, Joseph B.

    2015-01-01

    ABSTRACT Cocktails of monoclonal antibodies (MAbs) that target the surface glycoprotein (GP) of Ebola virus (EBOV) are effective in nonhuman primate models and have been used under emergency compassionate-treatment protocols in human patients. However, the amino acids that form the detailed binding epitopes for the MAbs in the ZMapp, ZMAb, and the related MB-003 cocktails have yet to be identified. Other binding properties that define how each MAb functionally interacts with GP—such as affinity, epitope conservation, and epitope accessibility—also remain largely unknown. To help define how each MAb interacts with GP, here we used comprehensive alanine-scanning mutagenesis (shotgun mutagenesis), neutralization escape, and whole virion binding to define each MAb's specific epitope, epitope accessibility, epitope conservation, and apparent affinity. Each of the six therapeutic MAbs binds nonidentical epitopes in the GP base, glycan cap, or mucin-like domain. Their apparent affinity, epitope complementarity, and epitope accessibility helps explain why MAbs 4G7 and 13C6 are more protective than 2G4 and 1H3. The mucin-like domain MAbs 6D8 and 13F6 bind with the strongest apparent affinity, helping to explain their effectiveness in vivo despite their inability to neutralize virus. IMPORTANCE Ebola virus disease (EVD) can be caused by four different filovirus family members, including Ebola virus (EBOV), which infected 10 times more people in western Africa over the last year than all previous EVD outbreaks combined, with a number of cases distributed across the globe by travelers. Cocktails of inhibitory monoclonal antibodies (MAbs), such as ZMAb, MB-003, and in particular ZMapp, have demonstrated in animal models some of the most significant therapeutic potential for treating EVD, and in 2014, 15 patients were treated with ZMapp or ZMAb under compassionate-use protocols. Here, we have defined the epitope features for the most important therapeutic MAbs against EBOV

  6. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches

    PubMed Central

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  7. 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

  8. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches.

    PubMed

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  9. 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

  10. Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses

    PubMed Central

    Frei, Julia C.; Nyakatura, Elisabeth K.; Zak, Samantha E.; Bakken, Russell R.; Chandran, Kartik; Dye, John M.; Lai, Jonathan R.

    2016-01-01

    Filoviruses (Ebola and Marburg) cause severe hemorrhagic fever. There are five species of ebolavirus; among these, the Ebola (Zaire) and Sudan viruses (EBOV and SUDV, respectively) are highly pathogenic and have both caused recurring, large outbreaks. However, the EBOV and SUDV glycoprotein (GP) sequences are 45% divergent and thus antigenically distinct. Few antibodies with cross-neutralizing properties have been described to date. We used antibody engineering to develop novel bispecific antibodies (Bis-mAbs) that are cross-reactive toward base epitopes on GP from EBOV and SUDV. These Bis-mAbs exhibit potent neutralization against EBOV and SUDV GP pseudotyped viruses as well as authentic pathogens, and confer a high degree (in one case 100%) post-exposure protection of mice from both viruses. Our studies show that a single agent that targets the GP base epitopes is sufficient for protection in mice; such agents could be included in panfilovirus therapeutic antibody cocktails. PMID:26758505

  11. Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses.

    PubMed

    Frei, Julia C; Nyakatura, Elisabeth K; Zak, Samantha E; Bakken, Russell R; Chandran, Kartik; Dye, John M; Lai, Jonathan R

    2016-01-01

    Filoviruses (Ebola and Marburg) cause severe hemorrhagic fever. There are five species of ebolavirus; among these, the Ebola (Zaire) and Sudan viruses (EBOV and SUDV, respectively) are highly pathogenic and have both caused recurring, large outbreaks. However, the EBOV and SUDV glycoprotein (GP) sequences are 45% divergent and thus antigenically distinct. Few antibodies with cross-neutralizing properties have been described to date. We used antibody engineering to develop novel bispecific antibodies (Bis-mAbs) that are cross-reactive toward base epitopes on GP from EBOV and SUDV. These Bis-mAbs exhibit potent neutralization against EBOV and SUDV GP pseudotyped viruses as well as authentic pathogens, and confer a high degree (in one case 100%) post-exposure protection of mice from both viruses. Our studies show that a single agent that targets the GP base epitopes is sufficient for protection in mice; such agents could be included in panfilovirus therapeutic antibody cocktails. PMID:26758505

  12. 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; Avšič-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

  13. [Detection of the Zaire Subtype of the Ebola Virus by Isothermal Multiple Self-matching Initiated Amplification].

    PubMed

    Li, Xinna; Nie, Kai; Wang, Ji; Zhang, Dan; Guan, Li; Liu, Jun; Ke, Yuehua; Zhou, Hangyu; Ma, Xuejun

    2016-01-01

    Given the Ebola outbreak in West Africa and the risks of spread to other regions, a rapid, sensitive and simple method for the detection of the Ebola virus (EBOV) is of great significance for the prevention and control of Ebola. We developed a simple colorimetric isothermal multiple self-matching initiated amplification (IMSA) for rapid detection of the Zaire subtype of the Ebola virus (EBOV-Z). This method employed six primers that recognized seven sites of the EBOV-Z nucleoprotein gene for amplification of nucleic acids under isothermal conditions at 63 degrees C for 1 h. Amplification products were detected through visual inspection of color change by pre-addition of hydroxyl naphthol blue dye. Relative sensitivity was validated by detection of serial tenfold dilutions of virus-like particles containing the partial EBOV-Z nucleoprotein gene and mock clinical sample. Specificity of IMSA was validated by detection of the plasma of 30 healthy volunteers, the dengue virus, and Japanese encephalitis virus. IMSA had comparable sensitivity to Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and cross-reaction with human plasma or other viruses was not observed. Reverse transcription-isothermal multiple self-matching initiated amplification (RT-IMSA) was also evaluated and compared in parallel with the commercial RT-qPCR kit for detection of EBOV-suspected samples of human blood in Sierra Leone. Sensitivity and specificity of the RT-IMSA was 91.4% and 100%, respectively. These data suggest that RT-IMSA is a valuable tool for the detection of the EBOV with the distinct advantages of simplicity and low cost compared with RT-qPCR. PMID:27295876

  14. Exposure-Specific and Age-Specific Attack Rates for Ebola Virus Disease in Ebola-Affected Households, Sierra Leone.

    PubMed

    Bower, Hilary; Johnson, Sembia; Bangura, Mohamed S; Kamara, Alie Joshua; Kamara, Osman; Mansaray, Saidu H; Sesay, Daniel; Turay, Cecilia; Checchi, Francesco; Glynn, Judith R

    2016-08-01

    Using histories of household members of Ebola virus disease (EVD) survivors in Sierra Leone, we calculated risk of EVD by age and exposure level, adjusting for confounding and clustering, and estimated relative risks. Of 937 household members in 94 households, 448 (48%) had had EVD. Highly correlated with exposure, EVD risk ranged from 83% for touching a corpse to 8% for minimal contact and varied by age group: 43% for children <2 years of age; 30% for those 5-14 years of age; and >60% for adults >30 years of age. Compared with risk for persons 20-29 years of age, exposure-adjusted relative risks were lower for those 5-9 (0.70), 10-14 (0.64), and 15-19 (0.71) years of age but not for children <2 (0.92) or 2-4 (0.97) years of age. Lower risk for 5-19-year-olds, after adjustment for exposure, suggests decreased susceptibility in this group. PMID:27144428

  15. Exposure-Specific and Age-Specific Attack Rates for Ebola Virus Disease in Ebola-Affected Households, Sierra Leone

    PubMed Central

    Bower, Hilary; Johnson, Sembia; Bangura, Mohamed S.; Kamara, Alie Joshua; Kamara, Osman; Mansaray, Saidu H.; Sesay, Daniel; Turay, Cecilia; Checchi, Francesco

    2016-01-01

    Using histories of household members of Ebola virus disease (EVD) survivors in Sierra Leone, we calculated risk of EVD by age and exposure level, adjusting for confounding and clustering, and estimated relative risks. Of 937 household members in 94 households, 448 (48%) had had EVD. Highly correlated with exposure, EVD risk ranged from 83% for touching a corpse to 8% for minimal contact and varied by age group: 43% for children <2 years of age; 30% for those 5–14 years of age; and >60% for adults >30 years of age. Compared with risk for persons 20–29 years of age, exposure-adjusted relative risks were lower for those 5–9 (0.70), 10–14 (0.64), and 15–19 (0.71) years of age but not for children <2 (0.92) or 2–4 (0.97) years of age. Lower risk for 5–19-year-olds, after adjustment for exposure, suggests decreased susceptibility in this group. PMID:27144428

  16. 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

  17. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection

    PubMed Central

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-01-01

    Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. PMID:27067649

  18. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.

    PubMed

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-01-01

    Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab')2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab')2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. PMID:27067649

  19. Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions.

    PubMed

    Geisbert, Thomas W; Hensley, Lisa E

    2004-09-21

    Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicized isolation of a new EBOV species in a suburb of Washington, DC, in 1989, together with the dramatic clinical presentation of EBOV infection and high case-fatality rate in Africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. Furthermore, there are no vaccines or effective therapies currently available. Progress in understanding the origins of the pathophysiological changes that make EBOV infections of humans so devastating has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the mechanisms of EBOV pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. Notably, identifying factors triggering the haemorrhagic complications that characterise EBOV infections led to the development of a strategy to modulate coagulopathy; this therapeutic modality successfully mitigated the effects of EBOV haemorrhagic fever in nonhuman primates. This review summarises our current understanding of EBOV pathogenesis and discusses various approaches to therapeutic intervention based on our current understanding of how EBOV produces a lethal infection. PMID:15383160

  20. Tyro3 Family-Mediated Cell Entry of Ebola and Marburg Viruses

    PubMed Central

    Shimojima, Masayuki; Takada, Ayato; Ebihara, Hideki; Neumann, Gabriele; Fujioka, Kouki; Irimura, Tatsuro; Jones, Steven; Feldmann, Heinz; Kawaoka, Yoshihiro

    2006-01-01

    Filoviruses, represented by the genera Ebolavirus and Marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. Although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family—Axl, Dtk, and Mer—in cell entry of filoviruses. Ectopic expression of these family members in lymphoid cells, which otherwise are highly resistant to filovirus infection, enhanced infection by pseudotype viruses carrying filovirus glycoproteins on their envelopes. This enhancement was reduced by antibodies to Tyro3 family members, Gas6 ligand, or soluble ectodomains of the members. Live Ebola viruses infected both Axl- and Dtk-expressing cells more efficiently than control cells. Antibody to Axl inhibited infection of pseudotype viruses in a number of Axl-positive cell lines. These results implicate each Tyro3 family member as a cell entry factor in filovirus infection. PMID:17005688

  1. 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

  2. A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles

    PubMed Central

    Ndungo, Esther; Herbert, Andrew S.; Raaben, Matthijs; Obernosterer, Gregor; Biswas, Rohan; Miller, Emily Happy; Wirchnianski, Ariel S.; Carette, Jan E.; Brummelkamp, Thijn R.; Whelan, Sean P.

    2016-01-01

    ABSTRACT Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell’s viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell’s viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1’s endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell’s viper are not susceptible to infection because EBOV

  3. A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles.

    PubMed

    Ndungo, Esther; Herbert, Andrew S; Raaben, Matthijs; Obernosterer, Gregor; Biswas, Rohan; Miller, Emily Happy; Wirchnianski, Ariel S; Carette, Jan E; Brummelkamp, Thijn R; Whelan, Sean P; Dye, John M; Chandran, Kartik

    2016-01-01

    Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell's viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell's viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1's endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell's viper are not susceptible to infection because EBOV cannot bind to

  4. BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.

    PubMed

    Taylor, Raymond; Kotian, Pravin; Warren, Travis; Panchal, Rekha; Bavari, Sina; Julander, Justin; Dobo, Sylvia; Rose, Angela; El-Kattan, Yahya; Taubenheim, Brian; Babu, Yarlagadda; Sheridan, William P

    2016-01-01

    The adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing. PMID:27095300

  5. 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

  6. Ethical and Practical Considerations in Providing Critical Care to Patients With Ebola Virus Disease

    PubMed Central

    Davey, Richard T.; Suffredini, Anthony F.; Chertow, Daniel S.

    2015-01-01

    Infectious disease epidemics in the past have given rise to psychologic and emotional responses among health-care workers (HCWs), stemming from fear of infection during patient care. Early experiences in the AIDS epidemic provide an example where fear of contagion resulted in differential treatment of patients infected with HIV. However, with a deeper understanding of AIDS pathogenesis and treatment, fear and discrimination diminished. Parallels exist between early experiences with AIDS and the present outbreak of Ebola virus disease in West Africa, particularly regarding discussions of medical futility in seriously ill patients. We provide a historical perspective on HCWs’ risk of infection during the provision of CPR, discuss physicians’ duty to treat in the face of perceived or actual HCW risk, and, finally, present the protocols implemented at the National Institutes of Health to reduce HCW risk while providing lifesaving and life-sustaining care. PMID:25764372

  7. Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model

    PubMed Central

    Cheresiz, S. V.; Semenova, E. A.; Chepurnov, A. A.

    2016-01-01

    Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups. PMID:26989413

  8. Historical Parallels, Ebola Virus Disease and Cholera: Understanding Community Distrust and Social Violence with Epidemics

    PubMed Central

    Cohn, Samuel; Kutalek, Ruth

    2016-01-01

    In the three West African countries most affected by the recent Ebola virus disease (EVD) outbreak, resistance to public health measures contributed to the startling speed and persistence of this epidemic in the region. But how do we explain this resistance, and how have people in these communities understood their actions? By comparing these recent events to historical precedents during Cholera outbreaks in Europe in the 19th century we show that these events have not been new to history or unique to Africa. Community resistance must be analysed in context and go beyond simple single-variable determinants. Knowledge and respect of the cultures and beliefs of the afflicted is essential for dealing with threatening disease outbreaks and their potential social violence. PMID:26865987

  9. 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

  10. Updates to the zoonotic niche map of Ebola virus disease in Africa.

    PubMed

    Pigott, David M; Millear, Anoushka I; Earl, Lucas; Morozoff, Chloe; Han, Barbara A; Shearer, Freya M; Weiss, Daniel J; Brady, Oliver J; Kraemer, Moritz Ug; Moyes, Catherine L; Bhatt, Samir; Gething, Peter W; Golding, Nick; Hay, Simon I

    2016-01-01

    As the outbreak of Ebola virus disease (EVD) in West Africa is now contained, attention is turning from control to future outbreak prediction and prevention. Building on a previously published zoonotic niche map (Pigott et al., 2014), this study incorporates new human and animal occurrence data and expands upon the way in which potential bat EVD reservoir species are incorporated. This update demonstrates the potential for incorporating and updating data used to generate the predicted suitability map. A new data portal for sharing such maps is discussed. This output represents the most up-to-date estimate of the extent of EVD zoonotic risk in Africa. These maps can assist in strengthening surveillance and response capacity to contain viral haemorrhagic fevers. PMID:27414263

  11. A case of severe Ebola virus infection complicated by gram-negative septicemia.

    PubMed

    Kreuels, Benno; Wichmann, Dominic; Emmerich, Petra; Schmidt-Chanasit, Jonas; de Heer, Geraldine; Kluge, Stefan; Sow, Abdourahmane; Renné, Thomas; Günther, Stephan; Lohse, Ansgar W; Addo, Marylyn M; Schmiedel, Stefan

    2014-12-18

    Ebola virus disease (EVD) developed in a patient who contracted the disease in Sierra Leone and was airlifted to an isolation facility in Hamburg, Germany, for treatment. During the course of the illness, he had numerous complications, including septicemia, respiratory failure, and encephalopathy. Intensive supportive treatment consisting of high-volume fluid resuscitation (approximately 10 liters per day in the first 72 hours), broad-spectrum antibiotic therapy, and ventilatory support resulted in full recovery without the use of experimental therapies. Discharge was delayed owing to the detection of viral RNA in urine (day 30) and sweat (at the last assessment on day 40) by means of polymerase-chain-reaction (PCR) assay, but the last positive culture was identified in plasma on day 14 and in urine on day 26. This case shows the challenges in the management of EVD and suggests that even severe EVD can be treated effectively with routine intensive care. PMID:25337633

  12. Epidemiology of Epidemic Ebola Virus Disease in Conakry and Surrounding Prefectures, Guinea, 2014–2015

    PubMed Central

    Brody, Debra; Coronado, Fátima; Rondy, Marc; Fiebig, Lena; Carcelen, Andrea; Deyde, Varough M.; Mesfin, Samuel; Retzer, Kyla D.; Bilivogui, Pepe; Keita, Sakoba; Dahl, Benjamin A.

