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Sample records for ebola virus reservoir

  1. Ebola (Ebola Virus Disease)

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Ebola (Ebola Virus Disease) Note: Javascript is disabled or is ... Tweet Share Compartir CDC's Ongoing Work to Contain Ebola in West Africa The Road to Zero: CDC’s ...

  2. Ebola (Ebola Virus Disease): Diagnosis

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  3. Ebola (Ebola Virus Disease): Prevention

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  4. Ebola (Ebola Virus Disease): Transmission

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  5. Ebola (Ebola Virus Disease): Treatment

    Science.gov (United States)

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  6. Search for the Ebola virus reservoir in Kikwit, Democratic Republic of the Congo

    DEFF Research Database (Denmark)

    Leirs, Herwig; Mills, James N.; Krebs, John W.

    1999-01-01

    A 3-month ecologic investigation was done to identify the reservoir of Ebola virus following the 1995 outbreak in Kikwit, Democratic Republic of the Congo, Efforts focused on the fields where the putative primary case had worked but included other habitats near Kikwit, Samples were collected from...... 3066 vertebrates and tested for the presence of antibodies to Ebola (subtype Zaire) virus: All tests were negative, and attempts to isolate Ebola virus were unsuccessful. The investigation was hampered by a lack of information beyond the daily activities of the primary case, a lack of information...... on Ebola virus ecology, which precluded the detailed study of select groups of animals, and sample-size limitations for rare species, The epidemiology of Ebola hemorrhagic fever suggests that humans have only intermittent contact with the virus, which complicates selection of target species. Further study...

  7. Ebola Virus and Marburg Virus

    Science.gov (United States)

    Diseases and Conditions Ebola virus and Marburg virus By Mayo Clinic Staff Ebola virus and Marburg virus are related viruses that cause hemorrhagic ... Africa, where sporadic outbreaks have occurred for decades. Ebola virus and Marburg virus live in animal hosts, ...

  8. Ebola Virus and Marburg Virus

    Science.gov (United States)

    Ebola virus and Marburg virus Overview By Mayo Clinic Staff Ebola virus and Marburg virus are related viruses that ... Africa, where sporadic outbreaks have occurred for decades. Ebola virus and Marburg virus live in animal hosts, ...

  9. Ebola Virus

    Directory of Open Access Journals (Sweden)

    Anusha Rangare Lakshman

    2015-09-01

    Full Text Available The disease Ebola takes its name from the Ebola River situated near a village in the Democratic Republic of Congo, where the disease first appeared in 1976. It is caused by a virus from the Filoviridae family (filovirus. The present outbreak of Ebola Virus Disease (EVD concerns four countries in West Africa, namely Guinea, Liberia, Sierra Leone and Nigeria till date. Further to widespread transmission of the disease, it has been declared as a Public Health Emergency of International Concern by the World Health Organisation on 8 August 2014. As of 4 August 2014, countries have reported 1,711 cases (1,070 confirmed, 436 probable, 205 suspect, including 932 deaths. This review paper enlightens about the awareness of Ebola virus and its preventive measures. [Archives Medical Review Journal 2015; 24(3.000: 296-305

  10. Understanding ebola virus transmission.

    Science.gov (United States)

    Judson, Seth; Prescott, Joseph; Munster, Vincent

    2015-02-03

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

  11. Understanding Ebola Virus Transmission

    Directory of Open Access Journals (Sweden)

    Seth Judson

    2015-02-01

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

  12. Virus Ebola Asia

    Directory of Open Access Journals (Sweden)

    Suharyono Wuryadi

    2012-09-01

    Full Text Available Virus Marburg dan Ebola diklasifikasikan sebagai virus yang sangat menular dan dimasukkan dalam klasifikasi sebagai virus/pathogen dengan derajat biosafety 4, sehingga untuk menanganinya diperlukan laboratorium khusus tingkat 4.

  13. Frequently Asked Questions on Ebola Virus Disease

    Science.gov (United States)

    ... disease Updated January 2016 1. What is Ebola virus disease? Ebola virus disease (formerly known as Ebola haemorrhagic fever) ... are the typical signs and symptoms of Ebola virus infection? Ebola symptoms vary but sudden onset of fever, intense ...

  14. Characteristics of Filoviridae: Marburg and Ebola Viruses

    Science.gov (United States)

    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.

  15. [Ebola virus disease].

    Science.gov (United States)

    Nazimek, Katarzyna; Bociaga-Jasik, Monika; Bryniarski, Krzysztof; Gałas, Aleksander; Garlicki, Aleksander; Gawda, Anna; Gawlik, Grzegorz; Gil, Krzysztof; Kosz-Vnenchak, Magdalena; Mrozek-Budzyn, Dorota; Olszanecki, Rafał; Piatek, Anna; Zawilińska, Barbara; Marcinkiewicz, Janusz

    2014-01-01

    Ebola is one of the most virulent zoonotic RNA viruses causing in humans haemorrhagic fever with fatality ratio reaching 90%. During the outbreak of 2014 the number of deaths exceeded 8.000. The "imported" cases reported in Western Europe and USA highlighted the extreme risk of Ebola virus spreading outside the African countries. Thus, haemorrhagic fever outbreak is an international epidemiological problem, also due to the lack of approved prevention and therapeutic strategies. The editorial review article briefly summarizes current knowledge on Ebola virus disease epidemiology, etiology, pathogenesis, clinical presentation, diagnosis as well as possible prevention and treatment.

  16. Postmortem stability of Ebola virus.

    Science.gov (United States)

    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.

  17. Ebola virus (image)

    Science.gov (United States)

    Ebola is a deadly disease caused by a virus. The 2014 outbreak has occurred mainly in West Africa. Symptoms often start with fever, severe headache, muscle pain, abdominal pain, diarrhea, and vomiting. Late symptoms ...

  18. [Ebola virus disease].

    Science.gov (United States)

    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.

  19. Ebola virus and other Filoviruses: an overview

    Directory of Open Access Journals (Sweden)

    Hasna Amdiouni

    2015-01-01

    Full Text Available Filoviruses, including Ebola and Marburg viruses, are recognized as a significant warning to public health. They are zoonotic agents with bats as primary reservoir. Those viruses can cause severe human infection with hemorrhagic syndrome leading to death. The mortality rate can be higher than 90%. In West Africa, recent Ebola virus outbreak occurred in March 2014, has caused more than 8300 infections with more than 4000 deaths. That shows the critical state of this country, and the critical context in worldwide. In order to fight this deadly scourge, it is necessary to understand the epidemiology of disease and to establish a good diagnosis protocols and protective measures. In recent decades, traditional techniques of virus isolation are replaced by molecular biology techniques which are faster, more sensitive and specific. Until now, no specific Ebola virus treatment or vaccine but many studies are in progress with promising results.

  20. Recent advances on Ebola virus

    Directory of Open Access Journals (Sweden)

    Yasir Waheed

    2017-02-01

    Full Text Available The 2014–2015 Ebola epidemic in West Africa was the largest of its kind, with more than 11 000 deaths and 28 637 cases. The epidemic mobilized a coalition of countries from US to China, European Union, and African countries. The international community was not prepared to face this unprecedented epidemic. Numbers of research groups are working to find a potent vaccine against Ebola. Ebola virus has the ability to dodge the immune system either by blocking interferon production or by glycoprotein-based immune diversion. Individuals who survived from the Ebola virus are facing different health issues after the infection. The rate of miscarriage is also high in Ebola survivors while there are variable reports of the presence of Ebola virus in semen of Ebola survivors. There are many asymptomatic Ebola patients under consideration. West African countries lack the basic healthcare system, for which the actual number of deaths by the Ebola outbreak are much more than the deaths caused by the direct viral infection. The hospitals were empty due to fear and death of nurses and doctors. Millions of children missed the vaccine against measles. Hundreds of thousands of people could not get food. The Ebola epidemic also affected the mental health of people living in endemic countries. The families affected by Ebola are facing discrimination in the society. There is a dire need to adopt United Nations Sustainable Development Goal 3, which stresses to prepare ourselves to face any national or global health risk.

  1. Ebola Virus Disease

    Centers for Disease Control (CDC) Podcasts

    2014-08-08

    This podcast provides general information about Ebola virus disease and the outbreak in West Africa. The program contains remarks from CDC Director Dr. Tom Frieden, as well as a brief description of CDC’s response efforts.  Created: 8/8/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/8/2014.

  2. [Ebola virus disease: Update].

    Science.gov (United States)

    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. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  3. Ebola virus disease

    Science.gov (United States)

    ... reported in: Nigeria Senegal Spain United States Mali United Kingdom Italy There are no current cases of Ebola ... Ebola can also spread by contact with ANY surfaces, objects, and materials that have been in contact ...

  4. Ebola virus: recommendations

    CERN Multimedia

    CERN Medical Service

    2014-01-01

    The CERN Medical Service has been closely following, in particular via the WHO, the development of the Ebola virus outbreak currently affecting some African countries. This infectious disease may be passed on through direct contact with the bodily fluids of a sick person.   Based on the recommendations of the WHO and the two Host States, Switzerland and France, as updated on their respective websites, so far there has been no ban on travel to the countries concerned. However, unless it is absolutely essential, you are advised not to visit any of the countries affected by Ebola (Guinea, Republic of Sierra Leone, Liberia, Nigeria). The two Host States have established an alert system, and a check is carried out on departure from the airports of those countries. It is strongly recommended that you contact the Medical Service if you are travelling to those countries. We remind you to observe the basic rules of hygiene such as frequent hand washing, whatever your destination. The Medical Service is...

  5. Ebola Virus ─ A Global Threat

    Directory of Open Access Journals (Sweden)

    Mejbah Uddin Ahmed

    2015-01-01

    Full Text Available Ebola virus is a filamentous, enveloped, non-segmented, single-stranded, negative-sense RNA virus. It belongs to the Filoviridae and was first recognized near the Ebola River valley in Zaire in 1976. Since then most of the outbreaks have occurred to both human and nonhuman primates in sub-Saharan Africa. Ebola virus causes highly fatal hemorrhagic fever in human and nonhuman primates. In addition to hemorrhagic fever, it could be used as a bioterrorism agent. Although its natural reservoir is yet to be proven, current data suggest that fruit bats are the possibility. Infection has also been documented through the handling of infected chimpanzees, gorillas, monkeys, forest antelope and porcupines. Human infection is caused through close contact with the blood, secretion, organ or other body fluids of infected animal. Human-to-human transmission is also possible. Ebola virus infections are characterized by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock. The virus constitutes an important public health threat in Africa and also worldwide as no effective treatment or vaccine is available till now

  6. Ebola Virus Persistence in Semen Ex Vivo.

    Science.gov (United States)

    Fischer, Robert J; Judson, Seth; Miazgowicz, Kerri; Bushmaker, Trent; Munster, Vincent J

    2016-02-01

    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.

  7. Ebola virus: bioterrorism for humans

    Directory of Open Access Journals (Sweden)

    Pramodkumar Pyarelal Gupta

    2015-01-01

    Full Text Available Ebola virus disease is a severe, often fatal, zoonotic infection caused by a virus of the Filoviridae family (genus Ebolavirus. Ebola virus (EBOV spreads by human to human transmission through contacts with body fluids from infected patients. Initial stages of EBOV are non-specific which makes the differential diagnosis broad. Here in this review article we focused on to show the details of EBOV, from its first case right up to the possible targets to cure this lethal disease. In this study we have shown the statistical survey, epidemiology, disease ontology, different genes coding for different proteins in EBOV and future aspects of it.

  8. Treatment of ebola virus disease.

    Science.gov (United States)

    Kilgore, Paul E; Grabenstein, John D; Salim, Abdulbaset M; Rybak, Michael

    2015-01-01

    In March 2014, the largest Ebola outbreak in history exploded across West Africa. As of November 14, 2014, the World Health Organization has reported a total of 21,296 Ebola virus disease (EVD) cases, including 13,427 laboratory-confirmed EVD cases reported from the three most affected countries (Guinea, Liberia, and Sierra Leone). As the outbreak of EVD has spread, clinical disease severity and national EVD case-fatality rates have remained high (21.2-60.8%). Prior to 2013, several EVD outbreaks were controlled by using routine public health interventions; however, the widespread nature of the current EVD outbreak as well as cultural practices in the affected countries have challenged even the most active case identification efforts. In addition, although treatment centers provide supportive care, no effective therapeutic agents are available for EVD-endemic countries. The ongoing EVD outbreak has stimulated investigation of several different therapeutic strategies that target specific viral structures and mechanisms of Ebola viruses. Six to eight putative pharmacotherapies or immunologically based treatments have demonstrated promising results in animal studies. In addition, agents composed of small interfering RNAs targeting specific proteins of Ebola viruses, traditional hyperimmune globulin isolated from Ebola animal models, monoclonal antibodies, and morpholino oligomers (small molecules used to block viral gene expression). A number of EVD therapeutic agents are now entering accelerated human trials in EVD-endemic countries. The goal of therapeutic agent development includes postexposure prevention and EVD cure. As knowledge of Ebola virus virology and pathogenesis grows, it is likely that new therapeutic tools will be developed. Deployment of novel Ebola therapies will require unprecedented cooperation as well as investment to ensure that therapeutic tools become available to populations at greatest risk for EVD and its complications. In this article, we

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

    Science.gov (United States)

    ... U.S. Q&A: 2014 Ebola Outbreak 2014 West Africa Ebola Outbreak Communication Resources Guinea Guinea-Bissau Liberia Sierra Leone ... EVD) Questions and Answers on the 2014 West Africa Ebola Outbreak File Formats Help: How do I view different ...

  10. A Case of Ebola Virus

    Centers for Disease Control (CDC) Podcasts

    2012-10-01

    Dr. Adam MacNeil, an epidemiologist at CDC, discusses Ebola virus.  Created: 10/1/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID); National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 10/1/2012.

  11. Ebola Virus Disease – Global Scenario & Bangladesh

    Directory of Open Access Journals (Sweden)

    Md Rezwanur Rahman

    2015-03-01

    Full Text Available Ebola virus disease (EVD, caused by one of the Ebola virus strains is an acute, serious illness which is often fatal when untreated. EVD, previously known as Ebola hemorrhagic fever, is a rare and deadly disease. It first appeared in 1976 in two simultaneous outbreaks, one in Nzara, Sudan, and the other in Yambuku, Democratic Republic of Congo. The latter occurred in a village near the Ebola River, from which the disease takes its name.1,2 On March 23, 2014, the World Health Organization (WHO was notified of an outbreak of EVD in Guinea. On August 8, WHO declared the epidemic to be a ‘Public health emergency of international concern’.3 The current 2014 outbreak in West Africa is the largest and most complex Ebola outbreak.1 It is to be noticed that the most severely affected countries, Guinea, Sierra Leone and Liberia have very weak health systems, lacking human and infrastructural resources and these countries recently emerged from long periods of conflict and instability.1 The virus family Filoviridae includes three genera: Cuevavirus, Marburgvirus, and Ebolavirus. Till date five species have been identified: Zaire, Bundibugyo, Sudan, Reston and Taï Forest. The recent outbreak belongs to the Zaire species which is the most lethal one, with an average case fatality rate of 78%.1,4 Till 6 December 2014, total 17,834 suspected cases and 6,678 deaths had been reported; however, WHO has said that these numbers may be vastly underestimated.5 The natural reservoir for Ebola has yet to be confirmed; however, fruit bats of the Pteropodidae family are considered to be the most likely candidate species.1,2,6 Ebola can be transmitted to human through close contact with the blood, secretions, organs or other bodily fluids of infected animals such as fruit bats, chimpanzees, gorillas, monkeys, etc. Ebola then spreads through human-to-human transmission via direct contact (through broken skin or mucous membranes with the blood, secretions, organs or

  12. Ebola virus and other Filoviruses:an overview

    Institute of Scientific and Technical Information of China (English)

    Hasna Amdiouni; Hicham El Rhaffouli

    2015-01-01

    Filoviruses, including Ebola and Marburg viruses, are recognized as a significant warning to public health. They are zoonotic agents with bats as primary reservoir. Those viruses can cause severe human infection with hemorrhagic syndrome leading to death. The mortality rate can be higher than 90%. In West Africa, recent Ebola virus outbreak occurred in March 2014, has caused more than 8 300 infections with more than 4 000 deaths. That shows the critical state of this country, and the critical context in worldwide. In order to fight this deadly scourge, it is necessary to understand the epidemiology of disease and to establish a good diagnosis protocols and protective measures. In recent decades, traditional techniques of virus isolation are replaced by molecular biology techniques which are faster, more sensitive and specific. Until now, no specific Ebola virus treatment or vaccine but many studies are in progress with promising results.

  13. Ebola virus: current and future perspectives.

    Science.gov (United States)

    Jadav, Surender Singh; Kumar, Anoop; Ahsan, Mohamed Jawed; Jayaprakash, Venkatesan

    2015-01-01

    The present outbreak associated with Ebola disease in Western countries of the African continent which is believed to be one of the massive eruptions caused by the Ebola viral infections. In the present scenario ebola has been transmitted to the European and American regions through the travelers from wide spread countries like Guinea, Liberia, Sierra Leone and Nigeria. The viral disease is spreading through the contact in any form by the infected persons or patients and creating huge risks to the mortals. The symptoms related to ebola virus are often highly pathogenic; about 70-80% of death cases are reported due to critical hemorrhagic fever. Early in infection, ebola virus infects macrophages and endothelial cells. It mainly produces a Viral Protein 24 (eVP24) which prevents interferon-based signals which are important for destruction of viruses. How ebola virus manipulates the function of the immune system is still unclear. Due to lack of this knowledge, no approved treatment is available. In this review, we have tried to compile the epidemiology, pathogenesis and treatment of ebola virus infection. The promising ligands against ebola virus have been also discussed which will be helpful for researchers to design drugs for the treatment of ebola virus disease.

  14. Phosphorylation sites within Ebola virus nucleoprotein

    Institute of Scientific and Technical Information of China (English)

    Sora; Yasri; Viroj; Wiwanitkit

    2015-01-01

    To understand the infection process, the viral multiplication and entry to the cell is widely studied. The Ebola virus nucleoprotein is the important problem for the pathological process. Focusing on the specific biological process, the post translational modification is needed. Here, the authors used the bioinformatics study to find the phosphorylation sites within the Ebola virus nucleoprotein and could identify many new sites.

  15. [Recent Advances in Vaccines and Drugs Against the Ebola Virus].

    Science.gov (United States)

    Zhu, Xiang; Yao, Chenguang; Wei, Yanhong; Kou, Zheng; Hu, Kanghong

    2015-05-01

    The Ebola virus belongs to the Filovirus family, which causes Ebola hemorrhagic fever (mortality, 25%-90%). An outbreak of infection by the Ebola virus is sweeping across West Africa, leading to high mortality and worldwide panic. The Ebola virus has caused a serious threat to public health, so intensive scientific studies have been carried out. Several vaccines (e.g., rVSV-ZEBOV, ChAd3-ZEBOV) have been put into clinical trials and antiviral drugs (e.g., TKM-Ebola, ZMAPP) have been administered in the emergency setting to patients infected by the Ebola virus. Here, recent advances in vaccines and drugs against the Ebola virus are reviewed.

  16. Ebola virus disease: radiology preparedness.

    Science.gov (United States)

    Bluemke, David A; Meltzer, Carolyn C

    2015-02-01

    At present, there is a major emphasis on Ebola virus disease (EVD) preparedness training at medical facilities throughout the United States. Failure to have proper EVD procedures in place was cited as a major reason for infection of medical personnel in the United States. Medical imaging does not provide diagnosis of EVD, but patient assessment in the emergency department and treatment isolation care unit is likely to require imaging services. The purpose of this article is to present an overview of relevant aspects of EVD disease and preparedness relevant to the radiologic community. © RSNA, 2014.

  17. Ebola Virus RNA in Semen from an HIV-Positive Survivor of Ebola

    Science.gov (United States)

    Rogers, Emerson; Baller, April; White, Stephen; Soka, Moses; Choi, Mary J.; Mahmoud, Nuha; Wasunna, Christine; Massaquoi, Moses; Kollie, Jomah; Dweh, Straker; Bemah, Philip; Ladele, Victor; Kpaka, Jonathan; Jawara, Mary; Mugisha, Margaret; Subah, Onyekachi; Faikai, Mylene; Bailey, Jeff A.; Rollin, Pierre; Marston, Barbara; Nyenswah, Tolbert; Gasasira, Alex; Knust, Barbara; Nichol, Stuart; Williams, Desmond

    2017-01-01

    Ebola virus is known to persist in semen of male survivors of Ebola virus disease (EVD). However, maximum duration of, or risk factors for, virus persistence are unknown. We report an EVD survivor with preexisting HIV infection, whose semen was positive for Ebola virus RNA 565 days after recovery from EVD. PMID:28287374

  18. Ebola Virus Disease

    Science.gov (United States)

    ... their partners and families should be shown respect, dignity and compassion. For more, read the Guidance on ... virus disease outbreaks Year Country Ebolavirus species Cases Deaths Case fatality 2015 Italy Zaire 1 0 0% ...

  19. A historial perpective af Ebola Virus

    DEFF Research Database (Denmark)

    Sørensen, Linda Løhde; Permin, Henrik; Fischer, Thea Kølsen

    2015-01-01

    The 2014 Ebola fever outbreak was the first of its kind in West Africa. This epidemic, affecting multiple countries, by far exceeded any previous outbreak in case counts and geographical spread. But Ebola viruses are not new to Africa, as they have occurred in epidemic proportion in the central...

  20. Ebola virus disease: past, present and future

    Institute of Scientific and Technical Information of China (English)

    Harish; Rajak; Deepak; Kumar; Jain; Avineesh; Singh; Ajay; Kumar; Sharma; Anshuman; Dixit

    2015-01-01

    Ebola virus disease is one of the most deadly ailments known to mankind due to its high mortality rate(up to 90%) accompanying with the disease. Ebola haemorrhagic fever(EHF) is an infectious disease of animal that can be transmitted to both human and non-human primates. The first epidemic of EHF occurred in 1976 in the Democratic Republic of the Congo. The incubation period of ebola is less than 21 days. Ebola virus infections are depicted by immune suppression and a systemic inflammatory response that leads to damage of the vascular, coagulation and immune systems, causing multi-organ failure and shock. Five genetically distinct members of the Filoviridae family responsible for EHF are as follows: Zaire ebolavirus, Sudan ebolavirus, C?te d’Ivoire ebolavirus, Bundibugyo ebolavirus and Reston ebolavirus. The ongoing 2014 West Africa ebola epidemic has been considered as the most serious panic in the medical field with respect to both the number of human cases and death toll. The natural host for ebola virus is unknown, thus it is not possible to carry out programs to regulate or abolish virus from transmission to people. The ebola virus infection provides little chance to develop acquired immunity causing rapid progression of the disease. It is pertinent to mention that at present, there is no antiviral therapy or vaccine that is helpful against ebola virus infection in humans. The impediment of EHF necessitates much better understanding of the epidemiology of the disease, particularly the role of wildlife, as well as bats, in the spread of ebola virus to humans.

  1. Ebola virus disease: past, present and future

    Directory of Open Access Journals (Sweden)

    Harish Rajak

    2015-05-01

    Full Text Available Ebola virus disease is one of the most deadly ailments known to mankind due to its high mortality rate (up to 90% accompanying with the disease. Ebola haemorrhagic fever (EHF is an infectious disease of animal that can be transmitted to both human and non-human primates. The first epidemic of EHF occurred in 1976 in the Democratic Republic of the Congo. The incubation period of ebola is less than 21 days. Ebola virus infections are depicted by immune suppression and a systemic inflammatory response that leads to damage of the vascular, coagulation and immune systems, causing multi-organ failure and shock. Five genetically distinct members of the Filoviridae family responsible for EHF are as follows: Zaire ebolavirus, Sudan ebolavirus, Côte d’Ivoire ebolavirus, Bundibugyo ebolavirus and Reston ebolavirus. The ongoing 2014 West Africa ebola epidemic has been considered as the most serious panic in the medical field with respect to both the number of human cases and death toll. The natural host for ebola virus is unknown, thus it is not possible to carry out programs to regulate or abolish virus from transmission to people. The ebola virus infection provides little chance to develop acquired immunity causing rapid progression of the disease. It is pertinent to mention that at present, there is no antiviral therapy or vaccine that is helpful against ebola virus infection in humans. The impediment of EHF necessitates much better understanding of the epidemiology of the disease, particularly the role of wildlife, as well as bats, in the spread of ebola virus to humans.

  2. Phosphorylation sites within Ebola virus nucleoprotein

    Directory of Open Access Journals (Sweden)

    Sora Yasri

    2015-07-01

    Full Text Available To understand the infection process, the viral multiplication and entry to the cell is widely studied. The Ebola virus nucleoprotein is the important problem for the pathological process. Focusing on the specific biological process, the post translational modification is needed. Here, the authors used the bioinformatics study to find the phosphorylation sites within the Ebola virus nucleoprotein and could identify many new sites.

  3. Interferon-γ Inhibits Ebola Virus Infection

    OpenAIRE

    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. F...

  4. THE STRENGTHS, WEAKNESSES, OPPORTUNITIES, AND THREATS (SWOTs) ANALYSES OF THE EBOLA VIRUS – PAPER RETRACTED

    Science.gov (United States)

    Babalola, Michael Oluyemi

    2016-01-01

    Background: Owing to the extreme virulence and case fatality rate of ebola virus disease (EVD), there had been so much furore, panic and public health emergency about the possible pandemic from the recent West African outbreak of the disease, with attendant handful research, both in the past and most recently. The magnitude of the epidemic of ebola virus disease has prompted global interest and urgency in the discovery of measures to mitigate the impact of the disease. Researchers in the academia and the industry were pressured to only focus on the development of effective and safe ebola virus vaccines, without consideration of the other aspects to this virus, which may influence the success or otherwise of a potential vaccine. The objective of this review was to adopt the SWOT concept to elucidate the biological Strengths, Weaknesses, Opportunities, and Threats to Ebola virus as a pathogen, with a view to understanding and devising holistic strategies at combating and overcoming the scourge of EVD. Method: This systematic review and narrative synthesis utilized Medline, PubMed, Google and other databases to select about 150 publications on ebola and ebola virus disease using text word searches to generate the specific terms. Relevant publications were reviewed and compared, findings were synthesized using a narrative method and summarized qualitatively. Results: Some of the identified strengths of ebola virus include: Ebola virus is an RNA virus with inherent capability to mutate, reassort and recombine to generate mutant or reassortant virulent strains; Ebola virus has a broad cellular tropism; Natural Reservoir of ebola virus is unconfirmed but fruit bats, arthropods, and plants are hypothesized; Ebola virus primarily targets and selectively destroys the immune system; Ebola viruses possess accessory proteins that inhibits the host’ immune responses; Secreted glycoprotein (sGP), a truncated soluble protein that triggers immune activation and increased vascular

  5. THE STRENGTHS, WEAKNESSES, OPPORTUNITIES, AND THREATS (SWOTs) ANALYSES OF THE EBOLA VIRUS - PAPER RETRACTED.

    Science.gov (United States)

    Babalola, Michael Oluyemi

    2016-01-01

    Owing to the extreme virulence and case fatality rate of ebola virus disease (EVD), there had been so much furore, panic and public health emergency about the possible pandemic from the recent West African outbreak of the disease, with attendant handful research, both in the past and most recently. The magnitude of the epidemic of ebola virus disease has prompted global interest and urgency in the discovery of measures to mitigate the impact of the disease. Researchers in the academia and the industry were pressured to only focus on the development of effective and safe ebola virus vaccines, without consideration of the other aspects to this virus, which may influence the success or otherwise of a potential vaccine. The objective of this review was to adopt the SWOT concept to elucidate the biological Strengths, Weaknesses, Opportunities, and Threats to Ebola virus as a pathogen, with a view to understanding and devising holistic strategies at combating and overcoming the scourge of EVD. This systematic review and narrative synthesis utilized Medline, PubMed, Google and other databases to select about 150 publications on ebola and ebola virus disease using text word searches to generate the specific terms. Relevant publications were reviewed and compared, findings were synthesized using a narrative method and summarized qualitatively. Some of the identified strengths of ebola virus include: Ebola virus is an RNA virus with inherent capability to mutate, reassort and recombine to generate mutant or reassortant virulent strains; Ebola virus has a broad cellular tropism; Natural Reservoir of ebola virus is unconfirmed but fruit bats, arthropods, and plants are hypothesized; Ebola virus primarily targets and selectively destroys the immune system; Ebola viruses possess accessory proteins that inhibits the host' immune responses; Secreted glycoprotein (sGP), a truncated soluble protein that triggers immune activation and increased vascular permeability is uniquely

  6. Interferon-γ Inhibits Ebola Virus Infection.

    Science.gov (United States)

    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.

  7. Interferon-γ Inhibits Ebola Virus Infection.

    Directory of Open Access Journals (Sweden)

    Bethany A Rhein

    Full Text Available 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.

  8. Ebola Virus Mutated to Become More Infectious, Scientists Say

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_161849.html Ebola Virus Mutated to Become More Infectious, Scientists Say Virologists ... 3, 2016 (HealthDay News) -- Mutations in the Ebola virus boosted its ability to infect people during the ...

  9. An Ebola virus-centered knowledge base.

    Science.gov (United States)

    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. © The Author(s) 2015. Published by Oxford University Press.

  10. [The Emergence of Ebola virus in humans: a long process not yet fully understood].

    Science.gov (United States)

    Leroy, Éric Maurice

    2015-01-01

    Since 1976 Ebola virus regularly has caused small deadly outbreaks in Central Africa, usually controlled in a few months. For the first time, an Ebola epidemic of exceptional magnitude dramatically engulfed several countries in West Africa since December 2013. Major failures of implementing measures to prevent human-to-human transmissions are the main cause of this large-scale Ebola outbreak. After about one-week incubation period, the Ebola virus disease is characterized by a sudden onset of high fever leading to multiple hemorrhages and to widespread organ failure. Several bat species constitute the main reservoirs of Ebola viruses. Human contamination would occur either directly from bats, widely consumed by the local populations, or through animal species susceptible to Ebola infection, such as chimpanzees and gorillas. Alongside this "natural cycle", an "epidemic cycle" involving domestic animals living in villages such as dogs or pigs, is seriously suggested. Thus, according to the diversity of concerned animals and their clinical infectionform, modalities of human contamination can be multiple and are still largely unknown. In this context, all efforts that could be made to unravel the mystery of the Ebola virus emergence in humans and clarify modalities of the virus transmission, would allow for predicting or for anticipating the future occurrence of epidemics. This review aims to provide an exhaustive inventory of the Ebola ecology to highlight events governing the virus transmission to humans that still remain unsolved.

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

    Science.gov (United States)

    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.

  12. Spermatogenic transmission of Marbug and ebola virus

    Institute of Scientific and Technical Information of China (English)

    Sora Yasri; Viroj Wiwanitkit

    2015-01-01

    The spermatogenic transmission of infectious disease is an interesting consideration in reproductive medicine. The problem can be serious and classified as sexually transmitted infection. The concern is on the new emerging viral infections because there is usually little information on those new viruses. In this short article, the authors specially review and discuss on Spermatogenic transmission of Marbug and ebola virus.

  13. Spermatogenic transmission of Marbug and ebola virus

    Directory of Open Access Journals (Sweden)

    Sora Yasri

    2015-03-01

    Full Text Available The spermatogenic transmission of infectious disease is an interesting consideration in reproductive medicine. The problem can be serious and classified as sexually transmitted infection. The concern is on the new emerging viral infections because there is usually little information on those new viruses. In this short article, the authors specially review and discuss on Spermatogenic transmission of Marbug and ebola virus.

  14. Questions and Answers about Ebola, Pets, and Other Animals

    Science.gov (United States)

    ... Posters Virus Ecology Graphic Questions and Answers about Ebola, Pets, and Other Animals Language: English Español ... Tweet Share Compartir How are animals involved in Ebola outbreaks? Because the natural reservoir host of Ebola ...

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

    Science.gov (United States)

    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.

  16. Packaging of actin into Ebola virus VLPs

    Directory of Open Access Journals (Sweden)

    Harty Ronald N

    2005-12-01

    Full Text Available Abstract The actin cytoskeleton has been implicated in playing an important role assembly and budding of several RNA virus families including retroviruses and paramyxoviruses. In this report, we sought to determine whether actin is incorporated into Ebola VLPs, and thus may play a role in assembly and/or budding of Ebola virus. Our results indicated that actin and Ebola virus VP40 strongly co-localized in transfected cells as determined by confocal microscopy. In addition, actin was packaged into budding VP40 VLPs as determined by a functional budding assay and protease protection assay. Co-expression of a membrane-anchored form of Ebola virus GP enhanced the release of both VP40 and actin in VLPs. Lastly, disruption of the actin cytoskeleton with latrunculin-A suggests that actin may play a functional role in budding of VP40/GP VLPs. These data suggest that VP40 may interact with cellular actin, and that actin may play a role in assembly and/or budding of Ebola VLPs.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

    2014-09-08

    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.

  19. Ebola

    Science.gov (United States)

    ... believed to carry the virus include gorillas, chimpanzees, monkeys, fruit bats, porcupines, and forest antelope. Ebola spreads ... doctor. © 1995- The Nemours Foundation. All rights reserved. Images provided by The Nemours Foundation, iStock, Getty Images, ...

  20. Immune Response to Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Alain Alonso Remedios

    2016-06-01

    Full Text Available Ebola virus belongs to the family Filoviridae and causes a highly lethal hemorrhagic fever. Affected patients show an impaired immune response as a result of the evasion mechanisms employed by the virus. Cathepsin is an enzyme present in the granules of phagocytes which cleaves viral surface glycoproteins, allowing virus entry into the host cell. In addition, this virus is resistant to the antiviral effects of type I interferon, promotes the synthesis of proinflammatory cytokines and induces apoptosis of monocytes and lymphocytes. It also induces an incomplete activation of dendritic cells, thus avoiding the presentation of viral antigens. Although specific antibodies are produced after the first week, their neutralizing capacity is doubtful. The virus evades the immune response and replicates uncontrollably in the host. This paper aims to summarize the main characteristics of the immune response to Ebola virus infection.

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

    Science.gov (United States)

    Na, Woonsung; Park, Nanuri; Yeom, Minju; Song, Daesub

    2015-01-01

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

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

    Science.gov (United States)

    2015-01-01

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

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

    OpenAIRE

    Na, Woonsung; Park, Nanuri; Yeom, Minjoo; Song, Daesub

    2015-01-01

    The 2014 outbreak of Ebola virus disease (EVD) in West Africa, caused by Ebola virus (Zaire Ebola virus species), is the largest outbreak of EVD in history. It cause hemorrhagic fever in human and nonhuman primates with high mortality rate up to 90% and can be transmitted by direct contact with blood, body fluids, skin of EVD patients or persons who have died of EVD. As of December 17, 2014, 450 healthcare personnel are known to have been infected with Ebola, of whom 244 died. For development...

  4. Ebola virus outbreaks in Africa: Past and present

    Directory of Open Access Journals (Sweden)

    J.J. Muyembe-Tamfum

    2012-06-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2012-06-20

    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.

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

    Directory of Open Access Journals (Sweden)

    Peter D. Karp

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. [Ebola and Marburg viruses: the humans strike back].

    Science.gov (United States)

    Alazard-Dany, Nathalie; Ottmann Terrangle, Michèle; Volchkov, Viktor

    2006-04-01

    Ebola and Marburg viruses are the causative agents of rapidly progressive hemorrhagic fevers with high mortality rates. Pre- or post-exposure treatments against the diseases are currently not available for human use. In the field, establishment of strict quarantine measures preventing further virus transmission are still the only way to fight the infections. However, our knowledge of Ebola and Marburg viruses has markedly increased as a result of two recent discoveries discussed in this review. Chandran et al. have elucidated the mechanism by which Ebola GP is converted to a fusion-active form. Infectivity of Ebola virus was shown to be dependent on the cleavage of GP by cellular endosomal proteases, cathepsin B and L, thus opening new therapeutic approaches options. As for Jones SM et al., they have successfully vaccinated monkeys with recombinant vesicular stomatitis virus expressing Ebola or Marburg virus surface glycoprotein GP, a promising vaccine approach.

  10. An Acute Hemorrhagic Infectious Disease:Ebola Virus Disease

    Institute of Scientific and Technical Information of China (English)

    JIAO Lei; XU An-hua; FENG Chao; QIU Qian-qian; TANG Qi-ling; LIU Xiao-huan

    2014-01-01

    Ebola virus disease (EVD) is an acute hemorrhagic infectious disease caused by ebola virus, with high infectivity and fatality rate. At present, it mainly occurs in areas of Central Africa and West Africa and no effective vaccine and antiviral drugs are available for the clinical treatment.

  11. Ebola Virus: The Role of Macrophages and Dendritic Cells in the Pathogenesis of Ebola Hemorrhagic Fever

    Science.gov (United States)

    2007-11-02

    Impairment of den- dritic cells and adaptive immunity by Ebola and Lassa viruses . J. Immunol., 170(6), 2797–2801. Reed, D. S., Hensley, L. E., Geisbert, J...The International Journal of Biochemistry & Cell Biology 37 (2005) 1560–1566 Medicine in focus Ebola virus : The role of macrophages and dendritic...In consequence, virus disseminates to these and other cell types throughout the body, causing multifocal necrosis and a syndrome resembling septic

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

    Science.gov (United States)

    Kuhn, Jens H; 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

    2014-11-20

    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.

  13. Ebola Virus Disease in Children, Sierra Leone, 2014–2015

    Science.gov (United States)

    Naveed, Asad; Wing, Kevin; Gbessay, Musa; Ross, J.C.G.; Checchi, Francesco; Youkee, Daniel; Jalloh, Mohammed Boie; Baion, David; Mustapha, Ayeshatu; Jah, Hawanatu; Lako, Sandra; Oza, Shefali; Boufkhed, Sabah; Feury, Reynold; Bielicki, Julia A.; Gibb, Diana M.; Klein, Nigel; Sahr, Foday; Yeung, Shunmay

    2016-01-01

    Little is known about potentially modifiable factors in Ebola virus disease in children. We undertook a retrospective cohort study of children Ebola holding units in the Western Area, Sierra Leone, during 2014–2015 to identify factors affecting outcome. Primary outcome was death or discharge after transfer to Ebola treatment centers. All 309 Ebola virus–positive children 2 days–12 years old were included; outcomes were available for 282 (91%). Case-fatality was 57%, and 55% of deaths occurred in Ebola holding units. Blood test results showed hypoglycemia and hepatic/renal dysfunction. Death occurred swiftly (median 3 days after admission) and was associated with younger age and diarrhea. Despite triangulation of information from multiple sources, data availability was limited, and we identified no modifiable factors substantially affecting death. In future Ebola virus disease epidemics, robust, rapid data collection is vital to determine effectiveness of interventions for children. PMID:27649367

  14. Immunobiology of Ebola and Lassa virus infections.

    Science.gov (United States)

    Prescott, Joseph B; Marzi, Andrea; Safronetz, David; Robertson, Shelly J; Feldmann, Heinz; Best, Sonja M

    2017-03-01

    Two of the most important contemporary emerging viruses that affect human health in Africa are Ebola virus (EBOV) and Lassa virus (LASV). The 2013-2016 West African outbreak of EBOV was responsible for more than 11,000 deaths, primarily in Guinea, Sierra Leone and Liberia. LASV is constantly emerging in these and surrounding West African countries, with an estimate of more than 500,000 cases of Lassa fever, and approximately 5,000 deaths, annually. Both EBOV and LASV are zoonotic, and human infection often results in a severe haemorrhagic fever in both cases. However, the contribution of specific immune responses to disease differs between EBOV and LASV. This Review examines innate and adaptive immune responses to these viruses with the goal of delineating responses that are associated with protective versus pathogenic outcomes.

