"If I die for touching him, let me die": a rapid ethnographic assessment of cultural practices and Ebola transmission in high-risk border regions of Tanzania.

BACKGROUND: Ebola Virus Disease (EVD) is a rare but contagious disease caused by Ebola Virus (EBOV). The first Ebola outbreaks were reported in the Democratic Republic of Congo (DRC) before subsequent reported cases in Western and East African countries, including Uganda, which borders Tanzania. Proximity to EVD-infected countries raises the prospect of cross-border transmission, raising alarm in Tanzania. This study aimed to explore the cultural practices likely to prevent or escalate EVD transmission in the event of its outbreak in the country. METHODS: This rapid ethnographic assessment employed observation, interviews, and focus group discussions to collect data from people with diverse characteristics in five regions of Tanzania Mainland namely, Kagera, Kigoma, Mwanza and Songwe regions and Zanzibar Island. The qualitative data was then subjected to thematic analysis. FINDINGS: Cultural practices may escalate the transmission of EVD and hinder its prevention and control. These cultural practices include caring sick people at home, confirmation of death, mourning, and body preparation for burial. Communal life, ceremonies, and social gatherings were other aspects observed to have the potential for compounding EVD transmission and hindering its containment in case of an outbreak. CONCLUSION: Cultural practices may escalate EVD transmission as identified in the study settings. As such, Risk Communication and Community Engagement (RCCE) activities should be interventionist in transforming cultural practices that may escalate the spread of EVD as part of preparedness, prevention, and control efforts in the event of an outbreak.

Novel proteolytic activation of Ebolavirus glycoprotein GP by TMPRSS2 and cathepsin L at an uncharted position can compensate for furin cleavage.

A multistep priming process involving furin and endosomal cathepsin B and L (CatB/L) has been described for the Orthoebolavirus zairense (EBOV) glycoprotein GP. Inhibition or knockdown of either furin or endosomal cathepsins, however, did not prevent virus multiplication in cell cultures. Moreover, an EBOV mutant lacking the furin cleavage motif (RRTRR→AGTAA) was able to replicate and cause fatal disease in nonhuman primates, indicating that furin cleavage may be dispensable for virus infectivity. Here, by using protease inhibitors and EBOV GP-carrying recombinant vesicular stomatitis virus (VSV) and transcription and replication-competent virus-like particles (trVLPs) we found that processing of EBOV GP is mediated by different proteases in different cell lines depending on the protease repertoire available. Endosomal cathepsins were essential for EBOV GP entry in Huh-7 but not in Vero cells, in which trypsin-like proteases and stably expressed trypsin-like transmembrane serine protease 2 (TMPRSS2) supported wild-type EBOV GP and EBOV GP_AGTAA mutant entry. Furthermore, we show that the EBOV GP_AGTAA mutant is cleaved into fusion-competent GP2 by TMPRSS2 and by CatL at a so far unknown site. Fluorescence microscopy co-localization studies indicate that EBOV GP cleavage by TMPRSS2 may occur in the TGN prior to virus release or in the late endosome at the stage of virus entry into a new cell. Our data show that EBOV GP must be proteolytically activated to support virus entry but has even greater flexibility in terms of proteases and the precise cleavage site than previously assumed.

Computational mining of B cell receptor repertoires reveals antigen-specific and convergent responses to Ebola vaccination.

Outbreaks of Ebolaviruses, such as Sudanvirus (SUDV) in Uganda in 2022, demonstrate that species other than the Zaire ebolavirus (EBOV), which is currently the sole virus represented in current licensed vaccines, remain a major threat to global health. There is a pressing need to develop effective pan-species vaccines and novel monoclonal antibody-based therapeutics for Ebolavirus disease. In response to recent outbreaks, the two dose, heterologous Ad26.ZEBOV/MVA-BN-Filo vaccine regimen was developed and was tested in a large phase II clinical trial (EBL2001) as part of the EBOVAC2 consortium. Here, we perform bulk sequencing of the variable heavy chain (VH) of B cell receptors (BCR) in forty participants from the EBL2001 trial in order to characterize the BCR repertoire in response to vaccination with Ad26.ZEBOV/MVA-BN-Filo. We develop a comprehensive database, EBOV-AbDab, of publicly available Ebolavirus-specific antibody sequences. We then use our database to predict the antigen-specific component of the vaccinee repertoires. Our results show striking convergence in VH germline gene usage across participants following the MVA-BN-Filo dose, and provide further evidence of the role of IGHV3-15 and IGHV3-13 antibodies in the B cell response to Ebolavirus glycoprotein. Furthermore, we found that previously described Ebola-specific mAb sequences present in EBOV-AbDab were sufficient to describe at least one of the ten most expanded BCR clonotypes in more than two thirds of our cohort of vaccinees following the boost, providing proof of principle for the utility of computational mining of immune repertoires.