    2016-01-01

    In 2014, Ebola virus disease (EVD) in West Africa was first reported during March in 3 southeastern prefectures in Guinea; from there, the disease rapidly spread across West Africa. We describe the epidemiology of EVD cases reported in Guinea’s capital, Conakry, and 4 surrounding prefectures (Coyah, Dubreka, Forecariah, and Kindia), encompassing a full year of the epidemic. A total of 1,355 EVD cases, representing ≈40% of cases reported in Guinea, originated from these areas. Overall, Forecariah had the highest cumulative incidence (4× higher than that in Conakry). Case-fatality percentage ranged from 40% in Conakry to 60% in Kindia. Cumulative incidence was slightly higher among male than female residents, although incidences by prefecture and commune differed by sex. Over the course of the year, Conakry and neighboring prefectures became the EVD epicenter in Guinea. PMID:26812047

  13. Reconsidering the ethical permissibility of the use of unregistered interventions against Ebola virus disease.

    PubMed

    Landry, Joshua T; Foreman, Thomas; Kekewich, Michael

    2015-07-01

    Ethical considerations for the use of unregistered interventions for Ebola virus disease have sparked considerable debate among academic and clinical ethicists. In August 2014 the World Health Organization (WHO) convened a panel of experts to discuss approaches to the outbreak in West Africa, with the goal of determining "whether it is ethical to use unregistered interventions with unknown adverse effects for possible treatment or prophylaxis". 1 The panel concluded that there would be an ethical imperative to provide such unregistered interventions if specific criteria could be met. This paper evaluates the WHO conclusion and argues that although it may be reasonable to provide unregistered interventions considering the circumstance, there is no clear ethical imperative to do so. PMID:26059962

  14. Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model.

    PubMed

    Cheresiz, S V; Semenova, E A; Chepurnov, A A

    2016-01-01

    Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups. PMID:26989413

  15. 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. PMID:26740836

  16. Updates to the zoonotic niche map of Ebola virus disease in Africa

    PubMed Central

    Pigott, David M; Millear, Anoushka I; Earl, Lucas; Morozoff, Chloe; Han, Barbara A; Shearer, Freya M; Weiss, Daniel J; Brady, Oliver J; Kraemer, Moritz UG; Moyes, Catherine L; Bhatt, Samir; Gething, Peter W; Golding, Nick; Hay, Simon I

    2016-01-01

    As the outbreak of Ebola virus disease (EVD) in West Africa is now contained, attention is turning from control to future outbreak prediction and prevention. Building on a previously published zoonotic niche map (Pigott et al., 2014), this study incorporates new human and animal occurrence data and expands upon the way in which potential bat EVD reservoir species are incorporated. This update demonstrates the potential for incorporating and updating data used to generate the predicted suitability map. A new data portal for sharing such maps is discussed. This output represents the most up-to-date estimate of the extent of EVD zoonotic risk in Africa. These maps can assist in strengthening surveillance and response capacity to contain viral haemorrhagic fevers. DOI: http://dx.doi.org/10.7554/eLife.16412.001 PMID:27414263

  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. Vaccines. An Ebola whole-virus vaccine is protective in nonhuman primates.

    PubMed

    Marzi, Andrea; Halfmann, Peter; Hill-Batorski, Lindsay; Feldmann, Friederike; Shupert, W Lesley; Neumann, Gabriele; Feldmann, Heinz; Kawaoka, Yoshihiro

    2015-04-24

    Zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in West Africa. Previously, we showed that a whole Ebola virus (EBOV) vaccine based on a replication-defective EBOV (EBOVΔVP30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted EBOV. Here, we demonstrate that EBOVΔVP30 protects nonhuman primates against lethal infection with EBOV. Although EBOVΔVP30 is replication-incompetent, we additionally inactivated the vaccine with hydrogen peroxide; the chemically inactivated vaccine remained antigenic and protective in nonhuman primates. EBOVΔVP30 thus represents a safe, efficacious, whole-EBOV vaccine candidate that differs from other EBOV vaccine platforms in that it presents all viral proteins and the viral RNA to the host immune system, which might contribute to protective immune responses. PMID:25814063

  19. Ethical and practical considerations in providing critical care to patients with Ebola virus disease.

    PubMed

    Torabi-Parizi, Parizad; Davey, Richard T; Suffredini, Anthony F; Chertow, Daniel S

    2015-06-01

    Infectious disease epidemics in the past have given rise to psychologic and emotional responses among health-care workers (HCWs), stemming from fear of infection during patient care. Early experiences in the AIDS epidemic provide an example where fear of contagion resulted in differential treatment of patients infected with HIV. However, with a deeper understanding of AIDS pathogenesis and treatment, fear and discrimination diminished. Parallels exist between early experiences with AIDS and the present outbreak of Ebola virus disease in West Africa, particularly regarding discussions of medical futility in seriously ill patients. We provide a historical perspective on HCWs' risk of infection during the provision of CPR, discuss physicians' duty to treat in the face of perceived or actual HCW risk, and, finally, present the protocols implemented at the National Institutes of Health to reduce HCW risk while providing lifesaving and life-sustaining care. PMID:25764372

  20. 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

  1. Ebola virus disease: epidemiology, clinical presentation, and diagnostic and therapeutic modalities.

    PubMed

    Dulaurier, Marlie; Moyer, Katherine; Wallihan, Rebecca

    2016-07-01

    Ebola virus disease (EVD) is a severe multisystem disease. Prehospital personnel, hospitals, and clinicians must be prepared to provide care for patients with EVD, with special attention to rigorous infection control in order to limit the spread of infection. Children with EVD are an especially challenging population, as the initial symptoms are nonspecific and difficult to differentiate from several common infections. For children presenting with a syndrome consistent with EVD, it is extremely important that healthcare workers identify epidemiologic risk factors, such as recent travel to an affected country or exposure to a patient with suspected or known EVD. Given the high morbidity and mortality of this disease, clinical efforts should focus on early diagnosis, appropriate infection control, and supportive care. PMID:27328168

  2. Assessing the Knowledge, Attitudes, and Practices of Students Regarding Ebola Virus Disease Outbreak

    PubMed Central

    HOLAKOUIE-NAIENI, Kourosh; AHMADVAND, Alireza; RAZA, Owais; ASSAN, Abraham; ELDUMA, Adel Hussein; JAMMEH, Alieu; KAMALI, Aram Salih Mohammed Amin; KAREEM, Ahang Abdullah; MUHAMMAD, Fatima Mahmud; SABAHAT, Hasnain; ABDULLAHI, Kabir Ozigi; SAEED, Raeed Ahmad; SAEED, Sami Najmaddin

    2015-01-01

    Background: The emergence and spread of Ebola outbreak is a growing problem worldwide, which represents a significant threat to public health. Evidence has shown that the level of knowledge, attitude, and practice of people in the society play major roles in controlling the spread of Ebola virus disease. This study was designed to determine knowledge, attitude and practice of students at School of Public Health, Tehran University of Medical Sciences towards Ebola. Methods: A cross-sectional survey was performed in Tehran, Iran in 2014 using a pretested self-administered questionnaire on a stratified sample of 400 students. Descriptive and multivariate analyses were used for statistical analysis. Results: All-in-all, 385 students returned the completed questionnaires making a response rate of 96.3%., 239 (62.2%) were females and 145 (37.8%) were males. The mean age of female and males were 28.44 and 30.3 years respectively. Of the 385 students, 83 (21.7%) were studying at PhD level, 210 (55.0%) at Masters Level (including MPH) and 89 (23.3%) at Bachelors level. knowledge of the students regarding EVD transmission was lowest among students of Department of Occupational Health (50.0%), followed by Health Education and Promotion Department (33.3%). Virology Department recorded the highest percentage of students who had selected correct answers regarding EVD prevention (100.0%) Conclusion: These findings will aid in the assessment of the adequacy of current students’ educational curriculum. Also, it will provide further insight in designing future multifaceted interventions to promote specific messages to change attitude and improve practice. PMID:26811818

  3. Transmission dynamics of Ebola virus disease and intervention effectiveness in Sierra Leone

    PubMed Central

    Fang, Li-Qun; Yang, Yang; Jiang, Jia-Fu; Yao, Hong-Wu; Kargbo, David; Li, Xin-Lou; Jiang, Bao-Gui; Kargbo, Brima; Tong, Yi-Gang; Wang, Ya-Wei; Liu, Kun; Kamara, Abdul; Dafae, Foday; Kanu, Alex; Jiang, Rui-Ruo; Sun, Ye; Sun, Ruo-Xi; Chen, Wan-Jun; Ma, Mai-Juan; Dean, Natalie E.; Thomas, Harold; Longini, Ira M.; Halloran, M. Elizabeth; Cao, Wu-Chun

    2016-01-01

    Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014−2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission. PMID:27035948

  4. Transmission dynamics of Ebola virus disease and intervention effectiveness in Sierra Leone.

    PubMed

    Fang, Li-Qun; Yang, Yang; Jiang, Jia-Fu; Yao, Hong-Wu; Kargbo, David; Li, Xin-Lou; Jiang, Bao-Gui; Kargbo, Brima; Tong, Yi-Gang; Wang, Ya-Wei; Liu, Kun; Kamara, Abdul; Dafae, Foday; Kanu, Alex; Jiang, Rui-Ruo; Sun, Ye; Sun, Ruo-Xi; Chen, Wan-Jun; Ma, Mai-Juan; Dean, Natalie E; Thomas, Harold; Longini, Ira M; Halloran, M Elizabeth; Cao, Wu-Chun

    2016-04-19

    Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014-2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission. PMID:27035948

  5. 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. χ2 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

  6. 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

  7. 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. PMID:26740849

  8. 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

  9. 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

  10. Dynamics and control of Ebola virus transmission in Montserrado, Liberia: a mathematical modeling analysis

    PubMed Central

    Lewnard, Joseph A.; Ndeffo Mbah, Martial L.; Alfaro-Murillo, Jorge A.; Altice, Frederick L.; Bawo, Luke; Nyenswah, Tolbert G.; Galvani, Alison P.

    2014-01-01

    Background A substantial scale-up in public health response is needed to control the unprecedented Ebola virus disease (EVD) epidemic in West Africa. Current international commitments seek to expand intervention capacity in three areas: new EVD Treatment Centers (ETCs); case ascertainment through contact tracing; and household protective kit allocation. Methods We developed a transmission model of Ebola virus that we fitted to reported EVD cases and deaths in Montserrado County, Liberia. We used this model to evaluate effectiveness of expanding ETCs, improving case ascertainment, and allocating protective kits for controlling the outbreak in Montserrado. Findings We estimated the basic reproductive number for EVD in Montserrado to be 2·49 [2·38–2·60]. We expect that allocating 4,800 additional ETC beds and increasing case ascertainment fivefold in November can avert 77312 [68400–85870] cases relative to the status quo by 15 December. Complementing these measures with protective kit allocation increases the expectation as high as 97940 [90096–105606] cases. If deployed by 15 October, equivalent interventions would have been expected to avert 137432 [129736–145874] cases. If delayed to 15 November, we expect the interventions will at best avert 53957 [49963–60490] cases. Interpretation The number of ETC beds needed to effectively control EVD in Montserrado substantially exceeds the total pledged by the United States to West Africa. Accelerated case ascertainment is required to maximize effectiveness of expanding ETC capacity. Distributing protective kits can further augment EVD prevention. Our findings highlight the rapidly closing window of opportunity for controlling the outbreak and averting a catastrophic toll of EVD cases and deaths. Funding NIH: U01-GM087719, U01-GM105627, K24-DA017072 PMID:25455986

  11. Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions.

    PubMed

    Zhao, Yuguang; Ren, Jingshan; Harlos, Karl; Stuart, David I

    2016-03-01

    Niemann-pick type C1 (NPC1) is an endo/lysosomal membrane protein involved in intracellular cholesterol trafficking, and its luminal domain C is an essential endosomal receptor for Ebola and Marburg viruses. We have determined the crystal structure of glycosylated NPC1 luminal domain C and find all seven possible sites are glycosylated. Mapping the disease mutations onto the glycosylated structure reveals a potential binding face for NPC2. Knowledge-based docking of NPC1 onto Ebola viral glycoprotein and sequence analysis of filovirus susceptible and refractory species reveals four critical residues, H418, Q421, F502 and F504, some or all of which are likely responsible for the species-specific susceptibility to the virus infection. PMID:26846330

  12. 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

  13. Experimental Inoculation of Egyptian Fruit Bats (Rousettus aegyptiacus) with Ebola Virus.

    PubMed

    Paweska, Janusz T; Storm, Nadia; Grobbelaar, Antoinette A; Markotter, Wanda; Kemp, Alan; Jansen van Vuren, Petrus

    2016-02-01

    Colonized Egyptian fruit bats (Rousettus aegyptiacus), originating in South Africa, were inoculated subcutaneously with Ebola virus (EBOV). No overt signs of morbidity, mortality, or gross lesions were noted. Bats seroconverted by Day 10-16 post inoculation (p.i.), with the highest mean anti-EBOV IgG level on Day 28 p.i. EBOV RNA was detected in blood from one bat. In 16 other tissues tested, viral RNA distribution was limited and at very low levels. No seroconversion could be demonstrated in any of the control bats up to 28 days after in-contact exposure to subcutaneously-inoculated bats. The control bats were subsequently inoculated intraperitoneally, and intramuscularly with the same dose of EBOV. No mortality, morbidity or gross pathology was observed in these bats. Kinetics of immune response was similar to that in subcutaneously-inoculated bats. Viral RNA was more widely disseminated to multiple tissues and detectable in a higher proportion of individuals, but consistently at very low levels. Irrespective of the route of inoculation, no virus was isolated from tissues which tested positive for EBOV RNA. Viral RNA was not detected in oral, nasal, ocular, vaginal, penile and rectal swabs from any of the experimental groups. PMID:26805873

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

    PubMed Central

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

    2015-01-01

    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 × 108 50% tissue culture infective dose per milliliter [TCID50 · ml−1]) and murine blood (EBOV concentration of 1 × 107 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

  15. High-Throughput Minigenome System for Identifying Small-Molecule Inhibitors of Ebola Virus Replication

    PubMed Central

    Edwards, Megan R.; Pietzsch, Colette; Vausselin, Thibaut; Shaw, Megan L.; Bukreyev, Alexander; Basler, Christopher F.

    2015-01-01

    Ebola virus (EBOV), a member of the family Filoviridae, is a nonsegmented negative-sense RNA virus that causes severe, often lethal, disease in humans. EBOV RNA synthesis is carried out by a complex that includes several viral proteins. The function of this machinery is essential for viral gene expression and viral replication and is therefore a potential target for antivirals. We developed and optimized a high-throughput screening (HTS) assay based on an EBOV minigenome assay, which assesses the function of the polymerase complex. The assay is robust in 384-well format and displays a large signal to background ratio and high Z-factor values. We performed a pilot screen of 2080 bioactive compounds, identifying 31 hits (1.5% of the library) with >70% inhibition of EBOV minigenome activity. We further identified eight compounds with 50% inhibitory concentrations below their 50% cytotoxic concentrations, five of which had selectivity index (SI) values >10, suggesting specificity against the EBOV polymerase complex. These included an inhibitor of inosine monophosphate dehydrogenase, a target known to modulate the EBOV replication complex. They also included novel classes of inhibitors, including inhibitors of protein synthesis and hypoxia inducible factor-1. Five compounds were tested for their ability to inhibit replication of a recombinant EBOV that expresses GFP (EBOV-GFP), and four inhibited EBOV-GFP growth at sub-cytotoxic concentrations. These data demonstrate the utility of the HTS minigenome assay for drug discovery and suggest potential directions for antifiloviral drug development. PMID:26284260

  16. Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

    NASA Astrophysics Data System (ADS)

    Muñoz, Antonio; Sigwalt, David; Illescas, Beatriz M.; Luczkowiak, Joanna; Rodríguez-Pérez, Laura; Nierengarten, Iwona; Holler, Michel; Remy, Jean-Serge; Buffet, Kevin; Vincent, Stéphane P.; Rojo, Javier; Delgado, Rafael; Nierengarten, Jean-François; Martín, Nazario

    2016-01-01

    The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called ‘superballs’, that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide-alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range.

