Laboratory-confirmed Ebola Virus Disease Research Articles

Effect of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Vaccination on Ebola Virus Disease Illness and Death, Democratic Republic of the Congo.

We conducted a retrospective cohort study to assess the effect vaccination with the live-attenuated recombinant vesicular stomatitis virus–Zaire Ebola virus vaccine had on deaths among patients who had laboratory-confirmed Ebola virus disease (EVD). We included EVD-positive patients coming to an Ebola Treatment Center in eastern Democratic Republic of the Congo during 2018–2020. Overall, 25% of patients vaccinated before symptom onset died compared with 63% of unvaccinated patients. Vaccinated patients reported fewer EVD-associated symptoms, had reduced time to clearance of viral load, and had reduced length of stay at the Ebola Treatment Center. After controlling for confounders, vaccination was strongly associated with decreased deaths. Reduction in deaths was not affected by timing of vaccination before or after EVD exposure. These findings support use of preexposure and postexposure recombinant vesicular stomatitis virus–Zaire Ebola virus vaccine as an intervention associated with improved death rates, illness, and recovery time among patients with EVD.

Factors associated with length of stay and treatment outcome of Ebola patients treated at an Ebola treatment center in Sierra Leone during the peak period of the West African Ebola outbreak 2013\u20132016

BackgroundThe World Health Organization (WHO) declared the West Africa Ebola epidemic as a Public Health Emergency of International Concern in August 2014. During the outbreak period, there were calls for the affected countries to construct Ebola treatment centres and reliable diagnostic laboratories closer to areas of transmission in order to improve the quality care of Ebola Virus Disease (EVD) patients. Delay in seeking treatment has been reported to have led to poor treatment outcome of EVD patients. Sierra Leone recorded more than 8000 probable and confirmed cases and more than 4000 EVD -related deaths nation-wide.MethodsIn this retrospective study, we investigated the effects of treatment delay, length of symptomatic period, EVD patients’ sex, age, occupation, region of residence, and clinical characteristics on the treatment outcome of 205 laboratory-confirmed EVD patients who were admitted at the Kenema Government Hospital Ebola Treatment Center (KGHETC) from 13/09/2014–26/11/2014; i.e. during the peak of 2013–2016 EVD outbreak in Sierra Leone. Specifically also, we determined the factors that were associated with the length of stay for EVD treatment for patients who were discharged alive.ResultsMajority (66.3%, n = 205/309) of the 309 suspected EVD patients with medical records at the KGHETC triage during the period under review were tested positive for EVD using reverse-transcriptase-polymerase chain reaction (RT-PCR) and had a definitive treatment outcome. Few (33.7%, n = 104/309) suspected EVD patients were not included in our analysis and were classified thus: 29.1% (n = 90/309) suspect EVD cases with negative RT-PCR results, 4.5% (n = 14/309) suspect cases with non-available RT-PCR result.Of the 205 patients, 99 (48.3%) had a fatal outcome. For EVD patients that survived, we recorded a significant association (− 0.06, 95% Confidence Interval (CI) = − 0.14 – - 0.02, p = 0.004) between the Length of Stay (LOS) and for each kilometer travelled to seek treatment at the KGHETC. However, the association between EVD patients that were low skilled workers (− 5.91, 95% CI = − 24.60 – 12.79, p = 0.73), EVD patients who were children and pupils in junior school (− 0.86, 95% CI = − 12.86 – 11.14, p = 0.73), health seeking delay for EVD patients who resided in Kenema District where the KGHETC was located (− 0.49, 95% CI = − 0.12 – 1.09, p = 0.24), sex (− 1.77, 95% CI = − 8.75 – 5.21, p = 0.50), age (0.21, 95% CI = − 0.36 – 0.77, p = 0.57), referral status (1.21, 95% CI = − 17.67 – 20.09, p = 0.89) and the LOS in surviving patients were not statistically significant.ConclusionThe high LOS for either treatment outcome for EVD patients that resided in the district in which the EVD treatment facility was located compared to those patients from other districts implies that health authorities should consider intensive health education with high priority given to seeking early EVD treatment, and the construction of strategic ETCs as important components in their response strategy.

