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Improving the provision of supportive care for patients with Ebola is an important quality improvement initiative. We designed a simulated Ebola Treatment Unit (ETU) to assess performance and safety of healthcare workers (HCWs) performing tasks wearing personal protective equipment (PPE) in hot (35 °C, 60% relative humidity) or thermo-neutral (20 °C, 20% relative humidity) conditions. In this pilot phase to determine the feasibility of study procedures, HCWs in PPE were non-randomly allocated to hot or thermo-neutral conditions to perform peripheral intravenous (PIV) and midline catheter (MLC) insertion and endotracheal intubation (ETI) on mannequins. Eighteen HCWs (13 physicians, 4 nurses, 1 nurse practitioner; 2 with prior ETU experience; 10 in hot conditions) spent 69 (10) (mean (SD)) minutes in the simulated ETU. Mean (SD) task completion times were 16 (6) min for PIV insertion; 33 (5) min for MLC insertion; and 16 (8) min for ETI. Satisfactory task completion was numerically higher for physicians vs. nurses. Participants' blood pressure was similar, but heart rate was higher ( p = 0.0005) post-simulation vs. baseline. Participants had a median (range) of 2.0 (0.0-10.0) minor PPE breaches, 2.0 (0.0-6.0) near-miss incidents, and 2.0 (0.0-6.0) health symptoms and concerns. There were eight health-assessment triggers in five participants, of whom four were in hot conditions. We terminated the simulation of two participants in hot conditions due to thermal discomfort. In summary, study tasks were suitable for physician participants, but they require redesign to match nurses' expertise for the subsequent randomized phase of the study. One-quarter of participants had a health-assessment trigger. This research model may be useful in future training and research regarding clinical care for patients with highly infectious pathogens in austere settings.

Objective: To study Ebola virus disease (EVD) in children aged 15 years and below, and to identify risk factors associated with death., Patients and Methods: Retrospective, multicenter, descriptive, and analytical study of files of children aged 15 years and below in Ebola treatment centers (ETC) of Donka from March 2014 to May 2015. We included all files of children aged 15 years and below hospitalized for EVD in the two ETCs., Results: A total of 739 patients hospitalized in both ETCs, 146 children aged 15 years and below (20%) were registered during the study period. The mean age of children was 6.73±4.26 years. Most children were aged above five years (65.8%) and the mean time to consultation was 4.34±3.21 days. The main clinical signs were asthenia (78.8%), fever (75.3%), anorexia (53.4%), headache (45.9%), vomiting (41.8%), abdominal pain (29.5%), and diarrhea (28.8%). The case fatality was 48%, including 54.3% in Coyah and 45% in Conakry. Older age (aOR=0.83, 95% CI [0.76-0.95]), fever (aOR=3.28, 95% CI [1.22-8.87]), diarrhea (aOR=2.98, 95% CI [1.19-4.48]), and hemorrhage (aOR=3.13, 95% CI [1.00-10.38]) were independently associated with death due to EVD., Conclusion: EVD remains serious especially in children, with high case fatality. Risk factors independently associated with death were young age, diarrhea, hemorrhage, and fever. Particular attention to these risk factors and vaccination will contribute to improving the prognosis of EVD in children., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The ebola epidemic that raged in West Africa between 2013 and 2016 was the largest since the discovery of the virus in 1976. During this epidemic, more than 11,000 cases were notified with a lethality of over 67%. Several means of transmission have been described. The great difficulty noted during the epidemic was the estimation of the number of asymptomatic and pauci symptomatic cases, however there is evidence that this population has been in contact with the virus for some time. Thus, they could be a source for the spread of the epidemic. In this paper, we report in Guinea-Conakry three stories of probable pauci-symptomatic form of ebola disease that would have been the cause of massive infection in a population sorely tried by the epidemic between 2014 and 2015 in Guinea., Competing Interests: The authors declare no competing interests., (Copyright: Ibrahima Camara et al.)