  17. Experimental Inoculation of Egyptian Fruit Bats (Rousettus aegyptiacus) with Ebola Virus

    PubMed Central

    Paweska, Janusz T.; Storm, Nadia; Grobbelaar, Antoinette A.; Markotter, Wanda; Kemp, Alan; Jansen van Vuren, Petrus

    2016-01-01

    Colonized Egyptian fruit bats (Rousettus aegyptiacus), originating in South Africa, were inoculated subcutaneously with Ebola virus (EBOV). No overt signs of morbidity, mortality, or gross lesions were noted. Bats seroconverted by Day 10–16 post inoculation (p.i.), with the highest mean anti-EBOV IgG level on Day 28 p.i. EBOV RNA was detected in blood from one bat. In 16 other tissues tested, viral RNA distribution was limited and at very low levels. No seroconversion could be demonstrated in any of the control bats up to 28 days after in-contact exposure to subcutaneously-inoculated bats. The control bats were subsequently inoculated intraperitoneally, and intramuscularly with the same dose of EBOV. No mortality, morbidity or gross pathology was observed in these bats. Kinetics of immune response was similar to that in subcutaneously-inoculated bats. Viral RNA was more widely disseminated to multiple tissues and detectable in a higher proportion of individuals, but consistently at very low levels. Irrespective of the route of inoculation, no virus was isolated from tissues which tested positive for EBOV RNA. Viral RNA was not detected in oral, nasal, ocular, vaginal, penile and rectal swabs from any of the experimental groups. PMID:26805873

  18. Cell-cell contact promotes Ebola virus GP-mediated infection.

    PubMed

    Miao, Chunhui; Li, Minghua; Zheng, Yi-Min; Cohen, Fredric S; Liu, Shan-Lu

    2016-01-15

    Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Here we provide evidence that cell-cell contact promotes infection mediated by the glycoprotein (GP) of EBOV. Interestingly, expression of EBOV GP alone, even in the absence of retroviral Gag-Pol, is sufficient to transfer a retroviral vector encoding Tet-off from cell to cell. Cell-to-cell infection mediated by EBOV GP is blocked by inhibitors of actin polymerization, but appears to be less sensitive to KZ52 neutralization. Treatment of co-cultured cells with cathepsin B/L inhibitors, or an entry inhibitor 3.47 that targets the receptor NPC1 for virus binding, also blocks cell-to-cell infection. Cell-cell contact also enhances spread of rVSV bearing GP in monocytes and macrophages, the primary targets of natural EBOV infection. Altogether, our study reveals that cell-cell contact promotes EBOV GP-mediated infection, and provides new insight into understanding EBOV spread and viral pathogenesis. PMID:26655238

  19. Two-mAb cocktail protects macaques against the Makona variant of Ebola virus.

    PubMed

    Qiu, Xiangguo; Audet, Jonathan; Lv, Ming; He, Shihua; Wong, Gary; Wei, Haiyan; Luo, Longlong; Fernando, Lisa; Kroeker, Andrea; Fausther Bovendo, Hugues; Bello, Alexander; Li, Feng; Ye, Pei; Jacobs, Michael; Ippolito, Giuseppe; Saphire, Erica Ollmann; Bi, Shengli; Shen, Beifen; Gao, George F; Zeitlin, Larry; Feng, Jiannan; Zhang, Boyan; Kobinger, Gary P

    2016-03-01

    The 2014-2015 Ebola virus (EBOV) outbreak in West Africa highlighted the urgent need for specific therapeutic interventions for infected patients. The human-mouse chimeric monoclonal antibody (mAb) cocktail ZMapp, previously shown to be efficacious in EBOV (variant Kikwit) lethally infected nonhuman primates (NHPs) when administration was initiated up to 5 days, was used in some patients during the outbreak. We show that a two-antibody cocktail, MIL77E, is fully protective in NHPs when administered at 50 mg/kg 3 days after challenge with a lethal dose of EBOV variant Makona, the virus responsible for the ongoing 2014-2015 outbreak, whereas a similar formulation of ZMapp protected two of three NHPs. The chimeric MIL77E mAb cocktail is produced in engineered Chinese hamster ovary cells and is based on mAbs c13C6 and c2G4 from ZMapp. The use of only two antibodies in MIL77E opens the door to a pan-ebolavirus cocktail. PMID:26962157

  20. 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

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

    PubMed Central

    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. DOI: http://dx.doi.org/10.7554/eLife.09015.001 PMID:26525597

  2. Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us.

    PubMed

    Varkey, Jay B; Ribner, Bruce S

    2016-06-01

    Ending the West Africa Ebola virus disease (EVD) outbreak required an unprecedented international response. For the United States, participation in the international response to the West Africa EVD outbreak provided an opportunity to learn important lessons in four key domains critical to preparing for future outbreaks of EVD and other serious communicable diseases: (i) safe and effective patient care, (ii) the role of experimental therapeutics and vaccines, (iii) infection control, and (iv) hospital and community preparedness. PMID:27337477

  3. Shed GP of Ebola Virus Triggers Immune Activation and Increased Vascular Permeability

    PubMed Central

    Escudero-Pérez, Beatriz; Volchkova, Valentina A.; Dolnik, Olga; Lawrence, Philip; Volchkov, Viktor E.

    2014-01-01

    During Ebola virus (EBOV) infection a significant amount of surface glycoprotein GP is shed from infected cells in a soluble form due to cleavage by cellular metalloprotease TACE. Shed GP and non-structural secreted glycoprotein sGP, both expressed from the same GP gene, have been detected in the blood of human patients and experimentally infected animals. In this study we demonstrate that shed GP could play a particular role during EBOV infection. In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines (TNFα, IL1β, IL6, IL8, IL12p40, and IL1-RA, IL10). Activation of these cells by shed GP correlates with the increase in surface expression of co-stimulatory molecules CD40, CD80, CD83 and CD86. Contrary to shed GP, secreted sGP activates neither DC nor macrophages while it could bind DCs. In this study, we show that shed GP activity is likely mediated through cellular toll-like receptor 4 (TLR4) and is dependent on GP glycosylation. Treatment of cells with anti-TLR4 antibody completely abolishes shed GP-induced activation of cells. We also demonstrate that shed GP activity is negated upon addition of mannose-binding sera lectin MBL, a molecule known to interact with sugar arrays present on the surface of different microorganisms. Furthermore, we highlight the ability of shed GP to affect endothelial cell function both directly and indirectly, demonstrating the interplay between shed GP, systemic cytokine release and increased vascular permeability. In conclusion, shed GP released from virus-infected cells could activate non-infected DCs and macrophages causing the massive release of pro- and anti-inflammatory cytokines and effect vascular permeability. These activities could be at the heart of the excessive and dysregulated inflammatory host reactions to infection and thus contribute to high virus pathogenicity. PMID:25412102

  4. Direct Visualization of Ebola Virus Fusion Triggering in the Endocytic Pathway

    PubMed Central

    Spence, Jennifer S.; Krause, Tyler B.; Mittler, Eva; Jangra, Rohit K.

    2016-01-01

    ABSTRACT Ebola virus (EBOV) makes extensive and intricate use of host factors in the cellular endosomal/lysosomal pathway to release its genome into the cytoplasm and initiate infection. Following viral internalization into endosomes, host cysteine proteases cleave the EBOV fusion glycoprotein (GP) to unmask the binding site for its intracellular receptor, the cholesterol transporter Niemann-Pick C1 (NPC1). GP-NPC1 interaction is required for viral entry. Despite these and other recent discoveries, late events in EBOV entry following GP-NPC1 binding and culminating in GP-catalyzed fusion between viral and cellular lipid bilayers remain enigmatic. A mechanistic understanding of EBOV membrane fusion has been hampered by the failure of previous efforts to reconstitute fusion in vitro or at the cell surface. This report describes an assay to monitor initial steps directly in EBOV membrane fusion—triggering of GP and virus-cell lipid mixing—by single virions in live cells. Fusogenic triggering of GP occurs predominantly in Rab7-positive (Rab7+) endosomes, absolutely requires interaction between proteolytically primed GP and NPC1, and is blocked by key GP-specific neutralizing antibodies with therapeutic potential. Unexpectedly, cysteine protease inhibitors do not inhibit lipid mixing by virions bearing precleaved GP, even though they completely block cytoplasmic entry by these viruses, as shown previously. These results point to distinct cellular requirements for different steps in EBOV membrane fusion and suggest a model in which host cysteine proteases are dispensable for GP fusion triggering after NPC1 binding but are required for the formation of fusion pores that permit genome delivery. PMID:26861015

  5. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

    PubMed

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-04-22

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. PMID:26953343

  6. Delivery of an Ebola Virus-Positive Stillborn Infant in a Rural Community Health Center, Sierra Leone, 2015.

    PubMed

    Bower, Hilary; Grass, Julian E; Veltus, Emily; Brault, Aaron; Campbell, Shelley; Basile, Alison Jane; Wang, David; Paddock, Christopher D; Erickson, Bobbie R; Salzer, Johanna S; Belser, Jessica; Chege, Eunice; Seneca, Dean; Saffa, Gbessay; Stroeher, Ute; Decroo, Tom; Caleo, Grazia M

    2016-02-01

    We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mother's last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women in an Ebola setting. PMID:26556830

  7. Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone

    PubMed Central

    Tiffany, Amanda; Vetter, Pauline; Mattia, John; Dayer, Julie-Anne; Bartsch, Maria; Kasztura, Miriam; Sterk, Esther; Tijerino, Ana Maria; Kaiser, Laurent; Ciglenecki, Iza

    2016-01-01

    Background. Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone. Methods. A survivor clinic opened within an Ebola treatment center compound in Freetown, Sierra Leone. At each visit, clinical and psychological assessments were conducted and free treatment was offered. Survivors were referred to a partner's hospitals if their condition could not be managed in the clinic. We used routinely collected data from the clinic to describe long-term complications of EVD and their risk factors. Results. A total of 1001 medical consultations for 166 patients were performed between 3 February and 21 June 2015. The most frequent complaints and diagnoses were arthralgia (n = 129 [77.7%]), fatigue (n = 116 [69.8%]), abdominal pain (n = 90 [54.2%]), headache (n = 87 [52.4%]), anemia (n = 83 [50%]), skin disorders (n = 81 [48.8%]), back pain (n = 54 [32.5%]), and alopecia (n = 53 [31.9%]). Ocular complications were diagnosed in 94 survivors (56.7%); uveitis was the most common (n = 57 [34%]). Survivors were 10 times more likely to develop uveitis post-EVD if they presented with red/injected eyes during the acute phase of their illness. Conclusions. Post-EVD complications among our patients were similar to those described previously and were detected early following the acute phase of disease. Follow-up of survivors should begin immediately after discharge to address sequelae as they arise and reduce the potential for development of long-term disabilities such as blindness. PMID:27001797

  8. Differences in the Comparative Stability of Ebola Virus Makona-C05 and Yambuku-Mayinga in Blood.

    PubMed

    Schuit, Michael; Miller, David M; Reddick-Elick, Mary S; Wlazlowski, Carly B; Filone, Claire Marie; Herzog, Artemas; Colf, Leremy A; Wahl-Jensen, Victoria; Hevey, Michael; Noah, James W

    2016-01-01

    In support of the response to the 2013-2016 Ebola virus disease (EVD) outbreak in Western Africa, we investigated the persistence of Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 (EBOV/Mak-C05) on non-porous surfaces that are representative of hospitals, airplanes, and personal protective equipment. We performed persistence studies in three clinically-relevant human fluid matrices (blood, simulated vomit, and feces), and at environments representative of in-flight airline passenger cabins, environmentally-controlled hospital rooms, and open-air Ebola treatment centers in Western Africa. We also compared the surface stability of EBOV/Mak-C05 to that of the prototype Ebola virus/H.sapiens-tc/COD/1976/Yambuku-Mayinga (EBOV/Yam-May), in a subset of these conditions. We show that on inert, non-porous surfaces, EBOV decay rates are matrix- and environment-dependent. Among the clinically-relevant matrices tested, EBOV persisted longest in dried human blood, had limited viability in dried simulated vomit, and did not persist in feces. EBOV/Mak-C05 and EBOV/Yam-May decay rates in dried matrices were not significantly different. However, during the drying process in human blood, EBOV/Yam-May showed significantly greater loss in viability than EBOV/Mak-C05 under environmental conditions relevant to the outbreak region, and to a lesser extent in conditions relevant to an environmentally-controlled hospital room. This factor may contribute to increased communicability of EBOV/Mak-C05 when surfaces contaminated with dried human blood are the vector and may partially explain the magnitude of the most recent outbreak, compared to prior outbreaks. These EBOV persistence data will improve public health efforts by informing risk assessments, structure remediation decisions, and response procedures for future EVD outbreaks. PMID:26849135

  9. Differences in the Comparative Stability of Ebola Virus Makona-C05 and Yambuku-Mayinga in Blood

    PubMed Central

    Schuit, Michael; Miller, David M.; Reddick-Elick, Mary S.; Wlazlowski, Carly B.; Filone, Claire Marie; Herzog, Artemas; Colf, Leremy A.; Wahl-Jensen, Victoria; Hevey, Michael; Noah, James W.

    2016-01-01

    In support of the response to the 2013–2016 Ebola virus disease (EVD) outbreak in Western Africa, we investigated the persistence of Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 (EBOV/Mak-C05) on non-porous surfaces that are representative of hospitals, airplanes, and personal protective equipment. We performed persistence studies in three clinically-relevant human fluid matrices (blood, simulated vomit, and feces), and at environments representative of in-flight airline passenger cabins, environmentally-controlled hospital rooms, and open-air Ebola treatment centers in Western Africa. We also compared the surface stability of EBOV/Mak-C05 to that of the prototype Ebola virus/H.sapiens-tc/COD/1976/Yambuku-Mayinga (EBOV/Yam-May), in a subset of these conditions. We show that on inert, non-porous surfaces, EBOV decay rates are matrix- and environment-dependent. Among the clinically-relevant matrices tested, EBOV persisted longest in dried human blood, had limited viability in dried simulated vomit, and did not persist in feces. EBOV/Mak-C05 and EBOV/Yam-May decay rates in dried matrices were not significantly different. However, during the drying process in human blood, EBOV/Yam-May showed significantly greater loss in viability than EBOV/Mak-C05 under environmental conditions relevant to the outbreak region, and to a lesser extent in conditions relevant to an environmentally-controlled hospital room. This factor may contribute to increased communicability of EBOV/Mak-C05 when surfaces contaminated with dried human blood are the vector and may partially explain the magnitude of the most recent outbreak, compared to prior outbreaks. These EBOV persistence data will improve public health efforts by informing risk assessments, structure remediation decisions, and response procedures for future EVD outbreaks. PMID:26849135

  10. 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

  11. Ebola (Ebola Virus Disease)

    MedlinePlus

    ... Ecology Graphic Language: English Español Français File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  12. 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

  13. 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

  14. 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

  15. Scientists Try to Stop Another Deadly Virus

    MedlinePlus

    ... Try to Stop Another Deadly Virus Junin, an Ebola-like disease in Argentina, has a death rate ... companies that developed a similar treatment against the Ebola virus during the 2014-2015 outbreak. That drug, ...

  16. 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

  17. 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

  18. Assessment of Community Event-Based Surveillance for Ebola Virus Disease, Sierra Leone, 2015.

    PubMed

    Ratnayake, Ruwan; Crowe, Samuel J; Jasperse, Joseph; Privette, Grayson; Stone, Erin; Miller, Laura; Hertz, Darren; Fu, Clementine; Maenner, Matthew J; Jambai, Amara; Morgan, Oliver

    2016-08-01

    In 2015, community event-based surveillance (CEBS) was implemented in Sierra Leone to assist with the detection of Ebola virus disease (EVD) cases. We assessed the sensitivity of CEBS for finding EVD cases during a 7-month period, and in a 6-week subanalysis, we assessed the timeliness of reporting cases with no known epidemiologic links at time of detection. Of the 12,126 CEBS reports, 287 (2%) met the suspected case definition, and 16 were confirmed positive. CEBS detected 30% (16/53) of the EVD cases identified during the study period. During the subanalysis, CEBS staff identified 4 of 6 cases with no epidemiologic links. These CEBS-detected cases were identified more rapidly than those detected by the national surveillance system; however, too few cases were detected to determine system timeliness. Although CEBS detected EVD cases, it largely generated false alerts. Future versions of community-based surveillance could improve case detection through increased staff training and community engagement. PMID:27434608

  19. Ebola virus disease: The use of fluorescents as markers of contamination for personal protective equipment

    PubMed Central

    Bell, Todd; Smoot, John; Patterson, Justin; Smalligan, Roger; Jordan, Richard

    2014-01-01

    The recent Ebola virus disease (EVD) outbreak has created interest in personal protective equipment (PPE) content and usage. PPE testing has historically been done by individual component, rather than as a bundle for contact isolation. Fluorescent agents are commonly used in training for infection control techniques. The purpose of our study was to compare 2 PPE bundles and to evaluate the feasibility of fluorescent markers as an assessment tool for PPE effectiveness. Eight healthcare providers volunteered for this preliminary study. Participants were randomized to 1 of 2 PPE bundles that meet current (October 20, 2014) CDC recommendations. One PPE bundle utilized commercial EVD-recommended components. The other PPE bundle used components already available at local hospitals or retail stores. Participants were also randomized to standard or high volume exposures (HVE) to simulate fluid splash. Each participant was assisted in PPE donning and doffing by an experienced trainer. A training mannequin was contaminated with fluorescent agents to simulate bodily fluids. Participants were then given clinical tasks to care for the EVD “patient.” De-gowned participants were examined under “black light” for fluorescence indicative of contamination. One participant in each PPE arm had evidence of contamination. One of the contamination events was suspected during the patient care exercise. The other contamination event was not suspected until black light examination. In spite of a large difference in cost of PPE, the two bundle arms performed similarly. Bundle testing using fluorescent markers could help identify optimal PPE systems. PMID:26793445

  20. Ebola Virus Disease: Preparedness and Infection Control Lessons Learned from Two Biocontainment Units

    PubMed Central

    Hewlett, Angela L.; Varkey, Jay B.; Smith, Philip W.; Ribner, Bruce S.

    2016-01-01

    Purpose of Review This review details infection control issues encountered in the management of patients with Ebola Virus Disease (EVD), with emphasis on how these issues were confronted in two biocontainment patient care units in the United States. Recent Findings There is a notable paucity of medical literature to guide infection control policies and procedures when caring for patients with EVD. Thus, the experience of the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital and the Nebraska Biocontainment Unit (NBU) at the University of Nebraska Medical Center serves as the basis for this review. Facility issues, staffing, transportation logistics, and appropriate use of personal protective equipment is detailed. Other topics addressed include the evaluation of patients under investigation (PUI) and ethical issues concerning the safe utilization of advanced life support. Summary This review intends to serve as a reference for facilities that are in the process of creating protocols for managing patients with EVD. Given the lack of literature to support many of the recommendations discussed, it is important to utilize the available referenced guidelines, along with the practical experiences of biocontainment units, to optimize the care provided to patients with EVD while strictly adhering to infection control principles. PMID:26098504

  1. Assessment of the severity of Ebola virus disease in Sierra Leone in 2014-2015.

    PubMed

    Wong, J Y; Zhang, W; Kargbo, D; Haque, U; Hu, W; Wu, P; Kamara, A; Chen, Y; Kargbo, B; Glass, G E; Yang, R; Cowling, B J; Liu, C

    2016-05-01

    The current Ebola virus disease (EVD) epidemic in West Africa is unprecedented in scale, and Sierra Leone is the most severely affected country. The case fatality risk (CFR) and hospitalization fatality risk (HFR) were used to characterize the severity of infections in confirmed and probable EVD cases in Sierra Leone. Proportional hazards regression models were used to investigate factors associated with the risk of death in EVD cases. In total, there were 17 318 EVD cases reported in Sierra Leone from 23 May 2014 to 31 January 2015. Of the probable and confirmed EVD cases with a reported final outcome, a total of 2536 deaths and 886 recoveries were reported. CFR and HFR estimates were 74·2% [95% credibility interval (CrI) 72·6-75·5] and 68·9% (95% CrI 66·2-71·6), respectively. Risks of death were higher in the youngest (0-4 years) and oldest (⩾60 years) age groups, and in the calendar month of October 2014. Sex and occupational status did not significantly affect the mortality of EVD. The CFR and HFR estimates of EVD were very high in Sierra Leone. PMID:27029911

  2. 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.