Innate and cellular immune response to the Ebola vaccine Ad26.ZEBOV, MVA-BN-Filo: an ancillary study of the EBL2001 phase II trial.

BACKGROUND: The EBL2001 phase 2 trial tested the two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine in Europe. Safety and humoral immunogenicity assessments led to EU market authorization in 2020. Complementary analyses of immune responses are warranted to better characterize vaccine effects. METHODS: We conducted an ancillary study to analyze changes in the serum and cellular responses. Serum biomarkers of activation/inflammation were evaluated using a Luminex assay. Vaccine-elicited T cell responses and functions were evaluated assessing their phenotype, cytokine production, proliferation and cytotoxic potential. Integrated data analysis was performed through correlation and principal component analysis of serum biomarkers and cellular immune responses. RESULTS: Forty-eight volunteers were included. The Ad26.ZEBOV, MVA-BN-Filo vaccine elicited: i) serum increase of inflammatory/activation markers mainly at 1 day after the Ad26.ZEBOV vaccine; ii) durable EBOV-specific T cell proliferation and CD8+ T cells exhibiting a cytotoxic phenotype after Ad26.ZEBOV prime, after MVA-BN-Filo boost and 6 months post vaccination. Integrated analysis revealed correlations between: i) EBOV-specific CD8+ T cell proliferation and cytotoxic phenotype; ii) high EBOV-specific CD8+ T cell cytotoxic phenotype and low inflammatory marker IL-8 at day 1 post vaccination. DISCUSSION: This study provides unique insights into the in vivo contribution of proliferation/cytotoxic CD8+ T cells and inflammation to the Ad26.ZEBOV, MVA-BN-Filo vaccine-induced potency.

Prevention and control of Ebola virus transmission: mathematical modelling and data fitting.

The Ebola virus disease (EVD) has been endemic since 1976, and the case fatality rate is extremely high. EVD is spread by infected animals, symptomatic individuals, dead bodies, and contaminated environment. In this paper, we formulate an EVD model with four transmission modes and a time delay describing the incubation period. Through dynamical analysis, we verify the importance of blocking the infection source of infected animals. We get the basic reproduction number without considering the infection source of infected animals. And, it is proven that the model has a globally attractive disease-free equilibrium when the basic reproduction number is less than unity; the disease eventually becomes endemic when the basic reproduction number is greater than unity. Taking the EVD epidemic in Sierra Leone in 2014-2016 as an example, we complete the data fitting by combining the effect of the media to obtain the unknown parameters, the basic reproduction number and its time-varying reproduction number. It is shown by parameter sensitivity analysis that the contact rate and the removal rate of infected group have the greatest influence on the prevalence of the disease. And, the disease-controlling thresholds of these two parameters are obtained. In addition, according to the existing vaccination strategy, only the inoculation ratio in high-risk areas is greater than 0.4, the effective reproduction number can be less than unity. And, the earlier the vaccination time, the greater the inoculation ratio, and the faster the disease can be controlled.

Dysglycaemia in Ebola virus disease: a retrospective analysis from the 2018 to 2020 outbreak.

