African Ebola Virus Disease Outbreak Research Articles

Neuropsychological long-term sequelae of Ebola virus disease survivors - A systematic review.

The recent West African Ebola virus disease (EVD) outbreak had catastrophic impact on populations, health care systems and economies of the affected countries. Somatic symptoms have been reported to persist long beyond the acute infection. This review was conducted to provide an overview on neuro- and socio-psychological long-term sequelae of EVD survivors. Utilizing Pubmed and PsycInfo databases, a systematic review prepared according to PRISMA guidelines. Only studies reporting quantitative data on neuropsychological sequelae three weeks or later after discharge from the Ebola-treating unit were included. Pooled proportions of common outcomes were calculated. In total, 224 papers were identified, of which 10 were included. Depression, insomnia, fatigue, anxiety and post-traumatic stress were common sequelae in EVD survivors. However, data from high-quality studies were scarce. EVD survivors have been thought to commonly face neuropsychological long-term sequelae. Methodological drawbacks and heterogeneity of current studies limit conclusions of the impact and magnitude of such sequelae. We advocate the preparation of a prospective, controlled cohort study protocol in preparation for a future outbreak.

Novel surveillance methods for the control of Ebola virus disease.

The unprecedented scale of the 2013-2016 West African Ebola virus disease (EVD) outbreak was in a large part due to failings in surveillance: contacts of confirmed cases were not systematically identified, monitored and diagnosed early, and new cases appearing in previously unaffected communities were similarly not rapidly identified, diagnosed and isolated. Over the course of this epidemic, traditional surveillance methods were strengthened and novel methods introduced. The wealth of experience gained, and the systems introduced in West Africa, should be used in future EVD outbreaks, as well as for other communicable diseases in the region and beyond.

Musculoskeletal manifestations of Ebola virus.

The 2014 West African Ebola virus disease outbreak shocked the world as it swept through the region leaving Guinea, Liberia and Sierra Leone struggling to gain control. As the largest Ebola virus disease outbreak to date, there are more survivors in its wake than ever before, with a spectrum of health problems requiring management. Here we review various musculoskeletal manifestations of the virus that can occur both during and after the infection, and consider possible pathogenesis.

Accelerating Vaccine Development During the 2013-2016 West African Ebola Virus Disease Outbreak.

The Ebola virus disease outbreak that began in Western Africa in December 2013 was unprecedented in both scope and spread, and the global response was slower and less coherent than was optimal given the scale and pace of the epidemic. Past experience with limited localized outbreaks, lack of licensed medical countermeasures, reluctance by first responders to direct scarce resources to clinical research, community resistance to outside interventions, and lack of local infrastructure were among the factors delaying clinical research during the outbreak. Despite these hurdles, the global health community succeeded in accelerating Ebola virus vaccine development, in a 5-month interval initiating phase I trials in humans in September 2014 and initiating phase II/III trails in February 2015. Each of the three Ebola virus disease-affected countries, Sierra Leone, Guinea, and Liberia, conducted a phase II/III Ebola virus vaccine trial. Only one of these trials evaluating recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein demonstrated vaccine efficacy using an innovative mobile ring vaccination trial design based on a ring vaccination strategy responsible for eradicating smallpox that reached areas of new outbreaks. Thoughtful and intensive community engagement in each country enabled the critical community partnership and acceptance of the phase II/III in each country. Due to the delayed clinical trial initiation, relative to the epidemiologic peak of the outbreak in the three countries, vaccine interventions may or may not have played a major role in bringing the epidemic under control. Having demonstrated that clinical trials can be performed during a large outbreak, the global research community can now build on the experience to implement trials more rapidly and efficiently in future outbreaks. Incorporating clinical research needs into planning for future health emergencies and understanding what kind of trial designs is needed for reliable results in an epidemic of limited duration should improve global response to future infectious disease outbreaks.

Comprehensive Characterization of Cellular Immune Responses Following Ebola Virus Infection.

The West African Ebola virus disease (EVD) outbreak was the largest EVD outbreak in history. However, data on lymphocyte dynamics and the antigen specificity of T cells in Ebola survivors are scarce, and our understanding of EVD pathophysiology is limited. A case of EVD survival in which the patient cleared Ebola virus (EBOV) infection without experimental drugs allowed for the detailed examination of lymphocyte dynamics. We demonstrate the persistence of T-cell activation well beyond viral clearance and detect EBOV-specific T cells. Our study provides significant insights into lymphocyte specificity during the recovery phase of EVD and may inform novel strategies to treat EVD.

A Brief History of Biocontainment.