  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. Assessment of Community Event–Based Surveillance for Ebola Virus Disease, Sierra Leone, 2015

    PubMed Central

    Crowe, Samuel J.; Jasperse, Joseph; Privette, Grayson; Stone, Erin; Miller, Laura; Hertz, Darren; Fu, Clementine; Maenner, Matthew J.; Jambai, Amara; Morgan, Oliver

    2016-01-01

    In 2015, community event–based surveillance (CEBS) was implemented in Sierra Leone to assist with the detection of Ebola virus disease (EVD) cases. We assessed the sensitivity of CEBS for finding EVD cases during a 7-month period, and in a 6-week subanalysis, we assessed the timeliness of reporting cases with no known epidemiologic links at time of detection. Of the 12,126 CEBS reports, 287 (2%) met the suspected case definition, and 16 were confirmed positive. CEBS detected 30% (16/53) of the EVD cases identified during the study period. During the subanalysis, CEBS staff identified 4 of 6 cases with no epidemiologic links. These CEBS-detected cases were identified more rapidly than those detected by the national surveillance system; however, too few cases were detected to determine system timeliness. Although CEBS detected EVD cases, it largely generated false alerts. Future versions of community-based surveillance could improve case detection through increased staff training and community engagement. PMID:27434608

  5. Management of accidental exposure to Ebola virus in the biosafety level 4 laboratory, Hamburg, Germany.

    PubMed

    Günther, Stephan; Feldmann, Heinz; Geisbert, Thomas W; Hensley, Lisa E; Rollin, Pierre E; Nichol, Stuart T; Ströher, Ute; Artsob, Harvey; Peters, Clarence J; Ksiazek, Thomas G; Becker, Stephan; ter Meulen, Jan; Olschläger, Stephan; Schmidt-Chanasit, Jonas; Sudeck, Hinrich; Burchard, Gerd D; Schmiedel, Stefan

    2011-11-01

    A needlestick injury occurred during an animal experiment in the biosafety level 4 laboratory in Hamburg, Germany, in March 2009. The syringe contained Zaire ebolavirus (ZEBOV) mixed with Freund's adjuvant. Neither an approved treatment nor a postexposure prophylaxis (PEP) exists for Ebola hemorrhagic fever. Following a risk-benefit assessment, it was recommended the exposed person take an experimental vaccine that had shown PEP efficacy in ZEBOV-infected nonhuman primates (NHPs) [12]. The vaccine, which had not been used previously in humans, was a live-attenuated recombinant vesicular stomatitis virus (recVSV) expressing the glycoprotein of ZEBOV. A single dose of 5 × 10(7) plaque-forming units was injected 48 hours after the accident. The vaccinee developed fever 12 hours later and recVSV viremia was detectable by polymerase chain reaction (PCR) for 2 days. Otherwise, the person remained healthy, and ZEBOV RNA, except for the glycoprotein gene expressed in the vaccine, was never detected in serum and peripheral blood mononuclear cells during the 3-week observation period. PMID:21987751

  6. Development of an antibody capture ELISA using inactivated Ebola Zaire Makona virus.

    PubMed

    Krähling, Verena; Becker, Dirk; Rohde, Cornelius; Eickmann, Markus; Eroğlu, Yonca; Herwig, Astrid; Kerber, Romy; Kowalski, Katharina; Vergara-Alert, Júlia; Becker, Stephan

    2016-04-01

    The 2014 Zaire Ebola virus (ZEBOV) outbreak in West Africa represents an international public health concern. Highly sensitive and precise diagnostic tools are needed. In the present study, we developed a ZEBOV-specific enzyme-linked immunosorbent assay (ELISA) using inactivated ZEBOV isolate Makona from March 2014. Mock antigen was used to address nonspecific binding. Specificity, reproducibility and precision were determined to measure assay performance. The ZEBOV ELISA proved to be specific (96 %), reproducible and precise (Intra-assay CV 8 %, Inter-assay CV 18 %). Using the human monoclonal antibody KZ52, we showed that the ELISA was able to detect conformation-specific antibodies. Monitoring antibody development in 29 PCR-positive EBOV disease (EVD) patients revealed seroconversion in all cases. In addition, the ELISA was used to detect ZEBOV glycoprotein (GP)-specific antibodies in a vaccinated volunteer from day 14 until 5 years post-vaccination with a VSV-ZEBOV candidate vaccine. The results demonstrate the high reproducibility, specificity and sensitivity of this newly developed ELISA, which is suitable for the detection of specific antibody responses directed against different ZEBOV proteins in EVD patients and against the ZEBOV surface glycoprotein GP in vaccinated individuals. PMID:26475282

  7. Differential regulation of interferon responses by Ebola and Marburg virus VP35 proteins

    PubMed Central

    Edwards, Megan R.; Liu, Gai; Mire, Chad E.; Sureshchandra, Suhas; Luthra, Priya; Yen, Benjamin; Shabman, Reed S.; Leung, Daisy W.; Messaoudi, Ilhem; Geisbert, Thomas W.; Amarasinghe, Gaya K.; Basler, Christopher F.

    2016-01-01

    SUMMARY Suppression of innate immune responses during filoviral infection contributes to disease severity. Ebola (EBOV) and Marburg (MARV) viruses each encode a VP35 protein that suppresses RIG-I-like receptor signaling and interferon-α/β (IFN-α/β) production by several mechanisms, including direct binding to double-stranded RNA (dsRNA). Here, we demonstrate that in cell culture MARV infection results in a greater upregulation of IFN responses as compared to EBOV infection. This correlates with differences in the efficiencies by which EBOV and MARV VP35s antagonize RIG-I signaling. Furthermore, structural and biochemical studies suggest that differential recognition of RNA elements by the respective VP35 C-terminal IFN inhibitory domain (IID) rather than affinity for RNA by the respective VP35s is critical for this observation. Our results reveal functional differences in EBOV versus MARV VP35 RNA binding result in unexpected differences in the host response to deadly viral pathogens. PMID:26876165

  8. Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins.

    PubMed

    Edwards, Megan R; Liu, Gai; Mire, Chad E; Sureshchandra, Suhas; Luthra, Priya; Yen, Benjamin; Shabman, Reed S; Leung, Daisy W; Messaoudi, Ilhem; Geisbert, Thomas W; Amarasinghe, Gaya K; Basler, Christopher F

    2016-02-23

    Suppression of innate immune responses during filoviral infection contributes to disease severity. Ebola (EBOV) and Marburg (MARV) viruses each encode a VP35 protein that suppresses RIG-I-like receptor signaling and interferon-α/β (IFN-α/β) production by several mechanisms, including direct binding to double stranded RNA (dsRNA). Here, we demonstrate that in cell culture, MARV infection results in a greater upregulation of IFN responses as compared to EBOV infection. This correlates with differences in the efficiencies by which EBOV and MARV VP35s antagonize RIG-I signaling. Furthermore, structural and biochemical studies suggest that differential recognition of RNA elements by the respective VP35 C-terminal IFN inhibitory domain (IID) rather than affinity for RNA by the respective VP35s is critical for this observation. Our studies reveal functional differences in EBOV versus MARV VP35 RNA binding that result in unexpected differences in the host response to deadly viral pathogens. PMID:26876165

  9. Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail.

    PubMed

    Pettitt, James; Zeitlin, Larry; Kim, Do H; Working, Cara; Johnson, Joshua C; Bohorov, Ognian; Bratcher, Barry; Hiatt, Ernie; Hume, Steven D; Johnson, Ashley K; Morton, Josh; Pauly, Michael H; Whaley, Kevin J; Ingram, Michael F; Zovanyi, Ashley; Heinrich, Megan; Piper, Ashley; Zelko, Justine; Olinger, Gene G

    2013-08-21

    Ebola virus (EBOV) remains one of the most lethal transmissible infections and is responsible for high fatality rates and substantial morbidity during sporadic outbreaks. With increasing human incursions into endemic regions and the reported possibility of airborne transmission, EBOV is a high-priority public health threat for which no preventive or therapeutic options are currently available. Recent studies have demonstrated that cocktails of monoclonal antibodies are effective at preventing morbidity and mortality in nonhuman primates (NHPs) when administered as a post-exposure prophylactic within 1 or 2 days of challenge. To test whether one of these cocktails (MB-003) demonstrates efficacy as a therapeutic (after the onset of symptoms), we challenged NHPs with EBOV and initiated treatment upon confirmation of infection according to a diagnostic protocol for U.S. Food and Drug Administration Emergency Use Authorization and observation of a documented fever. Of the treated animals, 43% survived challenge, whereas both the controls and all historical controls with the same challenge stock succumbed to infection. These results represent successful therapy of EBOV infection in NHPs. PMID:23966302

  10. Ebola virus disease outbreak in Nigeria: Transmission dynamics and rapid control.

    PubMed

    Althaus, C L; Low, N; Musa, E O; Shuaib, F; Gsteiger, S

    2015-06-01

    International air travel has already spread Ebola virus disease (EVD) to major cities as part of the unprecedented epidemic that started in Guinea in December 2013. An infected airline passenger arrived in Nigeria on July 20, 2014 and caused an outbreak in Lagos and then Port Harcourt. After a total of 20 reported cases, including 8 deaths, Nigeria was declared EVD free on October 20, 2014. We quantified the impact of early control measures in preventing further spread of EVD in Nigeria and calculated the risk that a single undetected case will cause a new outbreak. We fitted an EVD transmission model to data from the outbreak in Nigeria and estimated the reproduction number of the index case at 9.0 (95% confidence interval [CI]: 5.2-15.6). We also found that the net reproduction number fell below unity 15 days (95% CI: 11-21 days) after the arrival of the index case. Hence, our study illustrates the time window for successful containment of EVD outbreaks caused by infected air travelers. PMID:25979285

  11. 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

  12. Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb

    PubMed Central

    Qiu, Xiangguo; Audet, Jonathan; Wong, Gary; Fernando, Lisa; Bello, Alexander; Pillet, Stéphane; Alimonti, Judie B.; Kobinger, Gary P.

    2013-01-01

    Ebola virus (EBOV) is one of the most lethal filoviruses, with mortality rates of up to 90% in humans. Previously, we demonstrated 100% and 50% survival of EBOV-infected cynomologus macaques with a combination of 3 EBOV-GP-specific monoclonal antibodies (ZMAb) administered at 24 or 48 hours post-exposure, respectively. The survivors demonstrated EBOV-GP–specific humoral and cell-mediated immune responses. In order to evaluate whether the immune response induced in NHPs during the ZMAb treatment and EBOV challenge is sufficient to protect survivors against a subsequent exposure, animals that survived the initial challenge were rechallenged at 10 or 13 weeks after the initial challenge. The animals rechallenged at 10 weeks all survived whereas 4 of 6 animals survived a rechallenge at 13 weeks. The data indicate that a robust immune response was generated during the successful treatment of EBOV-infected NHPs with EBOV, which resulted in sustained protection against a second lethal exposure. PMID:24284388

  13. Structure of the Ebola virus glycoprotein bound to a human survivor antibody

    PubMed Central

    Lee, Jeffrey E.; Fusco, Marnie L.; Hessell, Ann J.; Oswald, Wendelien B.; Burton, Dennis R.; Saphire, Erica Ollmann

    2008-01-01

    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 N terminus of GP1. This structure now provides a template for unraveling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development. PMID:18615077

  14. Global Health Security: The Lessons from the West African Ebola Virus Disease Epidemic and MERS Outbreak in the Republic of Korea.

    PubMed

    Ghsa Preparation Task Force Team

    2015-12-01

    The Ebola virus disease outbreak in West Africa and the Middle East Respiratory Syndrome outbreak in the Republic of Korea have given huge impacts in different aspects. Health security is no more a new coinage. Global health security became more realistic in its practical application. In the perspective of global health, it will be helpful to peruse lessons learned from the Ebola outbreak in West Africa and MERS outbreak in Korea. PMID:27429901

  15. [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

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

    SciTech Connect

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

    2015-10-15

    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. - Highlights: • Recombinant Ebola virus (EBOV) derived from Makona variant was rescued. • New protocol for viral rescue allows 100% efficiency. • Modified EBOV expresses a green fluorescent protein from a VP40-fused protein. • Modified EBOV was tested as tool to screen antiviral compounds and measure neutralizing antibodies.

  17. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

    PubMed

    Berry, Scott M; Petzold, Elizabeth A; Dull, Peter; Thielman, Nathan M; Cunningham, Coleen K; Corey, G Ralph; McClain, Micah T; Hoover, David L; Russell, James; Griffiss, J McLeod; Woods, Christopher W

    2016-02-01

    The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US Food and Drug Administration. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of Ebola. (ClinicalTrials.gov Identifier: NCT02380625.) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for Ebola virus disease and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options. PMID:26768569

  18. Healthcare Workers' Attitudes Toward Patients With Ebola Virus Disease in The United States.

    PubMed

    Narasimhulu, Deepa Maheswari; Edwards, Vernee; Chazotte, Cynthia; Bhatt, Devika; Weedon, Jeremy; Minkoff, Howard

    2016-01-01

    Background.  We assessed healthcare workers' (HCWs) attitudes toward care of patients with Ebola virus disease (EVD). Methods.  We provided a self-administered questionnaire-based cross-sectional study of HCWs at 2 urban hospitals. Results.  Of 428 HCWs surveyed, 25.1% believed it was ethical to refuse care to patients with EVD; 25.9% were unwilling to provide care to them. In a multivariate analysis, female gender (32.9% vs 11.9%; odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.7), nursing profession (43.6% vs 12.8%; OR, 2.7; 95% CI, 1.4-5.2), ethical beliefs about refusing care to patients with EVD (39.1% vs 21.3%; OR, 3.71; 95% CI, 2.0-7.0), and increased concern about putting family, friends, and coworkers at risk (28.2% vs 0%; P = .003; OR, 11.1) were independent predictors of unwillingness to care for patients with EVD. Although beliefs about the ethics of refusing care were independently associated with willingness to care for patients with EVD, 21.3% of those who thought it was unethical to refuse care would be unwilling to care for patients with EVD. Healthcare workers in our study had concerns about potentially exposing their families and friends to EVD (90%), which was out of proportion to their degree of concern for personal risk (16.8%). Conclusion.  Healthcare workers' willingness to care for patients with Ebola patients did not precisely mirror their beliefs about the ethics of refusing to provide care, although they were strongly influenced by those beliefs. Healthcare workers may be balancing ethical beliefs about patient care with beliefs about risks entailed in rendering care and consequent risks to their families. Providing a safe work environment and measures to reduce risks to family, perhaps by arranging child care or providing temporary quarters, may help alleviate HCW's concerns. PMID:26788546

  19. Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

    PubMed Central

    Brainard, Julii; Pond, Katherine; Hooper, Lee; Edmunds, Kelly; Hunter, Paul

    2016-01-01

    Background The 2013–15 Ebola outbreak was unprecedented due to sustained transmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood

  20. Healthcare Workers' Attitudes Toward Patients With Ebola Virus Disease in The United States

    PubMed Central

    Narasimhulu, Deepa Maheswari; Edwards, Vernee; Chazotte, Cynthia; Bhatt, Devika; Weedon, Jeremy; Minkoff, Howard

    2016-01-01

    Background. We assessed healthcare workers' (HCWs) attitudes toward care of patients with Ebola virus disease (EVD). Methods. We provided a self-administered questionnaire-based cross-sectional study of HCWs at 2 urban hospitals. Results. Of 428 HCWs surveyed, 25.1% believed it was ethical to refuse care to patients with EVD; 25.9% were unwilling to provide care to them. In a multivariate analysis, female gender (32.9% vs 11.9%; odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4–7.7), nursing profession (43.6% vs 12.8%; OR, 2.7; 95% CI, 1.4–5.2), ethical beliefs about refusing care to patients with EVD (39.1% vs 21.3%; OR, 3.71; 95% CI, 2.0–7.0), and increased concern about putting family, friends, and coworkers at risk (28.2% vs 0%; P = .003; OR, 11.1) were independent predictors of unwillingness to care for patients with EVD. Although beliefs about the ethics of refusing care were independently associated with willingness to care for patients with EVD, 21.3% of those who thought it was unethical to refuse care would be unwilling to care for patients with EVD. Healthcare workers in our study had concerns about potentially exposing their families and friends to EVD (90%), which was out of proportion to their degree of concern for personal risk (16.8%). Conclusion. Healthcare workers' willingness to care for patients with Ebola patients did not precisely mirror their beliefs about the ethics of refusing to provide care, although they were strongly influenced by those beliefs. Healthcare workers may be balancing ethical beliefs about patient care with beliefs about risks entailed in rendering care and consequent risks to their families. Providing a safe work environment and measures to reduce risks to family, perhaps by arranging child care or providing temporary quarters, may help alleviate HCW's concerns. PMID:26788546

  1. 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.

