Search

Background: Emerging infectious diseases like the Ebola Virus Disease (EVD) pose significant global public health threats. Uganda has experienced multiple EVD outbreaks, the latest occurring in 2022. Frontline healthcare workers (HCWs) are at increased risk, yet there is insufficient evidence of existing knowledge of EVD of these HCWs. We aimed to assess the readiness of Uganda's emergency HCWs to manage EVD and identify their training needs to inform targeted capacity-building interventions for future outbreaks. Methods: This multicentre nationwide cross-sectional study was conducted from July to September 2023 among HCWs providing emergency care in 14 secondary and tertiary hospitals across Uganda. Participants were consecutively recruited using the probability-proportional-to-size sampling technique, and data was collected using a self-reported questionnaire. Factors associated with EVD knowledge were identified through a mixed-effect linear model. Results: Data from 691 eligible HCWs with a median age of 32 (IQR: 28–38) was analyzed (response rate: 92%). Only one-third (34.4%, n = 238) had received EVD training in the past year. The median EVD knowledge score was 77.4% (IQR: 71.2 − 83.4%). EVD knowledge was associated with longer professional experience in years (β: 0.21, 95% CI: 0.03 to 0.39, p = 0.024) and higher level of education: diploma (β: 3.37, 95% CI: 1.49 to 5.25, p < 0.001), undergraduate degree (β: 6.45, 95% CI: 4.11 to 8.79) and postgraduate degree (β: 7.13, 95% CI: 4.01 to 10.25, p < 0.001). Being a doctor (β: 2.55, 95% CI: 0.35 to 4.74, p = 0.023), providing care in the obstetrics/gynecology department (β: −1.90, 95% CI: −3.47 to − 0.32, p = 0.018), previous EVD training (β: 2.27, 95% CI: 0.96 to 3.59, p = 0.001) and accessing EVD information through social media (β: 2.52, 95% CI: 1.17 to 3.88, p < 0.001) were also significantly associated with EVD knowledge. HCWs were mostly interested in training on management (92.9%), infection prevention and control (87.1%), and clinical presentation (84.1%), and preferred physical (51.5%) and hybrid (38.2%) training modes. Conclusion: Our study shows that the readiness of HCWs in Uganda to respond to EVD outbreaks varies by individual factors and information sources. We recommend targeted training and suggest future research on educational innovations and social media's potential to fill knowledge gaps. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013–2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses. In this study, we characterize humoral immune responses in EVD survivors and their contacts in Eastern Sierra Leone. We found high levels of EBOV IgG in EVD survivors and lower yet substantial antibody levels in household contacts, suggesting subclinical transmission. Neutralizing antibody function was prevalent but variable in EVD survivors, raising questions about the durability of immune responses from natural infection with EBOV. Additionally, we found that certain discrete symptoms—ophthalmologic and auditory—are associated with EBOV IgG seropositivity, while an array of symptoms are associated with the presence of neutralizing antibody. [ABSTRACT FROM AUTHOR]

Nowadays, filovirus vaccine development may be seen as a paradigm for our response capabilities to emerging and re-emerging infectious diseases. Specifically, the West African Ebola virus disease (EVD) epidemic accelerated countermeasure licensure for several vaccine and therapeutic products. Those products have been successfully used to control EVD outbreaks in Central Africa over the past years. This positive development, however, has not yet reached beyond EVD. Therefore, it is pertinent to increase our efforts in the development of countermeasures for other human pathogenic members of the family Filoviridae as they continue to threaten public health in Sub-Saharan Africa. This review article summarizes the current filovirus vaccines in preclinical macaque studies and human clinical trials and discusses the most promising recent advancements. [ABSTRACT FROM AUTHOR]

Background: Viral infectious diseases of poverty (vIDPs) remain a significant global health challenge. Despite their profound impact, the burden of these diseases is not comprehensively quantified. This study aims to analyze the global burden of six major vIDPs, including coronavirus disease 2019 (COVID-19), HIV/AIDS, acute hepatitis, dengue, rabies, and Ebola virus disease (EVD), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021). Methods: Following the GBD 2021 framework, we analyzed the incidence, mortality, and disability-adjusted life years (DALYs) of the six vIDPs across 204 countries and territories from 1990 to 2021. We examined the association between the Socio-Demographic Index (SDI) and the burden of vIDPs. All estimates were reported as numbers and rates per 100,000 population, calculated using the Bayesian statistical model employed by GBD 2021, with 95% uncertainty intervals (UI). Results: In 2021, vIDPs caused approximately 8.7 million deaths and 259.2 million DALYs, accounting for 12.8% and 9.0% of the global all-cause totals, respectively. Globally, the burden of vIDPs varied significantly: COVID-19 caused around 7.9 million (95% UI: 7.5, 8.4) deaths and 212.0 million (95% UI 197.9, 234.7) DALYs in 2021. Acute hepatitis had the second-highest age-standardized incidence rate, with 3411.5 (95% UI: 3201.8, 3631.3) per 100,000 population, while HIV/AIDS had a high age-standardized prevalence rate, with 483.1 (95% UI: 459.0, 511.4) per 100,000 population. Dengue incidence cases rose from 26.5 million (95% UI: 3.9, 51.9) in 1990 to 59.0 million (95% UI: 15.5, 106.9) in 2021. Rabies, although reduced in prevalence, continued to pose a significant mortality risk. EVD had the lowest overall burden but significant outbreak impacts. Age-standardized DALY rates for vIDPs were significantly negatively correlated with SDI: acute hepatitis (r = −0.8, P < 0.0001), rabies (r = −0.7, P < 0.0001), HIV/AIDS (r = −0.6, P < 0.0001), COVID-19 (r = −0.5, P < 0.0001), dengue (r = −0.4, P < 0.0001), and EVD (r = −0.2, P < 0.005). Conclusions: VIDPs pose major public health challenges worldwide, with significant regional, age, and gender disparities. The results underscore the need for targeted interventions and international cooperation to mitigate the burden of these diseases. Policymakers can use these findings to implement cost-effective interventions and improve health outcomes, particularly in regions with high or increasing burdens. [ABSTRACT FROM AUTHOR]

With two endorsed and prophylactic vaccines against Zaire ebolavirus (referred to hereafter as EBOV), the number of individuals vaccinated against EBOV worldwide is estimated to range between 500 000 and 1 000 000 individuals, increasing with every renewed EBOV threat and vaccination campaign. Therefore, re-exposure of previously vaccinated health-care workers, and possibly community members, could become more frequent. In the absence of long-term data on vaccine efficacy and duration of protection, we urgently need to understand revaccination strategies that could maximise the level of protection. In this Personal View, we highlight the scarcity of available evidence to guide revaccination recommendations for the accumulating groups of previously vaccinated communities or front-line health-care workers that could be redeployed or re-exposed in the next EBOV outbreak(s). This evidence base is crucial to identify optimal target populations and the frequency of booster doses, and guide vaccine interchangeability (especially in settings with limited or unpredictable vaccine supplies), while preventing vaccine mistrust, equity concerns, and exclusion of vulnerable populations. We discuss five priority gaps (to whom, when, and how frequently, to provide booster doses; long-term correlates and thresholds of protection; the effect of vector-directed immunity and viral variant protection; comparative research in mix-and-match schedules; and implementation concerns) that should be urgently tackled to adapt the initial EBOV prophylactic vaccination strategies considering potential booster dose vaccinations. [ABSTRACT FROM AUTHOR]

