Project description:In October 2015, a new case of Ebola virus disease in Guinea was detected. Case investigation, serology, and whole-genome sequencing indicated possible transmission of the virus from an Ebola virus disease survivor to another person and then to the case-patient reported here. This transmission chain over 11 months suggests slow Ebola virus evolution.
Project description:We report 77 cases of occupational exposures for 57 healthcare workers at the Ebola Treatment Center in Conakry, Guinea, during the Ebola virus disease outbreak in 2014-2015. Despite the high incidence of 3.5 occupational exposures/healthcare worker/year, only 18% of workers were at high risk for transmission, and no infections occurred.
Project description:An epidemic of Ebola virus disease of unprecedented size continues in parts of west Africa. For the first time, large urban centres such as Conakry, the capital of Guinea, are affected. We did an observational study of patients with Ebola virus disease in three regions of Guinea, including Conakry, aiming to map the routes of transmission and assess the effect of interventions.Between Feb 10, 2014, and Aug 25, 2014, we obtained data from the linelist of all confirmed and probable cases in Guinea (as of Sept 16, 2014), a laboratory database of information about patients, and interviews with patients and their families and neighbours. With this information, we mapped chains of transmission, identified which setting infections most probably originated from (community, hospitals, or funerals), and computed the context-specific and overall reproduction numbers.Of 193 confirmed and probable cases of Ebola virus disease reported in Conakry, Boffa, and Télimélé, 152 (79%) were positioned in chains of transmission. Health-care workers contributed little to transmission. In March, 2014, individuals with Ebola virus disease who were not health-care workers infected a mean of 2·3 people (95% CI 1·6-3·2): 1·4 (0·9-2·2) in the community, 0·4 (0·1-0·9) in hospitals, and 0·5 (0·2-1·0) at funerals. After the implementation of infection control in April, the reproduction number in hospitals and at funerals reduced to lower than 0·1. In the community, the reproduction number dropped by 50% for patients that were admitted to hospital, but remained unchanged for those that were not. In March, hospital transmissions constituted 35% (seven of 20) of all transmissions and funeral transmissions constituted 15% (three); but from April to the end of the study period, they constituted only 9% (11 of 128) and 4% (five), respectively. 82% (119 of 145) of transmission occurred in the community and 72% (105) between family members. Our simulations show that a 10% increase in hospital admissions could have reduced the length of chains by 26% (95% CI 4-45).In Conakry, interventions had the potential to stop the epidemic, but reintroductions of the disease and poor cooperation of a few families led to prolonged low-level spread, showing the challenges of Ebola virus disease control in large urban centres. Monitoring of chains of transmission is crucial to assess and optimise local control strategies for Ebola virus disease.Labex IBEID, Reacting, PREDEMICS, NIGMS MIDAS initiative, Institut Pasteur de Dakar.
Project description:BackgroundThe 2013-2016 West African Ebola outbreak infected 28,616 people and caused 11,310 deaths by 11 May 2016, across six countries. The outbreak has also resulted in the largest number of EVD survivors in history-over 17,000. Guinea was declared Ebola-free on 1 June 2016. Reports from the outbreak documented 3814 cases resulting in 2544 deaths and 1270 survivors. EVD survivors face various neuropsychological and psycho-affective alterations that have not been fully identified yet. This study aims to document the depressive symptoms among adult survivors in Guinea.MethodsDepressive symptoms were investigated using the French version of the Center for Epidemiologic Studies-Depression Scale (CES-D) administered to all adult survivors (≥ 20 years) participating in the PostEboGui study and receiving care in Conakry. The study was combined with a clinical consultation by a psychiatrist at the Donka National Hospital in Conakry that ensured adapted care was provided when needed.ResultsOverall, 256 adult participants receiving care in Conakry participated in this study: 55% were women, median age 31 years [IQR: 26-40]. The median time since the Ebola Treatment Center (ETC) discharge was 8.1 months [IQR: 4.1-11.7]. 15% had a score above the threshold values indicating psychological suffering (15% for men and 14% for women). 33 people (16 women and 17 men) met with the psychiatrist, which resulted in the diagnosis of 3 cases of post-traumatic stress disorder (PTSD), 3 cases of mild depression, 13 cases of moderate depression, and 11 cases of severe depression, including 1 with kinesthetic hallucinations and another with visual hallucinations, and 1 with suicidal ideation and 3 with attempted suicide. Severe depression was diagnosed between 1 and 19 months after ETC discharge. The various identified forms of depression responded favorably to conventional drug therapies and cognitive behavioral therapy.ConclusionLong-term follow-up for EVD survivors will be necessary to understand the evolution of these pathologies. In the current post-epidemic context, these cases underscore the need to strengthen mental health diagnostic systems and treatment on a national scale.
