Science.gov

Sample records for virus ebola virus

  1. Ebola (Ebola Virus Disease)

    MedlinePLUS

    ... Confirmed Patients with Ebola Virus Disease in the United States What's New (Continued) More Information for Specific Groups Travelers U.S. Healthcare Workers and Settings Information for Families and Loved ...

  2. Ebola Virus Disease

    MedlinePLUS

    ... 2014 Fact sheets Features Commentaries 2014 Multimedia Contacts Ebola virus disease Fact sheet N°103 Updated January ... for survivors of Ebola virus disease Symptoms of Ebola virus disease The incubation period, that is, the ...

  3. Ebola virus disease

    MedlinePLUS

    Ebola hemorrhagic fever; Ebola virus infection; Viral hemorrhagic fever; Ebola ... There is currently no vaccine to protect against Ebola, although a vaccine is being tested. If you plan to travel to one of the countries ...

  4. Understanding Ebola Virus Transmission

    PubMed Central

    Judson, Seth; Prescott, Joseph; Munster, Vincent

    2015-01-01

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

  5. Ebola Virus Disease in West Africa

    MedlinePLUS

    ... Situation reports Publications Ebola virus disease outbreak Ebola virus disease Ebola virus disease (formerly known as Ebola haemorrhagic fever) is ... contact with sick people and deceased patients. Ebola virus disease outbreak website Cholera Cholera fact sheet Crimean- ...

  6. Ebola Virus Persistence in Semen Ex Vivo.

    PubMed

    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. PMID:26811984

  7. Ebola Virus Persistence in Semen Ex Vivo

    PubMed Central

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

    2016-01-01

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

  8. Ebola, the killer virus.

    PubMed

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

    2015-01-01

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

  9. Treatment of ebola virus disease.

    PubMed

    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 review several agents and strategies that are now under active development. PMID:25630412

  10. Fruit bats as reservoirs of Ebola virus.

    PubMed

    Leroy, Eric M; Kumulungui, Brice; Pourrut, Xavier; Rouquet, Pierre; Hassanin, Alexandre; Yaba, Philippe; Dlicat, Andr; Paweska, Janusz T; Gonzalez, Jean-Paul; Swanepoel, Robert

    2005-12-01

    The first recorded human outbreak of Ebola virus was in 1976, but the wild reservoir of this virus is still unknown. Here we test for Ebola in more than a thousand small vertebrates that were collected during Ebola outbreaks in humans and great apes between 2001 and 2003 in Gabon and the Republic of the Congo. We find evidence of asymptomatic infection by Ebola virus in three species of fruit bat, indicating that these animals may be acting as a reservoir for this deadly virus. PMID:16319873

  11. Characteristics of Filoviridae: Marburg and Ebola Viruses

    NASA Astrophysics Data System (ADS)

    Beer, Brigitte; Kurth, Reinhard; Bukreyev, Alexander

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

  12. Persistence of Ebola Virus in Sterilized Wastewater

    PubMed Central

    2015-01-01

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

  13. [Overview of Ebola virus vaccine].

    PubMed

    Yang, Limin; Li, Jing; Gao, George Fu; Liu, Wenjun

    2015-01-01

    Ebola virus (EBOV) causes hemorrhagic fever, resulting in mortality rates as high as 90% among infected humans and non-human primates (NHPs). The 2014 Ebola epidemic in West Africa is the severest in history, leading to WHO taking all control measures to stop any possibility of cross-border outbreaks. Because no licensed vaccines or effective therapeutics against EBOV are available, the current outbreak management has been limited to palliative care and barrier methods to prevent transmission. Several promising experimental EBOV vaccines have demonstrated protection in NHPs against lethal EBOV challenge, and some progresses have been made through clinical trials of EBOV vaccine candidates. It is believed there will be some licensed vaccine available in the near future to control EBOV outbreaks. In this review we provide some insights for further development of EBOV vaccines. PMID:26021076

  14. Virion nucleic acid of Ebola virus.

    PubMed Central

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

    1980-01-01

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

  15. Ebola Virus Disease.

    PubMed

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

    2015-12-01

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

  16. Successful Delivery of RRT in Ebola Virus Disease

    PubMed Central

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

    2015-01-01

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

  17. Interferon-γ Inhibits Ebola Virus Infection

    PubMed Central

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

    2015-01-01

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

  18. An Ebola virus-centered knowledge base

    PubMed Central

    Kamdar, Maulik R.; Dumontier, Michel

    2015-01-01

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

  19. Ebola virus disease: history, epidemiology and outbreaks.

    PubMed

    Weyer, Jacqueline; Grobbelaar, Antoinette; Blumberg, Lucille

    2015-05-01

    Over the past 40years, sporadic Ebola virus disease (EVD) outbreaks have occurred mostly in the central African region. In March 2014, an outbreak of EVD was recognized in Guinea which would become the most significant outbreak of haemorrhagic fever in Africa to date. The outbreak started in Guinea and rapidly spread to Liberia and Sierra Leone, claiming thousands of lives. Many questions still remain regarding the ecology of Ebola viruses, but it is believed that contact with infected bushmeat is an important risk factor for initial spill over of the virus into the human population. At present, there is still no registered prophylaxis or curative biologicals against EVD. PMID:25896751

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

    PubMed

    Murray, Michael J

    2015-09-01

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

  1. Development of therapeutics for treatment of Ebola virus infection.

    PubMed

    Li, Haoyang; Ying, Tianlei; Yu, Fei; Lu, Lu; Jiang, Shibo

    2015-02-01

    Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed. PMID:25498866

  2. An Ebola virus-centered knowledge base.

    PubMed

    Kamdar, Maulik R; Dumontier, Michel

    2015-01-01

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

  3. Ebola Virus: a Clear and Present Danger

    PubMed Central

    2014-01-01

    An epidemic of Ebola virus disease is occurring in Western Africa on a scale not seen before, particularly in the countries of Guinea, Liberia, and Sierra Leone. The continued spread is facilitated by insufficient medical facilities, poor sanitation, travel, and unsafe burial practices. Several patients diagnosed with Ebola virus disease in Africa have been evacuated to the United States for treatment, and several other patients have been diagnosed in the United States. It is important for laboratories to be aware of available tests, especially those granted emergency use authorization, as hospitals prepare protocols for the diagnosis and management of high-risk patients. PMID:25392362

  4. Ebola virus disease: from epidemiology to prophylaxis.

    PubMed

    Liu, Wen Bin; Li, Zi Xiong; Du, Yan; Cao, Guang Wen

    2015-01-01

    The outbreak of Ebola virus disease (EVD) continues to spread through West Africa. Since the first report of EVD in March 2014, the number of cases has increased rapidly, with the fatality rate of >50%. The most prevalent Ebola virus belongs to the species of Zaire ebolavirus, with a fatality rate as high as 90%. Although there were cases introduced into other continents, Africa is the endemic area where fruit bats and apes are suspected to be Ebola virus carriers. The virus might be transmitted from the host animals to humans if humans consume raw or not fully cooked and contaminated meats. However, human-to-human transmission via close contact is the major route of current outbreaks. EVD can occur during any season and affect people of any race and age group. Direct contact with body fluids of EVD patients or living in contaminated environments greatly increases the risk of being infected. Transmission via aerosol less likely, but transmission via virus-containing droplets is possible in humans. Thus, health care providers are facing danger of getting Ebola virus infection. To date, vaccines, drugs and/or therapies to prevent Ebola virus infection or treat EVD are limited. Medical workers should follow the current standard prophylactic procedures. The military can orchestrate efficient care to mass EVD patients. Although it is necessary to speed up the pace of developing effective vaccine and therapeutics for the prevention and treatment of EVD, public health prevention and management should be important issue at present to control the spread of this disease cost-effectively. PMID:26000173

  5. Ebola Virus Infection: What Should Be Known?

    PubMed Central

    Wiwanitkit, Viroj

    2014-01-01

    Ebola virus infection is the present global consideration. This deadly virus can result in a deadly acute febrile hemorrhagic illness. The patient can have several clinical manifestations. As a new emerging infection, the knowledge on this infection is extremely limited. The interesting issues to be discussed include a) the atypical clinical presentation, b) new diagnostic tool, c) new treatment, and d) disease prevention. Those topics will be discussed in this special review. PMID:25535601

  6. Ebola Virus Disease: Focus on Children.

    PubMed

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

    2015-08-01

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

  7. [Molecular mechanisms of Ebola virus reproduction].

    PubMed

    Subbotina, E L; Chepurnov, A A

    2007-01-01

    The review presents recent data on the molecular mechanisms of the stages of an Ebola virus replication cycle, on the interaction of viral and cellular components at each stage, as well as on the mechanisms responsible for he realization of viral genetic information in the infected cell. PMID:17338228

  8. Antibody-Dependent Enhancement of Ebola Virus Infection

    PubMed Central

    Takada, Ayato; Feldmann, Heinz; Ksiazek, Thomas G.; Kawaoka, Yoshihiro

    2003-01-01

    Most strains of Ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. Here we show that Ebola Zaire virus infection in humans induces antibodies that enhance viral infectivity. Plasma or serum from convalescing patients enhanced the infection of primate kidney cells by the Zaire virus, and this enhancement was mediated by antibodies to the viral glycoprotein and by complement component C1q. Our results suggest a novel mechanism of antibody-dependent enhancement of Ebola virus infection, one that would account for the dire outcome of Ebola outbreaks in human populations. PMID:12805454

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

    PubMed

    Ye, Ling; Yang, Chinglai

    2015-02-01

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

  10. [Ebola: a virus endemic to central Africa?].

    PubMed

    Georges-Courbot, M C; Leroy, E; Zeller, H

    2002-01-01

    From October 2001 to March 2002, an outbreak of Ebola haemorrhagic fever occurred in the North-Eastern Gabon (63 cases) and neighbouring Congo (57 cases). It was the fourth epidemic in North Eastern Gabon since 1994. Meanwhile this outbreak differed from the previous epidemics: at least five different emerging sources of the virus in the human population were observed from the local fauna resulting in fears of an endemic Ebola virus in the area. The control of the outbreak was uneasy because of the unfriendly attitude of the local population related to the restrictive measures for the isolation of suspected patients and the epidemiological surveillance. Such rejection process emphasizes the need of a continuous increasing public awareness. PMID:12244929

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

    PubMed

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

    2015-05-01

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

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

    PubMed

    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. PMID:25648530

  13. Ebola virus disease: preparedness in Japan.

    PubMed

    Ashino, Yugo; Chagan-Yasutan, Haorile; Egawa, Shinichi; Hattori, Toshio

    2015-02-01

    The current outbreak of Ebola virus disease (EVD) is due to a lack of resources, untrained medical personnel, and the specific contact-mediated type of infection of this virus. In Japan's history, education and mass vaccination of the native Ainu people successfully eradicated epidemics of smallpox. Even though a zoonotic virus is hard to control, appropriate precautions and personal protection, as well as anti-symptomatic treatment, will control the outbreak of EVD. Ebola virus utilizes the antibody-dependent enhancement of infection to seed the cells of various organs. The pathogenesis of EVD is due to the cytokine storm of pro-inflammatory cytokines and the lack of antiviral interferon-α2. Matricellular proteins of galectin-9 and osteopontin might also be involved in the edema and abnormality of the coagulation system in EVD. Anti-fibrinolytic treatment will be effective. In the era of globalization, interviews of travelers with fever within 3 weeks of departure from the affected areas will be necessary. Not only the hospitals designated for specific biohazards but every hospital should be aware of the biology of biohazards and establish measures to protect both patients and the community. PMID:25399765

  14. Ebola virus infection modeling and identifiability problems

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Overview of Ebola virus disease in 2014.

    PubMed

    Tseng, Chih-Peng; Chan, Yu-Jiun

    2015-01-01

    In late December 2013, a deadly infectious epidemic, Ebola virus disease (EVD), emerged from West Africa and resulted in a formidable outbreak in areas including Guinea, Liberia, Sierra Leone and Nigeria. EVD is a zoonotic disease with a high mortality rate. Person-to-person transmission occurs through blood or body fluid exposure, which can jeopardize first-line healthcare workers if there is a lack of stringent infection control or no proper personal protective equipment available. Currently, there is no standard treatment for EVD. To promptly identify patients and prevent further spreading, physicians should be aware of travel or contact history for patients with constitutional symptoms. PMID:25547820

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

  19. Favipiravir: a new medication for the Ebola virus disease pandemic.

    TOXLINE Toxicology Bibliographic Information

    Nagata T; Lefor AK; Hasegawa M; Ishii M

    2015-02-01

    The purpose of this report is to advocate speedy approval and less stringent regulations for the use of experimental drugs such as favipiravir in emergencies. Favipiravir is a new antiviral medication that can be used in emerging viral pandemics such as Ebola virus, 2009 pandemic influenza H1N1 virus, Lassa fever, and Argentine hemorrhagic fever. Although favipiravir is one of the choices for the treatment of patients with Ebola virus, several concerns exist. First, a clinical trial of favipiravir in patients infected with the Ebola virus has not yet been conducted, and further studies are required. Second, favipiravir has a risk for teratogenicity and embryotoxicity. Therefore, the Ministry of Health, Welfare and Labor of Japan has approved this medication with strict regulations for its production and clinical use. However, owing to the emerging Ebola virus epidemic in West Africa, on August 15, 2014, the Minister of Health, Welfare and Labor of Japan approved the use of favipiravir, if needed.

  20. Favipiravir: a new medication for the Ebola virus disease pandemic.

    PubMed

    Nagata, Takashi; Lefor, Alan K; Hasegawa, Manabu; Ishii, Masami

    2015-02-01

    The purpose of this report is to advocate speedy approval and less stringent regulations for the use of experimental drugs such as favipiravir in emergencies. Favipiravir is a new antiviral medication that can be used in emerging viral pandemics such as Ebola virus, 2009 pandemic influenza H1N1 virus, Lassa fever, and Argentine hemorrhagic fever. Although favipiravir is one of the choices for the treatment of patients with Ebola virus, several concerns exist. First, a clinical trial of favipiravir in patients infected with the Ebola virus has not yet been conducted, and further studies are required. Second, favipiravir has a risk for teratogenicity and embryotoxicity. Therefore, the Ministry of Health, Welfare and Labor of Japan has approved this medication with strict regulations for its production and clinical use. However, owing to the emerging Ebola virus epidemic in West Africa, on August 15, 2014, the Minister of Health, Welfare and Labor of Japan approved the use of favipiravir, if needed. PMID:25544306

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

    PubMed

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

    2016-02-01

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

  2. Ebola virus (EBOV) infection: Therapeutic strategies.

    PubMed

    De Clercq, Erik

    2015-01-01

    Within less than a year after its epidemic started (in December 2013) in Guinea, Ebola virus (EBOV), a member of the filoviridae, has spread over a number of West-African countries (Guinea, Sierra Leone and Liberia) and gained allures that have been unprecedented except by human immunodeficiency virus (HIV). Although EBOV is highly contagious and transmitted by direct contact with body fluids, it could be counteracted by the adequate chemoprophylactic and -therapeutic interventions: vaccines, antibodies, siRNAs (small interfering RNAs), interferons and chemical substances, i.e. neplanocin A derivatives (i.e. 3-deazaneplanocin A), BCX4430, favipiravir (T-705), endoplasmic reticulum (ER) ?-glucosidase inhibitors and a variety of compounds that have been found to inhibit EBOV infection blocking viral entry or by a mode of action that still has to be resolved. Much has to be learned from the mechanism of action of the compounds active against VSV (vesicular stomatitis virus), a virus belonging to the rhabdoviridae, that in its mode of replication could be exemplary for the replication of filoviridae. PMID:25481298

  3. Recombinant Vesicular Stomatitis VirusBased Vaccines Against Ebola and Marburg Virus Infections

    PubMed Central

    Feldmann, Heinz

    2011-01-01

    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. PMID:21987744

  4. Ebola virus vaccines: an overview of current approaches

    PubMed Central

    Marzi, Andrea; Feldmann, Heinz

    2016-01-01

    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. PMID:24575870

  5. [Ebola virus disease and accredited specialist health institutions].

    PubMed

    Rivire, Anne-Marie; Feuillette, Christophe; Moreau, Nathalie; Damme, Frdric; Rapp, Christophe

    2015-01-01

    Ebola virus disease (EVD) went in the space of a few months from being a forgotten tropical disease to a global "health emergency". The scope of this Ebola virus epidemic (Zaire strain), which has broken out in West Africa, its spread and the high number of deaths reported among frontline health workers are unprecedented. This article describes how a specialist hospital deals with imported cases of EVD. PMID:26145993

  6. Ebola Virus Preparedness: Emerging Viruses and Ethics in Laboratory Medicine.

    PubMed

    Dubov, Alex; Appleton, Julia H; Campbell, Sheldon

    2016-02-01

    Context .- Emerging pathogens have affected, and will continue to affect, the health care system in diverse ways. Clinical laboratories face ethical challenges in responding to emerging pathogens. We use the 2014-2015 outbreak of Ebola virus disease as a model to explore some of the ethical issues in laboratory medicine related to emerging infectious disease. Objective .- To describe the major ethical concerns raised in the clinical laboratory environment by emerging infections. Data Sources .- We assessed current guidelines and practices in the Ebola outbreak in developed-world clinical laboratories, reviewed risk assessment practices and the role of the clinical laboratory in providing care for patients with potential or confirmed Ebola, and reviewed the relevant literature on duty to provide care in the laboratory context. Conclusions .- Clinical laboratories in developed countries have to rely more on expert guidelines and theoretical risk assessments than on practice in less-developed areas. Risk minimization for clinical laboratory workers is essential but may conflict with the laboratory's duty to provide standard of care. Patients can be put at risk not only from loss of laboratory services from restriction of testing but also from impairment of laboratory services in cases of spills or accidents. Significant discrepancies in guidelines from professional and governmental sources exacerbate the difficulty and confusion inherent in dealing with a dynamic, emerging infectious disease crisis. The duty to provide care for laboratory workers is ill-defined. Balancing risks to patients and laboratory workers and benefits to patients presents challenges to laboratory professionals at all levels. PMID:26910222

  7. Characterization of Ebola Virus Entry by Using Pseudotyped Viruses: Identification of Receptor-Deficient Cell Lines

    PubMed Central

    Wool-Lewis, Rouven J.; Bates, Paul

    1998-01-01

    Studies analyzing Ebola virus replication have been severely hampered by the extreme pathogenicity of this virus. To permit analysis of the host range and function of the Ebola virus glycoprotein (Ebo-GP), we have developed a system for pseudotyping these glycoproteins into murine leukemia virus (MLV). This pseudotyped virus, MLV(Ebola), can be readily concentrated to titers which exceed 5 106 infectious units/ml and is effectively neutralized by antibodies specific for Ebo-GP. Analysis of MLV(Ebola) infection revealed that the host range conferred by Ebo-GP is very broad, extending to cells of a variety of species. Notably, all lymphoid cell lines tested were completely resistant to infection; we speculate that this is due to the absence of a cellular receptor for Ebo-GP on B and T cells. The generation of high-titer MLV(Ebola) pseudotypes will be useful for the analysis of immune responses to Ebola virus infection, development of neutralizing antibodies, analysis of glycoprotein function, and isolation of the cellular receptor(s) for the Ebola virus. PMID:9525641

  8. Comprehensive Analysis of Ebola Virus GP1 in Viral Entry

    PubMed Central

    Manicassamy, Balaji; Wang, Jizhen; Jiang, Haiqing; Rong, Lijun

    2005-01-01

    Ebola virus infection is initiated by interactions between the viral glycoprotein GP1 and its cognate receptor(s), but little is known about the structure and function of GP1 in viral entry, partly due to the concern about safety when working with the live Ebola virus and the difficulty of manipulating the RNA genome of Ebola virus. In this study, we have used a human immunodeficiency virus-based pseudotyped virus as a surrogate system to dissect the role of Ebola virus GP1 in viral entry. Analysis of more than 100 deletion and amino acid substitution mutants of GP1 with respect to protein expression, processing, viral incorporation, and viral entry has allowed us to map the region of GP1 responsible for viral entry to the N-terminal 150 residues. Furthermore, six amino acids in this region have been identified as critical residues for early events in Ebola virus entry, and among these, three are clustered and are implicated as part of a potential receptor-binding pocket. In addition, substitutions of some 30 residues in GP1 are shown to adversely affect GP1 expression, processing, and viral incorporation, suggesting that these residues are involved in the proper folding and/or overall conformation of GP. Sequence comparison of the GP1 proteins suggests that the majority of the critical residues for GP folding and viral entry identified in Ebola virus GP1 are conserved in Marburg virus. These results provide information for elucidating the structural and functional roles of the filoviral glycoproteins and for developing potential therapeutics to block viral entry. PMID:15795265

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

    PubMed Central

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

    1996-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    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

  12. Human Ebola virus infection results in substantial immune activation

    PubMed Central

    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

    2015-01-01

    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. PMID:25775592

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

    PubMed

    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. PMID:25625358

  14. Ultrastructure of Ebola virus particles in human liver.

    PubMed Central

    Ellis, D S; Simpson, I H; Francis, D P; Knobloch, J; Bowen, E T; Lolik, P; Deng, I M

    1978-01-01

    Electron microscopy of tissues from two necropsies carried out in the Sudan on patients with Ebola virus infection identified virus particles in lung and spleen, but the main concentrations of Ebola particles were seen in liver sections. Viral precursor proteins and cores were found in functional liver cells, often aligned in membrane-bound aggregations. Complete virions, usually found only extracellularly, were mainly seen as long tubular forms, some without cores. Many tubular forms had 'enlarged heads' or 'spores' and some branched and torus forms were identified. The size and structure of the Ebola virus forms appear to be virtually indistinguishable from those of Marburg virus. Images Figs 6, 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:641193

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

    PubMed

    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. PMID:26812218

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

  18. Analysis of Ebola Virus Entry Into Macrophages

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    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. PMID:26535889

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2014-10-24

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

  2. Knowledge and risk perceptions of the Ebola virus in the United States

    PubMed Central

    Rolison, Jonathan J.; Hanoch, Yaniv

    2015-01-01

    Objectives The Ebola epidemic has received extensive media coverage since the first diagnosed cases of the virus in the US. We investigated risk perceptions of Ebola among individuals living in the US and measured their knowledge of the virus. Method US residents completed an online survey (conducted 1418 November 2014) that assessed their Ebola knowledge and risk perceptions. Results Respondents who were more knowledgeable of Ebola perceived less risk of contracting the virus and were less worried about the virus, but also regarded Ebola as more serious than less knowledgeable respondents. The internet served as a major source of additional information among knowledgeable respondents. Conclusion The findings suggest that the provision of health information about Ebola may be effective in informing the public about Ebola risks and of preventive measures without curtailing the seriousness of the virus. Policymakers may seek to further exploit the internet as a means of delivering information about Ebola in the US and worldwide. PMID:26844081

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  6. Nurses leading the fight against Ebola virus disease.

    PubMed

    Sagar, Priscilla L

    2015-05-01

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

  7. Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission

    PubMed Central

    Kilianski, Andy; Evans, Nicholas G.

    2015-01-01

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

  8. Small molecules with antiviral activity against the Ebola virus

    PubMed Central

    Litterman, Nadia; Lipinski, Christopher; Ekins, Sean

    2015-01-01

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

  9. Professional development implications of Ebola virus disease education: part I.

    PubMed

    Smith, Elaine L; Kerner, Robert L; Schindler, Jaclyn S; DeVoe, Barbara

    2015-01-01

    This article is the first in a two-part series that explores how one large, integrated health care system swiftly responded to the emerging threat of Ebola virus disease. In this first article, the context and initial steps in planning staff education and training are outlined. PMID:25647314

  10. Professional development implications of Ebola virus disease education: part II.

    PubMed

    Smith, Elaine L; Kerner, Robert L; Schindler, Jaclyn S; DeVoe, Barbara

    2015-02-01

    This article is the second in a two-part series that explores how one large, integrated health care system swiftly responded to the emerging threat of Ebola virus disease. In this second article, the educational and training activities that were developed are described. PMID:25633300

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

    PubMed

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

    2015-02-01

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

  12. GB Virus C Coinfections in West African Ebola Patients

    PubMed Central

    Lauck, Michael; Bailey, Adam L.; Andersen, Kristian G.; Goldberg, Tony L.; Sabeti, Pardis C.

    2014-01-01

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

  13. Development of treatment strategies to combat Ebola and Marburg viruses.

    PubMed

    Paragas, Jason; Geisbert, Thomas W

    2006-02-01

    Ebola and Marburg viruses are emerging/re-emerging pathogens that pose a significant threat to human health. These naturally occurring viral infections frequently cause a lethal hemorrhagic fever in humans and nonhuman primates. The disastrous consequences of infection with these viruses have been pursued as potential biological weapons. To date, there are no therapeutic options available for the prophylaxis or treatment of infected individuals. The recognition that Ebola and Marburg viruses may be exploited as biological weapons has resulted in major efforts to develop modalities to counter infection. In this review, select technologies and approaches will be highlighted as part of the critical path for the development of therapeutics to ameliorate the invariably devastating outcomes of human filoviral infections. PMID:16441210

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

    PubMed Central

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

    1995-01-01

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

  15. VP40 Octamers Are Essential for Ebola Virus Replication

    PubMed Central

    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

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

    PubMed

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

    2015-06-01

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

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

    SciTech Connect

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

    1982-10-01

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

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

    SciTech Connect

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

    1982-10-01

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

  19. A case of Ebola virus infection.

    PubMed

    Emond, R T; Evans, B; Bowen, E T; Lloyd, G

    1977-08-27

    In November 1976 an investigator at the Microbiological Research Establishment accidentally inoculated himself while processing material from patients in Africa who had been suffering from a haemorrhagic fever of unknown cause. He developed an illness closely resembling Marburg disease, and a virus was isolated from his blood that resembled Marburg virus but was distinct serologically. The course of the illness was mild and may have been modified by treatment with human interferon and convalescent serum. Convalescence was protracted; there was evidence of bone-marrow depression and virus was excreted in low titre for some weeks. Recovery was complete. Infection was contained by barrier-nursing techniques using a negative-pressure plastic isolator and infection did not spread to attendant staff or to the community. PMID:890413

  20. A case of Ebola virus infection.

    PubMed Central

    Emond, R T; Evans, B; Bowen, E T; Lloyd, G

    1977-01-01

    In November 1976 an investigator at the Microbiological Research Establishment accidentally inoculated himself while processing material from patients in Africa who had been suffering from a haemorrhagic fever of unknown cause. He developed an illness closely resembling Marburg disease, and a virus was isolated from his blood that resembled Marburg virus but was distinct serologically. The course of the illness was mild and may have been modified by treatment with human interferon and convalescent serum. Convalescence was protracted; there was evidence of bone-marrow depression and virus was excreted in low titre for some weeks. Recovery was complete. Infection was contained by barrier-nursing techniques using a negative-pressure plastic isolator and infection did not spread to attendant staff or to the community. PMID:890413

  1. Molecular Evidence of Sexual Transmission of Ebola Virus.

    PubMed

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

    2015-12-17

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. A cellular automata model of Ebola virus dynamics

    NASA Astrophysics Data System (ADS)

    Burkhead, Emily; Hawkins, Jane

    2015-11-01

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

  6. Persistence of Ebola Virus in Ocular Fluid during Convalescence

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-18

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

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

    PubMed

    Kekul, Alexander S

    2015-07-01

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

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

    PubMed Central

    Kekulé, Alexander S.