Background: As the number of large-scale outbreaks continues to rise worldwide, clinical trials are increasingly engaging disease-affected peoples within the Minority World (nations with over 80% poverty rates). Yet global health research inadequately addresses potential ethical issues of including impoverished, disease-affected populations and their contextual vulnerabilities in medical research. Objective: This paper presents a mixed-method analysis from our 2022 semi-structured survey capturing the experiences of Liberian Ebola Virus Disease (EVD) survivors serving as study participants in the Partnership for Research on Ebola Virus in Liberia (PREVAIL) clinical trials. Methods: Firstly, we conducted an extensive literature review of the scholarship related to biomedical research and ethical standards protecting study participants to inform our survey method and design. Applying a theoretical framework on vulnerability, we then qualitatively explored the survey responses of 19 EVD survivors' perceptions and experiences taking part in PREVAIL, including their expectations, treatment, delivered benefits, and quality of care. We further quantitatively codified their statements for underlying themes of reported negative experiences against standard ethical regulations in biomedical research, conducting a statistical analysis to inform generalizability. Most of the 19 survivors reported facing extreme ongoing vulnerabilities related to their disease status, including physical impairments, psychosocial stress, and socio-economic inequity. Results: Initially, the survivors tended to experience a sense of hope and pride in volunteering for PREVAIL. One in five participants reported benefiting from PREVAIL's regular medical diagnoses. However, most of their survey responses indicated prevalent negative shared experiences, including continually being confused or misinformed of their study participant rights, roles, and benefits; being burdened by heavy participation transaction costs; and repeated incidents of poor treatment and discrimination by PREVAIL staff after initial recruitment. PREVAIL participant satisfaction ranking is negatively correlated with receiving insufficient financial compensation (r = −0.51), extensive time requirements for each medical visit (−0.40), and being poorly treated by clinical staff (−0.67). [ABSTRACT FROM AUTHOR]

Infection of Western aid workers with Ebola virus disease during the 2014-2016 West African outbreak demonstrated the need for medical evacuation to high-level isolation units in Europe and the United States. In Norway, an ad hoc preparedness team was established for aeromedical evacuation in case of need. In October 2014, this team transported an infected aid worker from the military section of Oslo Airport to Oslo University Hospital. To maintain and strengthen the capacity for domestic ambulance transport on the ground and in the air, the Norwegian Medical Emergency Response Team for High Consequence Infectious Diseases (in Norway known as "Nasjonalt medisinsk utrykningsteam for høyrisikosmitte"), or NORTH, was established as a permanent service in 2017. Recognizing the expertise of this domestic team, Norway was subsequently entrusted with the task of enhancing the European aeromedical transport capacity for high-consequence infectious diseases and establishing the Norwegian rescEU Jet Air Ambulance for Transport of Highly Infectious Patients, or NOJAHIP, in 2022. In this case study, we present experiences and lessons learned from these 2 services and discuss how they can be further developed. [ABSTRACT FROM AUTHOR]

Infectious disease physicians in England have been diagnosing and managing occasional cases of viral hemorrhagic fever since 1971, including the United Kingdom's first case of Ebola virus disease in 1976. Specialist isolation facilities to provide safe and effective care have been present since that time. Following the emergence of Middle East respiratory syndrome (MERS) in 2012, and the avian influenza A (H7N9) outbreak in 2013, and the 2014-2016 Ebola virus disease outbreak in West Africa, clinical and public health preparedness and response pathways in England have been strengthened for these types of diseases, now called high-consequence infectious diseases (HCIDs). The HCID program, led by NHS England and Public Health England between 2016 and 2018, helped to deliver these enhancements, which have since been used on multiple occasions for new UK cases and outbreaks of MERS, mpox, avian influenza, and Lassa fever. Additionally, HCID pathways were activated for COVID-19 during the first 3 months of 2020, before the pandemic had been declared and little was known about COVID-19 but HCID status had been assigned temporarily to COVID-19 as a precaution. The HCID program also led to the commissioning of a network of new airborne HCID treatment centers in England, to supplement the existing network of contact HCID treatment centers, which includes the United Kingdom's only 2 high-level isolation units. In this case study, the authors describe the airborne and contact HCID treatment center networks in England, including their formation and structures, their approach to safe and effective clinical management of patients with HCIDs in the United Kingdom, and challenges they may face going forward. [ABSTRACT FROM AUTHOR]

The article discusses the importance of international collaboration and preparedness in managing infectious diseases and health emergencies. It focuses on the Infectious Disease Emergency Specialist (IDES) training program in Japan, which was established after the Ebola outbreak in West Africa. The IDES program provides comprehensive training to Japanese physicians in responding to health emergencies, including a second-year international training component. The article also highlights the National Emerging Special Pathogens Training and Education Center (NETEC) in the United States as a model for collaboration and coordination in managing infectious diseases. The collaboration between NETEC and IDES has facilitated knowledge exchange and best practices in handling special pathogens and has contributed to Japan's readiness for future health crises. The article emphasizes the importance of international cooperation and the establishment of robust healthcare networks to strengthen global health security. [Extracted from the article]

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck's Ervebo (rVSV-ZEBOV) and Johnson & Johnson's two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination. In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination. [ABSTRACT FROM AUTHOR]

The Ebola virus poses a severe public health threat, yet understanding factors influencing disease outcomes remains incomplete. Our study aimed to identify critical pathways and hub genes associated with fatal and survivor Ebola disease outcomes. We analyzed differentially expressed hub genes (DEGs) between groups with fatal and survival outcomes, as well as a healthy control group. We conducted additional analysis to determine the functions and pathways associated with these DEGs. We found 13,198 DEGs in the fatal and 12,039 DEGs in the survival group compared to healthy controls, and 1873 DEGs in the acute fatal and survivor groups comparison. Upregulated DEGs in the comparison between the acute fatal and survivor groups were linked to ECM receptor interaction, complement and coagulation cascades, and PI3K‐Akt signaling. Upregulated hub genes identified from the acute fatal and survivor comparison (FGB, C1QA, SERPINF2, PLAT, C9, SERPINE1, F3, VWF) were enriched in complement and coagulation cascades; the downregulated hub genes (IL1B, 1L17RE, XCL1, CXCL6, CCL4, CD8A, CD8B, CD3D) were associated with immune cell processes. Hub genes CCL2 and F2 were unique to fatal outcomes, while CXCL1, HIST1H4F, and IL1A were upregulated hub genes unique to survival outcomes compared to healthy controls. Our results demonstrate for the first time the association of EVD outcomes to specific hub genes and their associated pathways and biological processes. The identified hub genes and pathways could help better elucidate Ebola disease pathogenesis and contribute to the development of targeted interventions and personalized treatment for distinct EVD outcomes. [ABSTRACT FROM AUTHOR]

