Ebola and Other Filoviruses

2018 ◽  
Author(s):  
Lisa M. Bebell
Keyword(s):  
Ebola Virus ◽  
Inflammatory Responses ◽  
Virus Disease ◽  
Treatment Strategies ◽  
Disease Outbreaks ◽  
Marburg Virus ◽  
Residual Effects ◽  
Long Term Outcomes ◽  
Pediatric Vaccination

Congenital and pediatric Ebola virus disease (EVD) and Marburg virus disease (MVD) are severe, even lethal infections. Historically, children have been underrepresented in filovirus disease outbreaks, and evidence-based treatment strategies are lacking. Existing data suggest that case fatalities are highest among children under four years of age, which is partially explained by higher virus concentrations in young children. Prevention and aggressive resuscitation, nutrition, and supportive care are the mainstays of management until filovirus-specific therapies can be developed. Differences in pediatric immune and inflammatory responses may necessitate unique approaches to pediatric vaccination and treatment. There are minimal safety or immunogenicity data in children, a crucial knowledge gap that must be addressed in future trials. Studying pediatric survivors of the 2014–2016 West Africa EVD outbreak will provide much-needed data on long-term outcomes and residual effects of filovirus disease while we await effective filovirus-specific vaccines and therapies.

scholarly journals Offering patients more: how the West Africa Ebola outbreak can shape innovation in therapeutic research for emerging and epidemic infections

2017 ◽  
Vol 372 (1721) ◽  
pp. 20160294 ◽  
Author(s):  
Amanda M. Rojek ◽  
Peter W. Horby
Keyword(s):  
West Africa ◽  
Ebola Virus ◽  
Virus Disease ◽  
Nipah Virus ◽  
Emerging Infectious Diseases ◽  
Disease Outbreaks ◽  
International Travel ◽  
Marburg Virus ◽  
World Health ◽  
The West

Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections. This is especially the case since there are no licensed therapeutics for some of the diseases considered by the World Health Organization as most likely to cause severe outbreaks—including Middle East respiratory syndrome coronavirus, Marburg virus, Crimean Congo haemorrhagic fever and Nipah virus. EVD, therefore, provides a timely exemplar to discuss the barriers, enablers and incentives needed to find effective treatments in advance of health emergencies caused by emerging infectious diseases. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.

scholarly journals Dose-dependent response to infection with Ebola virus in the ferret model and evidence of viral evolution in the eye.

2021 ◽  
Author(s):  
Robert J. Watson ◽  
Julia Tree ◽  
Susan A. Fotheringham ◽  
Yper Hall ◽  
Xiaofeng Dong ◽  
...  
Keyword(s):  
Large Scale ◽  
Ebola Virus ◽  
Virus Disease ◽  
Viral Evolution ◽  
Clinical Signs ◽  
Disease Outbreaks ◽  
The Body ◽  
Medical Interventions ◽  
Persistent Virus

Filoviruses are high consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterised animal models for the assessment of anti-viral agents and vaccines. Following large scale Ebola virus disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterisation of the ferret as a model for Ebola virus (EBOV) infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral and rectal swabs, and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long term EBOV persistence in immune-privileged sites. Importance Recent re-emergence of Ebola in Guinea that caused over 28000 cases between 2013-2016 has been linked to the original virus from that region. It appears the virus has remained in the region for at least 5 years and is likely to have been maintained in humans. Persistence of Ebola in areas of the body for extended periods of time has been observed such as in the eye and semen. Despite the importance of re-introduction of Ebola from this route, such events are rare in the population which makes studying medical interventions to clear persistent virus difficult. We studied various doses of Ebola in ferrets and detected virus in the eyes of most ferrets. We believe this model will enable the study of medical interventions that promote clearance of Ebola virus from sites that promote persistence.

