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

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’.

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Catching Chances: The Movement to Be on the Ground and Research Ready before an Outbreak

Viruses ◽

10.3390/v10080439 ◽

2018 ◽

Vol 10 (8) ◽

pp. 439 ◽

Cited By ~ 5

Author(s):

David Brett-Major ◽

James Lawler

Keyword(s):

West Africa ◽

Ebola Virus ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

Virus Disease ◽

Marburg Virus ◽

Just In Time ◽

The West ◽

The World ◽

Medical Countermeasures

After more than 28,000 Ebola virus disease cases and at least 11,000 deaths in West Africa during the 2014–2016 epidemic, the world remains without a licensed vaccine or therapeutic broadly available and demonstrated to alleviate suffering. This deficiency has been felt acutely in the two, short, following years with two Ebola virus outbreaks in the Democratic Republic of Congo (DRC), and a Marburg virus outbreak in Uganda. Despite billions of U.S. dollars invested in developing medical countermeasures for filoviruses in the antecedent decades, resulting in an array of preventative, diagnostic, and therapeutic products, none are available on commercial shelves. This paper explores why just-in-time research efforts in the field during the West Africa epidemic failed, as well as some recent initiatives to prevent similarly lost opportunities.

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Clinical and epidemiological features of the disease caused by the Ebola virus, at the present stage: pathogenetic basis of therapy

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid40848 ◽

2015 ◽

Vol 20 (1) ◽

pp. 32-39

Author(s):

O. I Kiselev ◽

L. M Tsybalova ◽

E. G Deeva ◽

V. V Tsvetkov ◽

G. S Golobokov ◽

...

Keyword(s):

West Africa ◽

Coming Out ◽

Ebola Virus ◽

Virus Disease ◽

Disease Outbreaks ◽

Multiple Organ ◽

World Health ◽

Pathogenetic Therapy ◽

Sporadic Cases ◽

Health Organization

Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever is severe acute infectious diseases accompanied by the development of severe systemic inflammatory response followed by the addition of disseminated intravascular coagulation and multiple organ failure. Since 1976 in Africa regularly observed disease outbreaks among humans caused by different types of Ebola virus. Modern epidemic in West Africa began in Guinea in February 2014 and is still going on, coming out of the country and distributed in Liberia, Sierra Leone and Nigeria. According to the World Health Organization (WHO) on December 14, 2014 recorded 18,603 cases of them confirmed EVD 11807, fatal 6915. From July 2014 to currently registered sporadic cases EVD among health care workers caring for patients, as well as among tourists returning from countries affected by the epidemic is already outside of West Africa. Due to the limited use of specific antiviral therapy with special attention to the management ofpatients with EVD should be paid to the intensive and timely pathogenetic therapy. Today, the only way to reduce morbidity and mortality among people from EVD is awareness on the risk factors of infection and the use ofpersonal protective measures.

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A systematic review and meta-analysis of patient data from the West Africa (2013–16) Ebola virus disease epidemic

Clinical Microbiology and Infection ◽

10.1016/j.cmi.2019.06.032 ◽

2019 ◽

Vol 25 (11) ◽

pp. 1307-1314 ◽

Cited By ~ 1

Author(s):

A.M. Rojek ◽

A. Salam ◽

R.J. Ragotte ◽

E. Liddiard ◽

A. Elhussain ◽

...

Keyword(s):

Systematic Review ◽

West Africa ◽

Ebola Virus ◽

Virus Disease ◽

Meta Analysis ◽

Patient Data ◽

Ebola Virus Disease ◽

The West

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

Prehospital and Disaster Medicine ◽

10.1017/s1049023x20000333 ◽

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.

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Descriptive analyses and risk of death due to Ebola Virus Disease, West Africa, 2014

The Journal of Infection in Developing Countries ◽

10.3855/jidc.6484 ◽

2015 ◽

Vol 9 (12) ◽

pp. 1298-1307 ◽

Cited By ~ 8

Author(s):

Folorunso Oludayo Fasina ◽

Olubukola T. Adenubi ◽

Samuel T. Ogundare ◽

Aminu Shittu ◽

Dauda G. Bwala ◽

...

Keyword(s):

West Africa ◽

Sierra Leone ◽

Healthcare Workers ◽

Ebola Virus ◽

Virus Disease ◽

Healthcare Delivery ◽

Ebola Virus Disease ◽

World Health ◽

Public Healthcare ◽

Risk Of Death

Introduction: Since the first case of Ebola virus disease (EVD) in Guinea in 2013, major outbreaks have been reported in West Africa. Methodology: Cases and fatalities of EVD caused by Zaire Ebola virus (ZEBOV) were evaluated, and the risks of dying in the general population and in healthcare workers were assessed. Results: The case fatality rate estimated for EVD was 76.4% in 20 studies. Cumulative proportion of fatal cases in West Africa was 42.9%, 30.1%, and 64.2% in Liberia, Sierra Leone, and Guinea, respectively. The proportion of total deaths in Liberia, Sierra Leone, and Guinea was 42.5%, 35.8%, and 21.6%, respectively. Healthcare workers were at higher risk of dying compared with the general public, and the same applied to intense transmission countries and to countries with sufficient bed capacities. The declaration of a health emergency “out-of-control” situation by the World Health Organization on 8 August 2014 reduced the risk of death among patients. Factors including deplorable healthcare delivery infrastructure in war-ravaged regions of Africa, the impotence of governments to enforce public health regulations, and the loss of confidence in public healthcare delivery programs were key among others factors that enhanced the spread and magnitude of outbreaks. Conclusions: The findings underscore the need for an overall re-appraisal of the healthcare systems in African countries and the ability to cope with widespread epidemic challenges. Outbreaks like that of Ebola diseases should be handled not just as a medical emergency but also a socio-economic problem with significant negative economic impacts.