Opinion statementThe concept of clinical biocontainment, otherwise known as high-level containment care (HLCC), had its birth among a confluence of near-simultaneous events in 1969. The U.S. Army’s Medical Research Institute of Infectious Diseases (USAMRIID) began construction of the first modern biocontainment unit that year, and opened the two-bed facility, often referred to as “the Slammer” in 1971. Over its 41-year existence, 21 persons exposed to highly hazardous infectious diseases were admitted to the Slammer, but none ever contracted the disease to which they had been exposed. Owing, in part, to this underutilization, some questioned the utility of HLCC units. This concern notwithstanding, Emory University and the University of Nebraska opened HLCC units in civilian academic medical centers in 2004 and 2005, respectively. These units, distinct from conventional infectious disease isolation wards found in most major medical centers, proved their worth during the West African Ebola Virus Disease (EVD) outbreak of 2014–2015. It is our opinion that such units, as well as the parallel high-level containment transport systems necessary to move patients to them, will continue to play an important role in the global response to emerging and highly hazardous contagious pathogens. Moreover, we feel that the lessons derived from their successful operation will lead to improvements in infection control procedures and practices throughout the healthcare system.

Ebola virus disease and critical illness.

As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa.EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death.Males and females have been equally affected, with children (0–14 years of age) accounting for 19 %, young adults (15–44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40–90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission.While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1325-2) contains supplementary material, which is available to authorized users.

Community-based reports of morbidity, mortality, and health-seeking behaviours in four Monrovia communities during the West African Ebola epidemic

ABSTRACTThe goal of this study was to assess morbidity, mortality, and health-seeking behaviours during the 2014 Ebola outbreak in Monrovia, Liberia. This study examined commonly reported symptoms of illness, pre-clinical diagnostic practices, typical healthcare-seeking strategies, and health resources available to populations, in order to identify salient needs and gaps in healthcare that would inform local emergency response efforts. Semi-structured interviews were conducted with household members in four Monrovia neighbourhoods. Researchers used a multi-stage cluster approach to recruit participants. Within 555 households sampled, 505 individuals were reported sick (69%) or recently sick (38%) or deceased (7%). Common self-diagnoses included malaria, hypertension, influenza, typhoid, and Ebola. The most cited health-seeking strategy was to purchase medications from the private sector. Respondents also obtained healthcare from community members known to have medical experience. Findings suggest that non-formal healthcare systems played an important role in managing morbidity during the West African Ebola virus disease (EVD) outbreak. Lay community members engaged in complex assessments of health symptoms and sought biomedical care at rates perhaps higher than anticipated during the response. This study highlights how informal networks of healthcare providers can play an important role in preventing and curbing future emerging disease outbreaks.

An Inactivated Rabies Virus-Based Ebola Vaccine, FILORAB1, Adjuvanted With Glucopyranosyl Lipid A in Stable Emulsion Confers Complete Protection in Nonhuman Primate Challenge Models.

The 2013-2016 West African Ebola virus (EBOV) disease outbreak was the largest filovirus outbreak to date. Over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. The magnitude and international impact of this EBOV outbreak has highlighted the urgent need for a safe and efficient EBOV vaccine. To this end, we demonstrate the immunogenicity and protective efficacy of FILORAB1, a recombinant, bivalent, inactivated rabies virus-based EBOV vaccine, in rhesus and cynomolgus monkeys. Our results demonstrate that the use of the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid A in stable emulsion (GLA-SE) as an adjuvant increased the efficacy of FILORAB1 to 100% protection against lethal EBOV challenge, with no to mild clinical signs of disease. Furthermore, all vaccinated subjects developed protective anti-rabies virus antibody titers. Taken together, these results support further development of FILORAB1/GLA-SE as an effective preexposure EBOV vaccine.

Ebola virus disease in children: towards a better clinical picture and improved management.

Ebola virus disease in children: towards a better clinical picture and improved management.

Aerosol Transmission of Filoviruses.

Filoviruses have become a worldwide public health concern because of their potential for introductions into non-endemic countries through international travel and the international transport of infected animals or animal products. Since it was first identified in 1976, in the Democratic Republic of Congo (formerly Zaire) and Sudan, the 2013–2015 western African Ebola virus disease (EVD) outbreak is the largest, both by number of cases and geographical extension, and deadliest, recorded so far in medical history. The source of ebolaviruses for human index case(s) in most outbreaks is presumptively associated with handling of bush meat or contact with fruit bats. Transmission among humans occurs easily when a person comes in contact with contaminated body fluids of patients, but our understanding of other transmission routes is still fragmentary. This review deals with the controversial issue of aerosol transmission of filoviruses.