Background: Management of Ebola virus disease (EVD) has historically focused on infection prevention, case detection and supportive care. Several specific anti-Ebola therapies have been investigated, including during the 2014-2016 West African outbreak. Our objective was to conduct a systematic review of the effect of anti-Ebola virus therapies on clinical outcomes to guide their potential use and future evaluation., Methods: We searched PubMed, EMBASE, Global Health, Cochrane Library, African Index Medicus, WHOLIS (inception-9 April 2018), and trial registries for observational studies or clinical trials, in any language, that enrolled patients with confirmed EVD who received therapy targeting Ebola virus and reported on mortality, symptom duration, or adverse effects., Results: From 11,257 citations and registered trials, we reviewed 55 full-text citations, of which 35 met eligibility criteria (1 randomized clinical trial (RCT), 8 non-randomized comparative studies, 9 case series and 17 case reports) and collectively examined 21 anti-Ebola virus agents. The 31 studies performed during the West African outbreak reported on 4.8% (1377/28616) of all patients with Ebola. The only RCT enrolled 72 patients (0.25% of all patients with Ebola) and compared the monoclonal antibody ZMapp vs. standard care (mortality, 22% vs. 37%; 95% confidence interval for risk difference, - 36 to 7%). Studies of convalescent plasma, interferon-β-1a, favipiravir, brincidofovir, artesunate-amodiaquine and TKM-130803 were associated with at least moderate risk of bias., Conclusions: Research evaluating anti-Ebola virus agents has reached very few patients with EVD, and inferences are limited by non-randomized study designs. ZMapp has the most promising treatment signal.

Background: During the 2014-2015 Ebola outbreak in West Africa, the lack of infection prevention and control (IPC) measures in health care facilities amplified human-to-human transmission and contributed to the magnitude of this humanitarian disaster.Case ReportIn the summer of 2014, the Geneva University Hospitals (HUG; Geneva, Switzerland) conducted an IPC assessment and developed a project based on the local needs and their expertise with the support of the Swiss Agency for Development and Cooperation and the Humanitarian Aid Unit (SDC/HA; Bern, Switzerland). The project consisted of building local capacity in the production of alcohol-based hand-rub solution (ABHRS) based on the World Health Organization (WHO; Geneva, Switzerland) formula in non-Ebola health facilities at the peak of the outbreak in Liberia (Fall 2014) and during recovery in Guinea (September 2015) to promote safer care. Twenty-one pharmacists in Liberia and 22 in Guinea were trained and one years' worth of laboratory equipment, chemical products, containers for personal use, and bioethanol were delivered to 10 hospitals per country with more than 8,000 100 ml bottles of solution produced at the end of the project.DiscussionHand hygiene using hand-rub solution is a critical component of safer care, especially in health care settings lacking runnable water. Throughout the Ebola outbreak, it was a timely moment to promote hand-rub solution and to reinforce IPC measures in non-Ebola health facilities. During the project implementation, a substantial challenge was the unavailability of bioethanol in Liberia and Guinea. In the long run, sustainability of the production can become an issue as it depends heavily on the local government's financial and political commitment, the capacity to create an on-going demand for hand-rub solution in health facilities, the local purchase and replacement of the materials and chemical products, as well as the availability of continuous local partners' support., Conclusion: The project demonstrated that it was feasible to build local capacity in ABHRS production during an emergency and in limited-resource settings when materials and training are provided. Future programs in similar contexts should identify and address the factors of sustainability during the implementation phase and provide regular, long-term technical support. Jacquerioz BauschFA, HellerO, BengalyL, Matthey-KhouityB, BonnabryP, TouréY, KervillainGJ, BahEI, ChappuisF, HagonO. Building local capacity in hand-rub solution production during the 2014-2016 Ebola outbreak disaster: the case of Liberia and Guinea.. Prehosp Disaster Med. 2018;33(6):660-667.