  15. Ebola Virus Infection Modelling and Identifiability Problems

    Directory of Open Access Journals (Sweden)

    Van-Kinh eNguyen

    2015-04-01

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

  16. Ebola virus disease. Short history, long impact

    Directory of Open Access Journals (Sweden)

    Mª Teófila Vicente-Herrero

    2015-07-01

    Full Text Available Ebola Virus infection is at present times a growing worldwide concern, although its history goes back to 1967, with subsequent outbreaks in 1979, 1980 and 1987, all of them by contact in workers in affected areas. The concern of the scientific community about this issue is partially reflected in publications included in MEDLINE (PUBMED database and in which, taking as a keyword in the search box “Ebola virus”, 2.151 publications are found, belonging 984 of them to the last 5 years (45.7% and 527 of these publications (53.5% to the years 2014-2015. The earliest publication dates back to 1977, attaching no listed authors either reference abstract, and the most recent to January of current year 2015. This means Ebola infection is a global problem and that concern the international scientific community. A review of some of the studies published in this matter, considered of interest and discussed by the authors, is performed in this work.

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

    Science.gov (United States)

    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.

  18. Reemerging Sudan Ebola Virus Disease in Uganda, 2011

    Science.gov (United States)

    Shoemaker, Trevor; Balinandi, Stephen; Campbell, Shelley; Wamala, Joseph Francis; McMullan, Laura K.; Downing, Robert; Lutwama, Julius; Mbidde, Edward; Ströher, Ute; Rollin, Pierre E.; Nichol, Stuart T.

    2012-01-01

    Two large outbreaks of Ebola hemorrhagic fever occurred in Uganda in 2000 and 2007. In May 2011, we identified a single case of Sudan Ebola virus disease in Luwero District. The establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities. PMID:22931687

  19. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.

    Science.gov (United States)

    Regules, Jason A; Beigel, John H; Paolino, Kristopher M; Voell, Jocelyn; Castellano, Amy R; Hu, Zonghui; Muñoz, Paula; Moon, James E; Ruck, Richard C; Bennett, Jason W; Twomey, Patrick S; Gutiérrez, Ramiro L; Remich, Shon A; Hack, Holly R; Wisniewski, Meagan L; Josleyn, Matthew D; Kwilas, Steven A; Van Deusen, Nicole; Mbaya, Olivier Tshiani; Zhou, Yan; Stanley, Daphne A; Jing, Wang; Smith, Kirsten S; Shi, Meng; Ledgerwood, Julie E; Graham, Barney S; Sullivan, Nancy J; Jagodzinski, Linda L; Peel, Sheila A; Alimonti, Judie B; Hooper, Jay W; Silvera, Peter M; Martin, Brian K; Monath, Thomas P; Ramsey, W Jay; Link, Charles J; Lane, H Clifford; Michael, Nelson L; Davey, Richard T; Thomas, Stephen J

    2017-01-26

    Background The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD. Methods We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. Results The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. Conclusions This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a

  20. Ebola virus – new threat to global health

    OpenAIRE

    Rina K. Kusumaratna

    2015-01-01

    Ebola hemorrhagic fever is a fatal infectious disease of humans and primates. The disease is caused by single-stranded RNA viruses belonging to the family Filoviridae. The Ebola virus started to emerge in 1976, in an outbreak that almost simultaneously attacked two countries, namely Zaire and Sudan. (1) Around 500 cases were reported, with a case fatality rate of  88% in Zaire and 53% in Sudan. Although occurring at the same time, the Ebola viruses in the two countries were of different speci...

  1. Serological evidence of Ebola virus infection in Indonesian orangutans.

    Directory of Open Access Journals (Sweden)

    Chairul A Nidom

    Full Text Available Ebola virus (EBOV and Marburg virus (MARV belong to the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates. Despite the discovery of EBOV (Reston virus in nonhuman primates and domestic pigs in the Philippines and the serological evidence for its infection of humans and fruit bats, information on the reservoirs and potential amplifying hosts for filoviruses in Asia is lacking. In this study, serum samples collected from 353 healthy Bornean orangutans (Pongo pygmaeus in Kalimantan Island, Indonesia, during the period from December 2005 to December 2006 were screened for filovirus-specific IgG antibodies using a highly sensitive enzyme-linked immunosorbent assay (ELISA with recombinant viral surface glycoprotein (GP antigens derived from multiple species of filoviruses (5 EBOV and 1 MARV species. Here we show that 18.4% (65/353 and 1.7% (6/353 of the samples were seropositive for EBOV and MARV, respectively, with little cross-reactivity among EBOV and MARV antigens. In these positive samples, IgG antibodies to viral internal proteins were also detected by immunoblotting. Interestingly, while the specificity for Reston virus, which has been recognized as an Asian filovirus, was the highest in only 1.4% (5/353 of the serum samples, the majority of EBOV-positive sera showed specificity to Zaire, Sudan, Cote d'Ivoire, or Bundibugyo viruses, all of which have been found so far only in Africa. These results suggest the existence of multiple species of filoviruses or unknown filovirus-related viruses in Indonesia, some of which are serologically similar to African EBOVs, and transmission of the viruses from yet unidentified reservoir hosts into the orangutan populations. Our findings point to the need for risk assessment and continued surveillance of filovirus infection of human and nonhuman primates, as well as wild and domestic animals, in Asia.

  2. Ebola virus vaccines: an overview of current approaches.

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Heinz

    2014-04-01

    Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible.

  3. Late Ebola virus relapse causing meningoencephalitis: a case report.

    Science.gov (United States)

    Jacobs, Michael; Rodger, Alison; Bell, David J; Bhagani, Sanjay; Cropley, Ian; Filipe, Ana; Gifford, Robert J; Hopkins, Susan; Hughes, Joseph; Jabeen, Farrah; Johannessen, Ingolfur; Karageorgopoulos, Drosos; Lackenby, Angie; Lester, Rebecca; Liu, Rebecca S N; MacConnachie, Alisdair; Mahungu, Tabitha; Martin, Daniel; Marshall, Neal; Mepham, Stephen; Orton, Richard; Palmarini, Massimo; Patel, Monika; Perry, Colin; Peters, S Erica; Porter, Duncan; Ritchie, David; Ritchie, Neil D; Seaton, R Andrew; Sreenu, Vattipally B; Templeton, Kate; Warren, Simon; Wilkie, Gavin S; Zambon, Maria; Gopal, Robin; Thomson, Emma C

    2016-07-30

    There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach. On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus. Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors

  4. Preparedness for ongoing Ebola virus infection: how to welcome it?

    Directory of Open Access Journals (Sweden)

    Sora Yasri

    2015-06-01

    Full Text Available The problem of Ebola virus infection is the big global concern. Preparedness for ongoing Ebola virus infection is the topic that should be discussed. In fact, it is necessary to set up a biosecurity system to protect against the present Ebola outbreak. The medical personnel have to prepare for fighting the problem. The management of the present outbreak requires international collaboration and control of cross-border disease transmission is also the big challenge. The good case study is the Hajj scenario.

  5. Update: Ebola virus disease outbreak--West Africa, October 2014.

    Science.gov (United States)

    2014-10-31

    CDC is assisting ministries of health and working with other organizations to control and end the ongoing outbreak of Ebola virus disease (Ebola) in West Africa. The updated data in this report were compiled from situation reports from the Guinea Interministerial Committee for Response Against the Ebola Virus and the World Health Organization, the Liberia Ministry of Health and Social Welfare, and the Sierra Leone Ministry of Health and Sanitation. Total case counts include all suspected, probable, and confirmed cases as defined by each country. These data reflect reported cases, which make up an unknown proportion of all actual cases and reporting delays that vary from country to country.

  6. Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein

    OpenAIRE

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

    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 fragment...

  7. Ebola--haemoragisk feber

    DEFF Research Database (Denmark)

    Fabiansen, Christian; Kronborg, Gitte; Thybo, Søren

    2008-01-01

    This review presents the latest findings on ebola. Ebola presents one of the highest case-fatality rates of all infectious diseases, and in 2007 outbreaks were observed first in the Democratic Republic of Congo and later in Uganda with a new subtype. Accumulating evidence suggests that fruit bats...... are a likely reservoir for the ebola virus. The frequency of filovirus outbreaks in Central Africa is increasing and the potential for introduction and patient care in Denmark is evaluated. Udgivelsesdato: 2008-Nov-24...

  8. Protection from Ebola Virus Mediated by Cytotoxic T Lymphocytes Specific for the Viral Nucleoprotein

    Science.gov (United States)

    2001-03-01

    be required for optimal protection from Ebola virus. Ebola viruses are associated with outbreaks of highly lethal hemorrhagic fever in humans and...nonhuman primates. The Ebola Zaire viruses responsible for outbreaks of human dis- ease in 1976 and 1995 had case-fatality rates of greater than 80...encoding the Ebola virus NP protein (12, 13) or with a control replicon encoding Lassa virus N (14). For booster vaccinations, animals 2660 VOL

  9. Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus Infection

    Science.gov (United States)

    2009-05-01

    specific PMOs in infected cells and mice during lethal Ebola virus challenge. Members of the Filoviridae family of viruses , Ebola virus (EBOV) and Marburg ...American Society for Microbiology. All Rights Reserved. Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus ...sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we

  10. Production of Potent Fully Human Polyclonal Antibodies Against Zaire Ebola Virus in Transchromosomal Cattle

    Science.gov (United States)

    2016-07-01

    1 Production of potent fully human polyclonal antibodies against Zaire Ebola virus in transchromosomal cattle John M. Dye1, Hua Wu2, Jay...mail: jjiao@sabbiotherapeutics.com Keywords: Ebola virus, virus neutralization assay, human polyclonal antibodies, transchromosomal bovine...recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV)-Makona isolate. Serum collected from these hyperimmunized Tc

  11. Ebola Virus Shedding and Transmission: Review of Current Evidence.

    Science.gov (United States)

    Vetter, Pauline; Fischer, William A; Schibler, Manuel; Jacobs, Michael; Bausch, Daniel G; Kaiser, Laurent

    2016-10-15

     The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community.  We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission.  Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

    Science.gov (United States)

    ... for Cleaning, Disinfection, and Waste Disposal in Commercial Passenger Aircraft Diagnosis Treatment Sierra Leone Vaccine Trial Q& ... column fluid) not easily reached by the immune system. CDC and other ... and will share information as it becomes available. Can Ebola stay in ...

  13. Ebola virus disease:a literature review

    Institute of Scientific and Technical Information of China (English)

    Hirokazu Kimura; Hiroyuki Tsukagoshi; Akihide Ryo; Yoshiroh Oda; Toshinobu Kawabata; Takashi Majima; Kunihisa Kozawa; Masayuki Shimojima

    2015-01-01

    Ebola virus disease (EVD) is a life-threatening viral disease with a fatality rate ranging from around 30%to 90%. The first EVD outbreak was reported in the 1970s in Zaire (now the Democratic Republic of the Congo). Until 2013, most outbreaks occurred in the Central Africa region, including Zaire, Sudan and Uganda. However, between March and October 2014, over 10 000 cases of EVD have been recorded in West Africa, such as in Guinea, Liberia, Sierra Leone, and Nigeria, and a few hospital or secondary infections of EVD have occurred in Spain and the United States of America. EVD is presently one of the world's most feared diseases. In this literature review, we describe the epidemiology, clinical features, diagnosis, and treatment of EVD.

  14. Ebola virus disease: a literature review

    Directory of Open Access Journals (Sweden)

    Hirokazu Kimura

    2015-02-01

    Full Text Available Ebola virus disease (EVD is a life-threatening viral disease with a fatality rate ranging from around 30% to 90%. The first EVD outbreak was reported in the 1970s in Zaire (now the Democratic Republic of the Congo. Until 2013, most outbreaks occurred in the Central Africa region, including Zaire, Sudan and Uganda. However, between March and October 2014, over 10 000 cases of EVD have been recorded in West Africa, such as in Guinea, Liberia, Sierra Leone, and Nigeria, and a few hospital or secondary infections of EVD have occurred in Spain and the United States of America. EVD is presently one of the world's most feared diseases. In this literature review, we describe the epidemiology, clinical features, diagnosis, and treatment of EVD.

  15. Ebola Virus Epidemiology and Evolution in Nigeria

    Science.gov (United States)

    Folarin, Onikepe A.; Ehichioya, Deborah; Schaffner, Stephen F.; Winnicki, Sarah M.; Wohl, Shirlee; Eromon, Philomena; West, Kendra L.; Gladden-Young, Adrianne; Oyejide, Nicholas E.; Matranga, Christian B.; Deme, Awa Bineta; James, Ayorinde; Tomkins-Tinch, Christopher; Onyewurunwa, Kenneth; Ladner, Jason T.; Palacios, Gustavo; Nosamiefan, Iguosadolo; Andersen, Kristian G.; Omilabu, Sunday; Park, Daniel J.; Yozwiak, Nathan L.; Nasidi, Abdusallam; Garry, Robert F.; Tomori, Oyewale; Sabeti, Pardis C.; Happi, Christian T.

    2016-01-01

    Containment limited the 2014 Nigerian Ebola virus (EBOV) disease outbreak to 20 reported cases and 8 fatalities. We present here clinical data and contact information for at least 19 case patients, and full-length EBOV genome sequences for 12 of the 20. The detailed contact data permits nearly complete reconstruction of the transmission tree for the outbreak. The EBOV genomic data are consistent with that tree. It confirms that there was a single source for the Nigerian infections, shows that the Nigerian EBOV lineage nests within a lineage previously seen in Liberia but is genetically distinct from it, and supports the conclusion that transmission from Nigeria to elsewhere did not occur. PMID:27377746

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

    Science.gov (United States)

    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).

  17. Functional CD8+ T Cell Responses in Lethal Ebola Virus Infection

    Science.gov (United States)

    2008-03-15

    2003. Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses . J. Immunol. 170: 2797–2801. 20. Bosio, C. M., B...Functional CD8 T Cell Responses in Lethal Ebola Virus Infection1 Steven B. Bradfute, Kelly L. Warfield, and Sina Bavari2 Ebola virus (EBOV) causes...the development of an effective adap- tive immune response, leading to overwhelming infection and death. Ebola virus (EBOV)3 is a single-stranded

  18. Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions

    Science.gov (United States)

    Dowall, S. D.; Graham, V. A.; Corbin-Lickfett, K.; Empig, C.; Schlunegger, K.; Bruce, C. B.; Easterbrook, L.; Hewson, R.

    2015-01-01

    Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab) has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus. PMID:25815346

  19. Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions

    Directory of Open Access Journals (Sweden)

    S. D. Dowall

    2015-01-01

    Full Text Available Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus.

  20. Ebola haemorrhagic fever virus: pathogenesis, immune responses, potential prevention.

    Science.gov (United States)

    Marcinkiewicz, Janusz; Bryniarski, Krzysztof; Nazimek, Katarzyna

    2014-01-01

    Ebola zoonotic RNA filovirus represents human most virulent and lethal pathogens, which induces acute hemorrhagic fever and death within few days in a range of 60-90% of symptomatic individuals. Last outbreak in 2014 in West Africa caused panic that Ebola epidemic can be spread to other continents. Number of deaths in late December reached almost 8,000 individuals out of more than 20,000 symptomatic patients. It seems that only a coordinated international response could counteract the further spread of Ebola. Major innate immunity mechanisms against Ebola are associated with the production of interferons, that are inhibited by viral proteins. Activation of host NK cells was recognized as a leading immune function responsible for recovery of infected people. Uncontrolled cell infection by Ebola leads to an impairment of immunity with cytokine storm, coagulopathy, systemic bleeding, multi-organ failure and death. Tested prevention strategies to induce antiviral immunity include: i. recombinant virus formulations (vaccines); ii. cocktail of monoclonal antibodies (serotherapy); iii. alternative RNA-interference-based antiviral methods. Maintaining the highest standards of aseptic and antiseptic precautions is equally important. Present brief review summarizes a current knowledge concerning pathogenesis of Ebola hemorrhagic disease and the virus interaction with the immune system and discusses recent advances in prevention of Ebola infection by vaccination and serotherapy.

  1. Human Ebola virus infection results in substantial immune activation.

    Science.gov (United States)

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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; Cerón, Olga M

    2016-02-01

    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.

  4. Sequencing of Ebola Virus Genomes Using Nanopore Technology

    Science.gov (United States)

    Hoenen, Thomas

    2017-01-01

    Sequencing of virus genomes during disease outbreaks can provide valuable information for diagnostics, epidemiology, and evaluation of potential countermeasures. However, particularly in remote areas logistical and technical challenges can be significant. Nanopore sequencing provides an alternative to classical Sanger and next-generation sequencing methods, and was successfully used under outbreak conditions (Hoenen et al., 2016; Quick et al., 2016). Here we describe a protocol used for sequencing of Ebola virus under outbreak conditions using Nanopore technology, which we successfully implemented at the CDC/NIH diagnostic laboratory (de Wit et al., 2016) located at the ELWA-3 Ebola virus Treatment Unit in Monrovia, Liberia, during the recent Ebola virus outbreak in West Africa.

  5. Providing nursing care to Ebola virus disease patients: China Ebola Treatment Unit experience

    Directory of Open Access Journals (Sweden)

    Cao Jie

    2015-12-01

    Full Text Available Principle of “Extreme Caution” is never to be underestimated in order to reach the “Zero Infection” goal among medical and nursing staff. Ebola virus disease is not a “horrible monsters” if medical and nursing staff strictly follow personal protection principles.

  6. Clinical Features and Outcome of Ebola Virus Disease in Pediatric Patients

    DEFF Research Database (Denmark)

    Damkjær, Mads; Rudolf, Frauke; Mishra, Sharmistha

    2017-01-01

    Clinical and outcome data on pediatric Ebola virus disease are limited. We report a case-series of 33 pediatric patients with Ebola virus disease in a single Ebola Treatment Center in 2014-2015. The case-fatality rate was 42%, with the majority of deaths occurring within 10 days of admission....

  7. Macromolecular Antiviral Agents against Zika, Ebola, SARS, and Other Pathogenic Viruses

    DEFF Research Database (Denmark)

    Schandock, Franziska; Riber, Camilla Frich; Röcker, Annika

    2017-01-01

    . This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure...

  8. Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.

    Science.gov (United States)

    Geisbert, Thomas W; Feldmann, Heinz

    2011-11-01

    The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.

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

    Science.gov (United States)

    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

  10. Protection of Nonhuman Primates Against Two Species of Ebola Virus Infection With a Single Complex Adenovirus Vector

    Science.gov (United States)

    2010-04-01

    Zaire Ebola virus . Virology 346:394–401. 21. Leffel, E. K., and D. S. Reed. 2004. Marburg and Ebola viruses as aerosol threats. Biosecur. Bioterror. 2...the event of a natural virus outbreak or biological threat. The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), cause outbreaks of severe...vaccine efficacy are justifiable. While the combination of the two CAdVax-based vectors for Ebola virus (EBO7) and Marburg virus (M8) GPs constitute the

  11. Disinfection of Ebola Virus in Sterilized Municipal Wastewater.

    Directory of Open Access Journals (Sweden)

    Kyle Bibby

    2017-02-01

    Full Text Available Concerns have been raised regarding handling of Ebola virus contaminated wastewater, as well as the adequacy of proposed disinfection approaches. In the current study, we investigate the inactivation of Ebola virus in sterilized domestic wastewater utilizing sodium hypochlorite addition and pH adjustment. No viral inactivation was observed in the one-hour tests without sodium hypochlorite addition or pH adjustment. No virus was recovered after 20 seconds (i.e. 4.2 log10 unit inactivation to detection limit following the addition of 5 and 10 mg L-1 sodium hypochlorite, which resulted in immediate free chlorine residuals of 0.52 and 1.11 mg L-1, respectively. The addition of 1 mg L-1 sodium hypochlorite resulted in an immediate free chlorine residual of 0.16 mg L-1, which inactivated 3.5 log10 units of Ebola virus in 20 seconds. Further inactivation was not evident due to the rapid consumption of the chlorine residual. Elevating the pH to 11.2 was found to significantly increase viral decay over ambient conditions. These results indicate the high susceptibility of the enveloped Ebola virus to disinfection in the presence of free chlorine in municipal wastewater; however, we caution that extension to more complex matrices (e.g. bodily fluids will require additional verification.

  12. Disinfection of Ebola Virus in Sterilized Municipal Wastewater

    Science.gov (United States)

    Fischer, Robert J.; Casson, Leonard W.; de Carvalho, Nathalia Aquino; Haas, Charles N.; Munster, Vincent J.

    2017-01-01

    Concerns have been raised regarding handling of Ebola virus contaminated wastewater, as well as the adequacy of proposed disinfection approaches. In the current study, we investigate the inactivation of Ebola virus in sterilized domestic wastewater utilizing sodium hypochlorite addition and pH adjustment. No viral inactivation was observed in the one-hour tests without sodium hypochlorite addition or pH adjustment. No virus was recovered after 20 seconds (i.e. 4.2 log10 unit inactivation to detection limit) following the addition of 5 and 10 mg L-1 sodium hypochlorite, which resulted in immediate free chlorine residuals of 0.52 and 1.11 mg L-1, respectively. The addition of 1 mg L-1 sodium hypochlorite resulted in an immediate free chlorine residual of 0.16 mg L-1, which inactivated 3.5 log10 units of Ebola virus in 20 seconds. Further inactivation was not evident due to the rapid consumption of the chlorine residual. Elevating the pH to 11.2 was found to significantly increase viral decay over ambient conditions. These results indicate the high susceptibility of the enveloped Ebola virus to disinfection in the presence of free chlorine in municipal wastewater; however, we caution that extension to more complex matrices (e.g. bodily fluids) will require additional verification. PMID:28146555

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

    Science.gov (United States)

    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.

  14. Ebola Virus Disease (EVD and Women's Health Care in Pregnancy

    Directory of Open Access Journals (Sweden)

    Arash Khaki

    2015-01-01

    Full Text Available Ebola virus (family Filoviridae, genus Ebolavirus, type species Zaire ebolavirus, Ebola hemorrhagic fever (EHF or Ebola is a disease of human and other primates, caused by an Ebola virüs(1-5. These agents cause a severe, unrelenting viral hemorrhagic fever with high mortality(1. EVD was first recognized in 1976, when two unrelated epidemics occurred in northern Zaire and southern Sudan(1-5. The largest outbreaks to date are the ongoing 2014 west African. Ebola outbreaks, which is affecting Guinea, Sierra Leone, Liberia and Nigeria(2-5. Transmission Ebola virus may be acquired upon contact with blood or bodily fluids of an infected animal. Spreading the air has not been documented in the natural environment. Fruit bats are believed to be a carrier and may spread the virus without being affected(1-2. Once human infection occurs, the disease may spread between people as well(2. Symptoms Clinical appearance is starts in 2 days to 3 weeks after contacting the virus, with fever, sore throat, muscle pain and headaches(1-5. Treatment A number of experimental treatment are being studied. The FDA has allowed two drugs, Zmapp and TKM-Ebola(2. Treatment is primarily supportive in natüre(1-5. The disease has a high risk of death, killing between 50% and 90% of those infected with the virüs(1-5, in conclusion No specific treatment for the disease is yet available. Prevention Includes decreasing the spread of disease from infected animals to humans(2. Prevention of epidemics rates on early recognition and initial cases and promp institution of barrier nursing. At the community level, properly sterilized injection equipment, protection from body fluid and skin during preparation of the dead, and routine barrier nursing precaution are probably adequate in most care(1-2. During the EHF epidemic in Kikwit, Democratic Republic of Congo the number of infected women was slightly higher than the man(6-7. Sex protection Saliva, breast milk, and semen, austerity from

  15. Human Adaptation of Ebola Virus during the West African Outbreak.

    Science.gov (United States)

    Urbanowicz, Richard A; McClure, C Patrick; Sakuntabhai, Anavaj; Sall, Amadou A; Kobinger, Gary; Müller, Marcel A; Holmes, Edward C; Rey, Félix A; Simon-Loriere, Etienne; Ball, Jonathan K

    2016-11-03

    The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa was the largest recorded. It began following the cross-species transmission of EBOV from an animal reservoir, most likely bats, into humans, with phylogenetic analysis revealing the co-circulation of several viral lineages. We hypothesized that this prolonged human circulation led to genomic changes that increased viral transmissibility in humans. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolate and introduced amino acid substitutions that defined viral lineages. Mutant GPs were used to generate a panel of pseudoviruses, which were used to infect different human and bat cell lines. These data revealed that specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells. Such increased infectivity may have enhanced the ability of EBOV to transmit among humans and contributed to the wide geographic distribution of some viral lineages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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

    2016-02-15

    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.

  17. Ebola Virus Uses Clathrin-Mediated Endocytosis as an Entry Pathway

    Science.gov (United States)

    2010-01-01

    Schmaljohn, A., Aman, M.J., 2002. Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses . J. Exp. Med. 195 (5...Ebola viruses . Cell 106 (1), 117–126. Chazal, N., Singer, G., Aiken, C., Hammarskjold, M.L., Rekosh, D., 2001. Human immunodeficiency virus type 1...taxonomic home for Marburg and Ebola viruses ? Intervirology 18 (1–2), 24–32. Kristiansen, J.E., Mortensen, I., 1987. Antibacterial effect of four

  18. Ebola virus – new threat to global health

    Directory of Open Access Journals (Sweden)

    Rina K. Kusumaratna

    2015-12-01

        The Ebola virus outbreak constitutes a serious warning that epidemics may occur anywhere and places every afflicted nation at risk. Therefore it is essential to institute measures to stop its spread and its future threat, which is a moral obligation of members of the health profession, whether academicians, researchers, or health ministry officials.

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

    Science.gov (United States)

    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.

  20. The Pathogenesis of Ebola Virus Disease.

    Science.gov (United States)

    Baseler, Laura; Chertow, Daniel S; Johnson, Karl M; Feldmann, Heinz; Morens, David M

    2017-01-24

    For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

  1. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

    Science.gov (United States)

    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

  2. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

    Directory of Open Access Journals (Sweden)

    Xiao-Xin Wu

    2015-11-01

    Full Text Available Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD in humans and non-human primates (NHPs. Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs, vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirus∆VP30, recombinant cytomegalovirus (CMV-based vaccines, recombinant rabies virus (RABV-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

  3. Ebola virus disease outbreak - West Africa, September 2014.

    Science.gov (United States)

    2014-10-03

    CDC is assisting ministries of health and working with other organizations to control and end the ongoing outbreak of Ebola virus disease (Ebola) in West Africa. The updated data in this report were compiled from ministry of health situation reports and World Health Organization (WHO) sources. Total case counts include all suspected, probable, and confirmed cases as defined by each country. These data reflect reported cases, which make up an unknown proportion of all actual cases. The data also reflect reporting delays that might vary from country to country.

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

    Science.gov (United States)

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

    2016-07-08

    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.

  5. Development of Treatment Strategies to Combat Ebola and Marburg Viruses

    Science.gov (United States)

    2006-02-02

    HIV, acyclovir for herpes simplex virus and ribavirin for the arenviruses and bunyaviruses. Filoviruses replicate and transcribe their genomes using a...treatment of experimental Ebola virus infections. J. Infect. Dis. 179(Suppl. 1), S224–S234 (1999). • Demonstrates that hyperimmune equine ...Virusol. 40(6), 270–273 (1995). • Reports that hyperimmune equine IgG protected a small cohort of baboons against challenge with a low dose of

  6. Laboratory Response to 2014 Ebola Virus Outbreak in Mali.

    Science.gov (United States)

    Diarra, Bassirou; Safronetz, David; Sarro, Yeya Dit Sadio; Kone, Amadou; Sanogo, Moumine; Tounkara, Sady; Togo, Antieme C G; Daou, Fatoumata; Maiga, Almoustapha I; Dao, Sounkalo; Rosenke, Kyle; Falzarano, Darryl; Doumbia, Seydou; Zoon, Kathryn C; Polis, Michael; Siddiqui, Sophia; Sow, Samba; Schwan, Tom G; Feldmann, Heinz; Diallo, Souleyman; Koita, Ousmane A

    2016-10-15

    Aware of the rapid spread of Ebola virus (EBOV) during the current West African epidemic, Mali took several proactive steps to rapidly identify cases within its borders. Under the Mali International Center for Excellence in Research program, a collaboration between the National Institute of Allergy and Infectious Diseases and the Malian Ministry of Higher Education and Scientific Research established a national EBOV diagnostic site at the University of Sciences, Techniques and Technologies of Bamako in the SEREFO Laboratory. Two separate introductions of EBOV occurred in Mali from neighboring Guinea, but both chains of transmission were quickly halted, and Mali was declared "Ebola free" on 18 January 2015 and has remained so since. The SEREFO Laboratory was instrumental in the success of Mali's Ebola response by providing timely and accurate diagnostics. As of today, the SEREFO Laboratory has tested 103 samples from 88 suspected cases, 10 of which were EBOV positive, since the Ebola diagnostics unit started in April 2014. The establishment of Ebola diagnostics in the SEREFO Laboratory, safety precautions, and diagnostics are described. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. Potential for large outbreaks of Ebola virus disease

    Directory of Open Access Journals (Sweden)

    A. Camacho

    2014-12-01

    Full Text Available 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.

  8. The Ebola virus: a review of progress and development in research

    Directory of Open Access Journals (Sweden)

    Yitades Gebre

    2014-12-01

    Full Text Available The Ebola virus was identified in the year 1976 and has caused periodic outbreaks in West African countries. The disease has a case fatality rate up to 90%. Ebola has been classified as a biosafety level four pathogen and there is no currently approved vaccine or treatment for the virus. However, remarkable progress has been demonstrated by researchers in understanding the pathogenicity of the Ebola virus. Several animal models have been cultivated to develop diagnostics, vaccines and therapeutic drugs.

  9. The Ebola virus:a review of progress and development in research

    Institute of Scientific and Technical Information of China (English)

    Yitades; Gebre; Teshome; Gebre; Abena; Peters

    2014-01-01

    The Ebola virus was identified in the year 1976 and has caused periodic outbreaks in West African countries.The disease has a case fatality rate up to 90%.Ebola has been classified as a biosafety level four pathogen and there is no currently approved vaccine or treatment for the virus.However,remarkable progress has been demonstrated by researchers in understanding the pathogenicity of the Ebola virus.Several animal models have been cultivated to develop diagnostics,vaccines and therapeutic drugs.

  10. High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

    Science.gov (United States)

    2010-06-01

    are heavily glycosylated and contain high-mannose. As a result, MBL binds to Ebola and Marburg viruses and mediates com- plement-dependent virus ...host cells. Therefore, MBL preferentially recognizes glycosylated viruses including influenza virus , human immunodeficiency virus , severe acute...respiratory syndrome coronovirus (SARS-CoV), Ebola virus , and Marburg virus . It also recognizes many glycosylated gram- positive and gram-negative bacteria [1

  11. [Ebola and Marburg hemorrhagic fever viruses: update on filoviruses].

    Science.gov (United States)

    Leroy, E; Baize, S; Gonzalez, J P

    2011-04-01

    The Ebola and Marburg viruses are the sole members of the Filoviridae family of viruses. They are characterized by a long filamentous form that is unique in the viral world. Filoviruses are among the most virulent pathogens currently known to infect humans. They cause fulminating disease characterized by acute fever followed by generalized hemorrhagic syndrome that is associated with 90% mortality in the most severe forms. Epidemic outbreaks of Marburg and Ebola viruses have taken a heavy toll on human life in Central Africa and devastated large ape populations in Gabon and Republic of Congo. Since their discovery in 1967 (Marburg) and 1976 (Ebola), more than 2,300 cases and 1,670 deaths have been reported. These numbers pale in comparison with the burden caused by malnutrition or other infectious disease scourges in Africa such as malaria, cholera, AIDS, dengue or tuberculosis. However, due to their extremely high lethality, association with multifocal hemorrhaging and specificity to the African continent, these hemorrhagic fever viruses have given rise to great interest on the part not only of the international scientific community but also of the general public because of their perceived potential as biological weapons. Much research has been performed on these viruses and major progress has been made in knowledge of their ecology, epidemiology and physiopathology and in development of vaccine candidates and therapeutic schemes. The purpose of this review is to present the main developments in these particular fields in the last decade.

  12. Vesicular stomatitis virus-based vaccines against Lassa and Ebola viruses.

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Friederike; Geisbert, Thomas W; Feldmann, Heinz; Safronetz, David

    2015-02-01

    We demonstrated that previous vaccination with a vesicular stomatitis virus (VSV)-based Lassa virus vaccine does not alter protective efficacy of subsequent vaccination with a VSV-based Ebola virus vaccine. These findings demonstrate the utility of VSV-based vaccines against divergent viral pathogens, even when preexisting immunity to the vaccine vector is present.

  13. Unconventional Secretion of Ebola Virus Matrix Protein VP40

    OpenAIRE

    Reynard, Olivier; Reid, St. Patrick; Page, Audrey; Mateo, Mathieu; Alazard-Dany, Nathalie; Raoul, Hervé; Basler, Christopher F.; Volchkov, Viktor E.

    2011-01-01

    The Ebola virus matrix protein VP40 plays an essential role in virus assembly and budding. In this study we reveal that transient VP40 expression results in the release into the culture medium of substantial amounts of soluble monomeric VP40 in addition to the release of virus-like particles containing an oligomeric form of this protein as previously described. We show that VP40 secretion is endoplasmic reticulum/Golgi–independent and is not associated with cell death. Soluble VP40 was observ...

  14. VP40 Octamers Are Essential for Ebola Virus Replication

    Science.gov (United States)

    Hoenen, Thomas; Volchkov, Viktor; Kolesnikova, Larissa; Mittler, Eva; Timmins, Joanna; Ottmann, Michelle; Reynard, Olivier; Becker, Stephan; Weissenhorn, Winfried

    2005-01-01

    Matrix protein VP40 of Ebola virus is essential for virus assembly and budding. Monomeric VP40 can oligomerize in vitro into RNA binding octamers, and the crystal structure of octameric VP40 has revealed that residues Phe125 and Arg134 are the most important residues for the coordination of a short single-stranded RNA. Here we show that full-length wild-type VP40 octamers bind RNA upon HEK 293 cell expression. While the Phe125-to-Ala mutation resulted in reduced RNA binding, the Arg134-to-Ala mutation completely abolished RNA binding and thus octamer formation. The absence of octamer formation, however, does not affect virus-like particle (VLP) formation, as the VLPs generated from the expression of wild-type VP40 and mutated VP40 in HEK 293 cells showed similar morphology and abundance and no significant difference in size. These results strongly indicate that octameric VP40 is dispensable for VLP formation. The cellular localization of mutant VP40 was different from that of wild-type VP40. While wild-type VP40 was present in small patches predominantly at the plasma membrane, the octamer-negative mutants were found in larger aggregates at the periphery of the cell and in the perinuclear region. We next introduced the Arg134-to-Ala and/or the Phe125-to-Ala mutation into the Ebola virus genome. Recombinant wild-type virus and virus expressing the VP40 Phe125-to-Ala mutation were both rescued. In contrast, no recombinant virus expressing the VP40 Arg134-to-Ala mutation could be recovered. These results suggest that RNA binding of VP40 and therefore octamer formation are essential for the Ebola virus life cycle. PMID:15650213

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-06

    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.

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

    Science.gov (United States)

    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.

  17. Ebola--haemorrhagic fever

    DEFF Research Database (Denmark)

    Fabiansen, C.; Kronborg, G.; Thybo, S.

    2008-01-01

    This review presents the latest findings on ebola. Ebola presents one of the highest case-fatality rates of all infectious diseases, and in 2007 outbreaks were observed first in the Democratic Republic of Congo and later in Uganda with a new subtype. Accumulating evidence suggests that fruit bats...... are a likely reservoir for the ebola virus. The frequency of filovirus outbreaks in Central Africa is increasing and the potential for introduction and patient care in Denmark is evaluated Udgivelsesdato: 2008/11/24...

  18. [Ebola haemorrhagic fever.

    DEFF Research Database (Denmark)

    Fabiansen, C.; Kronborg, G.; Thybo, S.

    2008-01-01

    This review presents the latest findings on ebola. Ebola presents one of the highest case-fatality rates of all infectious diseases, and in 2007 outbreaks were observed first in the Democratic Republic of Congo and later in Uganda with a new subtype. Accumulating evidence suggests that fruit bats...... are a likely reservoir for the ebola virus. The frequency of filovirus outbreaks in Central Africa is increasing and the potential for introduction and patient care in Denmark is evaluated Udgivelsesdato: 2008/11/24...

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

    Science.gov (United States)

    Bebell, Lisa M; Riley, Laura E

    2015-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    NARCIS (Netherlands)

    V. Veljkovic (Veljko); M. Goeijenbier (Marco); S. Glisic (Sanja); N. Veljkovic (Nevena); V.R. Perovic (Vladimir R.); M. Sencanski (Milan); D.R. Branch (Donald R.); S. Paessler (Slobodan)

    2015-01-01

    textabstractThe 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 li

  3. Binding site prediction within Ebola virus VP40 protein:clue for further drug development

    Institute of Scientific and Technical Information of China (English)

    Viroj; Wiwanitkit

    2014-01-01

    To the editor.The emerging African Ebola virus infection in 2014 is the global concernl I].To manage this deadly infection,there arestill no effective drugs and vaccines.Searching for new drug is the urgent requirement for successful control of the disease.Based on the new finding,it is noted that Ebola virus VP40

  4. Virus Genomes Reveal the Factors that Spread and Sustained the West African Ebola Epidemic

    Science.gov (United States)

    2016-08-09

    unprecedented magnitude, duration and impact. Extensive collaborative sequencing projects have produced a comprehensive collection of Ebola virus...Bausch, D. G. & Schwarz, L. Outbreak of Ebola Virus Disease in Guinea: Where Ecology Meets Economy . PLoS Negl. Trop. Dis. 8, e3056 (2014). 26

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

    Science.gov (United States)

    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

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

    NARCIS (Netherlands)

    V. Veljkovic (Veljko); M. Goeijenbier (Marco); S. Glisic (Sanja); N. Veljkovic (Nevena); V.R. Perovic (Vladimir R.); M. Sencanski (Milan); D.R. Branch (Donald R.); S. Paessler (Slobodan)

    2015-01-01

    textabstractThe 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

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

    Science.gov (United States)

    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.

  8. A cellular automata model of Ebola virus dynamics

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Olivier Reynard

    2015-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  11. Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein.

    Directory of Open Access Journals (Sweden)

    Luis Mario Rodríguez-Martínez

    Full Text Available 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.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.Antibody fragments might represent a useful, effective, and low cost alternative to full-length antibodies in Ebola related capture and diagnostics applications.