    2015-01-01

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

  10. The Ebola Virus Matrix Protein Penetrates into the Plasma Membrane

    PubMed Central

    Adu-Gyamfi, Emmanuel; Soni, Smita P.; Xue, Yi; Digman, Michelle A.; Gratton, Enrico; Stahelin, Robert V.

    2013-01-01

    Ebola, a fatal virus in humans and non-human primates, has no Food and Drug Administration-approved vaccines or therapeutics. The virus from the Filoviridae family causes hemorrhagic fever, which rapidly progresses and in some cases has a fatality rate near 90%. The Ebola genome encodes seven genes, the most abundantly expressed of which is viral protein 40 (VP40), the major Ebola matrix protein that regulates assembly and egress of the virus. It is well established that VP40 assembles on the inner leaflet of the plasma membrane; however, the mechanistic details of plasma membrane association by VP40 are not well understood. In this study, we used an array of biophysical experiments and cellular assays along with mutagenesis of VP40 to investigate the role of membrane penetration in VP40 assembly and egress. Here we demonstrate that VP40 is able to penetrate specifically into the plasma membrane through an interface enriched in hydrophobic residues in its C-terminal domain. Mutagenesis of this hydrophobic region consisting of Leu213, Ile293, Leu295, and Val298 demonstrated that membrane penetration is critical to plasma membrane localization, VP40 oligomerization, and viral particle egress. Taken together, VP40 membrane penetration is an important step in the plasma membrane localization of the matrix protein where oligomerization and budding are defective in the absence of key hydrophobic interactions with the membrane. PMID:23297401

  11. Potential for large outbreaks of Ebola virus disease

    PubMed Central

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

    2014-01-01

    Outbreaks of Ebola virus can cause substantial morbidity and mortality in affected regions. The largest outbreak of Ebola to date is currently underway in West Africa, with 3944 cases reported as of 5th September 2014. To develop a better understanding of Ebola transmission dynamics, we revisited data from the first known Ebola outbreak, which occurred in 1976 in Zaire (now Democratic Republic of Congo). By fitting a mathematical model to time series stratified by disease onset, outcome and source of infection, we were able to estimate several epidemiological quantities that have previously proved challenging to measure, including the contribution of hospital and community infection to transmission. We found evidence that transmission decreased considerably before the closure of the hospital, suggesting that the decline of the outbreak was most likely the result of changes in host behaviour. Our analysis suggests that the person-to-person reproduction number was 1.34 (95% CI: 0.922.11) in the early part of the outbreak. Using stochastic simulations we demonstrate that the same epidemiological conditions that were present in 1976 could have generated a large outbreak purely by chance. At the same time, the relatively high person-to-person basic reproduction number suggests that Ebola would have been difficult to control through hospital-based infection control measures alone. PMID:25480136

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2012-01-01

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

  14. Lack of Protection Against Ebola Virus from Chloroquine in Mice and Hamsters

    PubMed Central

    Falzarano, Darryl; Safronetz, David; Prescott, Joseph; Marzi, Andrea; Feldmann, Friederike

    2015-01-01

    The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes. PMID:25988934

  15. Lack of protection against ebola virus from chloroquine in mice and hamsters.

    PubMed

    Falzarano, Darryl; Safronetz, David; Prescott, Joseph; Marzi, Andrea; Feldmann, Friederike; Feldmann, Heinz

    2015-06-01

    The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes. PMID:25988934

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2016-03-18

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

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

    PubMed

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

    2015-12-01

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

  19. Prospects for immunisation against Marburg and Ebola viruses

    PubMed Central

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

    2012-01-01

    SUMMARY 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. PMID:20658513

  20. Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-07-10

    As of July 1, 2015, Guinea, Liberia, and Sierra Leone have reported a total of 27,443 confirmed, probable, and suspected Ebola virus disease (Ebola) cases and 11,220 deaths. Guinea and Sierra Leone have yet to interrupt transmission of Ebola virus. In January, 2016, Liberia successfully achieved Ebola transmission-free status, with no new Ebola cases occurring during a 42-day period; however, new Ebola cases were reported beginning June 29, 2015. Local cultural practices and beliefs have posed challenges to disease control, and therefore, targeted, timely health messages are needed to address practices and misperceptions that might hinder efforts to stop the spread of Ebola. As early as September 2014, Ebola spread to most counties in Liberia. To assess Ebola-related knowledge, attitudes, and practices (KAP) in the community, CDC epidemiologists who were deployed to the counties (field team), carried out a survey conducted by local trained interviewers. The survey was conducted in September and October 2014 in five counties in Liberia with varying cumulative incidence of Ebola cases. Survey results indicated several findings. First, basic awareness of Ebola was high across all surveyed populations (median correct responses = 16 of 17 questions on knowledge of Ebola transmission; range = 2-17). Second, knowledge and understanding of Ebola symptoms were incomplete (e.g., 61% of respondents said they would know if they had Ebola symptoms). Finally, certain fears about the disease were present: >90% of respondents indicated a fear of Ebola patients, >40% a fear of cured patients, and >50% a fear of treatment units (expressions of this last fear were greater in counties with lower Ebola incidence). This survey, which was conducted at a time when case counts were rapidly increasing in Liberia, indicated limited knowledge of Ebola symptoms and widespread fear of Ebola treatment units despite awareness of communication messages. Continued efforts are needed to address cultural practices and beliefs to interrupt Ebola transmission. PMID:26158352

  4. Productive replication of Ebola virus is regulated by the c-Abl1 tyrosine kinase.

    PubMed

    García, Mayra; Cooper, Arik; Shi, Wei; Bornmann, William; Carrion, Ricardo; Kalman, Daniel; Nabel, Gary J

    2012-02-29

    Ebola virus causes a fulminant infection in humans resulting in diffuse bleeding, vascular instability, hypotensive shock, and often death. Because of its high mortality and ease of transmission from human to human, Ebola virus remains a biological threat for which effective preventive and therapeutic interventions are needed. An understanding of the mechanisms of Ebola virus pathogenesis is critical for developing antiviral therapeutics. Here, we report that productive replication of Ebola virus is modulated by the c-Abl1 tyrosine kinase. Release of Ebola virus-like particles (VLPs) in a cell culture cotransfection system was inhibited by c-Abl1-specific small interfering RNA (siRNA) or by Abl-specific kinase inhibitors and required tyrosine phosphorylation of the Ebola matrix protein VP40. Expression of c-Abl1 stimulated an increase in phosphorylation of tyrosine 13 (Y(13)) of VP40, and mutation of Y(13) to alanine decreased the release of Ebola VLPs. Productive replication of the highly pathogenic Ebola virus Zaire strain was inhibited by c-Abl1-specific siRNAs or by the Abl-family inhibitor nilotinib by up to four orders of magnitude. These data indicate that c-Abl1 regulates budding or release of filoviruses through a mechanism involving phosphorylation of VP40. This step of the virus life cycle therefore may represent a target for antiviral therapy. PMID:22378924

  5. Ebola Virus: Another Challenge from the Deadly Viral Brigade.

    PubMed

    Bajpai, Smrati; Nadkar, M Y

    2014-09-01

    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 recent west African outbreak of Ebolavirus has brought this filoviral infection again in limelight, Indian government has issued guidelines to various airports to screen travelers coming from Africa and middle east Haj pilgrims to keep a check on this highly virulent infection. This viral hemorrhagic disease has remained confined majorly to Africa but its high outbreak potential makes it essential for all infectious disease clinicians and people dealing with travel medicine to be cautious. Management of these patients with symptomatic therapy is the current strategy which is followed. There is absence of any effective vaccine so further research is warranted in this direction. PMID:26259318

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

    PubMed

    Nadhem, Selmi; Nejib, Hachicha D

    2015-12-01

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

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Yuan, Shu

    2015-01-01

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

  10. Ebola

    MedlinePLUS

    ... Sledding, Skiing, Snowboarding, Skating Crushes What's a Booger? Ebola KidsHealth > For Kids > Ebola Print A A A Text Size en español Ébola What Is Ebola? Ebola is a dangerous virus that can cause ...

  11. Ebola

    MedlinePLUS

    ... Sledding, Skiing, Snowboarding, Skating Crushes What's a Booger? Ebola KidsHealth > For Kids > Ebola Print A A A Text Size en espaol bola What Is Ebola? Ebola is a dangerous virus that can cause ...

  12. Ebola

    MedlinePLUS

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

  13. A serological survey of Ebola virus infection in central African nonhuman primates.

    PubMed

    Leroy, E M; Telfer, P; Kumulungui, B; Yaba, P; Rouquet, P; Roques, P; Gonzalez, J-P; Ksiazek, T G; Rollin, P E; Nerrienet, E

    2004-12-01

    We used an ELISA to determine the prevalence of IgG antibodies specific for the Zaire subtype of Ebola virus in 790 nonhuman primates, belonging to 20 species, studied between 1985 and 2000 in Cameroon, Gabon, and the Republic of Congo. The seroprevalence rate of Ebola antibody in wild-born chimpanzees was 12.9%, indicating that (1) Ebola virus circulates in the forests of a large region of central Africa, including countries such as Cameroon, where no human cases of Ebola infections have been reported; (2) Ebola virus was present in the area before recent outbreaks in humans; (3) chimpanzees are continuously in contact with the virus; and (4) nonlethal Ebola infection can occur in chimpanzees. These results, together with the unexpected detection of Ebola-specific IgG in other species (5 drills, 1 baboon, 1 mandrill, and 1 Cercopithecus), may help to narrow the search for the reservoir of Ebola virus. They also suggest that future Ebola outbreaks may occur anywhere in the central African forest region. PMID:15529251

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

    PubMed

    Haque, Azizul; Hober, Didier; Blondiaux, Joel

    2015-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

  17. Productive Replication of Ebola Virus Is Regulated by the c-Abl1 Tyrosine Kinase

    PubMed Central

    García, Mayra; Cooper, Arik; Shi, Wei; Bornmann, William; Carrion, Ricardo; Kalman, Daniel; Nabel, Gary J.

    2016-01-01

    Ebola virus causes a fulminant infection in humans resulting in diffuse bleeding, vascular instability, hypotensive shock, and often death. Because of its high mortality and ease of transmission from human to human, Ebola virus remains a biological threat for which effective preventive and therapeutic interventions are needed. An understanding of the mechanisms of Ebola virus pathogenesis is critical for developing antiviral therapeutics. Here, we report that productive replication of Ebola virus is modulated by the c-Abl1 tyrosine kinase. Release of Ebola virus–like particles (VLPs) in a cell culture cotransfection system was inhibited by c-Abl1–specific small interfering RNA (siRNA) or by Abl-specific kinase inhibitors and required tyrosine phosphorylation of the Ebola matrix protein VP40. Expression of c-Abl1 stimulated an increase in phosphorylation of tyrosine 13 (Y13) of VP40, and mutation of Y13 to alanine decreased the release of Ebola VLPs. Productive replication of the highly pathogenic Ebola virus Zaire strain was inhibited by c-Abl1–specific siRNAs or by the Abl-family inhibitor nilotinib by up to four orders of magnitude. These data indicate that c-Abl1 regulates budding or release of filoviruses through a mechanism involving phosphorylation of VP40. This step of the virus life cycle therefore may represent a target for antiviral therapy. PMID:22378924

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

    PubMed

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

    2016-04-15

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

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

    PubMed

    Mirazimi, A

    2015-09-01

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

  20. Conformational plasticity of the Ebola virus matrix protein

    PubMed Central

    Radzimanowski, Jens; Effantin, Gregory; Weissenhorn, Winfried

    2014-01-01

    Filoviruses are the causative agents of a severe and often fatal hemorrhagic fever with repeated outbreaks in Africa. They are negative sense single stranded enveloped viruses that can cross species barriers from its natural host bats to primates including humans. The small size of the genome poses limits to viral adaption, which may be partially overcome by conformational plasticity. Here we review the different conformational states of the Ebola virus (EBOV) matrix protein VP40 that range from monomers, to dimers, hexamers, and RNA-bound octamers. This conformational plasticity that is required for the viral life cycle poses a unique opportunity for development of VP40 specific drugs. Furthermore, we compare the structure to homologous matrix protein structures from Paramyxoviruses and Bornaviruses and we predict that they do not only share the fold but also the conformational flexibility of EBOV VP40. PMID:25159197

  1. Against the clock towards new Ebola virus therapies.

    PubMed

    Martínez-Romero, Carles; García-Sastre, Adolfo

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Shen, Mingwang; Xiao, Yanni; Rong, Libin

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Shen, Mingwang; Xiao, Yanni; Rong, Libin

    2015-10-01

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

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

    PubMed Central

    Shen, Mingwang; Xiao, Yanni; Rong, Libin

    2015-01-01

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

  6. Vesicular Stomatitis Virus–Based Vaccines against Lassa and Ebola Viruses

    PubMed Central

    Marzi, Andrea; Feldmann, Friederike; Geisbert, Thomas W.; Feldmann, Heinz

    2015-01-01

    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. PMID:25625358

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

    PubMed Central

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

    2015-01-01

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

  8. Haemorrhagic fever in Gabon. I. Incidence of Lassa, Ebola and Marburg viruses in Haut-Ogoou.

    PubMed

    Ivanoff, B; Duquesnoy, P; Languillat, G; Saluzzo, J F; Georges, A; Gonzalez, J P; McCormick, J

    1982-01-01

    A serological enquiry aimed at determining the incidence of infection with Lassa, Ebola and Marburg viruses was conducted on the human population of the region of Haut-Ogoou (Gabon) and on primates. The results, obtained by the indirect immunofluorescence technique, showed that more than 6% of the human population had had contact with Ebola virus but no antibodies against Marburg or Lassa viruses were found. Most sera reacted to an Ebola antigen from a Zairian strain, but showed little or no reaction to an antigen from a Sudanese strain. PMID:7164137

  9. Euthanasia Assessment in Ebola Virus Infected Nonhuman Primates

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

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

    2015-04-14

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

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

    DOE PAGESBeta

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

    2015-04-14

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

  18. Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus

    PubMed Central

    Adu-Gyamfi, Emmanuel; Johnson, Kristen A.; Fraser, Mark E.; Scott, Jordan L.; Soni, Smita P.; Jones, Keaton R.; Digman, Michelle A.; Gratton, Enrico; Tessier, Charles R.

    2015-01-01

    ABSTRACT Lipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles. IMPORTANCE The lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry. PMID:26136573

  19. Ebola virus disease cases among health care workers not working in Ebola treatment units--Liberia, June-August, 2014.

    PubMed

    Matanock, Almea; Arwady, M Allison; Ayscue, Patrick; Forrester, Joseph D; Gaddis, Bethany; Hunter, Jennifer C; Monroe, Benjamin; Pillai, Satish K; Reed, Christie; Schafer, Ilana J; Massaquoi, Moses; Dahn, Bernice; De Cock, Kevin M

    2014-11-21

    West Africa is experiencing the largest Ebola virus disease (Ebola) epidemic in recorded history. Health care workers (HCWs) are at increased risk for Ebola. In Liberia, as of August 14, 2014, a total of 810 cases of Ebola had been reported, including 10 clusters of Ebola cases among HCWs working in facilities that were not Ebola treatment units (non-ETUs). The Liberian Ministry of Health and Social Welfare and CDC investigated these clusters by reviewing surveillance data, interviewing county health officials, HCWs, and contact tracers, and visiting health care facilities. Ninety-seven cases of Ebola (12% of the estimated total) were identified among HCWs; 62 HCW cases (64%) were part of 10 distinct clusters in non-ETU health care facilities, primarily hospitals. Early recognition and diagnosis of Ebola in patients who were the likely source of introduction to the HCWs (i.e., source patients) was missed in four clusters. Inconsistent recognition and triage of cases of Ebola, overcrowding, limitations in layout of physical spaces, lack of training in the use of and adequate supply of personal protective equipment (PPE), and limited supervision to ensure consistent adherence to infection control practices all were observed. Improving infection control infrastructure in non-ETUs is essential for protecting HCWs. Since August, the Liberian Ministry of Health and Social Welfare with a consortium of partners have undertaken collaborative efforts to strengthen infection control infrastructure in non-ETU health facilities. PMID:25412067

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-09-01

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

  2. Ebola Virus Disease in Mice with Transplanted Human Hematopoietic Stem Cells

    PubMed Central

    Ldtke, Anja; Oestereich, Lisa; Ruibal, Paula; Wurr, Stephanie; Pallasch, Elisa; Bockholt, Sabrina; Ip, Wing Hang; Rieger, Toni; Gmez-Medina, Sergio; Stocking, Carol; Rodrguez, Estefana; Gnther, Stephan

    2015-01-01

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

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

    SciTech Connect

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

    2009-01-20

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2016-03-15

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

  7. Being Ready to Treat Ebola Virus Disease Patients

    PubMed Central

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

    2015-01-01

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

  8. Being ready to treat Ebola virus disease patients.

    PubMed

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

    2015-02-01

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

  9. Therapeutics for postexposure treatment of Ebola virus infection

    PubMed Central

    Jerebtsova, Marina; Nekhai, Sergei

    2015-01-01

    The current Ebola virus disease (EVD) outbreak in West Africa is the largest with over 5100 deaths in four West African countries as of 14 November 2014. EVD has high case-fatality rates but no licensed treatment or vaccine is yet available. Several vaccine candidates that protected nonhuman primates are not yet available for clinical use. Slow development of vaccine-stimulated immunity, sporadic nature and fast progression of EVD underlines the need for the development of effective postexposure therapeutic drugs. WHO encouraged the use of untested drugs for EVD to curb the fast-spreading outbreak. Here, we summarize therapeutics for EVD including monoclonal antibody-based therapy and inhibitors of viral replication including our recently developed small-molecule inhibitors of VP30 dephosphorylation. PMID:26213559

  10. Prognostic Analysis of Patients with Ebola Virus Disease

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy

    PubMed Central

    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

    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. PMID:22247782

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

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

  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.

    PubMed

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

    2015-10-01

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

  17. Extracorporeal virus elimination for the treatment of severe Ebola virus disease--first experience with lectin affinity plasmapheresis.

    PubMed

    Büttner, Stefan; Koch, Benjamin; Dolnik, Olga; Eickmann, Markus; Freiwald, Tilo; Rudolf, Sarah; Engel, Jürgen; Becker, Stephan; Ronco, Claudio; Geiger, Helmut

    2014-01-01

    Therapeutic options for Ebola virus disease (EVD) are currently limited to (1) best supportive care, and (2) evolving virus-specific therapies, resulting from decades of analyzing one of the world's deadliest diseases. Supportive care ranges from oral or intravenous rehydration therapy and anti-emetics in developing countries to much more extensive life-support interventions in resource-rich countries. Current EVD-specific therapies attempt to either interfere with the earliest steps of viral replication or to elicit a strong immune response against the virus. An entirely new approach is the extracorporeal elimination of viruses and viral glycoproteins by lectin affinity plasmapheresis. Herein, we report for the first time the successful and safe use of lectin affinity plasmapheresis in a patient with severe Ebola virus disease. PMID:25676045

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

    PubMed

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

    2016-02-01

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

  19. ELISA for the detection of antibodies to Ebola viruses.

    PubMed

    Ksiazek, T G; West, C P; Rollin, P E; Jahrling, P B; Peters, C J

    1999-02-01

    EIAs for IgG and IgM antibodies directed against Ebola (EBO) viral antigens have been developed and evaluated using sera of animals and humans surviving infection with EBO viruses. The IgM capture assay detected anti-EBO (subtype Reston) antibodies in the sera of 5 of 5 experimentally infected animals at the time they succumbed to lethal infections. IgM antibodies were also detected in the serum of a human who was infected with EBO (subtype Reston) during a postmortem examination of an infected monkey. The antibody was detectable as early as day 6 after infection in experimentally infected animals and persisted for <90 days. The IgG response was less rapid; however, it persisted for >400 days in 3 animals who survived infection, and it persisted for approximately 10 years after infection in the sera of 2 humans. Although these data are limited by the number of sera available for verification, the IgM assay seems to have great promise as a diagnostic tool. Furthermore the long-term persistence of the IgG antibodies measured by this test strongly suggests that the ELISA will be useful in field investigations of EBO virus. PMID:9988184

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  2. Enzyme immunosorbent assay for Ebola virus antigens in tissues of infected primates.

    PubMed

    Ksiazek, T G; Rollin, P E; Jahrling, P B; Johnson, E; Dalgard, D W; Peters, C J

    1992-04-01

    A sandwich enzyme immunosorbent assay (EIA) using a mixture of mouse monoclonal antibodies for antigen capture and polyclonal hyperimmune rabbit anti-Ebola virus serum for antigen detection was developed and evaluated on the tissues of monkeys naturally or experimentally infected with strains of Ebola viruses. When compared with virus isolation, the antigen detection EIA was both sensitive and specific: 44 of 45 (97.7%) liver homogenates and 38 of 41 (92.7%) spleen homogenates that were culture positive and tested by both techniques were positive for viral antigen, while 85 of 87 (97.7%) culture-negative liver homogenates and 66 of 66 culture-negative spleen homogenates were found to be antigen negative. The assay, initially developed to detect antigens of prototype African strains of Ebola virus, reliably detected related strains of Ebola virus found during two recent outbreaks of Ebola virus infection among imported, quarantined Macaca fascicularis monkeys in the United States. The assay allows economical and rapid testing of large numbers of tissue specimens. Antigen was found in homogenates of spleen and liver and in serum. PMID:1572982

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-11-01

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

  5. Cathepsin B & L Are Not Required for Ebola Virus Replication

    PubMed Central

    Marzi, Andrea; Reinheckel, Thomas; Feldmann, Heinz

    2012-01-01

    Ebola virus (EBOV), family Filoviridae, emerged in 1976 on the African continent. Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen. The most pathogenic and best-studied species is Zaire ebolavirus (ZEBOV). EBOV encodes one viral surface glycoprotein (GP), which is essential for replication, a determinant of pathogenicity and an important immunogen. GP mediates viral entry through interaction with cellular surface molecules, which results in the uptake of virus particles via macropinocytosis. Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL), which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and fusion domain and productive infection. We studied the effect of CatB and CatL on in vitro and in vivo replication of EBOV. Similar to previous findings, our results show an effect of CatB, but not CatL, on ZEBOV entry into cultured cells. Interestingly, cell entry by other EBOV species (Bundibugyo, Côte d'Ivoire, Reston and Sudan ebolavirus) was independent of CatB or CatL as was EBOV replication in general. To investigate whether CatB and CatL have a role in vivo during infection, we utilized the mouse model for ZEBOV. Wild-type (control), catB−/− and catL−/− mice were equally susceptible to lethal challenge with mouse-adapted ZEBOV with no difference in virus replication and time to death. In conclusion, our results show that CatB and CatL activity is not required for EBOV replication. Furthermore, EBOV glycoprotein cleavage seems to be mediated by an array of proteases making targeted therapeutic approaches difficult. PMID:23236527

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

    PubMed

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

    2015-05-01

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

  7. Evasion of Interferon Responses by Ebola and Marburg Viruses

    PubMed Central

    Amarasinghe, Gaya K.

    2009-01-01

    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)-α/β production and inhibit signaling downstream of the IFN-α/β and the IFN-γ 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-ɛ 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-α/β 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-α 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 these deadly viruses counteract the IFN system. It will be of interest to determine how these differences influence pathogenesis. PMID:19694547

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

    PubMed

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

    2016-03-18

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

  9. Marburg, Ebola and Rift Valley Fever virus antibodies in East African primates.

    PubMed

    Johnson, B K; Gitau, L G; Gichogo, A; Tukei, P M; Else, J G; Suleman, M A; Kimani, R; Sayer, P D

    1982-01-01

    Sera from 464 primates held at four institutes in Kenya were tested by indirect immunofluorescence for the presence of antibodies against Marburg, Ebola, Congo haemorrhagic fever, Rift Valley fever and Lassa viruses. Four of 136 vervet monkeys were positive for Marburg virus antibodies and three of 184 baboons had antibodies against Ebola virus. One baboon was positive for Marburg virus antibodies. Two vervet monkeys, three baboons and one grivet monkey (of 56 tested) had antibodies against Rift Valley fever virus. No Congo or Lassa virus antibodies were detected. A sample of 88 sera of more arboreal primates (Sykes, blue and colobus monkeys) were negative against all five antigens, as were sera from 58 staff members of the institutes who worked with or near the animals. PMID:6810518

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

    SciTech Connect

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

    2012-12-05

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

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

    PubMed

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

    2016-01-15

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-09-01

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

  14. Three minimal sequences found in Ebola virus genomes and absent from human DNA

    PubMed Central

    Silva, Raquel M.; Pratas, Diogo; Castro, Luísa; Pinho, Armando J.; Ferreira, Paulo J. S. G.

