Exploring host-virus interaction to improve immunotherapy against Ebola virus.

Recent immunological advances have led to the development of FDA-approved immunotherapies against Ebola virus (EBOV). However, patients with high viral loads have not seen as large a benefit as mild cases. Here we discuss areas of investigation that may lead to adjunctive immune therapy for patients with severe EBOV disease.

Ebola virus disease: A review for the emergency medicine clinician.

INTRODUCTION: Ebolavirus, the causative agent of Ebola virus disease (EVD) has been responsible for sporadic outbreaks mainly in sub-Saharan Africa since 1976. EVD is associated with high risk of transmission, especially to healthcare workers during patient care. OBJECTIVE: The purpose of this review is to provide a concise review of EVD presentation, diagnosis, and management for emergency clinicians. DISCUSSION: EVD is spread through direct contact, including blood, bodily fluids or contact with a contaminated object. Patients may present with non-specific symptoms such as fevers, myalgias, vomiting, or diarrhea that overlap with other viral illnesses, but rash, bruising, and bleeding may also occur. Laboratory analysis may reveal transaminitis, coagulopathy, and disseminated intravascular coagulation. The average clinical course is approximately 8-10 days with an average case fatality rate of 50%. The mainstay of treatment is supportive care, with two U.S. Food and Drug Administration-approved monoclonal antibody treatments (Ebanga and Inmazeb). Survivors of the disease may have a complicated recovery, marked by long-term symptoms. CONCLUSION: EVD is a potentially deadly condition that can present with a wide range of signs and symptoms. Emergency clinicians must be aware of the presentation, evaluation, and management to optimize the care of these patients.

Interdisciplinary Collaboration in International Crisis Medical Relief: A Look at the Nepal Earthquake and Ebola Relief Efforts.

OBJECTIVE: This study explores interprofessional collaboration among medical and non-medical personnel planning and implementing international crisis health and medical relief efforts, and how disciplinary and professional background influences these activities. METHODS: This study analyzes semi-structured interviews with individuals involved in organizations medical or health services to the Ebola epidemic in West Africa (2014-2016) or the 2015 Nepal earthquake. RESULTS: Disciplinary background, sometimes coupled with organization role, shaped how relief workers engaged in the process of planning and implementing crisis medical relief. There were 3 thematic areas where these differences emerged: issue focus, problem -solving approaches, and decision-making approaches. Solutions from the field emerged as a fourth theme. CONCLUSIONS: The study demonstrates medical relief required collaboration across medical and non-medical professions and highlights the importance of relief workers' disciplinary background in shaping the planning and implementation of crisis medical relief. Successful collaboration requires that people involved in crisis relief communicate the relevance of their own expertise, identify limits of their own and others' disciplinary perspective(s), seek out strengths in others' expertise, and can identify/ respond appropriately to others who do not see their own disciplinary limits, as well as learn these skills before engaging in relief.

Understanding Experience of Patients With Highly Infectious Diseases During Extended Isolation: A Design Perspective.

OBJECTIVES: This study aimed to develop a better understanding of the unique needs of patients with highly infectious diseases and their perceptions of being placed in isolation. We explore the subjective experiences of patients treated for Ebola in a biocontainment unit (BCU) and the healthcare personnel who cared for them. BACKGROUND: The 2014 Ebola outbreak and the COVID-19 pandemic have brought to focus some major challenges of caring for patients with serious infectious diseases. Previous studies on BCU design have looked at ways to prevent self- and cross-contamination, but very few have examined how the built environment can support an improved patient experience. METHOD: A qualitative study was conducted with four patients treated for Ebola and two critical care nurses who provided direct care to them at a single BCU in the U.S. Data were collected through in-depth semi-structured interviews to capture the actual patients' perception and experience of isolation. The interviews were analyzed using the thematic analysis approach. RESULTS: The Ebola patients placed in source isolation perceived the BCU as an artificial environment where they lacked control, agency, autonomy, and independence. The physical separation from other patients, visitor restrictions, and staff wearing PPE contributed to feelings of social and emotional isolation, and loneliness. CONCLUSIONS: The isolation can take a toll on physiological and psychological well-being. A thoughtful design of isolation units may improve patients' experience by supporting human and social interactions, empowering patients through space flexibility and personalization of space, and supporting a more holistic approach to isolation care.