  2. Pregnancy, Labor, and Delivery after Ebola Virus Disease and Implications for Infection Control in Obstetric Services, United States

    PubMed Central

    Jamieson, Denise J.; Kpaduwa, Julius; Schrier, Sarah; Kim, Moon; Green, Nicole M.; Ströher, Ute; Muehlenbachs, Atis; Bell, Michael; Rollin, Pierre E.; Mascola, Laurene

    2016-01-01

    Many of the survivors of the 2014–2015 epidemic of Ebola virus disease (EVD) in West Africa were women of childbearing age. Limited clinical and laboratory data exist that describe these women’s pregnancies and outcomes. We report the case of an EVD survivor who became pregnant and delivered her child in the United States, and we discuss implications of this case for infection control practices in obstetric services. Hospitals in the United States must be prepared to care for EVD survivors. PMID:27191253

  3. Pregnancy, Labor, and Delivery after Ebola Virus Disease and Implications for Infection Control in Obstetric Services, United States.

    PubMed

    Kamali, Amanda; Jamieson, Denise J; Kpaduwa, Julius; Schrier, Sarah; Kim, Moon; Green, Nicole M; Ströher, Ute; Muehlenbachs, Atis; Bell, Michael; Rollin, Pierre E; Mascola, Laurene

    2016-07-01

    Many of the survivors of the 2014-2015 epidemic of Ebola virus disease (EVD) in western Africa were women of childbearing age. Limited clinical and laboratory data exist that describe these women's pregnancies and outcomes. We report the case of an EVD survivor who became pregnant and delivered her child in the United States, and we discuss implications of this case for infection control practices in obstetric services. Hospitals in the United States must be prepared to care for EVD survivors. PMID:27191253

  4. Public Confidence in the Health Care System 1 Year After the Start of the Ebola Virus Disease Outbreak - Sierra Leone, July 2015.

    PubMed

    Li, Wenshu; Jalloh, Mohamed F; Bunnell, Rebecca; Aki-Sawyerr, Yvonne; Conteh, Lansana; Sengeh, Paul; Redd, John T; Hersey, Sara; Morgan, Oliver; Jalloh, Mohammad B; O'Leary, Ann; Burdette, Erin; Hageman, Kathy

    2016-01-01

    Ensuring confidence in the health care system has been a challenge to Ebola virus disease (Ebola) response and recovery efforts in Sierra Leone (1). A national multistage cluster-sampled household survey to assess knowledge, attitudes, and practices (KAP) related to Sierra Leone's health care system was conducted in July 2015. Among 3,564 respondents, 93% were confident that a health care facility could treat suspected Ebola cases, and approximately 90% had confidence in the health system's ability to provide non-Ebola services, including immunizations, antenatal care, and maternity care. Respondents in districts with ongoing Ebola transmission ("active districts") and respondents with higher educational levels reported more confidence in the health care system than did respondents in nonactive districts and respondents with less education. Active districts were the focus of the Ebola response; these districts implemented intensified social mobilization and communication efforts, and established district response centers, Ebola-specific health care facilities, and ambulances. Greater infrastructure and response capacity might have resulted in higher confidence in the health care system in these areas. Respondents ranked Ebola and malaria as the country's most important health issues. Health system recovery efforts in Sierra Leone can build on existing public confidence in the health system. PMID:27254016

  5. Lassa fever, Marburg and Ebola virus diseases and other exotic diseases: is there a risk to Canada?

    PubMed Central

    Clayton, A. J.

    1979-01-01

    There are seven exotic diseases of concern; three of these, the most unpredictable and least understood, are Lassa fever, Marburg virus disease and Ebola virus disease. In this article the epidemiologic aspects of these diseases are discussed, with particular emphasis on exportation from their indigenous areas in Africa and on the occurrence of secondary cases. Any of these conditions could be brought into Canada either by aeromedical evacuation or inadvertently. Between 1972 and 1978 there were seven occasions when Canada could have been involved with handling cases of Lassa fever. The Government of Canada has purchased several containment bed and transit isolators. These units, with filtered air under negative pressure, accommodate infectious patients being transported and cared for without contaminating medical attendants or the environment. Images FIG. 1 FIG. 2 FIG. 3 PMID:570088

  6. [Multiple Ebola virus haemorrhagic fever outbreaks in Gabon, from October 2001 to April 2002].

    PubMed

    Nkoghe, D; Formenty, P; Leroy, E M; Nnegue, S; Edou, S Y Obame; Ba, J Iba; Allarangar, Y; Cabore, J; Bachy, C; Andraghetti, R; de Benoist, A C; Galanis, E; Rose, A; Bausch, D; Reynolds, M; Rollin, P; Choueibou, C; Shongo, R; Gergonne, B; Koné, L M; Yada, A; Roth, C; Mve, M Toung

    2005-09-01

    Outbreaks of Ebola virus haemorrhagic fever have been reported from 1994 to 1996 in the province of Ogooué Ivindo, a forest zone situated in the Northeast of Gabon. Each time, the great primates had been identified as the initial source of human infection. End of November 2001 a new alert came from this province, rapidly confirmed as a EVHV outbreak. The response was given by the Ministry of Health with the help of an international team under the aegis of WHO. An active monitoring system was implemented in the three districts hit by the epidemic (Zadié, Ivindo and Mpassa) to organize the detection of cases and their follow-up. A case definition has been set up, the suspected cases were isolated at hospital, at home or in lazarets and serological tests were performed. These tests consisted of the detection of antigen or specific IgG and the RT-PCR. A classification of cases was made according to the results of biological tests, clinical and epidemiological data. The contact subjects were kept watch over for 21 days. 65 cases were recorded among which 53 deaths. The first human case, a hunter died on the 28th of October 2001. The epidemic spreads over through family transmission and nosocomial contamination. Four distinct primary foci have been identified together with an isolated case situated in the South East of Gabon, 580 km away from the epicenter. Deaths happened within a delay of 6 days. The last death has been recorded on the 22nd of March 2002 and the end of the outbreak was declared on the 6th of May 2002. The epidemic spreads over the Gabon just next. Unexplained deaths of animals had been mentionned in the nearby forests as soon as August 2001: great primates and cephalophus. Samples taken from their carcasses confirmed a concomitant animal epidemic. PMID:16267965

  7. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

    PubMed

    Pallesen, Jesper; Murin, Charles D; de Val, Natalia; Cottrell, Christopher A; Hastie, Kathryn M; Turner, Hannah L; Fusco, Marnie L; Flyak, Andrew I; Zeitlin, Larry; Crowe, James E; Andersen, Kristian G; Saphire, Erica Ollmann; Ward, Andrew B

    2016-01-01

    The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene. PMID:27562261

  8. Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant

    PubMed Central

    Zeitlin, Larry; Pettitt, James; Scully, Corinne; Bohorova, Natasha; Kim, Do; Pauly, Michael; Hiatt, Andrew; Ngo, Long; Steinkellner, Herta; Whaley, Kevin J.; Olinger, Gene G.

    2011-01-01

    No countermeasures currently exist for the prevention or treatment of the severe sequelae of Filovirus (such as Ebola virus; EBOV) infection. To overcome this limitation in our biodefense preparedness, we have designed monoclonal antibodies (mAbs) which could be used in humans as immunoprotectants for EBOV, starting with a murine mAb (13F6) that recognizes the heavily glycosylated mucin-like domain of the virion-attached glycoprotein (GP). Point mutations were introduced into the variable region of the murine mAb to remove predicted human T-cell epitopes, and the variable regions joined to human constant regions to generate a mAb (h-13F6) appropriate for development for human use. We have evaluated the efficacy of three variants of h-13F6 carrying different glycosylation patterns in a lethal mouse EBOV challenge model. The pattern of glycosylation of the various mAbs was found to correlate to level of protection, with aglycosylated h-13F6 providing the least potent efficacy (ED50 = 33 μg). A version with typical heterogenous mammalian glycoforms (ED50 = 11 μg) had similar potency to the original murine mAb. However, h-13F6 carrying complex N-glycosylation lacking core fucose exhibited superior potency (ED50 = 3 μg). Binding studies using Fcγ receptors revealed enhanced binding of nonfucosylated h-13F6 to mouse and human FcγRIII. Together the results indicate the presence of Fc N-glycans enhances the protective efficacy of h-13F6, and that mAbs manufactured with uniform glycosylation and a higher potency glycoform offer promise as biodefense therapeutics. PMID:22143789

  9. Loss of Interleukin 1 Receptor Antagonist Enhances Susceptibility to Ebola Virus Infection.

    PubMed

    Hill-Batorski, Lindsay; Halfmann, Peter; Marzi, Andrea; Lopes, Tiago J S; Neumann, Gabriele; Feldmann, Heinz; Kawaoka, Yoshihiro

    2015-10-01

    The current outbreak of Ebola virus (EBOV) infection in West Africa is unprecedented, with nearly 26 000 confirmed cases and >10 000 deaths. Comprehensive data on the pathogenesis of EBOV infection are lacking; however, recent studies suggested that fatal EBOV infections are characterized by dysregulation of the innate immune response and a subsequent cytokine storm. Specifically, several studies suggested that hypersecretion of interleukin 1 receptor antagonist (IL-1Ra) correlates with lethal EBOV infections. To examine the significance of IL-1Ra in EBOV infections, we infected mice that lack the gene encoding IL-1Ra, Il1rn (IL-1RN-KO), and mice with wild-type Il1rn (IL-1RN-WT) with a mouse-adapted EBOV (MA-EBOV). Infected IL-1RN-KO mice lost more weight and had a lower survival rate than IL-1RN-WT mice infected with MA-EBOV. In addition, IL-1RN-KO mice infected with wild-type EBOV, which does not cause lethal infection in adult immunocompetent mice, such as C57BL/6 mice, experienced greater weight loss than IL-1RN-WT mice infected with wild-type EBOV. Further studies revealed that the levels of 6 cytokines in spleens-IL-1α, IL-1β, interleukin 12p40, interleukin 17, granulocyte colony-stimulating factor, and regulated on activation, normal T-cell expressed and secreted-were significantly different between IL-1RN-KO mice and IL-1RN-WT mice infected with MA-EBOV. Collectively, our data suggest that IL-1Ra may have a protective effect upon EBOV infection, likely by damping an overactive proinflammatory immune response. PMID:26209680

  10. Ebola Virus VP24 Binds Karyopherin α1 and Blocks STAT1 Nuclear Accumulation

    PubMed Central

    Reid, St. Patrick; Leung, Lawrence W.; Hartman, Amy L.; Martinez, Osvaldo; Shaw, Megan L.; Carbonnelle, Caroline; Volchkov, Viktor E.; Nichol, Stuart T.; Basler, Christopher F.

    2006-01-01

    Ebola virus (EBOV) infection blocks cellular production of alpha/beta interferon (IFN-α/β) and the ability of cells to respond to IFN-α/β or IFN-γ. The EBOV VP35 protein has previously been identified as an EBOV-encoded inhibitor of IFN-α/β production. However, the mechanism by which EBOV infection inhibits responses to IFNs has not previously been defined. Here we demonstrate that the EBOV VP24 protein functions as an inhibitor of IFN-α/β and IFN-γ signaling. Expression of VP24 results in an inhibition of IFN-induced gene expression and an inability of IFNs to induce an antiviral state. The VP24-mediated inhibition of cellular responses to IFNs correlates with the impaired nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1), a key step in both IFN-α/β and IFN-γ signaling. Consistent with this proposed function for VP24, infection of cells with EBOV also confers a block to the IFN-induced nuclear accumulation of PY-STAT1. Further, VP24 is found to specifically interact with karyopherin α1, the nuclear localization signal receptor for PY-STAT1, but not with karyopherin α2, α3, or α4. Overexpression of VP24 results in a loss of karyopherin α1-PY-STAT1 interaction, indicating that the VP24-karyopherin α1 interaction contributes to the block to IFN signaling. These data suggest that VP24 is likely to be an important virulence determinant that allows EBOV to evade the antiviral effects of IFNs. PMID:16698996

  11. Machine learning models identify molecules active against the Ebola virus in vitro.

    PubMed

    Ekins, Sean; Freundlich, Joel S; Clark, Alex M; Anantpadma, Manu; Davey, Robert A; Madrid, Peter

    2015-01-01

    The search for small molecule inhibitors of Ebola virus (EBOV) has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs) with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC 50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in vitro. PMID:26834994

  12. Machine learning models identify molecules active against the Ebola virus in vitro

    PubMed Central

    Ekins, Sean; Freundlich, Joel S.; Clark, Alex M.; Anantpadma, Manu; Davey, Robert A.; Madrid, Peter

    2016-01-01

    The search for small molecule inhibitors of Ebola virus (EBOV) has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs) with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC 50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in vitro. PMID:26834994

  13. Quantitative serology assays for determination of antibody responses to Ebola virus glycoprotein and matrix protein in nonhuman primates and humans.

    PubMed

    Vu, Hong; Shulenin, Sergey; Grolla, Allen; Audet, Jonathan; He, Shihua; Kobinger, Gary; Unfer, Robert C; Warfield, Kelly L; Aman, M Javad; Holtsberg, Frederick W

    2016-02-01

    The West Africa Ebola virus disease (EVD) outbreak has reached unprecedented magnitude and caused worldwide concerns for the spread of this deadly virus. Recent findings in nonhuman primates (NHPs) demonstrate that antibodies can be protective against EVD. However, the role of antibody response in vaccine-mediated protection is not fully understood. To address these questions quantitative serology assays are needed for measurement of the antibody response to key Ebola virus (EBOV) proteins. Serology enzyme-linked immunosorbent assays (ELISA's), using a reference detection antibody, were developed in order to standardize the quantitation of antibody levels in vaccinated NHPs or in humans exposed to EBOV or immunized with an EBOV vaccine. Critical reagents were generated to support the development of the serology ELISAs. Recombinant EBOV matrix protein (VP40) was expressed in Escherichia coli and purified. Two variants of the glycoprotein (GP), the ectodomain lacking the transmembrane domain (GPΔTM), and an engineered GP lacking the mucin-like domain (GPΔmuc) were expressed and purified from mammalian cell systems. Using these proteins, three ELISA methods were developed and optimized for reproducibility and robustness, including stability testing of critical reagents. The assay was used to determine the antibody response against VP40, GPΔTM, and GPΔmuc in a NHP vaccine study using EBOV virus-like particles (VLP) vaccine expressing GP, VP40 and the nucleoprotein. Additionally, these ELISAs were used to successfully detect antibody responses to VP40, GPΔTM and GPΔmuc in human sera from EBOV infected individuals. PMID:26681387

  14. The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein

    PubMed Central

    Zhao, Dianyuan; Han, Xintao; Zheng, Xuexing; Wang, Hualei; Yang, Zaopeng; Liu, Di; Han, Ke; Liu, Jing; Wang, Xiaowen; Yang, Wenting; Dong, Qingyang; Yang, Songtao; Xia, Xianzhu; Tang, Li; He, Fuchu

    2016-01-01

    Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response. PMID:26943817

  15. The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein.

    PubMed

    Zhao, Dianyuan; Han, Xintao; Zheng, Xuexing; Wang, Hualei; Yang, Zaopeng; Liu, Di; Han, Ke; Liu, Jing; Wang, Xiaowen; Yang, Wenting; Dong, Qingyang; Yang, Songtao; Xia, Xianzhu; Tang, Li; He, Fuchu

    2016-03-01

    Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response. PMID:26943817

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

    PubMed

    Saito, Tomoya

    2015-01-01

    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

  17. Further characterization of the immune response in mice to inactivated and live rabies vaccines expressing Ebola virus glycoprotein.

    PubMed

    Papaneri, Amy B; Wirblich, Christoph; Cooper, Kurt; Jahrling, Peter B; Schnell, Matthias J; Blaney, Joseph E

    2012-09-21

    We have previously developed (a) replication-competent, (b) replication-deficient, and (c) chemically inactivated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein (GP) that induce humoral immunity against each virus and confer protection from both lethal RABV and mouse-adapted EBOV challenge in mice. Here, we expand our investigation of the immunogenic properties of these bivalent vaccines in mice. Both live and killed vaccines induced primary EBOV GP-specific T-cells and a robust recall response as measured by interferon-γ ELISPOT assay. In addition to cellular immunity, an effective filovirus vaccine will likely require a multivalent humoral immune response against multiple virus species. As a proof-of-principle experiment, we demonstrated that inactivated RV-GP could be formulated with another inactivated RABV vaccine expressing the nontoxic fragment of botulinum neurotoxin A heavy chain (HC50) without a reduction in immunity to each component. Finally, we demonstrated that humoral immunity to GP could be induced by immunization of mice with inactivated RV-GP in the presence of pre-existing immunity to RABV. The ability of these novel vaccines to induce strong humoral and cellular immunity indicates that they should be further evaluated in additional animal models of infection. PMID:22884661

  18. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges

    PubMed Central

    Grant-Klein, Rebecca J; Altamura, Louis A; Badger, Catherine V; Bounds, Callie E; Van Deusen, Nicole M; Kwilas, Steven A; Vu, Hong A; Warfield, Kelly L; Hooper, Jay W; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2015-01-01

    Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-γ ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed. PMID:25996997

  19. 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

  20. 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

  1. Visual detection of Ebola virus using reverse transcription loop-mediated isothermal amplification combined with nucleic acid strip detection.