  12. Prospects for immunisation against Marburg and Ebola viruses.

    Science.gov (United States)

    Geisbert, Thomas W; Bausch, Daniel G; Feldmann, Heinz

    2010-11-01

    For more than 30 years the filoviruses, Marburg virus and Ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. The filoviruses are endemic primarily in resource-poor regions in Central Africa and are also potential agents of bioterrorism. Although no vaccines or antiviral drugs for Marburg or Ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines against filoviruses in nonhuman primate models. Due to the generally remote locations of filovirus outbreaks, a single-injection vaccine is desirable. Among the prospective vaccines that have shown efficacy in nonhuman primate models of filoviral hemorrhagic fever, two candidates, one based on a replication-defective adenovirus serotype 5 and the other on a recombinant VSV (rVSV), were shown to provide complete protection to nonhuman primates when administered as a single injection. The rVSV-based vaccine has also shown utility when administered for postexposure prophylaxis against filovirus infections. A VSV-based Ebola vaccine was recently used to manage a potential laboratory exposure.

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

    Science.gov (United States)

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

    2015-12-01

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

  14. Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein.

    Science.gov (United States)

    Rodríguez-Martínez, Luis Mario; Marquez-Ipiña, Alan Roberto; 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

    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. 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. Antibody fragments might represent a useful, effective, and low cost alternative to full-length antibodies in Ebola related capture and diagnostics applications.

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

    Science.gov (United States)

    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.

  16. Use of convalescent plasma in Ebola virus infection.

    Science.gov (United States)

    Garraud, Olivier

    2017-02-01

    The recent Ebola virus epidemics which threatened three West African countries (Dec.2014-Apr.2016) has urged global collaborative health organizations and countries to set up measures to stop the infection and to treat patients, near half of them being at risk of death. Convalescent plasma-recovered from rescued West Africans-was considered a feasible therapeutic option. Efficacy was difficult to evaluate because of numerous unknowns (especially evolution of neutralizing antibodies), prior to the cessation of active transmission. This raises a large body of questions spanning epidemiological, virological, immunological but also ethical, sociological and anthropological aspects, alongside with public health concerns, in order to be better prepared to the next outbreak. This essay summarizes efforts made by a large number of groups worldwide, and attempts to address still unanswered questions on the benefit of specific versus non-specific plasma on altered-leaking-vascular endothelia in Ebola infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The nexus between forest fragmentation in Africa and Ebola virus disease outbreaks

    Science.gov (United States)

    Rulli, Maria Cristina; Santini, Monia; Hayman, David T. S.; D’Odorico, Paolo

    2017-01-01

    Tropical forests are undergoing land use change in many regions of the world, including the African continent. Human populations living close to forest margins fragmented and disturbed by deforestation may be particularly exposed to zoonotic infections because of the higher likelihood for humans to be in contact with disease reservoirs. Quantitative analysis of the nexus between deforestation and the emergence of Ebola virus disease (EVD), however, is still missing. Here we use land cover change data in conjunction with EVD outbreak records to investigate the association between recent (2004–2014) outbreaks in West and Central Africa, and patterns of land use change in the region. We show how in these EVD outbreaks the index cases in humans (i.e. spillover from wildlife reservoirs) occurred mostly in hotspots of forest fragmentation. PMID:28195145

  18. The nexus between forest fragmentation in Africa and Ebola virus disease outbreaks

    Science.gov (United States)

    Rulli, Maria Cristina; Santini, Monia; Hayman, David T. S.; D'Odorico, Paolo

    2017-02-01

    Tropical forests are undergoing land use change in many regions of the world, including the African continent. Human populations living close to forest margins fragmented and disturbed by deforestation may be particularly exposed to zoonotic infections because of the higher likelihood for humans to be in contact with disease reservoirs. Quantitative analysis of the nexus between deforestation and the emergence of Ebola virus disease (EVD), however, is still missing. Here we use land cover change data in conjunction with EVD outbreak records to investigate the association between recent (2004-2014) outbreaks in West and Central Africa, and patterns of land use change in the region. We show how in these EVD outbreaks the index cases in humans (i.e. spillover from wildlife reservoirs) occurred mostly in hotspots of forest fragmentation.

  19. Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor Binding Site

    Science.gov (United States)

    2016-06-14

    1 Antibody treatment of Ebola and Sudan virus infection via a uniquely exposed epitope within the glycoprotein receptor-binding site Katie A...interaction with the endosomal receptor NPC-1, cross neutralizes Ebola (EBOV), Sudan (SUDV), and Bundibugyo viruses, and protects mice and guinea pigs...Filoviridae include two marburgviruses: Marburg virus (MARV) and Ravn virus (RAVV), and five ebolaviruses: Ebola virus (EBOV), Sudan virus (SUDV

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

    Science.gov (United States)

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

    2016-01-01

    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

  1. 埃博拉病毒的生态学%The ecology of Ebola virus

    Institute of Scientific and Technical Information of China (English)

    钟江

    2015-01-01

    埃博拉病毒疫情正在西非一些国家蔓延,成为历史上最大的一次埃博拉病毒流行,在当地造成极大损失,也对世界各国的公共卫生安全构成严重威胁。本文介绍了埃博拉病毒暴发流行的历史和特点、在自然界的贮存宿主、传播特征等方面研究的进展,以及需要重点关注的问题。%The largest ever Ebola virus epidemic in the history ,which is currently affecting some Western Africa countries ,has resulted in major losses in the region ,and is posing a threat to the public health of countries all over the world . This review summarizes the history of Ebola virus epidemics , the research advances in understanding the pattern of the epidemics ,the natural reservoir host ,and the transmission of the virus ,along with issues that need further attentions .

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

    Science.gov (United States)

    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.

  3. 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

    Science.gov (United States)

    2016-03-20

    Lefkowitz EJ, editors. Virus Taxonomy - 8 Ninth Report of the International Committee on Taxonomy of Viruses . London, UK: 9 Elsevier/Academic Press...Ebola virus variants that emerged in Guinea and the 16 Democratic Republic of the Congo in 2014. Viruses . 2014;6(11):4760-99. doi: 17 10.3390/v6114760...1 Informing the historical record of experimental nonhuman primate 1 infections with Ebola virus : genomic characterization of 2 USAMRIID Ebola

  4. A review on the Ebola virus, outbreak history and the current research tools to control the disease

    Institute of Scientific and Technical Information of China (English)

    Cesar Marcial Escobedo-Bonilla

    2015-01-01

    The Ebola virus is a zoonotic pathogen causing hemorrhagic fever disease with a high mortality rate. The distribution of this pathogen has been limited to woodlands from Central and West Africa and the forest-savannah ecotone in East Africa. The likely reservoir species are frugivorous bats living in these areas. This pathogen is becoming an increasing threat to human populations since its distribution range is expanding faster than expected. The current Ebola outbreaks in Western Africa and in the Democratic Republic of Congo have rapidly spread infecting high numbers of individuals in five African countries. The disease has reached the United States and Spain. This expansion is due partly to increasing global connectivity. This situation represents a new challenge to control the spread of the disease. Experimental drugs have been used to treat a few infected people with promising results. This gives hope for an effective treatment against Ebola hemorrhagic fever in the near future, though thousands of people remain at risk of infection. The present review aims to give an update of the knowledge on the disease, including features of the Ebola virus, the history of disease outbreaks in Africa and the tools that are being developed in order to control this re-emergent disease.

  5. A review on the Ebola virus, outbreak history and the current research tools to control the disease

    Directory of Open Access Journals (Sweden)

    Cesar Marcial Escobedo-Bonilla

    2015-01-01

    Full Text Available The Ebola virus is a zoonotic pathogen causing hemorrhagic fever disease with a high mortality rate. The distribution of this pathogen has been limited to woodlands from Central and West Africa and the forest-savannah ecotone in East Africa. The likely reservoir species are frugivorous bats living in these areas. This pathogen is becoming an increasing threat to human populations since its distribution range is expanding faster than expected. The current Ebola outbreaks in Western Africa and in the Democratic Republic of Congo have rapidly spread infecting high numbers of individuals in five African countries. The disease has reached the United States and Spain. This expansion is due partly to increasing global connectivity. This situation represents a new challenge to control the spread of the disease. Experimental drugs have been used to treat a few infected people with promising results. This gives hope for an effective treatment against Ebola hemorrhagic fever in the near future, though thousands of people remain at risk of infection. The present review aims to give an update of the knowledge on the disease, including features of the Ebola virus, the history of disease outbreaks in Africa and the tools that are being developed in order to control this re-emergent disease.

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

    OpenAIRE

    Sam Smith; Stella Smith

    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 we...

  7. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Institute of Scientific and Technical Information of China (English)

    Beuy Joob; Viroj Wiwanitkit

    2014-01-01

    The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present. Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus. The in-depth analysis of the viral protein to find the binding site, active pocket is needed. Here, the authors analyzed the envelope glycoprotein GP2 from Ebola virus. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus was done. According to this assessment, 7 active pockets with varied druggability could be identified.

  8. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Institute of Scientific and Technical Information of China (English)

    Beuy; Joob; Viroj; Wiwanitkit

    2014-01-01

    The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present.Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus.The in-depth analysis of the viral protein to find the binding site,active pocket is needed.Here,the authors analyzed the envelope glycoprotein GP2 from Ebola virus.Identification of active pocket and protein draggability within envelope glycoprotein GP2 from Ebola virus was done.According to this assessment,7 active pockets with varied draggability could be identified.

  9. Predicting Ebola Severity: A Clinical Prioritization Score for Ebola Virus Disease

    Science.gov (United States)

    Okoni-Williams, Harry Henry; Suma, Mohamed; Mancuso, Brooke; Al-Dikhari, Ahmed; Faouzi, Mohamed

    2017-01-01

    Background Despite the notoriety of Ebola virus disease (EVD) as one of the world’s most deadly infections, EVD has a wide range of outcomes, where asymptomatic infection may be almost as common as fatality. With increasingly sensitive EVD diagnosis, there is a need for more accurate prognostic tools that objectively stratify clinical severity to better allocate limited resources and identify those most in need of intensive treatment. Methods/Principal Findings This retrospective cohort study analyses the clinical characteristics of 158 EVD(+) patients at the GOAL-Mathaska Ebola Treatment Centre, Sierra Leone. The prognostic potential of each characteristic was assessed and incorporated into a statistically weighted disease score. The mortality rate among EVD(+) patients was 60.8% and highest in those aged 25 years (pEbola viral load (p = 0.1), potentially indicating a pathologic synergy between the infections. Similarly, referral-time interacted with viral load, and adjustment revealed referral-time as a significant determinant of mortality, thus quantifying the benefits of early reporting as a 12% mortality risk reduction per day (p = 0.012). Disorientation was the strongest unadjusted predictor of death (OR = 13.1, p = 0.014) followed by hiccups, diarrhoea, conjunctivitis, dyspnoea and myalgia. Including these characteristics in multivariate prognostic scores, we obtained a 91% and 97% ability to discriminate death at or after triage respectively (area under ROC curve). Conclusions/Significance This study proposes highly predictive and easy-to-use prognostic tools, which stratify the risk of EVD mortality at or after EVD triage. PMID:28151955

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

    Science.gov (United States)

    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.

  11. Sequencing ebola and marburg viruses genomes using microarrays.

    Science.gov (United States)

    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.

  12. Ebola virus disease in Africa: epidemiology and nosocomial transmission.

    Science.gov (United States)

    Shears, P; O'Dempsey, T J D

    2015-05-01

    The 2014 Ebola outbreak in West Africa, primarily affecting Guinea, Sierra Leone, and Liberia, has exceeded all previous Ebola outbreaks in the number of cases and in international response. There have been 20 significant outbreaks of Ebola virus disease in Sub-Saharan Africa prior to the 2014 outbreak, the largest being that in Uganda in 2000, with 425 cases and a mortality of 53%. Since the first outbreaks in Sudan and Zaire in 1976, transmission within health facilities has been of major concern, affecting healthcare workers and acting as amplifiers of spread into the community. The lack of resources for infection control and personal protective equipment are the main reasons for nosocomial transmission. Local strategies to improve infection control, and a greater understanding of local community views on the disease, have helped to bring outbreaks under control. Recommendations from previous outbreaks include improved disease surveillance to enable more rapid health responses, the wider availability of personal protective equipment, and greater international preparedness. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

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

    National Research Council Canada - National Science Library

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

    2016-01-01

    ...: we encapsulated scrambled Ebola RNA sequences inside of tobacco mosaic virus to create a biomimicry that is non-infectious, but stable, and could therefore serve as a positive control in Ebola diagnostic assays...

  14. Development of risk reduction behavioral counseling for Ebola virus disease survivors enrolled in the Sierra Leone Ebola Virus Persistence Study, 2015-2016.

    Science.gov (United States)

    Abad, Neetu; Malik, Tasneem; Ariyarajah, Archchun; Ongpin, Patricia; Hogben, Matthew; McDonald, Suzanna L R; Marrinan, Jaclyn; Massaquoi, Thomas; Thorson, Anna; Ervin, Elizabeth; Bernstein, Kyle; Ross, Christine; Liu, William J; Kroeger, Karen; Durski, Kara N; Broutet, Nathalie; Knust, Barbara; Deen, Gibrilla F

    2017-09-01

    During the 2014-2016 West Africa Ebola Virus Disease (EVD) epidemic, the public health community had concerns that sexual transmission of the Ebola virus (EBOV) from EVD survivors was a risk, due to EBOV persistence in body fluids of EVD survivors, particularly semen. The Sierra Leone Ebola Virus Persistence Study was initiated to investigate this risk by assessing EBOV persistence in numerous body fluids of EVD survivors and providing risk reduction counseling based on test results for semen, vaginal fluid, menstrual blood, urine, rectal fluid, sweat, tears, saliva, and breast milk. This publication describes implementation of the counseling protocol and the key lessons learned. The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol was developed from a framework used to prevent transmission of HIV and other sexually transmitted infections. The framework helped to identify barriers to risk reduction and facilitated the development of a personalized risk-reduction plan, particularly around condom use and abstinence. Pre-test and post-test counseling sessions included risk reduction guidance, and post-test counseling was based on the participants' individual test results. The behavioral counseling protocol enabled study staff to translate the study's body fluid test results into individualized information for study participants. The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol provided guidance to mitigate the risk of EBOV transmission from EVD survivors. It has since been shared with and adapted by other EVD survivor body fluid testing programs and studies in Ebola-affected countries.

  15. Ebola and Marburg virus diseases in Africa: increased risk of outbreaks in previously unaffected areas?

    Science.gov (United States)

    Changula, Katendi; Kajihara, Masahiro; Mweene, Aaron S; Takada, Ayato

    2014-09-01

    Filoviral hemorrhagic fever (FHF) is caused by ebolaviruses and marburgviruses, which both belong to the family Filoviridae. Egyptian fruit bats (Rousettus aegyptiacus) are the most likely natural reservoir for marburgviruses and entry into caves and mines that they stay in has often been associated with outbreaks of MVD. On the other hand, the natural reservoir for ebola viruses remains elusive; however, handling of wild animal carcasses has been associated with some outbreaks of EVD. In the last two decades, there has been an increase in the incidence of FHF outbreaks in Africa, some being caused by a newly found virus and some occurring in previously unaffected areas such as Guinea, Liberia and Sierra Leone, in which the most recent EVD outbreak occurred in 2014. Indeed, the predicted geographic distribution of filoviruses and their potential reservoirs in Africa includes many countries in which FHF has not been reported. To minimize the risk of virus dissemination in previously unaffected areas, there is a need for increased investment in health infrastructure in African countries, policies to facilitate collaboration between health authorities from different countries, implementation of outbreak control measures by relevant multi-disciplinary teams and education of the populations at risk.

  16. Youtube as a source of information on Ebola virus disease

    Directory of Open Access Journals (Sweden)

    Ranjan Pathak

    2015-01-01

    Full Text Available Background: The current West Africa epidemic of Ebola virus disease (EVD, which began from Guinea in December 2013, has been the longest and deadliest Ebola outbreak to date. With the propagation of the internet, public health officials must now compete with other official and unofficial sources of information to get their message out. Aims: This study aimed at critically appraising videos available on one popular internet video site (YouTube as a source of information for Ebola virus disease (EVD. Materials and Methods: Videos were searched in YouTube (http://www.youtube.com using the keyword "Ebola outbreak" from inception to November 1, 2014 with the default "relevance" filter. Only videos in English language under 10 min duration within first 10 pages of search were included. Duplicates were removed and the rest were classified as useful or misleading by two independent reviewers. Video sources were categorized by source. Inter-observer agreement was evaluated with kappa coefficient. Continuous and categorical variables were analyzed using the Student t-test and Chi-squared test, respectively. Results: One hundred and eighteen out of 198 videos were evaluated. Thirty-one (26.27% videos were classified as misleading and 87 (73.73% videos were classified as useful. The kappa coefficient of agreement regarding the usefulness of the videos was 0.68 (P < 0.001. Independent users were more likely to post misleading videos (93.55% vs 29.89%, OR = 34.02, 95% CI = 7.55-153.12, P < 0.001 whereas news agencies were most likely to post useful videos (65.52% vs 3.23%, OR = 57.00, 95% CI = 7.40-438.74, P < 0.001. Conclusions: This study demonstrates that majority of the internet videos about Ebola on YouTube were characterized as useful. Although YouTube seems to generally be a useful source of information on the current outbreak, increased efforts to disseminate scientifically correct information is desired to prevent unnecessary panic among the among

  17. Ebola virus disease and social media: A systematic review.

    Science.gov (United States)

    Fung, Isaac Chun-Hai; Duke, Carmen Hope; Finch, Kathryn Cameron; Snook, Kassandra Renee; Tseng, Pei-Ling; Hernandez, Ana Cristina; Gambhir, Manoj; Fu, King-Wa; Tse, Zion Tsz Ho

    2016-12-01

    We systematically reviewed existing research pertinent to Ebola virus disease and social media, especially to identify the research questions and the methods used to collect and analyze social media. We searched 6 databases for research articles pertinent to Ebola virus disease and social media. We extracted the data using a standardized form. We evaluated the quality of the included articles. Twelve articles were included in the main analysis: 7 from Twitter with 1 also including Weibo, 1 from Facebook, 3 from YouTube, and 1 from Instagram and Flickr. All the studies were cross-sectional. Eleven of the 12 articles studied ≥ 1of these 3 elements of social media and their relationships: themes or topics of social media contents, meta-data of social media posts (such as frequency of original posts and reposts, and impressions) and characteristics of the social media accounts that made these posts (such as whether they are individuals or institutions). One article studied how news videos influenced Twitter traffic. Twitter content analysis methods included text mining (n = 3) and manual coding (n = 1). Two studies involved mathematical modeling. All 3 YouTube studies and the Instagram/Flickr study used manual coding of videos and images, respectively. Published Ebola virus disease-related social media research focused on Twitter and YouTube. The utility of social media research to public health practitioners is warranted. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  18. Diagnosis of Ebola Virus Disease: Progress and Prospects

    Directory of Open Access Journals (Sweden)

    Mingjuan Yang

    2015-12-01

    Full Text Available Ebola virus disease (EVD represents one of the deadliest diseases in the world, with a fatality rate of over 70% and absence of effective vaccine and treatment. Rapid and specific diagnosis of EVD is essential for isolation, treatment of patients, and prevention of outbreak spread. Although many assays for EVD diagnosis have been reported, there is still an urgent requirement for practical assays for use in resource-limited areas, like Africa. Here we summarize the progresses of EVD diagnostic techniques.

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

    Science.gov (United States)

    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.

  20. Ebola Virus Disease in Pregnancy: Clinical, Histopathologic, and Immunohistochemical Findings.

    Science.gov (United States)

    Muehlenbachs, Atis; de la Rosa Vázquez, Olimpia; Bausch, Daniel G; Schafer, Ilana J; Paddock, Christopher D; Nyakio, Jean Paul; Lame, Papys; Bergeron, Eric; McCollum, Andrea M; Goldsmith, Cynthia S; Bollweg, Brigid C; Prieto, Miriam Alía; Lushima, Robert Shongo; Ilunga, Benoit Kebela; Nichol, Stuart T; Shieh, Wun-Ju; Ströher, Ute; Rollin, Pierre E; Zaki, Sherif R

    2017-01-01

    Here we describe clinicopathologic features of Ebola virus disease in pregnancy. One woman infected with Sudan virus in Gulu, Uganda, in 2000 had a stillbirth and survived, and another woman infected with Bundibugyo virus had a live birth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malarial parasite pigment-laden macrophages. These data suggest that trophoblast infection may be a mechanism of transplacental ebolavirus transmission. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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

    Directory of Open Access Journals (Sweden)

    Justin T. Baca

    2015-04-01

    Full Text Available 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. Media Messages and Perception of Risk for Ebola Virus Infection, United States

    Science.gov (United States)

    Boddie, Crystal; McGinty, Emma E.; Pollack, Keshia; Smith, Katherine Clegg; Burke, Thomas A.; Rutkow, Lainie

    2017-01-01

    News media have been blamed for sensationalizing Ebola in the United States, causing unnecessary alarm. To investigate this issue, we analyzed US-focused news stories about Ebola virus disease during July 1–November 30, 2014. We found frequent use of risk-elevating messages, which may have contributed to increased public concern. PMID:27983495

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

    Directory of Open Access Journals (Sweden)

    Ligui Wang

    2015-09-01

    Full Text Available 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.

  4. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells

    DEFF Research Database (Denmark)

    Hölzer, Martin; Krähling, Verena; Amman, Fabian

    2016-01-01

    The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result...... expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine...

  5. Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces.

    Science.gov (United States)

    Sagripanti, Jose-Luis; Rom, Amanda M; Holland, Louis E

    2010-12-01

    Ebola, Lassa, Venezuelan equine encephalitis, and Sindbis viruses were dried onto solid surfaces, incubated for various time periods under controlled conditions of temperature and relative humidity, and quantitatively eluted from surfaces, and viral titers in the recovered samples were determined. The viral inactivation kinetics that were obtained indicated that viral resistance to natural inactivation in the dark follows (in decreasing order of stability) alphavirus > Lassa virus > Ebola virus. The findings reported in this study on the natural decay in the dark should assist in understanding the biophysical properties of enveloped RNA viruses outside the host and in estimating the persistence of viruses in the environment during epidemics or after an accidental or intentional release.

  6. Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency

    Science.gov (United States)

    Alfson, Kendra J.; Worwa, Gabriella; Carrion, Ricardo

    2015-01-01

    ABSTRACT Ebola virus (EBOV) is an RNA virus that can cause hemorrhagic fever with high fatality rates, and there are no approved vaccines or therapies. Typically, RNA viruses have high spontaneous mutation rates, which permit rapid adaptation to selection pressures and have other important biological consequences. However, it is unknown if filoviruses exhibit high mutation frequencies. Ultradeep sequencing and a recombinant EBOV that carries the gene encoding green fluorescent protein were used to determine the spontaneous mutation frequency of EBOV. The effects of the guanosine analogue ribavirin during EBOV infections were also assessed. Ultradeep sequencing revealed that the mutation frequency for EBOV was high and similar to those of other RNA viruses. Interestingly, significant genetic diversity was not observed in viable viruses, implying that changes were not well tolerated. We hypothesized that this could be exploited therapeutically. In vitro, the presence of ribavirin increased the error rate, and the 50% inhibitory concentration (IC50) was 27 μM. In a mouse model of ribavirin therapy given pre-EBOV exposure, ribavirin treatment corresponded with a significant delay in time to death and up to 75% survival. In mouse and monkey models of therapy given post-EBOV exposure, ribavirin treatment also delayed the time to death and increased survival. These results demonstrate that EBOV has a spontaneous mutation frequency similar to those of other RNA viruses. These data also suggest a potential for therapeutic use of ribavirin for human EBOV infections. IMPORTANCE Ebola virus (EBOV) causes a severe hemorrhagic disease with high case fatality rates; there are no approved vaccines or therapies. We determined the spontaneous mutation frequency of EBOV, which is relevant to understanding the potential for the virus to adapt. The frequency was similar to those of other RNA viruses. Significant genetic diversity was not observed in viable viruses, implying that

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

    Science.gov (United States)

    Zumbrun, E E

    2015-01-01

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

  8. Euthanasia Assessment in Ebola Virus Infected Nonhuman Primates

    Directory of Open Access Journals (Sweden)

    Travis K. Warren

    2014-11-01

    Full Text Available 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.

  9. Antiviral Screening of Multiple Compounds against Ebola Virus

    Directory of Open Access Journals (Sweden)

    Stuart D. Dowall

    2016-10-01

    Full Text Available In light of the recent outbreak of Ebola virus (EBOV disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine. A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna. The three most promising compounds (17-DMAG; BGB324; and NCK-8 were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

  10. The 2014 Ebola virus disease outbreak in West Africa.

    Science.gov (United States)

    Gatherer, Derek

    2014-08-01

    On 23 March 2014, the World Health Organization issued its first communiqué on a new outbreak of Ebola virus disease (EVD), which began in December 2013 in Guinée Forestière (Forested Guinea), the eastern sector of the Republic of Guinea. Located on the Atlantic coast of West Africa, Guinea is the first country in this geographical region in which an outbreak of EVD has occurred, leaving aside the single case reported in Ivory Coast in 1994. Cases have now also been confirmed across Guinea as well as in the neighbouring Republic of Liberia. The appearance of cases in the Guinean capital, Conakry, and the transit of another case through the Liberian capital, Monrovia, presents the first large urban setting for EVD transmission. By 20 April 2014, 242 suspected cases had resulted in a total of 147 deaths in Guinea and Liberia. The causative agent has now been identified as an outlier strain of Zaire Ebola virus. The full geographical extent and degree of severity of the outbreak, its zoonotic origins and its possible spread to other continents are sure to be subjects of intensive discussion over the next months. © 2014 The Authors.

  11. Molecular Docking Study of Bioactive Compound of Andrographolide against Ebola Virus

    Directory of Open Access Journals (Sweden)

    R.Sharmila

    2016-05-01

    Full Text Available Ebola virus is a single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever in humans and nonhuman primates. This virus is resistance to many antibiotics also there is no proper treatment for EBOLA viral infection. In worldwide,thus many people affected by this virus and there is no drug available for treatment of Ebola virus infection. Therefore new drugs are need for therapy and prevention for this life threatening infection. Hence the current study deals with the evaluation of the potent bioactive compound Andrographolide against the three receptors of Ebola virus receptor proteins. The protein receptors VP40, VP35 and VP24 were docked with the Andrographolide and evaluated on the basis of total energy and binding affinity scores byAutoDock. Andrographolide showed a high docking score against the VP40, VP35 and VP24. Theestimated binding free energy of VP40 is −3.57 kcal/mol, the VP35 binding free energy is −7.18 kcal/mol. The VP24 binding free energy is −8.5 kcal/mol. This study showed that Andrographolide have high binding affinity and exhibit better interactions with all the Ebola Virus Protein receptors. This study will help to identify the new drug development for the EBOLA virus.

  12. Virtual screening of the inhibitors targeting at the viral protein 40 of Ebola virus

    Institute of Scientific and Technical Information of China (English)

    V.Karthick; N.Nagasundaram; C.George Priya Doss; Chiranjib Chakraborty; R.Siva; Aiping Lu; Ge Zhang

    2016-01-01

    Background:The Ebola virus is highly pathogenic and destructive to humans and other primates.The Ebola virus encodes viral protein 40 (VP40),which is highly expressed and regulates the assembly and release of viral particles in the host cell.Because VP40 plays a prominent role in the life cycle of the Ebola virus,it is considered as a key target for antiviral treatment.However,there is currently no FDA-approved drug for treating Ebola virus infection,resulting in an urgent need to develop effective antiviral inhibitors that display good safety profiles in a short duration.Methods:This study aimed to screen the effective lead candidate against Ebola infection.First,the lead molecules were filtered based on the docking score.Second,Lipinski rule of five and the other drug likeliness properties are predicted to assess the safety profile of the lead candidates.Finally,molecular dynamics simulations was performed to validate the lead compound.Results:Our results revealed that emodin-8-beta-D-glucoside from the Traditional Chinese Medicine Database (TCMD) represents an active lead candidate that targets the Ebola virus by inhibiting the activity of VP40,and displays good pharmacokinetic properties.Conclusion:This report will considerably assist in the development of the competitive and robust antiviral agents against Ebola infection.

  13. General introduction into the Ebola virus biology and disease.

    Science.gov (United States)

    Zawilińska, Barbara; Kosz-Vnenchak, Magdalena

    2014-01-01

    Epidemic of Ebola hemorrhagic fever which appeared in the countries of West Africa in 2014, is the largest outbreak which occurred so far. The virus causing this epidemic, Zaire Ebolavirus (ZEBOV), along with four other species of Ebolaviruses is classified to the genus Ebolavirus in the family Filoviridae. ZEBOV is one of the most virulent pathogens among the viral haemorrhagic fevers, and case fatality rates up to 90% have been reported. Mortality is the result of multi-organ failure and severe bleeding complications. The aim of this review is to present the general characteristics of the virus and its biological properties, pathogenicity and epidemiology, with a focus on laboratory methods used in the diagnosis of these infections.

  14. Awareness of Ebola: An Exotic Zoonotic Disease

    Directory of Open Access Journals (Sweden)

    NLPI Dharmayanti

    2015-03-01

    Full Text Available Filovirus including Ebola and Marburg hemorrhagic fever is a zoonotic disease that characterised by immune suppression and systemic inflammatory response causing impairment of the vascular and immune systems. It is leading to multiorgan failures with mortality varies from 50-90% in human and primate. The Ebola virus is currently divided into five species, namely Zaire ebolavirus (ZEBOV, Sudan ebolavirus (SEBOV, Tai Forest ebolavirus, Reston ebolavirus (REBOV and Bundibugyo ebolavirus. Geographical distribution of Ebola virus in the Afrotropics region is mainly in the rainforests of Central and West Africa, while REBOV was detected in the Philippines. Bats are suspected as reservoir host of the virus. Recently, Ebola cases had been reported in endemic areas in Africa and then distributed to other countries which was not endemic through human travellers. Ebola virus is also potentially used as a biological weapon, so Ebola virus becomes public health concern. This paper describes the characters of Ebola virus, its clinical signs, transmission and threat as an exotic disease in Indonesia. By understanding the disease, the emergence of Ebola virus in Indonesia can be anticipated quickly.

  15. In silico-based vaccine design against Ebola virus glycoprotein

    Directory of Open Access Journals (Sweden)

    Dash R

    2017-03-01

    Full Text Available Raju Dash,1 Rasel Das,2 Md Junaid,3 Md Forhad Chowdhury Akash,4 Ashekul Islam,5 SM Zahid Hosen1 1Molecular Modeling and Drug Design Laboratory (MMDDL, Pharmacology Research Division, Bangladesh Council of Scientific and Industrial Research (BCSIR, Chittagong, Bangladesh; 2Nanotechnology and Catalysis Research Center, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh; 4Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh; 5Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong, Bangladesh Abstract: Ebola virus (EBOV is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154–162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV. Keywords: Ebola virus, epitope, glycoprotein, vaccine design

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

    Science.gov (United States)

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

    2016-07-14

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

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

    Directory of Open Access Journals (Sweden)

    Martin N. Adokiya

    2016-05-01

    Full Text Available 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

  18. Lateral Flow Immunoassays for Ebola Virus Disease Detection in Liberia.

    Science.gov (United States)

    Phan, Jill C; Pettitt, James; George, Josiah S; Fakoli, Lawrence S; Taweh, Fahn M; Bateman, Stacey L; Bennett, Richard S; Norris, Sarah L; Spinnler, David A; Pimentel, Guillermo; Sahr, Phillip K; Bolay, Fatorma K; Schoepp, Randal J

    2016-10-15

     Lateral flow immunoassays (LFIs) are point-of-care diagnostic assays that are designed for single use outside a formal laboratory, with in-home pregnancy tests the best-known example of these tests. Although the LFI has some limitations over more-complex immunoassay procedures, such as reduced sensitivity and the potential for false-positive results when using complex sample matrices, the assay has the benefits of a rapid time to result and ease of use. These benefits make it an attractive option for obtaining rapid results in an austere environment. In an outbreak of any magnitude, a field-based rapid diagnostic assay would allow proper patient transport and for safe burials to be conducted without the delay caused by transport of samples between remote villages and testing facilities. Use of such point-of-care instruments in the ongoing Ebola virus disease (EVD) outbreak in West Africa would have distinct advantages in control and prevention of local outbreaks, but proper understanding of the technology and interpretation of results are important.  In this study, a LFI, originally developed by the Naval Medical Research Center for Ebola virus environmental testing, was evaluated for its ability to detect the virus in clinical samples in Liberia. Clinical blood and plasma samples and post mortem oral swabs submitted to the Liberian Institute for Biomedical Research, the National Public Health Reference Laboratory for EVD testing, were tested and compared to results of real-time reverse transcription-polymerase chain reaction (rRT-PCR), using assays targeting Ebola virus glycoprotein and nucleoprotein.  The LFI findings correlated well with those of the real-time RT-PCR assays used as benchmarks.  Rapid antigen-detection tests such as LFIs are attractive alternatives to traditional immunoassays but have reduced sensitivity and specificity, resulting in increases in false-positive and false-negative results. An understanding of the strengths, weaknesses

  19. Rapid Bedside Inactivation of Ebola Virus for Safe Nucleic Acid Tests

    DEFF Research Database (Denmark)

    Rosenstierne, Maiken Worsøe; Karlberg, Helen; Bragstad, Karoline

    2016-01-01

    Rapid bedside inactivation of Ebola virus would be a solution for the safety of medical and technical staff, risk containment, sample transport, and high-throughput or rapid diagnostic testing during an outbreak. We show that the commercially available Magna Pure lysis/binding buffer used...... for nucleic acid extraction inactivates Ebola virus. A rapid bedside inactivation method for nucleic acid tests is obtained by simply adding Magna Pure lysis/binding buffer directly into vacuum blood collection EDTA tubes using a thin needle and syringe prior to sampling. The ready-to-use inactivation vacuum...... tubes are stable for more than 4 months, and Ebola virus RNA is preserved in the Magna Pure lysis/binding buffer for at least 5 weeks independent of the storage temperature. We also show that Ebola virus RNA can be manually extracted from Magna Pure lysis/binding buffer-inactivated samples using...

  20. Experimental Treatment of Ebola Virus Disease with Brincidofovir

    Science.gov (United States)

    Dunning, Jake; Kennedy, Stephen B.; Antierens, Annick; Whitehead, John; Ciglenecki, Iza; Carson, Gail; Kanapathipillai, Rupa; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Grove, Jennifer; Scott, Janet; Lang, Trudie; Olliaro, Piero; Horby, Peter W.

    2016-01-01

    Background The nucleotide analogue brincidofovir was developed to prevent and treat infections caused by double-stranded DNA viruses. Based on in vitro data suggesting an antiviral effect against Ebola virus, brincidofovir was included in the World Health Organisation list of agents that should be prioritised for clinical evaluation in patients with Ebola virus disease (EVD) during the West African epidemic. Methods and Findings In this single-arm phase 2 trial conducted in Liberia, patients with laboratory-confirmed EVD (two months of age or older, enrolment bodyweight ≥50 kg) received oral brincidofovir 200 mg as a loading dose on day 0, followed by 100 mg brincidofovir on days 3, 7, 10, and 14. Bodyweight-adjusted dosing was used for patients weighing <50 kg at enrolment. The primary outcome was survival at Day 14 after the first dose of brincidofovir. Four patients were enrolled between 01 January 2015 and 31 January 2015. The trial was stopped following the decision by the manufacturer to terminate their program of development of brincidofovir for EVD. No Serious Adverse Reactions or Suspected Unexpected Serious Adverse Reactions were identified. All enrolled subjects died of an illness consistent with EVD. Conclusions Due to the small sample size it was not possible to determine the efficacy of brincidofovir for the treatment of EVD. The premature termination of the trial highlights the need to establish better practices for preclinical in-vitro and animal screening of therapeutics for potentially emerging epidemic infectious diseases prior to their use in patients. Trial Registration Pan African Clinical Trials Registry PACTR201411000939962 PMID:27611077

  1. Detection of Ebola Virus RNA through Aerosol Sampling of Animal Biosafety Level 4 Rooms Housing Challenged Nonhuman Primates

    Science.gov (United States)

    2016-08-02

    301- 619-4768(f). 1 2 3 4 5 6 7 8 Title: Detection of Ebola Virus RNA through Aerosol Sampling of Animal Biosafety Level 9 4...embedded in the texts. This is the first report demonstrating detection of Ebola virus 17 RNA from animal rooms housing infected nonhuman primates and...on Ebola virus disease and NHP animal models 34 of filovirus infections 35 • Dr. Robert Hawley, Private Consultant, bobhawley226@gmail.com, Former

  2. Current trends in the management of Ebola virus disease-an updated systematic review

    Directory of Open Access Journals (Sweden)

    Palanisamy Sivanandy

    2016-08-01

    Full Text Available The Ebola virus created a ripple of fear when its number of cases rose rapidly and drastically in recent years. Ebola infection is transmitted in humans when contact closely with blood, organs or other body fluids of infected animals or secretions. It is often mortal as it affects vascular system of the body, results in organ failure and serious internal bleeding. Hence, this review was aimed to summarize various essential aspects of Ebola virus disease and its management. A systematic review was carried out by collecting various literatures, published research articles, notes and other published date related to Ebola virus disease. Standard supporting care in a hospital setting such as replenishment of fluid and electrolytes, ventilation support, pain control and nutritional support is initiated to the patients to manage the symptoms and prevent any complications of Ebola disease since there are no Food and Drug Administrationapproved medications available. In terms of pharmacological drug therapy, favipiravir has been shown to be efficacious and safe in treating the Ebola virus disease. Nevertheless, there are some preventive measures as well to decrease the risk of getting the disease. Further, the review suggests the efficient control and prevention of Ebola epidemic require adequate political support from the government as well as the establishment of a robust public health infrastructure and medical reserve. Strengthening of contact tracing and quarantine policies are also important for the prevention of Ebola virus disease. There should be a well-designed disease surveillance system when a suspected case is reported. Given the elevated case-fatality rate and the absence of effective treatment, it is sensible to evade research ethics and develop the promising future of experimental vaccines. The collection of clinical and epidemiological information of Ebola should be vigorous and systematic in the endemic affected areas.

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

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    Benjamin A Pinsky

    Full Text Available 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.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.In summary, we found the Xpert® Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection is critical.

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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.

    2015-01-01

    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.

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

    Science.gov (United States)

    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.

  7. The Role of Exosomal VP40 in Ebola Virus Disease.

    Science.gov (United States)

    Pleet, Michelle L; DeMarino, Catherine; Lepene, Benjamin; Aman, M Javad; Kashanchi, Fatah

    2017-04-01

    Ebola virus (EBOV) can cause a devastating hemorrhagic disease, leading to death in a short period of time. After infection, the resulting EBOV disease results in high levels of circulating cytokines, endothelial dysfunction, coagulopathy, and bystander lymphocyte apoptosis in humans and nonhuman primates. The VP40 matrix protein of EBOV is essential for viral assembly and budding from the host cell. Recent data have shown that VP40 exists in the extracellular environment, including in exosomes, and exosomal VP40 can impact the viability of recipient immune cells, including myeloid and T cells, through the regulation of the RNAi and endosomal sorting complexes required for transport pathways. In this study, we discuss the latest findings of the impact of exosomal VP40 on immune cells in vitro and its potential implications for pathogenesis in vivo.

