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

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

Use of Ebola Vaccines - Worldwide, 2021-2023.

Ebola virus disease (Ebola) is a rare but severe illness in humans, with an average case fatality rate of approximately 50%. Two licensed vaccines are currently available against Orthoebolavirus zairense, the virus that causes Ebola: the 1-dose rVSVΔG-ZEBOV-GP (ERVEBO [Merck]) and the 2-dose regimen of Ad26.ZEBOV and MVA-BN-Filo (Zabdeno/Mvabea [Johnson & Johnson]). The Strategic Advisory Group of Experts on Immunization recommends the use of 1-dose ERVEBO during Ebola outbreaks, and in 2021, a global stockpile of ERVEBO was established to ensure equitable, timely, and targeted access to vaccine doses for future Ebola outbreaks. This report describes the use of Ebola vaccines and the role of the stockpile developed and managed by the International Coordinating Group (ICG) on Vaccine Provision during 2021-2023. A total of 145,690 doses have been shipped from the ICG stockpile since 2021. However, because outbreaks since 2021 have been limited and rapidly contained, most doses (139,120; 95%) shipped from the ICG stockpile have been repurposed for preventive vaccination of high-risk groups, compared with 6,570 (5%) used for outbreak response. Repurposing doses for preventive vaccination could be prioritized in the absence of Ebola outbreaks to prevent transmission and maximize the cost-efficiency and benefits of the stockpile.

Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen.

BACKGROUND: The exposure to parasites may influence the immune response to vaccines in endemic African countries. In this study, we aimed to assess the association between helminth exposure to the most prevalent parasitic infections, schistosomiasis, soil transmitted helminths infection and filariasis, and the Ebola virus glycoprotein (EBOV GP) antibody concentration in response to vaccination with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in African and European participants using samples obtained from three international clinical trials. METHODS/PRINCIPAL FINDINGS: We conducted a study in a subset of participants in the EBL2001, EBL2002 and EBL3001 clinical trials that evaluated the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against EVD in children, adolescents and adults from the United Kingdom, France, Burkina Faso, Cote d'Ivoire, Kenya, Uganda and Sierra Leone. Immune markers of helminth exposure at baseline were evaluated by ELISA with three commercial kits which detect IgG antibodies against schistosome, filarial and Strongyloides antigens. Luminex technology was used to measure inflammatory and activation markers, and Th1/Th2/Th17 cytokines at baseline. The association between binding IgG antibodies specific to EBOV GP (measured on day 21 post-dose 2 and on Day 365 after the first dose respectively), and helminth exposure at baseline was evaluated using a multivariable linear regression model adjusted for age and study group. Seventy-eight (21.3%) of the 367 participants included in the study had at least one helminth positive ELISA test at baseline, with differences of prevalence between studies and an increased prevalence with age. The most frequently detected antibodies were those to Schistosoma mansoni (10.9%), followed by Acanthocheilonema viteae (9%) and then Strongyloides ratti (7.9%). Among the 41 immunological analytes tested, five were significantly (p < .003) lower in participants with at least one positive helminth ELISA test result: CCL2/MCP1, FGFbasic, IL-7, IL-13 and CCL11/Eotaxin compared to participants with negative helminth ELISA tests. No significant association was found with EBOV-GP specific antibody concentration at 21 days post-dose 2, or at 365 days post-dose 1, adjusted for age group, study, and the presence of any helminth antibodies at baseline. CONCLUSIONS/SIGNIFICANCE: No clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen. TRIAL REGISTRATION: NCT02416453, NCT02564523, NCT02509494. ClinicalTrials.gov.

Engaging the public in decisions about emergency vaccine deployment strategies: Lessons from scenario-based discussions in Sierra Leone.