Clinical and epidemiological performance of WHO Ebola case definitions: a systematic review and meta-analysis

BackgroundEbola virus disease case definition is a crucial surveillance tool to detect suspected cases for referral and as a screening tool for clinicians to support admission and laboratory testing decisions at Ebola health facilities. We aimed to assess the performance of the WHO Ebola virus disease case definitions and other screening scores.MethodsIn this systematic review and meta-analysis, we searched PubMed, Scopus, Embase, and Web of Science for studies published in English between June 13, 1978, and Jan 14, 2020. We included studies that estimated the sensitivity and specificity of WHO Ebola virus disease case definitions, clinical and epidemiological characteristics (symptoms at admission and contact history), and predictive risk scores against the reference standard (laboratory-confirmed Ebola virus disease). Summary estimates of sensitivity and specificity were calculated using bivariate and hierarchical summary receiver operating characteristic (when four or more studies provided data) or random-effects meta-analysis (fewer than four studies provided data).FindingsWe identified 2493 publications, of which 14 studies from four countries (Sierra Leone, Guinea, Liberia, and Angola) were included in the analysis. 12 021 people with suspected disease were included, of whom 4874 were confirmed as positive for Ebola virus infection. Six studies explored the performance of WHO case definitions in non-paediatric populations, and in all of these studies, suspected and probable cases were combined and could not be disaggregated for analysis. The pooled sensitivity of the WHO Ebola virus disease case definitions from these studies was 81·5% (95% CI 74·1–87·2) and pooled specificity was 35·7% (28·5–43·6). History of contact or epidemiological link was a key predictor for the WHO case definitions (seven studies) and for risk scores (six studies). The most sensitive symptom was intense fatigue (79·0% [95% CI 74·4–83·0]), assessed in seven studies, and the least sensitive symptom was pain behind the eyes (1·0% [0·0–7·0]), assessed in three studies. The performance of fever as a symptom varied depending on the cutoff used to define fever.InterpretationWHO Ebola virus disease case definitions perform suboptimally to identify cases at both community level and during triage at Ebola health facilities. Inclusion of intense fatigue as a key symptom and contact history could improve the performance of case definitions, but implementation of these changes will require effective collaboration with, and trust of, affected communities.FundingMédecins sans Frontières.

Sociodemographic and clinical determinants of in-facility case fatality rate for 938 adult Ebola patients treated at Sierra Leone Ebola treatment center

BackgroundThe 2013–2016 West Africa Ebola Virus Disease (EVD) outbreak recorded the highest incidence and mortality since the discovery of the virus in Zaire in 1976; with more than 28,000 probable and confirmed EVD cases and 11,000 deaths. Studies relating to previous outbreaks usually involved small sample sizes. In this study we are set to identify those sociodemographic and clinical features that predict in-facility mortality among EVD patients using a large sample size.MethodsWe analysed the anonymized medical records of 938 laboratory-confirmed EVD patients 15 years old and above who received treatment at The 34 Military Hospital and The Police Training School EVD Treatment Centers in Sierra Leone in the period June 2014 to April 2015. We used both univariable and multivariable logistic regression to determine the predictors for in-facility mortality of these patients based on their sociodemographic and clinical characteristics.ResultsThe median age of the EVD cases was 33 years (interquartile range = 25 to 40 years). The majority of the EVD cases were male (59.0%) and had secondary level education (79.3%). We reported a low overall in-facility case fatality rate of 26.4%. The associations between case fatality rates and EVD patients who reported fever, abdominal pain, cough, diarrhoea, vomiting, fatigue, haemorrhage, dysphagia, conjunctival injection, dyspnea, and skin rash at the time of admission were all statistically significant (p < 0.05). Our preferred model with the age group 65 years and above alongside the following clinical symptoms; diarrhoea, vomiting, fatigue, dysphagia, conjunctival injection, dyspnea and cough produced a receiver operating characteristic (ROC) curve with an AUC (area under the curve) value of 0.93.ConclusionsWe constructed a simple model that can be optimally used alongside other rapid EVD diagnostic tools to identify EVD in-facility treatment mortality predictors based on the sociodemographic characteristics and clinical symptoms of adult EVD patients. We also reported low EVD cases among patients with secondary and tertiary education. These subpopulations of our patients who are generally informed about the signs and symptoms of EVD, alongside our treatment regimen may have been responsible for our comparatively lower case fatality rate.