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

    Directory of Open Access Journals (Sweden)

    Craig R. Miller

    2016-02-01

    Full Text Available 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.

  9. Prognostic Analysis of Patients with Ebola Virus Disease.

    Directory of Open Access Journals (Sweden)

    Xin Zhang

    2015-09-01

    Full Text Available 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.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 10(6 copies/ml presented significantly shorter survival time than those whose viral load were lower than 10(6 copies/ml (P = 0.005. Also, using Pearson chi-square test, we identified that chest pain, coma, and viral load (>10(6 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.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.

  10. What is Ebola?

    Science.gov (United States)

    Stein, R A

    2015-01-01

    On 23 March 2014, the World Health Organization first announced a new Ebola virus outbreak that started in December 2013 in the eastern part of the Republic of Guinea. Human infections shortly emerged in Liberia, Sierra Leone, and Nigeria. On 30 September 2014, the Centers for Disease Control and Prevention confirmed through laboratory testing the first Ebola virus infection diagnosed in the USA, in a patient who travelled from West Africa to Texas. On 6 October 2014, the first human infection occurring outside of Africa was reported, in a Spanish nurse who treated two priests, both of whom died, and on 23 October 2014, the first human infection was reported in New York City. To date, the 2014 Ebola virus outbreak is the longest, largest, and most persistent one since 1976, when the virus was first identified in humans, and the number of human cases exceeded, as of mid-September 2014, the cumulative number of infections from all the previous outbreaks. The early clinical presentation overlaps with other infectious diseases, opening differential diagnosis difficulties. Understanding the transmission routes and identifying the natural reservoir of the virus are additional challenges in studying Ebola hemorrhagic fever outbreaks. Ebola virus is as much a public health challenge for developing countries as it is for the developed world, and previous outbreaks underscored that the relative contribution of the risk factors may differ among outbreaks. The implementation of effective preparedness plans is contingent on integrating teachings from previous Ebola virus outbreaks with those from the current outbreak and with lessons provided by other infectious diseases, along with developing a multifaceted inter-disciplinary and cross-disciplinary framework that should be established and shaped by biomedical as well as sociopolitical sciences. © 2014 John Wiley & Sons Ltd.

  11. The landscape configuration of zoonotic transmission of Ebola virus disease in West and Central Africa: interaction between population density and vegetation cover

    OpenAIRE

    Michael G Walsh; MA Haseeb

    2015-01-01

    Ebola virus disease (EVD) is an emerging infectious disease of zoonotic origin that has been responsible for high mortality and significant social disruption in West and Central Africa. Zoonotic transmission of EVD requires contact between susceptible human hosts and the reservoir species for Ebolaviruses, which are believed to be fruit bats. Nevertheless, features of the landscape that may facilitate such points of contact have not yet been adequately identified. Nor have spatial dependencie...

  12. The Evolution of Ebola virus: Insights from the 2013–2016 Epidemic

    Science.gov (United States)

    Holmes, Edward C.; Dudas, Gytis; Rambaut, Andrew; Andersen, Kristian G.

    2017-01-01

    Preface The 2013–2016 epidemic of Ebola virus disease in West Africa was of unprecedented magnitude and changed our perspective on this lethal but sporadically emerging virus. This outbreak also marked the beginning of large-scale real-time molecular epidemiology. Herein, we show how evolutionary analyses of Ebola virus genome sequences provided key insights into virus origins, evolution, and spread during the epidemic. We provide basic scientists, epidemiologists, medical practitioners, and other outbreak responders with an enhanced understanding of the utility and limitations of pathogen genomic sequencing. This will be crucially important in our attempts to track and control future infectious disease outbreaks. PMID:27734858

  13. The organisation of Ebola virus reveals a capacity for extensive, modular polyploidy.

    Science.gov (United States)

    Beniac, Daniel R; Melito, Pasquale L; Devarennes, Shauna L; Hiebert, Shannon L; Rabb, Melissa J; Lamboo, Lindsey L; Jones, Steven M; Booth, Timothy F

    2012-01-01

    Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope.

  14. The organisation of Ebola virus reveals a capacity for extensive, modular polyploidy.

    Directory of Open Access Journals (Sweden)

    Daniel R Beniac

    Full Text Available BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope.

  15. Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

    Science.gov (United States)

    Kumar, Anoop

    2016-01-01

    Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

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

    Science.gov (United States)

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

    2015-01-01

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

  17. In silico-based vaccine design against Ebola virus glycoprotein

    Science.gov (United States)

    Dash, Raju; Das, Rasel; Junaid, Md; Akash, Md Forhad Chowdhury; Islam, Ashekul; Hosen, SM Zahid

    2017-01-01

    Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154–162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV. PMID:28356762

  18. Ebola virus derived G-quadruplexes: Thiazole orange interaction.

    Science.gov (United States)

    Krafčíková, Petra; Demkovičová, Erika; Víglaský, Viktor

    2016-12-13

    The Ebola and Marburg viruses are some of the deadliest viruses in the world. In this study a series of G-rich DNA sequences derived from these types of viruses which possess the potential to form G-quadruplex structures are analyzed. A set of DNA oligonucleotides derived from original viral isolates was used as a representative modeling sequence with which to demonstrate the influence of thiazole orange on circular dichroism (CD) spectral profiles. The results show the unique profile of the induced CD (ICD) signal in the visible region caused by interactions between the ligand and G-quadruplexes. This ligand was found to stabilize the G-quadruplex structure and can also induce topological changes and facilitate G-quadruplex multimerization. Thus, the ICD signatures can be used to determine whether specific unknown sequences can form G-quadruplex motifs. The viral sequences were analyzed using standard spectral and electrophoretic methods. In addition, the ability to target G-quadruplexes located in filoviruses offers researchers attractive therapeutic targets which would be of particular use in the development of novel antiviral therapies. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-03-28

    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.

  1. Ebola virus disease: caring for patients in Sierra Leone - a qualitative study.

    Science.gov (United States)

    Andertun, Sara; Hörnsten, Åsa; Hajdarevic, Senada

    2017-03-01

    The aim of this study was to describe Norwegian healthcare staffs' experiences of participating in care of patients with Ebola virus disease in Sierra Leone. Ebola is one of the most feared viruses known. Ebola virus disease is highly contagious with high mortality. The few qualitative studies made on experiences among healthcare professionals have highlighted problems as lack of protective resources, insufficient personnel and risk of societal stigmatization. Descriptive study with qualitative approach. Individual narrative and focus group interviews were obtained during 2015 with eight nurses and one physician who had worked in Ebola care in Sierra Leone. The interviews were analysed using qualitative content analysis. The analysis resulted in the two themes: 'Experiencing security by learning to manage risks'; and 'Developing courage and growth by facing personal fears'. Subthemes were: 'Relying on safeguard actions', 'Managing risk of contagion', 'Developing strategies for care despite risks', 'Constantly reminded of death', 'Successively defeating fears' and last, 'Increasing motivation through meaningfulness'. The participants described the reliance on training, organized effort, strict guidelines and equipment. They were respectful of the risk of transmission, made risk assessments, took responsibility, handled risky situations and were reminded of suffering and death. Despite challenges, the hazardous work with Ebola virus disease patients was experienced as meaningful which was an important motivator. Safe care was central in working with Ebola patients, but the care relation was challenged. © 2016 John Wiley & Sons Ltd.

  2. Characterization of a Novel Neutralizing Monoclonal Antibody Against Ebola Virus GP.

    Science.gov (United States)

    Reynard, Olivier; Volchkov, Viktor E

    2015-10-01

    Ebola virus is the etiological agent of a severe hemorrhagic fever with a high mortality rate. As the only protein exposed on the surface of viral particles, the spike glycoprotein GP is the unique target for neutralizing monoclonal antibodies. In this study, we demonstrate the strong neutralization capacity of the monoclonal antibody #3327 and characterize its activity. GP residues that are required for recognition and neutralization were found to be located both in the internal fusion loop and in the receptor-binding domain. Analysis of Ebola virus entry in the presence of #3327 allows us to hypothesize that this antibody binds to the virus particle before internalization and endosomal processing of GP and likely prevents the final viral fusion step. Importantly, #3327 is able to block entry of virions bearing GP that contain the Q508 escape mutation common to a number of virus-neutralizing antibodies, and therefore provides future perspectives for treatment strategies against Ebola virus infection.

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

    Directory of Open Access Journals (Sweden)

    Steven B Bradfute

    Full Text Available 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.

  4. Role of Natural Killer Cells in Innate Protection Against Lethal Ebola Virus Infection

    Science.gov (United States)

    2007-11-02

    acute, progressive hemorrhagic fever with mortality rates of up to 90% (1, 2). The key initiators of innate immunity, including monocytes, macrophages...particle vaccine (VRP) expressing Ebola VP40 or Lassa N (a gift of M.K. Hart, United States Army Medical Re- search Institute of Infectious Diseases...with VRP-encoding Ebola VP40 blocked IFN- se- cretion induced by the VLPs, whereas control sera from mice vaccinated with a VRP encoding the Lassa virus

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

    Directory of Open Access Journals (Sweden)

    Philip Baba Adongo

    Full Text Available 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.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.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.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.

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

    Science.gov (United States)

    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.

  7. Support services for survivors of ebola virus disease - Sierra Leone, 2014.

    Science.gov (United States)

    Lee-Kwan, Seung Hee; DeLuca, Nickolas; Adams, Monica; Dalling, Matthew; Drevlow, Elizabeth; Gassama, Gladys; Davies, Tina

    2014-12-19

    As of December 6, 2014, Sierra Leone reported 6,317 laboratory-confirmed cases of Ebola virus disease (Ebola), the highest number of reported cases in the current West Africa epidemic. The Sierra Leone Ministry of Health and Sanitation reported that as of December 6, 2014, there were 1,181 persons who had survived and were discharged. Survivors from previous Ebola outbreaks have reported major barriers to resuming normal lives after release from treatment, such as emotional distress, health issues, loss of possessions, and difficulty regaining their livelihoods. In August 2014, a knowledge, attitude, and practice survey regarding the Ebola outbreak in Sierra Leone, administered by a consortium of partners that included the Ministry of Health and Sanitation, UNICEF, CDC, and a local nongovernmental organization, Focus 1000, found that 96% of the general population respondents reported some discriminatory attitude towards persons with suspected or known Ebola. Access to increased psychosocial support, provision of goods, and family and community reunification programs might reduce these barriers. Survivors also have unique potential to contribute to the Ebola response, particularly because survivors might have some immunity to the same virus strain. In previous outbreaks, survivors served as burial team members, contact tracers, and community educators promoting messages that seeking treatment improves the chances for survival and that persons who survived Ebola can help their communities. As caregivers in Ebola treatment units, survivors have encouraged patients to stay hydrated and eat and inspired them to believe that they, too, can survive. Survivors regaining livelihood through participation in the response might offset the stigma associated with Ebola.

  8. 埃博拉出血热及埃博拉病毒的研究进展%Progress on Ebola Hemorrhagic Fever and Ebola Viruses

    Institute of Scientific and Technical Information of China (English)

    许黎黎; 张连峰

    2011-01-01

    Ebola virus, which was first identified in 1976 during outbreaks in Ebola River vally, is an zoonotic pathogen that causes highly lethal hemorrhagic fever syndrome in human and nonhuman primates. Since the high mortality rates of Ebola viruses, up to 88% in humans, Ebola viruses are listed in the most dangerous viruses to humans by World Health Organization. Comprehending the characterization and pathogenesis of Ebola hemorrhagic fever and Ebola viruses, is very important for the prevention and control of this disease.%埃博拉病毒町以引起一种人畜共患烈性传染病,即埃博托出血热,此病于1976年始发于埃博拉河流域,并且于该区域严重流行,故而得名.人类一旦感染埃博拉病毒,死亡率可高达88%,从而引起医学界的广泛关注,世界卫生组织已将埃博拉病毒列为对人类危害最为严重的病毒之一.深入地了解埃博拉出血热及埃博拉病毒,及其致病机理,对于埃博拉出血热的预防和控制具有非常重要的意义.

  9. Guidance to Companies on Referring to Registered Disinfectant Products that Meet the CDC Criteria for Use Against the Ebola Virus

    Science.gov (United States)

    There are no EPA-registered products with label claims against the Ebola virus, but enveloped viruses such as Ebola are susceptible to many hospital disinfectants used to disinfect hard, non-porous surfaces. CDC guidance addresses use of such products.

  10. Complete Genome Sequence of an Ebola Virus Isolate Imported from Sierra Leone to Germany Determined by Circle Sequencing

    Science.gov (United States)

    Mengel, Jan Philipp; Lissin, Artur; Biedenkopf, Nadine; Schultze, Tilman; Mannala, Gopala Krishna; Schudt, Gordian; Kann, Gerrit; Wolf, Timo; Eickmann, Markus; Becker, Stephan

    2016-01-01

    We report here a complete genome sequence of Ebola virus Makona from a nonfatal patient sample that originated in Sierra Leone during the last Ebola virus outbreak in West Africa (species Zaire ebolavirus) using a highly accurate circle sequencing (Cir-seq) method.

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

    Science.gov (United States)

    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.

  12. Individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with Lassa and Ebola viruses.

    Science.gov (United States)

    Pushko, P; Geisbert, J; Parker, M; Jahrling, P; Smith, J

    2001-12-01

    Lassa and Ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. Although lethal human disease outbreaks have been confined so far to sub-Saharan Africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into North America and Europe. In the present study, we developed experimental individual vaccines for Lassa virus and bivalent vaccines for Lassa and Ebola viruses that are based on an RNA replicon vector derived from an attenuated strain of Venezuelan equine encephalitis virus. The Lassa and Ebola virus genes were expressed from recombinant replicon RNAs that also encoded the replicase function and were capable of efficient intracellular self-amplification. For vaccinations, the recombinant replicons were incorporated into virus-like replicon particles. Guinea pigs vaccinated with particles expressing Lassa virus nucleoprotein or glycoprotein genes were protected from lethal challenge with Lassa virus. Vaccination with particles expressing Ebola virus glycoprotein gene also protected the animals from lethal challenge with Ebola virus. In order to evaluate a single vaccine protecting against both Lassa and Ebola viruses, we developed dual-expression particles that expressed glycoprotein genes of both Ebola and Lassa viruses. Vaccination of guinea pigs with either dual-expression particles or with a mixture of particles expressing Ebola and Lassa virus glycoprotein genes protected the animals against challenges with Ebola and Lassa viruses. The results showed that immune responses can be induced against multiple vaccine antigens coexpressed from an alphavirus replicon and suggested the possibility of engineering multivalent vaccines based upon alphavirus vectors for arenaviruses, filoviruses, and possibly other emerging pathogens.

  13. MANAGEMENT OF THE PATIENTS WITH EBOLA VIRUS DESEASE

    Directory of Open Access Journals (Sweden)

    Bondarenko A.V.

    2015-05-01

    Full Text Available The largest in the history of the Ebola virus disease (EVD outbreak was recorded in 2014. There are 9976 lethal cases from 24282 infected people (data up to 8 March 2015 within a year from the time of its announcement in West African countries. The outbreak started in Guinea then spread to neighbouring Sierra Leone and Liberia across land borders, to Senegal and Mali by ground transportation, and to Nigeria, Spain, United States of America and the United Kingdom by air transport. If in the previous years disease was the problem of endemic countries in Central Africa nowadays it became a major medical and social problem all over the world. The effective licensed drugs for the treatment and prevention of the disease does not currently exist, experimental drugs (ZMapp, TKM-100802, AVI 7537 Sarepta, Favipiravir T705, BCX4430 Biocryst, Brincidofovir, Nano Silver et al. are extremely limited, and they are still under investigation. Evidence their effectiveness is suggestive, but not based on solid scientific data from clinical trials. Safety is also unknown. There is consensus that the hyperimmune globulin or convalescent plasma containing high titres of specific neutralizing antibodies to Ebola virus, which leads to decrease the viral load in the blood, is considering to use in an epidemic area as a matter of priority. Experience has shown that the risk of EVD importation into Ukraine remains high despite all preventive measures. Thereby health care providers should be prepared to confront this problem and know how to manage the symptoms of the disease. The management of the patients with EVD mainly should be aimed to early recognition of severe disease and its complications, in combination with appropriate symptomatic therapy. Health care workers should pay careful attention to standard precautions and wear special protective clothing, including goggles, masks and gloves while providing clinical care. Management of intoxication, dehydration

  14. Laboratory support during and after the Ebola virus endgame: Towards a sustained laboratory infrastructure

    NARCIS (Netherlands)

    I. Goodfellow; C.B.E.M. Reusken (Chantal); M.P.G. Koopmans D.V.M. (Marion)

    2015-01-01

    textabstractThe Ebola virus epidemic in West Africa is on the brink of entering a second phase in which the (inter)national efforts to slow down virus transmission will be engaged to end the epidemic. The response community must consider the longevity of their current laboratory support, as it is es

  15. Laboratory support during and after the Ebola virus endgame: Towards a sustained laboratory infrastructure

    NARCIS (Netherlands)

    I. Goodfellow; C.B.E.M. Reusken (Chantal); M.P.G. Koopmans D.V.M. (Marion)

    2015-01-01

    textabstractThe Ebola virus epidemic in West Africa is on the brink of entering a second phase in which the (inter)national efforts to slow down virus transmission will be engaged to end the epidemic. The response community must consider the longevity of their current laboratory support, as it is

  16. Managing Potential Laboratory Exposure to Ebola Virus by Using a Patient Biocontainment Care Unit

    Science.gov (United States)

    2008-06-01

    et al. (8) with permission. †JEB, Japanese encephalitis virus B; Ebola/ Lassa , potential exposure to these viruses . ‡IP, immune plasma from...expo- sure to BSL-4 viruses , 8 involved percutaneous injury and 6 involved potential aerosol exposure. Eight persons (5 evaluated for exposure to Lassa ...potentially exposed to Lassa virus also received intrave- nous ribavirin. No patient developed disease or serocon- verted. From 1985 through 2003, no

  17. Animal models for Ebola and Marburg virus infections

    Directory of Open Access Journals (Sweden)

    Eri eNakayama

    2013-09-01

    Full Text Available 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 nonhuman 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.

  18. Animal models for Ebola and Marburg virus infections.

    Science.gov (United States)

    Nakayama, Eri; Saijo, Masayuki

    2013-09-05

    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.

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Nanikaly Moyen

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

  1. Virus genomes reveal factors that spread and sustained the Ebola epidemic

    DEFF Research Database (Denmark)

    Dudas, Gytis; Carvalho, Luiz Max; Bedford, Trevor

    2017-01-01

    The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We...... test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission...... had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions...

  2. Ebola vaccine and treatment.

    Science.gov (United States)

    Takada, Ayato

    2015-01-01

    Filoviruses (Ebola and Marburg viruses) cause severe hemorrhagic fever in humans and nonhuman primates. No effective prophylaxis or treatment for filovirus diseases is yet commercially available. The recent outbreak of Ebola virus disease in West Africa has accelerated efforts to develop anti-Ebola virus prophylaxis and treatment, and unapproved drugs were indeed used for the treatment of patients during the outbreak. This article reviews previous researches and the latest topics on vaccine and therapy for Ebola virus disease.

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

    Directory of Open Access Journals (Sweden)

    Sophie Smither

    2016-07-01

    Full Text Available 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.

  4. Ebola virus infection induces irregular dendritic cell gene expression.

    Science.gov (United States)

    Melanson, Vanessa R; Kalina, Warren V; Williams, Priscilla

    2015-02-01

    Filoviruses subvert the human immune system in part by infecting and replicating in dendritic cells (DCs). Using gene arrays, a phenotypic profile of filovirus infection in human monocyte-derived DCs was assessed. Monocytes from human donors were cultured in GM-CSF and IL-4 and were infected with Ebola virus Kikwit variant for up to 48 h. Extracted DC RNA was analyzed on SuperArray's Dendritic and Antigen Presenting Cell Oligo GEArray and compared to uninfected controls. Infected DCs exhibited increased expression of cytokine, chemokine, antiviral, and anti-apoptotic genes not seen in uninfected controls. Significant increases of intracellular antiviral and MHC I and II genes were also noted in EBOV-infected DCs. However, infected DCs failed to show any significant difference in co-stimulatory T-cell gene expression from uninfected DCs. Moreover, several chemokine genes were activated, but there was sparse expression of chemokine receptors that enabled activated DCs to home to lymph nodes. Overall, statistically significant expression of several intracellular antiviral genes was noted, which may limit viral load but fails to stop replication. EBOV gene expression profiling is of vital importance in understanding pathogenesis and devising novel therapeutic treatments such as small-molecule inhibitors.

  5. Evasion of interferon responses by Ebola and Marburg viruses.

    Science.gov (United States)

    Basler, Christopher F; Amarasinghe, Gaya K

    2009-09-01

    The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), cause frequently lethal viral hemorrhagic fever. These infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. Consistent with this, filoviruses have been found to encode proteins VP35 and VP24 that block host interferon (IFN)-alpha/beta production and inhibit signaling downstream of the IFN-alpha/beta and the IFN-gamma receptors, respectively. VP35, which is a component of the viral nucleocapsid complex and plays an essential role in viral RNA synthesis, acts as a pseudosubstrate for the cellular kinases IKK-epsilon and TBK-1, which phosphorylate and activate interferon regulatory factor 3 (IRF-3) and interferon regulatory factor 7 (IRF-7). VP35 also promotes SUMOylation of IRF-7, repressing IFN gene transcription. In addition, VP35 is a dsRNA-binding protein, and mutations that disrupt dsRNA binding impair VP35 IFN-antagonist activity while leaving its RNA replication functions intact. The phenotypes of recombinant EBOV bearing mutant VP35s unable to inhibit IFN-alpha/beta demonstrate that VP35 IFN-antagonist activity is critical for full virulence of these lethal pathogens. The structure of the VP35 dsRNA-binding domain, which has recently become available, is expected to provide insight into how VP35 IFN-antagonist and dsRNA-binding functions are related. The EBOV VP24 protein inhibits IFN signaling through an interaction with select host cell karyopherin-alpha proteins, preventing the nuclear import of otherwise activated STAT1. It remains to be determined to what extent VP24 may also modulate the nuclear import of other host cell factors and to what extent this may influence the outcome of infection. Notably, the Marburg virus VP24 protein does not detectably block STAT1 nuclear import, and, unlike EBOV, MARV infection inhibits STAT1 and STAT2 phosphorylation. Thus, despite their similarities, there are fundamental differences by which

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

    Science.gov (United States)

    Vingolo, Enzo Maria; Messano, Giuseppe Alessio; Fragiotta, Serena; 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

  7. Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys.

    Directory of Open Access Journals (Sweden)

    Wendelien B Oswald

    2007-01-01

    Full Text Available Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.

  8. Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Highly Protective, Non-infectious Vaccine Against Ebola Virus Challenge

    Science.gov (United States)

    2016-07-01

    challenge 2 Nicholas J. Lennemann1, #, Andrew S. Herbert2, Rachel Brouillette1, Bethany Rhein1, Russell A. 3 Bakken2, Katherine J. Perschbacher1...vaccination regime protected mice against lethal challenge with mouse-adapted 27 Ebola virus (MA-EBOV) in a dose-dependent manner. As N-linked glycans are...effective immunity. High doses of GP/VSV partially or fully 30 denuded of N-linked glycans on GP1 protected mice against MA-EBOV challenge . However, 31

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

    Science.gov (United States)

    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.

  10. hand hygiene practices post ebola virus disease outbreak in a ...

    African Journals Online (AJOL)

    2014-10-20

    Oct 20, 2014 ... The declaration of Nigeria as an Ebola-free country by the World Health ... and multivariate logistic regression were used to determine associations between predictors of ..... Lashley FR, Jerry D. Emerging infectious diseases: ...

  11. Ebola Virus: New Insights into Disease Aetiopathology and Possible Therapeutic Interventions

    Science.gov (United States)

    2007-11-02

    targeting conserved regions of influenza virus genes in mice (Ref. 135). Although there have been no published studies evaluating the efficacy of RNAi as a...administration in influenza -virus- infected mice (Ref. 135). Budding inhibitors EBOV budding is mediated by two proline-rich motifs – PPxY and PTAP...pathogenesis of an emerging paramyxoviral zoonosis . Am J Pathol 161, 2153- 2167, PubMed: 12466131 87 Murphy, F.A. (1978) Pathology of Ebola virus

  12. Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates

    OpenAIRE

    Geisbert, Thomas W.; Daddario-DiCaprio, Kathleen M.; Lewis, Mark G.; Geisbert, Joan B.; Allen Grolla; Anders Leung; Jason Paragas; Lennox Matthias; Smith, Mark A.; Jones, Steven M.; Hensley, Lisa E.; Heinz Feldmann; Jahrling, Peter B.

    2008-01-01

    Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatmen...

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

    Science.gov (United States)

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

    2015-09-01

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

  14. Computational Modelling and Optimal Control of Ebola Virus Disease with non-Linear Incidence Rate

    Science.gov (United States)

    Takaidza, I.; Makinde, O. D.; Okosun, O. K.

    2017-03-01

    The 2014 Ebola outbreak in West Africa has exposed the need to connect modellers and those with relevant data as pivotal to better understanding of how the disease spreads and quantifying the effects of possible interventions. In this paper, we model and analyse the Ebola virus disease with non-linear incidence rate. The epidemic model created is used to describe how the Ebola virus could potentially evolve in a population. We perform an uncertainty analysis of the basic reproductive number R 0 to quantify its sensitivity to other disease-related parameters. We also analyse the sensitivity of the final epidemic size to the time control interventions (education, vaccination, quarantine and safe handling) and provide the cost effective combination of the interventions.

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

    Science.gov (United States)

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

    2015-01-01

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

  16. A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.

    Directory of Open Access Journals (Sweden)

    Yoshimi Tsuda

    2011-08-01

    Full Text Available BACKGROUND: Human outbreaks of Ebola virus (EBOV are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV vector expressing a CD8+ T cell epitope from the nucleoprotein (NP of Zaire ebolavirus (ZEBOV (MCMV/ZEBOV-NP(CTL. MCMV/ZEBOV-NP(CTL induced high levels of long-lasting (>8 months CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations.

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

    Science.gov (United States)

    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

    2015-12-02

    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.

  18. The Ebola Virus VP30-NP Interaction Is a Regulator of Viral RNA Synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Kirchdoerfer, Robert N.; Moyer, Crystal L.; Abelson, Dafna M.; Saphire, Erica Ollmann (Scripps)

    2016-10-18

    Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays. We have found that the VP30 C-terminal domain interacts with a short peptide in the C-terminal region of NP. Further, we have solved crystal structures of the VP30-NP complex for both Ebola and Marburg viruses. These structures reveal that a conserved, proline-rich NP peptide binds a shallow hydrophobic cleft on the VP30 C-terminal domain. Structure-guided Ebola virus VP30 mutants have altered affinities for the NP peptide. Correlation of these VP30-NP affinities with the activity for each of these mutants in a cell-based mini-replicon assay suggests that the VP30-NP interaction plays both essential and inhibitory roles in Ebola virus RNA synthesis.

  19. Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.

    Science.gov (United States)

    Salata, Cristiano; Baritussio, Aldo; Munegato, Denis; Calistri, Arianna; Ha, Huy Riem; Bigler, Laurent; Fabris, Fabrizio; Parolin, Cristina; Palù, Giorgio; Mirazimi, Ali

    2015-07-01

    Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EVD.

  20. Ebola virus infection%埃博拉病毒感染

    Institute of Scientific and Technical Information of China (English)

    钱渊

    2015-01-01

    Ebola,known as Ebola hemorrhagic fever,is caused by infection with a virus of the fami-ly Filoviridae,genus Ebolavirus. Ebola is circulating in some of the west Africa countries and causing outb-reacks and epidemic with high mortality. The virus can be spread in humans by direct contact with blood or body fruit of infected one through broken skin or mucous membranes. The virus can not be spread by air or water. The symptoms of Ebola include fever,severe headache,muscle pain,weakness,fatigue,diarrhea,vomi-ting,abdominal( stomach) pain and unexplained hemorrhage. Symptoms of Ebola and complications are trea-ted as they appear. Recovery from Ebola depends on good supportive care and the patient′s immune response. Those people recovered from Ebola developed antibodies against Ebola virus and last long period. No ap-proved vaccine or medicine is available for Ebola.%埃博拉病毒属丝状病毒科埃博拉病毒属,感染人类所致疾病为埃博拉出血热,致死率高。在非洲一些国家流行,传播途径为人-人,方式为直接接触患者的血液或体液,病毒通过破损的皮肤或黏膜感染;不通过空气和水传播。感染的症状有发热、剧烈的头痛、肌肉疼痛、虚弱、疲劳、腹泻、呕吐、腹痛(胃疼)和无法解释的出血(大出血或者渗血)。治疗的方法为对症,疾病的恢复依靠支持疗法和患者的免疫反应,幸存者在恢复期产生埃博拉特异性抗体。尚无获批准的疫苗和药物。

  1. Distinct Mechanisms of Entry by Envelope Glycoproteins of Marburg and Ebola (Zaire) Viruses

    Science.gov (United States)

    Chan, Stephen Y.; Speck, Roberto F.; Ma, Melissa C.; Goldsmith, Mark A.

    2000-01-01

    Since the Marburg (MBG) and Ebola (EBO) viruses have sequence homology and cause similar diseases, we hypothesized that they associate with target cells by similar mechanisms. Pseudotype viruses prepared with a luciferase-containing human immunodeficiency virus type 1 backbone and packaged by the MBG virus or the Zaire subtype EBO virus glycoproteins (GP) mediated infection of a comparable wide range of mammalian cell types, and both were inhibited by ammonium chloride. In contrast, they exhibited differential sensitivities to treatment of target cells with tunicamycin, endoglycosidase H, or protease (pronase). Therefore, while they exhibit certain functional similarities, the MBG and EBO virus GP interact with target cells by distinct processes. PMID:10775638

  2. Designing Efficacious Vesicular Stomatitis Virus-Vectored Vaccines Against Ebola Virus.

    Science.gov (United States)

    Wong, Gary; Qiu, Xiangguo

    2016-01-01

    Infection with the Ebola virus (EBOV) causes an aggressive hemorrhagic disease in humans and nonhuman primates. Traditional approaches, such as vaccination with inactivated virion preparations, have had limited efficacy, whereas immunization with live-attenuated EBOV is not feasible due to the highly lethal nature of the pathogen. This has necessitated the development of other approaches towards an effective EBOV vaccine. Over the past decade, recombinant viruses expressing the EBOV glycoprotein (GP) have constituted the most promising platforms, as evidenced by their ability to protect naïve nonhuman primates from a lethal EBOV challenge. The vesicular stomatitis virus (VSV) is one such vector and is currently progressing through the clinical pipeline. This chapter presents methodologies for the design, cloning, rescue, and preparation of live, recombinant VSV vaccines expressing GP for research purposes.

  3. Preparedness of institutions around the world for managing patients with Ebola virus disease: an infection control readiness checklist

    NARCIS (Netherlands)

    Tartari, E.; Allegranzi, B.; Ang, B.; Calleja, N.; Collignon, P.; Hopman, J.; Lang, L.; Lee, L.C.; Ling, M.L.; Mehtar, S.; Tambyah, P.A.; Widmer, A.; Voss, A.

    2015-01-01

    BACKGROUND: In response to global concerns about the largest Ebola virus disease (EVD), outbreak to-date in West Africa documented healthcare associated transmission and the risk of global spread, the International Society of Chemotherapy (ISC) Infection Control Working Group created an Ebola Infect

  4. Preparedness of institutions around the world for managing patients with Ebola virus disease: an infection control readiness checklist

    NARCIS (Netherlands)

    Tartari, E.; Allegranzi, B.; Ang, B.; Calleja, N.; Collignon, P.; Hopman, J.; Lang, L.; Lee, L.C.; Ling, M.L.; Mehtar, S.; Tambyah, P.A.; Widmer, A.; Voss, A.

    2015-01-01

    BACKGROUND: In response to global concerns about the largest Ebola virus disease (EVD), outbreak to-date in West Africa documented healthcare associated transmission and the risk of global spread, the International Society of Chemotherapy (ISC) Infection Control Working Group created an Ebola

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

    Science.gov (United States)

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

    2016-03-01

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

  6. The rhetorical construction of the predatorial virus: a Burkian analysis of nonfiction accounts of the Ebola virus.

    Science.gov (United States)

    Weldon, R A

    2001-01-01

    Over the past 5 years, a new subgenre of horror films, referred to as plague films, has turned our focus to the threat of a hemorrhagic viral pandemic, comparable to the Spanish Flu epidemic of 1916. Based on the Ebola viral outbreaks of 1976, various writers have presented their accounts under the guise of increasing interest and prevention strategies. Disregarding inappropriate health care practices as the cause of these epidemics, accountability is refocused onto the rhetorically constructed, predatory nature of the virus. By employing Burke's theory of dramatism and pentadic analysis, the author examines this rhetorical construction of Ebola as a predatorial virus and its implications for public perceptions of public health endeavors.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    John A Stanturf

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

  9. Deciphering Dynamics of Recent Epidemic Spread and Outbreak in West Africa: The Case of Ebola Virus

    Science.gov (United States)

    Upadhyay, Ranjit Kumar; Roy, Parimita

    Recently, the 2014 Ebola virus (EBOV) outbreak in West Africa was the largest outbreak to date. In this paper, an attempt has been made for modeling the virus dynamics using an SEIR model to better understand and characterize the transmission trajectories of the Ebola outbreak. We compare the simulated results with the most recent reported data of Ebola infected cases in the three most affected countries Guinea, Liberia and Sierra Leone. The epidemic model exhibits two equilibria, namely, the disease-free and unique endemic equilibria. Existence and local stability of these equilibria are explored. Using central manifold theory, it is established that the transcritical bifurcation occurs when basic reproduction number passes through unity. The proposed Ebola epidemic model provides an estimate to the potential number of future cases. The model indicates that the disease will decline after peaking if multisectorial and multinational efforts to control the spread of infection are maintained. Possible implication of the results for disease eradication and its control are discussed which suggests that proper control strategies like: (i) transmission precautions, (ii) isolation and care of infectious Ebola patients, (iii) safe burial, (iv) contact tracing with follow-up and quarantine, and (v) early diagnosis are needed to stop the recurrent outbreak.

  10. The Macroeconomic Impact of Ebola Virus Disease (Evd: A Contribution to the Empirics of Growth

    Directory of Open Access Journals (Sweden)

    Obukohwo Oba Efayena

    2016-04-01

    Full Text Available The paper addressed the formulation of a macro model to capture the macroeconomic impact of the Ebola Virus Disease (EVD. Previous studies has adopted various models such as the dynamic computable general equilibrium (CGE model, endogenous model and the LINKAGE model, but there is dire need to generate a step-by-step model which will comprehensively capture how the Ebola Virus Disease (EVD impacts on macroeconomic variables. Adopting the traditional neoclassical growth model, the model aggregated the various macroeconomic variables as well as captured the epidemic’s strain on each of these variables. The paper also empirically shows that the Ebola Virus Disease (EVD has direct, indirect and deferred indirect cost implications for the economy. Using case studies of countries in Africa, the study evaluated how the Ebola Virus Disease (EVD has affected the macroeconomic status of selected economies. The findings imply that there is dire need to control the spread of the deadly plague. The paper contribute immensely to empirical studies in the field of macroeconomics.

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

    NARCIS (Netherlands)

    Richards, P.; Amara, J.; Ferme, M.C.; Kamara, P.; Mokuwa, E.; Sheriff, A.I.; Suluku, R.; Voors, M.J.

    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 humanto- human contact. Social factors are thus clearly important to understand the epidemic and ways in which it might be stopped, bu

  12. Genotypic anomaly in ebola virus strains circulating in magazine wharf Area, Freetown, Sierra Leone, 2015

    NARCIS (Netherlands)

    S.L. Smits (Saskia); S.D. Pas (Suzan); C.B.E.M. Reusken (Chantal); B.L. Haagmans (Bart); P. Pertile; C. Cancedda; K. Dierberg; I. Wurie; A. Kamara; D. Kargbo; S.L. Caddy; A. Arias; L. Thorne; J. Lu; U. Jah; I. Goodfellow; M.P.G. Koopmans D.V.M. (Marion)

    2015-01-01

    textabstractThe Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, simil

  13. Clinical management of ebola virus disease in the United States and Europe

    NARCIS (Netherlands)

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

    2016-01-01

    Background Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited. METHODS We reviewed available clinical, laboratory, and virologic data fro

  14. New Ebola virus in 2014:do identified mutated amino acids in the viral sequences sense?

    Institute of Scientific and Technical Information of China (English)

    Somsri; Wiwanitkit; Viroj; Wiwanitkit

    2014-01-01

    To the editor,The problem of new Ebola virus outbreak in 2014 is thepresent big consideration of medical society.The new infectionoccurs in West Africa and causes infection in thousands oflocal people,and the trend of the worldwide expansion leads to serious concerns of the medical society. The reason why the

  15. Biomarker Correlates of Survival in Pediatric Patients with Ebola Virus Disease

    Centers for Disease Control (CDC) Podcasts

    2014-08-19

    Dr. Mike Miller reads an abridged version of the article, Biomarker Correlates of Survival in Pediatric Patients with Ebola Virus Disease.  Created: 8/19/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/19/2014.

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

    Science.gov (United States)

    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.

  17. Ebola Virus RNA Stability in Human Blood and Urine in West Africa's Environmental Conditions.

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Protective Monotherapy Against Lethal Ebola Virus Infection by a Potently Neutralizing Antibody

    Science.gov (United States)

    2016-07-11

    These mAbs bind and neutralize recent and 53   previous outbreak strains of Ebola virus, and mediate antibody-dependent cell-54   mediated...dilution. 61   62   Antibody purification , labeling, genetic analysis, and reversion to germline. The 63   usage of VH and VL gene segments was

  20. Clinical management of ebola virus disease in the United States and Europe

    NARCIS (Netherlands)

    Uyeki, Timothy M.; Mehta, Aneesh K.; Davey, Richard T.; Liddell, Allison M.; Wolf, Timo; Vetter, Pauline; Schmiedel, Stefan; Grünewald, Thomas; Jacobs, Michael; Arribas, Jose R.; Evans, Laura; Hewlett, Angela L.; Brantsaeter, Arne B.; Ippolito, Giuseppe; Rapp, Christophe; Hoepelman, Andy I M|info:eu-repo/dai/nl/074382160; Gutman, Julie

    2016-01-01

    Background Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited. METHODS We reviewed available clinical, laboratory, and virologic data fro

  1. Clinical management of ebola virus disease in the United States and Europe

    NARCIS (Netherlands)

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

    2016-01-01

    Background Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited. METHODS We reviewed available clinical, laboratory, and virologic data

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

    NARCIS (Netherlands)

    Richards, P.; Amara, J.; Ferme, M.C.; Kamara, P.; Mokuwa, E.; Sheriff, A.I.; Suluku, R.; Voors, M.J.