ABSTRACTThe COVID-19 pandemic has amplified discussions on emergency vaccine deployment strategies, with current perspectives often neglecting extensive community involvement in ethical, logistical and political aspects. Existing social science literature predominantly delves into factors influencing trust, overlooking the untapped potential for community engagement.Our study examines community preparedness in Sierra Leone's Kambia District, exploring diverse viewpoints on vaccine deployment strategies, emphasising Ebola and COVID-19 vaccinations. Utilising extensive ethnographic research from the Ebola vaccine trials (EBOVAC Salone) conducted in Kambia District from 2015 to 2021, including participant observation and tailored focus group discussions, we investigated various deployment scenarios with community leaders and citizens.Our findings underscore the multifaceted contributions of social science research with communities in shaping emergency vaccination strategies. These contributions span logistical insights, aligning campaigns with local livelihoods and social structures, and grounded ethical concerns assessing social justice outcomes across epidemic scenarios. This study emphasises the imperative of integrating discussions on vaccine confidence and deployment. It highlights communities' proficiency in epidemiological reasoning and their ability to bring this in conversation with salient socio-cultural, economic and religious dimensions. We therefore promote the cultivation of public dialogue, collaborative creation of impactful vaccination initiatives alongside relevant communities in recognition of their invaluable perspectives .

Public health surveillance through community health workers: a scoping review of evidence from 25 low-income and middle-income countries.

BACKGROUND: The last 3 years have witnessed global health challenges, ranging from the pandemics of COVID-19 and mpox (monkeypox) to the Ebola epidemic in Uganda. Public health surveillance is critical for preventing these outbreaks, yet surveillance systems in resource-constrained contexts struggle to provide timely disease reporting. Although community health workers (CHWs) support health systems in low-income and middle-income countries (LMICs), very little has been written about their role in supporting public health surveillance. This review identified the roles, impacts and challenges CHWs face in public health surveillance in 25 LMICs. METHODS: We conducted a scoping review guided by Arksey and O'Malley's framework. We exported 1,156 peer-reviewed records from Embase, Global Health and PubMed databases. After multiple screenings, 29 articles were included in the final review. RESULTS: CHWs significantly contribute to public health surveillance in LMICs including through contact tracing and patient visitation to control major infectious diseases such as HIV/AIDS, malaria, tuberculosis, Ebola, neglected tropical diseases and COVID-19. Their public health surveillance roles typically fall into four main categories including community engagement; data gathering; screening, testing and treating; and health education and promotion. The use of CHWs in public health surveillance in LMICs has been impactful and often involves incorporation of various technologies leading to improved epidemic control and disease reporting. Nonetheless, use of CHWs can come with four main challenges including lack of education and training, lack of financial and other resources, logistical and infrastructural challenges as well as community engagement challenges. CONCLUSION: CHWs are important stakeholders in surveillance because they are closer to communities than other healthcare workers. Further integration and training of CHWs in public health surveillance would improve public health surveillance because CHWs can provide health data on 'hard-to-reach' populations. CHWs' work in public health surveillance would also be greatly enhanced by infrastructural investments.

Perceptions, attitudes, and willingness of healthcare and frontline workers to participate in an Ebola vaccine trial in Uganda.

BACKGROUND: Understanding the knowledge, perception and attitudes towards Ebola vaccines is an important factor in ensuring future use of these vaccines. A qualitative methods study embedded in an Ebola vaccine immunogenicity and safety trial (NCT04028349) was conducted to explore the knowledge and perceptions of healthcare (HCWs) and frontline workers (FLWs), about Ebola vaccines and their willingness to participate or recommend participation in Uganda. METHOD: We carried out focus group discussions and semi-structured interviews before and after vaccination, with 70 HCWs and FLWs who consented to participate in the trial, and in the qualitative component, from August to September 2019. Data were analysed using thematic content analysis. RESULTS: Respondents showed good knowledge about Ebola and the vaccines in general, and had wide access to information through several channels, including the study team. On prevention, particular attention was given to effective communication within health facilities. Misconceptions were mainly around route of transmission, animal origin and types of vaccines. Previous fears were based on rumours circulating in the community, mainly about the presence of the virus in the vaccine, side effects and intention to harm (e.g. by "the whites"), ultimately insisting on transparency, trust and involvement of local leaders. Acceptability of participation was motivated by the need to protect self and others, and the willingness to advance research. Majority were willing to recommend participation to their community. CONCLUSIONS: Overall, information sharing leads to a better understanding and acceptance of vaccine trials and a positive vaccination experience can be a deciding factor in the acceptance of others. Particular attention should be paid to involving the community in addressing misconceptions and fears, while ensuring that participants have access to vaccination sites in terms of transport, and that they are properly accommodated at the study site including staying for a reasonable period of time.