Ebola response in Sierra Leone: The impact on children

SummaryThe West African Ebola virus disease (EVD) outbreak is the largest ever seen, with over 28,000 cases and 11,300 deaths since early 2014. The magnitude of the outbreak has tested fragile governmental health systems and non-governmental organizations (NGOs) to their limit. Here we discuss the outbreak in the Western Area of Sierra Leone, the shape of the local response and the impact the response had on caring for children suspected of having contracted EVD. Challenges encountered in providing clinical care to children whilst working in the “Red Zone” where risk of EVD is considered to be highest, wearing full personal protective equipment are detailed. Suggestions and recommendations both for further research and for operational improvement in the future are made, with particular reference as to how a response could be more child-focused.

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

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

Tackling emerging infections: clinical and public health lessons from the West African Ebola virus disease outbreak, 2014–2015

The magnitude of the 2014-2015 West African Ebola virus disease outbreak was unforeseen at its onset and the initial international response was slow. The high mortality and the panic that this outbreak induced had a major effect on health systems. In this article we discuss some of the key public health and clinical lessons from this Ebola outbreak, including combining epidemiology, modelling and anthropology, and the initial evidence for the importance of fluid and antibiotic management.

Clinical features of patients isolated for suspected Ebola virus disease at Connaught Hospital, Freetown, Sierra Leone: a retrospective cohort study

The size of the west African Ebola virus disease outbreak led to the urgent establishment of Ebola holding unit facilities for isolation and diagnostic testing of patients with suspected Ebola virus disease. Following the onset of the outbreak in Sierra Leone, patients presenting to Connaught Hospital in Freetown were screened for suspected Ebola virus disease on arrival and, if necessary, were admitted to the on-site Ebola holding unit. Since demand for beds in this unit greatly exceeded capacity, we aimed to improve the selection of patients with suspected Ebola virus disease for admission by identifying presenting clinical characteristics that were predictive of a confirmed diagnosis. In this retrospective cohort study, we recorded the presenting clinical characteristics of suspected Ebola virus disease cases admitted to Connaught Hospital's Ebola holding unit. Patients were subsequently classified as confirmed Ebola virus disease cases or non-cases according to the result of Ebola virus reverse-transcriptase PCR (EBOV RT-PCR) testing. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of every clinical characteristic were calculated, to estimate the diagnostic accuracy and predictive value of each clinical characteristic for confirmed Ebola virus disease. Between May 29, 2014, and Dec 8, 2014, 850 patients with suspected Ebola virus disease were admitted to the holding unit, of whom 724 had an EBOV RT-PCR result recorded and were included in the analysis. In 464 (64%) of these patients, a diagnosis of Ebola virus disease was confirmed. Fever or history of fever (n=599, 83%), intense fatigue or weakness (n=495, 68%), vomiting or nausea (n=365, 50%), and diarrhoea (n=294, 41%) were the most common presenting symptoms in suspected cases. Presentation with intense fatigue, confusion, conjunctivitis, hiccups, diarrhea, or vomiting was associated with increased likelihood of confirmed Ebola virus disease. Three or more of these symptoms in combination increased the probability of Ebola virus disease by 3·2-fold (95% CI 2·3-4·4), but the sensitivity of this strategy for Ebola virus disease diagnosis was low. In a subgroup analysis, 15 (9%) of 161 confirmed Ebola virus disease cases reported neither a history of fever nor a risk factor for Ebola virus disease exposure. Discrimination of Ebola virus disease cases from patients without the disease is a major challenge in an outbreak and needs rapid diagnostic testing. Suspected Ebola virus disease case definitions that rely on history of fever and risk factors for Ebola virus disease exposure do not have sufficient sensitivity to identify all cases of the disease. None.

When Potentially Lifesaving Drugs are Both Experimental and in Very Short Supply: A Clinician's Story from the Front Lines of the Battle Against Ebola.