Sudan virus disease outbreak in Uganda: urgent research gaps.

The Sudan ebolavirus (SUDV) outbreak highlights our ongoing vulnerability to re-emerging high-consequence infectious diseases. Although the Minister of health in Uganda has initiated public health measures in collaboration with neighbouring countries and with support of the WHO, cases have continued to spread to several regions including the capital. The ongoing transmission, uncertain case numbers and no licensed vaccine or therapeutics available are a cause for concern. We searched four databases for SUDV research using the search terms "SUDV", "Sudan Virus" and "Ebola Sudan". Our analysis identified only 20 SUDV research studies. Most were implemented in the USA and only one in Uganda. Nine studies were on therapeutics, eight on vaccines, one on diagnostics, one in one health and one in social science. Our data highlight a lack of SUDV research and an urgent need for investment to identify an effective vaccine, and optimal supportive care and therapeutic strategies for all at risk groups as a key research priority. Research investments should be prioritised into vaccines and treatment strategies that will be accessible to high-risk populations in affected regions during the outbreak, to protect populations, improve individual outcomes and facilitate outbreak control.

The PA profession in Liberia: A case study in pioneering innovation and resiliency.

ABSTRACT: In Liberia, the physician assistant (PA) profession began in the mid-1960s. PAs have had a major role in providing access to healthcare for patients, many of whom live in poverty and reside in remote areas where access to physicians may be severely limited. In 1964, representatives from UNICEF selected Agnes N. Dagbe, MS, RN, to be the first director of a new PA program to be developed at the Tubman National Institute of Medical Arts. Dagbe was sent to Russia to learn about their feldsher profession, which served as a significant source of inspiration for the newly emerging PA profession in Liberia. To date, Liberia has faced extreme shortages of physicians, the ravages of two brutal civil wars over a 14-year period (1989-2003), as well as outbreaks of the Ebola and COVID-19 viruses. Now, more than 54 years since the first class graduated, PAs are vital for the delivery of essential healthcare services for the citizens of Liberia.

Fractional-Order Ebola-Malaria Coinfection Model with a Focus on Detection and Treatment Rate.

Coinfection of Ebola virus and malaria is widespread, particularly in impoverished areas where malaria is already ubiquitous. Epidemics of Ebola virus disease arise on a sporadic basis in African nations with a high malaria burden. An observational study discovered that patients in Sierra Leone's Ebola treatment centers were routinely infected with malaria parasites, increasing the risk of death. In this paper, we study Ebola-malaria coinfections under the generalized Mittag-Leffler kernel fractional derivative. The Banach fixed point theorem and the Krasnoselskii type are used to analyse the model's existence and uniqueness. We discuss the model stability using the Hyers-Ulam functional analysis. The numerical scheme for the Ebola-malaria coinfections using Lagrange interpolation is presented. The numerical trajectories show that the prevalence of Ebola-malaria coinfections ranged from low to moderate depending on memory. This means that controlling the disease requires adequate knowledge of the past history of the dynamics of both malaria and Ebola. The graphical dynamics of the detection rate indicate that a variation in the detection rate only affects the following compartments: individuals that are latently infected with the Ebola, Ebola virus afflicted people who went unnoticed, individuals who have been infected with the Ebola virus and have been diagnosed with the disease, and persons undergoing Ebola virus therapy.

Response to Mass-Casualty Incidents and Outbreaks: A Prehospital Disaster Training Package Developed for the National Emergency Medical Service in Sierra Leone.

Sierra Leone is a country highly prone to disasters, still recovering from the catastrophic 2014 Ebola epidemic. In 2018, the country launched its first National Emergency Medical Service (NEMS) aiming to strengthen the provision of essential health services to the population with the long-term goal of creating a resilient health system able to effectively respond to and recover from emergencies. The Center for Research and Training in Disaster Medicine, Humanitarian Aid, and Global Health (CRIMEDIM), together with the Italian NGO Doctors with Africa (CUAMM), under the direct supervision of the Ministry of Health and Sanitation (MoHS), developed a prehospital Disaster Training Package (DTP) to be delivered to all NEMS personnel to boost the prehospital management of mass-casualty incidents (MCIs) and outbreaks. The DTP included a first phase in which NEMS local trainers underwent a training-of-trainers (ToT) course, enabling them to deliver cascade trainings to 16 district ambulance supervisors, 441 paramedics, 441 ambulance drivers, and 36 operators working in the NEMS operation center. This on-going training package represents the first Disaster Medicine training course for prehospital health professionals in Sierra Leone.