Assessment of the integrated disease surveillance and response system implementation in health zones at risk for viral hemorrhagic fever outbreaks in North Kivu, Democratic Republic of the Congo, following a major Ebola outbreak, 2021.

BACKGROUND: The Democratic Republic of the Congo (DRC) experienced its largest Ebola Virus Disease Outbreak in 2018-2020. As a result of the outbreak, significant funding and international support were provided to Eastern DRC to improve disease surveillance. The Integrated Disease Surveillance and Response (IDSR) strategy has been used in the DRC as a framework to strengthen public health surveillance, and full implementation could be critical as the DRC continues to face threats of various epidemic-prone diseases. In 2021, the DRC initiated an IDSR assessment in North Kivu province to assess the capabilities of the public health system to detect and respond to new public health threats. METHODS: The study utilized a mixed-methods design consisting of quantitative and qualitative methods. Quantitative assessment of the performance in IDSR core functions was conducted at multiple levels of the tiered health system through a standardized questionnaire and analysis of health data. Qualitative data were also collected through observations, focus groups and open-ended questions. Data were collected at the North Kivu provincial public health office, five health zones, 66 healthcare facilities, and from community health workers in 15 health areas. RESULTS: Thirty-six percent of health facilities had no case definition documents and 53% had no blank case reporting forms, limiting identification and reporting. Data completeness and timeliness among health facilities were 53% and 75% overall but varied widely by health zone. While these indicators seemingly improved at the health zone level at 100% and 97% respectively, the health facility data feeding into the reporting structure were inconsistent. The use of electronic Integrated Disease Surveillance and Response is not widely implemented. Rapid response teams were generally available, but functionality was low with lack of guidance documents and long response times. CONCLUSION: Support is needed at the lower levels of the public health system and to address specific zones with low performance. Limitations in materials, resources for communication and transportation, and workforce training continue to be challenges. This assessment highlights the need to move from outbreak-focused support and funding to building systems that can improve the long-term functionality of the routine disease surveillance system.

Design and characterization of protective pan-ebolavirus and pan-filovirus bispecific antibodies.

Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation. Here, we explore a bsAb strategy for generation of pan-ebolavirus and pan-filovirus immunotherapeutics. Filoviruses, including Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV), cause severe hemorrhagic fever. Although there are two FDA-approved mAb therapies for EBOV infection, these do not extend to other filoviruses. Here, we combine Fvs from broad ebolavirus mAbs to generate novel pan-ebolavirus bsAbs that are potently neutralizing, confer protection in mice, and are resistant to viral escape. Moreover, we combine Fvs from pan-ebolavirus mAbs with those of protective MARV mAbs to generate pan-filovirus protective bsAbs. These results provide guidelines for broad antiviral bsAb design and generate new immunotherapeutic candidates.

Oral administration of obeldesivir protects nonhuman primates against Sudan ebolavirus.

Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside of remdesivir (RDV) and is presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV and its circulating parent nucleoside metabolite, GS-441524, have similar in vitro antiviral activity against filoviruses, including Marburg virus, Ebola virus, and Sudan virus (SUDV). We also report that once-daily oral ODV treatment of cynomolgus monkeys for 10 days beginning 24 hours after SUDV exposure confers 100% protection against lethal infection. Transcriptomics data show that ODV treatment delayed the onset of inflammation and correlated with antigen presentation and lymphocyte activation. Our results offer promise for the further development of ODV to control outbreaks of filovirus disease more rapidly.

Recent advances in the treatment of Ebola disease: A brief overview.

Ebola disease (EBOD) remains a significant and ongoing threat to African countries, characterized by a mortality rate of 25% to 90% in patients with high viral load and significant transmissibility. The most recent outbreak, reported in Uganda in September 2022, was declared officially over in January 2023. However, it was caused by the Sudan Ebola virus (SUDV), a culprit species not previously reported for a decade. Since its discovery in 1976, the management of EBOD has primarily relied on supportive care. Following the devastating outbreak in West Africa from 2014 to 2016 secondary to the Zaire Ebola virus (EBOV), where over 28,000 lives were lost, dedicated efforts to find effective therapeutic agents have resulted in considerable progress in treating and preventing disease secondary to EBOV. Notably, 2 monoclonal antibodies-Ebanga and a cocktail of monoclonal antibodies, called Inmazeb-received Food and Drug Administration (FDA) approval in 2020. Additionally, multiple vaccines have been approved for EBOD prevention by various regulatory bodies, with Ervebo, a recombinant vesicular stomatitis virus-vectored vaccine against EBOV being the first vaccine to receive approval by the FDA in 2019. This review covers the key signs and symptoms of EBOD, its modes of transmission, and the principles guiding supportive care. Furthermore, it explores recent advancements in treating and preventing EBOD, highlighting the unique properties of each therapeutic agent and the ongoing progress in discovering new treatments.

Lot-to-lot consistency, immunogenicity, and safety of the Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen: A phase 3, randomized, double-blind, placebo-controlled trial.

This phase-3, double-blind, placebo-controlled study (NCT04228783) evaluated lot-to-lot consistency of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. Participants were randomized (6:6:6:1) to receive the two-dose regimen from three consecutively manufactured lots of Ad26.ZEBOV on Day 1 paired with three consecutively manufactured lots of MVA-BN-Filo on Day 57 (Groups 1-3) or two doses of placebo (Group 4). An additional cohort also received an Ad26.ZEBOV booster or placebo 4 months post-dose 2. Equivalence of the immunogenicity at 21 days post-dose 2 between any two groups was demonstrated if the 95% confidence interval (CI) of the Ebola virus glycoprotein (EBOV GP)-binding antibody geometric mean concentration (GMC) ratio was entirely within the prespecified margin of 0.5-2.0. Lot-to-lot consistency (i.e., consecutive lots can be consistently manufactured) was accomplished if equivalence was shown for all three pairwise comparisons. Results showed that the primary objective in the per-protocol immunogenicity subset (n = 549) was established for each pairwise comparison (Group 1 vs 2: GMC ratio = 0.9 [95% CI: 0.8, 1.1], Group 1 vs 3: 0.9 [0.8, 1.1], Group 2 vs 3: 1.0 [0.9, 1.2]). Equivalence of the three groups for the Ad26.ZEBOV component only was also demonstrated at 56 days post-dose 1. EBOV GP-binding antibody responses (post-vaccination concentrations >2.5-fold from baseline) were observed in 419/421 (99.5%) vaccine recipients at 21 days post-dose 2 and 445/460 (96.7%) at 56 days post-dose 1. In the booster cohort (n = 39), GMCs increased 9.0- and 11.8-fold at 7 and 21 days post-booster, respectively, versus pre-booster. Ad26.ZEBOV, MVA-BN-Filo was well tolerated, and no safety issues were identified.

A novel MARV glycoprotein-specific antibody with potentials of broad-spectrum neutralization to filovirus.

Marburg virus (MARV) is one of the filovirus species that cause deadly hemorrhagic fever in humans, with mortality rates up to 90%. Neutralizing antibodies represent ideal candidates to prevent or treat virus disease. However, no antibody has been approved for MARV treatment to date. In this study, we identified a novel human antibody named AF-03 that targeted MARV glycoprotein (GP). AF-03 possessed a high binding affinity to MARV GP and showed neutralizing and protective activities against the pseudotyped MARV in vitro and in vivo. Epitope identification, including molecular docking and experiment-based analysis of mutated species, revealed that AF-03 recognized the Niemann-Pick C1 (NPC1) binding domain within GP1. Interestingly, we found the neutralizing activity of AF-03 to pseudotyped Ebola viruses (EBOV, SUDV, and BDBV) harboring cleaved GP instead of full-length GP. Furthermore, NPC2-fused AF-03 exhibited neutralizing activity to several filovirus species and EBOV mutants via binding to CI-MPR. In conclusion, this work demonstrates that AF-03 represents a promising therapeutic cargo for filovirus-caused disease.

Effects of Shock and Vibration on Product Quality during Last-Mile Transportation of Ebola Vaccine under Refrigerated Conditions1.

Analyzing vaccine stability under different storage and transportation conditions is critical to ensure that effectiveness and safety are not affected by distribution. In a simulation of the last mile in the supply chain, we found that shock and vibration had no effect on Ad26.ZEBOV/MVA-BN-Filo Ebola vaccine regimen quality under refrigerated conditions.

Evaluating the risk of conflict on recent Ebola outbreaks in Guinea and the Democratic Republic of the Congo.

BACKGROUND: Reducing Ebola virus transmission relies on the ability to identify cases and limit contact with infected bodily fluids through biosecurity, safe sex practices, safe burial and vaccination. Armed conflicts can complicate outbreak detection and interventions due to widespread disruption to governments and populations. Guinea and the Democratic Republic of the Congo (DRC) have historically reported the largest and the most recent Ebola virus outbreaks. Understanding if conflict played a role in these outbreaks may help in identifying key risks factors to improve disease control. METHODS: We used data from a range of publicly available data sources for both Ebola virus cases and conflict events from 2018 to 2021 in Guinea and the DRC. We fitted these data to conditional logistic regression models using the Self-Controlled Case Series methodology to evaluate the magnitude in which conflict increased the risk of reported Ebola virus cases in terms of incidence rate ratio. We re-ran the analysis sub-nationally, by conflict sub-event type and tested any lagged effects. RESULTS: Conflict was significantly associated with an increased risk of reported Ebola virus cases in both the DRC and Guinea in recent outbreaks. The effect was of a similar magnitude at 1.88- and 1.98-times increased risk for the DRC and Guinea, respectively. The greatest effects (often higher than the national values) were found in many conflict prone areas and during protest/riot-related conflict events. Conflict was influential in terms of Ebola virus risk from 1 week following the event and remained important by 10 weeks. CONCLUSION: Extra vigilance is needed following protests and riot-related conflict events in terms of Ebola virus transmission. These events are highly disruptive, in terms of access to transportation and healthcare and are often in urban areas with high population densities. Additional public health messaging around these types of conflict events, relating to the risks and clinical symptoms may be helpful in reducing transmission. Future work should aim to further understand and quantify conflict severity and intensity, to evaluate dose-response relationships in terms of disease risk.

Performance and impact of contact tracing in the Sudan virus outbreak in Uganda, September 2022-January 2023.

BACKGROUND: Contact tracing (CT) is critical for ebolavirus outbreak response. Ideally, all new cases after the index case should be previously-known contacts (PKC) before their onset, and spend minimal time ill in the community. We assessed the impact of CT during the 2022 Sudan Virus Disease (SVD) outbreak in Uganda. METHODS: We collated anonymized data from the SVD case and contacts database to obtain and analyze data on CT performance indicators, comparing confirmed cases that were PKC and were not PKC (NPKC) before onset. We assessed the effect of being PKC on the number of people infected using Poisson regression. RESULTS: There were 3844 contacts of 142 confirmed cases (mean: 22 contacts/case). Forty-seven (33%) confirmed cases were PKC. PKCs had fewer median days from onset to isolation (4 vs 6; P<0.007) and laboratory confirmation (4 vs 7; P<0.001) than NPKC. Being a PKC vs NPKC reduced risk of transmitting infection by 84% (IRR=0.16, 95% CI 0.08-0.32). CONCLUSION: Contact identification was sub-optimal during the outbreak. However, CT reduced the time SVD cases spent in the community before isolation and the number of persons infected in Uganda. Approaches to improve contact tracing, especially contact listing, may improve control in future outbreaks.

The economic burden of Ebola virus disease: a review and recommendations for analysis.

BACKGROUND: Ebola virus disease (EVD) continues to be a major public health threat globally, particularly in the low-and-middle-income countries (LMICs) of Africa. The social and economic burdens of EVD are substantial and have triggered extensive research into prevention and control. We aim to highlight the impact and economic implications, identify research gaps, and offer recommendations for future economic studies pertaining to EVD. METHOD: We conducted a comprehensive librarian-led search in PubMed/Medline, Embase, Google Scholar, EconLit and Scopus for economic evaluations of EVD. After study selection and data extraction, findings on the impact and economics of EVD were synthesized using a narrative approach, while identifying gaps, and recommending critical areas for future EVD economic studies. RESULTS: The economic evaluations focused on the burden of illness, vaccine cost-effectiveness, willingness-to-pay for a vaccine, EVD funding, and preparedness costs. The estimated economic impact of the 2014 EVD outbreak in Guinea, Liberia, and Sierra Leone across studies ranged from $30 billion to $50 billion. Facility construction and modification emerged as significant cost drivers for preparedness. The EVD vaccine demonstrated cost-effectiveness in a dynamic transmission model; resulting in an incremental cost-effectiveness ratio of about $96 per additional disability adjusted life year averted. Individuals exhibited greater willingness to be vaccinated if it incurred no personal cost, with a minority willing to pay about $1 for the vaccine. CONCLUSIONS: The severe impact of EVD puts pressure on governments and the international community for better resource utilization and re-allocation. Several technical and methodological issues related to economic evaluation of EVD remain to be addressed, especially for LMICs. We recommend conducting cost-of-sequelae and cost-of-distribution analyses in addition to adapting existing economic analytical methods to EVD. Characteristics of the affected regions should be considered to provide evidence-based economic plans and economic-evaluation of mitigations that enhance resource allocation for prevention and treatment.

Ebola virus disease (EVD) is a serious health problem, not only in Africa where there have been outbreaks but in other parts of the world as well. In addition to its severe health implications and resultant death, EVD also poses significant impact across several sectors, including food and agriculture, transportation, education, among others, ultimately impacting the economies of affected countries. While some studies have estimated the economic burden of EVD, there remains questions that need addressing. We conducted a review of published studies to estimate what is known about the economic burden of EVD, identified research gaps. Studies looked at how much money EVD costs in terms of prevention and treatment, while others reported on people's willingness to pay for a vaccine. The estimated economic impact of the 2014 EVD outbreak in Guinea, Liberia, and Sierra Leone ranged from approximately $30 billion to $50 billion across studies. Healthcare facility construction and modification were significant cost factors for response preparedness for EVD outbreaks. While the EVD vaccine showed cost-effectiveness, surveys of people across various regions revealed that more individuals were willing to get vaccinated if it was free, with a minority willing to pay a median of about $1 for the vaccine. The severe impact of EVD puts pressure on governments and the international community to use resources more efficiently. We recommend conducting analyses on the costs of long-term effects of EVD and costs of vaccine and treatment distribution, as well as adapting existing economic methods to the specific characteristics of affected regions. This would help create evidence-based economic plans and evaluations of strategies to enhance resource allocation for EVD prevention and treatment.

Translational success of fundamental virology: a VSV-vectored Ebola vaccine.

Ebola virus disease (EVD) caused by Ebola virus (EBOV) is a severe, often fatal, hemorrhagic disease. A critical component of the public health response to curb EVD epidemics is the use of a replication-competent, recombinant vesicular stomatitis virus (rVSV)-vectored Ebola vaccine, rVSVΔG-ZEBOV-GP (ERVEBO). In this Gem, we will discuss the past and ongoing development of rVSVΔG-ZEBOV-GP, highlighting the importance of basic science and the strength of public-private partnerships to translate fundamental virology into a licensed VSV-vectored Ebola vaccine.

Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Médecins Sans Frontières. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.