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Ebola and Other Filoviruses

10.1093/med/9780190604813.003.0002 ◽

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.

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A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups

Science Translational Medicine ◽

10.1126/scitranslmed.aaw1049 ◽

2019 ◽

Vol 11 (520) ◽

pp. eaaw1049 ◽

Cited By ~ 9

Author(s):

Lori E. Dodd ◽

Dean Follmann ◽

Michael Proschan ◽

Jing Wang ◽

Denis Malvy ◽

...

Keyword(s):

West Africa ◽

Mortality Risk ◽

Clinical Studies ◽

Ebola Virus ◽

Virus Disease ◽

Disease Outbreaks ◽

Ebola Virus Disease ◽

Control Group ◽

Control Groups ◽

Randomized Control

Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013–2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.

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The 2014 Ebola virus disease outbreak in West Africa

Journal of General Virology ◽

10.1099/vir.0.067199-0 ◽

2014 ◽

Vol 95 (8) ◽

pp. 1619-1624 ◽

Cited By ~ 139

Author(s):

Derek Gatherer

Keyword(s):

West Africa ◽

Ebola Virus ◽

Virus Disease ◽

Single Case ◽

Atlantic Coast ◽

Urban Setting ◽

Ebola Virus Disease ◽

World Health ◽

The Republic ◽

Health Organization

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

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Incorporating health workers’ perspectives into a WHO guideline on personal protective equipment developed during an Ebola virus disease outbreak

F1000Research ◽

10.12688/f1000research.12922.2 ◽

2018 ◽

Vol 7 ◽

pp. 45 ◽

Cited By ~ 1

Author(s):

Saskia Den Boon ◽

Constanza Vallenas ◽

Mauricio Ferri ◽

Susan L. Norris

Keyword(s):

Public Health ◽

West Africa ◽

Personal Protective Equipment ◽

Ebola Virus ◽

Expert Panel ◽

Health Workers ◽

Virus Disease ◽

Ebola Virus Disease ◽

World Health ◽

Protective Equipment

Background: Ebola virus disease (EVD) health facility transmission can result in infection and death of health workers. The World Health Organization (WHO) supports countries in preparing for and responding to public health emergencies, which often require developing new guidance in short timelines with scarce evidence. The objective of this study was to understand frontline physicians’ and nurses’ perspectives about personal protective equipment (PPE) use during the 2014-2016 EVD outbreak in West Africa and to incorporate these findings into the development process of a WHO rapid advice guideline. Methods: We surveyed frontline physicians and nurses deployed to West Africa between March and September of 2014. Results: We developed the protocol, obtained ethics approval, delivered the survey, analysed the data and presented the findings as part of the evidence-to-decision tables at the expert panel meeting where the recommendations were formulated within eight weeks. Forty-four physicians and nurses responded to the survey. They generally felt at low or extremely low risk of virus transmission with all types of PPE used. Eye protection reduced the ability to provide care, mainly due to impaired visibility because of fogging. Heat and dehydration were a major issue for 76% of the participants using goggles and for 64% using a hood. Both gowns and coveralls were associated with significant heat stress and dehydration. Most participants (59%) were very confident that they were using PPE correctly. Conclusion: Our study demonstrated that it was possible to incorporate primary data on end-users’ preferences into a rapid advice guideline for a public health emergency in difficult field conditions. Health workers perceived a balance between transmission protection and ability to care for patients effectively while wearing PPE. These findings were used by the guideline development expert panel to formulate WHO recommendations on PPE for frontline providers caring for EVD patients in outbreak conditions.

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An integrative review of the limited evidence on international travel bans as an emerging infectious disease disaster control measure

Journal of Emergency Management ◽

10.5055/jem.2020.0446 ◽

2020 ◽

Vol 18 (1) ◽

pp. 7-14 ◽

Cited By ~ 16

Author(s):

Nicole A. Errett, PhD, MSPH ◽

Lauren M. Sauer, MS ◽

Lainie Rutkow, PhD, JD, MPH

Keyword(s):

Ebola Virus ◽

Virus Disease ◽

Control Measure ◽

Middle Eastern ◽

Emerging Infectious Diseases ◽

Geographic Region ◽

International Travel ◽

Control Measures ◽

Integrative Review ◽

Global Spread

In our increasingly interconnected world, the potential for emerging infectious diseases (EIDs) to spread globally is of paramount concern. Travel bans—herein defined as the complete restriction of travel from at least one geographic region to at least one other international geographic region—are a potential policy solution to control the global spread of disease. The social, economic, and health-related consequences of travel bans, as well as the available evidence on the effectiveness of travel restrictions in preventing the global spread of influenza, have been previously described. However, the effectiveness of travel bans in reducing the spread of noninfluenza EIDs, characterized by different rates and modes of transmission, is less well understood. This study employs an integrative review approach to summarize the minimal evidence on effectiveness of travel bans to decrease the spread of severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS), Ebola virus disease (EVD), and Zika virus disease (ZVD). We describe and qualify the evidence presented in six modeling studies that assess the effectiveness of travel bans in controlling these noninfluenza EID events. We conclude that there is an urgent need for additional research to inform policy decisions on the use of travel bans and other control measures to control oninfluenza EIDs in advance of the next outbreak.

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