Recurrent Ebolavirus disease in the Democratic Republic of Congo: update and challenges.

The current Ebolavirus disease (EVD) outbreak in the provinces of North Kivu and Ituri is the tenth outbreak affecting the Democratic Republic of Congo (DRC); the first outbreak occurring in a war context, and the second most deadly Ebolavirus outbreak on record following the 2014 outbreak in West Africa. The DRC government's response consisted of applying a package of interventions including detection and rapid isolation of cases, contact tracing, population mapping, and identification of high-risk areas to inform a coordinated effort. The coordinated effort was to screen, ring vaccinate, and conduct laboratory diagnoses using GeneXpert (Cepheid) polymerase chain reaction. The effort also included ensuring safe and dignified burials and promoting risk communication, community engagement, and social mobilization. Following the adoption of the “Monitored Emergency Use of Unregistered Products Protocol,” a randomized controlled trial of four investigational treatments (mAb114, ZMapp, and REGN-EB3 and Remdesivir) was carried out with all consenting patients with laboratory-confirmed EVD. REGN-EB3 and mAb114 showed promise as treatments for EVD. In addition, one investigational vaccine (rVSV-ZEBOV-GP) was used first, followed by a second prophylactic vaccine (Ad26.ZEBOV/MVA-BN-Filo) to reinforce the prevention. Although the provision of clinical supportive care remains the cornerstone of EVD outbreak management, the DRC response faced daunting challenges including general insecurity, violence and community resistance, appalling poverty, and entrenched distrust of authority. Ebolavirus remains a public health threat. A fully curative treatment is unlikely to be a game-changer given the settings of transmission, zoonotic nature, limits of effectiveness of any therapeutic intervention, and timing of presentation.

Clinical Manifestations and Modes of Death among Patients with Ebola Virus Disease, Monrovia, Liberia, 2014.

.Although the high case fatality rate (CFR) associated with Ebola virus disease (EVD) is well documented, there are limited data on the actual modes of death. We conducted a retrospective, observational cohort study among patients with laboratory-confirmed EVD. The patients were all seen at the Eternal Love Winning Africa Ebola Treatment Unit in Monrovia, Liberia, from June to August 2014. Our primary objective was to describe the modes of death of our patients and to determine predictors of mortality. Data were available for 53 patients with laboratory-confirmed EVD, with a median age of 35 years. The most frequent presenting symptoms were weakness (91%), fever (81%), and diarrhea (78%). Visible hemorrhage was noted in 25% of the cases. The CFR was 79%. Odds of death were higher in patients with diarrhea (odds ratio = 26.1, P < 0.01). All patients with hemorrhagic signs died (P < 0.01). Among the 18 fatal cases for which clinical information was available, three distinct modes of death were observed: sudden death after a moderate disease process (44%), profuse hemorrhage (33%), and encephalopathy (22%). We found that these modes of death varied by age (P = 0.04), maximum temperature (P = 0.43), heart rate on admission (P = 0.04), time to death from symptom onset (P = 0.13), and duration of hospitalization (P = 0.04). Although further study is required, our findings provide a foundation for developing treatment strategies that factor in patients with specific disease phenotypes (which often require the use of aggressive hydration). These findings provide insights into underlying pathogenic mechanisms resulting in severe EVD and suggest direction for future research and development of effective treatment options.

An account of the Ebola virus disease outbreak in Nigeria: implications and lessons learnt

BackgroundThe 2014 Ebola virus disease (EVD) outbreak remains unprecedented both in the number of cases, deaths and geographic scope. The first case of EVD was confirmed in Lagos Nigeria on 23 July 2014 and spread to involve 19 laboratory-confirmed EVD cases. The EVD cases were not limited to Lagos State as Rivers State recorded 2 confirmed cases of EVD with 1 out of the 2 dying. Swift implementation of public health measures were sufficient to forestall a country -wide spread of this dreaded disease. This exploratory formative research describes the events of the Nigeria Ebola crisis in 2014.MethodsThis research was implemented through key informant in-depth interviews involving 15 stakeholders in the EVD outbreak in Nigeria by a team of two or three interviewers. Most of the interviews were conducted face-to-face at the various offices of the respondents and others were via the telephone. The interviews which lasted an hour on average were conducted in English, digitally recorded and notes were also taken.ResultsThis study elucidated the public health response to the Ebola outbreak led by Lagos State Government in conjunction with the Federal Ministry of Health. The principal strategy was an incident management approach which saw them identify and successfully follow up 894 contacts. The infected EVD cases were quarantined and treated. The Nigerian private sector and international organizations made significant contributions to the control efforts. Public health enlightenment programmes using multimodal communication strategies were rapidly deployed. Water and sanitary facilities were provided in many public schools in Lagos.ConclusionsThe 2014 Ebola outbreak in Nigeria was effectively controlled using the incident management approach with massive support provided by the private sector and international community. Eight of the confirmed cases of EVD in Nigeria eventually died (case fatality rate of 42.1%) and twelve were nursed back to good health. On October 20 2014 Nigeria was declared fee of EVD by the World Health Organization. The Nigerian EVD experience provides valuable insights to guide reforms of African health systems in preparation for future infectious diseases outbreaks.

