Assessment of Environmental Contamination and Environmental Decontamination Practices within an Ebola Holding Unit,Freetown, Sierra Leone

Evidence to inform decontamination practices at Ebola holding units (EHUs) and treatment centres is lacking. We conducted an audit of decontamination procedures inside Connaught Hospital EHU in Freetown, Sierra Leone, by assessing environmental swab specimens for evidence of contamination with Ebola virus by RT-PCR. Swabs were collected following discharge of Ebola Virus Disease (EVD) patients before and after routine decontamination. Prior to decontamination, Ebola virus RNA was detected within a limited area at all bedside sites tested, but not at any sites distant to the bedside. Following decontamination, few areas contained detectable Ebola virus RNA. In areas beneath the bed there was evidence of transfer of Ebola virus material during cleaning. Retraining of cleaning staff reduced evidence of environmental contamination after decontamination. Current decontamination procedures appear to be effective in eradicating persistence of viral RNA. This study supports the use of viral swabs to assess Ebola viral contamination within the clinical setting. We recommend that regular refresher training of cleaning staff and audit of environmental contamination become standard practice at all Ebola care facilities during EVD outbreaks.     

Development of therapeutics for treatment of Ebola virus infection

Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed.     

Ebola Virus Disease in Mice with Transplanted Human Hematopoietic Stem Cells

The development of treatments for Ebola virus disease (EVD) has been hampered by the lack of small-animal models that mimick human disease. Here we show that mice with transplanted human hematopoetic stem cells reproduce features typical of EVD. Infection with Ebola virus was associated with viremia, cell damage, liver steatosis, signs of hemorrhage, and high lethality. Our study provides a small-animal model with human components for the development of EVD therapies.     

Evaluating Clinical Trial Designs for Investigational Treatments of Ebola Virus Disease

BackgroundExperimental treatments for Ebola virus disease (EVD) might reduce EVD mortality. There is uncertainty about the ability of different clinical trial designs to identify effective treatments, and about the feasibility of implementing individually randomised controlled trials during an Ebola epidemic.ConclusionsThe MSA discards ineffective treatments quickly, while reliably providing evidence concerning effective treatments. The MSA is appropriate for the clinical evaluation of EVD treatments.     

Rapid establishment of a frontline field laboratory in response to an imported outbreak of Ebola virus disease in western Uganda,June 2019

The Democratic Republic of the Congo (DRC) declared an Ebola virus disease (EVD) outbreak in North Kivu in August 2018. By June 2019, the outbreak had spread to 26 health zones in northeastern DRC, causing >2,000 reported cases and >1,000 deaths. On June 10, 2019, three members of a Congolese family with EVD-like symptoms traveled to western Uganda’s Kasese District to seek medical care. Shortly thereafter, the Viral Hemorrhagic Fever Surveillance and Laboratory Program (VHF program) at the Uganda Virus Research Institute (UVRI) confirmed that all three patients had EVD. The Ugandan Ministry of Health declared an outbreak of EVD in Uganda’s Kasese District, notified the World Health Organization, and initiated a rapid response to contain the outbreak. As part of this response, UVRI and the United States Centers for Disease Control and Prevention, with the support of Uganda’s Public Health Emergency Operations Center, the Kasese District Health Team, the Superintendent of Bwera General Hospital, the United States Department of Defense’s Makerere University Walter Reed Project, and the United States Mission to Kampala’s Global Health Security Technical Working Group, jointly established an Ebola Field Laboratory in Kasese District at Bwera General Hospital, proximal to an Ebola Treatment Unit (ETU). The laboratory consisted of a rapid containment kit for viral inactivation of patient specimens and a GeneXpert Instrument for performing Xpert Ebola assays. Laboratory staff tested 76 specimens from alert and suspect cases of EVD; the majority were admitted to the ETU (89.3%) and reported recent travel to the DRC (58.9%). Although no EVD cases were detected by the field laboratory, it played an important role in patient management and epidemiological surveillance by providing diagnostic results in <3 hours. The integration of the field laboratory into Uganda’s National VHF Program also enabled patient specimens to be referred to Entebbe for confirmatory EBOV testing and testing for other hemorrhagic fever viruses that circulate in Uganda.     