Regulating clinical trials in a resource-limited setting during the Ebola public health emergency in Sierra Leone.

Clinical trials during public health emergencies of novel medical products such as therapeutics and vaccines in resource-limited settings are daunting due to the limited capacity for regulatory assessment. Regulating clinical trials during the Ebola outbreak in Sierra Leone required expedited evaluation to identify medical products that could be promptly introduced to combat the epidemic in the absence of approved treatment or prevention. This article explored the decisions taken by the Pharmacy Board of Sierra Leone through its Expert Committee on Medicine Safety and Clinical Trials regarding clinical trials oversight during the Ebola epidemic and the lessons learned. This independent expert committee assessed and provided scientific opinions to the Pharmacy Board of Sierra Leone to inform approval of all clinical trials within 10-15 working days. We also requested for assisted review from the African Vaccine Regulatory Forum and support from the US Food and Drug Administration through a unilateral recognition and reliance memorandum of understanding. In addition, the Agency-ensured structures and systems were in place for reporting and reviewing adverse events and serious adverse events, management of biological samples, submission and review of progress reports, and good clinical practice inspections. Unfortunately, the Ebola epidemic revealed many weaknesses in the country's clinical trials regulatory structure and processes. Government and partners should further offer more resources to build the clinical trial structures and systems so that the Agency will be better poised to handle future public health emergencies.

Homage to Ebola Fighters: Black Labor and Humanitarian Media Campaigns.

During the Ebola outbreak that hit Guinea in 2014, most of the people employed at the Wonkifong Ebola treatment unit were from Africa or Cuba. Despite the recruitment of black personnel, the unit exposes how the humanitarian infrastructure exploited Guinean workers as if their lives were less vulnerable than those of the foreign personnel. The Africanization of aid reveals a post-colonial segregation at the intersection of race, class, and locality. The article follows Guinean workers in the quarantine unit, as well as their enrolment in media campaigns. Their experience illuminates a triage at the core of Global Health according to which not only were local workers treated as expendable lives, but their stories were silenced. Yet how did Guinean workers inhabit this anti-black world? The article unfolds the journey of workers during the outbreak and three years later, exploring the strategies they used to produce their own narratives through personal archives. [humanitarian aid, humanitarian media campaigns, race, Ebola, archives].

Durant l'épidémie d'Ebola qui frappa la Guinée en 2014, la majorité des soignants du centre de traitement Ebola de Wonkifong provenait d'Afrique ou de Cuba. Cependant, malgré le recrutement d'un personnel majoritairement noir, l'infrastructure humanitaire a exploité les travailleurs guinéens comment si leurs vies étaient moins vulnérables que celles du personnel étranger. Ainsi l'africanisation de l'aide met en lumière une ségrégation postcoloniale à l'intersection de la race, de la classe et de la localité. Cet article explore le parcours des travailleurs guinéens dans l'unité de quarantaine ainsi qu'au travers de leur engagement dans des campagnes médiatiques. Leur expérience dévoile un tri au cœur de la santé globale au travers duquel les travailleurs locaux ont été non seulement traités comme des vies consommables mais leur histoire a également été passée sous silence. Cependant, comment les soignants guinéens sont-ils capables d'habiter cet univers anti-noir ? L'article suit ces travailleurs durant l'épidémie de même que trois ans plus tard, il explore ainsi les stratégies utilisées par ces derniers pour produire leurs propres récits au travers d'archives personnelles.

The Salience of Trust to the Client-Provider Relationship in Post-Ebola Guinea: Findings From a Qualitative Study.