Ebola virus disease in children during the 2014–2015 epidemic in Guinea: a nationwide cohort study

EVD is a major threat to child health, especially among children under 5years of age. To date, none of demographic and clinical features, except younger age, have been consistently shown to affect mortality outcome in children infected with Ebola virus. What is Known: • The 2014-2015 West Africa Ebola epidemic is the largest and most widespread outbreak of Ebola virus disease (EVD) in history, with more than 11,000 deaths in Guinea, Liberia, and Sierra Leone. • During ongoing outbreak investigations, it is suggested that young children aged less than 5years are particularly vulnerable and highly susceptible to death. What is New: • Demographic and clinical characteristics of the nationwide cohort of pediatric patients with laboratory-confirmed EVD in Guinea are reported. • The results confirm the high rate of death among EVD children under 5years of age, while none of demographic and clinical features, except younger age, could serve as a predictor of mortality outcome in pediatric patients with EVD.

Ebola Virus Disease and Pregnancy: A Retrospective Cohort Study of Patients Managed at 5 Ebola Treatment Units in West Africa.

Reliable data are lacking on pregnancy outcomes during Ebola virus disease (EVD) epidemics. We aimed to characterize symptoms and outcomes among pregnant women admitted to Ebola treatment units (ETUs) with suspected and confirmed EVD to better inform obstetric management. We analyzed a retrospective cohort of reproductive-aged women presenting to 5 West African ETUs from September 2014 to September 2015. We compared clinical symptoms, risk of EVD diagnosis, and mortality between pregnant and nonpregnant women. Of 729 reproductive-aged women admitted to study ETUs, 44 (6%) reported pregnancy. Thirteen of 44 pregnant women (30%) tested EVD positive; 6 of 13 (46%) died. Pregnant women were less likely than nonpregnant women to report anorexia, asthenia, diarrhea, fever, myalgias/arthralgias, nausea, or vomiting (P < .05) at admission. Pregnant women with suspected EVD had the same risk, however, of laboratory-confirmed EVD (30% vs 24%, P = .38). While pregnant women with confirmed EVD had similar Ebola viral loads on presentation to nonpregnant women, as measured by initial cycle threshold (26.4 vs 23.2, P = .16), they were less likely to have myalgias/arthralgias (P< .001) and vomiting (P = .02). Both all-cause mortality (14% vs 19%, P = .39) and EVD-specific mortality (46% vs 54%, P = .60) were not significantly different between pregnant and nonpregnant women. Two neonates born live in the ETU died within 8 days. We find no evidence to support a difference in the risk of death between pregnant women with suspected or confirmed EVD compared to nonpregnant women. Limited data suggest poor fetal and neonatal outcomes in EVD-affected pregnancies.

Sequelae and Other Conditions in Ebola Virus Disease Survivors, Sierra Leone, 2015.

We rapidly assessed the health of Ebola virus disease (EVD) survivors in Kenema, Sierra Leone, by reviewing medical charts of all patients attending the Survivor Clinic of Kenema Government Hospital. Data were abstracted on signs and symptoms at every attendance. As of November 2015, a total of 621 attendances by 115 survivors with laboratory-confirmed EVD were made to the Survivor Clinic. Most (60.9%) survivors were women. Survivors’ median age was 28 years (range 0.25–70 years). Survivors attended the clinic a median of 5 times (range 1–21 times) each, and the median time from EVD discharge to attendance was 261 days (range 4–504 days). The most commonly reported signs and symptoms among the 621 attendances were headache (63.1%), fever (61.7%), and myalgia (43.3%). Because health needs of EVD survivors are complex, rapid chart reviews at survivor clinics should be repeated regularly to assess the extent of illness and prioritize service delivery.