    2015-01-01

    Motivation: Ebola virus causes high mortality hemorrhagic fevers, with more than 25 000 cases and 10 000 deaths in the current outbreak. Only experimental therapies are available, thus, novel diagnosis tools and druggable targets are needed. Results: Analysis of Ebola virus genomes from the current outbreak reveals the presence of short DNA sequences that appear nowhere in the human genome. We identify the shortest such sequences with lengths between 12 and 14. Only three absent sequences of length 12 exist and they consistently appear at the same location on two of the Ebola virus proteins, in all Ebola virus genomes, but nowhere in the human genome. The alignment-free method used is able to identify pathogen-specific signatures for quick and precise action against infectious agents, of which the current Ebola virus outbreak provides a compelling example. Availability and Implementation: EAGLE is freely available for non-commercial purposes at http://bioinformatics.ua.pt/software/eagle. Contact: raquelsilva@ua.pt; pratas@ua.pt Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:25840045

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Chowell, Gerardo; Nishiura, Hiroshi

    2015-01-01

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

  3. Ebola Virus GP Gene Polyadenylation Versus RNA Editing.

    PubMed

    Volchkova, Valentina A; Vorac, Jaroslav; Repiquet-Paire, Laurie; Lawrence, Philip; Volchkov, Viktor E

    2015-10-01

    Synthesis of Ebola virus (EBOV) surface glycoprotein (GP) is dependent on transcriptional RNA editing. Northern blot analysis of EBOV-infected cells using GP-gene-specific probes reveals that, in addition to full-length GP messenger RNAs (mRNAs), a shorter RNA is also synthesized, representing >40% of the total amount of GP mRNA. Sequence analysis demonstrates that this RNA is a truncated version of the full-length GP mRNA that is polyadenylated at the editing site and thus lacks a stop codon. An absence of detectable levels of protein synthesis in cellulo is consistent with the existence of tight regulation of the translation of such mRNA. However, nonstop GP mRNA was shown to be only slightly less stable than the same mRNA containing a stop codon, against the general belief in nonstop decay mechanisms aimed at detecting and destroying mRNAs lacking a stop codon. In conclusion, we demonstrate that the editing site indeed serves as a cryptic transcription termination/polyadenylation site, which rarely also functions to edit GP mRNA for expression of surface GP. This new data suggest that the downregulation of surface GP expression is even more dramatic than previously thought, reinforcing the importance of the GP gene editing site for EBOV replication and pathogenicity. PMID:25838269

  4. Primordial Prevention: Promoting Preparedness for Ebola Virus Disease

    PubMed Central

    Jain, Meena; Sharma, Ankur; Arora, Kapil; Khari, Puneet Mohan; Jain, Vishal

    2015-01-01

    Background: India may face a danger of immediate spread of Ebola Virus Disease (EVD) if it enters the subcontinent. Preparedness for such a condition is a part of its prevention. Dentists form a sizeable chunk of healthcare in India and may help in augmenting the health care team at the time of such outbreaks. This paper details the development and evaluation of a specially tailored program for dental students and faculty for imparting knowledge on EVD and its prevention strategies. Aim: To assess the knowledge score for EVD and its prevention after attending a specially tailored program. Materials and Methods: A multidisciplinary team was selected for content development and providing an insight on the topic. The program was attended by students and faculty members of Manav Rachna Dental College. The knowledge of the attendees about EVD was assessed at the end of the program through a structured questionnaire. The response rate was 96%. Result: According to the knowledge score attained, 52.4% of the participant had good knowledge level and 2.8% had poor knowledge level. There was no significant difference in knowledge scores between the participants having prior knowledge and those having no previous knowledge about the disease (p = 0.135). Conclusion: High response rate and good knowledge level attained by most of the participants established evidence of a successful program. PMID:25954650

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

    PubMed

    Zhou, Yan; Sullivan, Nancy J

    2015-08-01

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

  6. [Current status of drug treatment against the disease caused by the Ebola virus].

    PubMed

    Reina, J

    2016-02-01

    The recent epidemic of disease caused by the Ebola virus has highlighted the need to develop specific drugs and have to deal with this entity. According to virological analysis they have been designed to give you some new drugs and are proven to others might be effective against this virus. The main lines of therapy are based on immunotherapy (convalescent serum of patients and specific monoclonal antibodies), antiviral drugs (favipiravir, BCX4430, brincidofovir), interfering RNAs (TKM-Ebola) and antisense oligonucleotides (morpholino phosphorodiamidate) and other drugs no antiviral (clomiphene NSC62914, FGI-103, amiloride and ouabain). Existing studies are scarce and mainly in animal models and clinical trials have been inconclusive most by the drastic reduction in the number of new cases. However, progress has been made in the biological knowledge of Ebola virus and have been located new therapeutic targets for the future development of specific antiviral. PMID:26785224

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

    PubMed

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

    2016-01-01

    As of February 17, 2016, a total of 14,122 cases (62% confirmed) of Ebola Virus Disease (Ebola) and 3,955 Ebola-related deaths had been reported in Sierra Leone since the epidemic in West Africa began in 2014 (1). A key focus of the Ebola response in Sierra Leone was the promotion and implementation of safe, dignified burials to prevent Ebola transmission by limiting contact with potentially infectious corpses. Traditional funeral practices pose a substantial risk for Ebola transmission through contact with infected bodies, body fluids, contaminated clothing, and other personal items at a time when viral load is high; however, the role of funeral practices in the Sierra Leone epidemic and ongoing Ebola transmission has not been fully characterized (2). In September 2014, a sudden increase in the number of reported Ebola cases occurred in Moyamba, a rural and previously low-incidence district with a population of approximately 260,000 (3). The Sierra Leone Ministry of Health and Sanitation and CDC investigated and implemented public health interventions to control this cluster of Ebola cases, including community engagement, active surveillance, and close follow-up of contacts. A retrospective analysis of cases that occurred during July 11-October 31, 2014, revealed that 28 persons with confirmed Ebola had attended the funeral of a prominent pharmacist during September 5-7, 2014. Among the 28 attendees with Ebola, 21 (75%) reported touching the man's corpse, and 16 (57%) reported having direct contact with the pharmacist before he died. Immediate, safe, dignified burials by trained teams with appropriate protective equipment are critical to interrupt transmission and control Ebola during times of active community transmission; these measures remain important during the current response phase. PMID:26938950

  8. A Replicating Cytomegalovirus-Based Vaccine Encoding a Single Ebola Virus Nucleoprotein CTL Epitope Confers Protection against Ebola Virus

    PubMed Central

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

    2011-01-01

    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-NPCTL). MCMV/ZEBOV-NPCTL 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. PMID:21858240

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

    PubMed Central

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

    2015-01-01

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

  10. The Ebola Virus Matrix Protein VP40 Selectively Induces Vesiculation from Phosphatidylserine-enriched Membranes*

    PubMed Central

    Soni, Smita P.; Stahelin, Robert V.

    2014-01-01

    Ebola virus is from the Filoviridae family of viruses and is one of the most virulent pathogens known with ∼60% clinical fatality. The Ebola virus negative sense RNA genome encodes seven proteins including viral matrix protein 40 (VP40), which is the most abundant protein found in the virions. Within infected cells VP40 localizes at the inner leaflet of the plasma membrane (PM), binds lipids, and regulates formation of new virus particles. Expression of VP40 in mammalian cells is sufficient to form virus-like particles that are nearly indistinguishable from the authentic virions. However, how VP40 interacts with the PM and forms virus-like particles is for the most part unknown. To investigate VP40 lipid specificity in a model of viral egress we employed giant unilamellar vesicles with different lipid compositions. The results demonstrate VP40 selectively induces vesiculation from membranes containing phosphatidylserine (PS) at concentrations of PS that are representative of the PM inner leaflet content. The formation of intraluminal vesicles was not significantly detected in the presence of other important PM lipids including cholesterol and polyvalent phosphoinositides, further demonstrating PS selectivity. Taken together, these studies suggest that PM phosphatidylserine may be an important component of Ebola virus budding and that VP40 may be able to mediate PM scission. PMID:25315776

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

    PubMed

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

    2015-12-01

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

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

    PubMed

    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. PMID:25933611

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

    PubMed

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

    2016-01-26

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

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

    PubMed

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

    2015-04-01

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

  15. Recurrence and reinfection-a new paradigm for the management of Ebola virus disease.

    PubMed

    MacIntyre, C Raina; Chughtai, Abrar Ahmad

    2016-02-01

    Ebola virus disease (EVD) is an understudied infection and many aspects of viral transmission and clinical course remain unclear. With over 17000 EVD survivors in West Africa, the World Health Organization has focused its strategy on managing survivors and the risk of re-emergence of outbreaks posed by persistence of the virus during convalescence. Sexual transmission from survivors has also been documented following the 2014 epidemic and there are documented cases of survivors readmitted to hospital with 'recurrence' of EVD symptoms. In addition to persistence of virus in survivors, there is also some evidence for 'reinfection' with Ebola virus. In this paper, the evidence for recurrence and reinfection of EVD and implications for epidemic control are reviewed. PMID:26711624

  16. Social Vulnerability and Ebola Virus Disease in Rural Liberia

    PubMed Central

    2015-01-01

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

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

    PubMed

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

    2015-09-01

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

  18. Ebola virus VP30 is an RNA binding protein.

    PubMed

    John, Sinu P; Wang, Tan; Steffen, Scott; Longhi, Sonia; Schmaljohn, Connie S; Jonsson, Colleen B

    2007-09-01

    The Ebola virus (EBOV) genome encodes for several proteins that are necessary and sufficient for replication and transcription of the viral RNAs in vitro; NP, VP30, VP35, and L. VP30 acts in trans with an RNA secondary structure upstream of the first transcriptional start site to modulate transcription. Using a bioinformatics approach, we identified a region within the N terminus of VP30 with sequence features that typify intrinsically disordered regions and a putative RNA binding site. To experimentally assess the ability of VP30 to directly interact with the viral RNA, we purified recombinant EBOV VP30 to >90% homogeneity and assessed RNA binding by UV cross-linking and filter-binding assays. VP30 is a strongly acidophilic protein; RNA binding became stronger as pH was decreased. Zn(2+), but not Mg(2+), enhanced activity. Enhancement of transcription by VP30 requires a RNA stem-loop located within nucleotides 54 to 80 of the leader region. VP30 showed low binding affinity to the predicted stem-loop alone or to double-stranded RNA but showed a good binding affinity for the stem-loop when placed in the context of upstream and downstream sequences. To map the region responsible for interacting with RNA, we constructed, purified, and assayed a series of N-terminal deletion mutations of VP30 for RNA binding. The key amino acids supporting RNA binding activity map to residues 26 to 40, a region rich in arginine. Thus, we show for the first time the direct interaction of EBOV VP30 with RNA and the importance of the N-terminal region for binding RNA. PMID:17567691

  19. Ebola Virus VP30 Is an RNA Binding Protein?

    PubMed Central

    John, Sinu P.; Wang, Tan; Steffen, Scott; Longhi, Sonia; Schmaljohn, Connie S.; Jonsson, Colleen B.

    2007-01-01

    The Ebola virus (EBOV) genome encodes for several proteins that are necessary and sufficient for replication and transcription of the viral RNAs in vitro; NP, VP30, VP35, and L. VP30 acts in trans with an RNA secondary structure upstream of the first transcriptional start site to modulate transcription. Using a bioinformatics approach, we identified a region within the N terminus of VP30 with sequence features that typify intrinsically disordered regions and a putative RNA binding site. To experimentally assess the ability of VP30 to directly interact with the viral RNA, we purified recombinant EBOV VP30 to >90% homogeneity and assessed RNA binding by UV cross-linking and filter-binding assays. VP30 is a strongly acidophilic protein; RNA binding became stronger as pH was decreased. Zn2+, but not Mg2+, enhanced activity. Enhancement of transcription by VP30 requires a RNA stem-loop located within nucleotides 54 to 80 of the leader region. VP30 showed low binding affinity to the predicted stem-loop alone or to double-stranded RNA but showed a good binding affinity for the stem-loop when placed in the context of upstream and downstream sequences. To map the region responsible for interacting with RNA, we constructed, purified, and assayed a series of N-terminal deletion mutations of VP30 for RNA binding. The key amino acids supporting RNA binding activity map to residues 26 to 40, a region rich in arginine. Thus, we show for the first time the direct interaction of EBOV VP30 with RNA and the importance of the N-terminal region for binding RNA. PMID:17567691

  20. Effects of Ebola Virus Glycoproteins on Endothelial Cell Activation and Barrier Function

    PubMed Central

    Wahl-Jensen, Victoria M.; Afanasieva, Tatiana A.; Seebach, Jochen; Strher, Ute; Feldmann, Heinz; Schnittler, Hans-Joachim

    2005-01-01

    Ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. Vascular instability and dysregulation are disease-decisive symptoms during severe infection. While the transmembrane glycoprotein GP1,2 has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms of target cell activation and/or increase of endothelial permeability. Here we show that virus-like particles (VLPs) consisting of the Ebola virus matrix protein VP40 and GP1,2 were able to activate endothelial cells and induce a decrease in barrier function as determined by impedance spectroscopy and hydraulic conductivity measurements. In contrast, the soluble glycoproteins sGP and ?-peptide did not activate endothelial cells or change the endothelial barrier function. The VLP-induced decrease in barrier function was further enhanced by the cytokine tumor necrosis factor alpha (TNF-?), which is known to induce a long-lasting decrease in endothelial cell barrier function and is hypothesized to play a key role in Ebola virus pathogenesis. Surprisingly, sGP, but not ?-peptide, induced a recovery of endothelial barrier function following treatment with TNF-?. Our results demonstrate that Ebola virus GP1,2 in its particle-associated form mediates endothelial cell activation and a decrease in endothelial cell barrier function. Furthermore, sGP, the major soluble glycoprotein of Ebola virus, seems to possess an anti-inflammatory role by protecting the endothelial cell barrier function. PMID:16051836

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

    PubMed

    Ohimain, Elijah Ige

    2016-01-01

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

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

    PubMed

    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. PMID:25547682

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

    PubMed

    Hacke, Moritz; Bjrkholm, Patrik; Hellwig, Andrea; Himmels, Patricia; de Almodvar, Carmen Ruiz; Brgger, Britta; Wieland, Felix; Ernst, Andreas M

    2015-01-01

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

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

    SciTech Connect

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

    2006-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. Ebola Virus Selectively Inhibits Responses to Interferons, but Not to Interleukin-1β, in Endothelial Cells

    PubMed Central

    Harcourt, Brian H.; Sanchez, Anthony; Offermann, Margaret K.

    1999-01-01

    Ebola virus infection is highly lethal and leads to severe immunosuppression. In this study, we demonstrate that infection of human umbilical vein endothelial cells (HUVECs) with Ebola virus Zaire (EZ) suppressed basal expression of the major histocompatibility complex class I (MHC I) family of proteins and inhibited the induction of multiple genes by alpha interferon (IFN-α) and IFN-γ, including those coding for MHC I proteins, 2′-5′ oligoadenylate synthetase [2′-5′(A)N], and IFN regulatory factor 1 (IRF-1). Induction of interleukin-6 (IL-6) and ICAM-1 by IL-1β was not suppressed by infection with EZ, suggesting that the inhibition of IFN signaling is specific. Gel shift analysis demonstrated that infection with EZ blocked the induction by IFNs of nuclear proteins that bind to IFN-stimulated response elements, gamma activation sequences, and IFN regulatory factor binding site (IRF-E). In contrast, infection with EZ did not block activation of the transcription factor NF-κB by IL-1β. The events that lead to the blockage of IFN signaling may be critical for Ebola virus-induced immunosuppression and would play a role in the pathogenesis of Ebola virus infection. PMID:10074208

  7. Supportive Care of the First 2 Ebola Virus Disease Patients at the Monrovia Medical Unit.

    PubMed

    Wong, Karen K; Perdue, Christopher L; Malia, Jennifer; Kenney, James L; Peng, Suzette; Gwathney, Jamal K; Raczniak, Gregory A

    2015-10-01

    We describe the first 2 patients admitted to the Monrovia Medical Unit, a facility established to treat Liberian and international response workers with suspected or known Ebola virus disease (EVD). Their recoveries illustrate the value of local point-of-care diagnostics, parenteral therapies, and electrolyte replacement in EVD supportive care. PMID:26021993

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2015-09-15

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

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

    PubMed Central

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

    2016-01-01

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

  11. Time From Infection to Disease and Infectiousness for Ebola Virus Disease, a Systematic Review.

    PubMed

    Velsquez, Gustavo E; Aibana, Omowunmi; Ling, Emilia J; Diakite, Ibrahim; Mooring, Eric Q; Murray, Megan B

    2015-10-01

    We systematically reviewed the literature to estimate the incubation and latent periods of Ebola virus disease. We found limited epidemiological data from individuals with discrete 1-day exposures. Available data suggest that the incubation and latent periods may differ, and mathematical models may be improved by distinguishing between the two periods. PMID:26129757

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

    PubMed

    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. PMID:26812135

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

    PubMed

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

    2016-01-01

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

  14. Controlling the last known cluster of Ebola virus disease - Liberia, January-February 2015.

    PubMed

    Nyenswah, Tolbert; Fallah, Mosoka; Sieh, Sonpon; Kollie, Karsor; Badio, Moses; Gray, Alvin; Dilah, Priscilla; Shannon, Marnijina; Duwor, Stanley; Ihekweazu, Chikwe; Cordier-Lassalle, Thierry; Cordier-Lasalle, Thierry; Shinde, Shivam A; Hamblion, Esther; Davies-Wayne, Gloria; Ratnesh, Murugan; Dye, Christopher; Yoder, Jonathan S; McElroy, Peter; Hoots, Brooke; Christie, Athalia; Vertefeuille, John; Olsen, Sonja J; Laney, A Scott; Neal, Joyce J; Yaemsiri, Sirin; Navin, Thomas R; Coulter, Stewart; Pordell, Paran; Lo, Terrence; Kinkade, Carl; Mahoney, Frank

    2015-05-15

    As one of the three West African countries highly affected by the 2014-2015 Ebola virus disease (Ebola) epidemic, Liberia reported approximately 10,000 cases. The Ebola epidemic in Liberia was marked by intense urban transmission, multiple community outbreaks with source cases occurring in patients coming from the urban areas, and outbreaks in health care facilities (HCFs). This report, based on data from routine case investigations and contact tracing, describes efforts to stop the last known chain of Ebola transmission in Liberia. The index patient became ill on December 29, 2014, and the last of 21 associated cases was in a patient admitted into an Ebola treatment unit (ETU) on February 18, 2015. The chain of transmission was stopped because of early detection of new cases; identification, monitoring, and support of contacts in acceptable settings; effective triage within the health care system; and rapid isolation of symptomatic contacts. In addition, a "sector" approach, which divided Montserrado County into geographic units, facilitated the ability of response teams to rapidly respond to community needs. In the final stages of the outbreak, intensive coordination among partners and engagement of community leaders were needed to stop transmission in densely populated Montserrado County. A companion report describes the efforts to enhance infection prevention and control efforts in HCFs. After February 19, no additional clusters of Ebola cases have been detected in Liberia. On May 9, the World Health Organization declared the end of the Ebola outbreak in Liberia. PMID:25974635

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-12-01

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

  17. Detection of Ebola-Reston (Filoviridae) virus antibody by dot-immunobinding assay.

    PubMed

    Kalter, S S; Heberling, R L; Barry, J D; Tian, P Y

    1995-10-01

    Thirty human and nonhuman primate sera tested at the Centers for Disease Control by enzyme-linked immunosorbent assay (ELISA), immunofluorescent antibody assay (IFA), and Western blotting were retested at the Virus Reference Laboratory, Inc. by the dot-immunobinding assay (DIA). The Ebola-Reston strain of virus received from the Centers for Disease Control was prepared into a suitable DIA antigen as described for other antigens. All six Western blotting-positive sera were also positive by DIA, as were the five ELISA-positive sera. Testing by IFA, the original test of choice, indicated an additional four seropositives, all negative by the other test systems. Of 288 randomly selected macaque sera, 19 were also found to be Ebola-Reston virus-positive by DIA. PMID:8569150

  18. Structure of an Antibody in Complex with Its Mucin Domain Linear Epitope That Is Protective against Ebola Virus

    PubMed Central

    Olal, Daniel; Kuehne, Ana I.; Bale, Shridhar; Halfmann, Peter; Hashiguchi, Takao; Fusco, Marnie L.; Lee, Jeffrey E.; King, Liam B.; Kawaoka, Yoshihiro; Dye, John M.

    2012-01-01

    Antibody 14G7 is protective against lethal Ebola virus challenge and recognizes a distinct linear epitope in the prominent mucin-like domain of the Ebola virus glycoprotein GP. The structure of 14G7 in complex with its linear peptide epitope has now been determined to 2.8 . The structure shows that this GP sequence forms a tandem ?-hairpin structure that binds deeply into a cleft in the antibody-combining site. A key threonine at the apex of one turn is critical for antibody interaction and is conserved among all Ebola viruses. This work provides further insight into the mechanism of protection by antibodies that target the protruding, highly accessible mucin-like domain of Ebola virus and the structural framework for understanding and characterizing candidate immunotherapeutics. PMID:22171276

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

    PubMed

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

    2015-02-27

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

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

    PubMed Central

    Choi, Jin Huk; Croyle, Maria A.

    2013-01-01

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

  1. Ebola virus disease in southern Sudan: hospital dissemination and intrafamilial spread

    PubMed Central

    Baron, Roy C.; McCormick, Joseph B.; Zubeir, Osman A.

    1983-01-01

    Between 31 July and 6 October 1979, 34 cases of Ebola virus disease (22 of which were fatal) occurred among five families in a rural district of southern Sudan; the disease was introduced into four of the families from a local hospital. Chains of secondary spread within the family units, accounting for 29 cases resulted from direct physical contact with an infected person. Among all persons with such contact in the family setting, those who provided nursing care had a 5.1-fold increased risk of infection, emphasizing the importance of intimate contact in the spread of this disease. The absence of illness among persons who were exposed to cases in confined spaces, but without physical contact, confirmed previous impressions that there is no risk of airborne transmission. While the ecology of Ebola virus is unknown, the presence of anti-Ebola antibodies in the sera of 18% of persons who were unassociated with the outbreak suggests that the region is an endemic focus of Ebola virus activity. PMID:6370486

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Summary Background The WHO declared the 2014 west African Ebola epidemic a public health emergency of international concern in view of its potential for further international spread. Decision makers worldwide are in need of empirical data to inform and implement emergency response measures. Our aim was to assess the potential for Ebola virus to spread across international borders via commercial air travel and assess the relative efficiency of exit versus entry screening of travellers at commercial airports. Methods We analysed International Air Transport Association data for worldwide flight schedules between Sept 1, 2014, and Dec 31, 2014, and historic traveller flight itinerary data from 2013 to describe expected global population movements via commercial air travel out of Guinea, Liberia, and Sierra Leone. Coupled with Ebola virus surveillance data, we modelled the expected number of internationally exported Ebola virus infections, the potential effect of air travel restrictions, and the efficiency of airport-based traveller screening at international ports of entry and exit. We deemed individuals initiating travel from any domestic or international airport within these three countries to have possible exposure to Ebola virus. We deemed all other travellers to have no significant risk of exposure to Ebola virus. Findings Based on epidemic conditions and international flight restrictions to and from Guinea, Liberia, and Sierra Leone as of Sept 1, 2014 (reductions in passenger seats by 51% for Liberia, 66% for Guinea, and 85% for Sierra Leone), our model projects 2·8 travellers infected with Ebola virus departing the above three countries via commercial flights, on average, every month. 91 547 (64%) of all air travellers departing Guinea, Liberia, and Sierra Leone had expected destinations in low-income and lower-middle-income countries. Screening international travellers departing three airports would enable health assessments of all travellers at highest risk of exposure to Ebola virus infection. Interpretation Decision makers must carefully balance the potential harms from travel restrictions imposed on countries that have Ebola virus activity against any potential reductions in risk from Ebola virus importations. Exit screening of travellers at airports in Guinea, Liberia, and Sierra Leone would be the most efficient frontier at which to assess the health status of travellers at risk of Ebola virus exposure, however, this intervention might require international support to implement effectively. Funding Canadian Institutes of Health Research. PMID:25458732

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

    PubMed Central

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

    2015-01-01

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

  10. Mapping of conserved and species-specific antibody epitopes on the Ebola virus nucleoprotein.

    PubMed

    Changula, Katendi; Yoshida, Reiko; Noyori, Osamu; Marzi, Andrea; Miyamoto, Hiroko; Ishijima, Mari; Yokoyama, Ayaka; Kajihara, Masahiro; Feldmann, Heinz; Mweene, Aaron S; Takada, Ayato

    2013-09-01

    Filoviruses (viruses in the genus Ebolavirus and Marburgvirus in the family Filoviridae) cause severe haemorrhagic fever in humans and nonhuman primates. Rapid, highly sensitive, and reliable filovirus-specific assays are required for diagnostics and outbreak control. Characterisation of antigenic sites in viral proteins can aid in the development of viral antigen detection assays such immunochromatography-based rapid diagnosis. We generated a panel of mouse monoclonal antibodies (mAbs) to the nucleoprotein (NP) of Ebola virus belonging to the species Zaire ebolavirus. The mAbs were divided into seven groups based on the profiles of their specificity and cross-reactivity to other species in the Ebolavirus genus. Using synthetic peptides corresponding to the Ebola virus NP sequence, the mAb binding sites were mapped to seven antigenic regions in the C-terminal half of the NP, including two highly conserved regions among all five Ebolavirus species currently known. Furthermore, we successfully produced species-specific rabbit antisera to synthetic peptides predicted to represent unique filovirus B-cell epitopes. Our data provide useful information for the development of Ebola virus antigen detection assays. PMID:23702199

  11. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.