Project description:SettingTen targeted health facilities supported by Damien Foundation (a Belgian Non Governmental Organization) and the National Tuberculosis (TB) Program in Conakry, Guinea.ObjectivesTo uphold TB program performance during the Ebola outbreak in the presence of a package of pre-emptive additional measures geared at reinforcing the routine TB program, and ensuring Ebola infection control, health-workers safety and motivation.DesignA retrospective comparative cohort study of a TB program assessing the performance before (2013) and during the (2014) Ebola outbreak.ResultsDuring the Ebola outbreak, all health facilities were maintained opened, there were no reported health-worker Ebola infections, drug stockouts or health staff absences. Of 2,475 presumptive pulmonary TB cases, 13% were diagnosed with TB in both periods (160/1203 in 2013 and 163/1272 in 2014). For new TB, treatment success improved from 84% before to 87% during the Ebola outbreak (P = 0.03). Adjusted Hazard-ratios (AHR) for an unfavorable outcome was alwo lower during the Ebola outbreak, AHR = 0.8, 95% CI:0.7-0.9, P = 0.04). Treatment success improved for HIV co-infected patients (72% to 80%, P<0.01). For retreatment patients, the proportion achieving treatment success was maintained (68% to 72%, P = 0.05). Uptake of HIV-testing and Cotrimoxazole Preventive Treatment was maintained over 85%, and Anti-Retroviral Therapy uptake increased from 77% in 2013 to 86% in 2014 (P<0.01).ConclusionContingency planning and health system and worker support during the 2014 Ebola outbreak was associated with encouraging and sustained TB program performance. This is of relevance to future outbreaks.
Project description:BackgroundDespite the notoriety of Ebola virus disease (EVD) as one of the world's most deadly infections, EVD has a wide range of outcomes, where asymptomatic infection may be almost as common as fatality. With increasingly sensitive EVD diagnosis, there is a need for more accurate prognostic tools that objectively stratify clinical severity to better allocate limited resources and identify those most in need of intensive treatment.Methods/principal findingsThis retrospective cohort study analyses the clinical characteristics of 158 EVD(+) patients at the GOAL-Mathaska Ebola Treatment Centre, Sierra Leone. The prognostic potential of each characteristic was assessed and incorporated into a statistically weighted disease score. The mortality rate among EVD(+) patients was 60.8% and highest in those aged <5 or >25 years (p<0.05). Death was significantly associated with malaria co-infection (OR = 2.5, p = 0.01). However, this observation was abrogated after adjustment to Ebola viral load (p = 0.1), potentially indicating a pathologic synergy between the infections. Similarly, referral-time interacted with viral load, and adjustment revealed referral-time as a significant determinant of mortality, thus quantifying the benefits of early reporting as a 12% mortality risk reduction per day (p = 0.012). Disorientation was the strongest unadjusted predictor of death (OR = 13.1, p = 0.014) followed by hiccups, diarrhoea, conjunctivitis, dyspnoea and myalgia. Including these characteristics in multivariate prognostic scores, we obtained a 91% and 97% ability to discriminate death at or after triage respectively (area under ROC curve).Conclusions/significanceThis study proposes highly predictive and easy-to-use prognostic tools, which stratify the risk of EVD mortality at or after EVD triage.
Project description:Rapidly identifying likely Ebola patients is difficult because of a broad case definition, overlap of symptoms with common illnesses, and lack of rapid diagnostics. However, rapid identification is critical for care and containment of contagion. We analyzed retrospective data from 252 Ebola-positive and 172 Ebola-negative patients at a Sierra Leone Ebola treatment center to develop easy-to-use risk scores, based on symptoms and laboratory tests (if available), to stratify triaged patients by their likelihood of having Ebola infection. Headache, diarrhea, difficulty breathing, nausea/vomiting, loss of appetite, and conjunctivitis comprised the symptom-based score. The laboratory-based score also included creatinine, creatine kinase, alanine aminotransferase, and total bilirubin. This risk score correctly identified 92% of Ebola-positive patients as high risk for infection; both scores correctly classified >70% of Ebola-negative patients as low or medium risk. Clinicians can use these risk scores to gauge the likelihood of triaged patients having Ebola while awaiting laboratory confirmation.
Project description:Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
Project description: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.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.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.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.).
Project description:BACKGROUND:The non-specific symptoms of Ebola Virus Disease (EVD) pose a major problem to triage and isolation efforts at Ebola Treatment Centres (ETCs). Under the current triage protocol, half the patients allocated to high-risk "probable" wards were EVD(-): a misclassification speculated to predispose nosocomial EVD infection. A better understanding of the statistical relevance of individual triage symptoms is essential in resource-poor settings where rapid, laboratory-confirmed diagnostics are often unavailable. METHODS/PRINCIPAL FINDINGS:This retrospective cohort study analyses the clinical characteristics of 566 patients admitted to the GOAL-Mathaska ETC in Sierra Leone. The diagnostic potential of each characteristic was assessed by multivariate analysis and incorporated into a statistically weighted predictive score, designed to detect EVD as well as discriminate malaria. Of the 566 patients, 28% were EVD(+) and 35% were malaria(+). Malaria was 2-fold more common in EVD(-) patients (p<0.05), and thus an important differential diagnosis. Univariate analyses comparing EVD(+) vs. EVD(-) and EVD(+)/malaria(-) vs. EVD(-)/malaria(+) cohorts revealed 7 characteristics with the highest odds for EVD infection, namely: reported sick-contact, conjunctivitis, diarrhoea, referral-time of 4-9 days, pyrexia, dysphagia and haemorrhage. Oppositely, myalgia was more predictive of EVD(-) or EVD(-)/malaria(+). Including these 8 characteristics in a triage score, we obtained an 89% ability to discriminate EVD(+) from either EVD(-) or EVD(-)/malaria(+). CONCLUSIONS/SIGNIFICANCE:This study proposes a highly predictive and easy-to-use triage tool, which stratifies the risk of EVD infection with 89% discriminative power for both EVD(-) and EVD(-)/malaria(+) differential diagnoses. Improved triage could preserve resources by identifying those in need of more specific differential diagnostics as well as bolster infection prevention/control measures by better compartmentalizing the risk of nosocomial infection.