Associations between Mental Health and Ebola-Related Health Behaviors: A Regionally Representative Cross-sectional Survey in Post-conflict Sierra Leone

BackgroundLittle attention has been paid to potential relationships between mental health, trauma, and personal exposures to Ebola virus disease (EVD) and health behaviors in post-conflict West Africa. We tested a conceptual model linking mental health and trauma to EVD risk behaviors and EVD prevention behaviors.ConclusionsIn post-conflict settings, past war trauma and mental health problems are associated with health behaviors related to combatting EVD. The associations between war trauma and both EVD risk behaviors and EVD prevention behaviors may be mediated through two key mental health variables: depression and PTSD symptoms. Considering the role of mental health in the prevention of disease transmission may help fight continuing and future Ebola outbreaks in post-conflict Sierra Leone. This sample is specific to Freetown and the Western Area and may not be representative of all of Sierra Leone. In addition, our main outcomes as well as personal EVD exposure, war exposures, and mental health predictors rely on self-report, and therefore raise the possibility of common methods bias. However, the findings of this study may be relevant for understanding dynamics related to EVD and mental health in other major capital cities in the EVD-affected countries of West Africa.     

Ebola Outbreak Response; Experience and Development of Screening Tools for Viral Haemorrhagic Fever (VHF) in a HIV Center of Excellence Near to VHF Epicentres

Introduction

There have been 3 outbreaks of viral hemorrhagic fever (VHF) in Uganda in the last 2 years. VHF often starts with non-specific symptoms prior to the onset of haemorrhagic signs. HIV clinics in VHF outbreak countries such as Uganda see large numbers of patients with HIV 1/2 infection presenting with non-specific symptoms every day. Whilst there are good screening tools for general health care facilities expecting VHF suspects, we were unable to find tools for use in HIV or other non-acute clinics.

Methods

We designed tools to help with communication to staff, infection control and screening of HIV patients with non-specific symptoms in a large HIV clinic during the outbreaks in Uganda. We describe our experiences in using these tools in 2 Ebola Virus Disease outbreaks in Uganda.

Results

During the Ebola Virus Disease (EVD) outbreaks, enhanced infection control and communication procedures were implemented within 24 hours of the WHO/Ministry of Health announcement of the outbreaks. During course of these outbreaks the clinic saw 12,544 patients with HIV 1/2 infection, of whom 3,713 attended without an appointment, suggesting new symptoms. Of these 4 were considered at risk of EVD and seen with full infection procedures; 3 were sent home after further investigation. One patient was referred to the National Referral Hospital VHF unit, but discharged on the same day. One additional VHF suspect was identified outside of a VHF outbreak; he was transferred to the National Referral Hospital and placed in isolation within 2 hours of arriving at the HIV clinic.

Discussion

Use of simple screening tools can be helpful in managing large numbers of symptomatic patients attending for routine and non-routine medical care (including HIV care) within a country experiencing a VHF outbreak, and can raise medical staff awareness of VHF outside of the epidemics.     

Facility-Based Delivery during the Ebola Virus Disease Epidemic in Rural Liberia: Analysis from a Cross-Sectional,Population-Based Household Survey

BackgroundThe Ebola virus disease (EVD) epidemic has threatened access to basic health services through facility closures, resource diversion, and decreased demand due to community fear and distrust. While modeling studies have attempted to estimate the impact of these disruptions, no studies have yet utilized population-based survey data.ConclusionsWe detected a 30% decreased odds of FBD after the start of EVD in a rural Liberian county with relatively few cases. Because health facilities never closed in Rivercess County, this estimate may under-approximate the effect seen in the most heavily affected areas. These are the first population-based survey data to show collateral disruptions to facility-based delivery caused by the West African EVD epidemic, and they reinforce the need to consider the full spectrum of implications caused by public health emergencies.     

Ebola in great apes – current knowledge,possibilities for vaccination,and implications for conservation and human health

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Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled,Single-Arm Proof-of-Concept Trial in Guinea

BackgroundEbola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care.Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies.ConclusionsIn the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia.

Trial registration

ClinicalTrials.gov NCT02329054     

Zoonotic risk factors associated with seroprevalence of Ebola virus GP antibodies in the absence of diagnosed Ebola virus disease in the Democratic Republic of Congo