    PubMed

    Carette, Jan E; Raaben, Matthijs; Wong, Anthony C; Herbert, Andrew S; Obernosterer, Gregor; Mulherkar, Nirupama; Kuehne, Ana I; Kranzusch, Philip J; Griffin, April M; Ruthel, Gordon; Dal Cin, Paola; Dye, John M; Whelan, Sean P; Chandran, Kartik; Brummelkamp, Thijn R

    2011-09-15

    Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification. Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1 (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann-Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents. PMID:21866103

  12. Mapping of the VP40-Binding Regions of the Nucleoprotein of Ebola Virus?

    PubMed Central

    Noda, Takeshi; Watanabe, Shinji; Sagara, Hiroshi; Kawaoka, Yoshihiro

    2007-01-01

    Expression of Ebola virus nucleoprotein (NP) in mammalian cells leads to the formation of helical structures, which serve as a scaffold for the nucleocapsid. We recently found that NP binding with the matrix protein VP40 is important for nucleocapsid incorporation into virions (T. Noda, H. Ebihara, Y. Muramoto, K. Fujii, A. Takada, H. Sagara, J. H. Kim, H. Kida, H. Feldmann, and Y. Kawaoka, PLoS Pathog. 2:e99, 2006). To identify the region(s) on the NP molecule required for VP40 binding, we examined the interaction of a series of NP deletion mutants with VP40 biochemically and ultrastructurally. We found that both termini of NP (amino acids 2 to 150 and 601 to 739) are essential for its interaction with VP40 and for its incorporation into virus-like particles (VLPs). We also found that the C terminus of NP is important for nucleocapsid incorporation into virions. Of interest is that the formation of NP helices, which involves the N-terminal 450 amino acids of NP, is dispensable for NP incorporation into VLPs. These findings enhance our understanding of Ebola virus assembly and in so doing move us closer to the identification of targets for the development of antiviral compounds to combat Ebola virus infection. PMID:17229682

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-14

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Barbarossa, Maria Vittoria; Dnes, Attila; Kiss, Gbor; Nakata, Yukihiko; Rst, Gergely; Vizi, Zsolt

    2015-01-01

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

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

    PubMed Central

    Gire, Stephen K.; Goba, Augustine; Andersen, Kristian G.; Sealfon, Rachel S. G.; Park, Daniel J.; Kanneh, Lansana; Jalloh, Simbirie; Momoh, Mambu; Fullah, Mohamed; Dudas, Gytis; Wohl, Shirlee; Moses, Lina M.; Yozwiak, Nathan L.; Winnicki, Sarah; Matranga, Christian B.; Malboeuf, Christine M.; Qu, James; Gladden, Adrianne D.; Schaffner, Stephen F.; Yang, Xiao; Jiang, Pan-Pan; Nekoui, Mahan; Colubri, Andres; Coomber, Moinya Ruth; Fonnie, Mbalu; Moigboi, Alex; Gbakie, Michael; Kamara, Fatima K.; Tucker, Veronica; Konuwa, Edwin; Saffa, Sidiki; Sellu, Josephine; Jalloh, Abdul Azziz; Kovoma, Alice; Koninga, James; Mustapha, Ibrahim; Kargbo, Kandeh; Foday, Momoh; Yillah, Mohamed; Kanneh, Franklyn; Robert, Willie; Massally, James L. B.; Chapman, Sinad 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-08-01

    In March 2014 the World Health Organization was notified of an outbreak of Ebola virus disease (EVD) in the forest region of Guinea. As of May 2015, the outbreak had become the most devastating EVD epidemic in history with more than 27,000 cases and more than 11,000 deaths. The introduction of EVD into noncontiguous countries, including the United States, from infected travelers highlights the importance of preparedness of all health care providers. Early identification and rapid isolation of patients suspected with EVD is critical to limiting the spread of Ebola virus. Additionally, enhanced understanding of EVD case definitions, clinical presentation, treatment procedures, and infection control strategies will improve the ability of health care workers to provide safe care for patients with EVD. PMID:26116335

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

    SciTech Connect

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

    1984-09-01

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

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

    PubMed

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

    2015-10-01

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

  3. Ebola Hemorrhagic Fever: Transmission

    MedlinePLUS

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

  4. Ebola Hemorrhagic Fever: Diagnosis

    MedlinePLUS

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

  5. Ebola Hemorrhagic Fever: Treatment

    MedlinePLUS

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

  6. Ebola Hemorrhagic Fever: Prevention

    MedlinePLUS

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    Lasala, Ftima; Arce, Eva; Otero, Joaqun 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-12-01

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

  11. Managing Potential Laboratory Exposure to Ebola Virus by Using a Patient Biocontainment Care Unit1

    PubMed Central

    Martin, James W.; Rusnak, Janice M.; Cieslak, Theodore J.; Warfield, Kelly L.; Anderson, Edwin L.; Ranadive, Manmohan V.

    2008-01-01

    In 2004, a scientist from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) was potentially exposed to a mouse-adapted variant of the Zaire species of Ebola virus. The circumstances surrounding the case are presented, in addition to an update on historical admissions to the medical containment suite at USAMRIID. Research facilities contemplating work with pathogens requiring Biosafety Level 4 laboratory precautions should be mindful of the occupational health issues highlighted in this article. PMID:18507897

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

    PubMed Central

    Gallaher, William R.; Garry, Robert F.

    2015-01-01

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

  13. Antigen capture enzyme-linked immunosorbent assay for specific detection of Reston Ebola virus nucleoprotein.

    PubMed

    Ikegami, Tetsuro; Niikura, Masahiro; Saijo, Masayuki; Miranda, Mary E; Calaor, Alan B; Hernandez, Marvin; Acosta, Luz P; Manalo, Daria L; Kurane, Ichiro; Yoshikawa, Yasuhiro; Morikawa, Shigeru

    2003-07-01

    Antigen capture enzyme-linked immunosorbent assay (ELISA) is one of the most useful methods to detect Ebola virus rapidly. We previously developed an antigen capture ELISA using a monoclonal antibody (MAb), 3-3D, which reacted not only to the nucleoprotein (NP) of Zaire Ebola virus (EBO-Z) but also to the NPs of Sudan (EBO-S) and Reston Ebola (EBO-R) viruses. In this study, we developed antigen capture ELISAs using two novel MAbs, Res2-6C8 and Res2-1D8, specific to the NP of EBO-R. Res2-6C8 and Res2-1D8 recognized epitopes consisting of 4 and 8 amino acid residues, respectively, near the C-terminal region of the EBO-R NP. The antigen capture ELISAs using these two MAbs detected the EBO-R NP in the tissues from EBO-R-infected cynomolgus macaques. The antigen capture ELISAs using Res2-6C8 and Res2-1D8 are useful for the rapid detection of the NP in EBO-R-infected cynomolgus macaques. PMID:12853385

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

    PubMed Central

    Swenson, Dana L.; Warfield, Kelly L.; Warren, Travis K.; Lovejoy, Candace; Hassinger, Jed N.; Ruthel, Gordon; Blouch, Robert E.; Moulton, Hong M.; Weller, Dwight D.; Iversen, Patrick L.; Bavari, Sina

    2009-01-01

    Phosphorodiamidate morpholino oligomers (PMOs) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mRNA translation. PMOs have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. We propose that antisense PMOs represent a promising class of therapeutic agents that may be useful for combating filoviral infections. We have previously shown that mice treated with a PMO whose 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 report on the abilities of two additional VP24-specific PMOs to reduce the cell-free translation of a VP24 reporter, to inhibit the in vitro replication of Ebola virus, and to protect mice against lethal challenge when the PMOs are delivered prior to infection. Additionally, structure-activity relationship evaluations were conducted to assess the enhancement of antiviral efficacy associated with PMO chemical modifications that included conjugation with peptides of various lengths and compositions, positioning of conjugated peptides to either the 5? or the 3? terminus, and the conferring of charge modifications by the addition of piperazine moieties. Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge. PMID:19223614

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-10-01

    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. PMID:25275333

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola Virus?

    PubMed Central

    Geisbert, Thomas W.; Geisbert, Joan B.; Leung, Anders; Daddario-DiCaprio, Kathleen M.; Hensley, Lisa E.; Grolla, Allen; Feldmann, Heinz

    2009-01-01

    The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSV?G/SEBOVGP, VSV?G/ZEBOVGP, and VSV?G/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSV?G/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species. PMID:19386702

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Zumbrun, E E

    2015-01-01

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

  9. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model.

    PubMed

    Smither, Sophie J; Eastaugh, Lin S; Steward, Jackie A; Nelson, Michelle; Lenk, Robert P; Lever, Mark S

    2014-04-01

    Filoviruses cause disease with high case fatality rates and are considered biological threat agents. Licensed post-exposure therapies that can be administered by the oral route are desired for safe and rapid distribution and uptake in the event of exposure or outbreaks. Favipiravir or T-705 has broad antiviral activity and has already undergone phase II and is undergoing phase III clinical trials for influenza. Here we report the first use of T-705 against Ebola virus. T-705 gave 100% protection against aerosol Ebola virus E718 infection; protection was shown in immune-deficient mice after 14 days of twice-daily dosing. T-705 was also shown to inhibit Ebola virus infection in cell culture. T-705 is likely to be licensed for use against influenza in the near future and could also be used with a new indication for filovirus infection. PMID:24462697

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2010-09-21

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

  12. Ebola Hemorrhagic Fever Associated with Novel Virus Strain, Uganda, 20072008

    PubMed Central

    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.

    2010-01-01

    During August 2007February 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 1.788.23). 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. PMID:20587179

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-18

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

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

    PubMed

    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. PMID:26582961

  18. Ebola virus disease epidemic in West Africa: lessons learned and issues arising from West African countries.

    PubMed

    Oleribe, Obinna O; Salako, Babatunde L; Ka, M Mourtalla; Akpalu, Albert; McConnochie, Mairi; Foster, Matthew; Taylor-Robinson, Simon D

    2015-02-01

    The current Ebola virus disease (EVD) outbreak ravaging three nations in West Africa has affected more than 14,000 persons and killed over 5,000. It is the longest and most widely spread Ebola epidemic ever seen. At the time of this overview (written November 2014), having affected eight different nations, Nigeria and Senegal were able to control and eliminate the virus within a record time. Ghana has successfully, to date, kept the virus away from the country, despite economic and social relationships with affected nations. What lessons can we learn from Nigeria, Senegal and Ghana in the current epidemic? How can the world improve the health systems in low- and middle-income countries to effectively manage future outbreaks? Recently, the Royal College of Physicians launched a new partnership with the West African College of Physicians to curtail the effects of HIV/AIDS, malaria and tuberculosis in the region. We believe that strengthened health systems, skilled human resources for health and national ownership of problems are key to effective management of outbreaks such as EVD. PMID:25650199

  19. Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

    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. PMID:25403361

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2016-03-17

    The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing. PMID:26934220

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

    PubMed

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

    2016-01-01

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

  4. Functional Genomics Reveals the Induction of Inflammatory Response and Metalloproteinase Gene Expression during Lethal Ebola Virus Infection?

    PubMed Central

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

    2011-01-01

    Ebola virus is the etiologic agent of a lethal hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Previous studies with Zaire Ebola virus (ZEBOV), mouse-adapted virus (MA-ZEBOV), and mutant viruses (ZEBOV-NPma, ZEBOV-VP24ma, and ZEBOV-NP/VP24ma) allowed us to identify the mutations in viral protein 24 (VP24) and nucleoprotein (NP) responsible for acquisition of high virulence in mice. To elucidate specific molecular signatures associated with lethality, we compared global gene expression profiles in spleen samples from mice infected with these viruses and performed an extensive functional analysis. Our analysis showed that the lethal viruses (MA-ZEBOV and ZEBOV-NP/VP24ma) elicited a strong expression of genes 72 h after infection. In addition, we found that although the host transcriptional response to ZEBOV-VP24ma was nearly the same as that to ZEBOV-NP/VP24ma, the contribution of a mutation in the NP gene was required for a lethal phenotype. Further analysis indicated that one of the most relevant biological functions differentially regulated by the lethal viruses was the inflammatory response, as was the induction of specific metalloproteinases, which were present in our newly identify functional network that was associated with Ebola virus lethality. Our results suggest that this dysregulated proinflammatory response increased the severity of disease. Consequently, the newly discovered molecular signature could be used as the starting point for the development of new drugs and therapeutics. To our knowledge, this is the first study that clearly defines unique molecular signatures associated with Ebola virus lethality. PMID:21734050

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

    PubMed

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

    2011-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-11-24

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

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

    PubMed

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

    2012-09-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Transmission dynamics and control of Ebola virus disease outbreak in Nigeria, July to September 2014.

    PubMed

    Fasina, F O; Shittu, A; Lazarus, D; Tomori, O; Simonsen, L; Viboud, C; Chowell, G

    2014-01-01

    We analyse up-to-date epidemiological data of the Ebola virus disease outbreak in Nigeria as of 1 October 2014 in order to estimate the case fatality rate, the proportion of healthcare workers infected and the transmission tree. We also model the impact of control interventions on the size of the epidemic. Results indicate that Nigerias quick and forceful implementation of control interventions was determinant in controlling the outbreak rapidly and avoiding a far worse scenario in this country. PMID:25323076

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

    PubMed

    Evans, Nicholas G

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-07-01

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

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

    SciTech Connect

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

    2011-10-25

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

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

    PubMed

    Hofmann-Winkler, Heike; Gnir, Kerstin; Wrensch, Florian; Phlmann, Stefan

    2015-10-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Erickson, Bobbie R.; Flietstra, Timothy D.; Rollin, Pierre E.; Nichol, Stuart T.; Towner, Jonathan S.; Spiropoulou, Christina F.

    2014-01-01

    Outbreaks of Ebola virus disease (EVD) occur sporadically in Africa and are associated with high case-fatality rates. Historically, children have been less affected than adults. The 20002001 Sudan virusassociated EVD outbreak in the Gulu district of Uganda resulted in 55 pediatric and 161 adult laboratory-confirmed cases. We used a series of multiplex assays to measure the concentrations of 55 serum analytes in specimens from patients from that outbreak to identify biomarkers specific to pediatric disease. Pediatric patients who survived had higher levels of the chemokine regulated on activation, normal T-cell expressed and secreted marker and lower levels of plasminogen activator inhibitor 1, soluble intracellular adhesion molecule, and soluble vascular cell adhesion molecule than did pediatric patients who died. Adult patients had similar levels of these analytes regardless of outcome. Our findings suggest that children with EVD may benefit from different treatment regimens than those for adults. PMID:25279581

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  6. Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of Ebola Virus

    PubMed Central

    Kuroda, Makoto; Fujikura, Daisuke; Nanbo, Asuka; Marzi, Andrea; Noyori, Osamu; Kajihara, Masahiro; Maruyama, Junki; Matsuno, Keita; Miyamoto, Hiroko; Yoshida, Reiko; Feldmann, Heinz

    2015-01-01

    ABSTRACT Multiple host molecules are known to be involved in the cellular entry of filoviruses, including Ebola virus (EBOV); T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) have been identified as attachment and fusion receptors, respectively. However, the molecular mechanisms underlying the entry process have not been fully understood. We found that TIM-1 and NPC1 colocalized and interacted in the intracellular vesicles where EBOV glycoprotein (GP)-mediated membrane fusion occurred. Interestingly, a TIM-1-specific monoclonal antibody (MAb), M224/1, prevented GP-mediated membrane fusion and also interfered with the binding of TIM-1 to NPC1, suggesting that the interaction between TIM-1 and NPC1 is important for filovirus membrane fusion. Moreover, MAb M224/1 efficiently inhibited the cellular entry of viruses from all known filovirus species. These data suggest a novel mechanism underlying filovirus membrane fusion and provide a potential cellular target for antiviral compounds that can be universally used against filovirus infections. IMPORTANCE Filoviruses, including Ebola and Marburg viruses, cause rapidly fatal diseases in humans and nonhuman primates. There are currently no approved vaccines or therapeutics for filovirus diseases. In general, the cellular entry step of viruses is one of the key mechanisms to develop antiviral strategies. However, the molecular mechanisms underlying the entry process of filoviruses have not been fully understood. In this study, we demonstrate that TIM-1 and NPC1, which serve as attachment and fusion receptors for filovirus entry, interact in the intracellular vesicles where Ebola virus GP-mediated membrane fusion occurs and that this interaction is important for filovirus infection. We found that filovirus infection and GP-mediated membrane fusion in cultured cells were remarkably suppressed by treatment with a TIM-1-specific monoclonal antibody that interfered with the interaction between TIM-1 and NPC1. Our data provide new insights for the development of antiviral compounds that can be universally used against filovirus infections. PMID:25855742

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

    PubMed

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

    2015-01-01

    Ebola Virus Disease (EVD) started as a minor infection in Uganda in 1974 and has been frequent in Central Africa Region for the past 40 years. For over 40 years, Ebola was treated as an African disease, called a fever and known by other names where occurrences have been frequent. EVD has become a global public health threat following the most recent outbreak in West Africa. By December 31, 2014, Ebola has infected more than 23,500 people in West Africa and killed over 9,500, nearly all in the three worst-affected countries of Guinea, Liberia and Sierra Leone. It is transmitted through blood, vomit, diarrhea and other bodily fluids but cultural attributes associate its etiology to man-made and supernatural causes, hence stemming public health approaches to contain EVD difficult. Distrust and conflict between two healing systems are rife necessitating an African Model of EVD care and prevention. The African model remains indispensable to understand EVD and developing appropriate EVD containing approaches. PMID:26740846

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

    PubMed Central

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

    2015-01-01

    Ebola Virus Disease (EVD) started as a minor infection in Uganda in 1974 and has been frequent in Central Africa Region for the past 40 years. For over 40 years, Ebola was treated as an African disease, called a fever and known by other names where occurrences have been frequent. EVD has become a global public health threat following the most recent outbreak in West Africa. By December 31, 2014, Ebola has infected more than 23,500 people in West Africa and killed over 9,500, nearly all in the three worst-affected countries of Guinea, Liberia and Sierra Leone. It is transmitted through blood, vomit, diarrhea and other bodily fluids but cultural attributes associate its etiology to man-made and supernatural causes, hence stemming public health approaches to contain EVD difficult. Distrust and conflict between two healing systems are rife necessitating an African Model of EVD care and prevention. The African model remains indispensable to understand EVD and developing appropriate EVD containing approaches. PMID:26740846

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

    PubMed Central

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

    2015-01-01

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

  10. YouTube as a Source of Information on Ebola Virus Disease

    PubMed Central

    Pathak, Ranjan; Poudel, Dilli Ram; Karmacharya, Paras; Pathak, Amrit; Aryal, Madan Raj; Mahmood, Maryam; Donato, Anthony A.

    2015-01-01

    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 the general population. PMID:26258077

  11. Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function.

    PubMed

    Garca-Dorival, Isabel; Wu, Weining; Dowall, Stuart; Armstrong, Stuart; Touzelet, Olivier; Wastling, Jonathan; Barr, John N; Matthews, David; Carroll, Miles; Hewson, Roger; Hiscox, Julian A

    2014-11-01

    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. PMID:25158218

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  15. Preparing for renal replacement therapy in patients with the Ebola virus disease.

    TOXLINE Toxicology Bibliographic Information

    Faubel S; Franch H; Vijayan A; Barron MA; Heung M; Liu KD; Koyner JL; Conner MJ Jr

    2014-01-01

    The Ebola virus disease (EVD) is a serious illness characterized by fever, severe vomiting and diarrhea, and, in severe cases, multi-organ failure requiring mechanical ventilation and renal replacement therapy. The current outbreak has centered in West Africa and affected over 15,000 individuals. EVD is transmitted by direct contact with blood or other infectious bodily fluid, and as such, numerous heath care workers caring for patients with EVD have become infected. During the current outbreak, a number of patients have received advanced supportive care for EVD in Europe and North America and therefore survived. Now, many hospitals in Europe and North America are planning to accept care for patients with EVD. In this review, we discussed the key issues related to the planning and delivery of advanced supportive care in patients with EVD with a focus on the factors necessary to provide renal replacement therapy (RRT). Since success in the treatment of patients with EVD rests on both patient outcome and prevention of transmission of disease to health care workers, we extensively discussed the modes of Ebola virus transmission and recommended protocols to protect health care workers. Experience now indicates that with appropriate planning and protocols, it is possible to successfully treat EVD patients with advanced supportive care (mechanical ventilation and RRT) while avoiding transmission to health care providers. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=371530

  16. Production and characterization of monoclonal antibodies against different epitopes of Ebola virus antigens.

    PubMed

    Shahhosseini, Soraya; Das, Dipankar; Qiu, Xiangguo; Feldmann, Heinz; Jones, Steven M; Suresh, Mavanur R

    2007-07-01

    Ebola virus (EBOV) causes hemorrhagic fever in humans and nonhuman primates with up to 90% mortality rate. In this study, Ebola virus like particles (EVLPs) and the aglycosyl subfragment of glycoprotein (GP(1) subfragment D) were used to generate monoclonal antibodies (MAbs) against different epitopes of the viral antigens. Such MAbs could be useful in diagnostics and potential therapeutics of viral infection and its hemorrhagic symptoms. Hybridoma cell fusion technology was used for production of MAbs. The MAbs were characterized using ELISA and Western blot analysis. Furthermore, five recombinant sub-domains of GP(1) subfragment D were produced, which were used as antigen in Western blot analysis for epitope mapping. Seventeen MAbs of different epitope specificities against EBOV antigens [virion protein (VP40), secreted glycoprotein (sGP), and GP(1) subfragment D] were developed. Based on epitope mapping studies, the anti-GP MAbs were categorized into six groups. The binding of the three anti-sGP MAbs with different epitope specificities were mostly between aa 157 and 221. The two anti-VP40 MAbs with the same or overlapping epitopes are potentially good candidates for developing antigen detection assays for early diagnosis of EBOV infection. The anti-GP MAbs with different epitope specificities as an oligoclonal cocktail could be tested for therapy. PMID:17368819

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

    PubMed

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

    2016-01-15

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

  18. Preparing for renal replacement therapy in patients with the Ebola virus disease.

    PubMed

    Faubel, Sarah; Franch, Harold; Vijayan, Anitha; Barron, Michelle A; Heung, Michael; Liu, Kathleen D; Koyner, Jay L; Conner, Michael J

    2014-01-01

    The Ebola virus disease (EVD) is a serious illness characterized by fever, severe vomiting and diarrhea, and, in severe cases, multi-organ failure requiring mechanical ventilation and renal replacement therapy. The current outbreak has centered in West Africa and affected over 15,000 individuals. EVD is transmitted by direct contact with blood or other infectious bodily fluid, and as such, numerous heath care workers caring for patients with EVD have become infected. During the current outbreak, a number of patients have received advanced supportive care for EVD in Europe and North America and therefore survived. Now, many hospitals in Europe and North America are planning to accept care for patients with EVD. In this review, we discussed the key issues related to the planning and delivery of advanced supportive care in patients with EVD with a focus on the factors necessary to provide renal replacement therapy (RRT). Since success in the treatment of patients with EVD rests on both patient outcome and prevention of transmission of disease to health care workers, we extensively discussed the modes of Ebola virus transmission and recommended protocols to protect health care workers. Experience now indicates that with appropriate planning and protocols, it is possible to successfully treat EVD patients with advanced supportive care (mechanical ventilation and RRT) while avoiding transmission to health care providers. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=371530. PMID:25675963

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Flint, Mike; Goodman, Christin H; Bearden, Scott; Blau, Dianna M; Amman, Brian R; Basile, Alison J; Belser, Jessica A; Bergeron, ric; 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, Cline; Turnsek, Maryann; Wang, David; Zemtsova, Galina E; Zivcec, Marko; Spiropoulou, Christina F; Strher, Ute; Towner, Jonathan S; Nichol, Stuart T; Bird, Brian H

    2015-10-01

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

  2. Personal protective equipment processes and rationale for the Nebraska Biocontainment Unit during the 2014 activations for Ebola virus disease.

    PubMed

    Beam, Elizabeth L; Schwedhelm, Shelly; Boulter, Kathleen; Kratochvil, Christopher; Lowe, John; Hewlett, Angela; Gibbs, Shawn G; Smith, Philip W

    2016-03-01

    In response to the Ebola virus disease outbreak of 2014, specific procedures for personal protective equipment use were developed in the Nebraska Biocontainment Unit for the isolation care of patients with the illness. This brief report describes the 2 different levels used for patient care and presents the rationales for the specialized processes. PMID:26559735

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

    ABSTRACT This study addresses the role of Ebola virus (EBOV) specific infectivity in virulence. Filoviruses are highly lethal, enveloped, single-stranded negative-sense RNA viruses that can cause hemorrhagic fever. No approved vaccines or therapies exist for filovirus infections, and infectious virus must be handled in maximum containment. Efficacy testing of countermeasures, in addition to investigations of pathogenicity and immune response, often requires a well-characterized animal model. For EBOV, an obstacle in performing accurate disease modeling is a poor understanding of what constitutes an infectious dose in animal models. One well-recognized consequence of viral passage in cell culture is a change in specific infectivity, often measured as a particle-to-PFU ratio. Here, we report that serial passages of EBOV in cell culture resulted in a decrease in particle-to-PFU ratio. Notably, this correlated with decreased potency in a lethal cynomolgus macaque (Macaca fascicularis) model of infection; animals were infected with the same viral dose as determined by plaque assay, but animals that received more virus particles exhibited increased disease. This suggests that some particles are unable to form a plaque in a cell culture assay but are able to result in lethal disease in vivo. These results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures. IMPORTANCE Ebola virus (EBOV) can cause severe hemorrhagic disease with a high case-fatality rate, and there are no approved vaccines or therapies. Specific infectivity can be considered the total number of viral particles per PFU, and its impact on disease is poorly understood. In stocks of most mammalian viruses, there are particles that are unable to complete an infectious cycle or unable to cause cell pathology in cultured cells. We asked if these particles cause disease in nonhuman primates by infecting monkeys with equal infectious doses of genetically identical stocks possessing either high or low specific infectivities. Interestingly, some particles that did not yield plaques in cell culture assays were able to result in lethal disease in vivo. Furthermore, the number of PFU needed to induce lethal disease in animals was very low. Our results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures. PMID:25903348

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. Ebola virus: a comparison, at ultrastructural level, of the behaviour of the Sudan and Zaire strains in monkeys.

    PubMed Central

    Ellis, D. S.; Bowen, E. T.; Simpson, D. I.; Stamford, S.

    1978-01-01

    Histopathological and electron microscopical examination of human liver specimens collected during the Ebola haemorrhagic fever outbreaks in Zaire and Sudan indicated that Zairean strains of the virus produced more extensive lesions. Experimental infection of rhesus monkeys wiht Zairean and Sudanese strains of Ebola virus produced similar changes to those found in man. In Zairean strain infections large numbers of virus particles were found in the liver, lung and spleen accompanied by extensive necrosis in the spleen. In Sudan strain infections particles were found only in the liver and in greatly reduced numbers. The main distinction lay in the high proportion of aberrant particles found with the Sudanese strain. The possibility of these being defective particles is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 PMID:106868

  10. Effect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities

    PubMed Central

    Plucinski, Mateusz M; Guilavogui, Timothée; Sidikiba, Sidibe; Diakité, Nouman; Diakité, Souleymane; Dioubaté, Mohamed; Bah, Ibrahima; Hennessee, Ian; Butts, Jessica K; Halsey, Eric S; McElroy, Peter D; Kachur, S Patrick; Aboulhab, Jamila; James, Richard; Keita, Moussa

    2015-01-01

    Summary Background The ongoing west Africa Ebola-virus-disease epidemic has disrupted the entire health-care system in affected countries. Because of the overlap of symptoms of Ebola virus disease and malaria, the care delivery of malaria is particularly sensitive to the indirect effects of the current Ebola-virus-disease epidemic. We therefore characterise malaria case management in the context of the Ebola-virus-disease epidemic and document the effect of the Ebola-virus-disease epidemic on malaria case management. Methods We did a cross-sectional survey of public health facilities in Guinea in December, 2014. We selected the four prefectures most affected by Ebola virus disease and selected four randomly from prefectures without any reported cases of the disease. 60 health facilities were sampled in Ebola-affected and 60 in Ebola-unaffected prefectures. Study teams abstracted malaria case management indicators from registers for January to November for 2013 and 2014 and interviewed health-care workers. Nationwide weekly surveillance data for suspect malaria cases reported between 2011 and 2014 were analysed independently. Data for malaria indicators in 2014 were compared with previous years. Findings We noted substantial reductions in all-cause outpatient visits (by 23 103 [11%] of 214 899), cases of fever (by 20249 [15%] of 131 330), and patients treated with oral (by 22 655 [24%] of 94 785) and injectable (by 5219 [30%] of 17 684) antimalarial drugs in surveyed health facilities. In Ebola-affected prefectures, 73 of 98 interviewed community health workers were operational (74%, 95% CI 65–83) and 35 of 73 were actively treating malaria cases (48%, 36–60) compared with 106 of 112 (95%, 89–98) and 102 of 106 (96%, 91–99), respectively, in Ebola-unaffected prefectures. Nationwide, the Ebola-virus-disease epidemic was estimated to have resulted in 74 000 (71 000–77 000) fewer malaria cases seen at health facilities in 2014. Interpretation The reduction in the delivery of malaria care because of the Ebola-virus-disease epidemic threatens malaria control in Guinea. Untreated and inappropriately treated malaria cases lead to excess malaria mortality and more fever cases in the community, impeding the Ebola-virus-disease response. Funding Global Fund to Fight AIDS, Tuberculosis and Malaria, and President’s Malaria Initiative. PMID:26116183

  11. Oligomerization of Ebola Virus VP40 Is Essential for Particle Morphogenesis and Regulation of Viral Transcription?

    PubMed Central

    Hoenen, T.; Biedenkopf, N.; Zielecki, F.; Jung, S.; Groseth, A.; Feldmann, H.; Becker, S.