BACKGROUND: Ebola virus disease (EVD) is associated with multisystem organ failure and high mortality. Severe hypoglycaemia is common, life-threatening, and correctable in critically ill patients, but glucose monitoring may be limited in EVD treatment units. METHODS: We conducted a retrospective review of patients admitted to EVD treatment units in Butembo and Katwa, Eastern DRC. Glucose measurements were done using a handheld glucometer at the bedside or using the Piccolo xpress Chemistry Analyzer on venous samples. FINDINGS: 384 patients (median age 30 years (interquartile range, IQR, 20-45), 57% female) and 6422 glucose measurements (median 11 per patient, IQR 4-22) were included in the analysis. Severe hypoglycaemia (≤2.2 mmol/L) and hyperglycaemia (>10 mmol/L) were recorded at least once during the ETU admission in 97 (25%) and 225 (59%) patients, respectively. A total of 2004 infusions of glucose-containing intravenous solutions were administered to 302 patients (79%) with a median cumulative dose of 175g (IQR 100-411). The overall case fatality rate was 157/384 (41%) and was 2.2-fold higher (95% CI 1.3-3.8) in patients with severe hypoglycaemia than those without hypoglycaemia (p = 0.0042). In a multivariable Cox proportional hazards model, periods of severe hypoglycaemia (adjusted hazard ratio (aHR) 6.2, 95% CI 3.2-12, p < 0.0001) and moderate hypoglycaemia (aHR 3.0, 95% CI 1.9-4.8, p < 0.0001) were associated with elevated mortality. INTERPRETATION: Hypoglycaemia is common in EVD, requires repeated correction with intravenous dextrose solutions, and is associated with mortality. FUNDING: This study was not supported by any specific funding.

Sentiment Analysis of Social Media Data on Ebola Outbreak Using Deep Learning Classifiers.

The Ebola virus disease (EVD) is an extremely contagious and fatal illness caused by the Ebola virus. Recently, Uganda witnessed an outbreak of EVD, which generated much attention on various social media platforms. To ensure effective communication and implementation of targeted health interventions, it is crucial for stakeholders to comprehend the sentiments expressed in the posts and discussions on these online platforms. In this study, we used deep learning techniques to analyse the sentiments expressed in Ebola-related tweets during the outbreak. We explored the application of three deep learning techniques to classify the sentiments in 8395 tweets as positive, neutral, or negative. The techniques examined included a 6-layer convolutional neural network (CNN), a 6-layer long short-term memory model (LSTM), and an 8-layer Bidirectional Encoder Representations from Transformers (BERT) model. The study found that the BERT model outperformed both the CNN and LSTM-based models across all the evaluation metrics, achieving a remarkable classification accuracy of 95%. These findings confirm the reported effectiveness of Transformer-based architectures in tasks related to natural language processing, such as sentiment analysis.

Evaluation of potency and metabolic stability of diphyllin-derived Vacuolar-ATPase inhibitors.

Diphyllin is a naturally occurring lignan comprised of an aryl naphthalene lactone scaffold that demonstrates beneficial biological activities in disease models of cancer, obesity, and viral infection. A target of diphyllin and naturally occurring derivatives is the vacuolar ATPase (V-ATPase) complex. Although diphyllin-related natural products are active with in vitro models for viral entry, the potencies and unknown pharmacokinetic properties limit well-designed in vivo evaluations. Previous studies demonstrated that diphyllin derivatives have the utility of blocking the Ebola virus cell entry pathway. However, diphyllin shows limited potency and poor oral bioavailability in mice. An avenue to improve the potency was used in a new library of synthetic derivatives of diphyllin. Diphyllin derivatives exploiting ether linkages at the 4-position with one-to-three carbon spacers to an oxygen or nitrogen atom provided compounds with EC50 values ranging from 7 to 600 nM potency and selectivity up to >500 against Ebola virus in infection assays. These relative potencies are reflected in the Ebola virus infection of primary macrophages, a cell type involved in early pathogenesis. A target engagement study reveals that reducing the ATPV0a2 protein expression enhanced the potency of diphyllin derivatives to block EBOV entry, consistent with effects on the endosomal V-ATPase function. Despite the substantial enhancement of antiviral potencies, limitations were identified, including rapid clearance predicted by in vitro microsome stability assays. However, compounds with similar or improved half-lives relative to diphyllin demonstrated improved pharmacokinetic profiles in vivo. Importantly, these derivatives displayed suitable plasma levels using oral administration, establishing the feasibility of in vivo antiviral testing.

(+)-fenchol and (-)-isopinocampheol derivatives targeting the entry process of filoviruses.

The increasing frequency of filovirus outbreaks in African countries has led to a pressing need for the development of effective antifilovirus agents. In continuation of our previous research on the antifilovirus activity of monoterpenoid derivatives, we synthesized a series of (+)-fenchol and (-)-isopinocampheol derivatives by varying the type of heterocycle and linker length. Derivatives with an N-alkylpiperazine cycle proved to be the most potent antiviral compounds, with half-maximal inhibitory concentration (IC50) 1.4-20 µÐœ against Lenti-EboV-GP infection and 11.3-47 µÐœ against Lenti-MarV-GP infection. Mechanism-of-action experiments revealed that the compounds may exert their action by binding to surface glycoproteins (GPs). It was demonstrated that the binding of the synthesized compounds to the Marburg virus GP is less efficient as compared to the Ebola virus GP. Furthermore, it was shown that the compounds possess lysosomotropic properties. Thus, the antiviral activity may be due to dual effects. This study offers new antiviral agents that are worthy of further exploration.