National public health emergency operations centers (PHEOCs) serve as hubs for coordinating information and resources for effective emergency management. In the International Health Regulations (IHR 2005) Monitoring and Evaluation Framework, a simulation exercise is 1 of 4 components that can be used to test the functionality of a country's emergency response capabilities in a simulated situation. To test the functionality of PHEOCs in World Health Organization African Region member states, a regional functional exercise simulating an Ebola virus disease outbreak was conducted. The public health actions taken in response to the simulated outbreak were evaluated against the exercise objectives. Thematic analysis was conducted to summarize key strengths and areas for improvement. From December 6 to 7, 2022, more than 1,000 representatives from 36 of the 47 African Region member states participated in the exercise from their respective PHEOCs. Approximately 95% of the 461 participants polled agreed with the positive responses to the postexercise survey. More than half of the PHEOC participants were able to test their existing emergency preparedness and response plans and became familiar with the expected roles to be fulfilled during an event. Of the participants who responded to the survey, over 90% reported that the exercise helped them understand their roles during emergency management. The exercise met its objectives and provided an opportunity to test the functionality of PHEOCs using realistic scenarios, and it helped participants understand existing response systems and procedures. However, the exercise also revealed areas for improvement in terms of the timing and preparation of participants. We recommend conducting functional exercises at the regional and national levels at least once a year, early or midyear, to allow many stakeholders to take part in the exercise. Moreover, there is a need to train country-level evaluators and controllers in designing and conducting functional exercises. [ABSTRACT FROM AUTHOR]

Background: In 2021, an Ebola virus disease (EVD) outbreak was declared in Guinea, linked to persistent virus from the 2014–2016 West Africa Epidemic. This paper analyzes factors associated with contact tracing reliability (defined as completion of a 21-day daily follow-up) during the 2021 outbreak, and transitively, provides recommendations for enhancing contact tracing reliability in future. Methods: We conducted a descriptive and analytical cross-sectional study using multivariate regression analysis of contact tracing data from 1071 EVD contacts of 23 EVD cases (16 confirmed and 7 probable). Results: Findings revealed statistically significant factors affecting contact tracing reliability. Unmarried contacts were 12.76× more likely to miss follow-up than those married (OR = 12.76; 95% CI [3.39–48.05]; p < 0.001). Rural-dwelling contacts had 99% lower odds of being missed during the 21-day follow-up, compared to those living in urban areas (OR = 0.01; 95% CI [0.00–0.02]; p < 0.01). Contacts who did not receive food donations were 3× more likely to be missed (OR = 3.09; 95% CI [1.68–5.65]; p < 0.001) compared to those who received them. Contacts in health areas with a single team were 8× more likely to be missed (OR = 8.16; 95% CI [5.57–11.96]; p < 0.01) than those in health areas with two or more teams (OR = 1.00; 95% CI [1.68–5.65]; p < 0.001). Unvaccinated contacts were 30.1× more likely to be missed compared to vaccinated contacts (OR = 30.1; 95% CI [5.12–176.83]; p < 0.001). Conclusion: Findings suggest that contact tracing reliability can be significantly influenced by various demographic and organizational factors. Considering and understanding these factors—and where possible addressing them—may be crucial when designing and implementing contact tracing strategies during future outbreaks in low-resource settings. [ABSTRACT FROM AUTHOR]

The Ebola virus (EBOV) has emerged as a significant global health concern, notably during the 2013–2016 outbreak in West Africa. Despite the clinical approval of two EBOV antibody drugs, there is an urgent need for more diverse and effective antiviral drugs, along with comprehensive understanding of viral-host interactions. In this study, we harnessed a biologically contained EBOVΔVP30-EGFP cell culture model which could recapitulate the entire viral life cycle, to conduct a genome-wide CRISPR/Cas9 screen. Through this, we identified PIK3C3 (phosphatidylinositide 3-kinase) and SLC39A9 (zinc transporter) as crucial host factors for EBOV infection. Genetic depletion of SLC39A9 and PIK3C3 lead to reduction of EBOV entry, but not impact viral genome replication, suggesting that SLC39A9 and PIK3C3 act as entry factors, facilitating viral entry into host cells. Moreover, PIK3C3 kinase activity is indispensable for the internalization of EBOV virions, presumably through the regulation of endocytic and autophagic membrane traffic, which has been previously recognized as essential for EBOV internalization. Notably, our study demonstrated that PIK3C3 kinase inhibitor could effectively block EBOV infection, underscoring PIK3C3 as a promising drug target. Furthermore, biochemical analysis showed that recombinant SLC39A9 protein could directly bind viral GP protein, which further promotes the interaction of viral GP protein with cellular receptor NPC1. These findings suggests that SLC39A9 plays dual roles in EBOV entry. Initially, it serves as an attachment factor during the early entry phase by engaging with the viral GP protein. Subsequently, SLC39A9 functions an adaptor protein, facilitating the interaction between virions and the NPC1 receptor during the late entry phase, prior to cathepsin cleavage on the viral GP. In summary, this study offers novel insights into virus-host interactions, contributing valuable information for the development of new therapies against EBOV infection. Author summary: Ebola virus (EBOV) remains a significant global health threat. The limited availability of high-containment (BSL-4) facilities hinders our understanding of the interaction of virus with host cells and the development of effective treatments. To address this, we utilized a biologically contained EBOVΔVP30-EGFP model to identify critical host factors necessary for EBOV infection through a genome-wide CRISPR/Cas9 screen conducted at BSL-2 lab. Our study revealed that two proteins, PIK3C3 and SLC39A9, are essential for the virus to enter host cells. We found that PIK3C3 is required for EBOV endosomal trafficking, and inhibiting its kinase activity can significantly reduce infection, making it a promising target for antiviral therapy. Additionally, we discovered that SLC39A9 facilitates viral entry by interacting with the viral glycoprotein (GP) and enhancing its binding to the cell's NPC1 receptor, rather than through its usual role in zinc transport. These findings offer new insights into how EBOV enters cells and highlight potential targets for developing therapies to combat Ebola virus infection. [ABSTRACT FROM AUTHOR]

Background: Recent outbreaks of Ebola virus disease (EVD) and Marburg virus disease (MVD) in sub-Saharan Africa illustrate the need to better understand animal reservoirs, burden of disease, and human transmission of filoviruses. This protocol outlines a systematic literature review to assess the prevalence of filoviruses that infect humans in sub-Saharan Africa. A secondary aim is to qualitatively describe and evaluate the assays used to assess prevalence. Methods: The data sources for this systematic review include PubMed, Embase, and Web of Science. Titles, abstracts, and full texts will be reviewed for inclusion by a primary reviewer and then by a team of secondary reviewers, and data will be extracted using a pre-specified and piloted data extraction form. The review will include human cross-sectional studies, cohort studies, and randomized controlled trials conducted in sub-Saharan Africa up until March 13, 2024 that have been published in peer-reviewed scientific journals, with no language restrictions. Prevalence will be stratified by pathogen, population, assay, and sampling methodology and presented in forest plots with estimated prevalence and 95% confidence intervals. If there are enough studies within a stratum, I2 statistics will be calculated (using R statistical software), and data will be pooled if heterogeneity is low. In addition, assays used to detect infection will be evaluated. All studies included in the review will be assessed for quality and risk of bias using the JBI Prevalence Critical Appraisal Tool and for certainty using the GRADE certainty ratings. Discussion: Accurately measuring the rate of exposure to filoviruses infecting humans in sub-Saharan Africa using prevalence provides an essential understanding of natural history, transmission, and the role of subclinical infection. This systematic review will identify research gaps and provide directions for future research seeking to improve our understanding of filovirus infections. Understanding the natural history, transmission, and the role of subclinical infection is critical for predicting the impact of an intervention on disease burden. Systematic Review Registration: In accordance with the guidelines outlined in the PRISMA-P methodology, this protocol was registered with PROSPERO on April 7, 2023 (ID: CRD42023415358). [ABSTRACT FROM AUTHOR]