Lack of trust in the health care system can serve as a barrier to service utilization, especially in pandemic and postemergency settings. Although previous research has identified domains of trust that contribute to individuals' trust in the health system, little research exists from low- and middle-income countries, particularly during and after infectious disease outbreaks. The current study-conducted to inform activities for a post-Ebola program-explored perceptions and experiences of health care provision in post-Ebola Guinea, with particular attention to trust. Researchers conducted in-depth interviews with health workers (n=15) and mothers of young children (n=29) along with 12 focus group discussions with grandmothers of young children and 12 with male heads of household. The study occurred in Basse Guinée and Guinée Forestière-2 areas hardest hit by Ebola. Respondents identified a breach of trust during the epidemic, with several domains emerging as relevant for renewed trust and care-seeking practices. At the core of a trusting client-provider relationship was the inherent belief that providers had an intrinsic duty to treat clients well. From there, perceived provider competence, the hospitality at the facility, provider empathy, transparency about costs, and commitment to confidentiality emerged as relevant influences on participant trust in providers. Community members and providers expressed similar viewpoints regarding trust and discussed the role of open communication and community mobilization in rebuilding trust. Study findings informed a variety of program activities, including the development of campaign messages and interpersonal communication trainings for health workers. This study provides valuable insight about some underlying components of trust that can provide key leverage points to rebuild trust and promote care seeking in postemergency settings. This insight is informing program activities in the current Ebola response in Guinea and could be useful in other crises, such as the global coronavirus disease (COVID-19) pandemic.

Cross-sectional study of mental health and sexual behaviours for Ebola Survivors in Beni, Butembo and Katwa health zones of the Democratic Republic of Congo.

OBJECTIVES: To understand the prevalence of mental health disorders in Ebola-affected communities and their association with condom use. DESIGN: Cross-sectional study. SETTING: Beni, Butembo and Katwa health zones, Democratic Republic of Congo (DRC). PARTICIPANTS: 223 adult Ebola survivors, 102 sexual partners and 74 comparison respondents. PRIMARY AND SECONDARY OUTCOME MEASURES: Post-traumatic stress disorder (PTSD), depression, anxiety, substance use, suicidal ideation and attempts, stigma, condom use and sexual behaviour. RESULTS: Most respondents reported to be married, Christian, from the Nande ethnic group, and farmers/herders. Survivors met symptom criteria for depression at higher rates than partners (23.5% (95% CI 18.0 to 29.1) vs 5.7 (1.2 to 10.1); p<0.001). PTSD symptom criteria for survivors (24.1%, 95% CI 18.5% to 29.7%) and partners (16.7%, 95% CI 9.4% to 23.9%) were four times greater than the comparison participants (6.0%, 95% CI 0.6% to 11.4%). Two times as many survivors as partners reported that sexual activity precautions were discussed at discharge (71.5% (95% CI 65.6 to 77.5) vs 36.2% (95% CI 26.9 to 45.5); p<0.001). The majority of survivors (95.0 (95% CI 85.1% to 98.5%) and partners 98.5% (95% CI 89.6% to 99.8%; p=0.26) participated in risky sexual behaviour after the survivor left the Ebola treatment centre. The ability to refuse sex or insist on condom use before Ebola had a threefold increase in the odds of condom use (adjusted OR 3.3, 95% CI 1.7 to 6.1, p<0.001). Up to 36% of the comparison group held discriminatory views of survivors. CONCLUSIONS: The new outbreaks in both Guinea and DRC show Ebola remains in semen longer than previously known. Understanding and addressing condom non-use and updating condom use guidelines are necessary to protect against future Ebola outbreaks, especially among sexual partners who did not have similar access to health information regarding sexual transmission of Ebola. Mental health treatment and decreasing stigma in Ebola areas is a priority.

'I can't leave everything in the hands of my husband': Economic constraints and gender roles in care-seeking in post-Ebola Guinea.

The 2014-2016 Ebola epidemic in West Africa had enduring effects on health systems and healthcare utilisation. This study explores the intersection of economic constraints and gender roles in Guinea to understand delays in care-seeking post-Ebola. In-depth interviews (n = 45) and focus group discussions (n = 24) were conducted with mothers, male heads of household, grandmothers, and health workers in rural and urban areas in Basse-Guinée and Guinée Forestière. A thematic analysis identified salient themes related to gender and economic constraints on health care-seeking. Participants, particularly men, emphasised the high cost of seeking care, which led to delays as women secured funds. Men's engagement in care-seeking included providing funds and permission, picking up medication, and giving appointment reminders. As principal actors when 'navigating' the healthcare system, women were intimately involved in economic decisions and responsible for securing funds for services - even when lacking direct financial control. Essentialist descriptions of men as 'providers' and women as 'navigators', therefore, masked nuances in care-seeking and economic responsibilities. Programmes must acknowledge men's engagement in care-seeking and address both the economic barriers women face when seeking care and their economic roles. Greater attention to the complex intersection of economic constraints and gender roles could address care-seeking delays.