Non-cases are suspect Ebola Virus Disease (EVD) cases testing negative by EVD RT-PCR after admission to an Ebola Treatment Centre (ETC). Admitting non-cases to an ETC prompts concerns on case- and workload in the ETC, risk for nosocomial EVD infection, and delays in diagnosis and disease-specific treatment. We retrospectively analysed characteristics, outcomes and determinants of death of EVD cases and non-cases admitted to the Conakry ETC in Guinea between 03/2014 and 09/2015. Of the 2362 admitted suspects who underwent full confirmatory PCR testing, 1540 (65.2%) were non-cases; among them 727 needed repeated confirmatory PCR testing resulting in 2.5 days (average) in the ETC isolation ward. Twenty-one patients tested positive on the repeat test, most in a period of flawed sampling for the initial test and none after introduction of PCR confirmation with geneXpert. No readmissions following nosocomial EVD infection were recorded. No combination of symptoms yielded acceptable sensitivity and specificity to allow differentiating confirmed from non-cases. Symptoms as ocular bleeding/redness have high specificity, but limited usefulness as not common. Admission delay and age distribution were not different for both groups. In total, 98 (20.6%) of 475 deaths in the ETC were non-cases. Most died within 24 hours after admission. Living in Conakry (aOR 1.78 (1.08-2.96)) was the strongest risk factor for death. Weeks with higher admission load had lower case fatality among non-cases, probably because more acute (and treatable) illnesses of contacts of known cases were admitted. These findings show high numbers of potentially critically ill non-cases need to be considered when setting up triage and referral of EVD suspect cases. Symptoms and risk factors alone do not allow differentiating the non-cases. Integration of highly-sensitive EVD diagnostic methods with short turnaround time in the triage of peripheral hospitals and dropping the systematic 2nd PCR for symptomatic early presenters could limit delays in access to adapted care of cases and seriously ill non-cases. Whether feasible without compromising outbreak control, and under which conditions, should be further assessed.

In March 2014, the World Health Organization declared an outbreak of Ebola virus disease in Guinea. In August 2014, a case caused by virus imported from Guinea occurred in Senegal, most likely resulting from nonsecure funerals and travel. Preparedness and surveillance in Senegal probably prevented secondary cases.

By using data from a 2015 clinical trial on Ebola convalescent-phase plasma in Guinea, we assessed the prevalence of electrolyte and metabolic abnormalities at admission and their predictive value to stratify patients into risk groups. Patients underwent testing with a point-of-care device. We used logistic regression to construct a prognostic model and summarized the predictive value with the area under the receiver operating curve. Abnormalities were common among patients, particularly hypokalemia, hypocalcemia, hyponatremia, raised creatinine, high anion gap, and anemia. Besides age and PCR cycle threshold value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently associated with increased risk for death. A prognostic model using all 5 factors was highly discriminatory (area under the receiver operating curve 0.95; 95% CI 0.90-0.99) and enabled the definition of risk criteria to guide targeted care. Most patients had a very low (<5%) or very high (>80%) risk for death.

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., (© The Author(s) 2016.)

Background: In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea., Methods: In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group., Results: A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed., Conclusions: The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).