    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 humanto- human contact. Social factors are thus clearly important to understand the epidemic and ways in which it might be stopped,

  3. [Eukaryotic Expression and Immunogenic Research of Recombination Ebola Virus Membrane Protein Gp-Fc].

    Science.gov (United States)

    Zhang, Xiaoguang; Yang, Ren; Wang, Jiao; Wang, Xuan; Hou, Mieling; An, Lina; Zhu, Ying; Cao, Yuxi; Zeng, Yi

    2016-01-01

    We used 293 cells to express the recombinant membrane protein of the Ebola virus. Then, the immunogenicity of the recombinant protein was studied by immunized BALB/c mice. According to the codon use frequency of humans, the gene encoding the extracellular domain of the Ebola virus membrane protein was optimized, synthesized, and inserted into the eukaryotic expression plasmid pXG-Fc to construct the human IgG Fc and Ebola GP fusion protein expression plasmid pXG-modGP-Fc. To achieve expression, the fusion protein expression vector was transfected into high-density 293 cells using transient transfection technology. The recombinant protein was purified by protein A affinity chromatography. BALB/c mice were immunized with the purified fusion protein, and serum antibody titers evaluated by an indirect enzyme-linked immunosorbent assay (ELISA). Purification and analyses of the protein revealed that the eukaryotic expression vector could express the recombinant protein GP-Fc effectively, and that the recombinant protein in the supernatant of the cell culture was present as a dimer. After immunization with the purified recombinant protein, a high titer of antigen-specific IgG could be detected in the serum of immunized mice by indirect ELISA, showing that the recombinant protein had good immunogenicity. These data suggest that we obtained a recombinant protein with good immunogenicity. Our study is the basis for development of a vaccine against the Ebola virus and for screening of monoclonal antibodies.

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

    Science.gov (United States)

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

    2015-10-01

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

  5. The Current Outbreak of Ebola virus is still Continue in Guinea, Liberia and Sierra Leone: A Fact Sheet

    Directory of Open Access Journals (Sweden)

    Tauseef Ahmad

    2015-01-01

    Full Text Available The current outbreak of the Ebola virus occurred in the West Africa and it is the largest and more lethal outbreak in the history of Ebola virus. Thousands of peoples were infected along with thousands of death. The first case of current outbreak of Ebola virus was reported from Guine and acute;e Forestie` re (Forested Guinea, eastern area of Guinea in December 2013 (Ahmad, 2014; Baize et al., 2014; Gatherer, 2014. But in March 2014 the diseases spread so much fast and infected the surrounding countries Liberia and Sierra Leone. While in August 2014 the Ebola virus were reported from the Nigeria (Ahmad, 2014. [Biomed Res Ther 2015; 2(1.000: 193-195

  6. Importation and containment of Ebola virus disease - Senegal, August-September 2014.

    Science.gov (United States)

    Mirkovic, Kelsey; Thwing, Julie; Diack, Papa Amadou

    2014-10-03

    On August 29, 2014, Senegal confirmed its first case of Ebola virus disease (Ebola) in a Guinean man, aged 21 years, who had traveled from Guinea to Dakar, Senegal, in mid-August to visit family. Senegalese medical and public health personnel were alerted about this patient after public health staff in Guinea contacted his family in Senegal on August 27. The patient had been admitted to a referral hospital in Senegal on August 26. He was promptly isolated, and a blood sample was sent for laboratory confirmation; Ebola was confirmed by reverse transcriptase-polymerase chain reaction at Institut Pasteur Dakar on August 29. The patient's mother and sister had been admitted to an Ebola treatment unit in Guinea on August 26, where they had named the patient as a contact and reported his recent travel to Senegal. Ebola was likely transmitted to the family from the brother of the patient, who had traveled by land from Sierra Leone to Guinea in early August seeking treatment from a traditional healer. The brother died in Guinea on August 10; family members, including the patient, participated in preparing the body for burial.

  7. Feasibility of using melatonin as a new treatment agent for Ebola virus infection: A gene ontology study

    Institute of Scientific and Technical Information of China (English)

    Beuy Joob; Viroj Wiwanitkit

    2016-01-01

    Dear Editor,The effective treatment of the present outbreak Ebola virus is the big challenge for the medical society.Several new therapeutic options are ongoing research.The development of new antiviral and vaccine is the hope for successful management of the infection.However,there are also other alternative ideas for treatment of the Ebola virus infection.An interesting idea is the

  8. Sensitivity to ultraviolet radiation of Lassa, vaccinia, and Ebola viruses dried on surfaces.

    Science.gov (United States)

    Sagripanti, Jose-Luis; Lytle, C David

    2011-03-01

    Germicidal UV (also known as UVC) provides a means to decontaminate infected environments as well as a measure of viral sensitivity to sunlight. The present study determined UVC inactivation slopes (and derived D(37) values) of viruses dried onto nonporous (glass) surfaces. The data obtained indicate that the UV resistance of Lassa virus is higher than that of Ebola virus. The UV sensitivity of vaccinia virus (a surrogate for variola virus) appeared intermediate between that of the two virulent viruses studied. In addition, the three viruses dried on surfaces showed a relatively small but significant population of virions (from 3 to 10 % of virus in the inoculum) that appeared substantially more protected by their environment from the effect of UV than the majority of virions tested. The findings reported in this study should assist in estimating the threat posed by the persistence of virus in environments contaminated during epidemics or after an accidental or intentional release.

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Small molecules with antiviral activity against the Ebola virus [v1; ref status: indexed, http://f1000r.es/523

    OpenAIRE

    Nadia Litterman; Christopher Lipinski; Sean Ekins

    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 r...

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

    Science.gov (United States)

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

    2015-12-01

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

  12. [Preparation of healthcare workers against the threat of Ebola virus disease in Ivory Coast].

    Science.gov (United States)

    Kouassi, Damus Paquin; Ekra, Kouadio Daniel; Angbo-Effi, Odile; Kouakou Ahoussou, Éric Martial; Bliabo, Guy Modeste; Yéo, Nawa Samuel; Coulibaly, Daouda; Dagnan, N Cho Simplice

    2016-01-01

    Since the declaration of the Ebola virus disease outbreak in West Africa, the government of Ivory Coast has organized the training of medical staff in all health regions of the country. This study was conducted one month after this training in order to assess the knowledge, attitudes and practices of health workers concerning Ebola virus disease in an Ivory Coast health region their preparation in relation to this disease. In May-June 2014, we conducted a descriptive cross-sectional study of 176 health workers from private and public health facilities in 5 health districts. Among the respondents, 15.5% attended the training on Ebola disease organized by the Ministry of Health. They knew that the disease is transmitted from animals to humans by body fluids (85.6%), and from human to human by body fluids of a sick person or a cadavre (82.8%). 96% said they were at risk of contracting the disease. In view of the persistent threat of the disease, ignorance of certain aspects of the disease could be a weakness in the prevention of nosocomial transmission of the disease. Knowledge of the disease should lead to adoption of prevention measures. However, routine use of protection equipment, including gloves, depends on its availability. The lack of infection prevention and control equipment could be a weak point in preparation of the response to an Ebola disease outbreak.

  13. Distinguishing epidemiological features of the 2013–2016 West Africa Ebola virus disease outbreak

    Science.gov (United States)

    Shultz, James M.; Espinel, Zelde; Espinola, Maria; Rechkemmer, Andreas

    2016-01-01

    ABSTRACT The 2013–2016 West Africa Ebola virus disease epidemic was notable for its scope, scale, and complexity. This briefing presents a series of distinguishing epidemiological features that set this outbreak apart. Compared to one concurrent and 23 previous outbreaks of the disease over 40 years, this was the only occurrence of Ebola virus disease involving multiple nations and qualifying as a pandemic. Across multiple measures of magnitude, the 2013–2016 outbreak was accurately described using superlatives: largest and deadliest in terms of numbers of cases and fatalities; longest in duration; and most widely dispersed geographically, with outbreak-associated cases occurring in 10 nations. In contrast, the case-fatality rate was much lower for the 2013–2016 outbreak compared to the other 24 outbreaks. A population of particular interest for ongoing monitoring and public health surveillance is comprised of more than 17,000 “survivors,” Ebola patients who successfully recovered from their illness. The daunting challenges posed by this outbreak were met by an intensive international public health response. The near-exponential rate of increase of incident Ebola cases during mid-2014 was successfully slowed, reversed, and finally halted through the application of multiple disease containment and intervention strategies. PMID:28229017

  14. Application of unweighted pair group methods with arithmetic average (UPGMA) for identification of kinship types and spreading of ebola virus through establishment of phylogenetic tree

    Science.gov (United States)

    Andriani, Tri; Irawan, Mohammad Isa

    2017-08-01

    Ebola Virus Disease (EVD) is a disease caused by a virus of the genus Ebolavirus (EBOV), family Filoviridae. Ebola virus is classifed into five types, namely Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Bundibugyo ebolavirus (BEBOV), Tai Forest ebolavirus also known as Cote d'Ivoire ebolavirus (CIEBOV), and Reston ebolavirus (REBOV). Identification of kinship types of Ebola virus can be performed using phylogenetic trees. In this study, the phylogenetic tree constructed by UPGMA method in which there are Multiple Alignment using Progressive Method. The results concluded that the phylogenetic tree formation kinship ebola virus types that kind of Tai Forest ebolavirus close to Bundibugyo ebolavirus but the layout state ebola epidemic spread far apart. The genetic distance for this type of Bundibugyo ebolavirus with Tai Forest ebolavirus is 0.3725. Type Tai Forest ebolavirus similar to Bundibugyo ebolavirus not inuenced by the proximity of the area ebola epidemic spread.

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

    Science.gov (United States)

    Ohimain, Elijah Ige

    2016-01-04

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

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

    Science.gov (United States)

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

    2016-02-01

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

  17. In Sillico Analysis of Newly Identified Potential Drug Lead Compound against VP40 for the Treatment of Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    *Biswadip Bandyopadhyay

    2016-11-01

    Full Text Available Ebola Virus (EBOV, also referred as Zaire Ebola Virus, member of filoviridae family, is a single stranded, filamentous, enveloped, mononegavirales virus. It causes acute hemorrhagic fever which is naturally resistant to various antibiotics. After the outbreak of Ebola virus, the CADD (Computer Aided Drug Discovery became necessary as classical model of drug discovery takes lots of time to find target protein and potential lead compound. Computational techniques made it much easier. The matrix protein of Ebola VP40 whose virulent activity and functions in pathogenesis affirmed it as a potential drug target. To inhibit Ebola infection, CADD and molecular docking approaches are one of the effective tools to discover new drug leads against these sporadic targets. In this study lead compounds identified that matches the drug likeliness criteria using “Lipinski’s rule of five” for different crystalline structures of target receptor protein. The discovery of such drug lead molecules which inhibits those protein molecules may constitute successful multidrug resistant Ebola virus infection.

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

    Energy Technology Data Exchange (ETDEWEB)

    Papaneri, Amy B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Cann, Jennifer A.; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Blaney, Joseph E., E-mail: jblaney@niaid.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)

    2012-12-05

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

  19. Outbreaks-of Ebola virus disease in the West African sub-region.

    Science.gov (United States)

    Osungbade, K O; Oni, A A

    2014-06-01

    Five West African countries, including Nigeria are currently experiencing the largest, most severe, most complex outbreak of Ebola virus disease in history. This paper provided a chronology of outbreaks of Ebola virus disease in the West African sub-region and provided an update on efforts at containing the present outbreak. Literature from Pubmed (MEDLINE), AJOL, Google Scholar and Cochrane database were reviewed. Outbreaks of Ebola, virus disease had frequently occurred mainly in Central and East African countries. Occasional outbreaks reported from outside of Africa were due to laboratory contamination and imported monkeys in quarantine facilities. The ongoing outbreak in West Africa is the largest and first in the sub-region; the number of suspected cases and deaths from this single current outbreak is already about three times the total of all cases and deaths from previous known outbreaks in 40 years. Prevention and control efforts are hindered not only by lack of a known vaccine and virus-specific treatment, but also by weak health systems, poor sanitation, poor personal hygiene and cultural beliefs and practices, including myths and misconceptions about Ebola virus disease--all of which are prevalent in affected countries. Constrained by this situation, the World Health Organisation departed from the global standard and recommended the use of not yet proven treatments to treat or prevent the disease in humans on ethical and evidential grounds. The large number of people affected by the present outbreak in West Africa and the high case-fatality rate calls for accelerated evaluation and development of the investigational medical interventions for life saving and curbing the epidemic. Meanwhile, existing interventions such as early detection and isolation, contact tracing and monitoring, and adherence to rigorous procedures of infection prevention and control should be intensified.

  20. Studies of Reservoir Hosts for Marburg virus

    DEFF Research Database (Denmark)

    Swanepoel, Robert; Smit, Sheilagh B; Rollin, Pierre E

    2007-01-01

    To determine reservoir hosts for Marburg virus (MARV), we examined the fauna of a mine in northeastern Democratic Republic of the Congo. The mine was associated with a protracted outbreak of Marburg hemorrhagic fever during 1998-2000. We found MARV nucleic acid in 12 bats, comprising 3.0%-3.6% of 2...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Corey H Basch

    2014-12-01

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

  3. Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates.

    Science.gov (United States)

    Geisbert, Thomas W; Daddario-DiCaprio, Kathleen M; Williams, Kinola J N; Geisbert, Joan B; Leung, Anders; Feldmann, Friederike; Hensley, Lisa E; Feldmann, Heinz; Jones, Steven M

    2008-06-01

    Recombinant vesicular stomatitis virus (VSV) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against Marburg virus when administered after exposure and can partially protect macaques after challenge with Zaire ebolavirus. Here, we administered a VSV vector expressing the Sudan ebolavirus (SEBOV) glycoprotein to four rhesus macaques shortly after exposure to SEBOV. All four animals survived SEBOV challenge, while a control animal that received a nonspecific vector developed fulminant SEBOV hemorrhagic fever and succumbed. This is the first demonstration of complete postexposure protection against an Ebola virus in nonhuman primates and provides further evidence that postexposure vaccination may have utility in treating exposures to filoviruses.

  4. Studies of reservoir hosts for Marburg virus.

    Science.gov (United States)

    Swanepoel, Robert; Smit, Sheilagh B; Rollin, Pierre E; Formenty, Pierre; Leman, Patricia A; Kemp, Alan; Burt, Felicity J; Grobbelaar, Antoinette A; Croft, Janice; Bausch, Daniel G; Zeller, Hervé; Leirs, Herwig; Braack, L E O; Libande, Modeste L; Zaki, Sherif; Nichol, Stuart T; Ksiazek, Thomas G; Paweska, Janusz T

    2007-12-01

    To determine reservoir hosts for Marburg virus (MARV), we examined the fauna of a mine in northeastern Democratic Republic of the Congo. The mine was associated with a protracted outbreak of Marburg hemorrhagic fever during 1998-2000. We found MARV nucleic acid in 12 bats, comprising 3.0%-3.6% of 2 species of insectivorous bat and 1 species of fruit bat. We found antibody to the virus in the serum of 9.7% of 1 of the insectivorous species and in 20.5% of the fruit bat species, but attempts to isolate virus were unsuccessful.

  5. Studies of Reservoir Hosts for Marburg virus

    DEFF Research Database (Denmark)

    Swanepoel, Robert; Smit, Sheilagh B; Rollin, Pierre E

    2007-01-01

    To determine reservoir hosts for Marburg virus (MARV), we examined the fauna of a mine in northeastern Democratic Republic of the Congo. The mine was associated with a protracted outbreak of Marburg hemorrhagic fever during 1998-2000. We found MARV nucleic acid in 12 bats, comprising 3.0%-3.6% of 2...... species of insectivorous bat and 1 species of fruit bat. We found antibody to the virus in the serum of 9.7% of 1 of the insectivorous species and in 20.5% of the fruit bat species, but attempts to isolate virus were unsuccessful. ...

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

    Science.gov (United States)

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

    2015-05-01

    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.

  7. 埃博拉病毒与天然免疫%Ebola virus and innate immunity

    Institute of Scientific and Technical Information of China (English)

    张景熙; 李成忠; 白冲

    2015-01-01

    埃博拉病毒(Ebola virus,EBOV)引起的埃博拉病毒病(Ebola virus disease,EVD)是迄今发现的最凶猛的烈性传染病之一.EVD传染性强、死亡率高,目前尚无特效治疗方法.EBOV感染后能够引起机体出现一系列免疫反应,宿主出现特异性及非特异性抗病毒免疫缺陷是EVD致死的重要原因.本文就EBOV对人体天然免疫功能的影响及其相应对策的研究进展作一综述.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Veljko eVeljkovic

    2015-02-01

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

  10. Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes.

    Science.gov (United States)

    Lüdtke, Anja; Ruibal, Paula; Becker-Ziaja, Beate; Rottstegge, Monika; Wozniak, David M; Cabeza-Cabrerizo, Mar; Thorenz, Anja; Weller, Romy; Kerber, Romy; Idoyaga, Juliana; Magassouba, N'Faly; Gabriel, Martin; Günther, Stephan; Oestereich, Lisa; Muñoz-Fontela, César

    2016-10-15

    A number of previous studies have identified antigen-presenting cells (APCs) as key targets of Ebola virus (EBOV), but the role of APCs in human Ebola virus disease (EVD) is not known. We have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (DCs) in peripheral blood of patients for whom EVD was diagnosed by the European Mobile Laboratory in Guinea. Acute EVD was characterized by reduced levels of circulating nonclassical CD16(+) monocytes with a poor activation profile. In survivors, CD16(+) monocytes were activated during recovery, coincident with viral clearance, suggesting an important role of this cell subset in EVD pathophysiology. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

    Science.gov (United States)

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

    2015-01-01

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

  12. Nucleoprotein-based indirect enzyme-linked immunosorbent assay(indirect ELISA) for detecting antibodies specific to Ebola virus and Marbug virus

    Institute of Scientific and Technical Information of China (English)

    Yi; Huang; Youjie; Zhu; Mengshi; Yang; Zhenqing; Zhang; Donglin; Song; Zhiming; Yuan

    2014-01-01

    Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in antiEbola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G(Ig G) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA’s ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.

  13. Nucleoprotein-based indirect enzyme-linked immunosorbent assay (indirect ELISA) for detecting antibodies specific to Ebola virus and Marbug virus.

    Science.gov (United States)

    Huang, Yi; Zhu, Youjie; Yang, Mengshi; Zhang, Zhenqing; Song, Donglin; Yuan, Zhiming

    2014-12-01

    Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays (ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in anti-Ebola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G (IgG) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.

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

    Science.gov (United States)

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

    2014-12-01

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

  15. Biosafety level-2 laboratory diagnosis of Zaire Ebola virus disease imported from Liberia to Nigeria

    Directory of Open Access Journals (Sweden)

    Olumuyiwa B. Salu

    2016-02-01

    Full Text Available Introduction: Global travel is an efficient route of transmission for highly infectious pathogens and increases the chances of such pathogens moving from high disease-endemic areas to new regions. We describe the rapid and safe identification of the first imported case of Ebola virus disease in a traveler to Lagos, Nigeria, using conventional reverse transcription polymerase chain reaction (RT-PCR in a biosafety level (BSL-2 facility.Case presentation: On 20 July 2014, a traveler arrived from Liberia at Lagos International Airport and was admitted to a private hospital in Lagos, with clinical suspicion of Ebola virus disease.Methodology and Outcome: Blood and urine specimens were collected, transported to the Virology Unit Laboratory at the College of Medicine, University of Lagos, and processed under stringent biosafety conditions for viral RNA extraction. RT-PCR was set-up to query the Ebola, Lassa and Dengue fever viruses. Amplicons for pan-filoviruses were detected as 300 bp bands on a 1.5% agarose gel image; there were no detectable bands for Lassa and Dengue viral RNA. Nucleotide BLAST and phylogenetic analysis of sequence data of the RNA-dependent RNA polymerase (L gene confirmed the sequence to be Zaire ebolavirus (EBOV/Hsap/ NGA/2014/LIB-NIG 01072014; Genbank: KM251803.1.Conclusion: Our BSL-2 facility in Lagos, Nigeria, was able to safely detect Ebola virus disease using molecular techniques, supporting the reliability of molecular detection of highly infectious viral pathogens under stringent safety guidelines in BSL-2 laboratories. This is a significant lesson for the many under-facilitated laboratories in resource-limited settings, as is predominantly found in sub-Saharan Africa.

  16. Gloves and Ebola virus:a consideration of the penetration possibility based on nanostructure consideration

    Institute of Scientific and Technical Information of China (English)

    Sora; Yasri; Viroj; Wiwanitkit

    2015-01-01

    <正>To the editor,Ebola virus infection is the new deadly viral infection that is presently problematic in many countries in Africa.The prevention of this disease seems to be difficult and the rapid distribution of disease becomes the important issue for further discussion.As noted by Muyembe-Tamfum et al.[1],one of the major disease control measures is the distribution of protective equipment to health care workers.Gloves are important protective equipments

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

    OpenAIRE

    Arwady, M. Allison; Bawo, Luke; Hunter, Jennifer C.; Massaquoi, Moses; Matanock, Almea; Dahn, Bernice; Ayscue, Patrick; Nyenswah, Tolbert; Forrester, Joseph D; Hensley, Lisa E.; Monroe, Benjamin; Schoepp, Randal J.; Chen, Tai-Ho; Schaecher, Kurt E.; George, Thomas

    2015-01-01

    Over the span of a few weeks during July and August 2014, events in West Africa changed perceptions of Ebola virus disease (EVD) from an exotic tropical disease to a priority for global health security. We describe observations during that time of a field team from the Centers for Disease Control and Prevention and personnel of the Liberian Ministry of Health and Social Welfare. We outline the early epidemiology of EVD within Liberia, including the practical limitations on surveillance and th...

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

    OpenAIRE

    Evans, Nicholas G.

    2015-01-01

    In 2014, the author was invited to present at the American Society for Nephrology’s annual conference in Philadelphia on the ethics of treating patients with Ebola virus disease. The argument was made that the status of health care workers, including nephrologists, was the dominant ethical standard that generated both the duty to treat and the conflicts between this commitment and other ethical commitments that arise in public health emergencies. Conflicts between duty to treat and personal s...

  19. Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence.

    Science.gov (United States)

    Simmons, Graham; Wool-Lewis, Rouven J; Baribaud, Frédéric; Netter, Robert C; Bates, Paul

    2002-03-01

    The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293T cells. In this study we provide evidence that GPs from the other pathogenic subtypes, Sudan and Côte d'Ivoire, as well as from Reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at lower levels than Zaire GP. Sequential removal of regions of potential O-linked glycosylation at the C terminus of GP1 led to a step-wise reduction in cell detachment without obviously affecting GP function, suggesting that such modifications are involved in inducing the detachment phenotype. While causing cell rounding and detachment in 293T cells, Ebola virus GP did not cause an increase in cell death. Indeed, following transient expression of GP, cells were able to readhere and continue to divide. Also, the rounding effect was not limited to 293T cells. Replication-deficient adenovirus vectors expressing Ebola virus GP induced the loss of cell adhesion in a range of cell lines and primary cell types, including those with proposed relevance to Ebola virus infection in vivo, such as endothelial cells and macrophages. In both transfected 293T and adenovirus-infected Vero cells, a reduction in cell surface expression of adhesion molecules such as integrin beta1 concurrent with the loss of cell adhesion was observed. A number of other cell surface molecules, however, including major histocompatibility complex class I and the epidermal growth factor receptor, were also down-modulated, suggesting a global mechanism for surface molecule down-regulation.

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

    Science.gov (United States)

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

    2003-01-01

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

  1. Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine.

    Directory of Open Access Journals (Sweden)

    Jason S Richardson

    Full Text Available BACKGROUND: The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP. The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. METHODOLOGY/PRINCIPAL FINDINGS: Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP. Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. CONCLUSIONS/SIGNIFICANCE: We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the

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

    OpenAIRE

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

    2016-01-01

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

  3. Influence of referral pathway on ebola virus disease case-fatality rate and effect of survival selection bias

    DEFF Research Database (Denmark)

    Rudolf, Frauke; Damkjær, Mads; Lunding, Suzanne

    2017-01-01

    Case-fatality rates in Ebola treatment centers (ETCs) varied widely during the Ebola virus disease (EVD) outbreak in West Africa. We assessed the influence of referral pathway on ETC case-fatality rates with a retrospective cohort of 126 patients treated at the Mathaska ETC in Port Loko, Sierra...... Leone. The patients consisted of persons who had confirmed EVD when transferred to the ETC or who had been diagnosed onsite. The case-fatality rate for transferred patients was 46% versus 67% for patients diagnosed onsite (p = 0.02). The difference was mediated by Ebola viral load at diagnosis...

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells

    Science.gov (United States)

    Hölzer, Martin; Krähling, Verena; Amman, Fabian; Barth, Emanuel; Bernhart, Stephan H.; Carmelo, Victor A. O.; Collatz, Maximilian; Doose, Gero; Eggenhofer, Florian; Ewald, Jan; Fallmann, Jörg; Feldhahn, Lasse M.; Fricke, Markus; Gebauer, Juliane; Gruber, Andreas J.; Hufsky, Franziska; Indrischek, Henrike; Kanton, Sabina; Linde, Jörg; Mostajo, Nelly; Ochsenreiter, Roman; Riege, Konstantin; Rivarola-Duarte, Lorena; Sahyoun, Abdullah H.; Saunders, Sita J.; Seemann, Stefan E.; Tanzer, Andrea; Vogel, Bertram; Wehner, Stefanie; Wolfinger, Michael T.; Backofen, Rolf; Gorodkin, Jan; Grosse, Ivo; Hofacker, Ivo; Hoffmann, Steve; Kaleta, Christoph; Stadler, Peter F.; Becker, Stephan; Marz, Manja

    2016-01-01

    The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections. PMID:27713552

  6. Ebola virus convalescent blood products: where we are now and where we may need to go.

    Science.gov (United States)

    Burnouf, Thierry; Seghatchian, Jerard

    2014-10-01

    The world is regularly exposed to emerging infections with the potential to burst into a pandemic. One possible way to treat patients, when no other treatment is yet developed,is passive immunization performed by transfusing blood, plasma or plasma immunoglobul infractions obtained from convalescent donors who have recovered from the disease and have developed protective antibodies. The most recent on-going epidemic is caused by the Ebola virus, a filovirus responsible for Ebola virus disease, a severe, often lethal, hemorrhagic fever. Recently, the use of convalescent blood products was proposed by the WHO as one early option for treating patients with Ebola virus disease. This publication provides an overview of the various convalescent blood products and technological options that could theoretically be considered when there is a need to rely on this therapeutic approach.In countries without access to advanced blood-processing technologies, the choice may initially be restricted to convalescent whole blood or plasma. In technologically advanced countries, additional options for convalescent blood products are available, including virally inactivated plasma and fractionated immunoglobulins. The preparation of minipool immunoglobulins is also a realistic option to consider.

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

    Directory of Open Access Journals (Sweden)

    William R. Gallaher

    2015-01-01

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

  8. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells.

    Science.gov (United States)

    Hölzer, Martin; Krähling, Verena; Amman, Fabian; Barth, Emanuel; Bernhart, Stephan H; Carmelo, Victor A O; Collatz, Maximilian; Doose, Gero; Eggenhofer, Florian; Ewald, Jan; Fallmann, Jörg; Feldhahn, Lasse M; Fricke, Markus; Gebauer, Juliane; Gruber, Andreas J; Hufsky, Franziska; Indrischek, Henrike; Kanton, Sabina; Linde, Jörg; Mostajo, Nelly; Ochsenreiter, Roman; Riege, Konstantin; Rivarola-Duarte, Lorena; Sahyoun, Abdullah H; Saunders, Sita J; Seemann, Stefan E; Tanzer, Andrea; Vogel, Bertram; Wehner, Stefanie; Wolfinger, Michael T; Backofen, Rolf; Gorodkin, Jan; Grosse, Ivo; Hofacker, Ivo; Hoffmann, Steve; Kaleta, Christoph; Stadler, Peter F; Becker, Stephan; Marz, Manja

    2016-10-07

    The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.

  9. Inhibition of Lassa virus and Ebola virus infection in host cells treated with the kinase inhibitors genistein and tyrphostin.

    Science.gov (United States)

    Kolokoltsov, Andrey A; Adhikary, Shramika; Garver, Jennifer; Johnson, Lela; Davey, Robert A; Vela, Eric M

    2012-01-01

    Arenaviruses and filoviruses are capable of causing hemorrhagic fever syndrome in humans. Limited therapeutic and/or prophylactic options are available for humans suffering from viral hemorrhagic fever. In this report, we demonstrate that pre-treatment of host cells with the kinase inhibitors genistein and tyrphostin AG1478 leads to inhibition of infection or transduction in cells infected with Ebola virus, Marburg virus, and Lassa virus. In all, the results demonstrate that a kinase inhibitor cocktail consisting of genistein and tyrphostin AG1478 is a broad-spectrum antiviral that may be used as a therapeutic or prophylactic against arenavirus and filovirus hemorrhagic fever.

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

    Science.gov (United States)

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

    2015-09-15

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

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

    Science.gov (United States)

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

    2016-06-01

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

  12. Prediction and identification of mouse cytotoxic T lymphocyte epitopes in Ebola virus glycoproteins

    Directory of Open Access Journals (Sweden)

    Wu Shipo

    2012-06-01

    Full Text Available Abstract Background Ebola viruses (EBOVs cause severe hemorrhagic fever with a high mortality rate. At present, there are no licensed vaccines or efficient therapies to combat EBOV infection. Previous studies have shown that both humoral and cellular immune responses are crucial for controlling Ebola infection. CD8+ T cells play an important role in mediating vaccine-induced protective immunity. The objective of this study was to identify H-2d-specific T cell epitopes in EBOV glycoproteins (GPs. Results Computer-assisted algorithms were used to predict H-2d-specific T cell epitopes in two species of EBOV (Sudan and Zaire GP. The predicted peptides were synthesized and identified in BALB/c mice immunized with replication-deficient adenovirus vectors expressing the EBOV GP. Enzyme-linked immunospot assays and intracellular cytokine staining showed that the peptides RPHTPQFLF (Sudan EBOV, GPCAGDFAF and LYDRLASTV (Zaire EBOV could stimulate splenoctyes in immunized mice to produce large amounts of interferon-gamma. Conclusion Three peptides within the GPs of two EBOV strains were identified as T cell epitopes. The identification of these epitopes should facilitate the evaluation of vaccines based on the Ebola virus glycoprotein in a BALB/c mouse model.

  13. Preliminary Evaluation of the Effect of Investigational Ebola Virus Disease Treatments on Viral Genome Sequences.

    Science.gov (United States)

    Whitmer, Shannon L M; Albariño, César; Shepard, Samuel S; Dudas, Gytis; Sheth, Mili; Brown, Shelley C; Cannon, Deborah; Erickson, Bobbie R; Gibbons, Aridth; Schuh, Amy; Sealy, Tara; Ervin, Elizabeth; Frace, Mike; Uyeki, Timothy M; Nichol, Stuart T; Ströher, Ute

    2016-10-15

     Several patients with Ebola virus disease (EVD) managed in the United States have received ZMapp monoclonal antibodies, TKM-Ebola small interfering RNA, brincidofovir, and/or convalescent plasma as investigational therapeutics.  To investigate whether treatment selected for Ebola virus (EBOV) mutations conferring resistance, viral sequencing was performed on RNA extracted from clinical blood specimens from patients with EVD following treatment, and putative viral targets were analyzed.  We observed no major or minor EBOV mutations within regions targeted by therapeutics.  This small subset of patients and clinical specimens suggests that evolution of resistance is not a direct consequence of antiviral treatment. As EVD antiviral treatments are introduced into wider use, it is essential that continuous viral full-genome surveillance is performed, to monitor for the emergence of escape mutations. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. The Role of Fear-Related Behaviors in the 2013-2016 West Africa Ebola Virus Disease Outbreak.

    Science.gov (United States)

    Shultz, James M; Cooper, Janice L; Baingana, Florence; Oquendo, Maria A; Espinel, Zelde; Althouse, Benjamin M; Marcelin, Louis Herns; Towers, Sherry; Espinola, Maria; McCoy, Clyde B; Mazurik, Laurie; Wainberg, Milton L; Neria, Yuval; Rechkemmer, Andreas

    2016-11-01

    The 2013-2016 West Africa Ebola virus disease pandemic was the largest, longest, deadliest, and most geographically expansive outbreak in the 40-year interval since Ebola was first identified. Fear-related behaviors played an important role in shaping the outbreak. Fear-related behaviors are defined as "individual or collective behaviors and actions initiated in response to fear reactions that are triggered by a perceived threat or actual exposure to a potentially traumatizing event. FRBs modify the future risk of harm." This review examines how fear-related behaviors were implicated in (1) accelerating the spread of Ebola, (2) impeding the utilization of life-saving Ebola treatment, (3) curtailing the availability of medical services for treatable conditions, (4) increasing the risks for new-onset psychological distress and psychiatric disorders, and (5) amplifying the downstream cascades of social problems. Fear-related behaviors are identified for each of these outcomes. Particularly notable are behaviors such as treating Ebola patients in home or private clinic settings, the "laying of hands" on Ebola-infected individuals to perform faith-based healing, observing hands-on funeral and burial customs, foregoing available life-saving treatment, and stigmatizing Ebola survivors and health professionals. Future directions include modeling the onset, operation, and perpetuation of fear-related behaviors and devising strategies to redirect behavioral responses to mass threats in a manner that reduces risks and promotes resilience.

  15. The Role of Fear-Related Behaviors in the 2013–2016 West Africa Ebola Virus Disease Outbreak

    Science.gov (United States)

    Shultz, James M.; Cooper, Janice L.; Baingana, Florence; Oquendo, Maria A.; Espinel, Zelde; Althouse, Benjamin M.; Marcelin, Louis Herns; Towers, Sherry; Espinola, Maria; McCoy, Clyde B.; Mazurik, Laurie; Wainberg, Milton L.; Neria, Yuval; Rechkemmer, Andreas

    2017-01-01

    The 2013–2016 West Africa Ebola virus disease pandemic was the largest, longest, deadliest, and most geographically expansive outbreak in the 40-year interval since Ebola was first identified. Fear-related behaviors played an important role in shaping the outbreak. Fear-related behaviors are defined as “individual or collective behaviors and actions initiated in response to fear reactions that are triggered by a perceived threat or actual exposure to a potentially traumatizing event. FRBs modify the future risk of harm.” This review examines how fear-related behaviors were implicated in (1) accelerating the spread of Ebola, (2) impeding the utilization of life-saving Ebola treatment, (3) curtailing the availability of medical services for treatable conditions, (4) increasing the risks for new-onset psychological distress and psychiatric disorders, and (5) amplifying the downstream cascades of social problems. Fear-related behaviors are identified for each of these outcomes. Particularly notable are behaviors such as treating Ebola patients in home or private clinic settings, the “laying of hands” on Ebola-infected individuals to perform faith-based healing, observing hands-on funeral and burial customs, foregoing available life-saving treatment, and stigmatizing Ebola survivors and health professionals. Future directions include modeling the onset, operation, and perpetuation of fear-related behaviors and devising strategies to redirect behavioral responses to mass threats in a manner that reduces risks and promotes resilience. PMID:27739026

  16. Ebola haemorrhagic fever

    Science.gov (United States)

    Feldmann, Heinz; Geisbert, Thomas W

    2012-01-01

    Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The exception is the species Reston Ebola virus, which has not been associated with human disease and is found in the Philippines. Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism. Ebola virus is thought to also have a detrimental effect on the great ape population in Africa. Case-fatality rates of the African species in man are as high as 90%, with no prophylaxis or treatment available. Ebola virus infections are characterised by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock. PMID:21084112

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  19. Ebola hemorrhagic fever associated with novel virus strain, Uganda, 2007-2008.

    Science.gov (United States)

    Wamala, Joseph F; Lukwago, Luswa; Malimbo, Mugagga; Nguku, Patrick; Yoti, Zabulon; Musenero, Monica; Amone, Jackson; Mbabazi, William; Nanyunja, Miriam; Zaramba, Sam; Opio, Alex; Lutwama, Julius J; Talisuna, Ambrose O; Okware, Sam I

    2010-07-01

    During August 2007-February 2008, the novel Bundibugyo ebolavirus species was identified during an outbreak of Ebola viral hemorrhagic fever in Bundibugyo district, western Uganda. To characterize the outbreak as a requisite for determining response, we instituted a case-series investigation. We identified 192 suspected cases, of which 42 (22%) were laboratory positive for the novel species; 74 (38%) were probable, and 77 (40%) were negative. Laboratory confirmation lagged behind outbreak verification by 3 months. Bundibugyo ebolavirus was less fatal (case-fatality rate 34%) than Ebola viruses that had caused previous outbreaks in the region, and most transmission was associated with handling of dead persons without appropriate protection (adjusted odds ratio 3.83, 95% confidence interval 1.78-8.23). Our study highlights the need for maintaining a high index of suspicion for viral hemorrhagic fevers among healthcare workers, building local capacity for laboratory confirmation of viral hemorrhagic fevers, and institutionalizing standard precautions.

  20. Molecular mechanisms of Ebola pathogenesis.

    Science.gov (United States)

    Rivera, Andrea; Messaoudi, Ilhem

    2016-11-01

    Ebola viruses (EBOVs) and Marburg viruses (MARVs) are among the deadliest human viruses, as highlighted by the recent and widespread Ebola virus outbreak in West Africa, which was the largest and longest epidemic of Ebola virus disease (EVD) in history, resulting in significant loss of life and disruptions across multiple continents. Although the number of cases has nearly reached its nadir, a recent cluster of 5 cases in Guinea on March 17, 2016, has extended the enhanced surveillance period to June 15, 2016. New, enhanced 90-d surveillance windows replaced the 42-d surveillance window to ensure the rapid detection of new cases that may arise from a missed transmission chain, reintroduction from an animal reservoir, or more important, reemergence of the virus that has persisted in an EVD survivor. In this review, we summarize our current understanding of EBOV pathogenesis, describe vaccine and therapeutic candidates in clinical trials, and discuss mechanisms of viral persistence and long-term health sequelae for EVD survivors. © Society for Leukocyte Biology.

  1. Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola.

    Science.gov (United States)

    Fedson, David S

    2016-11-01

    There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases. Most scientists work on new drugs that target viruses, and few accept the idea of treating the host response with generic drugs. A great deal of research will be needed to show conclusively that these drugs work, and this will require the support of public agencies and foundations. Investigators in developing countries should take an active role in this research. If the next Public Health Emergency of International Concern is caused by an emerging virus, a "top down" approach to developing specific new drug treatments is unlikely to be effective. However, a "bottom up" approach to treatment that targets the host response to these viruses by using widely available and inexpensive generic drugs could reduce mortality in any country with a basic health care system. In doing so, it would make an immeasurable contribution to global equity and global security.