    PubMed

    Xu, Changping; Wang, Hualei; Jin, Hongli; Feng, Na; Zheng, Xuexing; Cao, Zengguo; Li, Ling; Wang, Jianzhong; Yan, Feihu; Wang, Lina; Chi, Hang; Gai, Weiwei; Wang, Chong; Zhao, Yongkun; Feng, Yan; Wang, Tiecheng; Gao, Yuwei; Lu, Yiyu; Yang, Songtao; Xia, Xianzhu

    2016-05-01

    Ebola virus (species Zaire ebolavirus) (EBOV) is highly virulent in humans. The largest recorded outbreak of Ebola hemorrhagic fever in West Africa to date was caused by EBOV. Therefore, it is necessary to develop a detection method for this virus that can be easily distributed and implemented. In the current study, we developed a visual assay that can detect EBOV-associated nucleic acids. This assay combines reverse transcription loop-mediated isothermal amplification and nucleic acid strip detection (RT-LAMP-NAD). Nucleic acid amplification can be achieved in a one-step process at a constant temperature (58 °C, 35 min), and the amplified products can be visualized within 2-5 min using a nucleic acid strip detection device. The assay is capable of detecting 30 copies of artificial EBOV glycoprotein (GP) RNA and RNA encoding EBOV GP from 10(2) TCID50 recombinant viral particles per ml with high specificity. Overall, the RT-LAMP-NAD method is simple and has high sensitivity and specificity; therefore, it is especially suitable for the rapid detection of EBOV in African regions. PMID:26831931

  2. Development and Evaluation of a Rapid and Sensitive EBOV-RPA Test for Rapid Diagnosis of Ebola Virus Disease

    PubMed Central

    Yang, Mingjuan; Ke, Yuehua; Wang, Xuesong; Ren, Hang; Liu, Wei; Lu, Huijun; Zhang, Wenyi; Liu, Shiwei; Chang, Guohui; Tian, Shuguang; Wang, Lihua; Huang, Liuyu; Liu, Chao; Yang, Ruifu; Chen, Zeliang

    2016-01-01

    Confirming Ebola virus disease (EVD), a deadly infectious disease, requires real-time RT-PCR, which takes up to a few hours to yield results. Therefore, a rapid diagnostic assay is imperative for EVD diagnosis. A rapid nucleic acid test based on recombinase polymerase amplification (EBOV-RPA) was developed to specifically detect the 2014 outbreak strains. The EBOV-RPA assay was evaluated by testing samples from suspected EVD patients in parallel with RT-PCR. An EBOV-RPA, which could be completed in 20 min, was successfully developed. Of 271 patients who tested positive for Ebola virus by RT-PCR, 264 (sensitivity: 97%, 95% CI: 95.5–99.3%) were positive by EBOV-RPA; 101 of 104 patients (specificity: 97%, 95% CI: 93.9–100%) who tested negative by RT-PCR were also negative by EBOV-RPA. The sensitivity values for samples with a Ct value of <34, which accounted for 95.59% of the samples, was 100%. Discordant samples positive by RT-PCR but negative by EBOV-RPA had significantly high Ct values. Results of external quality assessment samples with EBOV-RPA were 100%, consistent with those of RT-PCR. The EBOV-RPA assay showed 97% sensitivity and 97% specificity for all EVD samples tested, making it a rapid and sensitive test for EVD diagnosis. PMID:27246147

  3. [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

  4. Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

    PubMed Central

    Olinger, Gene Garrard; Pettitt, James; Kim, Do; Working, Cara; Bohorov, Ognian; Bratcher, Barry; Hiatt, Ernie; Hume, Steven D.; Johnson, Ashley K.; Morton, Josh; Pauly, Michael; Whaley, Kevin J.; Lear, Calli M.; Biggins, Julia E.; Scully, Corinne; Hensley, Lisa; Zeitlin, Larry

    2012-01-01

    Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure. PMID:23071322

  5. 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

  6. Development and Evaluation of a Rapid and Sensitive EBOV-RPA Test for Rapid Diagnosis of Ebola Virus Disease.

    PubMed

    Yang, Mingjuan; Ke, Yuehua; Wang, Xuesong; Ren, Hang; Liu, Wei; Lu, Huijun; Zhang, Wenyi; Liu, Shiwei; Chang, Guohui; Tian, Shuguang; Wang, Lihua; Huang, Liuyu; Liu, Chao; Yang, Ruifu; Chen, Zeliang

    2016-01-01

    Confirming Ebola virus disease (EVD), a deadly infectious disease, requires real-time RT-PCR, which takes up to a few hours to yield results. Therefore, a rapid diagnostic assay is imperative for EVD diagnosis. A rapid nucleic acid test based on recombinase polymerase amplification (EBOV-RPA) was developed to specifically detect the 2014 outbreak strains. The EBOV-RPA assay was evaluated by testing samples from suspected EVD patients in parallel with RT-PCR. An EBOV-RPA, which could be completed in 20 min, was successfully developed. Of 271 patients who tested positive for Ebola virus by RT-PCR, 264 (sensitivity: 97%, 95% CI: 95.5-99.3%) were positive by EBOV-RPA; 101 of 104 patients (specificity: 97%, 95% CI: 93.9-100%) who tested negative by RT-PCR were also negative by EBOV-RPA. The sensitivity values for samples with a Ct value of <34, which accounted for 95.59% of the samples, was 100%. Discordant samples positive by RT-PCR but negative by EBOV-RPA had significantly high Ct values. Results of external quality assessment samples with EBOV-RPA were 100%, consistent with those of RT-PCR. The EBOV-RPA assay showed 97% sensitivity and 97% specificity for all EVD samples tested, making it a rapid and sensitive test for EVD diagnosis. PMID:27246147

  7. 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

    2015-01-01

    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

  8. Designed protein mimics of the Ebola virus glycoprotein GP2 α-helical bundle: Stability and pH effects

    PubMed Central

    Harrison, Joseph S; Higgins, Chelsea D; Chandran, Kartik; Lai, Jonathan R

    2011-01-01

    Ebola virus (EboV) belongs to the Filoviridae family of viruses that causes severe and fatal hemhorragic fever. Infection by EboV involves fusion between the virus and host cell membranes mediated by the envelope glycoprotein GP2 of the virus. Similar to the envelope glycoproteins of other viruses, the central feature of the GP2 ectodomain postfusion structure is a six-helix bundle formed by the protein's N- and C-heptad repeat regions (NHR and CHR, respectively). Folding of this six-helix bundle provides the energetic driving force for membrane fusion; in other viruses, designed agents that disrupt formation of the six-helix bundle act as potent fusion inhibitors. To interrogate determinants of EboV GP2-mediated membrane fusion, we designed model proteins that consist of the NHR and CHR segments linked by short protein linkers. Circular dichroism and gel filtration studies indicate that these proteins adopt stable α-helical folds consistent with design. Thermal denaturation indicated that the GP2 six-helix bundle is highly stable at pH 5.3 (melting temperature, Tm, of 86.8 ± 2.0°C and van't Hoff enthalpy, ΔHvH, of −28.2 ± 1.0 kcal/mol) and comparable in stability to other viral membrane fusion six-helix bundles. We found that the stability of our designed α-helical bundle proteins was dependent on buffering conditions with increasing stability at lower pH. Small pH differences (5.3–6.1) had dramatic effects (ΔTm = 37°C) suggesting a mechanism for conformational control that is dependent on environmental pH. These results suggest a role for low pH in stabilizing six-helix bundle formation during the process of GP2-mediated viral membrane fusion. PMID:21739501

  9. Ebola virus disease outbreak; the role of field epidemiology training programme in the fight against the epidemic, Liberia, 2014

    PubMed Central

    Lubogo, Mutaawe; Donewell, Bangure; Godbless, Lucas; Shabani, Sasita; Maeda, Justin; Temba, Herilinda; Malibiche, Theophil C; Berhanu, Naod

    2015-01-01

    The African Field Epidemiology Network (AFENET) is a public health network established in 2005 as a non-profit networking alliance of Field Epidemiology and Laboratory Training Programs (FELTPs) and Field Epidemiology Training Programs (FETPs) in Africa. AFENET is dedicated to supporting Ministries of Health in Africa build strong, effective and sustainable programs and capacity to improve public health systems by partnering with global public health experts. The Network's goal is to strengthen field epidemiology and public health laboratory capacity to contribute effectively to addressing epidemics and other major public health problems in Africa. The goal for the establishment of FETP and FELTP was and still is to produce highly competent multi-disciplinary public health professionals who would assume influential posts in the public health structures and tackle emerging and re-emerging communicable and non-communicable diseases. AFENET currently networks 12 FELTPs and FETPs in sub-Saharan Africa with operations in 20 countries. During the Ebola Virus Disease (EVD) outbreak in West Africa, African Union Support for the Ebola Outbreak in West Africa (ASEOWA) supported FETP graduates from Uganda, Zimbabwe, Ethiopia and Tanzania for the investigation and control of the EVD outbreak in Liberia. The graduates were posted in different counties in Liberia where they lead teams of other experts conduct EVD outbreak investigations, Infection Control and Prevention trainings among health workers and communities, Strengthening integrated disease surveillance, developing Standard Operating Procedures for infection control and case notification in the Liberian setting as well as building capacity of local surveillance officers’ conduct outbreak investigation and contact tracing. The team was also responsible for EVD data management at the different Counties in Liberia. The FETP graduates have been instrumental in the earlier successes registered in various counties in

  10. The Role of the Polio Program Infrastructure in Response to Ebola Virus Disease Outbreak in Nigeria 2014

    PubMed Central

    Vaz, Rui G.; Mkanda, Pascal; Banda, Richard; Komkech, William; Ekundare-Famiyesin, Olubowale O.; Onyibe, Rosemary; Abidoye, Sunday; Nsubuga, Peter; Maleghemi, Sylvester; Hannah-Murele, Bolatito; Tegegne, Sisay G.

    2016-01-01

    Background. The current West African outbreak of the Ebola virus disease (EVD) began in Guinea in December 2013 and rapidly spread to Liberia and Sierra Leone. On 20 July 2014, a sick individual flew into Lagos, Nigeria, from Monrovia, Liberia, setting off an outbreak in Lagos and later in Port Harcourt city. The government of Nigeria, supported by the World Health Organization and other partners, mounted a response to the outbreak relying on the polio program experiences and infrastructure. On 20 October 2014, the country was declared free of EVD. Methods. We examined the organization and operations of the response to the 2014 EVD outbreak in Nigeria and how experiences and support from the country's polio program infrastructure accelerated the outbreak response. Results. The deputy incident manager of the National Polio Emergency Operations Centre was appointed the incident manager of the Ebola Emergency Operations Centre (EEOC), the body that coordinated and directed the response to the EVD outbreak in the country. A total of 892 contacts were followed up, and blood specimens were collected from 61 persons with suspected EVD and tested in designated laboratories. Of these, 19 (31%) were positive for Ebola, and 11 (58%) of the case patients were healthcare workers. The overall case-fatality rate was 40%. EVD sensitization and training were conducted during the outbreak and for 2 months after the outbreak ended. The World Health Organization deployed its surveillance and logistics personnel from non–Ebola-infected states to support response activities in Lagos and Rivers states. Conclusions. The support from the polio program infrastructure, particularly the coordination mechanism adopted (the EEOC), the availability of skilled personnel in the polio program, and lessons learned from managing the polio eradication program greatly contributed to the speedy containment of the 2014 EVD outbreak in Nigeria. PMID:26908718

  11. Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors.

    PubMed

    Brudner, Matthew; Karpel, Marshall; 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

  12. 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

  13. 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

  14. 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

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

    PubMed Central

    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.

    2015-01-01

    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

  16. Shelf-Life of Chlorine Solutions Recommended in Ebola Virus Disease Response

    PubMed Central

    Iqbal, Qais; Lubeck-Schricker, Maya; Wells, Emma; Lantagne, Daniele

    2016-01-01

    In Ebola Virus Disease (EVD) outbreaks, it is widely recommended to wash living things (handwashing) with 0.05% (500 mg/L) chlorine solution and non-living things (surfaces, personal protective equipment, dead bodies) with 0.5% (5,000 mg/L) chlorine solution. Chlorine solutions used in EVD response are primarily made from powdered calcium hypochlorite (HTH), granular sodium dichloroisocyanurate (NaDCC), and liquid sodium hypochlorite (NaOCl), and have a pH range of 5–11. Chlorine solutions degrade following a reaction highly dependent on, and unusually sensitive to, pH, temperature, and concentration. We determined the shelf-life of 0.05% and 0.5% chlorine solutions used in EVD response, including HTH, NaDCC, stabilized NaOCl, generated NaOCl, and neutralized NaOCl solutions. Solutions were stored for 30 days at 25, 30, and 35°C, and tested daily for chlorine concentration and pH. Maximum shelf-life was defined as days until initial concentration fell to <90% of initial concentration in ideal laboratory conditions. At 25–35°C, neutralized-NaOCl solutions (pH = 7) had a maximum shelf-life of a few hours, NaDCC solutions (pH = 6) 2 days, generated NaOCl solutions (pH = 9) 6 days, and HTH and stabilized NaOCl solutions (pH 9–11) >30 days. Models were developed for solutions with maximum shelf-lives between 1–30 days. Extrapolating to 40°C, the maximum predicted shelf-life for 0.05% and 0.5% NaDCC solutions were 0.38 and 0.82 hours, respectively; predicted shelf-life for 0.05% and 0.5% generated NaOCl solutions were >30 and 5.4 days, respectively. Each chlorine solution type offers advantages and disadvantages to responders, as: NaDCC is an easy-to-import high-concentration effervescent powder; HTH is similar, but forms a precipitate that may clog pipes; and, NaOCl solutions can be made locally, but are difficult to transport. We recommend responders chose the most appropriate source chlorine compound for their use, and ensure solutions are stored at

  17. Shelf-Life of Chlorine Solutions Recommended in Ebola Virus Disease Response.

    PubMed

    Iqbal, Qais; Lubeck-Schricker, Maya; Wells, Emma; Wolfe, Marlene K; Lantagne, Daniele

    2016-01-01

    In Ebola Virus Disease (EVD) outbreaks, it is widely recommended to wash living things (handwashing) with 0.05% (500 mg/L) chlorine solution and non-living things (surfaces, personal protective equipment, dead bodies) with 0.5% (5,000 mg/L) chlorine solution. Chlorine solutions used in EVD response are primarily made from powdered calcium hypochlorite (HTH), granular sodium dichloroisocyanurate (NaDCC), and liquid sodium hypochlorite (NaOCl), and have a pH range of 5-11. Chlorine solutions degrade following a reaction highly dependent on, and unusually sensitive to, pH, temperature, and concentration. We determined the shelf-life of 0.05% and 0.5% chlorine solutions used in EVD response, including HTH, NaDCC, stabilized NaOCl, generated NaOCl, and neutralized NaOCl solutions. Solutions were stored for 30 days at 25, 30, and 35°C, and tested daily for chlorine concentration and pH. Maximum shelf-life was defined as days until initial concentration fell to <90% of initial concentration in ideal laboratory conditions. At 25-35°C, neutralized-NaOCl solutions (pH = 7) had a maximum shelf-life of a few hours, NaDCC solutions (pH = 6) 2 days, generated NaOCl solutions (pH = 9) 6 days, and HTH and stabilized NaOCl solutions (pH 9-11) >30 days. Models were developed for solutions with maximum shelf-lives between 1-30 days. Extrapolating to 40°C, the maximum predicted shelf-life for 0.05% and 0.5% NaDCC solutions were 0.38 and 0.82 hours, respectively; predicted shelf-life for 0.05% and 0.5% generated NaOCl solutions were >30 and 5.4 days, respectively. Each chlorine solution type offers advantages and disadvantages to responders, as: NaDCC is an easy-to-import high-concentration effervescent powder; HTH is similar, but forms a precipitate that may clog pipes; and, NaOCl solutions can be made locally, but are difficult to transport. We recommend responders chose the most appropriate source chlorine compound for their use, and ensure solutions are stored at appropriate

  18. Notes from the Field: Development of a Contact Tracing System for Ebola Virus Disease - Kambia District, Sierra Leone, January-February 2015.