BackgroundEbola virus (EBOV) is a zoonotic filovirus spread through exposure to infected bodily fluids of a human or animal. Though EBOV is capable of causing severe disease, referred to as Ebola Virus Disease (EVD), individuals who have never been diagnosed with confirmed, probable or suspected EVD can have detectable EBOV antigen-specific antibodies in their blood. This study aims to identify risk factors associated with detectable antibody levels in the absence of an EVD diagnosis.MethodologyData was collected from September 2015 to August 2017 from 1,366 consenting individuals across four study sites in the DRC (Boende, Kabondo-Dianda, Kikwit, and Yambuku). Seroreactivity was determined to EBOV GP IgG using Zaire Ebola Virus Glycoprotein (EBOV GP antigen) ELISA kits (Alpha Diagnostic International, Inc.) in Kinshasa, DRC; any result above 4.7 units/mL was considered seroreactive. Among the respondents, 113 (8.3%) were considered seroreactive. Several zoonotic exposures were associated with EBOV seroreactivity after controlling for age, sex, healthcare worker status, location, and history of contact with an EVD case, namely: ever having contact with bats, ever having contact with rodents, and ever eating non-human primate meat. Contact with monkeys or non-human primates was not associated with seroreactivity.ConclusionsThis analysis suggests that some zoonotic exposures that have been linked to EVD outbreaks can also be associated with EBOV GP seroreactivity in the absence of diagnosed EVD. Future investigations should seek to clarify the relationships between zoonotic exposures, seroreactivity, asymptomatic infection, and EVD.     

Transforming Clinical Data into Actionable Prognosis Models: Machine-Learning Framework and Field-Deployable App to Predict Outcome of Ebola Patients

BackgroundAssessment of the response to the 2014–15 Ebola outbreak indicates the need for innovations in data collection, sharing, and use to improve case detection and treatment. Here we introduce a Machine Learning pipeline for Ebola Virus Disease (EVD) prognosis prediction, which packages the best models into a mobile app to be available in clinical care settings. The pipeline was trained on a public EVD clinical dataset, from 106 patients in Sierra Leone.Conclusions/SignificanceThis method demonstrates how to address small sample sizes and missing data, while creating predictive models that can be readily deployed to assist treatment in future outbreaks of EVD and other infectious diseases. By generating an ensemble of predictors instead of relying on a single model, we are able to handle situations where patient data is partially available. The prognosis app can be updated as new data become available, and we made all the computational protocols fully documented and open-sourced to encourage timely data sharing, independent validation, and development of better prediction models in outbreak response.     

A Multi-Site Knowledge Attitude and Practice Survey of Ebola Virus Disease in Nigeria

Background

The 2014 Ebola Virus Disease (EVD) outbreak was characterised by fear, misconceptions and irrational behaviours. We conducted a knowledge attitude and practice survey of EVD in Nigeria to inform implementation of effective control measures.

Methods

Between July 30^th and September 30^th 2014, we undertook a cross sectional study on knowledge, attitude and practice (KAP) of Ebola Virus Disease (EVD) among adults of the general population and healthcare workers (HCW) in three states of Nigeria, namely Bayelsa, Cross River and Kano states. Demographic information and data on KAP were obtained using a self-administered standardized questionnaire. The percentage KAP scores were categorised as good and poor. Independent predictors of good knowledge of EVD were ascertained using a binary logistic regression model.

Results

Out of 1035 study participants with median age of 32 years, 648 (62.6%) were males, 846 (81.7%) had tertiary education and 441 (42.6%) were HCW. There were 218, 239 and 578 respondents from Bayelsa, Cross River and Kano states respectively. The overall median percentage KAP scores and interquartile ranges (IQR) were 79.46% (15.07%), 95.0% (33.33%) and 49.95% (37.50%) respectively. Out of the 1035 respondents, 470 (45.4%), 544(52.56%) and 252 (24.35%) had good KAP of EVD defined using 80%, 90% and 70% score cut-offs respectively. Independent predictors of good knowledge of EVD were being a HCW (Odds Ratio-OR-2.89, 95% Confidence interval-CI of 1.41–5.90), reporting ‘moderate to high fear of EVD’ (OR-2.15, 95% CI-(1.47–3.13) and ‘willingness to modify habit’ (OR-1.68, 95% CI-1.23–2.30).

Conclusion

Our results reveal suboptimal EVD-related knowledge, attitude and practice among adults in Nigeria. To effectively control future outbreaks of EVD in Nigeria, there is a need to implement public sensitization programmes that improve understanding of EVD and address EVD-related myths and misconceptions, especially among the general population.     

Predicting and Evaluating the Epidemic Trend of Ebola Virus Disease in the 2014-2015 Outbreak and the Effects of Intervention Measures

We constructed dynamic Ebola virus disease (EVD) transmission models to predict epidemic trends and evaluate intervention measure efficacy following the 2014 EVD epidemic in West Africa. We estimated the effective vaccination rate for the population, with basic reproduction number (R₀) as the intermediate variable. Periodic EVD fluctuation was analyzed by solving a Jacobian matrix of differential equations based on a SIR (susceptible, infective, and removed) model. A comprehensive compartment model was constructed to fit and predict EVD transmission patterns, and to evaluate the effects of control and prevention measures. Effective EVD vaccination rates were estimated to be 42% (31–50%), 45% (42–48%), and 51% (44–56%) among susceptible individuals in Guinea, Liberia and Sierra Leone, respectively. In the absence of control measures, there would be rapid mortality in these three countries, and an EVD epidemic would be likely recur in 2035, and then again 8~9 years later. Oscillation intervals would shorten and outbreak severity would decrease until the periodicity reached ~5.3 years. Measures that reduced the spread of EVD included: early diagnosis, treatment in isolation, isolating/monitoring close contacts, timely corpse removal, post-recovery condom use, and preventing or quarantining imported cases. EVD may re-emerge within two decades without control and prevention measures. Mass vaccination campaigns and control and prevention measures should be instituted to prevent future EVD epidemics.     

Effects of Mother’s Illness and Breastfeeding on Risk of Ebola Virus Disease in a Cohort of Very Young Children

Background

Young children who contract Ebola Virus Disease (EVD) have a high case fatality rate, but their sources of infection and the role of breastfeeding are unclear.

Methods/Principal Findings

Household members of EVD survivors from the Kerry Town Ebola Treatment Centre in Sierra Leone were interviewed four to 10 months after discharge to establish exposure levels for all members of the household, whether or not they became ill, and including those who died. We analysed a cohort of children under three years to examine associations between maternal illness, survival and breastfeeding, and the child’s outcome. Of 77 children aged zero to two years in the households we surveyed, 43% contracted EVD. 64 children and mothers could be linked: 25/40 (63%) of those whose mother had EVD developed EVD, compared to 2/24 (8%) whose mother did not have EVD, relative risk adjusted for age, sex and other exposures (aRR) 7·6, 95%CI 2·0–29·1. Among those with mothers with EVD, the risk of EVD in the child was higher if the mother died (aRR 1·5, 0·99–2·4), but there was no increased risk associated with breast-feeding (aRR 0·75, 0·46–1·2). Excluding those breastfed by infected mothers, half (11/22) of the children with direct contact with EVD cases with wet symptoms (diarrhoea, vomiting or haemorrhage) remained well.

Conclusion/Significance

This is the largest study of mother-child pairs with EVD to date, and the first attempt at assessing excess risk from breastfeeding. For young children the key exposure associated with contracting EVD was mother’s illness with EVD, with a higher risk if the mother died. Breast feeding did not confer any additional risk in this study but high risk from proximity to a sick mother supports WHO recommendations for separation. This study also found that many children did not become ill despite high exposures.     

Qualitative evidence syntheses of attitudes and preferences to inform guidelines on infant feeding in the context of Ebola Virus Disease (EVD) transmission risk

BackgroundBreast-feeding holds considerable potential to reduce infant mortality. Feeding choices, already complex, take on additional complexity against a backdrop of the risk of transmissible Ebola Virus. This review describes the factors that influence infant feeding and attitudes of pregnant women, mothers, family members and health practitioners, policy makers and providers (midwives) concerning infant feeding when there is a risk of Mother-to-Child (MTC) transmission of Ebola Virus Disease (EVD).MethodologyA systematic review of qualitative studies identified through rigorous searches of thirteen online databases and additional citation searches of included studies was undertaken. Search terms included breast-feeding, breast-feeding, infant feeding; Ebola; and qualitative, interview(s) and findings. Independent extraction of data by two reviewers using predefined extraction forms. Studies were assessed using the CASP Qualitative checklist.Principal findings5219 references were screened. 38 references related specifically to Ebola, and five papers met the inclusion criteria with data gathered from two settings: Guinea and Sierra Leone. The EVD outbreak had a significant impact on beliefs, attitudes, and resources to support infant feeding practices negatively affecting the nutritional status of children. The evidence from these studies highlight the need for guidance and appropriate psychosocial support need to be available to mothers who display symptoms and become infected and to front-line staff who are giving advice. Communities need to be engaged because stigma and fear may hinder uptake of appropriate interventions. The EVD outbreak caused multi-level system disruption akin to that seen following a natural disaster, meaning that logistics and coordination are critical and need adequate resourcing. Food production and distribution, and malnutrition screening are also disrupted and thereby compounding compromised nutritional status. The limited number of relevant studies highlights the need for further primary research, particularly in translation of messages to local settings.ConclusionsAn EVD outbreak causes multi-level disruption that negatively impacts infant feeding and child care practices. Negative impacts have multiple causes and successful planning for Ebola outbreaks requires that nutrition of infants and young children is a priority. Lessons from the Ebola pandemic have wider applicability to other pandemic contexts including Covid-19.