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

    Directory of Open Access Journals (Sweden)

    Christopher E. McCoy

    2014-11-01

    Full Text Available The 25th known outbreak of the Ebola Virus Disease (EVD is now a global public health emergency and the World Health Organization (WHO has declared the epidemic to be a Public Health Emergency of International Concern (PHEIC. Since the first cases of the West African epidemic were reported in March 2014, there has been an increase in infection rates of over 13,000% over a 6-month period. The Ebola virus has now arrived in the United States and public health professionals, doctors, hospitals, Emergency Medial Services Administrators, Medical Directors, and policy makers have been working with haste to develop strategies to prevent the disease from reaching epidemic proportions. Prehospital care providers (emergency medical technicians and paramedics and medical first responders (including but not limited to firefighters and law enforcement are the healthcare systems front lines when it comes to first medical contact with patients outside of the hospital setting. Risk of contracting Ebola can be particularly high in this population of first responders if the appropriate precautions are not implemented. This article provides a brief clinical overview of the Ebola Virus Disease and provides a comprehensive summary of the Center for Disease Control and Prevention’s Interim Guidance for Emergency Medical Services (EMS Systems and 9-1-1 Public Safety Answering Points (PSAPS for Management of Patients with Known of Suspected Ebola Virus Disease in the United States. [West J Emerg Med. 2014;15(7:-0.

  3. 埃博拉病毒病的研究进展%Progress in the Research of Ebola Virus Disease

    Institute of Scientific and Technical Information of China (English)

    张秋墨; 金丹

    2015-01-01

    The Ebola virus disease is a kind of zoonoses which can make human and primate animals produce hemorrhagic fever and the probability of human and animal death is extremely high. This paper wil introduce about the Ebola virus pathogenic characteristics, epidemiological characteristics, clinical manifestations and how to deal with Ebola virus invasion.%埃博拉病毒病是一种能引起人和灵长类动物产生出血热的人畜共患烈性传染病,致死性极高.本文主要对埃博拉病毒的病原学特征、流行病学特征、临床表现及如何应对埃博拉病毒的侵袭做介绍.

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

    Science.gov (United States)

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

    2015-01-30

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-09-01

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

  6. Surrogate testing suggests that chlorine dioxide gas exposure would not inactivate Ebola virus contained in environmental blood contamination.

    Science.gov (United States)

    Lowe, John J; Hewlett, Angela L; Iwen, Peter C; Smith, Philip W; Gibbs, Shawn G

    2015-05-08

    The ability to decontaminate a room potentially containing the Ebola virus is important to healthcare facilities in the United States. Ebola virus remains viable in body fluids, a room that has housed a patient with Ebola virus disease must have all surfaces manually wiped with an approved disinfectant, which increases occupational exposure risk. This study evaluated the efficacy of gaseous chlorine dioxide inactivation of bacterial organisms in blood as Ebola virus surrogates and as the organisms used by the Nebraska Biocontainment Unit to provide the margin of safety for decontamination. Bacillus anthracis, Escherichia coli, Enterococcus faecalis, and Mycobacterium smegmatis blood suspensions that were exposed to ClO2 gas concentrations and exposure limits. The log reduction in Colony Forming Units (CFU) was determined for each bacterial blood suspension. Exposure parameters approximating industry practices for ClO2 environmental decontamination (360ppm concentration to 780 ppm-hrs exposure, 65% relative humidity) as well as parameters exceeding current practice (1116 ppm concentration to 1400 ppm-hrs exposure; 1342ppm concentration to 1487 ppm-hrs exposure) were evaluated. Complete inactivation was not achieved for any of the bacterial blood suspensions tested. Reductions were observed in concentrations of B. anthracis spores (1.3 -3.76 log) and E. faecalis vegetative cells (1.3 log) whereas significant reductions in vegetative cell concentrations for E. coli and M. smegmatis blood suspensions were not achieved. Our results showed that bacteria in the presence of blood were not inactivated using gaseous ClO2 decontamination. ClO2 decontamination alone should not be used for Ebola virus, but decontamination processes should first include manual wiping of potentially contaminated blood; especially for microorganisms as infectious as the Ebola virus.

  7. Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples.

    Science.gov (United States)

    Matranga, Christian B; Andersen, Kristian G; Winnicki, Sarah; Busby, Michele; Gladden, Adrianne D; Tewhey, Ryan; Stremlau, Matthew; Berlin, Aaron; Gire, Stephen K; England, Eleina; Moses, Lina M; Mikkelsen, Tarjei S; Odia, Ikponmwonsa; Ehiane, Philomena E; Folarin, Onikepe; Goba, Augustine; Kahn, S Humarr; Grant, Donald S; Honko, Anna; Hensley, Lisa; Happi, Christian; Garry, Robert F; Malboeuf, Christine M; Birren, Bruce W; Gnirke, Andreas; Levin, Joshua Z; Sabeti, Pardis C

    2014-01-01

    We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies.

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

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Daisy W.; Shabman, Reed S.; Farahbakhsh, Mina; Prins, Kathleen C.; Borek, Dominika M.; Wang, Tianjiao; Mühlberger, Elke; Basler, Christopher F.; Amarasinghe, Gaya K. (Sinai); (BU-M); (Iowa State); (UTSMC)

    2010-09-21

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Sina Bavari

    2012-11-01

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

  11. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections.

    Science.gov (United States)

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

    2012-11-06

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

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

    Directory of Open Access Journals (Sweden)

    Kourosh HOLAKOUIE-NAIENI

    2015-12-01

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

  13. Marburg virus evades interferon responses by a mechanism distinct from ebola virus.

    Directory of Open Access Journals (Sweden)

    Charalampos Valmas

    2010-01-01

    Full Text Available Previous studies have demonstrated that Marburg viruses (MARV and Ebola viruses (EBOV inhibit interferon (IFN-alpha/beta signaling but utilize different mechanisms. EBOV inhibits IFN signaling via its VP24 protein which blocks the nuclear accumulation of tyrosine phosphorylated STAT1. In contrast, MARV infection inhibits IFNalpha/beta induced tyrosine phosphorylation of STAT1 and STAT2. MARV infection is now demonstrated to inhibit not only IFNalpha/beta but also IFNgamma-induced STAT phosphorylation and to inhibit the IFNalpha/beta and IFNgamma-induced tyrosine phosphorylation of upstream Janus (Jak family kinases. Surprisingly, the MARV matrix protein VP40, not the MARV VP24 protein, has been identified to antagonize Jak and STAT tyrosine phosphorylation, to inhibit IFNalpha/beta or IFNgamma-induced gene expression and to inhibit the induction of an antiviral state by IFNalpha/beta. Global loss of STAT and Jak tyrosine phosphorylation in response to both IFNalpha/beta and IFNgamma is reminiscent of the phenotype seen in Jak1-null cells. Consistent with this model, MARV infection and MARV VP40 expression also inhibit the Jak1-dependent, IL-6-induced tyrosine phosphorylation of STAT1 and STAT3. Finally, expression of MARV VP40 is able to prevent the tyrosine phosphorylation of Jak1, STAT1, STAT2 or STAT3 which occurs following over-expression of the Jak1 kinase. In contrast, MARV VP40 does not detectably inhibit the tyrosine phosphorylation of STAT2 or Tyk2 when Tyk2 is over-expressed. Mutation of the VP40 late domain, essential for efficient VP40 budding, has no detectable impact on inhibition of IFN signaling. This study shows that MARV inhibits IFN signaling by a mechanism different from that employed by the related EBOV. It identifies a novel function for the MARV VP40 protein and suggests that MARV may globally inhibit Jak1-dependent cytokine signaling.

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

    Directory of Open Access Journals (Sweden)

    Jessica L Abbate

    2016-05-01

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

  15. Functional Characterization of Adaptive Mutations during the West African Ebola Virus Outbreak.

    Science.gov (United States)

    Dietzel, Erik; Schudt, Gordian; Krähling, Verena; Matrosovich, Mikhail; Becker, Stephan

    2017-01-15

    The Ebola virus (EBOV) outbreak in West Africa started in December 2013, claimed more than 11,000 lives, threatened to destabilize a whole region, and showed how easily health crises can turn into humanitarian disasters. EBOV genomic sequences of the West African outbreak revealed nonsynonymous mutations, which induced considerable public attention, but their role in virus spread and disease remains obscure. In this study, we investigated the functional significance of three nonsynonymous mutations that emerged early during the West African EBOV outbreak. Almost 90% of more than 1,000 EBOV genomes sequenced during the outbreak carried the signature of three mutations: a D759G substitution in the active center of the L polymerase, an A82V substitution in the receptor binding domain of surface glycoprotein GP, and an R111C substitution in the self-assembly domain of RNA-encapsidating nucleoprotein NP. Using a newly developed virus-like particle system and reverse genetics, we found that the mutations have an impact on the functions of the respective viral proteins and on the growth of recombinant EBOVs. The mutation in L increased viral transcription and replication, whereas the mutation in NP decreased viral transcription and replication. The mutation in the receptor binding domain of the glycoprotein GP improved the efficiency of GP-mediated viral entry into target cells. Recombinant EBOVs with combinations of the three mutations showed a growth advantage over the prototype isolate Makona C7 lacking the mutations. This study showed that virus variants with improved fitness emerged early during the West African EBOV outbreak. The dimension of the Ebola virus outbreak in West Africa was unprecedented. Amino acid substitutions in the viral L polymerase, surface glycoprotein GP, and nucleocapsid protein NP emerged, were fixed early in the outbreak, and were found in almost 90% of the sequences. Here we showed that these mutations affected the functional activity of

  16. Individual and Bivalent Vaccines Based on Alphavirus Replicons Protect Guinea Pigs against Infection with Lassa and Ebola Viruses

    OpenAIRE

    Pushko, Peter; Geisbert, Joan; Parker, Michael; Jahrling, Peter; Smith, Jonathan

    2001-01-01

    Lassa and Ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. Although lethal human disease outbreaks have been confined so far to sub-Saharan Africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into North America and Europe. In the present study, we developed experimental individual vaccines for Lassa virus and bivalent vaccin...

  17. Analysis of Ebola Virus and VLP Release Using an Immunocapture Assay

    Science.gov (United States)

    2007-11-02

    vaccine efficacy. While other viral pro- teins such as VP40, VP24, VP30, and VP35 expressed by a Venezuelan encephalitis virus (VEE)-based replicon are...VLP release was also achieved by VP30 (Fig. 6). While mouse studies have shown some protective effect by Ebola VP35 expressed in replicons , VP35 is...vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates. Virology 251 (1), 28–37. uang, Y., Xu, L., Sun, Y., Nabel, G.J

  18. Oral and Conjunctival Exposure of Nonhuman Primates to Low Doses of Ebola Makona Virus

    Science.gov (United States)

    Mire, Chad E.; Geisbert, Joan B.; Agans, Krystle N.; Deer, Daniel J.; Fenton, Karla A.; Geisbert, Thomas W.

    2016-01-01

    Nonhuman primate (NHP) models of Ebola virus (EBOV) infection primarily use parenteral or aerosol routes of exposure. Uniform lethality can be achieved in these models at low doses of EBOV (≤100 plaque-forming units [PFU]). Here, we exposed NHPs to low doses of EBOV (Makona strain) by the oral or conjunctival routes. Surprisingly, animals exposed to 10 PFU by either route showed no signs of disease. Exposure to 100 PFU resulted in illness and/or lethal infection. These results suggest that these more natural routes require higher doses of EBOV to produce disease or that there may be differences between Makona and historical strains. PMID:27284090

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Luthra, Priya; Jordan, David S.; Leung, Daisy W.; Amarasinghe, Gaya K.; Basler, Christopher F.; Lyles, D. S.

    2015-03-04

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

  1. The Ebola virus disease outbreak and the mineral sectors of Guinea, Liberia, and Sierra Leone

    Science.gov (United States)

    Bermúdez-Lugo, Omayra; Menzie, William D.

    2015-01-01

    The mineral sector plays a key role in the economies of Guinea, Liberia, and Sierra Leone. The onset of the Ebola virus disease (EVD) outbreak in early 2014, together with changes in mineral market conditions, raised questions regarding the status of mining operations and of mineral development and exploration projects in all three countries. Mineral projects were the underpinnings of World Bank short-term forecasts of increases in gross domestic product (GDP) for all three countries and were expected to be the basis of future economic growth. The significant delay or cancellation of these projects could result in a major economic setback for all three countries.

  2. Ebola virus disease: How can African pharmacists respond to future outbreaks?

    Directory of Open Access Journals (Sweden)

    Peter Bai James

    2016-05-01

    Full Text Available In its forty years history (1976–2016, the West African region has recorded the most devastating form of the Ebola virus disease. The sparse knowledge of healthcare professionals and general public combined with lesser responses from international community are major factors for the dissemination of the disease. In the context of this outbreak, there is a need to highlight the roles and responsibilities of pharmacists, especially in the African healthcare setting. Moreover, the prerequisite of diagnostic kits for the timely detection of the infection as well as pharmacists’ awareness of the current therapeutic regimen are recommended.

  3. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening.

  4. Elucidation of the Cellular Interactome of Ebola Virus Nucleoprotein and Identification of Therapeutic Targets.

    Science.gov (United States)

    García-Dorival, Isabel; Wu, Weining; Armstrong, Stuart D; Barr, John N; Carroll, Miles W; Hewson, Roger; Hiscox, Julian A

    2016-12-02

    Ebola virus (EBOV) infection results in severe disease and in some cases lethal hemorrhagic fever. The infection is directed by seven viral genes that encode nine viral proteins. By definition, viruses are obligate intracellular parasites and require aspects of host cell biology in order to replicate their genetic material, assemble new virus particles, and subvert host cell antiviral responses. Currently licensed antivirals are targeted against viral proteins to inhibit their function. However, experience with treating HIV and influenza virus demonstrates that resistant viruses are soon selected. An emerging area in virology is to transiently target host cell proteins that play critical proviral roles in virus biology, especially for acute infections. This has the advantage that the protein being targeted is evolutionary removed from the genome of the virus. Proteomics can aid in discovery biology and identify cellular proteins that may be utilized by the virus to facilitate infection. This work focused on defining the interactome of the EBOV nucleoprotein and identified that cellular chaperones, including HSP70, associate with this protein to promote stability. Utilization of a mini-genome replication system based on a recent Makona isolate demonstrated that disrupting the stability of NP had an adverse effect on viral RNA synthesis.

  5. Ebola Virus Glycoprotein Induces an Innate Immune Response In vivo via TLR4

    Directory of Open Access Journals (Sweden)

    Chih-Yun Lai

    2017-08-01

    Full Text Available Ebola virus (EBOV, a member of the Filoviridae family, causes the most severe form of viral hemorrhagic fever. Although no FDA licensed vaccine or treatment against Ebola virus disease (EVD is currently available, Ebola virus glycoprotein (GP is the major antigen used in all candidate Ebola vaccines. Recent reports of protection as quickly as within 6 days of administration of the rVSV-based vaccine expressing EBOV GP before robust humoral responses were generated suggests that the innate immune responses elicited early after vaccination may contribute to the protection. However, the innate immune responses induced by EBOV GP in the absence of viral vectors or adjuvants have not been fully characterized in vivo. Our recent studies demonstrated that immunization with highly purified recombinant GP in the absence of adjuvants induced a robust IgG response and partial protection against EBOV infection suggesting that GP alone can induce protective immunity. In this study we investigated the early immune response to purified EBOV GP alone in vitro and in vivo. We show that GP was efficiently internalized by antigen presenting cells and subsequently induced production of key inflammatory cytokines. In vivo, immunization of mice with EBOV GP triggered the production of key Th1 and Th2 innate immune cytokines and chemokines, which directly governed the recruitment of CD11b+ macrophages and CD11c+ dendritic cells to the draining lymph nodes (DLNs. Pre-treatment of mice with a TLR4 antagonist inhibited GP-induced cytokine production and recruitment of immune cells to the DLN. EBOV GP also upregulated the expression of costimulatory molecules in bone marrow derived macrophages suggesting its ability to enhance APC stimulatory capacity, which is critical for the induction of effective antigen-specific adaptive immunity. Collectively, these results provide the first in vivo evidence that early innate immune responses to EBOV GP are mediated via the TLR4

  6. Catheterized guinea pigs infected with Ebola Zaire virus allows safer sequential sampling to determine the pharmacokinetic profile of a phosphatidylserine-targeting monoclonal antibody.

    Science.gov (United States)

    Dowall, Stuart; Taylor, Irene; Yeates, Paul; Smith, Leonie; Rule, Antony; Easterbrook, Linda; Bruce, Christine; Cook, Nicola; Corbin-Lickfett, Kara; Empig, Cyril; Schlunegger, Kyle; Graham, Victoria; Dennis, Mike; Hewson, Roger

    2013-02-01

    Sequential sampling from animals challenged with highly pathogenic organisms, such as haemorrhagic fever viruses, is required for many pharmaceutical studies. Using the guinea pig model of Ebola virus infection, a catheterized system was used which had the benefits of allowing repeated sampling of the same cohort of animals, and also a reduction in the use of sharps at high biological containment. Levels of a PS-targeting antibody (Bavituximab) were measured in Ebola-infected animals and uninfected controls. Data showed that the pharmacokinetics were similar in both groups, therefore Ebola virus infection did not have an observable effect on the half-life of the antibody.

  7. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

    DEFF Research Database (Denmark)

    Dunning, Jake; Sahr, Foday; Rojek, Amanda

    2016-01-01

    BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD...

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

    Science.gov (United States)

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

    2015-10-01

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

  9. Preparedness for admission of patients with suspected Ebola virus disease in European hospitals: A survey, August-September 2014

    NARCIS (Netherlands)

    M.D. de Jong (Menno); C.B.E.M. Reusken (Chantal); P. Horby; M.P.G. Koopmans D.V.M. (Marion); M. Bonten; J.D. Chiche; C. Giaquinto; T. Welte; F. Leus; J. Schotsman; H. Goossens

    2014-01-01

    textabstractIn response to the Ebola virus disease (EVD) outbreak in West Africa, the World Health Organization has advised all nations to prepare for the detection, investigation and management of confirmed and suspected EVD cases in order to prevent further spread through international travel. To

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

    Science.gov (United States)

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

    2016-03-01

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

  11. Preparedness for admission of patients with suspected Ebola virus disease in European hospitals: A survey, August-September 2014

    NARCIS (Netherlands)

    M.D. de Jong (Menno); C.B.E.M. Reusken (Chantal); P. Horby; M.P.G. Koopmans D.V.M. (Marion); M. Bonten; J.D. Chiche; C. Giaquinto; T. Welte; F. Leus; J. Schotsman; H. Goossens

    2014-01-01

    textabstractIn response to the Ebola virus disease (EVD) outbreak in West Africa, the World Health Organization has advised all nations to prepare for the detection, investigation and management of confirmed and suspected EVD cases in order to prevent further spread through international travel. To

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kelly L Warfield

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

  14. The Ebola virus VP35 protein is a suppressor of RNA silencing.

    Science.gov (United States)

    Haasnoot, Joost; de Vries, Walter; Geutjes, Ernst-Jan; Prins, Marcel; de Haan, Peter; Berkhout, Ben

    2007-06-01

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

  15. The Ebola virus VP35 protein is a suppressor of RNA silencing.

    Directory of Open Access Journals (Sweden)

    Joost Haasnoot

    2007-06-01

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

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

    Science.gov (United States)

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

    2015-08-06

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

  17. Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys

    Science.gov (United States)

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

    2016-01-01

    Summary The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae1. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications

  18. Public acceptance of a hypothetical Ebola virus vaccine in Aceh, Indonesia: A hospital-based survey

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    Harapan Harapan

    2017-04-01

    Full Text Available Objective: To determine the acceptance towards a hypothetical Ebola virus vaccine (EVV and associated factors in a non-affected country, Indonesia. Methods: A hospital-based, cross-sectional study was conducted in four regencies of Aceh, Indonesia. A set of pre-tested questionnaires was used to obtain information on acceptance towards EVV and a range of explanatory variables. Associations between EVV acceptance and explanatory variables were tested using multi-steps logistic regression analysis and the Spearman's rank correlation. Results: Participants who had knowledge on Ebola virus disease (EVD were 45.3% (192/424 and none of the participants achieved 80% correct answers on the knowledge regarding to EVD. About 73% of participants expressed their willingness to receive the EVV. Education attainment, occupation, monthly income, have heard regarding to EVD previously, socioeconomic level, attitude towards vaccination practice and knowledge regarding to EVD were associated significantly with acceptance towards EVV in univariate analysis (P < 0.05. In the final multivariate model, socio-economic level, attitude towards vaccination practice and knowledge regarding to EVD were the independent explanatory variables for EVV acceptance. Conclusions: The knowledge of EVD was low, but this minimally affected the acceptance towards EVV. However, to facilitate optimal uptake of EVV, dissemination of vaccine-related information prior to its introduction is required.

  19. Pre-Ebola virus disease laboratory system and related challenges in Liberia

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    Stephen B. Kennedy

    2016-10-01

    Full Text Available Prior to the Ebola virus disease outbreak in Liberia, the laboratory system was duplicativefragmented and minimally coordinated. The National Reference Laboratory was conceptualisedto address the existing challenges by promoting the implementation of effective and sustainablelaboratory services in Liberia. However, in a resource-limited environment such as Liberiaprogress regarding the rebuilding of the health system can be relatively slow, while efforts tosustain the transient gains remain a key challenge for the Ministry of Health. In this paper, wedescribe the pre-Ebola virus disease laboratory system in Liberia and its prevailing efforts toaddress future emerging infectious diseases, as well as current Infectious diseases, all of whichare exacerbated by poverty. We conclude that laboratory and diagnostic services in Liberiahave encountered numerous challenges regarding its efforts to strengthen the healthcaredelivery system. These challenges include limited trained human resource capacity, inadequateinfrastructure, and a lack of coordination. As with most countries in sub-Saharan Africa, whencomparing urban and rural settings, diagnostic and clinical services are generally skewedtoward urban health facilities and private, faith-based health facilities. We recommend thatstructured policy be directed at these challenges for national institutions to develop guidelinesto improve, strengthen and sustain diagnostic and curative laboratory services to effectivelyaddress current infectious diseases and prepare for future emerging and re-emerging infectiousdiseases.

  20. How Ebola and Marburg Viruses Battle the Immune System

    Science.gov (United States)

    2007-07-01

    adaptive immunity) • Late (fever, malaise, gastrointestinal distress, possible septicaemia, LPS?) B cell (?) CD8+ T cell Hepatocytes CD4+ T cell • High...specific antibodies; mitigation of virus-induced coagulation deficits using recombinant nematode anticoagulant protein c2; antisense compounds or small

  1. Trigger events: enviroclimatic coupling of Ebola hemorrhagic fever outbreaks

    Science.gov (United States)

    Pinzon, Jorge E.; Wilson, James M.; Tucker, Compton J.; Arthur, Ray; Jahrling, Peter B.; Formenty, Pierre

    2004-01-01

    We use spatially continuous satellite data as a correlate of precipitation within tropical Africa and show that the majority of documented Ebola hemorrhagic fever outbreaks were closely associated with sharply drier conditions at the end of the rainy season. We propose that these trigger events may enhance transmission of Ebola virus from its cryptic reservoir to humans. These findings suggest specific directions to help understand the sylvatic cycle of the virus and may provide early warning tools to detect possible future outbreaks of this enigmatic disease.

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

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    Gary L.White

    2012-10-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  5. Gene-specific countermeasures against Ebola virus based on antisense phosphorodiamidate morpholino oligomers.

    Directory of Open Access Journals (Sweden)

    Kelly L Warfield

    2006-01-01

    Full Text Available The filoviruses Marburg virus and Ebola virus (EBOV quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. The development of an effective therapeutic for EBOV is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. This report describes a successful strategy for interfering with EBOV infection using antisense phosphorodiamidate morpholino oligomers (PMOs. A combination of EBOV-specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure therapeutic regimens. In a prophylactic proof-of-principal trial, the PMOs also protected 75% of rhesus macaques from lethal EBOV infection. The work described here may contribute to development of designer, "druggable" countermeasures for filoviruses and other microbial pathogens.

  6. Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available The filoviruses Marburg virus and Ebola virus (EBOV quickly outpace host immune responses and cause hemorrhagic fever, resulting in case fatality rates as high as 90% in humans and nearly 100% in nonhuman primates. The development of an effective therapeutic for EBOV is a daunting public health challenge and is hampered by a paucity of knowledge regarding filovirus pathogenesis. This report describes a successful strategy for interfering with EBOV infection using antisense phosphorodiamidate morpholino oligomers (PMOs. A combination of EBOV-specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure therapeutic regimens. In a prophylactic proof-of-principal trial, the PMOs also protected 75% of rhesus macaques from lethal EBOV infection. The work described here may contribute to development of designer, "druggable" countermeasures for filoviruses and other microbial pathogens.

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

    Science.gov (United States)

    Peterson, A Townsend; Samy, Abdallah M

    2016-10-01

    Filoviruses represent a significant public health threat worldwide. West Africa recently experienced the largest-scale and most complex filovirus outbreak yet known, which underlines the need for a predictive understanding of the geographic distribution and potential for transmission to humans of these viruses. Here, we used ecological niche modeling techniques to understand the relationship between known filovirus occurrences and environmental characteristics. Our study derived a picture of the potential transmission geography of Ebola virus species and Marburg, paired with views of the spatial uncertainty associated with model-to-model variation in our predictions. We found that filovirus species have diverged ecologically, but only three species are sufficiently well known that models could be developed with significant predictive power. We quantified uncertainty in predictions, assessed potential for outbreaks outside of known transmission areas, and highlighted the Ethiopian Highlands and scattered areas across East Africa as additional potentially unrecognized transmission areas. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Ebola and Marburg Viruses Replicate in Monocyle- Derived Dendritic Cells without Inducing the Production of Cytokines and Full Maturation

    Science.gov (United States)

    2007-11-02

    secretion in response to a second IFN-inducing stimulus ( replication -defective alphavirus ) was also potently inhibited by both viruses. From these data...1630 • JID 2003:188 (1 December) • Bosio et al. M A J O R A R T I C L E Ebola and Marburg Viruses Replicate in Monocyte- Derived Dendritic Cells...immune responses. We demonstrate that EBOV and MARV infected and replicated in primary human DCs without inducing cytokine secretion. Infected DC

  9. [Illness due the Ebola virus: epidemiology and clinical manifestations within the context of an international public health emergency].

    Science.gov (United States)

    Carod-Artal, Francisco J

    2015-03-16

    Introduccion. La epidemia causada por el virus del Ebola en Africa occidental afecta a Guinea, Liberia, Sierra Leona, Nigeria, Mali y Senegal, y es la mas grave desde que se tiene noticia de este filovirus causante de fiebre hemorragica. En este articulo se revisan las caracteristicas epidemiologicas y las manifestaciones clinicas asociadas a la enfermedad por el virus del Ebola. Desarrollo. Hasta el 23 de febrero de 2015 se habian contabilizado 23.729 casos de ebola, con un 40,1% de mortalidad. En la actual epidemia, el virus se transmite al ser humano por tres vias: contacto con fluidos y secreciones de sujetos enfermos ya diagnosticados, contacto con cadaveres durante las ceremonias de enterramiento, y contagio a familiares y personal sanitario por enfermos sin diagnosticar. El Ebola causa una enfermedad grave en humanos. Tras un periodo de incubacion variable (2-21 dias), se inicia un sindrome febril, cefalea, mialgias, artralgias, vomitos y diarrea. La fase avanzada cursa con hemorragias, fracaso de multiples organos, hipotension y choque. Se desconoce la incidencia de manifestaciones neurologicas, aunque se han descrito hemorragias cerebrales y sindromes postinfecciosos en otras fiebres he­morragicas virales. Los cuidados de soporte son vitales. No existe un tratamiento efectivo demostrado, aunque varios pacientes han sido tratados con un coctel de anticuerpos monoclonales (ZMapp). Conclusiones. La identificacion y diagnostico precoz de casos sospechosos, el aislamiento de sujetos enfermos y las medidas de proteccion en el personal sanitario son fundamentales para contener esta epidemia.

  10. Influence of Referral Pathway on Ebola Virus Disease Case-Fatality Rate and Effect of Survival Selection Bias

    Science.gov (United States)

    Damkjær, Mads; Lunding, Suzanne; Dornonville de la Cour, Kenn; Young, Alyssa; Brooks, Tim; Sesay, Tom; Salam, Alex P.; Mishra, Sharmistha; Storgaard, Merete

    2017-01-01

    Case-fatality rates in Ebola treatment centers (ETCs) varied widely during the Ebola virus disease (EVD) outbreak in West Africa. We assessed the influence of referral pathway on ETC case-fatality rates with a retrospective cohort of 126 patients treated at the Mathaska ETC in Port Loko, Sierra Leone. The patients consisted of persons who had confirmed EVD when transferred to the ETC or who had been diagnosed onsite. The case-fatality rate for transferred patients was 46% versus 67% for patients diagnosed onsite (p = 0.02). The difference was mediated by Ebola viral load at diagnosis, suggesting a survival selection bias. Comparisons of case-fatality rates across ETCs and clinical management strategies should account for potential survival selection bias. PMID:28322693

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

    Science.gov (United States)

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

    2016-04-19

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

  12. Yoctomole electrochemical genosensing of Ebola virus cDNA by rolling circle and circle to circle amplification.

    Science.gov (United States)

    Carinelli, S; Kühnemund, M; Nilsson, M; Pividori, M I

    2017-07-15

    This work addresses the design of an Ebola diagnostic test involving a simple, rapid, specific and highly sensitive procedure based on isothermal amplification on magnetic particles with electrochemical readout. Ebola padlock probes were designed to detect a specific L-gene sequence present in the five most common Ebola species. Ebola cDNA was amplified by rolling circle amplification (RCA) on magnetic particles. Further re-amplification was performed by circle-to-circle amplification (C2CA) and the products were detected in a double-tagging approach using a biotinylated capture probe for immobilization on magnetic particles and a readout probe for electrochemical detection by square-wave voltammetry on commercial screen-printed electrodes. The electrochemical genosensor was able to detect as low as 200 ymol, corresponding to 120 cDNA molecules of L-gene Ebola virus with a limit of detection of 33 cDNA molecules. The isothermal double-amplification procedure by C2CA combined with the electrochemical readout and the magnetic actuation enables the high sensitivity, resulting in a rapid, inexpensive, robust and user-friendly sensing strategy that offers a promising approach for the primary care in low resource settings, especially in less developed countries. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. DNA Vaccines delivered by dermal electroporation elicit durable protective immunity against individual or simultaneous infections with lassa and ebola viruses in guinea pigs.

    Science.gov (United States)

    2017-08-22

    DNA vaccines elicit durable protective immunity against individual or simultaneous 1  infections with Lassa and Ebola viruses in guinea pigs 2  3...previously developed optimized DNA vaccines against both Lassa fever and Ebola 15  hemorrhagic fever viruses and demonstrated that they were protective...individually in 16  guinea pig and nonhuman primate models. In this study, we vaccinated groups of strain 17  13 guinea pigs two times, four weeks apart

  14. The Understanding of Ebola Virus Disease (EVD Among Medical Practitioners of Karachi, Pakistan

    Directory of Open Access Journals (Sweden)

    Sadia Shakeel

    2017-06-01

    Full Text Available The World Health Organization (WHO has acknowledged the large West African Ebola virus disease (EVD outbreak to be a community health disaster of global concern, and the spread of disease demands a synchronized response. Medical practitioners have an increased risk of contracting the disease as compared to others as they are directly exposed to patients’ blood or fluids. This study evaluated the knowledge of medical practitioners in Karachi regarding EVD. It was descriptive and exploratory in nature and took place over a period of 4 months, i.e., August 2016 to November 2016. The respondents were randomly selected by convenience sampling and surveyed with a 20-item questionnaire. Overall, 403 questionnaires were included in the study and a response rate of 80.6% was achieved. The majority (56.3% considered themselves to be somewhat knowledgeable; females had more knowledge as compared to male (p < 0.003. More than 80% knew about the 2014 Ebola outbreak in West Africa. Interestingly, the findings revealed that respondents’ knowledge about diagnosis and identification of EVD is good. Respondents considered EVD a severe disease and emphasized on the need for protective measures when contacting affected patients. Interventions should be tailored to focus on areas where respondents showed a lack of knowledge about the disease.

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

    Science.gov (United States)

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

    2015-05-09

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

  16. Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda

    Science.gov (United States)

    Towner, Jonathan S.; Sealy, Tara K.; Khristova, Marina L.; Albariño, César G.; Conlan, Sean; Reeder, Serena A.; Quan, Phenix-Lan; Lipkin, W. Ian; Downing, Robert; Tappero, Jordan W.; Okware, Samuel; Lutwama, Julius; Bakamutumaho, Barnabas; Kayiwa, John; Comer, James A.; Rollin, Pierre E.; Ksiazek, Thomas G.; Nichol, Stuart T.

    2008-01-01

    Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA) and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus) distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines. PMID:19023410

  17. Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda.

    Directory of Open Access Journals (Sweden)

    Jonathan S Towner

    2008-11-01

    Full Text Available Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines.

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

    Directory of Open Access Journals (Sweden)

    Paul Richards

    2015-04-01

    Full Text Available 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.

  19. Ebola management centre proximity associated with reduced delays of healthcare of Ebola Virus Disease (EVD) patients, Tonkolili, Sierra Leone, 2014–15

    Science.gov (United States)

    Danis, Kostas; Greig, Jane; Hoffmann, Alexandra; De Valk, Henriette; Jimissa, Augustine; Tejan, Sumaila; Sankoh, Mohammed; Kleijer, Karline; Turner, Will; Achar, Jay; Duncombe, Jennifer; Lokuge, Kamalini; Gayton, Ivan; Broeder, Rob; Kremer, Ronald; Caleo, Grazia

    2017-01-01

    Between August-December 2014, Ebola Virus Disease (EVD) patients from Tonkolili District were referred for care to two Médecins Sans Frontières (MSF) Ebola Management Centres (EMCs) outside the district (distant EMCs). In December 2014, MSF opened an EMC in Tonkolili District (district EMC). We examined the effect of opening a district-based EMC on time to admission and number of suspect cases dead on arrival (DOA), and identified factors associated with fatality in EVD patients, residents in Tonkolili District. Residents of Tonkolili district who presented between 12 September 2014 and 23 February 2015 to the district EMC and the two distant EMCs were identified from EMC line-lists. EVD cases were confirmed by a positive Ebola PCR test. We calculated time to admission since the onset of symptoms, case-fatality and adjusted Risk Ratios (aRR) using Binomial regression. Of 249 confirmed Ebola cases, 206 (83%) were admitted to the distant EMCs and 43 (17%) to the district EMC. Of them 110 (45%) have died. Confirmed cases dead on arrival (n = 10) were observed only in the distant EMCs. The median time from symptom onset to admission was 6 days (IQR 4,8) in distant EMCs and 3 days (IQR 2,7) in the district EMC (p3 days after symptom onset) in the distant compared with the district EMC, but were less likely (aRR = 0.8; 95%CI 0.6–1.0) to have a high viral load (cycle threshold ≤22). A fatal outcome was associated with a high viral load (aRR 2.6; 95%CI 1.8–3.6) and vomiting at first presentation (aRR 1.4; 95%CI 1.0–2.0). The opening of a district EMC was associated with earlier admission of cases to appropriate care facilities, an essential component of reducing EVD transmission. High viral load and vomiting at admission predicted fatality. Healthcare providers should consider the location of EMCs to ensure equitable access during Ebola outbreaks. PMID:28459838

  20. Ebola management centre proximity associated with reduced delays of healthcare of Ebola Virus Disease (EVD) patients, Tonkolili, Sierra Leone, 2014-15.

    Science.gov (United States)

    Theocharopoulos, Georgios; Danis, Kostas; Greig, Jane; Hoffmann, Alexandra; De Valk, Henriette; Jimissa, Augustine; Tejan, Sumaila; Sankoh, Mohammed; Kleijer, Karline; Turner, Will; Achar, Jay; Duncombe, Jennifer; Lokuge, Kamalini; Gayton, Ivan; Broeder, Rob; Kremer, Ronald; Caleo, Grazia

    2017-01-01

    Between August-December 2014, Ebola Virus Disease (EVD) patients from Tonkolili District were referred for care to two Médecins Sans Frontières (MSF) Ebola Management Centres (EMCs) outside the district (distant EMCs). In December 2014, MSF opened an EMC in Tonkolili District (district EMC). We examined the effect of opening a district-based EMC on time to admission and number of suspect cases dead on arrival (DOA), and identified factors associated with fatality in EVD patients, residents in Tonkolili District. Residents of Tonkolili district who presented between 12 September 2014 and 23 February 2015 to the district EMC and the two distant EMCs were identified from EMC line-lists. EVD cases were confirmed by a positive Ebola PCR test. We calculated time to admission since the onset of symptoms, case-fatality and adjusted Risk Ratios (aRR) using Binomial regression. Of 249 confirmed Ebola cases, 206 (83%) were admitted to the distant EMCs and 43 (17%) to the district EMC. Of them 110 (45%) have died. Confirmed cases dead on arrival (n = 10) were observed only in the distant EMCs. The median time from symptom onset to admission was 6 days (IQR 4,8) in distant EMCs and 3 days (IQR 2,7) in the district EMC (p3 days after symptom onset) in the distant compared with the district EMC, but were less likely (aRR = 0.8; 95%CI 0.6-1.0) to have a high viral load (cycle threshold ≤22). A fatal outcome was associated with a high viral load (aRR 2.6; 95%CI 1.8-3.6) and vomiting at first presentation (aRR 1.4; 95%CI 1.0-2.0). The opening of a district EMC was associated with earlier admission of cases to appropriate care facilities, an essential component of reducing EVD transmission. High viral load and vomiting at admission predicted fatality. Healthcare providers should consider the location of EMCs to ensure equitable access during Ebola outbreaks.

  1. [Establishment of Quality Control System of Nucleic Acid Detection for Ebola Virus in Sierra Leone-China Friendship Biological Safety Laboratory].

    Science.gov (United States)

    Wang, Qin; Zhang, Yong; Nie, Kai; Wang, Huanyu; Du, Haijun; Song, Jingdong; Xiao, Kang; Lei, Wenwen; Guo, Jianqiang; Wei, Hejiang; Cai, Kun; Wang, Yanhai; Wu, Jiang; Gerald, Bangura; Kamara, Idrissa Laybohr; Liang, Mifang; Wu, Guizhen; Dong, Xiaoping

    2016-03-01

    The quality control process throughout the Ebola virus nucleic acid detection in Sierra Leone-China Friendship Biological Safety Laboratory (SLE-CHN Biosafety Lab) was described in detail, in order to comprehensively display the scientific, rigorous, accurate and efficient practice in detection of Ebola virus of first batch detection team in SLE-CHN Biosafety Lab. Firstly, the key points of laboratory quality control system was described, including the managements and organizing, quality control documents and information management, instrument, reagents and supplies, assessment, facilities design and space allocation, laboratory maintenance and biosecurity. Secondly, the application of quality control methods in the whole process of the Ebola virus detection, including before the test, during the test and after the test, was analyzed. The excellent and professional laboratory staffs, the implementation of humanized management are the cornerstone of the success; High-level biological safety protection is the premise for effective quality control and completion of Ebola virus detection tasks. And professional logistics is prerequisite for launching the laboratory diagnosis of Ebola virus. The establishment and running of SLE-CHN Biosafety Lab has landmark significance for the friendship between Sierra Leone and China, and the lab becomes the most important base for Ebola virus laboratory testing in Sierra Leone.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Topoisomerase II Inhibitors Induce DNA Damage-Dependent Interferon Responses Circumventing Ebola Virus Immune Evasion

    Science.gov (United States)

    Luthra, Priya; Aguirre, Sebastian; Yen, Benjamin C.; Pietzsch, Colette A.; Sanchez-Aparicio, Maria T.; Tigabu, Bersabeh; Morlock, Lorraine K.; García-Sastre, Adolfo; Leung, Daisy W.; Williams, Noelle S.; Fernandez-Sesma, Ana; Bukreyev, Alexander

    2017-01-01

    ABSTRACT Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication. PMID:28377530

  6. Alisporivir Has Limited Antiviral Effects Against Ebola Virus Strains Makona and Mayinga.

    Science.gov (United States)

    Chiramel, Abhilash I; Banadyga, Logan; Dougherty, Jonathan D; Falzarano, Darryl; Martellaro, Cynthia; Brees, Dominique; Taylor, R Travis; Ebihara, Hideki; Best, Sonja M

    2016-10-15

    Antiviral therapeutics with existing clinical safety profiles would be highly desirable in an outbreak situation, such as the 2013-2016 emergence of Ebola virus (EBOV) in West Africa. Although, the World Health Organization declared the end of the outbreak early 2016, sporadic cases of EBOV infection have since been reported. Alisporivir is the most clinically advanced broad-spectrum antiviral that functions by targeting a host protein, cyclophilin A (CypA). A modest antiviral effect of alisporivir against contemporary (Makona) but not historical (Mayinga) EBOV strains was observed in tissue culture. However, this effect was not comparable to observations for an alisporivir-susceptible virus, the flavivirus tick-borne encephalitis virus. Thus, EBOV does not depend on (CypA) for replication, in contrast to many other viruses pathogenic to humans. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein.

    Directory of Open Access Journals (Sweden)

    Joseph R Francica

    Full Text Available Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV glycoprotein (GP was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection.

  8. Topoisomerase II Inhibitors Induce DNA Damage-Dependent Interferon Responses Circumventing Ebola Virus Immune Evasion

    Directory of Open Access Journals (Sweden)

    Priya Luthra

    2017-04-01

    Full Text Available Ebola virus (EBOV protein VP35 inhibits production of interferon alpha/beta (IFN by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication.

  9. 埃博拉病毒的研究%Research on Ebola virus

    Institute of Scientific and Technical Information of China (English)

    刘振宇; 郑连群; 王丽; 何晨光

    2004-01-01

    从人类第一次“见识”埃博拉病毒(Ebola virus)至今已经过去28年了,它是人类迄今为止发现死亡率最高的一种病毒,死亡率高达50%~90%。据世界卫生组织公布的数字,自1976年发现此病毒以来,已有感染者1600多例,其中死亡1000多例。EBV是需要实行最高级生物安全防护的烈性病毒,很有可能被用作为生物战剂。

  10. A Perspective on the Development of Plant-Made Vaccines in the Fight against Ebola Virus

    Science.gov (United States)

    Rosales-Mendoza, Sergio; Nieto-Gómez, Ricardo; Angulo, Carlos

    2017-01-01

    The Ebola virus (EBOV) epidemic indicated a great need for prophylactic and therapeutic strategies. The use of plants for the production of biopharmaceuticals is a concept being adopted by the pharmaceutical industry, with an enzyme for human use currently commercialized since 2012 and some plant-based vaccines close to being commercialized. Although plant-based antibodies against EBOV are under clinical evaluation, the development of plant-based vaccines against EBOV essentially remains an unexplored area. The current technologies for the production of plant-based vaccines include stable nuclear expression, transient expression mediated by viral vectors, and chloroplast expression. Specific perspectives on how these technologies can be applied for developing anti-EBOV vaccines are provided, including possibilities for the design of immunogens as well as the potential of the distinct expression modalities to produce the most relevant EBOV antigens in plants considering yields, posttranslational modifications, production time, and downstream processing. PMID:28344580

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-02-11

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

  12. Ebola virus infection induces autoimmunity against dsDNA and HSP60

    Science.gov (United States)

    Fausther-Bovendo, H.; Qiu, X.; McCorrister, S.; Westmacott, G.; Sandstrom, P.; Castilletti, C.; Di Caro, A.; Ippolito, G.; Kobinger, G. P.

    2017-01-01

    Ebola virus (EBOV) survivors are affected by a variety of serious illnesses of unknown origin for years after viral clearance from the circulation. Identifying the causes of these persistent illnesses is paramount to develop appropriate therapeutic protocols. In this study, using mouse and non-human primates which survived EBOV challenge, ELISA, western blot, mass spectrometry and flow cytometry were used to screen for autoantibodies, identify their main targets, investigate the mechanism behind their induction and monitor autoantibodies accumulation in various tissues. In infected mice and NHP, polyclonal B cell activation and autoantigens secretion induced autoantibodies against dsDNA and heat shock protein 60 as well as antibody accumulation in tissues associated with long-term clinical manifestations in humans. Finally, the presence of these autoantibodies was confirmed in human EBOV survivors. Overall, this study supports the concept that autoimmunity is a causative parameter that contributes to the various illnesses observed in EBOV survivors. PMID:28181533

  13. Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak.

    Science.gov (United States)

    Bornholdt, Zachary A; Turner, Hannah L; Murin, Charles D; Li, Wen; Sok, Devin; Souders, Colby A; Piper, Ashley E; Goff, Arthur; Shamblin, Joshua D; Wollen, Suzanne E; Sprague, Thomas R; Fusco, Marnie L; Pommert, Kathleen B J; Cavacini, Lisa A; Smith, Heidi L; Klempner, Mark; Reimann, Keith A; Krauland, Eric; Gerngross, Tillman U; Wittrup, Karl D; Saphire, Erica Ollmann; Burton, Dennis R; Glass, Pamela J; Ward, Andrew B; Walker, Laura M

    2016-03-01

    Antibodies targeting the Ebola virus surface glycoprotein (EBOV GP) are implicated in protection against lethal disease, but the characteristics of the human antibody response to EBOV GP remain poorly understood. We isolated and characterized 349 GP-specific monoclonal antibodies (mAbs) from the peripheral B cells of a convalescent donor who survived the 2014 EBOV Zaire outbreak. Remarkably, 77% of the mAbs neutralize live EBOV, and several mAbs exhibit unprecedented potency. Structures of selected mAbs in complex with GP reveal a site of vulnerability located in the GP stalk region proximal to the viral membrane. Neutralizing antibodies targeting this site show potent therapeutic efficacy against lethal EBOV challenge in mice. The results provide a framework for the design of new EBOV vaccine candidates and immunotherapies.

  14. Diagnostics in Ebola Virus Disease in Resource-Rich and Resource-Limited Settings.

    Directory of Open Access Journals (Sweden)

    Robert J Shorten

    2016-10-01

    Full Text Available The Ebola virus disease (EVD outbreak in West Africa was unprecedented in scale and location. Limited access to both diagnostic and supportive pathology assays in both resource-rich and resource-limited settings had a detrimental effect on the identification and isolation of cases as well as individual patient management. Limited access to such assays in resource-rich settings resulted in delays in differentiating EVD from other illnesses in returning travellers, in turn utilising valuable resources until a diagnosis could be made. This had a much greater impact in West Africa, where it contributed to the initial failure to contain the outbreak. This review explores diagnostic assays of use in EVD in both resource-rich and resource-limited settings, including their respective limitations, and some novel assays and approaches that may be of use in future outbreaks.

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

    Science.gov (United States)

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

    2015-01-01

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

  16. The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo

    Science.gov (United States)

    Groseth, Allison; Marzi, Andrea; Hoenen, Thomas; Herwig, Astrid; Gardner, Don; Becker, Stephan; Ebihara, Hideki; Feldmann, Heinz

    2012-01-01

    Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence for such a role in the context of virus infection has been notably lacking. In order to assess the role of GP in EBOV virulence, we have developed a novel reverse genetics system for REBOV, which we report here. Together with a previously published full-length clone for Zaire ebolavirus (ZEBOV), this provides a unique possibility to directly investigate the role of an entire filovirus protein in pathogenesis. To this end we have generated recombinant ZEBOV (rZEBOV) and REBOV (rREBOV), as well as chimeric viruses in which the glycoproteins from these two virus species have been exchanged (rZEBOV-RGP and rREBOV-ZGP). All of these viruses could be rescued and the chimeras replicated with kinetics similar to their parent virus in tissue culture, indicating that the exchange of GP in these chimeric viruses is well tolerated. However, in a mouse model of infection rZEBOV-RGP demonstrated markedly decreased lethality and prolonged time to death when compared to rZEBOV, confirming that GP does indeed contribute to the full expression of virulence by ZEBOV. In contrast, rREBOV-ZGP did not show any signs of virulence, and was in fact slightly attenuated compared to rREBOV, demonstrating that GP alone is not sufficient to confer a lethal phenotype or exacerbate disease in this model. Thus, while these findings provide direct evidence that GP contributes to filovirus virulence in vivo, they also clearly indicate that other factors are needed for the acquisition of full virulence. PMID:22876185

  17. Etiology for Ebola virus disease%埃博拉病毒病之病原学

    Institute of Scientific and Technical Information of China (English)

    饶贤才

    2015-01-01

    埃博拉病毒病(Ebola virus disease,EVD),以往称埃博拉出血热(Ebola haemorrhagic fever,EHF),是迄今发现的凶猛烈性传染病之一.自1976年发现于非洲的扎伊尔和苏丹后,至今已有8次较大规模的人群流行,均发生在非洲,平均病死率高达67.98%.EVD的病原体埃博拉病毒(Ebola virus,EBOV)是一种人兽共患病原体,虽然其自然储存宿主尚不完全清楚,但EBOV能造成非人灵长类动物(如黑猩猩、猴等)感染,并具有致死性.EBOV在分类上属于丝状病毒科(Filoviridae)的埃博拉病毒属(Ebolavirus),属内有5个种.各种间的毒力存在差异,以扎伊尔埃博拉病毒(Zaire-EBOV)致病性最强,也是引起2014年西非大规模流行的元凶.EBOV呈丝状,形态多样,以长丝分枝状为常见;病毒体由核心、核衣壳和包膜3部分构成,病毒基因组为单股负链RNA,可编码7种结构蛋白,在病毒复制、感染和致病中发挥重要作用.EBOV主要通过接触传播,目前对其致病机制尚不完全清楚.EBOV为生物危害度最高的4级病原体,与活病毒相关的检验和实验必须在生物安全4级(BSL-4)实验室中进行,其感染的临床诊断以检测血清中抗体、抗原和核酸为主,实时荧光定量反转录PCR检测阳性可作出诊断.EVD尚无特效治疗方法,疫苗尚在研制之中,临床上以辅助性支持疗法为主.

  18. 埃博拉病毒及其致病机制%Ebola virus and its pathogenesis

    Institute of Scientific and Technical Information of China (English)

    瞿涤; 袁正宏; 闻玉梅

    2014-01-01

    自2014年2~3月,西非埃博拉病毒感染的暴发流行已呈播散趋势,受到世界卫生组织的高度重视。我国也提高了防止埃博拉病毒进入国内的警示,并采取了相应措施。现将有关埃博拉病毒的生物学特性、致病机制及相关流行病学与防治策略作简要综述,供参考。%The 2014 outbreak of Ebola virus in West Africa has shown the potential to spread to other regions .This has been highly alerted by World Health Organization ,and China also has adopted measures to prevent Ebola virus crossing the border .In this short review ,we introduce the virology and pathogenesis of this deadly virus ,while the epidemiology and prevention and treatment for Ebola virus infection are also included .

  19. 埃博拉疫苗研究新进展%Recent advances in Ebola virus vaccine development

    Institute of Scientific and Technical Information of China (English)

    郑学星; 杨松涛; 王化磊; 夏咸柱

    2013-01-01

    埃博拉病毒是一种高致病性病原体,致死率高达90%.目前尚未有批准的疫苗用于其暴露前后的预防.近年来一些自然感染的埃博拉病例数增加,且埃博拉病毒被视为生物战剂,对公共安全构成威胁,因此研究埃博拉疫苗具有十分重要的意义.近年来埃博拉疫苗研究取得了明显的进步,一些候选疫苗证实可以保护非人灵长类动物.这些疫苗包括复制缺陷型腺病毒载体、可复制VSV、HPIV-3载体疫苗,以及病毒样颗粒疫苗.由于暴露后免疫十分重要,尤其是用于自然偶发感染,保护实验室相关人员,以及应对生物攻击.因此,当前的研究主要集中在高效的暴露后疫苗,特别是一次注射即可完全保护的疫苗.%The Ebola virus is a highly infectious pathogen with a fatality rate as high as 90%.Currently,there is no licensed Ebola virus vaccine for pre-or post-exposure treatments.In recent years,the frequency of natural human Ebola virus infections has increased and it can potentially be used as a bioterrorism agent,thus posing a threat to public safety.These facts have highlighted the significance of developing an Ebola vaccine.Recently,significant progress has been made in research on the Ebola vaccine,and several promising vaccine candidates including replication-deficient adenovirus vectors,replication competent VSV,HPIV-3 vectors,and virus-like particle preparations have proven successful in protecting NHPs against lethal infection.Post-exposure protection is particularly important to limiting outbreaks and providing biodefense,and it can also help clinical and laboratory personnel in the event of accidental exposure.Therefore,current research has focused on the development of effective post-exposure vaccines,and particularly on single-dose vaccines that can confer full protection to humans following exposure to the Ebola virus.

  20. Ebola viral selenoproteins: a metallomics analysis

    Directory of Open Access Journals (Sweden)

    Somsri Wiwanitkit

    2015-01-01

    Full Text Available Ebola virus infection is the present public health problem. The trend of worldwide epidemic becomes the serious consideration for this infection. The Ebola virus infection has main clinical manifestation as acute febrile illness with hemorrhagic episode. The problem of hemostatic disturbance can be seen. Focusing on the pathophysiology, selenium plays an important role in the blood clotting regulation. The study on the selenoprotein of the Ebola virus can be useful for further understanding on the pathology of the infection. Here, the authors use metallomics analysis for assessment of Ebola virus genome. According to this study, the selenoprotein portion within Ebola virus genome can be detected at position 1046-1115.

  1. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.

    Science.gov (United States)

    Martines, Roosecelis Brasil; Ng, Dianna L; Greer, Patricia W; Rollin, Pierre E; Zaki, Sherif R

    2015-01-01

    Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  5. Complex of a Protective Antibody with its Ebola Virus GP Peptide Epitope: Unusual Features of a Vlambdalx Light Chain

    Science.gov (United States)

    2008-01-01

    Fields Virology (Fields, B. N., Knipe, D. M. & Howley, P. M., eds), 3rd edit., vol. 1, pp. 1161–1176, Lippincott-Raven Press, Inc., Philadelphia, PA. 2...S187. 40. Sanchez, A., Khan, A. S., Zaki, S. R., Nabel, G. J., Ksiazek, T. G. & Peters, C. J. (2001). Filoviridae: Marburg and Ebola viruses. In Fields ... Virology (Knipe, D. M. & Howley, P. M., eds), pp. 1279–1304, Lippincott, Williams, and Wilkins, Philadelphia. 41. Tsurushita, N., Hinton, P. R

  6. Monitoring of Persons with Risk for Exposure to Ebola Virus Disease - United States, November 3, 2014-March 8, 2015.

    Science.gov (United States)

    Stehling-Ariza, Tasha; Fisher, Emily; Vagi, Sara; Fechter-Leggett, Ethan; Prudent, Natasha; Dott, Mary; Daley, Randolph; Avchen, Rachel Nonkin

    2015-07-03

    On October 27, 2014, CDC released guidance for monitoring and movement of persons with potential Ebola virus disease (Ebola) exposure in the United States. For persons with possible exposure to Ebola, this guidance recommended risk categorization, daily monitoring during the 21-day incubation period, and, for persons in selected risk categories, movement restrictions. The purpose of the guidance was to delineate methods for early identification of symptoms among persons at potential risk for Ebola so that they could be isolated, tested, and if necessary, treated to improve their chance of survival and reduce transmission. Within 7 days, all 50 states and two local jurisdictions (New York City [NYC] and the District of Columbia [DC]) had implemented the guidelines. During November 3, 2014-March 8, 2015, a total of 10,344 persons were monitored for up to 21 days with >99% complete monitoring. This public health response demonstrated the ability of state, territorial, and local health agencies to rapidly implement systems to effectively monitor thousands of persons over a sustained period.

  7. The development of a massive open online course during the 2014-15 Ebola virus disease epidemic.

    Science.gov (United States)

    Evans, Dabney P; Luffy, Samantha M; Parisi, Stephanie; Del Rio, Carlos

    2017-08-12

    Timely training was urgently needed at the onset of the 2014 Ebola virus disease epidemic. Massive open online courses (MOOCs) have grown in popularity, though little is known about their utility in time-sensitive situations, including infectious disease outbreaks. We created the first English language massive open online course on Ebola virus disease. Designed by a team representing various units of Emory University and six partner institutions, the six module course was aimed at a global general audience but also relevant for health care professionals. Over 7,000 learners from 170 countries participated in the initial course offering. More than a third of learners were from emerging economies, including seven percent from Africa, and another 13% from countries outside the United States who received individuals requiring treatment for Ebola virus disease. Creating and producing the first English language MOOC on EVD in a short time period required effective collaboration and strong coordination between subject matter and course development experts from Emory. Through these collaborative efforts, the development team was able to provide urgently needed training and educational materials while the epidemic of EVD continued to radiate through West Africa. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-08-06

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

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

    Science.gov (United States)

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

    2016-04-22

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

  10. Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

    Science.gov (United States)

    Vernet, Marie-Astrid; Reynard, Stéphanie; Fizet, Alexandra; Schaeffer, Justine; Pannetier, Delphine; Rives, Max; Georges, Nadia; Garcia-Bonnet, Nathalie; Sylla, Aboubacar I.; Grovogui, Péma; Kerherve, Jean-Yves; Savio, Christophe; Savio-Coste, Sylvie; de Séverac, Marie-Laure; Linares, Sandrine; Harouna, Souley; Abdoul, Bing M’Lebing; Petitjean, Frederic; Samake, Nenefing; Kinda, Moumouni; Koundouno, Fara Roger; Mateo, Mathieu; Lecine, Patrick; Page, Audrey; Tchamdja, Tang Maleki; Schoenhals, Matthieu; Barbe, Solenne; Simon, Bernard; Tran-Minh, Tuan; L’Hériteau, François

    2017-01-01

    BACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P. falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of

  11. Ebola: Implications and Perspectives.

    Science.gov (United States)

    Del Rio, Carlos; Guarner, Jeannette

    2015-01-01

    The 2014 Ebola virus disease outbreak in West Africa has been the largest in recorded history. During this Ebola epidemic, the media has focused much attention to the magnitude of the problem in West Africa but has also overplayed the potential for an Ebola virus pandemic as patients have been transported for treatment to the United States and Europe causing panic and paranoia in the population. Knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and prevention of this infection will allow a better understanding of the disease and decrease irrational fear of spread.

  12. Ebola: Implications and Perspectives

    Science.gov (United States)

    Del Rio, Carlos; Guarner, Jeannette

    2015-01-01

    The 2014 Ebola virus disease outbreak in West Africa has been the largest in recorded history. During this Ebola epidemic, the media has focused much attention to the magnitude of the problem in West Africa but has also overplayed the potential for an Ebola virus pandemic as patients have been transported for treatment to the United States and Europe causing panic and paranoia in the population. Knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and prevention of this infection will allow a better understanding of the disease and decrease irrational fear of spread. PMID:26330663

  13. Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function.

    Science.gov (United States)

    García-Dorival, Isabel; Wu, Weining; Dowall, Stuart; Armstrong, Stuart; Touzelet, Olivier; Wastling, Jonathan; Barr, John N; Matthews, David; Carroll, Miles; Hewson, Roger; Hiscox, Julian A

    2014-11-07

    Viral pathogenesis in the infected cell is a balance between antiviral responses and subversion of host-cell processes. Many viral proteins specifically interact with host-cell proteins to promote virus biology. Understanding these interactions can lead to knowledge gains about infection and provide potential targets for antiviral therapy. One such virus is Ebola, which has profound consequences for human health and causes viral hemorrhagic fever where case fatality rates can approach 90%. The Ebola virus VP24 protein plays a critical role in the evasion of the host immune response and is likely to interact with multiple cellular proteins. To map these interactions and better understand the potential functions of VP24, label-free quantitative proteomics was used to identify cellular proteins that had a high probability of forming the VP24 cellular interactome. Several known interactions were confirmed, thus placing confidence in the technique, but new interactions were also discovered including one with ATP1A1, which is involved in osmoregulation and cell signaling. Disrupting the activity of ATP1A1 in Ebola-virus-infected cells with a small molecule inhibitor resulted in a decrease in progeny virus, thus illustrating how quantitative proteomics can be used to identify potential therapeutic targets.

  14. Measuring the strength of interaction between the Ebola fusion peptide and lipid rafts: implications for membrane fusion and virus infection.

    Directory of Open Access Journals (Sweden)

    Mônica S Freitas

    Full Text Available The Ebola fusion peptide (EBO₁₆ is a hydrophobic domain that belongs to the GP2 membrane fusion protein of the Ebola virus. It adopts a helical structure in the presence of mimetic membranes that is stabilized by the presence of an aromatic-aromatic interaction established by Trp8 and Phe12. In spite of its infectious cycle becoming better understood recently, several steps still remain unclear, a lacuna that makes it difficult to develop strategies to block infection. In order to gain insight into the mechanism of membrane fusion, we probed the structure, function and energetics of EBO₁₆ and its mutant W8A, in the absence or presence of different lipid membranes, including isolated domain-resistant membranes (DRM, a good experimental model for lipid rafts. The depletion of cholesterol from living mammalian cells reduced the ability of EBO₁₆ to induce lipid mixing. On the other hand, EBO₁₆ was structurally sensitive to interaction with lipid rafts (DRMs, but the same was not observed for W8A mutant. In agreement with these data, W8A showed a poor ability to promote membrane aggregation in comparison to EBO₁₆. Single molecule AFM experiments showed a high affinity force pattern for the interaction of EBO₁₆ and DRM, which seems to be a complex energetic event as observed by the calorimetric profile. Our study is the first to show a strong correlation between the initial step of Ebola virus infection and cholesterol, thus providing a rationale for Ebola virus proteins being co-localized with lipid-raft domains. In all, the results show how small fusion peptide sequences have evolved to adopt highly specific and strong interactions with membrane domains. Such features suggest these processes are excellent targets for therapeutic and vaccine approaches to viral diseases.

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

    Directory of Open Access Journals (Sweden)

    Michael Schuit

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

  16. Ebola Can Linger in Lungs, Study Finds

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162904.html Ebola Can Linger in Lungs, Study Finds Discovery in ... Researchers say they've discovered signs that the Ebola virus could lurk in the lungs and reproduce ...

  17. Ebola Vaccine Appears Very Effective in Trial

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_162715.html Ebola Vaccine Appears Very Effective in Trial Drug manufacturer says ... Dec. 23, 2016 (HealthDay News) -- An experimental Ebola vaccine was highly effective against the deadly virus in ...

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

    Science.gov (United States)

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

    2015-10-01

    Rapid inactivation of Ebola virus (EBOV) is crucial for high-throughput testing of clinical samples in low-resource, outbreak scenarios. The EBOV inactivation efficacy of Buffer AVL (Qiagen) was tested against marmoset serum (EBOV concentration of 1 × 10(8) 50% tissue culture infective dose per milliliter [TCID50 · ml(-1)]) and murine blood (EBOV concentration of 1 × 10(7) TCID50 · ml(-1)) at 4:1 vol/vol buffer/sample ratios. Posttreatment cell culture and enzyme-linked immunosorbent assay (ELISA) analysis indicated that treatment with Buffer AVL did not inactivate EBOV in 67% of samples, indicating that Buffer AVL, which is designed for RNA extraction and not virus inactivation, cannot be guaranteed to inactivate EBOV in diagnostic samples. Murine blood samples treated with ethanol (4:1 [vol/vol] ethanol/sample) or heat (60°C for 15 min) also showed no viral inactivation in 67% or 100% of samples, respectively. However, combined Buffer AVL and ethanol or Buffer AVL and heat treatments showed total viral inactivation in 100% of samples tested. The Buffer AVL plus ethanol and Buffer AVL plus heat treatments were also shown not to affect the extraction of PCR quality RNA from EBOV-spiked murine blood samples. © Crown copyright 2015.

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

    Science.gov (United States)

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

    2016-01-22

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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. An Outbreak of Ebola Virus Disease in the Lassa Fever Zone.

    Science.gov (United States)

    Goba, Augustine; Khan, S Humarr; Fonnie, Mbalu; Fullah, Mohamed; Moigboi, Alex; Kovoma, Alice; Sinnah, Vandi; Yoko, Nancy; Rogers, Hawa; Safai, Siddiki; Momoh, Mambu; Koroma, Veronica; Kamara, Fatima K; Konowu, Edwin; Yillah, Mohamed; French, Issa; Mustapha, Ibraham; Kanneh, Franklyn; Foday, Momoh; McCarthy, Helena; Kallon, Tiangay; Kallon, Mustupha; Naiebu, Jenneh; Sellu, Josephine; Jalloh, Abdul A; Gbakie, Michael; Kanneh, Lansana; Massaly, James L B; Kargbo, David; Kargbo, Brima; Vandi, Mohamed; Gbetuwa, Momoh; Gevao, Sahr M; Sandi, John D; Jalloh, Simbirie C; Grant, Donald S; Blyden, Sylvia O; Crozier, Ian; Schieffelin, John S; McLellan, Susan L; Jacob, Shevin T; Boisen, Matt L; Hartnett, Jessica N; Cross, Robert W; Branco, Luis M; Andersen, Kristian G; Yozwiak, Nathan L; Gire, Stephen K; Tariyal, Ridhi; Park, Daniel J; Haislip, Allyson M; Bishop, Christopher M; Melnik, Lilia I; Gallaher, William R; Wimley, William C; He, Jing; Shaffer, Jeffrey G; Sullivan, Brian M; Grillo, Sonia; Oman, Scott; Garry, Courtney E; Edwards, Donna R; McCormick, Stephanie J; Elliott, Deborah H; Rouelle, Julie A; Kannadka, Chandrika B; Reyna, Ashley A; Bradley, Benjamin T; Yu, Haini; Yenni, Rachael E; Hastie, Kathryn M; Geisbert, Joan B; Kulakosky, Peter C; Wilson, Russell B; Oldstone, Michael B A; Pitts, Kelly R; Henderson, Lee A; Robinson, James E; Geisbert, Thomas W; Saphire, Erica Ollmann; Happi, Christian T; Asogun, Danny A; Sabeti, Pardis C; Garry, Robert F

    2016-10-15

     Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs.  Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities.  Augustine Goba, director of the KGH Lassa laboratory, diagnosed the first documented case of EVD in Sierra Leone, on 25 May 2014. Thereafter, KGH received and cared for numbers of patients with EVD that quickly overwhelmed the capacity for safe management. Numerous healthcare workers contracted and lost their lives to EVD. The vast majority of subsequent EVD cases in West Africa can be traced back to a single transmission chain that includes this first diagnosed case.  Responding to the challenges of confronting 2 hemorrhagic fever viruses will require continued investments in the development of countermeasures (vaccines, therapeutic agents, and diagnostic assays), infrastructure, and human resources. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. Digital sensing and sizing of vesicular stomatitis virus pseudotypes in complex media: a model for Ebola and Marburg detection.

    Science.gov (United States)

    Daaboul, George G; Lopez, Carlos A; Chinnala, Jyothsna; Goldberg, Bennett B; Connor, John H; Unlü, M Selim

    2014-06-24

    Rapid, sensitive, and direct label-free capture and characterization of nanoparticles from complex media such as blood or serum will broadly impact medicine and the life sciences. We demonstrate identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (VSV), defective VSV, and Ebola- and Marburg-pseudotyped VSV with high sensitivity and specificity. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of nonspecifically bound particles to achieve a limit-of-detection (LOD) of 5 × 10(3) pfu/mL for the Ebola and Marburg VSV pseudotypes. We demonstrate the simultaneous detection of multiple viruses in a single sample (composed of serum or whole blood) for screening applications and uncompromised detection capabilities in samples contaminated with high levels of bacteria. By employing affinity-based capture, size discrimination, and a "digital" detection scheme to count single virus particles, we show that a robust and sensitive virus/nanoparticle sensing assay can be established for targets in complex samples. The nanoparticle microscopy system is termed the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) and is capable of high-throughput and rapid sizing of large numbers of biological nanoparticles on an antibody microarray for research and diagnostic applications.

  3. Infection of XC cells by MLVs and Ebola virus is endosome-dependent but acidification-independent.

    Science.gov (United States)

    Kamiyama, Haruka; Kakoki, Katsura; Yoshii, Hiroaki; Iwao, Masatomo; Igawa, Tsukasa; Sakai, Hideki; Hayashi, Hideki; Matsuyama, Toshifumi; Yamamoto, Naoki; Kubo, Yoshinao

    2011-01-01

    Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells.

  4. Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses.

    Science.gov (United States)

    Geisbert, Thomas W; Daddario-Dicaprio, Kathleen M; Geisbert, Joan B; Reed, Douglas S; Feldmann, Friederike; Grolla, Allen; Ströher, Ute; Fritz, Elizabeth A; Hensley, Lisa E; Jones, Steven M; Feldmann, Heinz

    2008-12-09

    Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.

  5. Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Thomas W Geisbert

    2008-11-01

    Full Text Available Ebola virus (EBOV is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVDeltaG/ZEBOVGP in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV. All six animals showed no evidence of illness associated with the VSVDeltaG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.

  6. Label free checkerboard assay to determine overlapping epitopes of Ebola virus VP-40 antibodies using surface plasmon resonance.

    Science.gov (United States)

    Anderson, George P; Liu, Jinny L; Zabetakis, Dan; Legler, Patricia M; Goldman, Ellen R

    2017-03-01

    Immunoassay formats, in which antibodies provide sensitivity and specificity, are often utilized to provide rapid and simple diagnostic tests. Surface plasmon resonance is frequently used to evaluate the suitability of antibodies by determining binding kinetics to agents or surrogate antigens. We used SPR to evaluate a number of commercial monoclonal antibodies as well as single domain antibodies produced in-house. All the antibodies targeted the Ebola virus viral protein 40 (VP40). We determined the ability of each antibody to bind to immobilized VP40, and ensured they did not bind Ebola glycoprotein or the nucleoprotein. A subset of the monoclonal antibodies was immobilized to characterize antigen capture in solution. It can be advantageous to utilize antibodies that recognize distinct epitopes when choosing reagents for detection and diagnostic assays. We determined the uniqueness of the epitope recognized by the anti-VP40 antibodies using a checkerboard format that exploits the 6×6 array of interactions monitored by the Bio-Rad ProteOn XPR36 SPR instrument. The results demonstrate the utility of surface plasmon resonance to characterize monoclonal and recombinant antibodies. Additionally, the analysis presented here enabled the identification of pairs of anti-VP40 antibodies which could potentially be utilized in sandwich type immunoassays for the detection of Ebola virus.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  9. Evaluating clinical trial designs for investigational treatments of Ebola virus disease.

    Directory of Open Access Journals (Sweden)

    Ben S Cooper

    2015-04-01

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

  10. Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone.

    Science.gov (United States)

    Ji, Ying-Jie; Duan, Xue-Zhang; Gao, Xu-Dong; Li, Lei; Li, Chen; Ji, Dong; Li, Wen-Gang; Wang, Li-Fu; Meng, Yu-Hua; Yang, Xiao; Ling, Bin-Fang; Song, Xue-Ai; Gu, Mei-Lei; Jiang, Tao; Koroma, She-Ku M; Bangalie, James; Duan, Hui-Juan

    2016-11-03

    Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥10(6) copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients' survival was less than 15 % when blood viral load was greater than 10(6) copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1-4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients.

  11. 浅析埃博拉病毒致病机制%Brief summary on pathogenic mechanism of Ebola virus

    Institute of Scientific and Technical Information of China (English)

    盛子洋; 范东瀛; 安静

    2014-01-01

    埃博拉病毒(Ebola virus,EBOV)属于丝状病毒科的单股负链RNA病毒,人体感染后可导致致命的埃博拉病毒病(Ebola viral disease,EVD).当前EBOV广泛流行于非洲大陆,传染性强、致死率高、曾造成多次大暴发,严重威胁着疫区人们的健康和生命.然而目前EBOV的致病机制尚不明确,本文仅就EHF发病机制的最新进展做一综述,供广大同行参考.

  12. Long-term survival of an urban fruit bat seropositive for Ebola and Lagos bat viruses.

    Directory of Open Access Journals (Sweden)

    David T S Hayman

    Full Text Available Ebolaviruses (EBOV (family Filoviridae cause viral hemorrhagic fevers in humans and non-human primates when they spill over from their wildlife reservoir hosts with case fatality rates of up to 90%. Fruit bats may act as reservoirs of the Filoviridae. The migratory fruit bat, Eidolon helvum, is common across sub-Saharan Africa and lives in large colonies, often situated in cities. We screened sera from 262 E. helvum using indirect fluorescent tests for antibodies against EBOV subtype Zaire. We detected a seropositive bat from Accra, Ghana, and confirmed this using western blot analysis. The bat was also seropositive for Lagos bat virus, a Lyssavirus, by virus neutralization test. The bat was fitted with a radio transmitter and was last detected in Accra 13 months after release post-sampling, demonstrating long-term survival. Antibodies to filoviruses have not been previously demonstrated in E. helvum. Radio-telemetry data demonstrates long-term survival of an individual bat following exposure to viruses of families that can be highly pathogenic to other mammal species. Because E. helvum typically lives in large urban colonies and is a source of bushmeat in some regions, further studies should determine if this species forms a reservoir for EBOV from which spillover infections into the human population may occur.

  13. FORMACIÓN DE PORO EN MEMBRANA CELULAR POR MEDIO DE LA PEQUEÑA GLICOPROTEÍNA DE SECRECIÓN DEL VIRUS DE EBOLA ZAIRE

    Directory of Open Access Journals (Sweden)

    Nury EsperanzaVargas-Alejo

    2004-12-01

    Full Text Available Uno de los patógenos capaces de inducir fiebres hemorrágicas es el virus de Ebola, clasificado en la familia filoviridae con cuatro subtipos, de los cuales el más analizado es el subtipo de Ebola Zaire, identificando en su genoma siete proteínas estructurales y una de secreción denominada pequeña glicoproteína de secreción del virus de Ebola Zaire.Utilizando las herramientas de bioinformática y los diferentes estudios realizados al virus de Ebola Zaire a escala estructural y funcional, se logró predecir la estructura terciaria de su pequeña glicoproteína de secreción (SSGP EBO-Z. Basados en esta estructura se generó un posible modelo del mecanismo de entrada del virus de Ebola Zaire a la célula huésped, donde juegan un papel importante los receptores y ligandos de la membrana celular; permitiendo a la vez explicar los daños patológicos encontrados en los pacientes.

  14. 埃博拉病毒生物学特性研究进展%Biological characteristics of Ebola virus:research advances

    Institute of Scientific and Technical Information of China (English)

    张毅; 钱军; 曲英龙; 郭振东; 赵思言; 付莹莹; 赵红艳; 王中一; 赵宗正; 刘林娜

    2015-01-01

    Ebola virus disease , which can cause ebola hemorrhagic fever , is a potent zoonotic infectious virus disease . In 2014 , Ebola virus spread across West Africa and it has become a new major threat to global public health .This article summarizes the structural features of Ebola virus , transmission characteristics , interactions ,animal models .%埃博拉病毒病是一种能够引发埃博拉出血热的人畜共患烈性传染病。2014年蔓延西非三国的埃博拉病毒(Ebola virus,EBOV)已经成为全球性公共卫生新的重大威胁。该文综述了EBOV的结构特征、传播特点、作用方式、动物模型等方面的研究进展,旨在对EBOV生物学特性的全面了解及针对该病新型疫苗和抗病毒药物的研制奠定基础。

  15. Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

    Directory of Open Access Journals (Sweden)

    Joseph E Blaney

    Full Text Available We have previously described the generation of a novel Ebola virus (EBOV vaccine platform based on (a replication-competent rabies virus (RABV, (b replication-deficient RABV, or (c chemically inactivated RABV expressing EBOV glycoprotein (GP. Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

  16. Clinical characteristics and treatment of Ebola virus disease%埃博拉病毒病临床特征与治疗

    Institute of Scientific and Technical Information of China (English)

    张健; 苏海滨

    2016-01-01

    Ebola virus disease (EVD) is a fatal disease caused by Ebola virus infection with high morbidity rate. Clinical manifestations of EVD are not specific and the diagnosis of EVD is confirmed mainly by etiology examination. So far, the mainstay therapy is supportive care, and efforts to develop other potential therapies are ongoing. This article focuses on the clinical characteristics and treatment of EVD.%埃博拉病毒病(Ebola virus disease, EVD)是由埃博拉病毒引起的烈性传染病,致死率高.EVD 临床表现无特异性,确诊主要依靠病原学检查.目前以对症支持治疗为主,其他可能的治疗方案在不断研究探索中.本文对 EVD 的临床特征及治疗进行综述.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-05-20

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

  18. Molecular Characterization of the Monoclonal Antibodies Composing ZMAb: A Protective Cocktail Against Ebola Virus

    Science.gov (United States)

    Audet, Jonathan; Wong, Gary; Wang, Han; Lu, Guangwen; Gao, George F.; Kobinger, Gary; Qiu, Xiangguo

    2014-01-01

    Ebola virus (EBOV) causes severe viral hemorrhagic fever in humans and non-human primates, with a case fatality rate of up to 88% in human outbreaks. Over the past 3 years, monoclonal antibody (mAb) cocktails have demonstrated high efficacy as treatments against EBOV infection. One such cocktail is ZMAb, which consists of three mouse antibodies, 1H3, 2G4, and 4G7. Here, we present the epitope binding properties of mAbs 1H3, 2G4, and 4G7. We showed that these antibodies have different variable region sequences, suggesting that the individual mAbs are not clonally related. All three antibodies were found to neutralize EBOV variant Mayinga. Additionally, 2G4 and 4G7 were shown to cross-inhibit each other in vitro and select for an escape mutation at the same position on the EBOV glycoprotein (GP), at amino acid 508. 1H3 selects an escape mutant at amino acid 273 on EBOV GP. Surface plasmon resonance studies showed that all three antibodies have dissociation constants on the order of 10−7. In combination with previous studies evaluating the binding sites of other protective antibodies, our results suggest that antibodies targeting the GP1-GP2 interface and the glycan cap are often selected as efficacious antibodies for post-exposure interventions against EBOV. PMID:25375093

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

    Directory of Open Access Journals (Sweden)

    Todd Bell

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

  1. A chaotic model for the epidemic of Ebola virus disease in West Africa (2013-2016).

    Science.gov (United States)

    Mangiarotti, Sylvain; Peyre, Marisa; Huc, Mireille

    2016-11-01

    An epidemic of Ebola Virus Disease (EVD) broke out in Guinea in December 2013. It was only identified in March 2014 while it had already spread out in Liberia and Sierra Leone. The spill over of the disease became uncontrollable and the epidemic could not be stopped before 2016. The time evolution of this epidemic is revisited here with the global modeling technique which was designed to obtain the deterministic models from single time series. A generalized formulation of this technique for multivariate time series is introduced. It is applied to the epidemic of EVD in West Africa focusing on the period between March 2014 and January 2015, that is, before any detected signs of weakening. Data gathered by the World Health Organization, based on the official publications of the Ministries of Health of the three main countries involved in this epidemic, are considered in our analysis. Two observed time series are used: the daily numbers of infections and deaths. A four-dimensional model producing a very complex dynamical behavior is obtained. The model is tested in order to investigate its skills and drawbacks. Our global analysis clearly helps to distinguish three main stages during the epidemic. A characterization of the obtained attractor is also performed. In particular, the topology of the chaotic attractor is analyzed and a skeleton is obtained for its structure.