    PubMed

    Levine, Rebecca; Ghiselli, Margherita; Conteh, Agnes; Turay, Bobson; Kemoh, Andrew; Sesay, Foday; Kamara, Alfred; Gaeta, Aldo; Davis, Clinton; Hersey, Sara

    2016-01-01

    Kambia District is located in northwestern Sierra Leone along the international border with Guinea. The district is dominated by forest and swamp habitat and has a population of approximately 270,000 persons (approximately 5% of the nation's population) who live in rural villages and predominantly subsist on farming and trading. During 2014-2015, the remoteness of the area, a highly porous border with Guinea, and strong traditional beliefs about health care and sickness led to unique challenges in controlling the Ebola Virus Disease (Ebola) outbreak within the district. PMID:27100119

  19. Design and analysis considerations in the Ebola_Tx trial evaluating convalescent plasma in the treatment of Ebola virus disease in Guinea during the 2014–2015 outbreak

    PubMed Central

    Edwards, Tansy; Semple, Malcolm G; De Weggheleire, Anja; Claeys, Yves; De Crop, Maaike; Menten, Joris; Ravinetto, Raffaella; Temmerman, Sarah; Lynen, Lutgarde; Bah, Elhadj Ibrahima; Smith, Peter G; van Griensven, Johan

    2016-01-01

    The Ebola virus disease outbreak in 2014–2015 led to a huge caseload with a high case fatality rate. No specific treatments were available beyond supportive care for conditions such as dehydration and shock. Evaluation of treatment with convalescent plasma from Ebola survivors was identified as a priority. We evaluated this intervention in an emergency setting, where randomization was unacceptable. The original trial design was an open-label study comparing patients receiving convalescent plasma and supportive care to patients receiving supportive care alone. The comparison group comprised patients recruited at the start of the trial before convalescent plasma became available, as well as patients presenting during the trial for whom there was insufficient blood group–compatible plasma or no staffing capacity to provide additional transfusions. However, during the trial, convalescent plasma was available to treat all new patients. The design was changed to use a comparator group comprising patients previously treated at the same Ebola treatment center prior to the start of the trial. In the analysis, it was planned to adjust for any differences in prognostic variables between intervention and comparison groups, specifically baseline polymerase chain reaction cycle threshold and age. In addition, adjustment was planned for other potential confounders, identified in the analysis, such as patient presenting symptoms and time to treatment seeking. Because plasma treatment started up to 3 days after diagnosis and we could not define a similar time-point for the comparator group, patients who died before the third day after confirmation of diagnosis were excluded from both intervention and comparison groups in a per-protocol analysis. Some patients received additional experimental treatments soon after plasma treatment, and these were excluded. We also analyzed mortality including all patients from the time of confirmed diagnosis, irrespective of whether those in

  20. Design and analysis considerations in the Ebola_Tx trial evaluating convalescent plasma in the treatment of Ebola virus disease in Guinea during the 2014-2015 outbreak.

    PubMed

    Edwards, Tansy; Semple, Malcolm G; De Weggheleire, Anja; Claeys, Yves; De Crop, Maaike; Menten, Joris; Ravinetto, Raffaella; Temmerman, Sarah; Lynen, Lutgarde; Bah, Elhadj Ibrahima; Smith, Peter G; van Griensven, Johan

    2016-02-01

    The Ebola virus disease outbreak in 2014-2015 led to a huge caseload with a high case fatality rate. No specific treatments were available beyond supportive care for conditions such as dehydration and shock. Evaluation of treatment with convalescent plasma from Ebola survivors was identified as a priority. We evaluated this intervention in an emergency setting, where randomization was unacceptable. The original trial design was an open-label study comparing patients receiving convalescent plasma and supportive care to patients receiving supportive care alone. The comparison group comprised patients recruited at the start of the trial before convalescent plasma became available, as well as patients presenting during the trial for whom there was insufficient blood group-compatible plasma or no staffing capacity to provide additional transfusions. However, during the trial, convalescent plasma was available to treat all new patients. The design was changed to use a comparator group comprising patients previously treated at the same Ebola treatment center prior to the start of the trial. In the analysis, it was planned to adjust for any differences in prognostic variables between intervention and comparison groups, specifically baseline polymerase chain reaction cycle threshold and age. In addition, adjustment was planned for other potential confounders, identified in the analysis, such as patient presenting symptoms and time to treatment seeking. Because plasma treatment started up to 3 days after diagnosis and we could not define a similar time-point for the comparator group, patients who died before the third day after confirmation of diagnosis were excluded from both intervention and comparison groups in a per-protocol analysis. Some patients received additional experimental treatments soon after plasma treatment, and these were excluded. We also analyzed mortality including all patients from the time of confirmed diagnosis, irrespective of whether those in the

  1. 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.

  2. Flavonoids as Multi-target Inhibitors for Proteins Associated with Ebola Virus: In Silico Discovery Using Virtual Screening and Molecular Docking Studies.

    PubMed

    Raj, Utkarsh; Varadwaj, Pritish Kumar

    2016-06-01

    Ebola virus is a single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever in humans and non-human primates. This virus is unreceptive to a large portion of the known antiviral drugs, and there is no valid treatment as on date for disease created by this pathogen. Looking into its ability to create a pandemic scenario across globe, there is an utmost need for new drugs and therapy to combat this life-threatening infection. The current study deals with the evaluation of the inhibitory activity of flavonoids against the four selected Ebola virus receptor proteins, using in silico studies. The viral proteins VP40, VP35, VP30 and VP24 were docked with small molecules obtained from flavonoid class and its derivatives and evaluated on the basis of energetics, stereochemical considerations and pharmacokinetic properties to identify potential lead compounds. The results showed that both top-ranking screened flavonoids, i.e., Gossypetin and Taxifolin, showed better docking scores and binding energies in all the EBOV receptors when compared to those of the reported compound. All the screened flavonoids have known antiviral activity, acceptable pharmacokinetic properties and are being used on human and thus can be taken as anti-Ebola therapy without the time lag for clinical trial. PMID:26286008

  3. Notes from the Field: Ebola Virus Disease Response Activities During a Mass Displacement Event After Flooding--Freetown, Sierra Leone, September-November, 2015.

    PubMed

    Ratto, Jeffrey; Ivy, Wade; Purfield, Anne; Bangura, James; Omoko, Anthony; Boateng, Isaac; Duffy, Nadia; Sims, George; Beamer, Bryan; Pi-Sunyer, Teresa; Kamara, Sarian; Conteh, Sulaiman; Redd, John

    2016-02-26

    Since the start of the Ebola virus disease (Ebola) outbreak in West Africa, Sierra Leone has reported 8,706 confirmed Ebola cases and 3,956 deaths. During September 15-16, 2015, heavy rains flooded the capital, Freetown, resulting in eight deaths, home and property destruction, and thousands of persons in need of assistance. By September 27, approximately 13,000 flood-affected persons registered for flood relief services from the government. On September 17, two stadiums in Freetown were opened to provide shelter and assistance to flood-affected residents; a total of approximately 3,000 persons stayed overnight in both stadiums (Sierra Leone Ministry of Health and Sanitation, personal communication, September 2015). On the same day the stadiums were opened to flood-affected persons, the Ministry of Health and Sanitation (MoHS) and Western Area Ebola Response Center (WAERC) staff members from CDC, the World Health Organization (WHO), and the African Union evaluated the layout, logistics, and services at both stadiums and identified an immediate need to establish Ebola response activities. The patient in the last Ebola case in the Western Area, which includes Freetown, had died 37 days earlier, on August 11; however, transmission elsewhere in Sierra Leone was ongoing, and movement of persons throughout the country was common. PMID:26914633

  4. Backs against the Wall: Novel and Existing Strategies Used during the 2014-2015 Ebola Virus Outbreak

    PubMed Central

    Wong, Gary

    2015-01-01

    SUMMARY The 2014-2015 outbreak of Ebola virus (EBOV), originating from Guinea, is now responsible for the infection of >20,000 people in 9 countries. Whereas past filovirus outbreaks in sub-Saharan Africa have been rapidly brought under control with comparably few cases, this outbreak has been particularly resistant to containment efforts. Both the general population and primary health care workers have been affected by this outbreak, with hundreds of doctors and nurses being infected in the line of duty. In the absence of approved therapeutics, several caregivers have turned to investigational new drugs as well as experimental therapies in an effort to save lives. This review aims to summarize the candidates currently under consideration for postexposure use in infected patients during the largest EBOV outbreak in history. PMID:25972518

  5. The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States

    PubMed Central

    Kraft, Colleen S.; Hewlett, Angela L.; Koepsell, Scott; Winkler, Anne M.; Kratochvil, Christopher J.; Larson, LuAnn; Varkey, Jay B.; Mehta, Aneesh K.; Lyon, G. Marshall; Friedman-Moraco, Rachel J.; Marconi, Vincent C.; Hill, Charles E.; Sullivan, James N.; Johnson, Daniel W.; Lisco, Steven J.; Mulligan, Mark J.; Uyeki, Timothy M.; McElroy, Anita K.; Sealy, Tara; Campbell, Shelley; Spiropoulou, Christina; Ströher, Ute; Crozier, Ian; Sacra, Richard; Connor, Michael J.; Sueblinvong, Viranuj; Franch, Harold A.; Smith, Philip W.; Ribner, Bruce S.; Smith, Philip; Hewlett, Angela; Schwedhelm, Shelly; Boulter, Kate; Beam, Elizabeth; Gibbs, Shawn; Lowe, John; Kratochvil, Chris; Sullivan, James; Johnson, Dan; Lisco, Steve; Piquette, Craig; Bailey, Kristina; Auxier, Joseph; Boer, Brian; Hanson, Travis; Kaseman, Julia; Khan, M. Salman; Rhee, Ji Hyun; Wells, Adam; Florescu, Diana; Kalil, Andre; Rupp, Mark; Becker, Valerie; Boeckman, Bridget; Elder, Erica; Fitch, Abby; Flood, Elizabeth; Freml, Meagan; Frigge, Roman; Hanzlik, Kelly Ann; Jensen, Lois; Kraus, Nicole; Molacek, Drew; Nevins, Jerry; Parker, Alicia; Peters, Jeff; Rand, Cheryl; Roesler, Karen; Ryalls, Kendall; Shradar, Morgan; Strain, Amanda; Sunderman, Timothy; Sundermeier, Jennifer; Swanhorst, John; Vasa, Angela; Bellinghausen, Jean; Freihaut, Frank; Denny, Susan; Mainelli, Lauren; Pinkney, Dee; Ray, Deborah; Jevne, Jay; Knight, Kalen; McCroy, Derrick; Nadeau, Ralph; Nightser, Anna; Iwen, Pete; Sambol, Tony; Herrera, Vicki; Morgan, David; Trotter, Sarah; Kerby, Amy; Peters, Sue; Southern, Timothy; Murphy, Caitlin; Morris, Rosanna; Nuss, Sue; Franco, Theresa; Ogden, Connie; Lazure, Julie; Straub, Dawn; Koepsell, Scott; Hinrichs, Steve; Plumb, Troy; Florescu, Marius; Becker, John; Souchek, Jenna; Beck, Jon; Larson, Luann; Heires, Peggy; Gordon, Bruce; Paulsen, Gail; Wolford, Barb; Petersen, Jill; Marion, Nedra; Hayes, Kim; Tyner, Kate; Wilson, Taylor; Baltes, Paul; Nowatzke, Jenny; Nguyen, Jonathan; Turner, Paul; Boonstra, Barb; Jelden, Katelyn; Portrey, Randy; Stringfield, Doug; Scofield, Bryan; Svanda, Gary; Horihan, Jolene; Dahl, Chris; Bruno, Megan; Malm, Kelsey; Litz, Ron; Fehringer, Jessica; Paladino, Katie; Opp, Tammy; Bell, Sonia; Adams, Anne; Allen, Mary Beth; Bachman, Robert; Bornstein, William; Cantrell, Dee; Cosper, Pam; Feistritzer, Nancye; Fox, John; Gartland, Bryce; Goodman, Jen; Grant, Susan; Howard-Crow, Dallis; Horowitz, Ira; Pugh, David; Ritenour, Chad; Ash, Toni; Barnes, Christopher; Calhoun, Jason; Chapman, Lauren; Daye, Tracey; Durr, Haley; Evans, Shunasee; Gentry, Janice; Ginnane, Jan; Grant, Susan; Haynes, Chris; Hill, Carolyn; Hillis, Dustin; Johnson, Crystal; Loomis, Jessica; Mamora, Josia; Mitchell, Laura; Morgan, Jill; Osakwe, Nancy; Owen, Jacqueline; Piazza, Sarah; Shirley, Kristina; Siddens, Jodi; Silas, Carrie; Slabach, Jason; Tirador, Elaina; Todd, Donnette; Vanairsdale, Sharon; Brammer, Nicole; Buchanan, Juli; Burd, Eileen; Cardella, John; Eaves, Brenda; Evans, Crystal; Hostetler, Krista; Jenkins, Karen; Lindsey, Maureen; Magee, Jordan; Powers, Randall; Ritchie, James; Ryan, Emily; Bonds, Shannon; Emamifar, Amir; Kuban, Tish; Pack, Jan; Rogers, Susan; Golston, George; Kaufman, Sean; Olinger, Patricia; Olinger, Sean; Rengarajan, Kalpana; Thomaston, Scott; Beck, Emily; Desroches, Paula; Hall, Cynthia; Walker, Celeste; Bryant, Connie; Hackman, Betsy; Howard, Regina; Jones, Marolyn; Broughton, Jeff; Frisle, Brian; Jackson, Robert; Lewis, Jerry; Brown-Haithco, Robin; Gartin, Miranda Lynn; Geralds-Washington, Erica; James-Jones, Rhonda; Miller, Donald; Stark, Dan; McGee, Gentrice; Jones, Porcia; Scott-Harris, Linda; Cain, James; Davis, Roderick; Johnson, Tyrone; Pickett, Tyrone; Shaw, Anthony; Truesdale, Tenina; Blum, Jim; Hill, Laureen; Sevransky, Jon; Zivot, Joel; Walker, Seth; Klopman, Matthew; Matkins, Ricky; Meechan, Cathy; Meechan, Paul; Schwock, Kathy; Schuck, Jen; Stack, Kathy; Wolf, Francis; Bray, Bruce; Isakov, Alex; Shartar, Sam; Miles, Wade; Jamison, Aaro; Arevalo, John; Stallings, Gail; Christenbury, Janet; Dollard, Vince; De Gennaro, Melanie; Korschun, Holly; Seideman, Nancy; Ziegler, Tom; Griffith, Daniel P.; Dave, Nisha; Wall, Susan; Hall, Melida; McGhee, Dwania; Clarke, Tim; Vaught, Rachel; Peterson-Pileri, Katrina

    2015-01-01

    Background. The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. Methods. We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. Results. While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. Conclusions. It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD. PMID:25904375

  6. Characterization of oligomerization of a peptide from the ebola virus glycoprotein by small-angle neutron scattering

    NASA Astrophysics Data System (ADS)

    Egorov, V. V.; Gorshkov, A. N.; Murugova, T. N.; Vasin, A. V.; Lebedev, D. V.; Isaev-Ivanov, V. V.; Kiselev, O. I.

    2016-01-01

    Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) studies showed that model peptides QNALVCGLRQ (G33) and QNALVCGLRG (G31) corresponding to region 551-560 of the GP protein of the Sudan Ebola virus are prone to oligomerization in solution. Both peptides can form amyloid-like fibrills. The G33 peptide forms fibrils within one day of incubation, whereas the fibrillogenesis of the G31 peptide is observed only after incubation for several months. The possible role of the observed processes in the pathogenesis and the possibility of applying a combination of the TEM and SANS techniques to search for new compounds that are able to influence the protein oligomerization are discussed.

  7. Structure and dynamics of Ebola virus matrix protein VP40 by a coarse-grained Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Pandey, Ras; Farmer, Barry

    Ebola virus matrix protein VP40 (consisting of 326 residues) plays a critical role in viral assembly and its functions such as regulation of viral transcription, packaging, and budding of mature virions into the plasma membrane of infected cells. How does the protein VP40 go through structural evolution during the viral life cycle remains an open question? Using a coarse-grained Monte Carlo simulation we investigate the structural evolution of VP40 as a function of temperature with the input of a knowledge-based residue-residue interaction. A number local and global physical quantities (e.g. mobility profile, contact map, radius of gyration, structure factor) are analyzed with our large-scale simulations. Our preliminary data show that the structure of the protein evolves through different state with well-defined morphologies which can be identified and quantified via a detailed analysis of structure factor.

  8. Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection

    PubMed Central

    Dowall, Stuart David; Callan, Jo; Zeltina, Antra; Al-Abdulla, Ibrahim; Strecker, Thomas; Fehling, Sarah K.; Krähling, Verena; Bosworth, Andrew; Rayner, Emma; Taylor, Irene; Charlton, Sue; Landon, John; Cameron, Ian; Hewson, Roger; Nasidi, Abdulsalami; Bowden, Thomas A.; Carroll, Miles W.

    2016-01-01

    The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease. PMID:26715676

  9. 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/ΔNPNTD 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.

  10. Ebola virus disease: Case management in the Institute of Infectious Diseases, University Hospital of Sassari, Sardinia, Italy.

    PubMed

    Bertoli, Giulia; Mannazzu, Marco; Madeddu, Giordano; Are, Riccardo; Muredda, Alberto; Babudieri, Sergio; Calia, Giovanna; Lovigu, Carla; Maida, Ivana; Contini, Luciana; Miscali, Anna; Rubino, Salvatore; Delogu, Fiorenzo; Mura, Maria Stella

    2016-01-01

    Since the onset of the worst epidemic of Ebola virus disease in December 2013, 28,637 cases were reported as confirmed, probable, or suspected. Since the week of 3 January 2016, no more cases have been reported. The total number of deaths have amounted to 11,315 (39.5%). In developed countries, seven cases have been diagnosed: four in the United States, one in Spain, one in the United Kingdom, and one in Italy. On 20 July 2015, Italy was declared Ebola-free. On 9 May 2015, an Italian health worker came back to Italy after a long stay in Sierra Leone working for a non-governmental organization. Forty-eight hours after his arrival, he noticed headache, weakness, muscle pains, and slight fever. The following day, he was safely transported to the Infectious Diseases Unit of University Hospital of Sassari. The patient was hospitalized for 19 hours until an Italian Air Force medical division transferred him to Rome, to the Lazzaro Spallanzani Institute. Nineteen people who had contacts with the patient were monitored daily for 21 days by the Public Health Office of Sassari and none presented any symptoms. So far, neither vaccine nor treatment is available to be proposed on an international scale. Ebola is considered a re-emerging infectious disease which, unlike in the past, has been a worldwide emergency. This case study aimed to establish a discussion about the operative and logistic difficulties to be faced and about the discrepancy arising when protocols clash with the reality of facts. PMID:27249532

  11. Development and evaluation of a real-time RT-PCR assay for the detection of Ebola virus (Zaire) during an Ebola outbreak in Guinea in 2014-2015.