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!)

SummaryBackgroundrVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.MethodsWe did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6–17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.FindingsIn the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3–100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae.InterpretationThe results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters.FundingWHO, UK Wellcome Trust, the UK Government through the Department of International Development, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development).

Development of a Prediction Model for Ebola Virus Disease: A Retrospective Study in Nzérékoré Ebola Treatment Center, Guinea.

The 2014 Ebola epidemic has shown the importance of accurate and rapid triage tools for patients with suspected Ebola virus disease (EVD). Our objective was to create a predictive score for EVD. We retrospectively reviewed all suspected cases admitted to the Ebola treatment center (ETC) in Nzérékoré, Guinea, between December 2, 2014, and February 23, 2015. We used a multivariate logistic regression model to identify clinical and epidemiological factors associated with EVD, which were used to create a predictive score. A bootstrap sampling method was applied to our sample to determine characteristics of the score to discriminate EVD. Among the 145 patients included in the study (48% male, median age 29 years), EVD was confirmed in 76 (52%) patients. One hundred and eleven (77%) patients had at least one epidemiological risk factor. Optimal cutoff value of fever to discriminate EVD was 38.5°C. After adjustment on presence of a risk factor, temperature higher than 38.5°C (odds ratio [OR] = 18.1, 95% confidence interval [CI] = 7.6-42.9), and anorexia (OR = 2.5, 95% CI = 1.1-6.1) were independently associated with EVD. The score had an area under curve of 0.85 (95% CI = 0.78-0.91) for the prediction of laboratory-confirmed EVD. Classification of patients in a high-risk group according to the score had a lower sensitivity (71% versus 86%) but higher specificity (85% versus 41%) than the existing World Health Organization algorithm. This score, which requires external validation, may be used in high-prevalence settings to identify different levels of risk in EVD suspected patients and thus allow a better orientation in different wards of ETC.

Inpatient signs and symptoms and factors associated with death in children aged 5 years and younger admitted to two Ebola management centres in Sierra Leone, 2014: a retrospective cohort study.

Médecins Sans Frontières (MSF) opened Ebola management centres (EMCs) in Sierra Leone in Kailahun in June, 2014, and Bo in September, 2014. Case fatality in the west African Ebola virus disease epidemic has been highest in children younger than 5 years. Clinical data on outcomes can provide important evidence to guide future management. However, such data on children are scarce and disaggregated clinical data across all ages in this epidemic have focussed on symptoms reported on arrival at treatment facilities, rather than symptoms and signs observed during admission. We aimed to describe the clinical characteristics of children aged 5 years and younger admitted to the MSF EMCs in Bo and Kailahun, and any associations between these characteristics and mortality. In a retrospective cohort study, we included data from children aged 5 years and younger with laboratory-confirmed Ebola virus disease admitted to EMCs between June and December, 2014. We described epidemiological, demographic, and clinical characteristics and viral load (measured using Ebola virus cycle thresholds [Ct]), and assessed their association with death using Cox regression modelling. We included 91 children in analysis; 52 died (57·1%). Case fatality was higher in children aged less than 2 years (76·5% [26/34]) than those aged 2-5 years (45·6% [26/57]; adjusted HR 3·5 [95% CI 1·5-8·5]) and in those with high (Ct<25) versus low (Ct≥25) viral load (81·8% [18/22] vs 45·9% [28/61], respectively; adjusted HR 9·2 [95% CI 3·8-22·5]). Symptoms observed during admission included: weakness 74·7% (68); fever 70·8% (63/89); distress 63·7% (58); loss of appetite 60·4% (55); diarrhoea 59·3% (54); and cough 52·7% (48). At admission, 25% (19/76) of children were afebrile. Signs significantly associated with death were fever, vomiting, and diarrhoea. Hiccups, bleeding, and confusion were observed only in children who died. This description of the clinical features of Ebola virus disease over the duration of illness in children aged 5 years and younger shows symptoms associated with death and a high prevalence of distress, with implications for clinical management. Collection and analysis of age-specific data on Ebola is very important to ensure that the specific vulnerabilities of children are addressed. No specific funding was received for this study. EB is supported by the National Health and Medical Research Council of Australia.