  2. Detection of Viral RNA in Tissues following Plasma Clearance from an Ebola Virus Infected Patient

    Science.gov (United States)

    Bordi, Licia; Castilletti, Concetta; Colavita, Francesca; Quartu, Serena; Nicastri, Emanuele; Lauria, Francesco Nicola; Petrosillo, Nicola; Lanini, Simone; Kobinger, Gary; Zumla, Alimuddin; Di Caro, Antonino; Ippolito, Giuseppe; Capobianchi, Maria Rosaria; Lalle, Eleonora

    2017-01-01

    An unprecedented Ebola virus (EBOV) epidemic occurred in 2013–2016 in West Africa. Over this time the epidemic exponentially grew and moved to Europe and North America, with several imported cases and many Health Care Workers (HCW) infected. Better understanding of EBOV infection patterns in different body compartments is mandatory to develop new countermeasures, as well as to fully comprehend the pathways of human-to-human transmission. We have longitudinally explored the persistence of EBOV-specific negative sense genomic RNA (neg-RNA) and the presence of positive sense RNA (pos-RNA), including both replication intermediate (antigenomic-RNA) and messenger RNA (mRNA) molecules, in the upper and lower respiratory tract, as compared to plasma, in a HCW infected with EBOV in Sierra Leone, who was hospitalized in the high isolation facility of the National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), Rome, Italy. We observed persistence of pos-RNA and neg-RNAs in longitudinally collected specimens of the lower respiratory tract, even after viral clearance from plasma, suggesting possible local replication. The purpose of the present study is to enhance the knowledge on the biological features of EBOV that can contribute to the human-to-human transmissibility and to develop effective intervention strategies. However, further investigation is needed in order to better understand the clinical meaning of viral replication and shedding in the respiratory tract. PMID:28056096

  3. Sequelae and Other Conditions in Ebola Virus Disease Survivors, Sierra Leone, 2015

    Science.gov (United States)

    Vandy, Alren O.; Stretch, Rebecca; Otieno, David; Prajapati, Mukesh; Calderon, Mauricio; Vandi, Mohamed

    2017-01-01

    We rapidly assessed the health of Ebola virus disease (EVD) survivors in Kenema, Sierra Leone, by reviewing medical charts of all patients attending the Survivor Clinic of Kenema Government Hospital. Data were abstracted on signs and symptoms at every attendance. As of November 2015, a total of 621 attendances by 115 survivors with laboratory-confirmed EVD were made to the Survivor Clinic. Most (60.9%) survivors were women. Survivors’ median age was 28 years (range 0.25–70 years). Survivors attended the clinic a median of 5 times (range 1–21 times) each, and the median time from EVD discharge to attendance was 261 days (range 4–504 days). The most commonly reported signs and symptoms among the 621 attendances were headache (63.1%), fever (61.7%), and myalgia (43.3%). Because health needs of EVD survivors are complex, rapid chart reviews at survivor clinics should be repeated regularly to assess the extent of illness and prioritize service delivery. PMID:27983503

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

    Science.gov (United States)

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

    2016-01-01

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

  5. A chaotic model for the epidemic of Ebola virus disease in West Africa (2013-2016)

    Science.gov (United States)

    Mangiarotti, Sylvain; Peyre, Marisa; Huc, Mireille

    2016-11-01

    An epidemic of Ebola Virus Disease (EVD) broke out in Guinea in December 2013. It was only identified in March 2014 while it had already spread out in Liberia and Sierra Leone. The spill over of the disease became uncontrollable and the epidemic could not be stopped before 2016. The time evolution of this epidemic is revisited here with the global modeling technique which was designed to obtain the deterministic models from single time series. A generalized formulation of this technique for multivariate time series is introduced. It is applied to the epidemic of EVD in West Africa focusing on the period between March 2014 and January 2015, that is, before any detected signs of weakening. Data gathered by the World Health Organization, based on the official publications of the Ministries of Health of the three main countries involved in this epidemic, are considered in our analysis. Two observed time series are used: the daily numbers of infections and deaths. A four-dimensional model producing a very complex dynamical behavior is obtained. The model is tested in order to investigate its skills and drawbacks. Our global analysis clearly helps to distinguish three main stages during the epidemic. A characterization of the obtained attractor is also performed. In particular, the topology of the chaotic attractor is analyzed and a skeleton is obtained for its structure.

  6. The laboratory health system and its response to the Ebola virus disease outbreak in Liberia

    Directory of Open Access Journals (Sweden)

    Stephen B. Kennedy

    2016-10-01

    Full Text Available The laboratory system in Liberia has generally been fragmented and uncoordinatedAccordingly, the country’s Ministry of Health established the National Reference Laboratoryto strengthen and sustain laboratory services. However, diagnostic testing services were oftenlimited to clinical tests performed in health facilities, with the functionality of the NationaReference Laboratory restricted to performing testing services for a limited number ofepidemic-prone diseases. The lack of testing capacity in-country for Lassa fever and otherhaemorrhagic fevers affected the response of the country’s health system during the onset ofthe Ebola virus disease (EVD outbreak. Based on the experiences of the EVD outbreak, effortswere initiated to strengthen the laboratory system and infrastructure, enhance human resourcecapacity, and invest in diagnostic services and public health surveillance to inform admittancetreatment, and discharge decisions. In this article, we briefly describe the pre-EVD laboratorycapability in Liberia, and extensively explore the post-EVD strengthening initiatives to enhancecapacity, mobilise resources and coordinate disaster response with international partners torebuild the laboratory infrastructure in the country. Now that the EVD outbreak has endedadditional initiatives are needed to revise the laboratory strategic and operational plan forpost-EVD relevance, promote continual human resource capacity, institute accreditation andvalidation programmes, and coordinate the investment strategy to strengthen and sustain thepreparedness of the laboratory sector to mitigate future emerging and re-emerging infectiousdiseases.

  7. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa.

    Science.gov (United States)

    Leroy, E M; Gonzalez, J-P; Baize, S

    2011-07-01

    Ebola and Marburg viruses are the only members of the Filoviridae family (order Mononegavirales), a group of viruses characterized by a linear, non-segmented, single-strand negative RNA genome. They are among the most virulent pathogens for humans and great apes, causing acute haemorrhagic fever and death within a matter of days. Since their discovery 50 years ago, filoviruses have caused only a few outbreaks, with 2317 clinical cases and 1671 confirmed deaths, which is negligible compared with the devastation caused by malnutrition and other infectious diseases prevalent in Africa (malaria, cholera, AIDS, dengue, tuberculosis …). Yet considerable human and financial resourses have been devoted to research on these viruses during the past two decades, partly because of their potential use as bioweapons. As a result, our understanding of the ecology, host interactions, and control of these viruses has improved considerably.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Julii Brainard

    2016-02-01

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

  10. With strengthened guidelines for health care workers, the CDC ups its game against the deadly Ebola virus.

    Science.gov (United States)

    2014-12-01

    Informed by the cases of two nurses who contracted Ebola virus disease (EVD) while caring for a patient with the disease in Dallas, TX, the Centers for Disease Control and Prevention (CDC) in Atlanta, GA, has unveiled strengthened guidance for health care workers. Further, nursing organizations are pledging to work together to identify gaps and make system-level improvements to protect both patients and caregivers. The CDC's new recommendations emphasize rigorous training for health care workers in how to put on and take off personal protective equipment (PPE), and they state that this activity should always be carefully supervised by a monitor. The guidance also states that health care workers should use either an N-95' respirator mask or a powered air purifying respirator (PAPR) when they are providing care to a patient with Ebola. Experts stress that the new guidance does not change the fundamental issue that Ebola is transmitted through contact with infectious substances from patients. Nursing organizations are pledging to work together to identify problems and improve safety for both caregivers and patients.

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

    Science.gov (United States)

    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.

  12. Public health and public trust: Survey evidence from the Ebola Virus Disease epidemic in Liberia.

    Science.gov (United States)

    Blair, Robert A; Morse, Benjamin S; Tsai, Lily L

    2017-01-01

    Trust in government has long been viewed as an important determinant of citizens' compliance with public health policies, especially in times of crisis. Yet evidence on this relationship remains scarce, particularly in the developing world. We use results from a representative survey conducted during the 2014-15 Ebola Virus Disease (EVD) epidemic in Monrovia, Liberia to assess the relationship between trust in government and compliance with EVD control interventions. We find that respondents who expressed low trust in government were much less likely to take precautions against EVD in their homes, or to abide by government-mandated social distancing mechanisms designed to contain the spread of the virus. They were also much less likely to support potentially contentious control policies, such as "safe burial" of EVD-infected bodies. Contrary to stereotypes, we find no evidence that respondents who distrusted government were any more or less likely to understand EVD's symptoms and transmission pathways. While only correlational, these results suggest that respondents who refused to comply may have done so not because they failed to understand how EVD is transmitted, but rather because they did not trust the capacity or integrity of government institutions to recommend precautions and implement policies to slow EVD's spread. We also find that respondents who experienced hardships during the epidemic expressed less trust in government than those who did not, suggesting the possibility of a vicious cycle between distrust, non-compliance, hardships and further distrust. Finally, we find that respondents who trusted international non-governmental organizations (INGOs) were no more or less likely to support or comply with EVD control policies, suggesting that while INGOs can contribute in indispensable ways to crisis response, they cannot substitute for government institutions in the eyes of citizens. We conclude by discussing the implications of our findings for future

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

    Directory of Open Access Journals (Sweden)

    Bradley W. M. Cook

    2015-04-01

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

  14. Fruit bats as a natural reservoir of zoonotic viruses

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    As a natural reservoir of manifold zoonotic viruses, fruit bats have been involved in at least three emerging zoonoses in recent years. This paper aims to introduce the epidemiological characteristics of these diseases emerged in the Australasian region between 1994 and 1999, transmission pathways of the newly discovered viruses and the relationship between the changed entironment of fruit bats and occurrences of these emerging diseases and provide a clue for the epidemiological investigations of SARS.

  15. Living Under the Constant Threat of Ebola: A Phenomenological Study of Survivors and Family Caregivers During an Ebola Outbreak.

    Science.gov (United States)

    Matua, Gerald Amandu; Wal, Dirk Mostert Van der

    2015-09-01

    Ebola is a highly infectious disease that is caused by viruses of the family Filoviridae and transmitted to humans by direct contact with animals infected from unknown natural reservoirs. Ebola virus infection induces acute fever and death within a few days in up to 90% of symptomatic individuals, causing widespread fear, panic, and antisocial behavior. Uganda is vulnerable to future Ebola outbreaks. Therefore, the survivors of Ebola and their family caregivers are likely to continue experiencing related antisocial overtones, leading to negative health outcomes. This study articulated the lived experiences of survivors and their family caregivers after an Ebola outbreak in Kibale District, Western Uganda. Eliciting a deeper understanding of these devastating lifetime experiences provides opportunities for developing and implementing more compassionate and competent nursing care for affected persons. Ebola survivors and their family caregivers were recruited using a purposive sampling method. Twelve (12) adult survivors and their family caregivers were recruited and were interviewed individually between May and July 2013 in Kibale, a rural district in Western Uganda close to the border of the Democratic Republic of the Congo, where Ebola virus was first discovered in 1976. Oral and written informed consent was obtained before all in-depth interviews, and the researchers adhered to principles of anonymity and confidentiality. The interviews were recorded digitally, and data analysis employed Wertz's Empirical Psychological Reflection method, which is grounded in descriptive phenomenology. Living under the constant threat of Ebola is experienced through two main categories: (a) defining features of the experience and (b) responding to the traumatizing experience. Five themes emerged in the first category: (a) fear, ostracism, and stigmatization; (b) annihilation of sufferer's actualities and possibilities; (c) the lingering nature of the traumatic experience; (d

  16. Ebola (For Parents)

    Science.gov (United States)

    ... Teaching Kids to Be Smart About Social Media Ebola KidsHealth > For Parents > Ebola Print A A A ... take precautions to avoid becoming infected. What Is Ebola? Ebola, or Ebola hemorrhagic fever ( Ebola HF) , is ...

  17. Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain

    OpenAIRE

    Ou Wu; Delisle Josie; Jacques Jerome; Shih Joanna; Price Graeme; Kuhn Jens H; Wang Vivian; Verthelyi Daniela; Kaplan Gerardo; Wilson Carolyn A

    2012-01-01

    Abstract Background The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2) is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD). We hypothesized that immunization with MLD-deleted GP1,2 (GPΔMLD) would induce cross-species immunity by makin...

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

    Energy Technology Data Exchange (ETDEWEB)

    Albariño, César G., E-mail: calbarino@cdc.gov; Wiggleton Guerrero, Lisa; Lo, Michael K.; Nichol, Stuart T.; Towner, Jonathan S.

    2015-10-15

    Previous studies have demonstrated the potential application of reverse genetics technology in studying a broad range of aspects of viral biology, including gene regulation, protein function, cell entry, and pathogenesis. Here, we describe a highly efficient reverse genetics system used to generate recombinant Ebola virus (EBOV) based on a recent isolate from a human patient infected during the 2014–2015 outbreak in Western Africa. We also rescued a recombinant EBOV expressing a fluorescent reporter protein from a cleaved VP40 protein fusion. Using this virus and an inexpensive method to quantitate the expression of the foreign gene, we demonstrate its potential usefulness as a tool for screening antiviral compounds and measuring neutralizing antibodies. - Highlights: • Recombinant Ebola virus (EBOV) derived from Makona variant was rescued. • New protocol for viral rescue allows 100% efficiency. • Modified EBOV expresses a green fluorescent protein from a VP40-fused protein. • Modified EBOV was tested as tool to screen antiviral compounds and measure neutralizing antibodies.

  19. RT-PCR using glycoprotein target is more sensitive for the detection of Ebola virus in clinical samples.

    Science.gov (United States)

    Yang, Mingjuan; Ke, Yuehua; Zhang, Wenyi; Liu, Chao; Yang, Ruifu; Chen, Zeliang

    2017-03-01

    The recent largest ever Ebola virus disease (EVD) outbreak in West Africa has been of worldwide concern, causing huge economic losses and constituting serious threat to the local residents and health care workers. Rapid detection of Ebola virus (EBOV) using RT-PCR has been suggested to be of great value in stopping the outbreak, because it is highly sensitive and specific and can return results within hours. In this study, 210 clinical samples, including 109 blood and 101 nasopharyngeal swab samples were used to compare the performance of glycoprotein (GP) and nucleoprotein (NP) gene targets for the detection of EBOV. The analytical sensitivity of both assays were 10 molecules/μL. For clinical samples, the sensitivity of the assay targeting GP gene is higher than that of NP gene (respectively 98% and 94%) and the specificities for both targets were 100%. In addition, the positive samples in the RT-PCR assay targeting GP showed lower cycle threshold values and higher virus loads than NP gene.

  20. Ebola Virus Replication and Disease Without Immunopathology in Mice Expressing Transgenes to Support Human Myeloid and Lymphoid Cell Engraftment.

    Science.gov (United States)

    Spengler, Jessica R; Lavender, Kerry J; Martellaro, Cynthia; Carmody, Aaron; Kurth, Andreas; Keck, James G; Saturday, Greg; Scott, Dana P; Nichol, Stuart T; Hasenkrug, Kim J; Spiropoulou, Christina F; Feldmann, Heinz; Prescott, Joseph

    2016-10-15

    The study of Ebola virus (EBOV) pathogenesis in vivo has been limited to nonhuman primate models or use of an adapted virus to cause disease in rodent models. Herein we describe wild-type EBOV (Makona variant) infection of mice engrafted with human hematopoietic CD34(+) stem cells (Hu-NSG™-SGM3 mice; hereafter referred to as SGM3 HuMice). SGM3 HuMice support increased development of myeloid immune cells, which are primary EBOV targets. In SGM3 HuMice, EBOV replicated to high levels, and disease was observed following either intraperitoneal or intramuscular inoculation. Despite the high levels of viral antigen and inflammatory cell infiltration in the liver, the characteristic histopathology of Ebola virus disease was not observed, and this absence of severe immunopathology may have contributed to the recovery and survival of some of the animals. Future investigations into the underlying mechanisms of the atypical disease presentation in SGM3 HuMice will provide additional insights into the immunopathogenesis of severe EBOV disease. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Rapid detection and quantification of Ebola Zaire virus by one-step real-time quantitative reverse transcription-polymerase chain reaction.

    Science.gov (United States)

    Ro, Young-Tae; Ticer, Anysha; Carrion, Ricardo; Patterson, Jean L

    2017-04-01

    Given that Ebola virus causes severe hemorrhagic fever in humans with mortality rates as high as 90%, rapid and accurate detection of this virus is essential both for controlling infection and preventing further transmission. Here, a one-step qRT-PCR assay for rapid and quantitative detection of an Ebola Zaire strain using GP, VP24 or VP40 genes as a target is introduced. Routine assay conditions for hydrolysis probe detection were established from the manufacturer's protocol used in the assays. The analytical specificity and sensitivity of each assay was evaluated using in vitro synthesized viral RNA transcripts. The assays were highly specific for the RNA transcripts, no cross-reactivity being observed among them. The limits of detection of the assays ranged from 10(2) to 10(3) copies per reaction. The assays were also evaluated using viral RNAs extracted from cell culture-propagated viruses (Ebola Zaire, Sudan and Reston strains), confirming that they are gene- and strain-specific. The RT-PCR assays detected viral RNAs in blood samples from virus-infected animal, suggesting that they can be also a useful method for identifying Ebola virus in clinical samples. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  2. Detection and classification of ebola on microfluidic chips

    Science.gov (United States)

    Lin, Xue; Jin, Xiangyu; Fan, Yunqian; Huang, Qin; Kou, Yue; Zu, Guo; Huang, Shiguang; Liu, Xiaosheng; Huang, Guoliang

    2016-10-01

    Point-of-care testing (POCT) for an infectious diseases is the prerequisite to control of the disease and limitation of its spread. A microfluidic chip for detection and classification of four strains of Ebola virus was developed and evaluated. This assay was based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific primers for Ebola Zaire virus, Ebola Sudan virus, Ebola Tai Forest virus and Ebola Bundibugyo virus were designed. The sensitivity of the microfluidic chip was under 103 copies per milliliter, as determined by ten repeated tests. This assay is unique in its ability to enable diagnosis of the Ebola infections and simultaneous typing of Ebola virus on a single chip. It offers short reaction time, ease of use and high specificity. These features should enable POCT in remote area during outbreaks of Ebola virus.

  3. Using a mHealth tutorial application to change knowledge and attitude of frontline health workers to Ebola virus disease in Nigeria: a before-and-after study.

    Science.gov (United States)

    Otu, Akaninyene; Ebenso, Bassey; Okuzu, Okey; Osifo-Dawodu, Egbe

    2016-02-12

    The Ebola epidemic exposed the weak state of health systems in West Africa and their devastating effect on frontline health workers and the health of populations. Fortunately, recent reviews of mobile technology demonstrate that mHealth innovations can help alleviate some health system constraints such as balancing multiple priorities, lack of appropriate tools to provide services and collect data, and limited access to training in health fields such as mother and child health, HIV/AIDS and sexual and reproductive health. However, there is little empirical evidence of mHealth improving health system functions during the Ebola epidemic in West Africa. We conducted quantitative cross-sectional surveys in 14 health facilities in Ondo State, Nigeria, to assess the effect of using a tablet computer tutorial application for changing the knowledge and attitude of health workers regarding Ebola virus disease. Of 203 participants who completed pre- and post-intervention surveys, 185 people (or 91%) were female, 94 participants (or 46.3%) were community health officers, 26 people (13 %) were nurses/midwives, 8 people (or 4%) were laboratory scientists and 75 people (37%) belonged to a group called others. Regarding knowledge of Ebola: 178 participants (or 87.7%) had foreknowledge of Ebola before the study. Further analysis showed an 11% improvement in average knowledge levels between pre- and post-intervention scores with statistically significant differences (P intervention scores from 83 to 92%, 57 to 64% and 67 to 79%, respectively. Moreover, more participants (from 95 to 97%) reported a willingness to practice frequent hand washing and disinfecting surfaces and equipment following the intervention, and more health workers were willing (from 94 to 97%) to use personal protective equipment to prevent the transmission of Ebola. The modest improvements in knowledge and reported attitudinal change toward Ebola virus disease suggests mHealth tutorial applications could hold

  4. Development and evaluation of a real-time RT-PCR assay for the detection of Ebola virus (Zaire) during an Ebola outbreak in Guinea in 2014-2015.

    Science.gov (United States)

    Dedkov, V G; Magassouba, N' F; Safonova, M V; Deviatkin, A A; Dolgova, A S; Pyankov, O V; Sergeev, A A; Utkin, D V; Odinokov, G N; Safronov, V A; Agafonov, A P; Maleev, V V; Shipulin, G A

    2016-02-01

    In early February 2014, an outbreak of the Ebola virus disease caused by Zaire ebolavirus (EBOV) occurred in Guinea; cases were also recorded in other West African countries with a combined population of approximately 25 million. A rapid, sensitive and inexpensive method for detecting EBOV is needed to effectively control such outbreak. Here, we report a real-time reverse-transcription PCR assay for Z. ebolavirus detection used by the Specialized Anti-epidemic Team of the Russian Federation during the Ebola virus disease prevention mission in the Republic of Guinea. The analytical sensitivity of the assay is 5 × 10(2) viral particles per ml, and high specificity is demonstrated using representative sampling of viral, bacterial and human nucleic acids. This assay can be applied successfully for detecting the West African strains of Z. ebolavirus as well as on strains isolated in the Democratic Republic of the Congo in 2014.

  5. 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".

    Science.gov (United States)

    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.

  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".

    Directory of Open Access Journals (Sweden)

    Jeffrey R Kugelman

    Full Text Available 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.

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

    Science.gov (United States)

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

    2011-12-20

    No countermeasures currently exist for the prevention or treatment of the severe sequelae of Filovirus (such as Ebola virus; EBOV) infection. To overcome this limitation in our biodefense preparedness, we have designed monoclonal antibodies (mAbs) which could be used in humans as immunoprotectants for EBOV, starting with a murine mAb (13F6) that recognizes the heavily glycosylated mucin-like domain of the virion-attached glycoprotein (GP). Point mutations were introduced into the variable region of the murine mAb to remove predicted human T-cell epitopes, and the variable regions joined to human constant regions to generate a mAb (h-13F6) appropriate for development for human use. We have evaluated the efficacy of three variants of h-13F6 carrying different glycosylation patterns in a lethal mouse EBOV challenge model. The pattern of glycosylation of the various mAbs was found to correlate to level of protection, with aglycosylated h-13F6 providing the least potent efficacy (ED(50) = 33 μg). A version with typical heterogenous mammalian glycoforms (ED(50) = 11 μg) had similar potency to the original murine mAb. However, h-13F6 carrying complex N-glycosylation lacking core fucose exhibited superior potency (ED(50) = 3 μg). Binding studies using Fcγ receptors revealed enhanced binding of nonfucosylated h-13F6 to mouse and human FcγRIII. Together the results indicate the presence of Fc N-glycans enhances the protective efficacy of h-13F6, and that mAbs manufactured with uniform glycosylation and a higher potency glycoform offer promise as biodefense therapeutics.

  8. Shelf-Life of Chlorine Solutions Recommended in Ebola Virus Disease Response.

    Science.gov (United States)

    Iqbal, Qais; Lubeck-Schricker, Maya; Wells, Emma; Wolfe, Marlene K; Lantagne, Daniele

    2016-01-01

    In Ebola Virus Disease (EVD) outbreaks, it is widely recommended to wash living things (handwashing) with 0.05% (500 mg/L) chlorine solution and non-living things (surfaces, personal protective equipment, dead bodies) with 0.5% (5,000 mg/L) chlorine solution. Chlorine solutions used in EVD response are primarily made from powdered calcium hypochlorite (HTH), granular sodium dichloroisocyanurate (NaDCC), and liquid sodium hypochlorite (NaOCl), and have a pH range of 5-11. Chlorine solutions degrade following a reaction highly dependent on, and unusually sensitive to, pH, temperature, and concentration. We determined the shelf-life of 0.05% and 0.5% chlorine solutions used in EVD response, including HTH, NaDCC, stabilized NaOCl, generated NaOCl, and neutralized NaOCl solutions. Solutions were stored for 30 days at 25, 30, and 35°C, and tested daily for chlorine concentration and pH. Maximum shelf-life was defined as days until initial concentration fell to 30 days. Models were developed for solutions with maximum shelf-lives between 1-30 days. Extrapolating to 40°C, the maximum predicted shelf-life for 0.05% and 0.5% NaDCC solutions were 0.38 and 0.82 hours, respectively; predicted shelf-life for 0.05% and 0.5% generated NaOCl solutions were >30 and 5.4 days, respectively. Each chlorine solution type offers advantages and disadvantages to responders, as: NaDCC is an easy-to-import high-concentration effervescent powder; HTH is similar, but forms a precipitate that may clog pipes; and, NaOCl solutions can be made locally, but are difficult to transport. We recommend responders chose the most appropriate source chlorine compound for their use, and ensure solutions are stored at appropriate temperatures and used or replaced before expiring.

  9. Contrasting academic and lay press print coverage of the 2013-2016 Ebola Virus Disease outbreak

    Science.gov (United States)

    Kieh, Mark D.; Cho, Elim M.

    2017-01-01

    Under a traditional paradigm, only those with the expected background knowledge consume academic literature. The lay press, as well as government and non-government agencies, play a complementary role of extracting findings of high interest or importance and translating them for general viewing. The need for accurate reporting and public advising is paramount when attempting to tackle epidemic outbreaks through behavior change. Yet, public trust in media outlets is at a historic low. The Crisis and Emergency Risk Communication (CERC) model for media reporting on public health emergencies was established in 2005 and has subsequently been used to analyze media reporting on outbreaks of influenza and measles as well as smoking habits and medication compliance. However, no media analysis had yet been performed on the 2013–2016 Ebola Virus Disease (EVD) outbreak. This study compared the EVD information relayed by lay press sources with general review articles in the academic literature through a mixed-methods analysis. These findings suggest that comprehensive review articles could not serve as a source to clarify and contextualize the uncertainties around the EVD outbreak, perhaps due to adherence to technical accuracy at the expense of clarity within the context of outbreak conditions. This finding does not imply inferiority of the academic literature, nor does it draw direct causation between confusion in review articles and public misunderstanding. Given the erosion of the barriers siloing academia, combined with the demands of today’s fast-paced media environment, contemporary researchers should realize that no study is outside the public forum and to therefore consider shifting the paradigm to take personal responsibility in the process of accurately translating their scientific words into public policy actions to best serve as a source of clarity. PMID:28640889

  10. Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection [v2; ref status: indexed, http://f1000r.es/53d

    Directory of Open Access Journals (Sweden)

    Veljko Veljkovic

    2015-02-01

    Full Text Available 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.

  11. Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection [v1; ref status: indexed, http://f1000r.es/51s

    Directory of Open Access Journals (Sweden)

    Veljko Veljkovic

    2015-02-01

    Full Text Available 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.

  12. The landscape configuration of zoonotic transmission of Ebola virus disease in West and Central Africa: interaction between population density and vegetation cover.

    Science.gov (United States)

    Walsh, Michael G; Haseeb, Ma

    2015-01-01

    Ebola virus disease (EVD) is an emerging infectious disease of zoonotic origin that has been responsible for high mortality and significant social disruption in West and Central Africa. Zoonotic transmission of EVD requires contact between susceptible human hosts and the reservoir species for Ebolaviruses, which are believed to be fruit bats. Nevertheless, features of the landscape that may facilitate such points of contact have not yet been adequately identified. Nor have spatial dependencies between zoonotic EVD transmission and landscape structures been delineated. This investigation sought to describe the spatial relationship between zoonotic EVD transmission events, or spillovers, and population density and vegetation cover. An inhomogeneous Poisson process model was fitted to all precisely geolocated zoonotic transmissions of EVD in West and Central Africa. Population density was strongly associated with spillover; however, there was significant interaction between population density and green vegetation cover. In areas of very low population density, increasing vegetation cover was associated with a decrease in risk of zoonotic transmission, but as population density increased in a given area, increasing vegetation cover was associated with increased risk of zoonotic transmission. This study showed that the spatial dependencies of Ebolavirus spillover were associated with the distribution of population density and vegetation cover in the landscape, even after controlling for climate and altitude. While this is an observational study, and thus precludes direct causal inference, the findings do highlight areas that may be at risk for zoonotic EVD transmission based on the spatial configuration of important features of the landscape.

  13. The landscape configuration of zoonotic transmission of Ebola virus disease in West and Central Africa: interaction between population density and vegetation cover

    Directory of Open Access Journals (Sweden)

    Michael G. Walsh

    2015-01-01

    Full Text Available Ebola virus disease (EVD is an emerging infectious disease of zoonotic origin that has been responsible for high mortality and significant social disruption in West and Central Africa. Zoonotic transmission of EVD requires contact between susceptible human hosts and the reservoir species for Ebolaviruses, which are believed to be fruit bats. Nevertheless, features of the landscape that may facilitate such points of contact have not yet been adequately identified. Nor have spatial dependencies between zoonotic EVD transmission and landscape structures been delineated. This investigation sought to describe the spatial relationship between zoonotic EVD transmission events, or spillovers, and population density and vegetation cover. An inhomogeneous Poisson process model was fitted to all precisely geolocated zoonotic transmissions of EVD in West and Central Africa. Population density was strongly associated with spillover; however, there was significant interaction between population density and green vegetation cover. In areas of very low population density, increasing vegetation cover was associated with a decrease in risk of zoonotic transmission, but as population density increased in a given area, increasing vegetation cover was associated with increased risk of zoonotic transmission. This study showed that the spatial dependencies of Ebolavirus spillover were associated with the distribution of population density and vegetation cover in the landscape, even after controlling for climate and altitude. While this is an observational study, and thus precludes direct causal inference, the findings do highlight areas that may be at risk for zoonotic EVD transmission based on the spatial configuration of important features of the landscape.

  14. Small molecules with antiviral activity against the Ebola virus [v1; ref status: indexed, http://f1000r.es/523

    Directory of Open Access Journals (Sweden)

    Nadia Litterman

    2015-02-01

    Full Text Available 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.

  15. Determination of specific antibody responses to the six species of ebola and Marburg viruses by multiplexed protein microarrays.

    Science.gov (United States)

    Kamata, Teddy; Natesan, Mohan; Warfield, Kelly; Aman, M Javad; Ulrich, Robert G

    2014-12-01

    Infectious hemorrhagic fevers caused by the Marburg and Ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. The highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. We assembled a protein microarray displaying nucleoprotein (NP), virion protein 40 (VP40), and glycoprotein (GP) antigens from isolates representing the six species of filoviruses for use as a surveillance and diagnostic platform. Using the microarrays, we examined serum antibody responses of rhesus macaques vaccinated with trivalent (GP, NP, and VP40) virus-like particles (VLP) prior to infection with the Marburg virus (MARV) (i.e., Marburg marburgvirus) or the Zaire virus (ZEBOV) (i.e., Zaire ebolavirus). The microarray-based assay detected a significant increase in antigen-specific IgG resulting from immunization, while a greater level of antibody responses resulted from challenge of the vaccinated animals with ZEBOV or MARV. Further, while antibody cross-reactivities were observed among NPs and VP40s of Ebola viruses, antibody recognition of GPs was very specific. The performance of mucin-like domain fragments of GP (GP mucin) expressed in Escherichia coli was compared to that of GP ectodomains produced in eukaryotic cells. Based on results with ZEBOV and MARV proteins, antibody recognition of GP mucins that were deficient in posttranslational modifications was comparable to that of the eukaryotic cell-expressed GP ectodomains in assay performance. We conclude that the described protein microarray may translate into a sensitive assay for diagnosis and serological surveillance of infections caused by multiple species of filoviruses.

  16. Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial.

    Science.gov (United States)

    ElSherif, May S; Brown, Catherine; MacKinnon-Cameron, Donna; Li, Li; Racine, Trina; Alimonti, Judie; Rudge, Thomas L; Sabourin, Carol; Silvera, Peter; Hooper, Jay W; Kwilas, Steven A; Kilgore, Nicole; Badorrek, Christopher; Ramsey, W Jay; Heppner, D Gray; Kemp, Tracy; Monath, Thomas P; Nowak, Teresa; McNeil, Shelly A; Langley, Joanne M; Halperin, Scott A

    2017-06-19

    The 2013-2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSVΔG-ZEBOV-GP) was evaluated in humans. In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18-65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo. Follow-up visits spanned 180 days postvaccination for safety monitoring, immunogenicity testing and any rVSV virus shedding. Forty participants were injected with rVSVΔG-ZEBOV-GP vaccine (n = 30) or saline placebo (n = 10). No serious adverse events related to the vaccine or participant withdrawals were reported. Solicited adverse events during the 14-day follow-up period were mild to moderate and self-limited, with the exception of injection-site pain and headache. Viremia following vaccination was transient and no longer detectable after study day 3, with no virus shedding in saliva or urine. All vaccinated participants developed serum immunoglobulin G (IgG), as measured by Ebola virus envelope glycoprotein-based enzyme-linked immunosorbent assay (ELISA). Immunogenicity was comparable across all dose groups, and sustained IgG titers were detectable through to the last visit, at study day 180. In this phase 1 study, there were no safety concerns after a single dose of rVSVΔG-ZEBOV-GP vaccine. IgG ELISA showed persistent high titers at 180 days postimmunization. There was a period of reactogenicity, but in general, the vaccine was well tolerated. This study provides evidence of the safety and immunogenicity of rVSVΔG-ZEBOV-GP vaccine and importance of its further investigation. Trial registration: Clinical-Trials.gov no., NCT02374385. © 2017 Canadian Medical Association or its licensors.

  17. Discovery and Description of Ebola Zaire Virus in 1976 and Relevance to the West African Epidemic During 2013-2016.

    Science.gov (United States)

    Breman, Joel G; Heymann, David L; Lloyd, Graham; McCormick, Joseph B; Miatudila, Malonga; Murphy, Frederick A; Muyembé-Tamfun, Jean-Jacques; Piot, Peter; Ruppol, Jean-François; Sureau, Pierre; van der Groen, Guido; Johnson, Karl M

    2016-10-15

     In 1976, the first cases of Ebola virus disease in northern Democratic Republic of the Congo (then referred to as Zaire) were reported. This article addresses who was responsible for recognizing the disease; recovering, identifying, and naming the virus; and describing the epidemic. Key scientific approaches used in 1976 and their relevance to the 3-country (Guinea, Sierra Leone, and Liberia) West African epidemic during 2013-2016 are presented.  Field and laboratory investigations started soon after notification, in mid-September 1976, and included virus cell culture, electron microscopy (EM), immunofluorescence antibody (IFA) testing of sera, case tracing, containment, and epidemiological surveys. In 2013-2016, medical care and public health work were delayed for months until the Ebola virus disease epidemic was officially declared an emergency by World Health Organization, but research in pathogenesis, clinical presentation, including sequelae, treatment, and prevention, has increased more recently.  Filoviruses were cultured and observed by EM in Antwerp, Belgium (Institute of Tropical Medicine); Porton Down, United Kingdom (Microbiological Research Establishment); and Atlanta, Georgia (Centers for Disease Control and Prevention). In Atlanta, serological testing identified a new virus. The 1976 outbreak (280 deaths among 318 cases) stopped in 2 years. Transmission indices (R0) are higher in all 3 countries than in 1976.  An international commission working harmoniously in laboratories and with local communities was essential for rapid success in 1976. Control and understanding of the recent West African outbreak were delayed because of late recognition and because authorities were overwhelmed by many patients and poor community involvement. Despite obstacles, research was a priority in 1976 and recently. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is

  18. Large serological survey showing cocirculation of Ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus

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    Rollin Pierre E

    2009-09-01

    Full Text Available Abstract Background Ebola and Marburg viruses cause highly lethal hemorrhagic fevers in humans. Recently, bats of multiple species have been identified as possible natural hosts of Zaire ebolavirus (ZEBOV in Gabon and Republic of Congo, and also of marburgvirus (MARV in Gabon and Democratic Republic of Congo. Methods We tested 2147 bats belonging to at least nine species sampled between 2003 and 2008 in three regions of Gabon and in the Ebola epidemic region of north Congo for IgG antibodies specific for ZEBOV and MARV. Results Overall, IgG antibodies to ZEBOV and MARV were found in 4% and 1% of bats, respectively. ZEBOV-specific antibodies were found in six bat species (Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Micropteropus pusillus, Mops condylurus and Rousettus aegyptiacus, while MARV-specific antibodies were only found in Rousettus aegyptiacus and Hypsignathus monstrosus. The prevalence of MARV-specific IgG was significantly higher in R. aegyptiacus members captured inside caves than elsewhere. No significant difference in prevalence was found according to age or gender. A higher prevalence of ZEBOV-specific IgG was found in pregnant females than in non pregnant females. Conclusion These findings confirm that ZEBOV and MARV co-circulate in Gabon, the only country where bats infected by each virus have been found. IgG antibodies to both viruses were detected only in Rousettus aegyptiacus, suggesting that this bat species may be involved in the natural cycle of both Marburg and Ebola viruses. The presence of MARV in Gabon indicates a potential risk for a first human outbreak. Disease surveillance should be enhanced in areas near caves.

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

    Science.gov (United States)

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

    2015-01-01

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

  20. Febrile illness in healthcare workers caring for Ebola virus disease patients in a high-resource setting.

    Science.gov (United States)

    Fink, Douglas; Cropley, Ian; Jacobs, Michael; Mepham, Stephen

    2017-01-26

    Ebola virus disease (EVD) patients treated in high-resource facilities are cared for by large numbers of healthcare staff. Monitoring these healthcare workers (HCWs) for any illness that may represent transmission of Ebola virus is important both for the individuals and to minimise the community risk. International policies for monitoring HCWs vary considerably and their effectiveness is unknown. Here we describe the United Kingdom (UK) experience of illness in HCWs who cared for three patients who acquired EVD in West Africa. Five of these 93 high-level isolation unit (HLIU) HCWs presented with fever within 21 days of working on the unit; one of these five presented outside of the UK. This article discusses different approaches to monitoring of HCW symptom reporting. The potential impact of these approaches on HLIU staff recruitment, including travel restrictions, is also considered. An international surveillance system enhancing collaboration between national public health authorities may assist HLIU HCW monitoring in case they travel. This article is copyright of The Authors, 2017.