Ebola virus-induced eye sequelae: a murine model for evaluating glycoprotein-targeting therapeutics.

BACKGROUND: Ebola virus disease (EVD) survivors experience ocular sequelae including retinal lesions, cataracts, and vision loss. While monoclonal antibodies targeting the Ebola virus glycoprotein (EBOV-GP) have shown promise in improving prognosis, their effectiveness in mitigating ocular sequelae remains uncertain. METHODS: We developed and characterized a BSL-2-compatible immunocompetent mouse model to evaluate therapeutics targeting EBOV-GP by inoculating neonatal mice with vesicular stomatitis virus expressing EBOV-GP (VSV-EBOV). To examine the impact of anti-EBOV-GP antibody treatment on acute retinitis and ocular sequelae, VSV-EBOV-infected mice were treated with polyclonal antibodies or monoclonal antibody preparations with antibody-dependent cellular cytotoxicity (ADCC-mAb) or neutralizing activity (NEUT-mAb). FINDINGS: Treatment with all anti-EBOV-GP antibodies tested dramatically reduced viremia and improved survival. Further, all treatments reduced the incidence of cataracts. However, NEUT-mAb alone or in combination with ADCC-mAb reduced viral load in the eyes, downregulated the ocular immune and inflammatory responses, and minimized retinal damage more effectively. INTERPRETATION: Anti-EBOV-GP antibodies can improve survival among EVD patients, but improved therapeutics are needed to reduce life altering sequelae. This animal model offers a new platform to examine the acute and long-term effect of the virus in the eye and the relative impact of therapeutic candidates targeting EBOV-GP. Results indicate that even antibodies that improve systemic viral clearance and survival can differ in their capacity to reduce acute ocular inflammation, and long-term retinal pathology and corneal degeneration. FUNDING: This study was partly supported by Postgraduate Research Fellowship Awards from ORISE through an interagency agreement between the US DOE and the US FDA.

Identification of Prospective Ebola Virus VP35 and VP40 Protein Inhibitors from Myxobacterial Natural Products.

The Ebola virus (EBOV) is a lethal pathogen causing hemorrhagic fever syndrome which remains a global health challenge. In the EBOV, two multifunctional proteins, VP35 and VP40, have significant roles in replication, virion assembly, and budding from the cell and have been identified as druggable targets. In this study, we employed in silico methods comprising molecular docking, molecular dynamic simulations, and pharmacological properties to identify prospective drugs for inhibiting VP35 and VP40 proteins from the myxobacterial bioactive natural product repertoire. Cystobactamid 934-2, Cystobactamid 919-1, and Cittilin A bound firmly to VP35. Meanwhile, 2-Hydroxysorangiadenosine, Enhypyrazinone B, and Sorangiadenosine showed strong binding to the matrix protein VP40. Molecular dynamic simulations revealed that, among these compounds, Cystobactamid 919-1 and 2-Hydroxysorangiadenosine had stable interactions with their respective targets. Similarly, molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations indicated close-fitting receptor binding with VP35 or VP40. These two compounds also exhibited good pharmacological properties. In conclusion, we identified Cystobactamid 919-1 and 2-Hydroxysorangiadenosine as potential ligands for EBOV that target VP35 and VP40 proteins. These findings signify an essential step in vitro and in vivo to validate their potential for EBOV inhibition.

On alert for Ebola: public health risk assessment of travellers from Uganda to the USA during the 2022 outbreak.

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

Ebola virus circulation in a non-epidemic Guinean rural area: A mixed-method approach to assessing endemicity.