Despite a half-century-long global eradication effort, polio continues to have a devastating impact on individuals and communities worldwide, especially in low-income countries affected by conflict or geographic barriers to immunization programs. In response, the World Health Organization (WHO) Global Polio Eradication Initiative (GPEI) employs disease surveillance and vaccination campaigns coordinated through the WHO Regional Office for Africa (AFRO) Geographic Information System (GIS) Centre. Established in 2017, the AFRO GIS Centre played a key role in the eradication of wild-type polioviruses (WPVs) in 2020, but the COVID-19 pandemic, emergence of circulating vaccine-derived polioviruses, and transmission of WPV1 from Central Asia have led to a resurgence of polio in Sub-Saharan Africa. The AFRO GIS comprises a set of mobile device or cloud-based tools for geospatial data collection, analysis, and visualization. Using tools such as Auto-Visual Acute Flaccid Paralysis Detection and Reporting, electronic surveillance, and Integrated Supportive Supervision, GIS personnel collect polio case numbers and locations, track field worker activities, follow the movements of nomadic populations vulnerable to polio and other diseases, and determine needs for further healthcare deployments. The system is location specific and operates in real time, enabling the AFRO GIS to promptly target its responses to polio, COVID-19, Ebola virus disease, and other public health crises and natural disasters. The present review describes the components of the AFRO GIS and how the AFRO GIS Centre coordinated on-the-ground polio eradication efforts to help secure Africa's certification as WPV free. It also examines current and prospective challenges regarding other disease outbreaks in the COVID-19 era and how the AFRO GIS Centre is addressing these ongoing public health needs. [ABSTRACT FROM AUTHOR]

Background Skeletal muscle injury in Ebola virus disease (EVD) has been reported, but its association with morbidity and mortality remains poorly defined. Methods This retrospective study included patients admitted to 2 EVD treatment units over an 8-month period in 2019 during an EVD epidemic in the Democratic Republic of the Congo. Results An overall 333 patients (median age, 30 years; 58% female) had at least 1 creatine kinase (CK) measurement (n = 2229; median, 5/patient [IQR, 1–11]). Among patients, 271 (81%) had an elevated CK level (>380 U/L); 202 (61%) had rhabdomyolysis (CK >1000 IU/L); and 45 (14%) had severe rhabdomyolysis (≥5000 U/L). Among survivors, the maximum CK level was a median 1600 (IQR, 550–3400), peaking 3.4 days after admission (IQR, 2.3–5.5) and decreasing thereafter. Among fatal cases, the CK rose monotonically until death, with a median maximum CK level of 2900 U/L (IQR, 1500–4900). Rhabdomyolysis at admission was an independent predictor of acute kidney injury (adjusted odds ratio, 2.2 [95% CI, 1.2–3.8]; P =.0065) and mortality (adjusted hazard ratio, 1.7 [95% CI, 1.03–2.9]; P =.037). Conclusions Rhabdomyolysis is associated with acute kidney injury and mortality in patients with EVD. These findings may inform clinical practice by identifying laboratory monitoring priorities and highlighting the importance of fluid management. [ABSTRACT FROM AUTHOR]

Background: The 2014 outbreak of the Ebola virus disease highlighted the importance of overhauling and transforming healthcare systems in West Africa to improve the ability of individual countries to deal with infectious diseases. As part of this effort, in November 2016 the West African Health Organization (WAHO) began the process of institutionalizing the One Health (OH) approach to health security across the Economic Community of West African States (ECOWAS). The lack of clear metrics and evaluation frameworks to measure the progress of OH implementation in West Africa has been reported as a challenge. Therefore, this study sought to assess and explore whether the existing metrics of global health security frameworks can measure the successful implementation of OH activities, evaluate the progress made since 2016, and identify key areas for improvement in the region. Method: The study employed predetermined keywords to select indicators from the International Health Regulations (IHR) Monitoring Frameworks, specifically the State Party Self-Assessment Annual Report (SPAR) and Joint External Evaluation (JEE), deemed relevant to the OH approach. In addition, the COVID-19 performance index scores (severity and recovery) for June 2022 were extracted from the Global COVID-19 Index (GCI). The GCI Recovery Index evaluated the major recovery parameters reported daily to indicate how a country performed on the path to recovery from the COVID-19 pandemic compared to other countries. National documents were also analyzed using categorical variables to assess the performance status of OH platforms across implementing countries. A quantitative analysis of these indicators was conducted and supplemented with qualitative data gathered through interviews with key stakeholders. Between March and April 2022, we conducted 18 key informant interviews with purposively selected representatives from regional governmental agencies and international multilateral agencies, including ECOWAS member states. Interviews were conducted online, transcribed, and analysed following the tenets of thematic analysis. Results: Our quantitative analysis revealed no significant association between the implementation status of OH activities and any of the selected indicators from SPAR and JEE. The descriptive analysis of the JEE scores at the country level revealed that countries with existing OH platforms scored relatively higher on the selected JEE indicators than other countries in the pre-implementation stage. OH implementation status did not significantly affect COVID-19 recovery and severity indices. The qualitative findings with relevant stakeholders revealed noteworthy challenges related to insufficient human capacity, inadequate coordination, and a lack of government funding for the sustainability of OH initiatives. Nonetheless, countries in the ECOWAS region are making progress toward the integration of OH into their health security systems. Conclusion: Standardized metrics were used to assess the implementation and efficacy of OH systems in the ECOWAS region. Current indicators for monitoring global health security frameworks lack specificity and fail to comprehensively capture essential OH components, particularly at the sub-national level. To ensure consistency and effectiveness across countries, OH implementation metrics that align with global frameworks such as IHR should be developed. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has catalyzed debates about how the public and leaders respond to health threats and the role that the media and emotions play in these responses. Predating COVID‐19, the 2014 Ebola outbreak can serve as a case to examine the constructions and pervasiveness of fear discourse and other emotions in news and social media. In this mixed‐method study, we examine fear discourse in web‐based and traditional newspaper headlines and emergent emotions in social media data (Twitter) during the peak of Ebola coverage. Users discuss fear on Twitter in a variety of ways and there was an increase in Tweets following the first Ebola case in the United States. However, it is humor, not fear, that is the most dominant theme in Twitter responses. Claims by health leaders and media scholars, that information technology and social media spread fear, receive limited support. Prevalence of different emotions vary across format (headlines and social media) and have important implications for understanding the myths and realities of public responses to health threats. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

During the 2018–2020 Ebola virus disease outbreak in Democratic Republic of the Congo, a phase 3 trial of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine (DRC-EB-001) commenced in Goma, with participants being offered the two-dose regimen given 56 days apart. Suspension of trial activities in 2020 due to the COVID-19 pandemic led to some participants receiving a late dose 2 outside the planned interval. Blood samples were collected from adults, adolescents, and children prior to their delayed dose 2 vaccination and 21 days after, and tested for IgG binding antibodies against Ebola virus glycoprotein using the Filovirus Animal Nonclinical Group (FANG) ELISA. Results from 133 participants showed a median two-dose interval of 9.3 months. The pre-dose 2 antibody geometric mean concentration (GMC) was 217 ELISA Units (EU)/mL (95% CI 157; 301) in adults, 378 EU/mL (281; 510) in adolescents, and 558 EU/mL (471; 661) in children. At 21 days post-dose 2, the GMC increased to 22,194 EU/mL (16,726; 29,449) in adults, 37,896 EU/mL (29,985; 47,893) in adolescents, and 34,652 EU/mL (27,906; 43,028) in children. Participants receiving a delayed dose 2 had a higher GMC at 21 days post-dose 2 than those who received a standard 56-day regimen in other African trials, but similar to those who received the regimen with an extended interval. [ABSTRACT FROM AUTHOR]

During the 2018–2020 Ebola virus disease (EVD) outbreak, residents in Goma, Democratic Republic of the Congo, were offered a two-dose prophylactic EVD vaccine. This was the first study to evaluate the safety of this vaccine in pregnant women. Adults, including pregnant women, and children aged ≥1 year old were offered the Ad26.ZEBOV (day 0; dose 1), MVA-BN-Filo (day 56; dose 2) EVD vaccine through an open-label clinical trial. In total, 20,408 participants, including 6635 (32.5%) children, received dose 1. Fewer than 1% of non-pregnant participants experienced a serious adverse event (SAE) following dose 1; one SAE was possibly related to the Ad26.ZEBOV vaccine. Of the 1221 pregnant women, 371 (30.4%) experienced an SAE, with caesarean section being the most common event. No SAEs in pregnant women were considered related to vaccination. Of 1169 pregnancies with a known outcome, 55 (4.7%) ended in a miscarriage, and 30 (2.6%) in a stillbirth. Eleven (1.0%) live births ended in early neonatal death, and five (0.4%) had a congenital abnormality. Overall, 188/891 (21.1%) were preterm births and 79/1032 (7.6%) had low birth weight. The uptake of the two-dose regimen was high: 15,328/20,408 (75.1%). The vaccine regimen was well-tolerated among the study participants, including pregnant women, although further data, ideally from controlled trials, are needed in this crucial group. [ABSTRACT FROM AUTHOR]

Abstract Background Emerging infectious diseases like the Ebola Virus Disease (EVD) pose significant global public health threats. Uganda has experienced multiple EVD outbreaks, the latest occurring in 2022. Frontline healthcare workers (HCWs) are at increased risk, yet there is insufficient evidence of existing knowledge of EVD of these HCWs. We aimed to assess the readiness of Uganda’s emergency HCWs to manage EVD and identify their training needs to inform targeted capacity-building interventions for future outbreaks. Methods This multicentre nationwide cross-sectional study was conducted from July to September 2023 among HCWs providing emergency care in 14 secondary and tertiary hospitals across Uganda. Participants were consecutively recruited using the probability-proportional-to-size sampling technique, and data was collected using a self-reported questionnaire. Factors associated with EVD knowledge were identified through a mixed-effect linear model. Results Data from 691 eligible HCWs with a median age of 32 (IQR: 28–38) was analyzed (response rate: 92%). Only one-third (34.4%, n = 238) had received EVD training in the past year. The median EVD knowledge score was 77.4% (IQR: 71.2 − 83.4%). EVD knowledge was associated with longer professional experience in years (β: 0.21, 95% CI: 0.03 to 0.39, p = 0.024) and higher level of education: diploma (β: 3.37, 95% CI: 1.49 to 5.25, p

INTRODUCTION. Marburg and Ebola viruses cause severe haemorrhagic fever in humans and primates. Currently, there are no licensed prophylactic vaccines that can simultaneously prevent the spread or reduce the severity of both diseases caused by these filoviruses. The development of effective prophylactic vaccines requires studies aimed at selecting the most immunogenic forms of protective antigens.AIM. This study aimed to evaluate humoral immune induction in animals after administration of recombinant adenoviral vectors expressing various forms of Ebola and Marburg virus glycoproteins (GPs).MATERIALS AND METHODS. Samples of recombinant human adenovirus type 5 (rAd5) were obtained using homologous recombination in Escherichia coli, growth in HEK293 cells, and purification by CsCl gradient ultracentrifugation. The resulting rAd5 samples were characterised in terms of their identity (PCR and whole-genome sequencing), the concentration of viral particles (fluorescence spectroscopy), and the concentration of infectious viral particles (TCID50 assay). Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the GP-specific IgG titres in the sera of immunised mice.RESULTS. The authors constructed rAd5 samples, and each construct contained an expression cassette with a GP gene form encoding a full-length GP, a GP without the mucin-like domain, or a GP without both the glycan cap and the mucin-like domain. Each of these forms was studied using the GPs of four filoviruses, including Zaire Ebola virus, Sudan Ebola virus, Bundibugyo Ebola virus, and Marburg virus. Neither of the forms had a critical effect on the rAd5 replicative capacity. Three weeks after immunisation, the highest GP-specific IgG production was induced by the rAd5 samples encoding either the full-length GP or the GP without the mucin-like domain. The GP without both the glycan cap and the mucin-like domain was the least immunogenic antigen regardless of the filovirus species.CONCLUSIONS. The most promising constructs for the development of filovirus vaccines based on recombinant adenoviral vectors are the constructs that include the genes encoding the fulllength GP or the GP without the mucin-like domain.

The review presents the main results of scientific and technical cooperation between the Russian Federation and the Republic of Guinea over 10 years of joint work, since the deployment of a group of Russian specialists and mobile laboratories from the mobile complex of the specialized anti-epidemic team of the Rospotrebnadzor in August 2014 to provide practical and methodological assistance in eliminating the epidemic caused by the Ebola virus. The main areas of cooperation are the strengthening of laboratory and hospital facilities, joint research and training of specialists from specialized institutions in Guinea on biosafety issues. During the implementation of the Russian Federation programs of assistance to the Republic of Guinea in combating infectious diseases, public-private partnership mechanisms with UC “RUSAL” were involved, which made it possible to bring Russia’s participation in eradicating the epidemic of Ebola virus disease and subsequently strengthening Guinea’s national capacity to combat biological threats to the maximum effect.

To date, only three studies investigated the mental health of youth affected by Ebola virus disease (EVD). None explored anxiety and psychological distress symptoms in survivors or orphans. This study aimed to investigate the prevalence and determinants of anxiety and psychological distress symptoms among survivors and orphans of the 2018–2020 Ebola epidemic in Eastern Democratic Republic of the Congo (DRC) during the COVID-19 pandemic. A representative sample of 416 participants (mean age = 13.37, SD = 2.79, 51.20 % girls, 146 survivors, 233 orphans, and 34 orphan-survivor participants) completed measures evaluating anxiety, psychological distress, exposure, resilience, stigmatization related to Ebola and COVID-19. 55.88 % and 55.96 % of survivors and orphans experienced severe symptoms of anxiety and psychological distress. Participants who were both survivors and orphans presented higher prevalence of anxiety and psychological distress (94.12 % and 100 %) compared to survivors (74.03 % and 81.82 %) or orphans (37.99 % and 33.33 %), χ 2 = 70.63, p <.001; χ 2 = 113.50, p <.001. Ebola and COVID-19 related stigmatization were the most important determinants of anxiety (B = 0.40, p <.001; B = 0.37, p <.001) and psychological distress (B = 0.48, p <.001; B = 0.44, p <.001). Resilience was negatively associated with both anxiety and psychological distress. The final regression models explained 49 % and 85 % of the variance of anxiety and psychological distress. The cross-sectional design used prevents to establish causal link. Ebola children and adolescents' survivors and orphans are at major risk of experiencing anxiety and psychological distress in Eastern RDC affected by years of armed conflict. Massive resources are needed to develop and implement programs to reduce stigma and support mental health. • Only 3 studies examine mental health of children affected by Ebola, including two in survivors. • Ebola Child and adolescent survivors and orphans are at major risk of experiencing anxiety and psychological distress symptoms. • Ebola and COVID-19 related stigma were the most important determinants of anxiety and psychological distress symptoms. • Resilience was negatively associated with both anxiety and psychological distress symptoms. [ABSTRACT FROM AUTHOR]

Ebola virus disease (EVD) is a rare, highly contagious and a deadly disease with a variable fatality rate ranging from 30% to 90%. Over the past two decades, Ebola pandemic has severely affected the sub-Sahara region including Democratic Republic of the Congo (DRC), and Uganda. The causative agents of the most EVD cases are three distinct species out of six Ebolaviruses namely Zaire Ebolavirus (ZEBOV), Sudan Ebolavirus (SUDV) and Bundibugyo Ebolavirus (BDBV). In recent years, significant strides have been made in therapeutic interventions. Notably, the US Food and Drug Administration has approved two monoclonal antibodies: InmazebTM (REGN-EB3) and Ansuvimab or Ebanga™. Additionally, many small molecules are currently in the developmental stage, promising further progress in medical treatment. Addressing the critical need for preventive measures, this review provides an in-depth analysis of the licensed Ebola vaccines-Ervebo and the combination of Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) as well as the vaccines which are currently being tested for their efficacy and safety in clinical studies. These vaccines might play an important role in curbing the spread and mitigating the impact of this lethal disease. The current treatment landscape for EVD encompasses both nutritional (supportive) and drug therapies. The review comprehensively details the origin, pathogenesis, and epidemiology of EVD, shedding light on the ongoing efforts to combat this devastating disease. It explores small molecules in various stages of the development, discusses patents filed or granted, and delves into the clinical and supportive therapies that form the cornerstone of EVD management. This review aims to provide the recent developments made in the design and synthesis of small molecules for scientific community to facilitate a deeper understanding of the disease and fostering the development of effective strategies for prevention, treatment, and control of EVD.

Abstract Background Communities affected by Ebola disease (EBOD) may face resulting increases in mental health disorders. We evaluated the prevalence of and factors associated with mental health disorders among persons affected by the 2022 Sudan virus disease (SVD) outbreak in Uganda. Methods We conducted a cross-sectional study among SVD survivors and family members of survivors and fatal cases from 15–31 January 2023. We included only laboratory-confirmed SVD survivors and family members who lived with or cared for confirmed SVD patients during their illness. The Hospital Anxiety and Depression Scale was used to evaluate anxiety and depression. The post-traumatic stress disorder (PTSD) checklist for the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition was used to evaluate PTSD. Modified Poisson regression was used to determine factors associated with each mental health disorder. Results We enrolled 54 survivors and 82 family members; median age was 30 years (range, 15–73) and 54% were female. The prevalence of anxiety (55%) and depression (50%) was higher than PTSD (17%). The prevalence of all mental health disorders was similar between survivors and family members. Household size was associated with both anxiety and PTSD. Number of SVD deaths in the household was associated with depression. Conclusion Approximately two-thirds of SVD survivors and family members of patients in the 2022 outbreak in Uganda had ≥ 1 mental health disorders shortly after the outbreak ended. Strengthening mental health services during and after Ebola virus outbreaks for survivors and family members of patients may enhance the quality of outbreak response.

Abstract 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.

Abstract 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.

Abstract Background The COVID-19 pandemic forced governments, multilateral public health organisations and research institutions to undertake research quickly to inform their responses to the pandemic. Most COVID-19-related studies required swift approval, creating ethical and practical challenges for regulatory authorities and researchers. In this paper, we examine the landscape of ethics review processes in Africa during public health emergencies (PHEs). Methods We searched four electronic databases (Web of Science, PUBMED, MEDLINE Complete, and CINAHL) to identify articles describing ethics review processes during public health emergencies and/or pandemics. We selected and reviewed those articles that were focused on Africa. We charted the data from the retrieved articles including the authors and year of publication, title, country and disease(s) reference, broad areas of (ethical) consideration, paper type, and approach. Results Of an initial 4536 records retrieved, we screened the titles and abstracts of 1491 articles, and identified 72 articles for full review. Nine articles were selected for inclusion. Of these nine articles, five referenced West African countries including Liberia, Guinea and Sierra Leone, and experiences linked to the Ebola virus disease. Two articles focused on South Africa and Kenya, while the other two articles discussed more general experiences and pitfalls of ethics review during PHEs in Africa more broadly. We found no articles published on ethics review processes in Africa before the 2014 Ebola outbreak, and only a few before the COVID-19 outbreak. Although guidelines on protocol review and approval processes for PHEs were more frequently discussed after the 2014 Ebola outbreak, these did not focus on Africa specifically. Conclusions There is a gap in the literature about ethics review processes and preparedness within Africa during PHEs. This paper underscores the importance of these processes to inform practices that facilitate timely, context-relevant research that adequately recognises and reinforces human dignity within the quest to advance scientific knowledge about diseases. This is important to improve fast responses to PHEs, reduce mortality and morbidity, and enhance the quality of care before, during, and after pandemics.

Background: Communities affected by Ebola disease (EBOD) may face resulting increases in mental health disorders. We evaluated the prevalence of and factors associated with mental health disorders among persons affected by the 2022 Sudan virus disease (SVD) outbreak in Uganda. Methods: We conducted a cross-sectional study among SVD survivors and family members of survivors and fatal cases from 15–31 January 2023. We included only laboratory-confirmed SVD survivors and family members who lived with or cared for confirmed SVD patients during their illness. The Hospital Anxiety and Depression Scale was used to evaluate anxiety and depression. The post-traumatic stress disorder (PTSD) checklist for the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition was used to evaluate PTSD. Modified Poisson regression was used to determine factors associated with each mental health disorder. Results: We enrolled 54 survivors and 82 family members; median age was 30 years (range, 15–73) and 54% were female. The prevalence of anxiety (55%) and depression (50%) was higher than PTSD (17%). The prevalence of all mental health disorders was similar between survivors and family members. Household size was associated with both anxiety and PTSD. Number of SVD deaths in the household was associated with depression. Conclusion: Approximately two-thirds of SVD survivors and family members of patients in the 2022 outbreak in Uganda had ≥ 1 mental health disorders shortly after the outbreak ended. Strengthening mental health services during and after Ebola virus outbreaks for survivors and family members of patients may enhance the quality of outbreak response. [ABSTRACT FROM AUTHOR]

This article discusses the urgent need for therapeutics to prevent local outbreaks of the Marburg virus from potentially spreading globally. The Marburg virus is a highly pathogenic virus that causes severe hemorrhagic fever in humans and nonhuman primates. Currently, there are no approved therapeutics for Marburg virus disease (MVD), highlighting the need for extensive research. Various potential treatments, including antiviral drugs and vaccines, are being explored, but further research is needed to develop effective countermeasures against MVD. The article emphasizes the importance of investing in research and innovation to address the challenges posed by emerging infectious diseases like Marburg. The text discusses the development of vaccines and therapeutics for Marburg virus disease (MVD). Several vaccine candidates are currently undergoing clinical trials, including one that combines Marburg and Ebola virus antigens. However, none of the vaccine candidates have reached advanced clinical trial stages yet. The text emphasizes the need for collaborative research efforts and standardized approaches to address the public health threat posed by Marburg virus. It also highlights the challenges of diagnosing and handling the virus due to its high pathogenicity and the need for Biosafety Level 4 containment. The natural reservoir of Marburg virus is the Egyptian fruit bat, and pigs can act as intermediate hosts. The text calls for a multipronged approach to prevent future MVD outbreaks, including strengthening public health infrastructure, conducting research on diagnostics and therapeutics, and raising awareness among the public and healthcare workers. The text acknowledges the [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Following the apparent final case in an Ebola virus disease (EVD) outbreak, the decision to declare the outbreak over must balance societal benefits of relaxing interventions against the risk of resurgence. Estimates of the end-of-outbreak probability (the probability that no future cases will occur) provide quantitative evidence that can inform the timing of an end-of-outbreak declaration. An existing modeling approach for estimating the end-of-outbreak probability requires comprehensive contact tracing data describing who infected whom to be available, but such data are often unavailable or incomplete during outbreaks. Here, we develop a Markov chain Monte Carlo-based approach that extends the previous method and does not require contact tracing data. Considering data from two EVD outbreaks in the Democratic Republic of the Congo, we find that data describing who infected whom are not required to resolve uncertainty about when to declare an outbreak over. [ABSTRACT FROM AUTHOR]

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013–2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic. [ABSTRACT FROM AUTHOR]

Health-care providers and front-line workers are at risk of contracting Ebola virus disease during an Ebola virus outbreak and consequently of becoming drivers of the disease. We aimed to assess the long-term immunogenicity of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen and the safety of and immune memory response to an Ad26.ZEBOV booster vaccination at 1 year or 2 years after the first dose in this at-risk population. This open-label, single-centre, randomised, phase 2 trial was conducted at one study site within a hospital in Boende, Democratic Republic of the Congo. Adult health-care providers and front-line workers, excluding those with a known history of Ebola virus disease, were vaccinated with a two-dose heterologous regimen administered at a 56-day interval via a 0·5 mL intramuscular injection in the deltoid muscle, comprising Ad26.ZEBOV as the first dose and MVA-BN-Filo as the second dose. After the initial vaccination on day 1, participants were randomly assigned (1:1) via randomisation envelopes, opened in a sequential order, to receive an Ad26.ZEBOV booster vaccination at 1 year (group 1) or 2 years (group 2) after the first dose. We present the secondary and exploratory objectives of the trial—results of the primary objective have been published elsewhere. We measured immunogenicity at six timepoints per group as geometric mean concentrations (GMCs) of Ebola virus glycoprotein-specific IgG binding antibodies, using the Filovirus Animal Non-Clinical Group ELISA. We assessed serious adverse events occurring up to 6 months after the last dose and local and systemic solicited and unsolicited adverse events reported for 7 days after the booster vaccination. Antibody responses were analysed per protocol, serious adverse events per full analysis set (FAS), and adverse events for all boosted FAS participants. This trial is registered as completed on ClinicalTrials.gov (NCT04186000). Between Dec 18, 2019, and Feb 8, 2020, 699 health-care providers and front-line workers were enrolled and 698 were randomly assigned (350 to group 1 and 348 to group 2 [FAS]); 534 (77%) participants were male and 164 (23%) were female. 319 in group 1 and 317 in group 2 received the booster. 29 (8%) in group 1 and 26 (7%) in group 2 did not complete the study, mostly due to loss to follow-up or moving out of the study area. In both groups, injection-site pain or tenderness (87 [27%] of 319 group 1 participants vs 90 [28%] of 317 group 2 participants) and headache (91 [29%] vs 93 [29%]) were the most common solicited adverse events related to the investigational product. One participant (in group 2) had a related serious adverse event after booster vaccination (fever of ≥40·0°C). Before booster vaccination, Ebola virus glycoprotein-specific IgG binding antibody GMCs were 279·9 ELISA units (EU) per mL (95% CI 250·6–312·7) in 314 group 1 participants (1 year after first dose) and 274·6 EU/mL (242·1–311·5) in 310 group 2 participants (2 years after first dose). These values were 5·2 times higher in group 1 and 4·9 times higher in group 2 than before vaccination on day 1. 7 days after booster vaccination, these values increased to 10 781·6 EU/mL (9354·4–12 426·4) for group 1 and 10 746·9 EU/mL (9208·7–12 542·0) for group 2, which were approximately 39 times higher than before booster vaccination in both groups. 1 year after booster vaccination in 299 group 1 participants, a GMC that was 7·6-times higher than before booster vaccination was still observed (2133·1 EU/mL [1827·7–2489·7]). Overall, the vaccine regimen and booster dose were well tolerated. A similar and robust humoral immune response was observed for participants boosted 1 year and 2 years after the first dose, supporting the use of the regimen and flexibility of booster dose administration for prophylactic vaccination in at-risk populations. Innovative Medicines Initiative 2 Joint Undertaking and Coalition for Epidemic Preparedness Innovations. [ABSTRACT FROM AUTHOR]

Introduction The purpose of this review is to examine African Ebola outbreaks from their first discovery to the present, to determine how the medical and public health response has changed and identify the causes for those changes. We sought to describe what is now known about the epidemiology and spread of Ebola virus disease (EVD) from the significant outbreaks that have occurred and outbreak control methods applied under often challenging circumstances. Given the substantial role that the U.S. Government and the U.S. DoD have played in the 2014 to 2016 West African Ebola outbreak, the role of the DoD and the U.S. Africa Command in controlling EVD is described. Materials and Methods A descriptive method design was used to collect and analyze all available Ebola outbreak literature using the PubMed database. An initial literature search was conducted by searching for, obtaining, and reading original source articles on all major global Ebola outbreaks. To conduct a focused search, we used initial search terms "Ebola outbreak," "Ebola virus disease," "Ebola response," "Ebola countermeasures," and also included each country's name where Ebola cases are known to have occurred. From the 4,673 unique articles obtained from this search and subsequent article title review, 307 articles were identified for potential inclusion. Following abstract and article review, 45 original source articles were used to compile the history of significant Ebola outbreaks. From this compilation, articles focused on each respective subsection of this review to delineate and describe the history of EVD and response, identifying fundamental changes, were obtained and incorporated. Results We present known Ebola virus and disease attributes, including a general description, seasonality and location, transmission capacity, clinical symptoms, surveillance, virology, historical EVD outbreaks and response, international support for Ebola outbreak response, U.S. DoD support, medical countermeasures supporting outbreak response, remaining gaps to include policy limitations, regional instability, climate change, migration, and urbanization, public health education and infrastructure, and virus persistence and public awareness. Conclusions The health and societal impacts of EVD on Africa has been far-reaching, with about 35,000 cases and over 15,000 deaths, with small numbers of cases spreading globally. However, the history of combatting EVD reveals that there is considerable hope for African nations to quickly and successfully respond to Ebola outbreaks, through use of endemic resources including Africa CDC and African Partner Outbreak Response Alliance and the U.S. Africa Command with greater DoD reachback. Although there remains much to be learned about the Ebola virus and EVD including whether the potential for novel strains to become deadly emerging infections, invaluable vaccines, antivirals, and public health measures are now part of the resources that can be used to combat this disease. [ABSTRACT FROM AUTHOR]