Treatment strategies and long-term outcomes for primary intramedullary spinal germinomas: an institutional experience

2014 ◽  
Vol 121 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Liang Wu ◽  
Tao Yang ◽  
Xiaofeng Deng ◽  
Chenlong Yang ◽  
Jingyi Fang ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Long Term Outcomes ◽  
Institutional Experience

scholarly journals Virus-Vectored Ebola Vaccines

Acta Naturae ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 4-11 ◽  
Author(s):  
I. V. Dolzhikova ◽  
E. A. Tokarskaya ◽  
A. S. Dzharullaeva ◽  
A. I. Tukhvatulin ◽  
D. V. Shcheblyakov ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Immune Response ◽  
West Africa ◽  
Protective Immunity ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Virus Disease ◽  
Genetically Engineered ◽  
Preclinical Trials

The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014-2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.

Palliative care for children with communicable illnesses

2021 ◽  
pp. 304-322
Author(s):  
Michelle Meiring ◽  
Tonya Arscott-Mills
Keyword(s):  
Palliative Care ◽  
Ebola Virus ◽  
Virus Disease ◽  
Communicable Disease ◽  
Disease Outbreaks ◽  
Communicable Diseases ◽  
Humanitarian Response ◽  
Care Approach ◽  
Health Related ◽  
Communicable Illness

Whilst non-communicable diseases provided the impetus for the development of children’s palliative care (CPC) in the developed world, it was a single communicable illness human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) that was the catalyst for the development of many CPC programmes in the developing world. Whilst considerable gains have been made in preventing and controlling paediatric AIDS globally, there is still benefit to an integrated palliative care approach to the care of these children and especially for those living in countries without access to anti-retrovirals. Furthermore, there are many other communicable diseases associated with significant health-related suffering in children that could benefit from palliative care. This chapter proposes grouping these diseases using the well-known Association for Children with Terminal Conditions (ACT) categorization and discusses examples of important communicable diseases in each category. The need for improved CPC as part of the humanitarian response to acute communicable disease outbreaks such as Ebola virus disease is also explored.

scholarly journals Short- and long-term outcomes of treatment strategies for isolated penetrating aortic ulcers (PAUs)

2020 ◽  
Vol 59 (5) ◽  
pp. e31
Author(s):  
Safa Salim ◽  
Rossella Locci ◽  
Guy Martin ◽  
Rick Gibbs ◽  
Michael Jenkins ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Long Term Outcomes ◽  
Short And Long Term

The Epidemiological Presentation Pattern of Ebola Virus Disease Outbreaks: Changes from 1976 to 2019

2020 ◽  
Vol 35 (3) ◽  
pp. 247-253
Author(s):  
Pedro Arcos González ◽  
Ángel Fernández Camporro ◽  
Anneli Eriksson ◽  
Carmen Alonso Llada
Keyword(s):  
At Risk ◽  
Ebola Virus ◽  
Virus Disease ◽  
Disease Outbreaks ◽  
Case Fatality ◽  
Ebola Virus Disease ◽  
World Health ◽  
Study Objective ◽  
Population At Risk ◽  
Case Fatality Ratio

AbstractIntroduction:Ebola Virus Disease (EVD) is the international health emergency paradigm due to its epidemiological presentation pattern, impact on public health, resources necessary for its control, and need for a national and international response.Study Objective:The objective of this work is to study the evolution and progression of the epidemiological presentation profile of Ebola disease outbreaks since its discovery in 1976 to the present, and to explore the possible reasons for this evolution from different perspectives.Methods:Retrospective observational study of 38 outbreaks of Ebola disease occurred from 1976 through 2019, excluding laboratory accidents. United Nations agencies and programs; Ministries of Health; the US Centers for Disease Control and Prevention (CDC); ReliefWeb; emergency nongovernmental organizations; and publications indexed in PubMed, EmBase, and Clinical Key have been used as sources of data. Information on the year of the outbreak, date of beginning and end, duration of the outbreak in days, number of cases, number of deaths, population at risk, geographic extension affected in Km2, and time of notification of the first cases to the World Health Organization (WHO) have been searched and analyzed.Results:Populations at risk have increased (P = .024) and the geographical extent of Ebola outbreaks has grown (P = .004). Reporting time of the first cases of Ebola to WHO has been reduced (P = .017) and case fatality (P = .028) has gone from 88% to 62% in the period studied. There have been differences (P = .04) between the outbreaks produced by the Sudan and Zaire strains of the virus, both in terms of duration and case fatality ratio (Sudan strain 74.5 days on average and 62.7% of case fatality ratio versus Zaire strain with 150 days on average and 55.4% case fatality ratio).Conclusion:There has been a change in the epidemiological profile of the Ebola outbreaks from 1976 through 2019 with an increase in the geographical extent of the outbreaks and the population at risk, as well as a significant decrease in the outbreaks case fatality rate. There have been advances in the detection and management capacity of outbreaks, and the notification time to the WHO has been reduced. However, there are social, economic, cultural, and political obstacles that continue to greatly hinder a more efficient epidemiological approach to Ebola disease, mainly in Central Africa.