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., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The case fatality ratio (CFR) of Ebola virus disease (EVD) can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investigate whether viremia in EVD patients may be used to evaluate baseline EVD CFRs., Methods and Findings: We analyzed the laboratory and epidemiological records of patients with EVD confirmed by reverse transcription PCR hospitalized in the Conakry area, Guinea, between 1 March 2014 and 28 February 2015. We used viremia and other variables to model the CFR. Data for 699 EVD patients were analyzed. In the week following symptom onset, mean viremia remained stable, and the CFR increased with viremia, V, from 21% (95% CI 16%-27%) for low viremia (V < 104.4 copies/ml) to 53% (95% CI 44%-61%) for intermediate viremia (104.4 ≤ V < 105.2 copies/ml) and 81% (95% CI 75%-87%) for high viremia (V ≥ 105.2 copies/ml). Compared to adults (15-44 y old [y.o.]), the CFR was larger in young children (0-4 y.o.) (odds ratio [OR]: 2.44; 95% CI 1.02-5.86) and older adults (≥ 45 y.o.) (OR: 2.84; 95% CI 1.81-4.46) but lower in children (5-14 y.o.) (OR: 0.46; 95% CI 0.24-0.86). An order of magnitude increase in mean viremia in cases after July 2014 compared to those before coincided with a 14% increase in the CFR. Our findings come from a large hospital-based study in Conakry and may not be generalizable to settings with different case profiles, such as with individuals who never sought care., Conclusions: Viremia in EVD patients was a strong predictor of death that partly explained variations in CFR in the study population. This study provides baseline CFRs by viremia group, which allow appropriate adjustment when estimating efficacy in treatment studies. In randomized controlled trials, stratifying analysis on viremia groups could reduce sample size requirements by 25%. We hypothesize that monitoring the viremia of hospitalized patients may inform the ability of surveillance systems to detect EVD patients from the different severity strata.

In an observational cohort study including 89 Ebola patients, predictive factors of death were analyzed. The crude mortality rate was 43.8%. Myalgia (adjusted odds ratio [OR], 4.04; P = .02), hemorrrhage (adjusted OR, 3.5; P = .02), and difficulty breathing (adjusted OR, 5.75; P = .01) were independently associated with death., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Anecdotal reports suggesting that survival rates among hospitalized patients with Ebola virus disease in Guinea are higher than the 29.2% rate observed in the current epidemic in West Africa., Methods: Survival after symptom onset was determined using Kaplan Meier survival methods among patients with confirmed Ebola virus disease treated in Conakry, Guinea from March 25, 2014, to August 5, 2014. We analyzed the relationship between survival and patient factors, including demographics and clinical features., Results: Of the 70 patients analyzed [mean age ± standard deviation (SD), 34 ± 14.1; 44 were men], 42 were discharged alive with a survival rate among hospitalized patients of 60% (95% confidence interval, 41.5-78.5%). The survival rate was 28 (71.8%) among 39 patients under 34 years of age, and 14 (46.7%) among 30 patients aged 35 years or greater (p = 0.034). The rates of myalgia (3 of 42 versus 7 of 28, p = 0.036) and hiccups (1 of 42 versus 5 of 28, p = 0.023) were significantly lower among patients who survived., Conclusions: Our results provide insights into a cohort of hospitalized patients with Ebola virus disease in whom survival is prominently higher than seen in other cohorts of hospitalized patients.

Background: In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date., Methods: From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors., Results: Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007)., Conclusions: Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.

Objectives: The authors studied the epidemiological, clinical, and outcome features of the Ebola virus disease in patients hospitalized at the Ebola treatment center (ETC) in Conakry to identify clinical factors associated with death., Materials and Methods: A prospective study was conducted from March 25 to August 20, 2014. The diagnosis of Ebola virus infection was made on real-time PCR., Results: Ninety patients, with a positive test result, were hospitalized. Their mean age was 34.12±14.29 years and 63% were male patients. Most worked in the informal sector (38%) and in the medical and paramedical staff (physicians 12%, nurses 6%, and laboratory technicians 1%). Most patients lived in the Conakry suburbs (74%) and in Boffa (11%). The main clinical signs were physical asthenia (80%) and fever (72%). Hemorrhagic signs were observed in 26% of patients. The comparison of clinical manifestations showed that hiccups (P=0.04), respiratory distress (P=0.04), and hemorrhagic symptoms (P=0.01) were more frequent among patients who died. Malaria (72%) and diabetes (2%) were the most frequent co-morbidities. The crude case fatality rate was 44% [95% confidence interval (33-54%)]. The average hospital stay was 7.96±5.81 days., Conclusion: The first Ebola outbreak in Conakry was characterized by the young age of patients, discrete hemorrhagic signs related to lethality. Its control relies on a strict use of preventive measures., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen.