Ebola Virus Disease Outbreak Research Articles

RVSV-ZEBOV vaccination in people with pre-existing immunity to Ebolavirus: an open-label safety and immunogenicity study in Guinean communities affected by Ebola virus disease (l’essai proches)

BackgroundZaire Ebolavirus disease (EVD) outbreaks can be controlled using rVSV-ZEBOV vaccination and other public health measures. People in high-risk areas may have pre-existing antibodies from asymptomatic Ebolavirus exposure that might affect response to rVSV-ZEBOV. Therefore, we assessed the impact pre-existing immunity had on post-vaccination IgG titre, virus neutralisation, and reactogenicity following vaccination.MethodsIn this prospective cohort study, 2115 consenting close contacts (“proches”) of EVD survivors were recruited. Proches were vaccinated with rVSV-ZEBOV and followed up for 28 days for safety and immunogenicity. Anti-GP IgG titre at baseline and day 28 was assessed by ELISA. Samples from a representative subset were evaluated using live virus neutralisation.ResultsTen percent were seropositive at baseline. At day 28, IgG in baseline seronegative (GMT 0.106 IU/ml, 95% CI: 0.100 to 0.113) and seropositive (GMT 0.237 IU/ml, 0.210 to 0.267) participants significantly increased from baseline (both p < 0.0001). There was strong correlation between antibody titres and virus neutralisation in day 28 samples (Spearman’s rho 0.75). Vaccinees with baseline IgG antibodies against Zaire Ebolavirus had similar safety profiles to those without detectable antibodies (63.6% vs 66.1% adults experienced any adverse event; 49.1% vs 60.9% in children), with almost all adverse events graded as mild. No serious adverse events were attributed to vaccination. No EVD survivors tested positive for Ebolavirus by RT-PCR.ConclusionsThese data add further evidence of rVSV-ZEBOV safety and immunogenicity, including in people with pre-existing antibodies from suspected natural ZEBOV infection whose state does not blunt rVSV-ZEBOV immune response. Pre-vaccination serological screening is not required.

Readiness to manage Ebola Virus Disease among emergency healthcare workers in Uganda: a nationwide multicenter survey

BackgroundEmerging 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.MethodsThis 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.ResultsData 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.ConclusionOur 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.

Ebola Virus-Specific Neutralizing Antibody Persists at High Levels in Survivors 2 Years After Resolution of Disease in a Sierra Leonean Cohort.

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.

Establishing Vitreoretinal Surgery Capacity in Sierra Leone: Challenges and Opportunities to Address Retinal Health Disparities in Resource-limited Settings.

A range of challenges exists regarding vitreoretinal (VR) surgical services in resource-limited settings, including Sierra Leone. As a result, retinal pathologies may contribute to vision loss and blindness. In the wake of the 2013 to 2016 outbreak of Ebola virus disease in West Africa, gaps in ophthalmic care were underscored as survivors were experiencing a constellation of sequelae, including uveitis and VR disease. Given the unmet needs in addressing VR disease, systems for retinal surgical care were required. To further understand long-term ocular complications in Ebola survivors and molecular and immunologic factors associated with this, research infrastructure was developed for retinal evaluation and surgery. The 5 "S'" framework was implemented and considered staff, space, stuff, systems, and social support. The ongoing development of retinal health infrastructure has helped to address challenges related to program implementation, development of surgical capacity, and alignment with local stakeholders and collaborator objectives. VR surgical services have been established in Sierra Leone through multidisciplinary partnerships and collaboration and serve patients in-country, as well as others in West Africa who have traveled for care. Continued engagement across stakeholders can aim to address challenges and promote effective care delivery.

Corneal and Conjunctival Abnormalities in a Cohort of Survivors from the Western African Ebola Virus Disease Outbreak

PurposeTo characterize corneal and conjunctival abnormalities (CCAs) and their impact on visual acuity in a cohort of survivors from the Western African Ebola virus disease (EVD) outbreak. DesignA post hoc analysis of 121 patients, who had previously undergone screening for the Ebola Virus Persistence in Ocular Tissues and Fluids study, was performed. MethodsPatients underwent a comprehensive ophthalmic exam at the Lowell and Ruth Gess Eye Hospital in Freetown, Sierra Leone. Demographic (including age, sex, and the number of days spent in the Ebola treatment unit and examination (such as visual acuity, and ocular complications) data were collected and used for the analysis. Visual acuity was either uncorrected or corrected with spectacles. Descriptive and inferential statistical analyses were performed, and a p-value < 0.05 was considered statistically significant. ResultsA total of 242 eyes (121 patients) were included in this study. The mean age was 31.5 ± 16.1 years, and 70% were female. Of 242 eyes, 28 (11.5%) eyes of 15 patients (12.4%) presented with at least one or more corneal or conjunctival abnormalities. Within eyes that demonstrated CCAs, the findings included dry eye (28.6% of eyes), band keratopathy (25% of eyes), and corneal scar (21.4% of eyes). Corneal edema was found in 14.3% of eyes, while pterygium and epithelial bullae were each found in 7.1% of affected eyes. Patients without CCAs had better visual acuity compared to patients with CCAs although the difference was not statistically significant (0.82 ± 1.17 vs 1.01 ± 1.29, p=0.4). A subset of patients with CCAs also reported ocular symptoms including eye pain, light sensitivity, excessive tearing, and blurry vision. ConclusionIn this post hoc analysis, we observed CCAs in 12% of EVD survivors. These findings highlight the potential for corneal and conjunctival sequelae during EVD survivorship and the need for ongoing ophthalmic care for this vulnerable population.

Global Health Security in Vision Care: Health Systems Strengthening During Ebola Virus Disease Outbreak Responses.

During the last decade, global health security has been threatened by major Ebola virus disease outbreaks in Western Africa (2014 to 2016) and in eastern Democratic Republic of the Congo (2018 to 2020). Particularly in Western Africa, the outbreak initially overwhelmed health care capacity in already fragile health systems. Thousands of survivors were at risk of newly recognized postacute ocular complications, and their need for urgent ophthalmic care challenged national vision health systems with scarce eye care services. In these unprecedently large outbreaks with implications for global health security, agile eye care responses were challenging, including in regard to decision coordination and requisite logistical needs. In this report, we detail vision care initiatives implemented in response to these outbreaks and highlight the need to include vision care as a critical component of the response to infectious disease outbreaks with eye health implications.

Screening for Eye Disease in Ebola Virus Disease Survivors: Program Implementation During an Active Outbreak in the North Kivu and Ituri Provinces, Democratic Republic of the Congo.

First identified in the Democratic Republic of the Congo (DRC, formerly Zaire) in 1976, Ebola virus disease (EVD) outbreaks have afflicted thousands of Congolese over the past several decades. The nation's largest outbreak of EVD in 2018-2020 was complicated by security challenges as well as large case numbers across an expansive geographic region. These factors provided challenges for logistical considerations as well as clinical coverage. In conjunction with the EVD survivor care program spearheaded by the Ministry of Health in DRC, the DRC Intitut National de Recherche Biomédicale, (DRC Institut National de Recherche Biomedicale, DRC National Institute of Biomedical Research) and others, we launched a multidimensional effort to provide ophthalmic care to EVD survivors. During the engagement period, 237 EVD survivors were screened, 56% of which were women. The 237 EVD survivors constituted ∼75% of the total EVD survivors who were discharged at the time of the intervention. The mean time from EVD symptom onset to evaluation was 4.6 months ± 1.8 SD (range: 24d to 8.5mo). Ninety-seven (41%) of EVD survivors screened reported ocular symptoms during or after acute illness, such as itchy eyes (49%), eye pain (25%), and tears (24%). Ophthalmic findings, including retinal scarring, active uveitis, dry eye disease, cataracts, and glaucoma, were also identified. The need for continued monitoring and longitudinal care for EVD survivors is evident from the expanding body of literature pertaining to post-acute sequelae, including ophthalmic manifestations. Initiatives for such care should be conducted across and in conjunction with multidisciplinary stakeholders for contextualization and effectiveness.

Performance of an envelope glycoprotein-based multiplex immunoassay for Ebola virus antibody detection in a cohort of Ebola virus disease survivors

Serological surveillance in animal and human hosts can be a cost-effective strategy for orthoebolavirus detection, but is challenged by accurate estimates of seroprevalence, potential pauci-symptomatic disease presentation, and antigenic cross-reactivity. Here, we describe the use of an envelope glycoprotein (GP)-based multiplex microsphere immunoassay, consisting of nine filovirus GP antigens, for the detection of anti-Ebola virus (EBOV) antibodies in a well-characterized cohort of Guinean Ebola virus disease (EVD) survivors and contacts from the 2013 – 2016 West African EVD outbreak. We examined sensitivity and specificity for the detection of anti-EBOV antibodies by GP expressed as recombinant trimeric ectodomains, yielding an assay performance of 95.96% sensitivity and 98.61% specificity. Additionally, agreement between the multiplex test and a whole virus ELISA and virus neutralization test showed strong correlations. The results demonstrate this filovirus multiplex test is a sensitive tool for high-throughput serosurveillance

Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England.

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.

Evaluation of centralised and decentralised models of care during the 2020 Ebola Virus Disease outbreak in Equateur Province, Democratic Republic of the Congo: A brief report.

Traditionally in the Democratic Republic of the Congo (DRC), centralised Ebola treatment centres (ETCs) have been set exclusively for Ebola virus disease (EVD) case management during outbreaks. During the 2020 EVD outbreak in DRC's Equateur Province, existing health centres were equipped as decentralised treatment centres (DTC) to improve access for patients with suspected EVD. Between ETCs and DTCs, we compared the time from symptom onset to admission and diagnosis among patients with suspected EVD. This was a cohort study based on analysis of a line-list containing demographic and clinical information of patients with suspected EVD admitted to any EVD health facility during the outbreak. Of 2359 patients with suspected EVD, 363 (15%) were first admitted to a DTC. Of 1996 EVD-suspected patients initially admitted to an ETC, 72 (4%) were confirmed as EVD-positive. Of 363 EVD-suspected patients initially admitted to a DTC, 6 (2%) were confirmed and managed as EVD-positive in the DTC. Among all EVD-suspected patients, the median (interquartile range) duration between symptom onset and admission was 2 (1-4) days in a DTC compared to 4 (2-7) days in an ETC (p<0.001). Similarly, time from symptom onset to admission was significantly shorter among EVD-suspected patients ultimately diagnosed as EVD-negative. Since <5% of the EVD-suspected patients admitted were eventually diagnosed with EVD, there is a need for better screening to optimise resource utilization and outbreak control. Only one in seven EVD-suspected patients were admitted to a DTC first, as the DTCs were piloted in a limited and phased manner. However, there is a case to be made for considering decentralized care especially in remote and hard-to-reach areas in places like the DRC to facilitate early access to care, contain viral shedding by patients with EVD and ensure no disrupted provision of non-EVD services.

Development of a clinical prediction score for Ebola virus disease screening at triage centers in the Democratic Republic of the Congo.

The 2018-2020 Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) was the largest since the disease's discovery in 1976. Rapid identification and isolation of EVD patients are crucial during triage. This study aimed to develop a clinical prediction score for EVD using clinical and epidemiological predictors. We conducted a retrospective cross-sectional study using surveillance data from EVD outbreak, collected during routine clinical care at the Ebola Transit Center (ETC) in Beni, DRC, from 2018 to 2020. The Spiegelhalter and Knill-Jones method was used for score development, including potential predictors with an adjusted likelihood ratio above 2 or below 0.50. Validation was performed using a dataset previously published in PLOSOne by Tshomba et al. Among 3725 patients screened, 3698 fulfilled the inclusion criteria, with 571 (15.4%) testing positive for EVD via RT-PCR Test. Seven predictive factors were identified: asthenia, sore throat, conjunctivitis, bleeding gums, hematemesis, contact with a sick person, and contact with a traditional healer. The prediction score achieved an Area under the receiver operating characteristic (AUROC) of 0.764, with 81.4% sensitivity and 53.6% specificity at a -1 cutoff. External validation demonstrated an AUROC of 0.766, with 80.8% sensitivity and 41.4% specificity at the -1 cutoff. Our study developed a screening tool to assess the risk of suspected patients developing EVD and being admitted to ETUs for RT-PCR testing and treatment. External validation results affirmed the model's reliability and generalizability in similar settings, suggesting its potential integration into clinical practice. Given the severity and urgency of EVD as well as the risk nosocomial EVD transmission, it is essential to continuously update these models with real-time data on symptoms, disease progression, patient outcomes and validated RDT during EVD outbreaks. This approach will enhance model accuracy, enabling more precise risk assessments and more effective outbreak management.

Nonstandard finite difference schemes for some epidemic optimal control problems

We construct and analyse nonstandard finite difference (NSFD) schemes for two epidemic optimal control problems. Firstly, we consider the well-known MSEIR system that can be used to model childhood diseases such as the measles, with the vaccination as a control intervention. The second optimal control problem is related to the 2014–2016 West Africa Ebola Virus Disease (EVD) outbreak, that came with the unprecedented challenge of the disease spreading simultaneously in three different countries, namely Guinea, Liberia and Sierra Leone, where it was difficult to control the considerable migrations and travels of people inbound and outbound. We develop an extended SEIRD metapopulation model modified by the addition of compartments of quarantined and isolated individuals. The control parameters are the exit screening of travelers and the vaccination of the susceptible individuals. For the two optimal control problems, we provide the results on: (i) the (global) stability of the disease-free and/or endemic equilibria of the state variable systems; (ii) the positivity and boundedness of solutions of the state variables systems; (iii) the existence, uniqueness and characterization of the optimal control solutions that minimizes the cost functional. On the other hand: (iv) we design Euler-based nonstandard finite difference versions of the Forward-Backward Sweep Method (NSFD-FBSM) that are dynamically consistent with the state variable systems; (v) we provide numerical simulations that support the theory and show the superiority of the nonstandard approach over the classical FBSM. The numerical simulations suggest that significantly increasing the coverage of the vaccine with its implementation for adults as well is essential if the recurrence of measles outbreaks is to be stopped in South Africa. They also show that the optimal control vaccination for the 2014-2016 EVD is more efficient than the exit screening intervention.

Prevalence of human filovirus infections in sub-Saharan Africa: A systematic review and meta-analysis protocol

BackgroundRecent 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.MethodsThe 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.DiscussionAccurately 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 RegistrationIn accordance with the guidelines outlined in the PRISMA-P methodology, this protocol was registered with PROSPERO on April 7, 2023 (ID: CRD42023415358).

Effectiveness of rVSV-ZEBOV vaccination during the 2018-20 Ebola virus disease epidemic in the Democratic Republic of the Congo: a retrospective test-negative study.

The recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only WHO prequalified vaccine recommended for use to respond to outbreaks of Ebola virus (species Zaire ebolavirus) by WHO's Strategic Advisory Group of Experts on Immunization. Despite the vaccine's widespread use during several outbreaks, no real-world effectiveness estimates are currently available in the literature. We conducted a retrospective test-negative analysis to estimate effectiveness of rVSV-ZEBOV vaccination against Ebola virus disease during the 2018-20 epidemic in the Democratic Republic of the Congo, using data on suspected Ebola virus disease cases collected from Ebola treatment centres. Those eligible for inclusion had an available Ebola virus RT-PCR result, available key data, were eligible for vaccination during the outbreak, and had symptom onset aligning with the period in which a ring-vaccination protocol was in use. After imputing missing data, each individual confirmed by RT-PCR to be Ebola virus disease-positive (defined as a case) was matched to one individual negative for Ebola virus disease (control) by sex, age, health zone, and month of symptom onset. Effectiveness was estimated from the odds ratio of being vaccinated (≥10 days before symptom onset) versus being unvaccinated among cases and controls, after adjusting for the matching factors. The imputation, matching and effectiveness estimation, was repeated 500 times. 1273 (4·8%) of 26 438 eligible individuals were positive for Ebola virus disease (cases) and 25 165 (95·2%) were negative (controls). 40 (3·1%) cases and 1271 (5·1%) controls were reported as being vaccinated at least 10 days before symptom onset. After selecting individuals who reported exposure to an individual with Ebola virus disease within the 21 days before symptom onset and matching, the analysis datasets comprised a median of 309 cases and 309 controls. 10 days or more after vaccination, the effectiveness of rVSV-ZEBOV against Ebola virus disease was estimated to be 84% (95% credible interval 70-92). This analysis is the first to provide estimates of the real-world effectiveness of the rVSV-ZEBOV vaccine against Ebola virus disease, amid the widespread use of the vaccine during a large Ebola virus disease outbreak. Our findings confirm that rVSV-ZEBOV is highly protective against Ebola virus disease and support its use during outbreaks, even in challenging contexts such as in the eastern Democratic Republic of the Congo. Médecins Sans Frontières. For the French translation of the abstract see Supplementary Materials section.

National burden of Ebola virus disease in Democratic Republic of the Congo: the urgency to act.

Ebola virus disease (EVD) has long been a major public health concern for Democratic Republic of the Congo (DR Congo). First identified in DR Congo in 1976, the country has witnessed more than 25 outbreaks of this deadly disease, which has a case fatality rate of nearly 90% and manifesting with symptoms such as diarrhoea, vomiting, stomachache and haemorrhagic fever. African fruit bats have been speculated to be the reservoir of this virus. DR Congo is currently facing another EVD outbreak simultaneously with other communicable diseases, rendering it vulnerable to a shortage of medical and paramedical staff along with distrust among remote communities towards local authorities due to armed conflict and political instability. Moreover, lack of ring vaccinations and inefficient surveillance of suspected individuals are some other significant hurdles in disease control. Despite the availability of rVSV-ZEBOV/Erbevo vaccine and many antibody-based vaccines, challenges including politicization, low access to remote communities, and illiteracy have limited their effectiveness. Recently, the Congolese govt. has put in efforts such as building local capacities at the health zone level, outbreak control intervention, community engagement and social mobilization to counter the rising EVD cases. Four successive Strategic Response Plans have been implemented to increase resource mobilization by DR Congo and her partners. The Spread of zoonotics such as EVD can be confronted by implementing the One Health approach, which involves medical staff, veterinarians and public health officials.

Delivery and Safety of a Two-Dose Preventive Ebola Virus Disease Vaccine in Pregnant and Non-Pregnant Participants during an Outbreak in the Democratic Republic of the Congo.

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.

Immunogenicity of an Extended Dose Interval for the Ad26.ZEBOV, MVA-BN-Filo Ebola Vaccine Regimen in Adults and Children in the Democratic Republic of the Congo.

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.

Comparison of Routes of Administration, Frequency, and Duration of Favipiravir Treatment in Mouse and Guinea Pig Models of Ebola Virus Disease.

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.

Optimizing the timing of an end-of-outbreak declaration: Ebola virus disease in the Democratic Republic of the Congo.

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.

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

BackgroundThe 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.MethodWe 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.ResultsThe 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.ConclusionHigh 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.