(Re)arranging "systems of care" in the early Ebola response in Sierra Leone: An interdisciplinary analysis.

Despite an expanding literature on Ebola-response, few studies detail or reflect on the responses of diverse systems of care. Little is known about how, why or in what ways, strategies of ill-health management were enacted locally, how health-systems power, authority and hierarchy were perceived and contested, or how other social systems, institutions and relationships shaped the response. This paper presents an interdisciplinary analysis of local responses in two early affected districts in Sierra Leone. Drawing on anthropological theories of social ordering and assemblage, we present an analysis of contrasting infection chains in three extended case studies from Bo and Moyamba districts. In contrast to previous scholarship which has understood local actions as being reactive (supporting or obstructing) to a national Ebola response, we show that local arrangements lead and shape responses. Our cases show how multiple, entangled, dynamic and co-existing systems of care influence these responses. Some individuals and communities collaborated with health authorities on measures like reporting and quarantine, others actively opposed them, or played an intermediary role. Collectively, formal health systems actors, local authorities and ordinary citizens negotiated and enacted new arrangements. These arrangements involved compromise and sometimes power was reconfigured. They were also shaped by wider political and historical contexts and by availability or absence of formal healthcare resources. Our research shows the critical importance of understanding how institutions and people involved in healthcare enact diverse "systems of care" and thereby shape Ebola response. Most importantly, our work underlines the need for alignment between formal health-systems and wider social, cultural, political and economic forms of organisation at family and community levels to improve crisis-response and promote sustainable care. In particular, health systems responders need to identify and engage with key brokers - or arrangers - in frontline care systems, with whom mutually acceptable, and effective, reconfigurations of care can be achieved.

Therapeutic vaccination strategies against EBOV by rVSV-EBOV-GP: the role of innate immunity.

Zaire Ebola virus (EBOV) is a member of the Filoviridae family. Infection with EBOV causes Ebola virus disease (EVD) characterized by excessive inflammation, lymphocyte death, coagulopathy, and multi-organ failure. In 2019, the FDA-approved the first anti-EBOV vaccine, rVSV-EBOV-GP (Ervebo® by Merck). This live-recombinant vaccine confers both prophylactic and therapeutic protection to nonhuman primates and humans. While mechanisms conferring prophylactic protection are well-investigated, those underlying protection conferred shortly before and after exposure to EBOV remain poorly understood. In this review, we review data from in vitro and in vivo studies analyzing early immune responses to rVSV-EBOV-GP and discuss the role of innate immune activation in therapeutic protection.

Identification and Characterization of a Novel Single Domain Antibody Against Ebola Virus.

Ebola virus (EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for treating EBOV infection. However, clinical studies have demonstrated that the mortality rate of the patients who received these two antibody drugs remains above 30%. Therefore, novel therapeutics with better efficacy is still desired. The isolated human IgG1 constant domain 2 (CH2 domain) has been proposed as a scaffold for the development of C-based single domain antibodies (C-sdAbs) as therapeutic candidates against viral infections and other diseases. Here, we screened and identified a novel C-sdAb termed M24 that targets EBOV glycoprotein (GP) from a C-sdAb phage display library. M24 neutralizes the pseudotype EBOV with IC50 of 0.8 nmol/L (12 ng/mL) and has modest neutralizing activity against authentic EBOV. Epitope determination, including molecular docking and site mutation analysis, discloses that M24 binds to the internal fusion loop (IFL) within GP2, a transmembrane subunit of GP. Interestingly, we found that the binding of M24 to GP at pH 5.5 has dramatically decreased compared to the binding at pH 7.5, which may lead to weak efficacy in the neutralization of authentic EBOV. Since no sdAb against EBOV infection has been reported to date, our results not only give a proof of concept that sdAbs could be utilized for the development of potential therapeutic candidates against EBOV infection, but also provide useful information for the discovery and improvement of anti-EBOV agents.