On the night of July 31, 2014, Kent Brantly, a physician working with Samaritan’s Purse (Monrovia, Liberia), received a dose of ZMapp (Mapp Pharmaceuticals, San Diego, CA), an experimental cocktail of three Ebola virus glycoproteinspecific monoclonal antibodies, thus becoming the first patient in the west African Ebola virus disease (EVD) outbreak to receive an experimental therapy. He contracted EVD while working in Liberia and became a patient under the direct care of his SIM (Monrovia, Liberia) and Samaritan’s Purse colleagues. Nancy Writebol, a missionary who was also Ebola virus-infected and worked with Brantly at the Eternal Love Winning Africa (ELWA, Monrovia, Liberia) Ebola Treatment Center, was designated to be the sole recipient of ZMapp that night. Brantly had graciously offered to give Writebol the only course of treatment (a full course of treatment is administered in three doses). As one of the physicians overseeing the clinical care of these two patients in Liberia, I examined Brantly and noted his persistent fever, tachypnea, tachycardia, worsening rash, and headache. He was already receiving supportive care including intravenous fluids, antimalarial prophylaxis, and antibiotics per Medecins Sans Frontieres, Geneva, Switzerland, guidelines. Despite these efforts, over several hours, before the scheduled administration of ZMapp to Writebol, Brantly’s condition continued to deteriorate. He was critically ill, and worsening. My colleagues and I had read the original research articles in which ZMapp conferred a survival benefit in animal models when administered early the course of EVD. 1 However, administering an experimental drug whose safety had not been tested in a human clinical trial was daunting and potentially dangerous. As a vial of ZMapp thawed under Writebol’s arm, Lance Plyler, the medical director of the Samaritan’s Purse Disaster Response Unit, who was responsible for obtaining ZMapp from Mapp Pharmaceuticals, was preparing to administer the drug to Writebol. We discussed Brantly’s condition and, given his rapid deterioration, decided to administer a dose of ZMapp. I drew up a dose of dexamethasone to be used in the event he developed an allergic reaction and set it at his bedside. Informed consent was given, and I started the ZMapp infusion. I anxiously waited with physician assistant Allison Rolston, watching for an adverse reaction. Rolston had worked tirelessly for days providing care to dozens of EVD patients. I had been wearing heavy personal protective equipment (PPE) for almost 3 hours, and had to step outside. Tim Mosher, a nurse practitioner, donned PPE and moved to the

Global health security now

The concept of security as an important dimension of health divides opinions. To invoke the idea of security risks giving permission to more authoritarian-minded governments to use health crises as justification for sometimes extreme curbs on liberty or the political, economic, and social rights of citizens. During the Ebola virus disease outbreak, photographs appeared in news media of police brutally attacking the public for breaching curfews. Invoking arguments of global health security might further encourage this kind of violent response. Alternatively, security could more constructively mean protecting and empowering people, a view promulgated by the UN's Commission on Human Security in 2003. 1 Commission on Human SecurityHuman security now. Commission on Human Security, New York2003 Google Scholar This week, The Lancet looks at the implications of a security lens applied to health in the aftermath of the Ebola outbreak in west Africa. 2 Heymann DL Chen L Takemi K et al. Global health security: the wider lessons from the west African Ebola virus disease epidemic. Lancet. 2015; 385: 1884-1901 Summary Full Text Full Text PDF PubMed Scopus (266) Google Scholar , 3 Gostin LO Friedman EA A retrospective and prospective analysis of the west African Ebola virus disease epidemic: robust national health systems at the foundation and an empowered WHO at the apex. Lancet. 2015; 385: 1902-1909 Summary Full Text Full Text PDF PubMed Scopus (127) Google Scholar , 4 Kruk ME Myers M Varpilah ST Dahn BT What is a resilient health system? Lessons from Ebola. Lancet. 2015; 385: 1910-1912 Summary Full Text Full Text PDF PubMed Scopus (254) Google Scholar Thanks to Ebola, global health security is now a priority, not only for ministers of health but also for heads of state. Global health security: the wider lessons from the west African Ebola virus disease epidemicThe 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. Full-Text PDF A retrospective and prospective analysis of the west African Ebola virus disease epidemic: robust national health systems at the foundation and an empowered WHO at the apexThe Ebola virus disease outbreak in west Africa is pivotal for the worldwide health system. Just as the depth of the crisis ultimately spurred an unprecedented response, the failures of leadership suggest the need for innovative reforms. Such reforms would transform the existing worldwide health system architecture into a purposeful, organised system with an empowered, highly capable WHO at its apex and enduring, equitable national health systems at its foundation. It would be designed not only to provide security against epidemic threats, but also to meet everyday health needs, thus realising the right to health. Full-Text PDF What is a resilient health system? Lessons from EbolaThe fragility of health systems has never been of greater interest—or importance—than at this moment, in the aftermath of the worst Ebola virus disease epidemic to date. The loss of life, massive social disruption, and collapse of even the most basic health-care services shows what happens when a crisis hits and health systems are not prepared.1 This did not happen only in west Africa—we saw it in Texas too: the struggle to provide a coherent response and manage public sentiment (which often manifests as fear) in a way that ensures that disease does not spread while also allowing day-to-day life to continue. Full-Text PDF

An Analysis of the International and Domestic Health Hazards Posed by the 2014 West African Ebola Virus Disease Outbreak

An epidemic of "ebolavirus" in West Africa, which was first identified in March 2014, is now the largest Ebola Virus Disease (EVD) outbreak on record. The West African epidemic will only be quelled through widespread adherence of public health initiatives promoting barrier-nursing techniques, health education, and the rapid identification of cases. The ongoing EVD outbreak in West Africa is unlikely to affect public health in the U.S. significantly.