OBJECTIVES: This study aimed to investigate the prevalence of orthoebolavirus antibodies in Madina Oula, a non-epidemic rural area in Guinea, in 2022. METHODS: A cross-sectional study was conducted from March 14 to April 3, 2022 involving recording household and socio-demographic characteristics, lifestyle data, and collecting dried blood spots from 878 individuals in 235 households. Dried blood spots were tested using multiplex serology to detect antibodies to different orthoebolaviruses: Ebola virus, Bundibugyo virus, Sudan virus, Reston virus, and Bombali virus. Seroprevalence was estimated with a 95% confidence interval and a Z-test was performed to compare the seropositivity between children aged under 15 years and those over 15 years. Household and participant characteristics were analyzed using descriptive statistic, and socio-historical conditions were discussed. RESULTS: The serological analysis conducted in 2022 on 878 participants revealed varying reactivity to orthoebolavirus antigens, notably, with glycoprotein antigens, particularly, glycoprotein Sudan virus (16%). A total of 21 samples exhibited reactivity with at least two antigens, with a median age of 27 years (interquartile range 10.00-35.00), ranging from 2 to 80 years. There is no significant difference between seropositivity in children aged under 15 (2.86%) years and those over 15 (2.14%) years. The antibody presence varied per village, with the highest prevalence observed in Ouassou and Dar-es-Salam. CONCLUSIONS: Serological data in a region unaffected by recent Ebola outbreaks indicate possible orthoebolavirus endemicity, emphasizing the need for preparedness against known or novel orthoebolaviruses with potential cross-reactivity.

Prevalence of somatic symptoms among Ebola Virus Disease (EVD) survivors in Africa: a systematic review and meta-analysis.

BACKGROUND: Many Ebola virus disease (EVD) survivors have reported somatic and neuropsychological symptoms after discharge from the Ebola Treatment Unit (ETU). Since the 2014-2016 Ebola epidemic in West Africa, various studies have investigated and identified these symptoms. Evidence on somatic symptoms is widely available in the literature, however, there is no concise overview of the prevalence across different time intervals. METHODS: This meta-analysis was conducted following the (PRISMA) guidelines. A database search was conducted to identify original studies that reported the prevalence of symptoms. The primary outcome measure was the prevalence rate of several somatic symptoms. Results were pooled, and prevalence rates were assessed over time, to elucidate any particular trends. RESULTS: We included 23 studies (5,714 participants). The pooled prevalence was: arthralgia 50% (95% CI: 41%-59%); headache 44% (95% CI: 36%-52%); myalgia 32% (95% CI: 26%-38%); abdominal pain 27% (95% CI: 15%-39%); fatigue 25% (95% CI: 19%-31%); numbness of feet 16% (95% CI: 14%-18%); numbness of hands 12% (95% CI: 10%-14%) and hearing loss 9% (95% CI: 5%-12%). Prevalence across different time intervals revealed significant patterns. All the symptoms persisted for more than 2 years after discharge except for abdominal pain. CONCLUSION: The pooled prevalence rates of somatic symptoms are notably high. Arthralgia and headache are the most prevalent of the symptoms, with hearing loss and numbness in hands and feet being the least. We found that arthralgia, myalgia, and abdominal pain decreased over time. However, headache, fatigue, numbness of hands and feet, and hearing loss increased over time.

Psychological distress among healthcare professionals in Mbarara, following the 2022 Ebola Virus Disease outbreak in Uganda: a mixed methods study.

BACKGROUND: The 2022 Ebola Virus Disease (EVD) outbreak occurred at a time when Uganda was still battling the social and psychological challenges of the COVID-19 pandemic; placing health care professionals (HCPs) at a much higher risk of developing psychological distress. Psychological distress among HCPs can cause decreased workplace productivity and ineffective management of their patients. The current study aimed to investigate and understand psychological distress among HCPS in Mbarara city in Southwestern Uganda following the 2022 EVD outbreak. METHOD: We enrolled 200 HCPs through convenient sampling from one private and one public health facility in Mbarara city in Southwestern Uganda, in a cross-sectional convergent parallel mixed method approach where qualitative and quantitative data were collected concurrently. Quantitative data, utilizing the Kessler Psychological Distress (K10) Scale, provided us with a quantitative measure of the prevalence of psychological distress among HCPs, and were analyzed using STATA version 16. Qualitative data, on the other hand, offered deeper insights into the nature, perceptions, and contextual factors influencing this distress, and were analyzed using emergent theme analysis. RESULTS: The prevalence of psychological distress was 59.5% and it was higher among females (63.9%) compared to males (36.1%). HCPs vividly expressed distress and anxiety, with heightened suspicion that every patient might be an EVD carrier, creating a pervasive sense of unsafety in the workplace. However, the outbreak had an educational affect where concerns about the announcement of another EVD outbreak were diverse, with HCPs expressing anxiety, despair, and dissatisfaction with the country's management of potential outbreaks. CONCLUSION: High levels of psychological distress were experienced by HCPs in Southwestern Uganda as a result of the 2022 EVD pandemic. HCPs express a wide range of feelings, such as dread, anxiety, despair, pessimism, and discontent with the way the outbreaks are handled throughout the nation. We recommend implementation of comprehensive psychosocial support programs tailored to the unique needs of HCPs, including counseling services, stress management workshops, and peer support networks.