Prognostic Analysis of Patients with Ebola Virus Disease.

BackgroundThe 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 FindingsSixty 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/SignificanceThese 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.

Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial

A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2 × 10(7) plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.

Epidemiology and risk factors for Ebola virus disease in Sierra Leone-23 May 2014 to 31 January 2015.

Sierra Leone has the most cases of Ebola virus disease (EVD) ever reported. Trends in laboratory-confirmed EVD, symptom presentation, and risk factors have not been fully described. EVD cases occurring from 23 May 2014 to 31 January 2015 are presented by geography, demographics, and risk factors for all persons who had laboratory-confirmed EVD, which was identified by Ebola virus-specific reverse-transcription polymerase chain reaction-based testing. During the study period, 8056 persons had laboratory-confirmed EVD. Their median age was 28 years; 51.7% were female. Common symptoms included fever (90.4%), fatigue (88.3%), loss of appetite (87.0%), headache (77.9%), joint pain (73.7%), vomiting (71.2%), and diarrhea (70.6%). Among persons with confirmed cases, 47.9% reported having had contact with someone with suspected EVD or any sick person, and 25.5% reported having attended a funeral, of whom 66.2% reported touching the body. The incidence of EVD was highest during 1-30 November 2014, at 7.5 per 100 000 population per week, and decreased to 2.1 per week during 1-31 January 2015. Between 23 May and 30 August 2014, two districts had the highest incidence of 3.8 and 7.0 per 100 000 population per week which decreased >97% by 1-31 January 2015. In comparison, the districts that include the capital city reported a 10-fold increase in incidence per week during the same time periods. Almost half of patients with EVD in Sierra Leone reported physical contact with a person ill with EVD or a dead body, highlighting prevention opportunities.

Derivation and Internal Validation of the Ebola Prediction Score for Risk Stratification of Patients With Suspected Ebola Virus Disease

The current outbreak of Ebola virus disease in West Africa is the largest on record and has overwhelmed the capacity of local health systems and the international community to provide sufficient isolation and treatment of all suspected cases. The goal of this study is to develop a clinical prediction model that can help clinicians risk-stratify patients with suspected Ebola virus disease in the context of such an epidemic. A retrospective analysis was performed of patient data collected during routine clinical care at the Bong County Ebola Treatment Unit in Liberia during its first 16 weeks of operation. The predictive power of 14 clinical and epidemiologic variables was measured against the primary outcome of laboratory-confirmed Ebola virus disease, using logistic regression to develop a final prediction model. Bootstrap sampling was used to assess the internal validity of the model and estimate its performance in a simulated validation cohort. Ebola virus disease testing results were available for 382 (97%) of 395 patients admitted to the Ebola treatment unit during the study period. A total of 160 patients (42%) tested positive for Ebola virus disease. Logistic regression analysis identified 6 variables independently predictive of laboratory-confirmed Ebola virus disease, including sick contact, diarrhea, loss of appetite, muscle pains, difficulty swallowing, and absence of abdominal pain. The Ebola Prediction Score, constructed with these 6 variables, had an area under the receiver operator characteristic curve of 0.75 (95% confidence interval 0.70 to 0.80) for the prediction of laboratory-confirmed Ebola virus disease. Patients with higher Ebola Prediction Scores had higher likelihoods of laboratory-confirmed Ebola virus disease. The Ebola Prediction Score can be used by clinicians as an adjunct to current Ebola virus disease case definitions to risk-stratify patients with suspected Ebola virus disease. Clinicians can use this new tool for the purpose of cohorting patients within the suspected-disease ward of an Ebola treatment unit or community-based isolation center to prevent nosocomial infection or as a triage tool when patient numbers overwhelm available capacity. Given the inherent limitations of clinical prediction models, however, a low-cost, point-of-care test that can rapidly and definitively exclude Ebola virus disease in patients should be a research priority.

Clinical Presentation of Patients with Ebola Virus Disease in Conakry, Guinea

BackgroundIn 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.MethodsFrom 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.ResultsOf 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).ConclusionsPatients 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%.

Treatment of ebola virus disease.

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.