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Sample records for ebola virus challenge

  1. Ebola (Ebola Virus Disease): Prevention

    MedlinePlus

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  2. Ebola (Ebola Virus Disease): Transmission

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  3. Ebola (Ebola Virus Disease): Treatment

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  4. Ebola (Ebola Virus Disease): Diagnosis

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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. 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

  7. 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

  8. 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 ...

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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 ...

  16. [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

  17. 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

  18. 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

  19. 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

  20. 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

  1. [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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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 ...

  7. 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

  8. 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 ...

  9. 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.

  10. 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

  11. 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

  12. 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 ...

  13. An Ebola virus-centered knowledge base

    PubMed Central

    Kamdar, Maulik R.; Dumontier, Michel

    2015-01-01

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

  14. 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

  15. 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

  16. 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

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

    PubMed Central

    Phua, Kai-Lit

    2015-01-01

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

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

    PubMed

    Phua, Kai-Lit

    2015-01-01

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

  19. 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

  20. 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 ...

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

    PubMed Central

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

    2006-01-01

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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  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. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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).

  2. 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

  3. 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

  4. 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

  5. Ethical challenges of containing Ebola: the Nigerian experience.

    PubMed

    Maduka, Omosivie; Odia, Osaretin

    2015-11-01

    Responding effectively to an outbreak of disease often requires routine processes to be set aside in favour of unconventional approaches. Consequently, an emergency response situation usually generates ethical dilemmas. The emergence of the Ebola virus in the densely populated cities of Lagos and Port Harcourt in Nigeria brought bleak warnings of a rapidly expanding epidemic. However, these fears never materialised largely due to the swift reaction of emergency response and incident management organisations, and the WHO has now declared Nigeria free of Ebola. However, numerous ethical issues arose in relation to the response to the outbreak. This paper discusses some of these ethical challenges and the vital lessons learned. Ethical challenges relating to confidentiality, the dignity of persons, non-maleficence, stigma and the ethical obligations of health workers are examined. Interventions implemented to ensure that confidentiality and the dignity of persons improved and stigma was reduced, included community meetings, knowledge communication and the training of media personnel in the ethical reporting of Ebola issues. In addition, training in infection prevention and control helped to allay the fears of health workers. A potential disaster was also averted when the use of an experimental medicine was reconsidered. Other countries currently battling the epidemic can learn a lot from the Nigerian experience. PMID:26091816

  6. Informing the Historical Record of Experimental Nonhuman Primate Infections with Ebola Virus: Genomic Characterization of USAMRIID Ebola Virus/H.sapiens-tc/COD/1995/Kikwit-9510621 Challenge Stock “R4368” and Its Replacement “R4415”

    PubMed Central

    Kugelman, Jeffrey R.; Rossi, Cynthia A.; Wiley, Michael R.; Ladner, Jason T.; Nagle, Elyse R.; Pfeffer, Bradley P.; Garcia, Karla; Prieto, Karla; Wada, Jiro; Kuhn, Jens H.; Palacios, Gustavo

    2016-01-01

    The creation of licensed medical countermeasures against Select Agents such as Ebola virus (EBOV) is critically dependent on the use of standardized reagents, assays, and animal models. We performed full genome reconstruction, population genomics, contaminant analysis, and characterization of the glycoprotein gene editing site of historical United States Army Medical Research Institute of Infectious Diseases (USAMRIID) nonhuman-primate challenge stock Ebola virus Kikwit “R4368” and its 2014 replacement “R4415.” We also provide characterization of the master stock used to create “R4415.” The obtained data are essential to understanding the quality of the seed stock reagents used in pivotal animal studies that have been used to inform medical countermeasure development. Furthermore, these data might add to the understanding of the influence of EBOV variant populations on pathogenesis and disease outcome and inform attempts to avoid the evolution of EBOV escape mutants in response to current therapeutics. Finally, as the primary challenge stocks have changed over time, these data will provide a baseline for understanding and correlating past and future animal study results. PMID:27002733

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. Ebola crisis of 2014: are current strategies enough to meet the long-run challenges ahead?

    PubMed

    Gimm, Gilbert; Nichols, Len M

    2015-05-01

    The outbreak of the Ebola virus disease (EVD) in 2014 mobilized international efforts to contain a global health crisis. The emergence of the deadly virus in the United States and Europe among health care workers intensified fears of a worldwide epidemic. Market incentives for pharmaceutical firms to allocate their research and development resources toward Ebola treatments were weak because the limited number of EVD cases were previously confined to rural areas of West Africa. We discuss 3 policy recommendations to address the long-term challenges of EVD in an interconnected world. PMID:25790395

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

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

    PubMed Central

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

    2015-01-01

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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Ebola: lessons learned and future challenges for Europe.

    PubMed

    Quaglio, GianLuca; Goerens, Charles; Putoto, Giovanni; Rübig, Paul; Lafaye, Pierre; Karapiperis, Theodoros; Dario, Claudio; Delaunois, Paul; Zachariah, Rony

    2016-02-01

    The Ebola virus epidemic has topped media and political agendas for months; several countries in west Africa have faced the worst Ebola epidemic in history. At the beginning of the disease outbreak, European Union (EU) policies were notably absent regarding how to respond to the crisis. Although the epidemic is now receding from public view, this crisis has undoubtedly changed the European public perception of Ebola virus disease, which is no longer regarded as a bizarre entity confined in some unknown corner in Africa. Policy makers and researchers in Europe now have an opportunity to consider the lessons learned. In this Personal View, we discuss the EU's response to the Ebola crisis in west Africa. Unfortunately, although ample resources and opportunities for humanitarian and medical action existed, the EU did not use them to promote a rapid and well coordinated response to the Ebola crisis. Lessons learned from this crisis should be used to improve the role of the EU in similar situations in the future, ensuring that European aid can be effectively deployed to set up an improved emergency response system, and supporting the establishment of sustainable health-care services in west Africa. PMID:26627138

  19. 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

  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. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. [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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  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. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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 ...

  5. 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

  6. 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

  7. 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

  8. 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

  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 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Challenges in controlling the Ebola outbreak in two prefectures in Guinea: why did communities continue to resist?

    PubMed Central

    Thiam, Sylla; Delamou, Alexandre; Camara, Soriba; Carter, Jane; Lama, Eugene Kaman; Ndiaye, Bara; Nyagero, Josephat; Nduba, John; Ngom, Mor

    2015-01-01

    Introduction The Ebola outbreak emerged in a remote corner of Guinea in December 2013, and spread into Liberia and Sierra Leone in the context of weak health systems. In this paper, we report on the main challenges faced by frontline health services and by communities including their perceptions and views on the current Ebola response in the Prefectures of Coyah and Forecariah in Guinea. Methods A cross-sectional study was conducted in December 2014 using mixed approaches: (i) Desk review; (ii) Interviews; and (iii) Direct observation. Results Almost one year after the beginning of the Ebola virus disease outbreak in West Africa, the perceptions of stakeholders and the observed reality were that the level of preparedness in the two health districts was low. The study identified poor coordination mechanisms, inadequate training of human resources and lack of equipment and supplies to field teams and health facilities as key elements that affected the response. The situation was worsened by the inadequate communication strategy, misconceptions around the disease, ignorance of local culture and customs and lack of involvement of local communities in the control strategies, within the context of poor socioeconomic development. As a result distrust developed between communities and those seeking to control the epidemic and largely contributed to the reluctance of the communities to participate and contribute to the effort. Conclusion There is a need to rethink the way disease control interventions in the context of an emergency such as Ebola virus disease are designed, planned and implemented in low income countries. PMID:26740850

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

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

    PubMed

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

    2015-10-01

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

  6. 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

  7. 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

  8. 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

  9. 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

  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

    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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. [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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Clinical development of Ebola vaccines

    PubMed Central

    Sridhar, Saranya

    2015-01-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  13. Clinical development of Ebola vaccines.

    PubMed

    Sridhar, Saranya

    2015-09-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  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. 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

  16. 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

  17. The Ebola epidemic in West Africa: challenges, opportunities, and policy priority areas.

    PubMed

    Buseh, Aaron G; Stevens, Patricia E; Bromberg, Mel; Kelber, Sheryl T

    2015-01-01

    The ongoing Ebola epidemic in West Africa has drawn attention to global health inequalities, in particular the inadequacies of health care systems in sub-Saharan African countries for appropriately managing and containing infectious diseases. The purpose of this article is to examine the sociopolitical and economic conditions that created the environment for the Ebola epidemic to occur, identify challenges to and opportunities for the prevention and control of Ebola and future outbreaks, and discuss policy recommendations and priority areas for addressing the Ebola epidemic and future outbreaks in West Africa. Articles in peer-reviewed journals on health system reforms in developing countries and periodicals of international organizations were used to gather the overview reported in this article. We identify individual, structural, and community challenges that must be addressed in an effort to reduce the spread of Ebola in West Africa. The Ebola epidemic in West Africa underscores the need for the overhaul and transformation of African health care systems to build the capacity in these countries to address infectious diseases. Public-private partnerships for investment in developing countries' health care systems that involve the international community are critical in addressing the current Ebola epidemic and future outbreaks. PMID:25645480

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. Ebola

    MedlinePlus

    ... touching or eating infected animals. Tropical animals in Africa believed to carry the virus include great apes, ... a few outbreaks of the disease in western Africa, Uganda, and Sudan. What Do Kids Need to ...

  20. 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

  1. 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

  2. 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

  3. [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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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