    2010-01-01

    The morphogenesis and budding of virus particles represent an important stage in the life cycle of viruses. For Ebola virus, this process is driven by its major matrix protein, VP40. Like the matrix proteins of many other nonsegmented, negative-strand RNA viruses, VP40 has been demonstrated to oligomerize and to occur in at least two distinct oligomeric states: hexamers and octamers, which are composed of antiparallel dimers. While it has been shown that VP40 oligomers are essential for the viral life cycle, their function is completely unknown. Here we have identified two amino acids essential for oligomerization of VP40, the mutation of which blocked virus-like particle production. Consistent with this observation, oligomerization-deficient VP40 also showed impaired intracellular transport to budding sites and reduced binding to cellular membranes. However, other biological functions, such as the interaction of VP40 with the nucleoprotein, NP, remained undisturbed. Furthermore, both wild-type VP40 and oligomerization-deficient VP40 were found to negatively regulate viral genome replication, a novel function of VP40, which we have recently reported. Interestingly, while wild-type VP40 was also able to negatively regulate viral genome transcription, oligomerization-deficient VP40 was no longer able to fulfill this function, indicating that regulation of viral replication and transcription by VP40 are mechanistically distinct processes. These data indicate that VP40 oligomerization not only is a prerequisite for intracellular transport of VP40 and efficient membrane binding, and as a consequence virion morphogenesis, but also plays a critical role in the regulation of viral transcription by VP40. PMID:20463076

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

    PubMed

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

    2015-08-01

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

  13. Assessment of ebola virus disease, health care infrastructure, and preparedness - four counties,Southeastern Liberia, august 2014.

    PubMed

    Forrester, Joseph D; Pillai, Satish K; Beer, Karlyn D; Neatherlin, John; Massaquoi, Moses; Nyenswah, Tolbert G; Montgomery, Joel M; De Cock, Kevin

    2014-10-10

    Ebola virus disease (Ebola) is a multisystem disease caused by a virus of the genus Ebolavirus. In late March 2014, Ebola cases were described in Liberia, with epicenters in Lofa County and later in Montserrado County. While information about case burden and health care infrastructure was available for the two epicenters, little information was available about remote counties in southeastern Liberia. Over 9 days, August 6-14, 2014, Ebola case burden, health care infrastructure, and emergency preparedness were assessed in collaboration with the Liberian Ministry of Health and Social Welfare in four counties in southeastern Liberia: Grand Gedeh, Grand Kru, River Gee, and Maryland. Data were collected by health care facility visits to three of the four county referral hospitals and by unstructured interviews with county and district health officials, hospital administrators, physicians, nurses, physician assistants, and health educators in all four counties. Local burial practices were discussed with county officials, but no direct observation of burial practices was conducted. Basic information about Ebola surveillance and epidemiology, case investigation, contact tracing, case management, and infection control was provided to local officials. PMID:25299605

  14. Ebola Virus Matrix VP40 Protein Uses the COPII Transport System for Its Intracellular Transport

    PubMed Central

    Yamayoshi, Seiya; Noda, Takeshi; Ebihara, Hideki; Goto, Hideo; Morikawa, Yuko; Lukashevich, Igor S.; Neumann, Gabriele; Feldmann, Heinz; Kawaoka, Yoshihiro

    2008-01-01

    Summary The Ebola virus matrix protein VP40 plays an important role in virion formation and release from cells. Several host proteins have been shown to play an important role in VP40-mediated virus-like particles production; however, the host cell proteins and mechanisms responsible for VP40 intracellular transport prior to its contribution to virion formation remain to be elucidated. We therefore used coimmunoprecipitation and mass spectrometric analyses to identify host proteins interacting with VP40. We found that Sec24C, a component of the COPII transport system, interacts specifically with VP40 via the region at amino acids 303-307. Coimmunoprecipitation and dominant-negative mutant studies indicated that the COPII transport system plays a critical role in VP40 intracellular transport to the plasma membrane. Marburg virus VP40 was also shown to use the COPII transport system for intracellular transport. These findings enhance our understanding of filovirus replication and provide a new target for development of antiviral drugs. PMID:18329616

  15. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.

    PubMed

    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. PMID:25297522

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Detection of antibodies against the four subtypes of ebola virus in sera from any species using a novel antibody-phage indicator assay.

    PubMed

    Meissner, Felix; Maruyama, Toshiaki; Frentsch, Marco; Hessell, Ann J; Rodriguez, Luis L; Geisbert, Tom W; Jahrling, Peter B; Burton, Dennis R; Parren, Paul W H I

    2002-09-01

    The natural host for Ebola virus, presumed to be an animal, has not yet been identified despite an extensive search following several major outbreaks in Africa. A straightforward approach used to determine animal contact with Ebola virus is by assessing the presence of specific antibodies in serum. This approach however has been made very difficult by the absence of specific reagents required for the detection of antibodies from the majority of wild animal species. In this study, we isolated a human monoclonal antibody Fab fragment, KZ51, that reacts with an immunodominant epitope on Ebola virus nucleoprotein (NP) that is conserved on all four Ebola virus subtypes. The antibody KZ51 represents a major specificity as sera from all convalescent patients tested (10/10) and sera from guinea pigs infected with each of the four Ebola virus subtypes competed strongly with KZ51 for binding to radiation-inactivated Ebola virus. These features allowed us to develop a novel assay for the detection of seroconversion irrespective of Ebola virus subtype or animal species. In this assay, the binding of KZ51 Fab-phage particles is used as an indicator assay and the presence of specific antibodies against Ebola virus in sera is indicated by binding competition. A prominent feature of the assay is that the Fab-phage particles may be prestained with a dye so that detection of binding can be directly determined by visual inspection. The assay is designed to be both simple and economical to enable its use in the field. PMID:12350354

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

    PubMed

    Bebell, Lisa M; Riley, Laura E

    2015-06-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-09-15

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

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

    PubMed

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

    2015-10-01

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

  3. Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak.

    PubMed

    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. PMID:26912366

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

    The Ebola virus disease, as a first epidemic in West Africa, stands as the most deadly one throughout history. Guinea, the source of the epidemic, Sierra Leone and Liberia remain the most strongly affected. That epidemic thoroughly destabilized the health system of those countries. Following Nigeria, Senegal received its first imported case from the neighboring Republic of Guinea. In that sub regional psychotic context, such a situation has been handled and managed starting from the potential of a health system that is already suitably structured. The organization of the response, the management of the communication system and the rigorous monitoring of contacts have been decisive in the control of the epidemic. Our countries have to be prepared in order to face health threats, and that is the reason why the need to empower our health systems is important. PMID:26740836

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

    PubMed Central

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

    2015-01-01

    Zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in West Africa. Previously, we showed that a whole Ebola virus (EBOV) vaccine based on a replication-defective EBOV (EBOV?VP30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted EBOV. Here, we demonstrate that EBOV?VP30 protects nonhuman primates against lethal infection with EBOV. Although EBOV?VP30 is replication-incompetent, we additionally inactivated the vaccine with hydrogen peroxide; the chemically inactivated vaccine remained antigenic and protective in nonhuman primates. EBOV?VP30 thus represents a safe, efficacious, whole-EBOV vaccine candidate that differs from other EBOV vaccine platforms in that it presents all viral proteins and the viral RNA to the host immune system, which might contribute to protective immune responses. PMID:25814063

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

    PubMed Central

    Cohn, Samuel; Kutalek, Ruth

    2016-01-01

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

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

    PubMed

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

    2015-01-01

    The Ebola virus disease, as a first epidemic in West Africa, stands as the most deadly one throughout history. Guinea, the source of the epidemic, Sierra Leone and Liberia remain the most strongly affected. That epidemic thoroughly destabilized the health system of those countries. Following Nigeria, Senegal received its first imported case from the neighboring Republic of Guinea. In that sub regional psychotic context, such a situation has been handled and managed starting from the potential of a health system that is already suitably structured. The organization of the response, the management of the communication system and the rigorous monitoring of contacts have been decisive in the control of the epidemic. Our countries have to be prepared in order to face health threats, and that is the reason why the need to empower our health systems is important. PMID:26740836

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

    PubMed

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

    2014-12-18

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

  10. Development, characterization and use of monoclonal VP40-antibodies for the detection of Ebola virus.

    PubMed

    Lucht, Andreas; Grunow, Roland; Mller, Peggy; Feldmann, Heinz; Becker, Stephan

    2003-07-01

    Ebola virus (EBOV) causes uncommon but dramatic outbreaks in remote regions of Africa, where diagnostic facilities are limited. In order to develop diagnostic tests, which can be handled and distributed easily, monoclonal antibodies (mAbs) to EBOV, species Zaire, were produced from mice immunized with inactivated viral particles. Nine stable hybridoma cell lines were obtained producing specific mAbs directed against the viral structural protein VP40. These mAbs were characterized by enzyme-linked immunosorbent, immunoblot and immunofluorescence assays. Subsequently, an antigen capture enzyme-linked immunosorbent assay was established, which detects VP40 of all known species of EBOV. This assay could detect viral material in spiked human serum that has been sodium dodecylsulfate-inactivated. The established enzyme-linked immunosorbent assay therefore has the ability to become a very useful tool for obtaining an accurate diagnosis in the field, limiting the risk of laboratory infections. PMID:12821193

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Cohn, Samuel; Kutalek, Ruth

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

    Rapid, sensitive, and direct label-free capture and characterization of nanoparticles from complex media such as blood or serum will broadly impact medicine and the life sciences. We demonstrate identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (VSV), defective VSV, and Ebola- and Marburg-pseudotyped VSV with high sensitivity and specificity. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of non-specifically bound particles to achieve a limit-of-detection (LOD) of 5103 pfu/mL for the Ebola and Marburg VSV pseudotypes. We demonstrate the simultaneous detection of multiple viruses in a single sample (composed of serum or whole blood) for screening applications and uncompromised detection capabilities in samples contaminated with high levels of bacteria. By employing affinity-based capture, size discrimination, and a digital detection scheme to count single virus particles, we show that a robust and sensitive virus/nanoparticle sensing assay can been established for targets in complex samples. The nanoparticle microscopy system is termed the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) and is capable of high-throughput and rapid sizing of large numbers of biological nanoparticles on an antibody microarray for research and diagnostic applications. PMID:24840765

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Ilesanmi, Olayinka Stephen

    2015-01-01

    Introduction Sierra Leone was in the process of strengthening tracing of Ebola Virus Disease (EVD) contact with training of contact tracers, continuous mentoring and monitoring, supervision and continuous support. This was through various national and international organizations. This study aimed at identifying the challenges of contact tracers with a view of improving contact tracing activities in Tonkolili District, Sierra Leone. Methods In-depth interview was conducted among contact tracers who were actively involved in contact tracing within the 4 weeks preceding the interview. In-depth interview guide was used to interview the contact tracers. Questions were asked about the state of EVD outbreak, challenges of contact tracing, ways to improving contact tracers activities and ways to ensure community participation and follow up action. Results A total of 12 Contact tracers were interviewed. Most of the contact tracers saw the lifting of ban by the Government on movement as a delay to stopping the outbreak. Some of them were being threatened by their communities and insulted. Some communities with EVD cases felt it was no longer in Sierra Leone and that the contact tracers were the ones infecting the people with Ebola. More than 80% of the participants indicated that retraining of contact tracers and re-orientation of community members would help in putting a stop to the outbreak. Conclusion All participants indicated interest in improving their activities and performance. They suggested that more social mobilization is needed to ensure the cooperation of their communities. PMID:26740849

  20. Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

    PubMed Central

    Strong, James E.; Wong, Gary; Jones, Shane E.; Grolla, Allen; Theriault, Steven; Kobinger, Gary P.; Feldmann, Heinz

    2008-01-01

    Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV jumps from an infected animal to a person and is subsequently transmitted between persons by direct contact with infected blood or body fluids. This study was undertaken to investigate the mechanism by which EBOV can persistently infect and then escape from model cell and animal reservoir systems. We report a model system in which infection of mouse and bat cell lines with EBOV leads to persistence, which can be broken with low levels of lipopolysaccharide or phorbol-12-myristate-13-acetate (PMA). This reactivation depends on the Ras/MAPK pathway through inhibition of RNA-dependent protein kinase and eukaryotic initiation factor 2? phosphorylation and occurs at the level of protein synthesis. EBOV also can be evoked from mice 7 days after infection by PMA treatment, indicating that a similar mechanism occurs in vivo. Our findings suggest that EBOV may persist in nature through subclinical infection of a reservoir species, such as bats, and that appropriate physiological stimulation may result in increased replication and transmission to new hosts. Identification of a presumptive mechanism responsible for EBOV emergence from its reservoir underscores the hit-and-run nature of the initiation of human and/or nonhuman primate EBOV outbreaks and may provide insight into possible countermeasures to interfere with transmission. PMID:18981410

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

    PubMed Central

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

    2015-01-01

    Objective To develop, teach and evaluate a training workshop that could rapidly prepare large numbers of health professionals working in hospitals in the Philippines to detect and safely manage Ebola virus disease (EVD). The strategy was to train teams (each usually with five members) of key health professionals from public, private and local government hospitals across the Philippines who could then guide Ebola preparedness in their hospitals. Methods The workshop was developed collaboratively by the Philippine Department of Health and the country office of the World Health Organization. It was evaluated using a pre- and post-workshop test and two evaluation forms. χ2 tests and linear regression analyses were conducted comparing pre- and post-workshop test results. Results A three-day workshop was developed and used to train 364 doctors, nurses and medical technologists from 78 hospitals across the Philippines in three initial batches. Knowledge about EVD increased significantly (P < 0.009) although knowledge on transmission remained suboptimal. Confidence in managing EVD increased significantly (P = 0.018) with 96% of participants feeling more prepared to safely manage EVD cases. Discussion: The three-day workshop to prepare hospital staff for EVD was effective at increasing the level of knowledge about EVD and the level of confidence in managing EVD safely. This workshop could be adapted for use as baseline training in EVD in other developing countries to prepare large numbers of hospital staff to rapidly detect, isolate and safely manage EVD cases. PMID:25960920

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Geisbert, Thomas W.; Daddario-DiCaprio, Kathleen M.; Lewis, Mark G.; Geisbert, Joan B.; Grolla, Allen; Leung, Anders; Paragas, Jason; Matthias, Lennox; Smith, Mark A.; Jones, Steven M.; Hensley, Lisa E.; Feldmann, Heinz; 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 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 (VSV?G/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSV?G/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. PMID:19043556

  4. Ebola Virus Glycoprotein 1: Identification of Residues Important for Binding and Postbinding Events?

    PubMed Central

    Brindley, Melinda A.; Hughes, Laura; Ruiz, Autumn; McCray, Paul B.; Sanchez, Anthony; Sanders, David A.; Maury, Wendy

    2007-01-01

    The filoviruses Ebola virus (EBOV) and Marburg virus (MARV) are responsible for devastating hemorrhagic fever outbreaks. No therapies are available against these viruses. An understanding of filoviral glycoprotein 1 (GP1) residues involved in entry events would facilitate the development of antivirals. Towards this end, we performed alanine scanning mutagenesis on selected residues in the amino terminus of GP1. Mutant GPs were evaluated for their incorporation onto feline immunodeficiency virus (FIV) particles, transduction efficiency, receptor binding, and ability to be cleaved by cathepsins L and B. FIV virions bearing 39 out of 63 mutant glycoproteins transduced cells efficiently, whereas virions bearing the other 24 had reduced levels of transduction. Virions pseudotyped with 23 of the poorly transducing GPs were characterized for their block in entry. Ten mutant GPs were very poorly incorporated onto viral particles. Nine additional mutant GPs (G87A/F88A, K114A/K115A, K140A, G143A, P146A/C147A, F153A/H154A, F159A, F160A, and Y162A) competed poorly with wild-type GP for binding to permissive cells. Four of these nine mutants (P146A/C147A, F153A/H154A, F159A, and F160A) were also inefficiently cleaved by cathepsins. An additional four mutant GPs (K84A, R134A, D150A, and E305/E306A) that were partially defective in transduction were found to compete effectively for receptor binding and were readily cleaved by cathepsins. This finding suggested that this latter group of mutants might be defective at a postbinding, cathepsin cleavage-independent step. In total, our study confirms the role of some GP1 residues in EBOV entry that had previously been recognized and identifies for the first time other residues that are important for productive entry. PMID:17475648

  5. Ebola virus glycoprotein 1: identification of residues important for binding and postbinding events.

    PubMed

    Brindley, Melinda A; Hughes, Laura; Ruiz, Autumn; McCray, Paul B; Sanchez, Anthony; Sanders, David A; Maury, Wendy

    2007-07-01

    The filoviruses Ebola virus (EBOV) and Marburg virus (MARV) are responsible for devastating hemorrhagic fever outbreaks. No therapies are available against these viruses. An understanding of filoviral glycoprotein 1 (GP1) residues involved in entry events would facilitate the development of antivirals. Towards this end, we performed alanine scanning mutagenesis on selected residues in the amino terminus of GP1. Mutant GPs were evaluated for their incorporation onto feline immunodeficiency virus (FIV) particles, transduction efficiency, receptor binding, and ability to be cleaved by cathepsins L and B. FIV virions bearing 39 out of 63 mutant glycoproteins transduced cells efficiently, whereas virions bearing the other 24 had reduced levels of transduction. Virions pseudotyped with 23 of the poorly transducing GPs were characterized for their block in entry. Ten mutant GPs were very poorly incorporated onto viral particles. Nine additional mutant GPs (G87A/F88A, K114A/K115A, K140A, G143A, P146A/C147A, F153A/H154A, F159A, F160A, and Y162A) competed poorly with wild-type GP for binding to permissive cells. Four of these nine mutants (P146A/C147A, F153A/H154A, F159A, and F160A) were also inefficiently cleaved by cathepsins. An additional four mutant GPs (K84A, R134A, D150A, and E305/E306A) that were partially defective in transduction were found to compete effectively for receptor binding and were readily cleaved by cathepsins. This finding suggested that this latter group of mutants might be defective at a postbinding, cathepsin cleavage-independent step. In total, our study confirms the role of some GP1 residues in EBOV entry that had previously been recognized and identifies for the first time other residues that are important for productive entry. PMID:17475648

  6. [Ebola virus disease in West Africa and Germany : clinical presentation, management and practical experience with medevacuated patients in Germany].

    PubMed

    Schmiedel, Stefan; Kreuels, B

    2015-07-01

    Ebolaviruses are the causative pathogens of a severe form of viral haemorrhagic fever with cytokine induced shock and multi-organ failure and a high case fatality rate in humans (50-90?%, more than 70?% in the beginning of the current outbreak), designated Ebola haemorrhagic fever or Ebola virus disease (EVD). Ebola is endemic in regions of Central and West Africa. Ebolavirus Zaire (EBOV) is the most aggressive Ebola virus species and is causing the current epidemic. Currently, beginning in late 2013, an unprecedented epidemic with several thousand cases and deaths (as per WHO report 24.12.2014: 19,497 documented cases,7588 death, 2352 cases in past 3 weeks) is unfolding in Guinea, Liberia and Sierra Leone, and spreading to other countries in Africa, Europe and the USA, where isolated cases have occurred. Ebola transmission occurs exclusively through direct contact with body fluids through mucosal surfaces, skin abrasions, or by parenteral introduction-an aerolised transmission has not been reported so far. Infections in healthcare personnel have not only occurred after needle stick injuries but also after unsafe doffing procedures of personal protection equipment (PPE). The protection of healthcare personnel caring for Ebola patients, therefore, requires that high standards in the use of PPE are mandatory. In high-income countries the management and treatment of EVD patients in specialized centres is recommended. Using negative pressure rooms and positive pressure suits may provide additional safety. Due to the high degree of training and monitoring needed to prevent occupational risks, treatment of EVD patients in non-specialized hospitals should not take place. PMID:25963641

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa.

    PubMed

    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. PMID:21722250

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-15

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. Measuring the Strength of Interaction between the Ebola Fusion Peptide and Lipid Rafts: Implications for Membrane Fusion and Virus Infection

    PubMed Central

    Freitas, Mnica S.; Follmer, Cristian; Costa, Lilian T.; Vilani, Ceclia; Bianconi, M. Lucia; Achete, Carlos Alberto; Silva, Jerson L.

    2011-01-01

    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. PMID:21249196

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

    PubMed

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

    2016-01-01

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

  5. A Highly Conserved GEQYQQLR Epitope Has Been Identified in the Nucleoprotein of Ebola Virus by Using an In Silico Approach

    PubMed Central

    Ali, Mohammad Tuhin; Islam, Md Ohedul

    2015-01-01

    Ebola virus (EBOV) is a deadly virus that has caused several fatal outbreaks. Recently it caused another outbreak and resulted in thousands afflicted cases. Effective and approved vaccine or therapeutic treatment against this virus is still absent. In this study, we aimed to predict B-cell epitopes from several EBOV encoded proteins which may aid in developing new antibody-based therapeutics or viral antigen detection method against this virus. Multiple sequence alignment (MSA) was performed for the identification of conserved region among glycoprotein (GP), nucleoprotein (NP), and viral structural proteins (VP40, VP35, and VP24) of EBOV. Next, different consensus immunogenic and conserved sites were predicted from the conserved region(s) using various computational tools which are available in Immune Epitope Database (IEDB). Among GP, NP, VP40, VP35, and VP30 protein, only NP gave a 100% conserved GEQYQQLR B-cell epitope that fulfills the ideal features of an effective B-cell epitope and could lead a way in the milieu of Ebola treatment. However, successful in vivo and in vitro studies are prerequisite to determine the actual potency of our predicted epitope and establishing it as a preventing medication against all the fatal strains of EBOV. PMID:25709646

  6. Live Virus Smallpox Vaccine

    MedlinePLUS

    ... Ebola virus E. coli Food safety threats Glanders Lassa fever Marburg virus Melioidosis Plague Case Definitions and Report ... Investigation Infection Control Other Resources Typhoid fever Viral hemorrhagic fevers Treatment & Infection Control Specimen Submission & Lab Testing Education & ...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-09-18

    The 20142015 Ebola virus disease (Ebola) epidemic is the largest in history and represents the first time Ebola has been diagnosed in the United States. On July 9, 2014, CDC activated its Emergency Operations Center and established an Ebola clinical consultation service to assist U.S. state and local public health officials and health care providers with the evaluation of suspected cases. CDC reviewed all 89 inquiries received by the consultation service during July 9, 2014 January 4, 2015, about children (persons aged ?18 years). Most (56 [63%]) children had no identifiable epidemiologic risk factors for Ebola; among the 33 (37%) who did have an epidemiologic risk factor, in every case this was travel from an Ebola-affected country. Thirty-two of these children met criteria for a person under investigation (PUI) because of clinical signs or symptoms. Fifteen PUIs had blood samples tested for Ebola virus RNA by reverse transcriptionpolymerase chain reaction; all tested negative. Febrile children who have recently traveled from an Ebola-affected country can be expected to have other common diagnoses, such as malaria and influenza, and in the absence of epidemiologic risk factors for Ebola, the likelihood of Ebola is extremely low. Delaying evaluation and treatment for these other more common illnesses might lead to poorer clinical outcomes. Additionally, many health care providers expressed concerns about whether and how parents should be allowed in the isolation room. While maintaining an appropriate level of vigilance for Ebola, public health officials and health care providers should ensure that pediatric PUIs receive timely triage, diagnosis, and treatment of other more common illnesses, and care reflecting best practices in supporting childrens psychosocial needs. PMID:26390343

  9. Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection.

    PubMed

    Zhang, Xu; Ao, Zhujun; Bello, Alexander; Ran, Xiaozhuo; Liu, Shuiping; Wigle, Jeffrey; Kobinger, Gary; Yao, Xiaojian

    2016-03-01

    Currently, no approved antiviral therapeutic is available for treatment or prevention of Ebola virus (EBOV) infection. In this study, we characterized an EBOV-glycoprotein (GP) pseudotyped HIV-1-based vector system in different cell cultures, including human umbilical vein endothelial cells (HUVECs) and human macrophages, for the screening of anti-EBOV-GP agent(s). Based on this system, we demonstrated that an aqueous extract (CHPV) from the Chinese herb Prunella vulgaris displayed a potent inhibitory effect on EBOV-GP pseudotyped virus (EBOV-GP-V)-mediated infection in various cell lines, including HUVEC and macrophage. In addition, our results indicated that CHPV was able to block an eGFP-expressing Zaire ebola virus (eGFP-ZEBOV) infection in VeroE6 cells. The anti-EBOV activity of CHPV was exhibited in a dose-dependent manner. At a 12.5 μg/ml concentration, the CHPV showed a greater than 80% inhibition of EBOV-GP-V and eGFP-EBOV infections. Likewise, our studies suggested that the inhibitory effect of CHPV occurred by binding directly to EBOV-GP-Vs and blocking the early viral events. Interestingly, our results have shown that CHPV was able to enhance the anti-EBOV activity of the monoclonal antibody MAb 2G4 against EBOV-GP. Overall, this study provides evidence that CHPV has anti-EBOV activity and may be developed as a novel antiviral approach against EBOV infection. PMID:26778707

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-10-01

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

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

    SciTech Connect

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

    2010-06-05

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

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

    SciTech Connect

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

    2009-05-20

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. Ebola virus entry requires the host-programmed recognition of an intracellular receptor.

    PubMed

    Miller, Emily Happy; Obernosterer, Gregor; Raaben, Matthijs; Herbert, Andrew S; Deffieu, Maika S; Krishnan, Anuja; Ndungo, Esther; Sandesara, Rohini G; Carette, Jan E; Kuehne, Ana I; Ruthel, Gordon; Pfeffer, Suzanne R; Dye, John M; Whelan, Sean P; Brummelkamp, Thijn R; Chandran, Kartik

    2012-04-18

    Ebola and Marburg filoviruses cause deadly outbreaks of haemorrhagic fever. Despite considerable efforts, no essential cellular receptors for filovirus entry have been identified. We showed previously that Niemann-Pick C1 (NPC1), a lysosomal cholesterol transporter, is required for filovirus entry. Here, we demonstrate that NPC1 is a critical filovirus receptor. Human NPC1 fulfills a cardinal property of viral receptors: it confers susceptibility to filovirus infection when expressed in non-permissive reptilian cells. The second luminal domain of NPC1 binds directly and specifically to the viral glycoprotein, GP, and a synthetic single-pass membrane protein containing this domain has viral receptor activity. Purified NPC1 binds only to a cleaved form of GP that is generated within cells during entry, and only viruses containing cleaved GP can utilize a receptor retargeted to the cell surface. Our findings support a model in which GP cleavage by endosomal cysteine proteases unmasks the binding site for NPC1, and GP-NPC1 engagement within lysosomes promotes a late step in entry proximal to viral escape into the host cytoplasm. NPC1 is the first known viral receptor that recognizes its ligand within an intracellular compartment and not at the plasma membrane. PMID:22395071

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-02-23

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-02-01

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

  9. Determination of Specific Antibody Responses to the Six Species of Ebola and Marburg Viruses by Multiplexed Protein Microarrays

    PubMed Central

    Kamata, Teddy; Natesan, Mohan; Warfield, Kelly; Aman, M. Javad

    2014-01-01

    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. PMID:25230936

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

    PubMed

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

    2013-01-29

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

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

    PubMed Central

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

    2016-01-01

    Background The 2013–15 Ebola outbreak was unprecedented due to sustained transmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood. PMID:26927697

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    Background.?We assessed healthcare workers' (HCWs) attitudes toward care of patients with Ebola virus disease (EVD). Methods.?We provided a self-administered questionnaire-based cross-sectional study of HCWs at 2 urban hospitals. Results.?Of 428 HCWs surveyed, 25.1% believed it was ethical to refuse care to patients with EVD; 25.9% were unwilling to provide care to them. In a multivariate analysis, female gender (32.9% vs 11.9%; odds ratio [OR], 3.2; 95% confidence interval [CI], 1.47.7), nursing profession (43.6% vs 12.8%; OR, 2.7; 95% CI, 1.45.2), ethical beliefs about refusing care to patients with EVD (39.1% vs 21.3%; OR, 3.71; 95% CI, 2.07.0), and increased concern about putting family, friends, and coworkers at risk (28.2% vs 0%; P = .003; OR, 11.1) were independent predictors of unwillingness to care for patients with EVD. Although beliefs about the ethics of refusing care were independently associated with willingness to care for patients with EVD, 21.3% of those who thought it was unethical to refuse care would be unwilling to care for patients with EVD. Healthcare workers in our study had concerns about potentially exposing their families and friends to EVD (90%), which was out of proportion to their degree of concern for personal risk (16.8%). Conclusion.?Healthcare workers' willingness to care for patients with Ebola patients did not precisely mirror their beliefs about the ethics of refusing to provide care, although they were strongly influenced by those beliefs. Healthcare workers may be balancing ethical beliefs about patient care with beliefs about risks entailed in rendering care and consequent risks to their families. Providing a safe work environment and measures to reduce risks to family, perhaps by arranging child care or providing temporary quarters, may help alleviate HCW's concerns. PMID:26788546

  14. A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding, and Egress

    PubMed Central

    Adu-Gyamfi, Emmanuel; Soni, Smita P.; Jee, Clara S.; Digman, Michelle A.; Gratton, Enrico; Stahelin, Robert V.

    2014-01-01

    Ebola virus (EBOV) causes viral hemorrhagic fever in humans and can have clinical fatality rates of ~60%. The EBOV genome consists of negative sense RNA that encodes seven proteins including viral protein 40 (VP40). VP40 is the major Ebola virus matrix protein and regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane of human cells to regulate viral budding where VP40 can produce virus like particles (VLPs) without other Ebola virus proteins present. The mechanistic details, however, of VP40 lipid-interactions and protein-protein interactions that are important for viral release remain to be elucidated. Here, we mutated a loop region in the N-terminal domain of VP40 (Lys127, Thr129, and Asn130) and find that mutations (K127A, T129A, and N130A) in this loop region reduce plasma membrane localization of VP40. Additionally, using total internal reflection fluorescence microscopy and number and brightness analysis we demonstrate these mutations greatly reduce VP40 oligomerization. Lastly, VLP assays demonstrate these mutations significantly reduce VLP release from cells. Taken together, these studies identify an important loop region in VP40 that may be essential to viral egress. PMID:25330123

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

    SciTech Connect

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

    2010-10-11

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

  16. Importin-?7 Is Involved in the Formation of Ebola Virus Inclusion Bodies but Is Not Essential for Pathogenicity in Mice.

    PubMed

    Gabriel, Glsah; Feldmann, Friederike; Reimer, Rudolph; Thiele, Swantje; Fischer, Meike; Hartmann, Enno; Bader, Michael; Ebihara, Hideki; Hoenen, Thomas; Feldmann, Heinz

    2015-10-01

    Ebola virus (EBOV) protein 24 antagonizes the host interferon (IFN) response by hijacking select nuclear importin-? isoforms. Thereby, it blocks STAT1-mediated IFN-?/? and IFN-? synthesis. However, owing to the lack of importin-? knockout animal models in the past, their role in EBOV pathogenesis remained largely unknown. Here, we demonstrate that importin-?7 is involved in the formation of EBOV inclusion bodies and replication. However, deletion of the gene encoding importin-?7 was not sufficient to increase survival rates among mice infected with EBOV. PMID:26185094

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

    PubMed Central

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

    2014-01-01

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

  18. Recombinant lentogenic Newcastle disease virus expressing Ebola virus GP infects cells independently of exogenous trypsin and uses macropinocytosis as the major pathway for cell entry

    PubMed Central

    2013-01-01

    Background Using reverse genetics, we generated a recombinant low-pathogenic LaSota strain Newcastle disease virus (NDV) expressing the glycoprotein (GP) of Ebola virus (EBOV), designated rLa-EBOVGP, and evaluated its biological characteristic in vivo and in vitro. Results The introduction and expression of the EBOV GP gene did not increase the virulence of the NDV vector in poultry or mice. EBOV GP was incorporated into the particle of the vector virus and the recombinant virus rLa-EBOVGP infected cells and spread within them independently of exogenous trypsin. rLa-EBOVGP is more resistant to NDV antiserum than the vector NDV and is moderately sensitive to EBOV GP antiserum. More importantly, infection with rLa-EBOVGP was markedly inhibited by IPA3, indicating that rLa-EBOVGP uses macropinocytosis as the major internalization pathway for cell entry. Conclusions The results demonstrate that EBOV GP in recombinant NDV particles functions independently to mediate the viral infection of the host cells and alters the cell-entry pathway. PMID:24209904

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2005-09-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1

    PubMed Central

    Lennemann, Nicholas J.; Rhein, Bethany A.; Ndungo, Esther; Chandran, Kartik; Qiu, Xiangguo; Maury, Wendy

    2014-01-01

    ABSTRACT Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca2+-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. PMID:24473128

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

    PubMed Central

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

    2016-01-01

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

  5. Influences of glycosylation on antigenicity, immunogenicity, and protective efficacy of ebola virus GP DNA vaccines.

    PubMed

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

    2007-02-01

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

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

    PubMed Central

    Clayton, A. J.

    1979-01-01

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

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

    PubMed

    Albario, Csar G; Wiggleton Guerrero, Lisa; Lo, Michael K; Nichol, Stuart T; Towner, Jonathan S

    2015-10-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Vu, Hong; Shulenin, Sergey; Grolla, Allen; Audet, Jonathan; He, Shihua; Kobinger, Gary; Unfer, Robert C; Warfield, Kelly L; Aman, M Javad; Holtsberg, Frederick W

    2016-02-01

    The West Africa Ebola virus disease (EVD) outbreak has reached unprecedented magnitude and caused worldwide concerns for the spread of this deadly virus. Recent findings in nonhuman primates (NHPs) demonstrate that antibodies can be protective against EVD. However, the role of antibody response in vaccine-mediated protection is not fully understood. To address these questions quantitative serology assays are needed for measurement of the antibody response to key Ebola virus (EBOV) proteins. Serology enzyme-linked immunosorbent assays (ELISA's), using a reference detection antibody, were developed in order to standardize the quantitation of antibody levels in vaccinated NHPs or in humans exposed to EBOV or immunized with an EBOV vaccine. Critical reagents were generated to support the development of the serology ELISAs. Recombinant EBOV matrix protein (VP40) was expressed in Escherichia coli and purified. Two variants of the glycoprotein (GP), the ectodomain lacking the transmembrane domain (GPΔTM), and an engineered GP lacking the mucin-like domain (GPΔmuc) were expressed and purified from mammalian cell systems. Using these proteins, three ELISA methods were developed and optimized for reproducibility and robustness, including stability testing of critical reagents. The assay was used to determine the antibody response against VP40, GPΔTM, and GPΔmuc in a NHP vaccine study using EBOV virus-like particles (VLP) vaccine expressing GP, VP40 and the nucleoprotein. Additionally, these ELISAs were used to successfully detect antibody responses to VP40, GPΔTM and GPΔmuc in human sera from EBOV infected individuals. PMID:26681387

  10. The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein

    PubMed Central

    Zhao, Dianyuan; Han, Xintao; Zheng, Xuexing; Wang, Hualei; Yang, Zaopeng; Liu, Di; Han, Ke; Liu, Jing; Wang, Xiaowen; Yang, Wenting; Dong, Qingyang; Yang, Songtao; Xia, Xianzhu; Tang, Li; He, Fuchu

    2016-01-01

    Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response. PMID:26943817

  11. With strengthened guidelines for health care workers, the CDC ups its game against the deadly Ebola virus.

    PubMed

    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. PMID:25522493

  12. Public health challenges and legacies of Japan's response to the Ebola virus disease outbreak in West Africa 2014 to 2015.

    PubMed

    Saito, Tomoya

    2015-11-01

    The largest outbreak of Ebola virus disease occurred in West Africa in 2014 and resulted in unprecedented transmission even in distant countries. In Japan, only nine individuals were screened for Ebola and there was no confirmed case. However, the government promoted the reinforcement of response measures and interagency collaboration, with training and simulation exercises conducted country-wide. The legacies included: publication of a communication policy on case disclosure, a protocol for collaboration between public health and other agencies, and establishing an expert committee to assemble the limited available expertise. There were challenges in taking proportionate and flexible measures in the management of people identified to be at high risk at entry points to Japan, in the decentralised medical response strategy, and in the medical countermeasures preparedness. The Ebola outbreak in West Africa provided a crucial opportunity to reveal the challenges and improve the preparedness for rare but high impact emerging diseases that are prone to be neglected. Efforts to uphold the lessons learnt and maintain public health preparedness should help prepare for future emerging diseases, including bioterrorist acts and pandemics. PMID:26559148

  13. The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein.

    PubMed

    Zhao, Dianyuan; Han, Xintao; Zheng, Xuexing; Wang, Hualei; Yang, Zaopeng; Liu, Di; Han, Ke; Liu, Jing; Wang, Xiaowen; Yang, Wenting; Dong, Qingyang; Yang, Songtao; Xia, Xianzhu; Tang, Li; He, Fuchu

    2016-03-01

    Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response. PMID:26943817

  14. [Health Communication: Preventing the Spread of Ebola Virus Disease in the Portuguese Spoken African Countries--Methodology KISS & KEYWORDS].

    PubMed

    Santiago, Isabel De; Miguel, Jos Pereira; Antunes, Francisco

    2015-01-01

    In this work, Health Communication is considered as an important discipline in medicine and health sciences for his role as true determinant of health. We highlight their contribution to health promotion and disease prevention. Thus, the Health Communication Plan (PCS): Preventing the spread of Ebola virus disease in the Portuguese Speaking African Countries - KISS & KEYWORDS methodology is a tool that aims to minimize the risk of infection by Ebola virus in the Portuguese Speaking African Countries and also train for a general improvement of health conditions of the local populations. In the PCS design are especially considered the social and cultural contexts of the target populations, especially the customs, traditions and religion. Health Communication is considered as an Essential Function of Public Health and its main is to provide a population-based approach. The target of communication actions are population groups in addition to the individual communication, target-audiences are people without access to the media, in Guinea Bissau, Cape Verde and Sao Tome and Principe. Under the communication plan uses the methodology, models and practices both by media professionals as health. A proximity approach and cultural mediation, previously identified key facts, are defined objectives; outlines to the Plan in concrete and its implementation methodology (target-audience and following intervention, materials to be used and key-messages and partners to mobilize) following the World Health Organisation standards. PMID:26061502

  15. Ebola Virus Disease: Rapid Diagnosis and Timely Case Reporting are Critical to the Early Response for Outbreak Control.

    PubMed

    Stamm, Lola V

    2015-09-01

    Ebola virus disease (EVD) is a life-threatening zoonosis caused by infection with the Ebola virus. Since the first reported EVD outbreak in the Democratic Republic of the Congo, several small outbreaks have been reported in central Africa with about 2,400 cases occurring between 1976 and 2013. The 2013-2015 EVD outbreak in west Africa is the first documented outbreak in this region and the largest ever with over 27,000 cases and more than 11,000 deaths. Although EVD transmission rates have recently decreased in west Africa, this crisis continues to threaten global health and security, particularly since infected travelers could spread EVD to other resource-limited areas of the world. Because vaccines and drugs are not yet licensed for EVD, outbreak control is dependent on the use of non-pharmaceutical interventions (e.g., infection control practices, isolation of EVD cases, contact tracing with follow-up and quarantine, sanitary burial, health education). However, delays in diagnosing and reporting EVD cases in less accessible rural areas continue to hamper control efforts. New advances in rapid diagnostics for identifying presumptive EVD cases and in mobile-based technologies for communicating critical health-related information should facilitate deployment of an early response to prevent the amplification of sporadic EVD cases into large-scale outbreaks. PMID:26175026

  16. Development and deployment of a rapid recombinase polymerase amplification Ebola virus detection assay in Guinea in 2015.

    PubMed

    Faye, Oumar; Faye, Ousmane; Soropogui, Barré; Patel, Pranav; El Wahed, Ahmed Abd; Loucoubar, Cheikh; Fall, Gamou; Kiory, Davy; Magassouba, N'Faly; Keita, Sakoba; Kondé, Mandy Kader; Diallo, Alpha Amadou; Koivogui, Lamine; Karlberg, Helen; Mirazimi, Ali; Nentwich, Oliver; Piepenburg, Olaf; Niedrig, Matthias; Weidmann, Manfred; Sall, Amadou Alpha

    2015-01-01

    In the absence of a vaccine or specific treatments for Ebola virus disease (EVD), early identification of cases is crucial for the control of EVD epidemics. We evaluated a new extraction kit (SpeedXtract (SE), Qiagen) on sera and swabs in combination with an improved diagnostic reverse transcription recombinase polymerase amplification assay for the detection of Ebola virus (EBOV-RT-RPA). The performance of combined extraction and detection was best for swabs. Sensitivity and specificity of the combined SE and EBOV-RT-RPA were tested in a mobile laboratory consisting of a mobile glovebox and a Diagnostics-in-a-Suitcase powered by a battery and solar panel, deployed to Matoto Conakry, Guinea as part of the reinforced surveillance strategy in April 2015 to reach the goal of zero cases. The EBOV-RT-RPA was evaluated in comparison to two real-time PCR assays. Of 928 post-mortem swabs, 120 tested positive, and the combined SE and EBOV-RT-RPA yielded a sensitivity and specificity of 100% in reference to one real-time RT-PCR assay. Another widely used real-time RT-PCR was much less sensitive than expected. Results were provided very fast within 30 to 60 min, and the field deployment of the mobile laboratory helped improve burial management and community engagement. PMID:26558690

  17. Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays

    PubMed Central

    Sozhamannan, Shanmuga; Holland, Mitchell Y.; Hall, Adrienne T.; Negrón, Daniel A.; Ivancich, Mychal; Koehler, Jeffrey W.; Minogue, Timothy D.; Campbell, Catherine E.; Berger, Walter J.; Christopher, George W.; Goodwin, Bruce G.; Smith, Michael A.

    2015-01-01

    Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

  18. Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays.

    PubMed

    Sozhamannan, Shanmuga; Holland, Mitchell Y; Hall, Adrienne T; Negrn, Daniel A; Ivancich, Mychal; Koehler, Jeffrey W; Minogue, Timothy D; Campbell, Catherine E; Berger, Walter J; Christopher, George W; Goodwin, Bruce G; Smith, Michael A

    2015-06-01

    Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

  19. Ebola virus disease outbreak; the role of field epidemiology training programme in the fight against the epidemic, Liberia, 2014

    PubMed Central

    Lubogo, Mutaawe; Donewell, Bangure; Godbless, Lucas; Shabani, Sasita; Maeda, Justin; Temba, Herilinda; Malibiche, Theophil C; Berhanu, Naod

    2015-01-01

    The African Field Epidemiology Network (AFENET) is a public health network established in 2005 as a non-profit networking alliance of Field Epidemiology and Laboratory Training Programs (FELTPs) and Field Epidemiology Training Programs (FETPs) in Africa. AFENET is dedicated to supporting Ministries of Health in Africa build strong, effective and sustainable programs and capacity to improve public health systems by partnering with global public health experts. The Network's goal is to strengthen field epidemiology and public health laboratory capacity to contribute effectively to addressing epidemics and other major public health problems in Africa. The goal for the establishment of FETP and FELTP was and still is to produce highly competent multi-disciplinary public health professionals who would assume influential posts in the public health structures and tackle emerging and re-emerging communicable and non-communicable diseases. AFENET currently networks 12 FELTPs and FETPs in sub-Saharan Africa with operations in 20 countries. During the Ebola Virus Disease (EVD) outbreak in West Africa, African Union Support for the Ebola Outbreak in West Africa (ASEOWA) supported FETP graduates from Uganda, Zimbabwe, Ethiopia and Tanzania for the investigation and control of the EVD outbreak in Liberia. The graduates were posted in different counties in Liberia where they lead teams of other experts conduct EVD outbreak investigations, Infection Control and Prevention trainings among health workers and communities, Strengthening integrated disease surveillance, developing Standard Operating Procedures for infection control and case notification in the Liberian setting as well as building capacity of local surveillance officers’ conduct outbreak investigation and contact tracing. The team was also responsible for EVD data management at the different Counties in Liberia. The FETP graduates have been instrumental in the earlier successes registered in various counties in Liberia in the control of the Ebola virus disease. Such efforts should be sustained by supporting local authorities develop strong health systems that are able to respond to epidemic of such magnitude in the near future. PMID:26779298

  20. Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo

    PubMed Central

    Moyen, Nanikaly; Thirion, Laurence; Emmerich, Petra; Dzia-Lepfoundzou, Amelia; Richet, Hervé; Boehmann, Yannik; Dimi, Yannick; Gallian, Pierre; Gould, Ernest A.; Günther, Stephan; de Lamballerie, Xavier

    2015-01-01

    Background Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV. Methodology and Findings In 2011, we conducted a MARV and EBOV seroprevalence study amongst 809 blood donors recruited in rural (75; 9.3%) and urban (734; 90.7%) areas of the Republic of Congo. Serum titres of IgG antibodies to MARV and EBOV were assessed by indirect double-immunofluorescence microscopy. MARV seroprevalence was 0.5% (4 in 809) without any identified risk factors. Prevalence of IgG to EBOV was 2.5%, peaking at 4% in rural areas and in Pointe Noire. Independent risk factors identified by multivariate analysis were contact with bats and exposure to birds. Conclusions/Significance This MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors. PMID:26047124

  1. Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors.

    PubMed

    Brudner, Matthew; Karpel, Marshall; Lear, Calli; Chen, Li; Yantosca, L Michael; Scully, Corinne; Sarraju, Ashish; Sokolovska, Anna; Zariffard, M Reza; Eisen, Damon P; Mungall, Bruce A; Kotton, Darrell N; Omari, Amel; Huang, I-Chueh; Farzan, Michael; Takahashi, Kazue; Stuart, Lynda; Stahl, Gregory L; Ezekowitz, Alan B; Spear, Gregory T; Olinger, Gene G; Schmidt, Emmett V; Michelow, Ian C

    2013-01-01

    Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes. PMID:23573288

  2. Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

    PubMed Central

    Lear, Calli; Chen, Li; Yantosca, L. Michael; Scully, Corinne; Sarraju, Ashish; Sokolovska, Anna; Zariffard, M. Reza; Eisen, Damon P.; Mungall, Bruce A.; Kotton, Darrell N.; Omari, Amel; Huang, I-Chueh; Farzan, Michael; Takahashi, Kazue; Stuart, Lynda; Stahl, Gregory L.; Ezekowitz, Alan B.; Spear, Gregory T.; Olinger, Gene G.; Schmidt, Emmett V.; Michelow, Ian C.

    2013-01-01

    Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes. PMID:23573288

  3. Chains of transmission and control of Ebola Virus Disease in Conakry, Guinea in 2014

    PubMed Central

    Faye, Ousmane; Bolle, Pierre-Yves; Heleze, Emmanuel; Faye, Oumar; Loucoubar, Cheikh; Magassouba, NFaly; Soropogui, Barr; Keita, Sakoba; Gakou, Tata; Bah, El Hadji Ibrahima; Koivogui, Lamine; Sall, Amadou Alpha; Cauchemez, Simon

    2015-01-01

    Background An Ebola Virus Disease (EVD) epidemic of unprecedented magnitude is ongoing in West Africa, affecting for the first time large urban centers like Conakry, the capital of Guinea. Methods Interviews of EVD patients, relatives and neighbors and laboratory databases were used to reconstruct EVD chains of transmission in Conakry, from March to August 2014. Findings Out of 193 confirmed and probable EVD cases reported in Conakry, Boffa and Tliml, 152 (79%) were positioned in the chains of transmission. In March, non-Health Care Workers cases infected on average 2.3 (95% CI: 1.6, 3.2) persons, breaking down into 1.4 (95% CI: 0.9, 2.2) persons in the community, 0.4 (95% CI: 0.1, 0.9) in the hospital and 0.5 (95% CI: 0.2, 1.0) at funerals. Following implementation of infection control in April, the reproduction number in the hospital and at funerals reduced below 0.1. In the community, the reproduction number, which was positively correlated with patients viremia, dropped by 50% for hospitalized cases but remained unchanged for those not hospitalized. Hospital and funeral transmission represented 35% (7/20) and 15% (3/20) of all transmissions in March; but only 9% (11/128) and 4% (5/128) from April onward. Overall, 82% (119/145) of transmission occurred in the community and 72% (105/145) between family members. Simulations showed that a 10% increase in hospitalizations could have reduced the length of chains by 26% (95% CI: 4%, 45%). Interpretation Monitoring chains of transmission is critical to evaluate and optimize local control strategies for EVD. In Conakry, interventions had the potential to stop the epidemic but reintroductions of the disease and lack of cooperation of a small number of families led to prolonged low-level spread, highlighting challenges of EVD control in large urban centers. Funding Labex IBEID, Reacting, PREDEMICS, NIGMS MIDAS initiative, Institut Pasteur de Dakar. PMID:25619149

  4. Development of a TaqMan Array Card for Acute-Febrile-Illness Outbreak Investigation and Surveillance of Emerging Pathogens, Including Ebola Virus.

    PubMed

    Liu, Jie; Ochieng, Caroline; Wiersma, Steve; Ströher, Ute; Towner, Jonathan S; Whitmer, Shannon; Nichol, Stuart T; Moore, Christopher C; Kersh, Gilbert J; Kato, Cecilia; Sexton, Christopher; Petersen, Jeannine; Massung, Robert; Hercik, Christine; Crump, John A; Kibiki, Gibson; Maro, Athanasia; Mujaga, Buliga; Gratz, Jean; Jacob, Shevin T; Banura, Patrick; Scheld, W Michael; Juma, Bonventure; Onyango, Clayton O; Montgomery, Joel M; Houpt, Eric; Fields, Barry

    2016-01-01

    Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. Convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR-based TaqMan array card (TAC) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 AFI-associated organisms, including 15 viruses (chikungunya, Crimean-Congo hemorrhagic fever [CCHF] virus, dengue, Ebola virus, Bundibugyo virus, Sudan virus, hantaviruses [Hantaan and Seoul], hepatitis E, Marburg, Nipah virus, o'nyong-nyong virus, Rift Valley fever virus, West Nile virus, and yellow fever virus), 8 bacteria (Bartonella spp., Brucella spp., Coxiella burnetii, Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, and Yersinia pestis), and 3 protozoa (Leishmania spp., Plasmodium spp., and Trypanosoma brucei). Two extrinsic controls (phocine herpesvirus 1 and bacteriophage MS2) were included to ensure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, interassay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and the TAC exhibited an overall 88% (278/315; 95% confidence interval [CI], 84% to 92%) sensitivity and a 99% (5,261/5,326, 98% to 99%) specificity. This TaqMan array card can be used in field settings as a rapid screen for outbreak investigation or for the surveillance of pathogens, including Ebola virus. PMID:26491176

  5. Hanta virus (image)

    MedlinePLUS

    Hanta virus is a distant cousin of Ebola virus, but is found worldwide. The virus is spread by human contact with rodent waste. Dangerous respiratory illness develops. Effective treatment is not yet available and over 50% of cases end in fatality.

  6. Relationship Between Ebola Virus Real-Time Quantitative Polymerase Chain Reaction-Based Threshold Cycle Value and Virus Isolation From Human Plasma.

    PubMed

    Spengler, Jessica R; McElroy, Anita K; Harmon, Jessica R; Strher, Ute; Nichol, Stuart T; Spiropoulou, Christina F

    2015-10-01

    We performed a longitudinal analysis of plasma samples obtained from 4 patients with Ebola virus (EBOV) disease (EVD) to determine the relationship between the real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based threshold cycle (Ct) value and the presence of infectious EBOV. EBOV was not isolated from plasma samples with a Ct value of >35.5 or >12 days after onset of symptoms. EBOV was not isolated from plasma samples in which anti-EBOV nucleoprotein immunoglobulin G was detected. These data demonstrate the utility of interpreting qRT-PCR results in the context of the course of EBOV infection and associated serological responses for patient-management decisions. PMID:25941333

  7. Evaluation of a National Call Center and a Local Alerts System for Detection of New Cases of Ebola Virus Disease - Guinea, 2014-2015.

    PubMed

    Lee, Christopher T; Bulterys, Marc; Martel, Lise D; Dahl, Benjamin A

    2016-01-01

    The epidemic of Ebola virus disease (Ebola) in West Africa began in Guinea in late 2013 (1), and on August 8, 2014, the World Health Organization (WHO) declared the epidemic a Public Health Emergency of International Concern (2). Guinea was declared Ebola-free on December 29, 2015, and is under a 90 day period of enhanced surveillance, following 3,351 confirmed and 453 probable cases of Ebola and 2,536 deaths (3). Passive surveillance for Ebola in Guinea has been conducted principally through the use of a telephone alert system. Community members and health facilities report deaths and suspected Ebola cases to local alert numbers operated by prefecture health departments or to a national toll-free call center. The national call center additionally functions as a source of public health information by responding to questions from the public about Ebola. To evaluate the sensitivity of the two systems and compare the sensitivity of the national call center with the local alerts system, the CDC country team performed probabilistic record linkage of the combined prefecture alerts database, as well as the national call center database, with the national viral hemorrhagic fever (VHF) database; the VHF database contains records of all known confirmed Ebola cases. Among 17,309 alert calls analyzed from the national call center, 71 were linked to 1,838 confirmed Ebola cases in the VHF database, yielding a sensitivity of 3.9%. The sensitivity of the national call center was highest in the capital city of Conakry (11.4%) and lower in other prefectures. In comparison, the local alerts system had a sensitivity of 51.1%. Local public health infrastructure plays an important role in surveillance in an epidemic setting. PMID:26963195

  8. Design and analysis considerations in the Ebola_Tx trial evaluating convalescent plasma in the treatment of Ebola virus disease in Guinea during the 2014–2015 outbreak

    PubMed Central

    Edwards, Tansy; Semple, Malcolm G; De Weggheleire, Anja; Claeys, Yves; De Crop, Maaike; Menten, Joris; Ravinetto, Raffaella; Temmerman, Sarah; Lynen, Lutgarde; Bah, Elhadj Ibrahima; Smith, Peter G; van Griensven, Johan

    2016-01-01

    The Ebola virus disease outbreak in 2014–2015 led to a huge caseload with a high case fatality rate. No specific treatments were available beyond supportive care for conditions such as dehydration and shock. Evaluation of treatment with convalescent plasma from Ebola survivors was identified as a priority. We evaluated this intervention in an emergency setting, where randomization was unacceptable. The original trial design was an open-label study comparing patients receiving convalescent plasma and supportive care to patients receiving supportive care alone. The comparison group comprised patients recruited at the start of the trial before convalescent plasma became available, as well as patients presenting during the trial for whom there was insufficient blood group–compatible plasma or no staffing capacity to provide additional transfusions. However, during the trial, convalescent plasma was available to treat all new patients. The design was changed to use a comparator group comprising patients previously treated at the same Ebola treatment center prior to the start of the trial. In the analysis, it was planned to adjust for any differences in prognostic variables between intervention and comparison groups, specifically baseline polymerase chain reaction cycle threshold and age. In addition, adjustment was planned for other potential confounders, identified in the analysis, such as patient presenting symptoms and time to treatment seeking. Because plasma treatment started up to 3 days after diagnosis and we could not define a similar time-point for the comparator group, patients who died before the third day after confirmation of diagnosis were excluded from both intervention and comparison groups in a per-protocol analysis. Some patients received additional experimental treatments soon after plasma treatment, and these were excluded. We also analyzed mortality including all patients from the time of confirmed diagnosis, irrespective of whether those in the trial series actually received plasma, as an intention-to-treat analysis. Per-protocol and intention-to-treat approaches gave similar conclusions. An important caveat in the interpretation of the findings is that it is unlikely that all potential sources of confounding, such as any variation in supportive care over time, were eliminated. Protocols and electronic data capture systems have now been extensively field-tested for emergency evaluation of treatment with convalescent plasma. Ongoing studies seek to quantify the level of neutralizing antibodies in different plasma donations to determine whether this influences the response and survival of treated patients. PMID:26768570

  9. Design and analysis considerations in the Ebola_Tx trial evaluating convalescent plasma in the treatment of Ebola virus disease in Guinea during the 2014-2015 outbreak.

    PubMed

    Edwards, Tansy; Semple, Malcolm G; De Weggheleire, Anja; Claeys, Yves; De Crop, Maaike; Menten, Joris; Ravinetto, Raffaella; Temmerman, Sarah; Lynen, Lutgarde; Bah, Elhadj Ibrahima; Smith, Peter G; van Griensven, Johan

    2016-02-01

    The Ebola virus disease outbreak in 2014-2015 led to a huge caseload with a high case fatality rate. No specific treatments were available beyond supportive care for conditions such as dehydration and shock. Evaluation of treatment with convalescent plasma from Ebola survivors was identified as a priority. We evaluated this intervention in an emergency setting, where randomization was unacceptable. The original trial design was an open-label study comparing patients receiving convalescent plasma and supportive care to patients receiving supportive care alone. The comparison group comprised patients recruited at the start of the trial before convalescent plasma became available, as well as patients presenting during the trial for whom there was insufficient blood group-compatible plasma or no staffing capacity to provide additional transfusions. However, during the trial, convalescent plasma was available to treat all new patients. The design was changed to use a comparator group comprising patients previously treated at the same Ebola treatment center prior to the start of the trial. In the analysis, it was planned to adjust for any differences in prognostic variables between intervention and comparison groups, specifically baseline polymerase chain reaction cycle threshold and age. In addition, adjustment was planned for other potential confounders, identified in the analysis, such as patient presenting symptoms and time to treatment seeking. Because plasma treatment started up to 3 days after diagnosis and we could not define a similar time-point for the comparator group, patients who died before the third day after confirmation of diagnosis were excluded from both intervention and comparison groups in a per-protocol analysis. Some patients received additional experimental treatments soon after plasma treatment, and these were excluded. We also analyzed mortality including all patients from the time of confirmed diagnosis, irrespective of whether those in the trial series actually received plasma, as an intention-to-treat analysis. Per-protocol and intention-to-treat approaches gave similar conclusions. An important caveat in the interpretation of the findings is that it is unlikely that all potential sources of confounding, such as any variation in supportive care over time, were eliminated. Protocols and electronic data capture systems have now been extensively field-tested for emergency evaluation of treatment with convalescent plasma. Ongoing studies seek to quantify the level of neutralizing antibodies in different plasma donations to determine whether this influences the response and survival of treated patients. PMID:26768570

  10. Notes from the Field: Ebola Virus Disease Response Activities During a Mass Displacement Event After Flooding - Freetown, Sierra Leone, September-November, 2015.

    PubMed

    Ratto, Jeffrey; Ivy, Wade; Purfield, Anne; Bangura, James; Omoko, Anthony; Boateng, Isaac; Duffy, Nadia; Sims, George; Beamer, Bryan; Pi-Sunyer, Teresa; Kamara, Sarian; Conteh, Sulaiman; Redd, John

    2016-01-01

    Since the start of the Ebola virus disease (Ebola) outbreak in West Africa, Sierra Leone has reported 8,706 confirmed Ebola cases and 3,956 deaths (1). During September 15-16, 2015, heavy rains flooded the capital, Freetown, resulting in eight deaths, home and property destruction, and thousands of persons in need of assistance (2). By September 27, approximately 13,000 flood-affected persons registered for flood relief services from the government (3). On September 17, two stadiums in Freetown were opened to provide shelter and assistance to flood-affected residents; a total of approximately 3,000 persons stayed overnight in both stadiums (Sierra Leone Ministry of Health and Sanitation, personal communication, September 2015). On the same day the stadiums were opened to flood-affected persons, the Ministry of Health and Sanitation (MoHS) and Western Area Ebola Response Center (WAERC) staff members from CDC, the World Health Organization (WHO), and the African Union evaluated the layout, logistics, and services at both stadiums and identified an immediate need to establish Ebola response activities. The patient in the last Ebola case in the Western Area, which includes Freetown, had died 37 days earlier, on August 11; however, transmission elsewhere in Sierra Leone was ongoing, and movement of persons throughout the country was common (4,5). PMID:26914633

  11. Development and evaluation of a real-time RT-PCR assay for the detection of Ebola virus (Zaire) during an Ebola outbreak in Guinea in 2014-2015.

    PubMed

    Dedkov, V G; Magassouba, N' F; Safonova, M V; Deviatkin, A A; Dolgova, A S; Pyankov, O V; Sergeev, A A; Utkin, D V; Odinokov, G N; Safronov, V A; Agafonov, A P; Maleev, V V; Shipulin, G A

    2016-02-01

    In early February 2014, an outbreak of the Ebola virus disease caused by Zaire ebolavirus (EBOV) occurred in Guinea; cases were also recorded in other West African countries with a combined population of approximately 25 million. A rapid, sensitive and inexpensive method for detecting EBOV is needed to effectively control such outbreak. Here, we report a real-time reverse-transcription PCR assay for Z. ebolavirus detection used by the Specialized Anti-epidemic Team of the Russian Federation during the Ebola virus disease prevention mission in the Republic of Guinea. The analytical sensitivity of the assay is 5×10(2) viral particles per ml, and high specificity is demonstrated using representative sampling of viral, bacterial and human nucleic acids. This assay can be applied successfully for detecting the West African strains of Z. ebolavirus as well as on strains isolated in the Democratic Republic of the Congo in 2014. PMID:26597659

  12. Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

    SciTech Connect

    Usami, Katsuaki; Matsuno, Keita; Igarashi, Manabu; Denda-Nagai, Kaori; Takada, Ayato; Irimura, Tatsuro

    2011-04-01

    Highlights: {yields} Ebola virus infection is mediated by binding to and fusion with the target cells. {yields} Structural feature of the viral glycoprotein determines the infectivity. {yields} Surface C-type lectin, MGL, of macrophages and dendritic cells mediate the infection. {yields} GP2, one of glycoprotein subunits, plays an essential role in MGL-mediated infection. {yields} There is a critical amino acid residue involved in high infectivity. -- Abstract: Ebola virus (EBOV) infection is initiated by the interaction of the viral surface envelope glycoprotein (GP) with the binding sites on target cells. Differences in the mortality among different species of the Ebola viruses, i.e., Zaire ebolavirus (ZEBOV) and Reston ebolavirus (REBOV), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the GPs in cells expressing macrophage galactose-type calcium-type lectin (MGL/CD301). Through mutagenesis of GP2, the transmembrane-anchored subunit of GP, we found that residues 502-527 of the GP2 sequence determined the different infectivity between VSV-ZEBOV GP and -REBOV GP in MGL/CD301-expressing cells and a histidine residue at position 516 of ZEBOV GP2 appeared essential in the differential infectivity. These findings may provide a clue to clarify a molecular basis of different pathogenicity among EBOV species.

  13. Characterization of oligomerization of a peptide from the ebola virus glycoprotein by small-angle neutron scattering

    NASA Astrophysics Data System (ADS)

    Egorov, V. V.; Gorshkov, A. N.; Murugova, T. N.; Vasin, A. V.; Lebedev, D. V.; Isaev-Ivanov, V. V.; Kiselev, O. I.

    2016-01-01

    Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) studies showed that model peptides QNALVCGLRQ (G33) and QNALVCGLRG (G31) corresponding to region 551-560 of the GP protein of the Sudan Ebola virus are prone to oligomerization in solution. Both peptides can form amyloid-like fibrills. The G33 peptide forms fibrils within one day of incubation, whereas the fibrillogenesis of the G31 peptide is observed only after incubation for several months. The possible role of the observed processes in the pathogenesis and the possibility of applying a combination of the TEM and SANS techniques to search for new compounds that are able to influence the protein oligomerization are discussed.

  14. Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection.

    PubMed

    Dowall, Stuart David; Callan, Jo; Zeltina, Antra; Al-Abdulla, Ibrahim; Strecker, Thomas; Fehling, Sarah K; Krähling, Verena; Bosworth, Andrew; Rayner, Emma; Taylor, Irene; Charlton, Sue; Landon, John; Cameron, Ian; Hewson, Roger; Nasidi, Abdulsalami; Bowden, Thomas A; Carroll, Miles W

    2016-04-01

    The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease. PMID:26715676

  15. Backs against the wall: novel and existing strategies used during the 2014-2015 Ebola virus outbreak.

    PubMed

    Wong, Gary; Kobinger, Gary P

    2015-07-01

    The 2014-2015 outbreak of Ebola virus (EBOV), originating from Guinea, is now responsible for the infection of >20,000 people in 9 countries. Whereas past filovirus outbreaks in sub-Saharan Africa have been rapidly brought under control with comparably few cases, this outbreak has been particularly resistant to containment efforts. Both the general population and primary health care workers have been affected by this outbreak, with hundreds of doctors and nurses being infected in the line of duty. In the absence of approved therapeutics, several caregivers have turned to investigational new drugs as well as experimental therapies in an effort to save lives. This review aims to summarize the candidates currently under consideration for postexposure use in infected patients during the largest EBOV outbreak in history. PMID:25972518

  16. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    SciTech Connect

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; Shabman, Reed  S.; Chiu, Wah; Davey, Robert  A.; Otwinowski, Zbyszek; Basler, Christopher  F.; Amarasinghe, Gaya  K.

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.

  17. Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection

    PubMed Central

    Dowall, Stuart David; Callan, Jo; Zeltina, Antra; Al-Abdulla, Ibrahim; Strecker, Thomas; Fehling, Sarah K.; Krähling, Verena; Bosworth, Andrew; Rayner, Emma; Taylor, Irene; Charlton, Sue; Landon, John; Cameron, Ian; Hewson, Roger; Nasidi, Abdulsalami; Bowden, Thomas A.; Carroll, Miles W.

    2016-01-01

    The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease. PMID:26715676

  18. Surveillance and Outbreak Response Management System (SORMAS) to support the control of the Ebola virus disease outbreak in West Africa.

    PubMed

    Fähnrich, C; Denecke, K; Adeoye, O O; Benzler, J; Claus, H; Kirchner, G; Mall, S; Richter, R; Schapranow, M P; Schwarz, N; Tom-Aba, D; Uflacker, M; Poggensee, G; Krause, G

    2015-01-01

    In the context of controlling the current outbreak of Ebola virus disease (EVD), the World Health Organization claimed that 'critical determinant of epidemic size appears to be the speed of implementation of rigorous control measures', i.e. immediate follow-up of contact persons during 21 days after exposure, isolation and treatment of cases, decontamination, and safe burials. We developed the Surveillance and Outbreak Response Management System (SORMAS) to improve efficiency and timeliness of these measures. We used the Design Thinking methodology to systematically analyse experiences from field workers and the Ebola Emergency Operations Centre (EOC) after successful control of the EVD outbreak in Nigeria. We developed a process model with seven personas representing the procedures of EVD outbreak control. The SORMAS system architecture combines latest In-Memory Database (IMDB) technology via SAP HANA (in-memory, relational database management system), enabling interactive data analyses, and established SAP cloud tools, such as SAP Afaria (a mobile device management software). The user interface consists of specific front-ends for smartphones and tablet devices, which are independent from physical configurations. SORMAS allows real-time, bidirectional information exchange between field workers and the EOC, ensures supervision of contact follow-up, automated status reports, and GPS tracking. SORMAS may become a platform for outbreak management and improved routine surveillance of any infectious disease. Furthermore, the SORMAS process model may serve as framework for EVD outbreak modeling. PMID:25846493

  19. Successful Control of Ebola Virus Disease: Analysis of Service Based Data from Rural Sierra Leone

    PubMed Central

    Lokuge, Kamalini; Caleo, Grazia; Greig, Jane; Duncombe, Jennifer; McWilliam, Nicholas; Squire, James; Lamin, Manjo; Veltus, Emily; Wolz, Anja; Kobinger, Gary; de la Vega, Marc-Antoine; Gbabai, Osman; Nabieu, Sao; Lamin, Mohammed; Kremer, Ronald; Danis, Kostas; Banks, Emily; Glass, Kathryn

    2016-01-01

    Introduction The scale and geographical distribution of the current outbreak in West Africa raised doubts as to the effectiveness of established methods of control. Ebola Virus Disease (EVD) was first detected in Sierra Leone in May 2014 in Kailahun district. Despite high case numbers elsewhere in the country, transmission was eliminated in the district by December 2014. We describe interventions underpinning successful EVD control in Kailahun and implications for EVD control in other areas. Methods Internal service data and published reports from response agencies were analysed to describe the structure and type of response activities, EVD case numbers and epidemic characteristics. This included daily national situation reports and District-level data and reports of the Sierra Leone Ministry of Health and Sanitation, and Médecins Sans Frontières (MSF) patient data and internal epidemiological reports. We used EVD case definitions provided by the World Health Organisation over the course of the outbreak. Characteristics assessed included level of response activities and epidemiological features such as reported exposure (funeral-related or not), time interval between onset of illness and admission to the EVD Management Centre (EMC), work-related exposures (health worker or not) and mortality. We compared these characteristics between two time periods—June to July (the early period of response), and August to December (when coverage and quality of response had improved). A stochastic model was used to predict case numbers per generation with different numbers of beds and a varying percentage of community cases detected. Results There were 652 probable/confirmed EVD cases from June-December 2014 in Kailahun. An EMC providing patient care opened in June. By August 2014 an integrated detection, treatment, and prevention strategy was in place across the district catchment zone. From June-July to August-December 2014 surveillance and contact tracing staff increased from 1.0 to 8.8 per confirmed EVD case, EMC capacity increased from 32 to 100 beds, the number of burial teams doubled, and health promotion activities increased in coverage. These improvements in response were associated with the following changes between the same periods: the proportion of confirmed/probable cases admitted to the EMC increased from 35% to 83% (χ2 p-value<0·001), the proportion of confirmed patients admitted to the EMC <3 days of symptom onset increased from 19% to 37% (χ2 p-value <0·001), and reported funeral contact in those admitted decreased from 33% to 16% (χ2 p-value <0·001). Mathematical modelling confirmed the importance of both patient management capacity and surveillance and contact tracing for EVD control. Discussion Our findings demonstrate that control of EVD can be achieved using established interventions based on identification and appropriate management of those who are at risk of and develop EVD, including in the context of ongoing transmission in surrounding regions. Key attributes in achieving control were sufficient patient care capacity (including admission to specialist facilities of suspect and probable cases for assessment), integrated with adequate staffing and resourcing of community-based case detection and prevention activities. The response structure and coverage targets we present are of value in informing effective control in current and future EVD outbreaks. PMID:26959413

  20. Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies

    PubMed Central

    Iversen, Patrick L.; Saoud, Jay B.; Sazani, Peter; Charleston, Jay S.; Axtelle, Tim; Wong, Michael; Smith, William B.; Vutikullird, Apinya; Kaye, Edward

    2014-01-01

    Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMOplus) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates in previous studies. AVI-6002 (a combination of AVI-7537 and AVI-7539) or AVI-6003 (a combination of AVI-7287 and AVI-7288) were administered as sequential intravenous (i.v.) infusions of a 1:1 fixed dose ratio of the two subcomponents. In each study, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in six-dose escalation cohorts of five subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg/kg per component) or placebo in a 4:1 ratio. Both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied. A maximum tolerated dose was not observed in either study. The four chemically similar PMOplus components exhibited generally similar PK profiles. The mean peak plasma concentration and area under the concentration-time curve values of the four components exhibited dose-proportional PK. The estimated plasma half-life of all four components was 2 to 5 h. The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence. PMID:25155593

  1. Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

    PubMed Central

    Kuhn, Jens H.; Andersen, Kristian G.; Baize, Sylvain; Bào, Yīmíng; Bavari, Sina; Berthet, Nicolas; Blinkova, Olga; Brister, J. Rodney; Clawson, Anna N.; Fair, Joseph; Gabriel, Martin; Garry, Robert F.; Gire, Stephen K.; Goba, Augustine; Gonzalez, Jean-Paul; Günther, Stephan; Happi, Christian T.; Jahrling, Peter B.; Kapetshi, Jimmy; Kobinger, Gary; Kugelman, Jeffrey R.; Leroy, Eric M.; Maganga, Gael Darren; Mbala, Placide K.; Moses, Lina M.; Muyembe-Tamfum, Jean-Jacques; N’Faly, Magassouba; Nichol, Stuart T.; Omilabu, Sunday A.; Palacios, Gustavo; Park, Daniel J.; Paweska, Janusz T.; Radoshitzky, Sheli R.; Rossi, Cynthia A.; Sabeti, Pardis C.; Schieffelin, John S.; Schoepp, Randal J.; Sealfon, Rachel; Swanepoel, Robert; Towner, Jonathan S.; Wada, Jiro; Wauquier, Nadia; Yozwiak, Nathan L.; Formenty, Pierre

    2014-01-01

    In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures. PMID:25421896

  2. Nomenclature- and database-compatible names for the two Ebola virus variants that emerged in Guinea and the Democratic Republic of the Congo in 2014.

    PubMed

    Kuhn, Jens H; Andersen, Kristian G; Baize, Sylvain; Bo, Y?mng; Bavari, Sina; Berthet, Nicolas; Blinkova, Olga; Brister, J Rodney; Clawson, Anna N; Fair, Joseph; Gabriel, Martin; Garry, Robert F; Gire, Stephen K; Goba, Augustine; Gonzalez, Jean-Paul; Gnther, Stephan; Happi, Christian T; Jahrling, Peter B; Kapetshi, Jimmy; Kobinger, Gary; Kugelman, Jeffrey R; Leroy, Eric M; Maganga, Gael Darren; Mbala, Placide K; Moses, Lina M; Muyembe-Tamfum, Jean-Jacques; N'Faly, Magassouba; Nichol, Stuart T; Omilabu, Sunday A; Palacios, Gustavo; Park, Daniel J; Paweska, Janusz T; Radoshitzky, Sheli R; Rossi, Cynthia A; Sabeti, Pardis C; Schieffelin, John S; Schoepp, Randal J; Sealfon, Rachel; Swanepoel, Robert; Towner, Jonathan S; Wada, Jiro; Wauquier, Nadia; Yozwiak, Nathan L; Formenty, Pierre

    2014-11-01

    In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: "Makona", Middle Africa: "Lomela") and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures. PMID:25421896

  3. Field Evaluation of Capillary Blood Samples as a Collection Specimen for the Rapid Diagnosis of Ebola Virus Infection During an Outbreak Emergency

    PubMed Central

    Strecker, Thomas; Palyi, Bernadett; Ellerbrok, Heinz; Jonckheere, Sylvie; de Clerck, Hilde; Bore, Joseph Akoi; Gabriel, Martin; Stoecker, Kilian; Eickmann, Markus; van Herp, Michel; Formenty, Pierre; Di Caro, Antonino; Becker, Stephan

    2015-01-01

    Background. Reliable reverse transcription polymerase chain reaction (RT-PCR)–based diagnosis of Ebola virus infection currently requires a blood sample obtained by intravenous puncture. During the current Ebola outbreak in Guinea, we evaluated the usability of capillary blood samples collected from fingersticks of patients suspected of having Ebola virus disease (EVD) for field diagnostics during an outbreak emergency. Methods. A total of 120 venous and capillary blood samples were collected from 53 patients admitted to the Ebola Treatment Centre in Guéckédou, Guinea, between July and August 2014. All sample specimens were analyzed by RT-PCR using the RealStar Filovirus Screen RT-PCR Kit 1.0 from altona Diagnostics (Germany). We compared samples obtained by venipuncture and those obtained by capillary blood sampling absorbed onto swab devices. Results. The resulting sensitivity and specificity of tests performed with capillary blood samples were 86.8% (95% confidence interval [CI], 71.9%–95.6%; 33/38 patients) and 100% (95% CI, 84.6%–100%; 22/22 patients), respectively. Conclusions. Our data suggest that capillary blood samples could serve as an alternative to venous blood samples for the diagnosis of EVD in resource-limited settings during a crisis. This can be of particular advantage in cases when venipuncture is difficult to perform—for example, with newborns and infants or when adult patients reject venipuncture for cultural or religious reasons. PMID:25991465

  4. Ebola Virus Disease 2013-2014 Outbreak in West Africa: An Analysis of the Epidemic Spread and Response

    PubMed Central

    Cenciarelli, Orlando; Pietropaoli, Stefano; Carestia, Mariachiara; D'Amico, Fabrizio; Sassolini, Alessandro; Di Giovanni, Daniele; Rea, Silvia; Gabbarini, Valentina; Tamburrini, Annalaura; Palombi, Leonardo; Bellecci, Carlo; Gaudio, Pasquale

    2015-01-01

    The Ebola virus epidemic burst in West Africa in late 2013, started in Guinea, reached in a few months an alarming diffusion, actually involving several countries (Liberia, Sierra Leone, Nigeria, Senegal, and Mali). Guinea and Liberia, the first nations affected by the outbreak, have put in place measures to contain the spread, supported by international organizations; then they were followed by the other nations affected. In the present EVD outbreak, the geographical spread of the virus has followed a new route: the achievement of large urban areas at an early stage of the epidemic has led to an unprecedented diffusion, featuring the largest outbreak of EVD of all time. This has caused significant concerns all over the world: the potential reaching of far countries from endemic areas, mainly through fast transports, induced several countries to issue information documents and health supervision for individuals going to or coming from the areas at risk. In this paper the geographical spread of the epidemic was analyzed, assessing the sequential appearance of cases by geographic area, considering the increase in cases and mortality according to affected nations. The measures implemented by each government and international organizations to contain the outbreak, and their effectiveness, were also evaluated. PMID:25852754

  5. Enzyme-linked immunosorbent assays for detection of antibodies to Ebola and Marburg viruses using recombinant nucleoproteins.

    PubMed

    Saijo, M; Niikura, M; Morikawa, S; Ksiazek, T G; Meyer, R F; Peters, C J; Kurane, I

    2001-01-01

    The full-length nucleoprotein (NP) of Ebola virus (EBO) was expressed as a His-tagged recombinant protein (His-EBO-NP) by a baculovirus system. Carboxy-terminal halves of NPs of EBO and Marburg virus (MBG) were expressed as glutathione S-transferase-tagged recombinant proteins in an Escherichia coli system. The antigenic regions on the NPs of EBO and MBG were determined by both Western blotting and enzyme-linked immunosorbent assay (ELISA) to be located on the C-terminal halves. The C-terminal 110 and 102 amino acids of the NPs of EBO and MBG, respectively, possess strong antigenicity. The full-length NP of EBO was strongly expressed in insect cells upon infection with the recombinant baculovirus, while expression of the full-length NP of MBG was weak. We developed an immunoglobulin G (IgG) ELISA using His-EBO-NP and the C-terminal halves of the NPs of EBO and MBG as antigens. We evaluated the IgG ELISA for the ability to detect IgG antibodies to EBO and MBG, using human sera collected from EBO and MBG patients. The IgG ELISA with the recombinant NPs showed high sensitivity and specificity in detecting EBO and MBG antibodies. The results indicate that ELISA systems prepared with the recombinant NPs of EBO and MBG are valuable tools for the diagnosis of EBO and MBG infections and for seroepidemiological field studies. PMID:11136739

  6. Recombinant Ebola virus nucleoprotein and glycoprotein (Gabon 94 strain) provide new tools for the detection of human infections.