2019 has been the most violent year on record for health workers in the Democratic Republic of the Congo. Attacks on healthcare coincided with the first-ever Ebola outbreak in an active conflict zone. Many of the attacks on the Ebola response were perpetrated by civilians who intended to disrupt the response, which in turn contributed to the spread of the virus. Why would communities attack the very people trying to protect them from disease? This mixed-method study examines the case of violence against Ebola responders during the Democratic Republic of the Congo's tenth Ebola outbreak from 2018 to 2020. First, an 'explaining-outcome' process tracing reconstructs key events that led to the violent resistance of the population. I find that – contrary to popular belief – distrust alone was not the main driver. Rather, I argue that the politicization of the response provoked violent popular resistance. Second, an interrupted time-series model shows that the exclusion of three regions from the presidential election due to Ebola led to a significant increase in attacks on Ebola responders. The analysis demonstrates that the behavior of healthcare responders has limited ability to build trust when other political dynamics are at work. The article illustrates how combining process tracing with quantitative causal inference methods enables the simultaneous inquiry of cause, mechanism, and effect. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model. Author summary: Outbreaks caused by ebolaviruses and Lassa virus have made headlines worldwide in recent years. Most recently, in 2023 a Marburg virus outbreak resulted in 49 confirmed or probable cases, 41 of which were fatal. Apart from vaccines against Ebola virus, no licensed vaccine exists to protect against viral haemorrhagic fevers caused by filoviruses. An ideal vaccine against viral haemorrhagic fevers would induce long-lasting immunity to, and protection from, viruses causing disease and concomitant fatalities. We developed vaccines which can target multiple orthoebolaviruses, the closely related Marburg virus and Lassa virus. The geographical ranges of these viruses overlap in West and Central Africa. We used viral vector platform technologies to generate these vaccines; ChAdOx1 has now been administered worldwide as part of COVID-19 vaccine rollouts, and MVA has been used in numerous clinical trials thus far. We found that both long lasting, antigen specific T cell and antibody responses were induced after vaccination. Lastly, we demonstrated that these vaccines could protect small animals against challenge with Ebola virus, Sudan virus and Marburg virus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The rVSVΔG-ZEBOV-GP vaccine constitutes a valuable tool to control Ebola virus disease outbreaks. This retrospective cohort study aimed to assess the protective effect of the vaccine against death among patients with confirmed Ebola virus disease. In this retrospective cohort analysis of patients with confirmed Ebola virus disease admitted to Ebola health facilities in the Democratic Republic of the Congo between July 27, 2018, and April 27, 2020, we performed univariate and multivariate analyses to assess case fatality risk and cycle threshold for nucleoprotein according to vaccination status, Ebola virus disease-specific treatments (eg, mAb114 and REGN-EB3), and other risk factors. We analysed all 2279 patients with confirmed Ebola virus disease. Of these 2279 patients, 1300 (57%) were female and 979 (43%) were male. Vaccination significantly lowered case fatality risk (vaccinated: 25% [106/423] vs not vaccinated: 56% [570/1015]; p<0·0001). In adjusted analyses, vaccination significantly lowered the risk of death compared with no vaccination, with protection increasing as time elapsed from vaccination to symptom onset (vaccinated ≤2 days before onset: 27% [27/99], adjusted relative risk 0·56 [95% CI 0·36–0·82, p=0·0046]; 3–9 days before onset: 20% [28/139], 0·44 [0·29–0·65, p=0·0001]; ≥10 days before onset: 18% [12/68], 0·40 [0·21–0·69; p=0·0022]; vaccination date unknown: 33% [39/117], 0·69 [0·48–0·96; p=0·0341]; and vaccination status unknown: 52% [441/841], 0·80 [0·70–0·91, p=0·0011]). Longer time from symptom onset to admission significantly increased risk of death (49% [1117/2279], 1·03 [1·02–1·05; p<0·0001]). Cycle threshold values for nucleoprotein were significantly higher—indicating lower viraemia—among patients who were vaccinated compared with those who were not vaccinated; the highest difference was observed among those vaccinated 21 days or longer before symptom onset (median 30·0 cycles [IQR 24·6–33·7]) compared with patients who were not vaccinated (21·4 cycles [18·4–25·9], p<0·0001). To our knowledge, this is the first observational study describing the protective effect of rVSVΔG-ZEBOV-GP vaccination against death among patients with confirmed Ebola virus disease admitted to an Ebola health facility. Vaccination was protective against death for all patients, even when adjusted for Ebola virus disease-specific treatment, age group, and time from symptom onset to admission. Médecins Sans Frontières. For the French translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Ebolavirus disease (EVD) is an often‐lethal disease caused by the genus Ebolavirus (EBOV). Although vaccines are being developed and recently used, outbreak control still relies on a combination of various factors, including rapid identification of EVD cases. This allows rapid patient isolation and control measure implementation. Ebolavirus diagnosis is performed in treatment centers or reference laboratories, which usually takes a few hours to days to confirm the outbreak or deliver a clear result. A fast and field‐deployable molecular detection method, such as the isothermal amplification recombinase‐aided amplification (RAA), could significantly reduce sample‐to‐result time. In this study, a RT‐RAA assay was evaluated for EBOV detection. Various primer and probe combinations were screened; analytical sensitivity and cross‐specificity were tested. A total of 40 archived samples from the 2014 to 2016 Ebola outbreak in West Africa were tested with both the reference method real‐time RT‐PCR and the established RT‐RAA assay. The assay could detect down to 22.6 molecular copies per microliter. No other pathogens were detected with the Ebolavirus RT‐RAA assay. Testing 40 samples yield clinical sensitivity and specificity of 100% each. This rapid isothermal RT‐RAA assay can replace the previous RT‐RPA and continue to offer rapid EBOV diagnostics. [ABSTRACT FROM AUTHOR]

The article discusses research which found a surrogate Ebola virus (EBOV) lethal mice model of recombinant vesicular stomatitis viruses (VSV) that could be used as a platform for EBOV glycoprotein-targeting prophylactic vaccines evaluation in biosafety level-2 (BSL-2) laboratories. The study determined the susceptibility of immunodeficient mice to VSV-EBOV. It determined tissue tropism and organ virus load in infected mice and observed outcomes in mice following VSV-EBOV infection.

The Ebola virus (EBOV) is a member of the Orthoebolavirus genus, Filoviridae family, which causes severe hemorrhagic diseases in humans and non-human primates (NHPs), with a case fatality rate of up to 90%. The development of countermeasures against EBOV has been hindered by the lack of ideal animal models, as EBOV requires handling in biosafety level (BSL)-4 facilities. Therefore, accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against EBOV. In this study, a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein (VSV-EBOV/GP) was constructed and applied as a surrogate virus, establishing a lethal infection in hamsters. Following infection with VSV-EBOV/GP, 3-week-old female Syrian hamsters exhibited disease signs such as weight loss, multi-organ failure, severe uveitis, high viral loads, and developed severe systemic diseases similar to those observed in human EBOV patients. All animals succumbed at 2-3 days post-infection (dpi). Histopathological changes indicated that VSV-EBOV/GP targeted liver cells, suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV (WT EBOV). Notably, the pathogenicity of the VSV-EBOV/GP was found to be species-specific, age-related, gender-associated, and challenge route-dependent. Subsequently, equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this model. Overall, this surrogate model represents a safe, effective, and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions, which would accelerate technological advances and breakthroughs in confronting Ebola virus disease. [ABSTRACT FROM AUTHOR]