scholarly journals Correction to ‘Long-term wildlife mortality surveillance in northern Congo: a model for the detection of Ebola virus disease epizootics’

2019 ◽  
Vol 374 (1786) ◽  
pp. 20190658
Author(s):  
Eeva Kuisma ◽  
Sarah H. Olson ◽  
Kenneth N. Cameron ◽  
Patricia E. Reed ◽  
William B. Karesh ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Ebola Virus Disease ◽  
Mortality Surveillance ◽  
Wildlife Mortality

scholarly journals Macaque Monoclonal Antibodies Targeting Novel Conserved Epitopes within Filovirus Glycoprotein

2015 ◽  
Vol 90 (1) ◽  
pp. 279-291 ◽  
Author(s):  
Zhen-Yong Keck ◽  
Sven G. Enterlein ◽  
Katie A. Howell ◽  
Hong Vu ◽  
Sergey Shulenin ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Disease ◽  
Protective Efficacy ◽  
Hemorrhagic Fever ◽  
Marburg Virus ◽  
Human Pathogens ◽  
Content Type ◽  
The Core

ABSTRACTFiloviruses cause highly lethal viral hemorrhagic fever in humans and nonhuman primates. Current immunotherapeutic options for filoviruses are mostly specific to Ebola virus (EBOV), although other members ofFiloviridaesuch as Sudan virus (SUDV), Bundibugyo virus (BDBV), and Marburg virus (MARV) have also caused sizeable human outbreaks. Here we report a set of pan-ebolavirus and pan-filovirus monoclonal antibodies (MAbs) derived from cynomolgus macaques immunized repeatedly with a mixture of engineered glycoproteins (GPs) and virus-like particles (VLPs) for three different filovirus species. The antibodies recognize novel neutralizing and nonneutralizing epitopes on the filovirus glycoprotein, including conserved conformational epitopes within the core regions of the GP1 subunit and a novel linear epitope within the glycan cap. We further report the first filovirus antibody binding to a highly conserved epitope within the fusion loop of ebolavirus and marburgvirus species. One of the antibodies binding to the core GP1 region of all ebolavirus species and with lower affinity to MARV GP cross neutralized both SUDV and EBOV, the most divergent ebolavirus species. In a mouse model of EBOV infection, this antibody provided 100% protection when administered in two doses and partial, but significant, protection when given once at the peak of viremia 3 days postinfection. Furthermore, we describe novel cocktails of antibodies with enhanced protective efficacy compared to individual MAbs. In summary, the present work describes multiple novel, cross-reactive filovirus epitopes and innovative combination concepts that challenge the current therapeutic models.IMPORTANCEFiloviruses are among the most deadly human pathogens. The 2014-2015 outbreak of Ebola virus disease (EVD) led to more than 27,000 cases and 11,000 fatalities. While there are five species ofEbolavirusand several strains of marburgvirus, the current immunotherapeutics primarily target Ebola virus. Since the nature of future outbreaks cannot be predicted, there is an urgent need for therapeutics with broad protective efficacy against multiple filoviruses. Here we describe a set of monoclonal antibodies cross-reactive with multiple filovirus species. These antibodies target novel conserved epitopes within the envelope glycoprotein and exhibit protective efficacy in mice. We further present novel concepts for combination of cross-reactive antibodies against multiple epitopes that show enhanced efficacy compared to monotherapy and provide complete protection in mice. These findings set the stage for further evaluation of these antibodies in nonhuman primates and development of effective pan-filovirus immunotherapeutics for use in future outbreaks.

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