    PubMed

    Dedkov, V G; Magassouba, N' F; Safonova, M V; Deviatkin, A A; Dolgova, A S; Pyankov, O V; Sergeev, A A; Utkin, D V; Odinokov, G N; Safronov, V A; Agafonov, A P; Maleev, V V; Shipulin, G A

    2016-02-01

    In early February 2014, an outbreak of the Ebola virus disease caused by Zaire ebolavirus (EBOV) occurred in Guinea; cases were also recorded in other West African countries with a combined population of approximately 25 million. A rapid, sensitive and inexpensive method for detecting EBOV is needed to effectively control such outbreak. Here, we report a real-time reverse-transcription PCR assay for Z. ebolavirus detection used by the Specialized Anti-epidemic Team of the Russian Federation during the Ebola virus disease prevention mission in the Republic of Guinea. The analytical sensitivity of the assay is 5 × 10(2) viral particles per ml, and high specificity is demonstrated using representative sampling of viral, bacterial and human nucleic acids. This assay can be applied successfully for detecting the West African strains of Z. ebolavirus as well as on strains isolated in the Democratic Republic of the Congo in 2014. PMID:26597659

  12. Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials.

    PubMed

    Madelain, Vincent; Nguyen, Thi Huyen Tram; Olivo, Anaelle; de Lamballerie, Xavier; Guedj, Jérémie; Taburet, Anne-Marie; Mentré, France

    2016-08-01

    The 2014-2015 outbreak of Ebola virus disease is the largest epidemic to date in terms of the number of cases, deaths, and affected areas. In October 2015, no antiviral agents had proven antiviral efficacy in patients. However, in September 2014, the World Health Organization inventoried and has since regularly updated a list of potential drug candidates with demonstrated antiviral efficacy in in vitro or animal models. This includes agents belonging to various therapeutic classes, namely direct antiviral agents (favipiravir and BCX4430), a combination of antibodies (ZMapp), type I interferons, RNA interference-based drugs (TKM-Ebola and AVI-7537), and anticoagulant drugs (rNAPc2). Here, we review the pharmacokinetic and pharmacodynamic information presently available for these drugs, using data obtained in healthy volunteers for pharmacokinetics and data obtained in human clinical trials or animal models for pharmacodynamics. Future studies evaluating these drugs in clinical trials are critical to confirm their efficacy in humans, propose appropriate doses, and evaluate the possibility of treatment combinations. PMID:26798032

  13. Preparedness for admission of patients with suspected Ebola virus disease in European hospitals: a survey, August-September 2014.

    PubMed

    de Jong, M D; Reusken, C; Horby, P; Koopmans, M; Bonten, M; Chiche, Jd; Giaquinto, C; Welte, T; Leus, F; Schotsman, J; Goossens, H

    2014-01-01

    In response to the Ebola virus disease (EVD) outbreak in West Africa, the World Health Organization has advised all nations to prepare for the detection, investigation and management of confirmed and suspected EVD cases in order to prevent further spread through international travel. To gain insights into the state of preparedness of European hospitals, an electronic survey was circulated in August–September 2014 to 984 medical professionals representing 736 hospitals in 40 countries. The survey addressed the willingness and capacity to admit patients with suspected EVD as well as specific preparedness activities in response to the current Ebola crisis. Evaluable responses were received from representatives of 254 (32%) hospitals in 38 countries, mostly tertiary care centres, of which 46% indicated that they would admit patients with suspected EVD. Patient transfer agreements were in place for the majority of hospitals that would not admit patients. Compared with non-admitting hospitals, admitting hospitals were more frequently engaged in various preparedness activities and more often contained basic infrastructural characteristics such as admission rooms and laboratories considered important for infection control, but some gaps and concerns were also identified. The results of this survey help to provide direction towards further preparedness activities and prioritisation thereof. PMID:25496571

  14. Surveillance and Outbreak Response Management System (SORMAS) to support the control of the Ebola virus disease outbreak in West Africa.

    PubMed

    Fähnrich, C; Denecke, K; Adeoye, O O; Benzler, J; Claus, H; Kirchner, G; Mall, S; Richter, R; Schapranow, M P; Schwarz, N; Tom-Aba, D; Uflacker, M; Poggensee, G; Krause, G

    2015-01-01

    In the context of controlling the current outbreak of Ebola virus disease (EVD), the World Health Organization claimed that 'critical determinant of epidemic size appears to be the speed of implementation of rigorous control measures', i.e. immediate follow-up of contact persons during 21 days after exposure, isolation and treatment of cases, decontamination, and safe burials. We developed the Surveillance and Outbreak Response Management System (SORMAS) to improve efficiency and timeliness of these measures. We used the Design Thinking methodology to systematically analyse experiences from field workers and the Ebola Emergency Operations Centre (EOC) after successful control of the EVD outbreak in Nigeria. We developed a process model with seven personas representing the procedures of EVD outbreak control. The SORMAS system architecture combines latest In-Memory Database (IMDB) technology via SAP HANA (in-memory, relational database management system), enabling interactive data analyses, and established SAP cloud tools, such as SAP Afaria (a mobile device management software). The user interface consists of specific front-ends for smartphones and tablet devices, which are independent from physical configurations. SORMAS allows real-time, bidirectional information exchange between field workers and the EOC, ensures supervision of contact follow-up, automated status reports, and GPS tracking. SORMAS may become a platform for outbreak management and improved routine surveillance of any infectious disease. Furthermore, the SORMAS process model may serve as framework for EVD outbreak modeling. PMID:25846493

  15. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

    PubMed Central

    Rojek, Amanda; Gannon, Fiona; Carson, Gail; Idriss, Baimba; Massaquoi, Thomas; Gandi, Regina; Joseph, Sebatu; Osman, Hassan K.; Brooks, Timothy J. G.; Simpson, Andrew J. H.; Goodfellow, Ian; Thorne, Lucy; Arias, Armando; Merson, Laura; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Hope-Gill, Benjamin; Ferri, Mauricio; Grove, Jennifer; Kowalski, Mark; Stepniewska, Kasia; Lang, Trudie; Whitehead, John; Olliaro, Piero; Samai, Mohammed; Horby, Peter W.

    2016-01-01

    Background TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. Methods and Findings In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Conclusions Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Trial registration Pan African Clinical Trials Registry PACTR201501000997429 PMID:27093560

  16. Successful Control of Ebola Virus Disease: Analysis of Service Based Data from Rural Sierra Leone

    PubMed Central

    Lokuge, Kamalini; Caleo, Grazia; Greig, Jane; Duncombe, Jennifer; McWilliam, Nicholas; Squire, James; Lamin, Manjo; Veltus, Emily; Wolz, Anja; Kobinger, Gary; de la Vega, Marc-Antoine; Gbabai, Osman; Nabieu, Sao; Lamin, Mohammed; Kremer, Ronald; Danis, Kostas; Banks, Emily; Glass, Kathryn

    2016-01-01

    Introduction The scale and geographical distribution of the current outbreak in West Africa raised doubts as to the effectiveness of established methods of control. Ebola Virus Disease (EVD) was first detected in Sierra Leone in May 2014 in Kailahun district. Despite high case numbers elsewhere in the country, transmission was eliminated in the district by December 2014. We describe interventions underpinning successful EVD control in Kailahun and implications for EVD control in other areas. Methods Internal service data and published reports from response agencies were analysed to describe the structure and type of response activities, EVD case numbers and epidemic characteristics. This included daily national situation reports and District-level data and reports of the Sierra Leone Ministry of Health and Sanitation, and Médecins Sans Frontières (MSF) patient data and internal epidemiological reports. We used EVD case definitions provided by the World Health Organisation over the course of the outbreak. Characteristics assessed included level of response activities and epidemiological features such as reported exposure (funeral-related or not), time interval between onset of illness and admission to the EVD Management Centre (EMC), work-related exposures (health worker or not) and mortality. We compared these characteristics between two time periods—June to July (the early period of response), and August to December (when coverage and quality of response had improved). A stochastic model was used to predict case numbers per generation with different numbers of beds and a varying percentage of community cases detected. Results There were 652 probable/confirmed EVD cases from June-December 2014 in Kailahun. An EMC providing patient care opened in June. By August 2014 an integrated detection, treatment, and prevention strategy was in place across the district catchment zone. From June-July to August-December 2014 surveillance and contact tracing staff increased

  17. Knowledge, Attitude and Perception of Ebola Virus Disease among Secondary School Students in Ondo State, Nigeria, October, 2014

    PubMed Central

    Ilesanmi, Olayinka; Alele, Faith Osaretin

    2016-01-01

    Introduction: The first case of Ebola Virus Disease (EVD) in Nigeria was imported on 20th July 2014, by an air traveller. On 8th August, 2014, WHO declared the Ebola outbreak in West Africa a Public Health Emergency of International Concern (PHEIC). This study aimed at assessing the knowledge, perception and attitude of secondary school students towards EVD and adopting disease preventive behaviour. Methods: A descriptive cross sectional study of 440 students from a mixed secondary school in Owo, Ondo State was done. Data was collected in October 2014 when Nigeria was yet to be declared EVD free.Simple random sampling was used to select the school while Systematic random sampling was used in the selection of participants. A semi-structured, interviewer administered questionnaire was used to collect data. Data was analyzed with SPSS version 21. Descriptive statistics and Chi-square test were done, level of statistical significant was 5%. Results: Mean age of respondents was 13.7±1.9 years. Females were 48.2%. Most of the respondents had heard of Ebola Virus Disease (95.4%). Female respondents (51.3%), those who were 15 years and above (51.1%) and in the senior class (54.1%), and had good general knowledge of EVD and across all domains. Being in the senior secondary class and seeking for health care in the hospital were positively associated with good general knowledge (p-value: 0.029, and <0.001 respectively). Three commonest modes of spread of EVD mentioned were contact between infected animals and men (74.8%), touching body fluids of a person who is sick of EVD (57.0%), and contact (55.2%). The top three signs of EVD mentioned were abnormal bleeding from any part of the body (56.10%), vomiting (47.0%) and fever (42.3%). Conclusion: Our results revealed suboptimal EVD-related knowledge, attitude and practice among the students. Promotion of health messages and training of students on prevention of EVD to effectively control past and future outbreaks of EVD in

  18. Clinical Features of and Risk Factors for Fatal Ebola Virus Disease, Moyamba District, Sierra Leone, December 2014–February 2015

    PubMed Central

    Haaskjold, Yngvar Lunde; Bolkan, Håkon Angell; Krogh, Kurt Østhuus; Jongopi, James; Lundeby, Karen Marie; Mellesmo, Sindre; Garcés, Pedro San José; Jøsendal, Ola; Øpstad, Åsmund; Svensen, Erling; Fuentes, Luis Matias Zabala; Kamara, Alfred Sandy; Riera, Melchor; Arranz, Javier; Roberts, David P.; Stamper, Paul D.; Austin, Paula; Moosa, Alfredo J.; Marke, Dennis; Hassan, Shoaib; Eide, Geir Egil; Berg, Åse

    2016-01-01

    The 2013–2016 outbreak of Ebola virus disease (EVD) in West Africa infected >28,000 people, including >11,000 who died, and disrupted social life in the region. We retrospectively studied clinical signs and symptoms and risk factors for fatal outcome among 31 Ebola virus–positive patients admitted to the Ebola Treatment Center in Moyamba District, Sierra Leone. We found a higher rate of bleeding manifestations than reported elsewhere during the outbreak. Significant predictors for death were shorter time from symptom onset to admission, male sex, high viral load on initial laboratory testing, severe pain, diarrhea, bloody feces, and development of other bleeding manifestations during hospitalization. These risk factors for death could be used to identify patients in need of more intensive medical support. The lack of fever in as many as one third of EVD cases may have implications for temperature-screening practices and case definitions. PMID:27268303

  19. Performance of the GeneXpert Ebola Assay for Diagnosis of Ebola Virus Disease in Sierra Leone: A Field Evaluation Study

    PubMed Central

    Richards, Jade; Foster, Geraldine M.; Simpson, Andrew J. H.; Logue, Christopher H.; Kelly, J. Daniel; Miller, Ann; Brooks, Tim J. G.; Murray, Megan; Pollock, Nira R.

    2016-01-01

    Background Throughout the Ebola virus disease (EVD) epidemic in West Africa, field laboratory testing for EVD has relied on complex, multi-step real-time reverse transcription PCR (RT-PCR) assays; an accurate sample-to-answer RT-PCR test would reduce time to results and potentially increase access to testing. We evaluated the performance of the Cepheid GeneXpert Ebola assay on clinical venipuncture whole blood (WB) and buccal swab (BS) specimens submitted to a field biocontainment laboratory in Sierra Leone for routine EVD testing by RT-PCR (“Trombley assay”). Methods and Findings This study was conducted in the Public Health England EVD diagnostic laboratory in Port Loko, Sierra Leone, using residual diagnostic specimens remaining after clinical testing. EDTA-WB specimens (n = 218) were collected from suspected or confirmed EVD patients between April 1 and July 20, 2015. BS specimens (n = 71) were collected as part of a national postmortem screening program between March 7 and July 20, 2015. EDTA-WB and BS specimens were tested with Xpert (targets: glycoprotein [GP] and nucleoprotein [NP] genes) and Trombley (target: NP gene) assays in parallel. All WB specimens were fresh; 84/218 were tested in duplicate on Xpert to compare WB sampling methods (pipette versus swab); 43/71 BS specimens had been previously frozen. In all, 7/218 (3.2%) WB and 7/71 (9.9%) BS samples had Xpert results that were reported as “invalid” or “error” and were excluded, leaving 211 WB and 64 BS samples with valid Trombley and Xpert results. For WB, 22/22 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 84.6%–100%), and 181/189 Trombley-negative samples were Xpert-negative (specificity 95.8%, 95% confidence interval (CI) 91.8%–98.2%). Seven of the eight Trombley-negative, Xpert-positive (Xpert cycle threshold [Ct] range 37.7–43.4) WB samples were confirmed to be follow-up submissions from previously Trombley-positive EVD patients, suggesting a revised

  20. Detection and Analysis of Ebola Virus in Sierra Leone-China Friendship Biosafety Laboratory from March 11 to April 20, 2015.

    PubMed

    Wang, Qin; Zhang, Yong; Wang, Huan Yu; DU, Hai Jun; Nie, Kai; Song, Jing Dong; Xiao, Kang; Lei, Wen Wen; Guo, Jian Qiang; Wei, He Jiang; Cai, Kun; Wang, Yan Hai; Wu, Jiang; Bangura, Gerald; Kamara, Idrissa Laybohr; Dong, Xiao Ping

    2016-06-01

    Ebola virus disease reemerged in Western Africa in 2014. Chinese Center for Disease Control and Prevention dispatched the first Ebola virus (EBOV) detection team to run newly established Sierra Leone-China Friendship Biological Safety Laboratory. The aims of study were to understand epidemiology, clinical manifestations and survival time of EBOV in patient's blood. A total of 913 specimens were tested between March 11 and April 20, 2015. EBOV positivity occurred in 7.37% of the blood and 0.53% in throat swabs. Most commonly reported symptoms of laboratory confirmed patients were intense fatigue, anorexia, and fever. EBOV RNAs persisted in blood for almost 4 weeks and the real-time RT-PCR Ct values showed close correlation with the sampling time after onset. PMID:27470105

  1. 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

    Kuhn, Jens H; Andersen, Kristian G; Baize, Sylvain; Bào, Yīmíng; 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

    2014-11-01

    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

  2. Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications.

    PubMed

    Nelson, Elizabeth A; Barnes, Alyson B; Wiehle, Ronald D; Fontenot, Gregory K; Hoenen, Thomas; White, Judith M

    2016-01-01

    The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors. PMID:27490565

  3. 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

  4. Persistence of Ebola virus in various body fluids during convalescence: evidence and implications for disease transmission and control.

    PubMed

    Chughtai, A A; Barnes, M; Macintyre, C R

    2016-06-01

    The aim of this study was to review the current evidence regarding the persistence of Ebola virus (EBOV) in various body fluids during convalescence and discuss its implication on disease transmission and control. We conducted a systematic review and searched articles from Medline and EMBASE using key words. We included studies that examined the persistence of EBOV in various body fluids during the convalescent phase. Twelve studies examined the persistence of EBOV in body fluids, with around 800 specimens tested in total. Available evidence suggests that EBOV can persist in some body fluids after clinical recovery and clearance of virus from the blood. EBOV has been isolated from semen, aqueous humor, urine and breast milk 82, 63, 26 and 15 days after onset of illness, respectively. Viral RNA has been detectable in semen (day 272), aqueous humor (day 63), sweat (day 40), urine (day 30), vaginal secretions (day 33), conjunctival fluid (day 22), faeces (day 19) and breast milk (day 17). Given high case fatality and uncertainties around the transmission characteristics, patients should be considered potentially