    PubMed

    Prehaud, C; Hellebrand, E; Coudrier, D; Volchkov, V E; Volchkova, V A; Feldmann, H; Le Guenno, B; Bouloy, M

    1998-11-01

    After cloning and sequencing the glycoprotein (GP) gene of one of the Gabonese strains of Ebola virus isolated during the 1994-1996 outbreak, it was shown that the circulating virus was of the Zaire subtype. This was confirmed in this study by cloning and sequencing the nucleoprotein (NP) gene of this strain. These two structural proteins were also expressed as recombinant proteins and used in ELISA tests. NP was expressed as a His-tagged fusion protein in Escherichia coli and was purified on resins charged with nickel ions. GP was expressed by means of recombinant baculoviruses in Spodoptera frugiperda cells. Both recombinant proteins reacted positively in ELISAs for the detection of IgG antibodies in convalescent human sera from Gabon and Zaire. The difference in the relative titres of anti-NP and -GP antibodies was variable, depending on the sera. In addition, the recombinant NP reacted with heterologous sera from Cte d'Ivoire and was used successfully to detect IgM antibodies by mu-capture ELISA in sera from Gabonese patients. PMID:9820131

  7. Terminal decontamination of the Royal Free London's high-level isolation unit after a case of Ebola virus disease using hydrogen peroxide vapor.

    PubMed

    Otter, Jonathan A; Mepham, Stephen; Athan, Breda; Mack, Damien; Smith, Robin; Jacobs, Michael; Hopkins, Susan

    2016-02-01

    We report the decontamination of the high-level isolation unit at the Royal Free London after the discharge of a patient with Ebola virus disease, who was repatriated from West Africa. Hydrogen peroxide vapor (HPV) was used to decontaminate the patient care isolators and the rooms housing them. HPV decontamination was completed without incident and allowed the unit to be returned to service more quickly than the previous protocol of using formaldehyde. PMID:26521699

  8. Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material

    PubMed Central

    Trefry, John C.; Wollen, Suzanne E.; Nasar, Farooq; Shamblin, Joshua D.; Kern, Steven J.; Bearss, Jeremy J.; Jefferson, Michelle A.; Chance, Taylor B.; Kugelman, Jeffery R.; Ladner, Jason T.; Honko, Anna N.; Kobs, Dean J.; Wending, Morgan Q.S.; Sabourin, Carol L.; Pratt, William D.; Palacios, Gustavo F.; Pitt, M. Louise M.

    2015-01-01

    Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein’s poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations. PMID:26703716

  9. Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material.

    PubMed

    Trefry, John C; Wollen, Suzanne E; Nasar, Farooq; Shamblin, Joshua D; Kern, Steven J; Bearss, Jeremy J; Jefferson, Michelle A; Chance, Taylor B; Kugelman, Jeffery R; Ladner, Jason T; Honko, Anna N; Kobs, Dean J; Wending, Morgan Q S; Sabourin, Carol L; Pratt, William D; Palacios, Gustavo F; Pitt, M Louise M

    2015-01-01

    Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein's poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of nave and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In nave animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations. PMID:26703716

  10. Analysis of the Highly Diverse Gene Borders in Ebola Virus Reveals a Distinct Mechanism of Transcriptional Regulation

    PubMed Central

    Brauburger, Kristina; Boehmann, Yannik; Tsuda, Yoshimi; Hoenen, Thomas; Olejnik, Judith; Schümann, Michael; Ebihara, Hideki

    2014-01-01

    ABSTRACT Ebola virus (EBOV) belongs to the group of nonsegmented negative-sense RNA viruses. The seven EBOV genes are separated by variable gene borders, including short (4- or 5-nucleotide) intergenic regions (IRs), a single long (144-nucleotide) IR, and gene overlaps, where the neighboring gene end and start signals share five conserved nucleotides. The unique structure of the gene overlaps and the presence of a single long IR are conserved among all filoviruses. Here, we sought to determine the impact of the EBOV gene borders during viral transcription. We show that readthrough mRNA synthesis occurs in EBOV-infected cells irrespective of the structure of the gene border, indicating that the gene overlaps do not promote recognition of the gene end signal. However, two consecutive gene end signals at the VP24 gene might improve termination at the VP24-L gene border, ensuring efficient L gene expression. We further demonstrate that the long IR is not essential for but regulates transcription reinitiation in a length-dependent but sequence-independent manner. Mutational analysis of bicistronic minigenomes and recombinant EBOVs showed no direct correlation between IR length and reinitiation rates but demonstrated that specific IR lengths not found naturally in filoviruses profoundly inhibit downstream gene expression. Intriguingly, although truncation of the 144-nucleotide-long IR to 5 nucleotides did not substantially affect EBOV transcription, it led to a significant reduction of viral growth. IMPORTANCE Our current understanding of EBOV transcription regulation is limited due to the requirement for high-containment conditions to study this highly pathogenic virus. EBOV is thought to share many mechanistic features with well-analyzed prototype nonsegmented negative-sense RNA viruses. A single polymerase entry site at the 3′ end of the genome determines that transcription of the genes is mainly controlled by gene order and cis-acting signals found at the gene borders. Here, we examined the regulatory role of the structurally unique EBOV gene borders during viral transcription. Our data suggest that transcriptional regulation in EBOV is highly complex and differs from that in prototype viruses and further the understanding of this most fundamental process in the filovirus replication cycle. Moreover, our results with recombinant EBOVs suggest a novel role of the long IR found in all filovirus genomes during the viral replication cycle. PMID:25142600

  11. Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995.

    PubMed

    Ksiazek, T G; Rollin, P E; Williams, A J; Bressler, D S; Martin, M L; Swanepoel, R; Burt, F J; Leman, P A; Khan, A S; Rowe, A K; Mukunu, R; Sanchez, A; Peters, C J

    1999-02-01

    Ebola hemorrhagic fever (EHF) patients treated at Kikwit General Hospital during the 1995 outbreak were tested for viral antigen, IgG and IgM antibody, and infectious virus. Viral antigen could be detected in virtually all patients during the acute phase of illness, while antibody was not always detectable before death. Virus was also isolated from patients during the course of their febrile illness, but attempts to quantify virus in Vero E6 cells by standard plaque assay were often unsuccessful. IgG and IgM antibody appeared at approximately the same time after disease onset (8-10 days), but IgM persisted for a much shorter period among the surviving convalescent patients. IgG antibody was detectable in surviving patients through about 2 years after onset, the latest time that samples were obtained. Detection of Ebola virus antigens or virus isolation appears to be the most reliable means of diagnosis for patients with suspected acute EHF, since patients with this often-fatal disease (80% mortality) may not develop detectable antibodies before death. PMID:9988182

  12. [Recent Lassa, Marbourg and Ebola viruses in African tropical viruses. I. Semiology--physiopathology--diagnosis--treatment (author's transl)].

    PubMed

    Brs, P

    1978-09-30

    Three new viruses have been identified in Africa during the present decade. They may cause sporadic cases or limited outbreaks, and they are probably endemic in areas which are still ill-defined. Severe forms of infection lead to the haemorrhagic syndrome or to hypovolemic shock, the physiopathology of which is being studied. The case-fatality ratio of severe cases is between 30 and 85 per cent. Nosocomial outbreaks have been observed, but they can be avoided if appropriate barrier nursing measures are carried out for the treatment of patients or adequate protection measures for sampling and examination of laboratory specimens. As such cases may be transferred outside the endemic zone, this implies that countries receiving travellers from Africa should have hospitals with specialized units for strict isolation and treatment of these patients. PMID:569288

  13. Innovative Technological Approach to Ebola Virus Disease Outbreak Response in Nigeria Using the Open Data Kit and Form Hub Technology.

    PubMed

    Tom-Aba, Daniel; Olaleye, Adeniyi; Olayinka, Adebola Tolulope; Nguku, Patrick; Waziri, Ndadilnasiya; Adewuyi, Peter; Adeoye, Olawunmi; Oladele, Saliu; Adeseye, Aderonke; Oguntimehin, Olukayode; Shuaib, Faisal

    2015-01-01

    The recent outbreak of Ebola Virus Disease (EVD) in West Africa has ravaged many lives. Effective containment of this outbreak relies on prompt and effective coordination and communication across various interventions; early detection and response being critical to successful control. The use of information and communications technology (ICT) in active surveillance has proved to be effective but its use in Ebola outbreak response has been limited. Due to the need for timeliness in reporting and communication for early discovery of new EVD cases and promptness in response; it became imperative to empower the response team members with technologies and solutions which would enable smooth and rapid data flow. The Open Data Kit and Form Hub technology were used in combination with the Dashboard technology and ArcGIS mapping for follow up of contacts, identification of cases, case investigation and management and also for strategic planning during the response. A remarkable improvement was recorded in the reporting of daily follow-up of contacts after the deployment of the integrated real time technology. The turnaround time between identification of symptomatic contacts and evacuation to the isolation facility and also for receipt of laboratory results was reduced and informed decisions could be taken by all concerned. Accountability in contact tracing was ensured by the use of a GPS enabled device. The use of innovative technologies in the response of the EVD outbreak in Nigeria contributed significantly to the prompt control of the outbreak and containment of the disease by providing a valuable platform for early warning and guiding early actions. PMID:26115402

  14. Innovative Technological Approach to Ebola Virus Disease Outbreak Response in Nigeria Using the Open Data Kit and Form Hub Technology

    PubMed Central

    Nguku, Patrick; Waziri, Ndadilnasiya; Adewuyi, Peter; Adeoye, Olawunmi; Adeseye, Aderonke; Oguntimehin, Olukayode; Shuaib, Faisal

    2015-01-01

    The recent outbreak of Ebola Virus Disease (EVD) in West Africa has ravaged many lives. Effective containment of this outbreak relies on prompt and effective coordination and communication across various interventions; early detection and response being critical to successful control. The use of information and communications technology (ICT) in active surveillance has proved to be effective but its use in Ebola outbreak response has been limited. Due to the need for timeliness in reporting and communication for early discovery of new EVD cases and promptness in response; it became imperative to empower the response team members with technologies and solutions which would enable smooth and rapid data flow. The Open Data Kit and Form Hub technology were used in combination with the Dashboard technology and ArcGIS mapping for follow up of contacts, identification of cases, case investigation and management and also for strategic planning during the response. A remarkable improvement was recorded in the reporting of daily follow-up of contacts after the deployment of the integrated real time technology. The turnaround time between identification of symptomatic contacts and evacuation to the isolation facility and also for receipt of laboratory results was reduced and informed decisions could be taken by all concerned. Accountability in contact tracing was ensured by the use of a GPS enabled device. The use of innovative technologies in the response of the EVD outbreak in Nigeria contributed significantly to the prompt control of the outbreak and containment of the disease by providing a valuable platform for early warning and guiding early actions. PMID:26115402

  15. Evolving RNA Virus Pandemics: HIV, HCV, Ebola, Dengue, Chikunguya, and now Zika!

    PubMed

    Barreiro, Pablo

    2016-01-01

    The Zika virus (ZIKV), a flavivirus related to yellow fever, dengue, and West Nile, originated in the Zika forest in Uganda and was discovered in a rhesus monkey in 1947. The disease now has "explosive" pandemic potential, with outbreaks in Africa, Southeast Asia, the Pacific Islands, and the Americas. To date, the CDC has issued travel alerts for at least 30 countries and territories in Latin America, the Caribbean, Polynesia, and Cape Verde in Africa. PMID:27028271

  16. Molecular architecture of the nucleoprotein C-terminal domain from the Ebola and Marburg viruses.

    PubMed

    Baker, Laura E; Ellena, Jeffrey F; Handing, Katarzyna B; Derewenda, Urszula; Utepbergenov, Darkhan; Engel, Daniel A; Derewenda, Zygmunt S

    2016-01-01

    The Filoviridae family of negative-sense, single-stranded RNA (ssRNA) viruses is comprised of two species of Marburgvirus (MARV and RAVV) and five species of Ebolavirus, i.e. Zaire (EBOV), Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV) and Bundibugyo (BDBV). In each of these viruses the ssRNA encodes seven distinct proteins. One of them, the nucleoprotein (NP), is the most abundant viral protein in the infected cell and within the viral nucleocapsid. It is tightly associated with the viral RNA in the nucleocapsid, and during the lifecycle of the virus is essential for transcription, RNA replication, genome packaging and nucleocapsid assembly prior to membrane encapsulation. The structure of the unique C-terminal globular domain of the NP from EBOV has recently been determined and shown to be structurally unrelated to any other known protein [Dziubańska et al. (2014), Acta Cryst. D70, 2420-2429]. In this paper, a study of the C-terminal domains from the NP from the remaining four species of Ebolavirus, as well as from the MARV strain of Marburgvirus, is reported. As expected, the crystal structures of the BDBV and TAFV proteins show high structural similarity to that from EBOV, while the MARV protein behaves like a molten globule with a core residual structure that is significantly different from that of the EBOV protein. PMID:26894534

  17. Ebola Virus Disease Outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and Outcomes

    PubMed Central

    Kratz, Thomas; Roddy, Paul; Tshomba Oloma, Antoine; Jeffs, Benjamin; Pou Ciruelo, Diana; de la Rosa, Olimpia; Borchert, Matthias

    2015-01-01

    Data collected during the 2012 Ebola virus disease (EVD) epidemic in the Democratic Republic of the Congo were analysed for clinical signs, symptoms and case fatality of EVD caused by Bundibugyo virus (BDBV), establishment of differential diagnoses, description of medical treatment and evaluation of the quality of clinical documentation. In a quantitative observational prospective study, global epidemiological data from 52 patients (34 patients within the community, 18 patients treated in the Ebola Treatment Centre) were entered anonymously into a database, subsequently matched and analysed. Relevant findings include an over-representation of females among community EVD cases (85.3%) and of community EVD cases in the age group of 15-54 years (82.4%). All ETC patients had fever (55.6% of all 18 ETC patients during their hospital stay) or self-reported fever (88.2% upon admission) at some point of time during their illness. Major symptoms of ETC patients during hospital stay included asthenia (82.4%), anorexia (82.4%), myalgia (70.6%), sore throat/difficulty swallowing (70.6%), arthralgia (76.5%) and nausea (70.6%). Gastrointestinal signs and symptoms (nausea, diarrhoea, vomiting) (76.4%) as well as general pain (94.1%) were frequent in ETC patients. The median duration of EVD was 18 days, while the mean incubation period was 11.3 days. Differential diagnosis of EVD included malaria (28.3%), intestinal parasitosis (10.9%), and infectious syndrome (10.9%). There was also an important variation in clinical evolvement. Quality of documentation was adversely affected by the way patient file contents were transferred from inside to outside the high-risk zone, entailing a mean mismatch value of 27.3% between patient file contents inside vs. outside the high-risk zone. This study adds further description of EVD (frequently non-specific signs and symptoms, non frequent bleeding, a long incubation period, long duration of disease) and emphasizes the need for improving clinical monitoring and documentation in EVD outbreak settings. PMID:26107529

  18. The effect of Ebola Virus Disease outbreak on hand washing among secondary school students in Ondo State Nigeria, October, 2014

    PubMed Central

    Ilesanmi, Olayinka Stephen; Alele, Faith Osaretin

    2015-01-01

    Introduction Hand washing with soap and water is one of the cheapest, most effective ways of limiting the spread of Ebola Virus Disease (EVD). Despite its importance the prevalence of hand washing was low before the EVD outbreak in Nigeria. This study aimed at determining the factors associated with improved hand washing practices following the EVD outbreak. Methods A descriptive cross sectional study of 440 students from a secondary school in Owo, Ondo State was done. Data was collected in October 2014 when Nigeria was yet to be declared EVD free. Systematic random sampling was used. A semi-structured, interviewer administered questionnaire was used. Data was analysed with epi info version 7, descriptive statistics were done, Chi square test was used for the assessment of significant associations between proportions. Determinants of good hand washing practices was identified using logistics regression analysis at 5% level of significance. Results Of 440 respondents, mean age was 13.71.9 years. Females were 48.2%. Only 4.6% have never heard of Ebola Virus Disease.Level of hand washing with soap and water improved by62.6%. Significant improvement in hand washing was in 75.8% of those who heard through social media (p < 0.001), 70.5% of Newspaper readers(p < 0.001), 65.6% of radio listeners (p = 0.001), 75.4% of family members p < 0.001, 76.3% talk in church p < 0.001, 77.6% peers p = 0.02, 72.4% TV p < 0.001.Change in hand washing practices was associated with watching television (AOR: 2.2; CI 95%: 1.1-4.3) and listening to health education in church (AOR: 2.4; CI 95%: 1.2-4.7).Major reason for change in hand washing practices was because of EVD deadly nature, 170(40.5%). Conclusion Watching health education messages on television and listening to it in church are the determinants of change in hand washing practices. Promotion of hand washing with soap and water needs to be sustained to prevent other diseases. Training of students on prevention of EVD was conducted in selected schools. PMID:26740852

  19. A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus.

    PubMed

    McCarthy, Stephen D S; Majchrzak-Kita, Beata; Racine, Trina; Kozlowski, Hannah N; Baker, Darren P; Hoenen, Thomas; Kobinger, Gary P; Fish, Eleanor N; Branch, Donald R

    2016-01-01

    To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs), requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs) IFN-α and IFN-ß, a panel of viral polymerase inhibitors (lamivudine (3TC), zidovudine (AZT) tenofovir (TFV), favipiravir (FPV), the active metabolite of brincidofovir, cidofovir (CDF)), and the estrogen receptor modulator, toremifene (TOR), in inhibiting viral replication in dose-response and time course studies. We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-ß inhibited viral replication 24 hours post-infection (IC50 0.038μM and 0.016μM, respectively). 3TC, AZT and TFV inhibited Ebola replication when used alone (50-62%) or in combination (87%). They exhibited lower IC50 (0.98-6.2μM) compared with FPV (36.8μM), when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25-25μM). When dosed >50μM, CDF treatment enhanced viral infection. IFN-ß exhibited strong synergy with 3TC (97.3% inhibition) or in triple combination with 3TC and AZT (95.8% inhibition). This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug resistance. PMID:26752302

  20. A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus

    PubMed Central

    McCarthy, Stephen D. S.; Majchrzak-Kita, Beata; Racine, Trina; Kozlowski, Hannah N.; Baker, Darren P.; Hoenen, Thomas; Kobinger, Gary P.; Fish, Eleanor N.; Branch, Donald R.

    2016-01-01

    To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs), requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs) IFN-α and IFN-ß, a panel of viral polymerase inhibitors (lamivudine (3TC), zidovudine (AZT) tenofovir (TFV), favipiravir (FPV), the active metabolite of brincidofovir, cidofovir (CDF)), and the estrogen receptor modulator, toremifene (TOR), in inhibiting viral replication in dose-response and time course studies. We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-ß inhibited viral replication 24 hours post-infection (IC50 0.038μM and 0.016μM, respectively). 3TC, AZT and TFV inhibited Ebola replication when used alone (50–62%) or in combination (87%). They exhibited lower IC50 (0.98–6.2μM) compared with FPV (36.8μM), when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25–25μM). When dosed >50μM, CDF treatment enhanced viral infection. IFN-ß exhibited strong synergy with 3TC (97.3% inhibition) or in triple combination with 3TC and AZT (95.8% inhibition). This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug resistance. PMID:26752302

  1. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.

    PubMed

    Qiu, Xiangguo; Wong, Gary; Audet, Jonathan; Bello, Alexander; Fernando, Lisa; Alimonti, Judie B; Fausther-Bovendo, Hugues; Wei, Haiyan; Aviles, Jenna; Hiatt, Ernie; Johnson, Ashley; Morton, Josh; Swope, Kelsi; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Kim, Do; Pauly, Michael H; Velasco, Jesus; Pettitt, James; Olinger, Gene G; Whaley, Kevin; Xu, Bianli; Strong, James E; Zeitlin, Larry; Kobinger, Gary P

    2014-10-01

    Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use. PMID:25171469

  2. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp™

    PubMed Central

    Qiu, Xiangguo; Wong, Gary; Audet, Jonathan; Bello, Alexander; Fernando, Lisa; Alimonti, Judie B.; Fausther-Bovendo, Hugues; Wei, Haiyan; Aviles, Jenna; Hiatt, Ernie; Johnson, Ashley; Morton, Josh; Swope, Kelsi; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Kim, Do; Pauly, Michael H.; Velasco, Jesus; Pettitt, James; Olinger, Gene G.; Whaley, Kevin; Xu, Bianli; Strong, James E.; Zeitlin, Larry; Kobinger, Gary P.

    2014-01-01

    Without an approved vaccine or treatment, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp™), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viremia, and abnormalities in blood count and chemistry were evident in many animals before ZMapp™ intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal hemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp™ is cross-reactive with the Guinean variant of Ebola. ZMapp™ currently exceeds all previous descriptions of efficacy with other therapeutics, and results warrant further development of this cocktail for clinical use. PMID:25171469

  3. Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease

    PubMed Central

    Misasi, John; Sullivan, Nancy J.

    2014-01-01

    Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and non-human primates. Ebola protein interactions with host cellular proteins disrupt Type I and Type II interferon responses, RNAi anti-viral responses, antigen presentation, T-cell mediated antibody responses, humoral antibodies and cell mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and “cytokine storm” that is characteristic of fatal ebolavirus infection. Here we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade anti-viral defenses. PMID:25417101

  4. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    DOE PAGESBeta

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; et al

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludesmore » a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.« less

  5. The development of a protocol for post-mortem management of Ebola virus disease in the setting of developed countries.

    PubMed

    Leditschke, Jodie; Rose, Toby; Cordner, Stephen; Woodford, Noel; Pollanen, Michael

    2015-06-01

    The management of the recent Ebola virus disease (EVD) epidemic continues to pose currently insuperable challenges to health care providers in the resource-deprived countries of West Africa. In an age where air travel facilitates rapid movement of people between countries and continents, there is an urgent requirement for health systems around the globe to develop management strategies and protocols in the event that EVD cases are suspected or confirmed. Departments of forensic pathology play an important, and underestimated, role in public health service delivery, particularly at times of novel infectious disease emergence. This role can include disease identification, characterization, and notification, as well as close engagement with agencies responsible for disease surveillance and treatment provision. A mass outbreak of EVD in the Western world is considered highly unlikely; however, there is clear responsibility on departments of forensic pathology to develop protocols for rapid assessment of sporadic or suspected cases while ensuring the health and safety of mortuary and pathology personnel. The Ontario Forensic Pathology Service and the Victorian Institute of Forensic Medicine have collaborated on the development of a protocol for management of EVD cases presenting at a scene or in the mortuary. It is hoped that this trans-national, inter-departmental exercise will serve as a model for future co-operative endeavors. The protocol has been distributed to forensic pathology departments around Australia and may be modified to accommodate local resource capabilities. PMID:25616524

  6. Preparation of an intensive care unit in France for the reception of a confirmed case of Ebola virus infection.

    PubMed

    Dubost, Clément; Pasquier, Pierre; Kearns, Kévin; Ficko, Cécile; Rapp, Christophe; Wolff, Michel; Richard, Jean-Christophe; Diehl, Jean-Luc; Le Tulzo, Yves; Mérat, Stéphane

    2015-12-01

    The current Ebola Virus Disease (EVD) outbreak in West Africa is a major challenge for the worldwide medical community. On April 29th 2015, the World Health Organization (WHO) declared 26,277 infected cases; among them, 10,884 have deceased. The epidemic is still ongoing, particularly in Sierra Leone. It is now clear that northern countries will be implicated in the care of EVD patients, both in the field and back at home. Because of the severity of EVD, a fair amount of patients may require intensive care. It is highly probable that intensive care would be able to significantly reduce the mortality linked with EVD. The preparation of a modern Intensive Care Unit (ICU) to treat an EVD patient in good conditions requires time and specific equipment. The cornerstone of this preparation includes two main goals: treating the patient and protecting healthcare providers. Staff training is time consuming and must be performed far in advance of patient arrival. To be efficient, preparation should be planned at a national level with help from public authorities, as was the case in France during the summer of 2014. Due to the severity of the disease, the high risk of transmission and scarce knowledge on EVD treatment, our propositions are necessarily original and innovative. Our review includes four topics: a brief report on the actual outbreak, where to receive and hospitalize the patients, the specific organization of the ICU and finally ethical aspects. PMID:26620545

  7. Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics

    PubMed Central

    Sanchez-Lockhart, Mariano; Andersen, Kristian G.; Gire, Stephen; Park, Daniel J.; Sealfon, Rachel; Lin, Aaron E.; Wohl, Shirlee; Sabeti, Pardis C.

    2015-01-01

    ABSTRACT  Until recently, Ebola virus (EBOV) was a rarely encountered human pathogen that caused disease among small populations with extraordinarily high lethality. At the end of 2013, EBOV initiated an unprecedented disease outbreak in West Africa that is still ongoing and has already caused thousands of deaths. Recent studies revealed the genomic changes this particular EBOV variant undergoes over time during human-to-human transmission. Here we highlight the genomic changes that might negatively impact the efficacy of currently available EBOV sequence-based candidate therapeutics, such as small interfering RNAs (siRNAs), phosphorodiamidate morpholino oligomers (PMOs), and antibodies. Ten of the observed mutations modify the sequence of the binding sites of monoclonal antibody (MAb) 13F6, MAb 1H3, MAb 6D8, MAb 13C6, and siRNA EK-1, VP24, and VP35 targets and might influence the binding efficacy of the sequence-based therapeutics, suggesting that their efficacy should be reevaluated against the currently circulating strain. PMID:25604787

  8. HSPA5 is an essential host factor for Ebola virus infection.

    PubMed

    Reid, St Patrick; Shurtleff, Amy C; Costantino, Julie A; Tritsch, Sarah R; Retterer, Cary; Spurgers, Kevin B; Bavari, Sina

    2014-09-01

    Development of novel strategies targeting the highly virulent ebolaviruses is urgently required. A proteomic study identified the ER chaperone HSPA5 as an ebolavirus-associated host protein. Here, we show using the HSPA5 inhibitor (-)- epigallocatechin gallate (EGCG) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. Furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal infection model. These findings demonstrate that HSPA5 is vital for replication and can serve as a viable target for the design of host-based countermeasures. PMID:25017472

  9. Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus.

    PubMed

    Mire, Chad E; Matassov, Demetrius; Geisbert, Joan B; Latham, Theresa E; Agans, Krystle N; Xu, Rong; Ota-Setlik, Ayuko; Egan, Michael A; Fenton, Karla A; Clarke, David K; Eldridge, John H; Geisbert, Thomas W

    2015-04-30

    The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primates against ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first-generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately tenfold lower vaccine-associated viraemia compared to the first-generation vaccine and both provided complete, single-dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV. PMID:25853476

  10. Single dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus

    PubMed Central

    Geisbert, Joan B.; Latham, Theresa E.; Ag