Resilience of mental health services amidst Ebola disease outbreaks in Africa.

Introduction: Health systems including mental health (MH) systems are resilient if they protect human life and produce better health outcomes for all during disease outbreaks or epidemics like Ebola disease and their aftermaths. We explored the resilience of MH services amidst Ebola disease outbreaks in Africa; specifically, to (i) describe the pre-, during-, and post-Ebola disease outbreak MH systems in African countries that have experienced Ebola disease outbreaks, (ii) determine the prevalence of three high burden MH disorders and how those prevalences interact with Ebola disease outbreaks, and, (iii) describe the resilience of MH systems in the context of these outbreaks. Methods: This was a scoping review employing an adapted PRISMA statement. We conducted a five-step Boolean strategy with both free text and Medical Subject Headings (MeSH) to search 9 electronic databases and also searched WHO MINDbank and MH Atlas. Results: The literature search yielded 1,230 publications. Twenty-five studies were included involving 13,449 participants. By 2023, 13 African nations had encountered a total of 35 Ebola outbreak events. None of these countries had a metric recorded in MH Atlas to assess the inclusion of MH in emergency plans. The three highest-burden outbreak-associated MH disorders under the MH and Psychosocial Support (MHPSS) framework were depression, post-traumatic stress disorder (PTSD), and anxiety with prevalence ranges of 1.4-7%, 2-90%, and 1.3-88%, respectively. Furthermore, our analysis revealed a concerning lack of resilience within the MH systems, as evidenced by the absence of pre-existing metrics to gauge MH preparedness in emergency plans. Additionally, none of the studies evaluated the resilience of MH services for individuals with pre-existing needs or examined potential post-outbreak degradation in core MH services. Discussion: Our findings revealed an insufficiency of resilience, with no evaluation of services for individuals with pre-existing needs or post-outbreak degradation in core MH services. Strengthening MH resilience guided by evidence-based frameworks must be a priority to mitigate the long-term impacts of epidemics on mental well-being.

Invisible and undervalued: A qualitative study of laboratory workers' experiences and perceptions of laboratory strengthening in Sierra Leone.

Background: The 2013-2016 West Africa Ebola outbreak highlighted the importance of laboratory capacity to outbreak response while also revealing its long-standing neglect. The outbreak prompted massive international investment into strengthening laboratory services across multiple healthcare settings. Objective: In this article, we explore hospital-based clinical laboratory workers' experiences and perceptions of their everyday working environment in Sierra Leone, and how recent investments in laboratory strengthening have shaped these. Methods: This qualitative study draws on in-depth interviews with eight laboratory workers and participant observation of laboratory practices at a tertiary referral hospital in Freetown between April 2019 and December 2019. Interview and observational data were coded and analysed using a reflexive thematic approach. Results: The Ebola outbreak prompted international investments in automated devices, biosafety training, and a new dedicated infectious diseases laboratory. However, little investment was made in the infrastructure and supply systems needed to sustain routine laboratory work or keep machines functioning. Laboratory workers perceived their work to be under-recognised and undervalued by the government, hospital managers and clinical staff, a perception compounded by under-use of the hospital's laboratory services by clinicians. Conclusion: Understanding laboratory technicians' views, experiences, and priorities is essential to any sustainable laboratory-strengthening effort. Investments in personnel should match investments in technologies and infrastructure for outbreak response. What this study adds: This study contributes to an understanding of how clinical laboratory personnel in Sierra Leone view and experience their work, and introduces the concept of social invisibility to explain these experiences.

Knowledge, attitudes, and practices and long-term immune response after rVSVΔG-ZEBOV-GP Ebola vaccination in healthcare workers in high-risk districts in Uganda.

BACKGROUND: The rVSVΔG-ZEBOV-GP Ebola vaccine (rVSV-ZEBOV) has been used in response to Ebola disease outbreaks caused by Ebola virus (EBOV). Understanding Ebola knowledge, attitudes, and practices (KAP) and the long-term immune response following rVSV-ZEBOV are critical to inform recommendations on future use. METHODS: We administered surveys and collected blood samples from healthcare workers (HCWs) from seven Ugandan healthcare facilities. Questionnaires collected information on demographic characteristics and KAP related to Ebola and vaccination. IgG ELISA, virus neutralization, and interferon gamma ELISpot measured immunological responses against EBOV glycoprotein (GP). RESULTS: Overall, 37 % (210/565) of HCWs reported receiving any Ebola vaccination. Knowledge that rVSV-ZEBOV only protects against EBOV was low among vaccinated (32 %; 62/192) and unvaccinated (7 %; 14/200) HCWs. Most vaccinated (91 %; 192/210) and unvaccinated (92 %; 326/355) HCWs wanted to receive a booster or initial dose of rVSV-ZEBOV, respectively. Median time from rVSV-ZEBOV vaccination to sample collection was 37.7 months (IQR: 30.5, 38.3). IgG antibodies against EBOV GP were detected in 95 % (61/64) of HCWs with vaccination cards and in 84 % (162/194) of HCWs who reported receiving a vaccination. Geometric mean titer among seropositive vaccinees was 0.066 IU/mL (95 % CI: 0.058-0.076). CONCLUSION: As Uganda has experienced outbreaks of Sudan virus and Bundibugyo virus, for which rVSV-ZEBOV does not protect against, our findings underscore the importance of continued education and risk communication to HCWs on Ebola and other viral hemorrhagic fevers. IgG antibodies against EBOV GP were detected in most vaccinated HCWs in Uganda 2─4 years after vaccination; however, the duration and correlates of protection warrant further investigation.

Enmity then empathy: How militarisation facilitated collaborative but exclusive exchange in Sierra Leone's Ebola response.

In the autumn of 2014, with the 2013-16 West Africa Ebola epidemic spiralling out of control, the United Kingdom announced a bespoke military mission to support-and in some ways lead-numerous Ebola response functions in Sierra Leone. This study examines the nature and effect of the civil-military relationships that subsequently developed between civilian and military Ebola response workers (ERWs). In total, 110 interviews were conducted with key involved actors, and the findings were analysed by drawing on the neo-Durkheimian theory of organisations. This paper finds that stereotypical opposition between humanitarian and military actors helps to explain how and why there was initial cooperative and collaborative challenges. However, all actors were found to have similar hierarchical structures and operations, which explains how and why they were later able to cooperate and collaborate effectively. It also explains how and why civilian ERWs might have served to exclude and further marginalise some local actors.

Assessment of health care workers preparedness to epidemics: A case of Ebola virus disease preparedness in private hospitals in Kampala, Uganda.

INTRODUCTION: Unrecognized Ebola Virus Disease (EVD) can lead to multiple chains of transmissions if the first caretakers are not trained and prepared. This study aimed to assess healthcare workers (HCWs) preparedness in private hospitals located in Kampala, to detect, respond and prevent EVD. METHODOLOGY: A descriptive cross-sectional study was carried out among HCWs in direct clinical care provision in four private hospitals, and in one Ebola Treatment Unit (ETU) using a self-administered questionnaire from March to June 2020. RESULTS: 222 HCWs agreed to participate aged from 19 to 64 years and with 6 months to 38 years of practice where most were nurses (44%). 3/5 hospitals did not have written protocols on EVD case management, and only one (ETU) had an exclusive emergency team. 59% were not sure whether contact tracing was taking place. Private hospitals were not included in EVD trainings organized by the Ministry of Health (MoH). In addition, HCWs in private hospitals were not empowered by the MoH to take part in EVD case management. Despite these shortcomings, only 66% of HCWs showed an interest to be immunized. Knowledge about potential Ebola vaccines was generally poor. CONCLUSIONS: In Kampala, Uganda, establishment of a more comprehensive preparedness and response strategy for EVD outbreaks is imperative for HCWs in private facilities, including a wide vaccination educational program on Ebola vaccination. The findings from this study if addressed will likely improve the preparedness and management of future Ebola outbreaks in Uganda.