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.

Computational and experimental identification of keystone interactions in Ebola virus matrix protein VP40 dimer formation.

The Ebola virus (EBOV) is a lipid-enveloped virus with a negative sense RNA genome that can cause severe and often fatal viral hemorrhagic fever. The assembly and budding of EBOV is regulated by the matrix protein, VP40, which is a peripheral protein that associates with anionic lipids at the inner leaflet of the plasma membrane. VP40 is sufficient to form virus-like particles (VLPs) from cells, which are nearly indistinguishable from authentic virions. Due to the restrictions of studying EBOV in BSL-4 facilities, VP40 has served as a surrogate in cellular studies to examine the EBOV assembly and budding process from the host cell plasma membrane. VP40 is a dimer where inhibition of dimer formation halts budding and formation of new VLPs as well as VP40 localization to the plasma membrane inner leaflet. To better understand VP40 dimer stability and critical amino acids to VP40 dimer formation, we integrated computational approaches with experimental validation. Site saturation/alanine scanning calculation, combined with molecular mechanics-based generalized Born with Poisson-Boltzmann surface area (MM-GB/PBSA) method and molecular dynamics simulations were used to predict the energetic contribution of amino acids to VP40 dimer stability and the hydrogen bonding network across the dimer interface. These studies revealed several previously unknown interactions and critical residues predicted to impact VP40 dimer formation. In vitro and cellular studies were then pursued for a subset of VP40 mutations demonstrating reduction in dimer formation (in vitro) or plasma membrane localization (in cells). Together, the computational and experimental approaches revealed critical residues for VP40 dimer stability in an alpha-helical interface (between residues 106-117) as well as in a loop region (between residues 52-61) below this alpha-helical region. This study sheds light on the structural origins of VP40 dimer formation and may inform the design of a small molecule that can disrupt VP40 dimer stability.

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.

Computational and stability analysis of Ebola virus epidemic model with piecewise hybrid fractional operator.

In this manuscript, we developed a nonlinear fractional order Ebola virus with a novel piecewise hybrid technique to observe the dynamical transmission having eight compartments. The existence and uniqueness of a solution of piecewise derivative is treated for a system with Arzel'a-Ascoli and Schauder conditions. We investigate the effects of classical and modified fractional calculus operators, specifically the classical Caputo piecewise operator, on the behavior of the model. A model shows that a completely continuous operator is uniformly continuous, and bounded according to the equilibrium points. The reproductive number R0 is derived for the biological feasibility of the model with sensitivity analysis with different parameters impact on the model. Sensitivity analysis is an essential tool for comprehending how various model parameters affect the spread of illness. Through a methodical manipulation of important parameters and an assessment of their impact on Ro, we are able to learn more about the resiliency and susceptibility of the model. Local stability is established with next Matignon method and global stability is conducted with the Lyapunov function for a feasible solution of the proposed model. In the end, a numerical solution is derived with Newton's polynomial technique for a piecewise Caputo operator through simulations of the compartments at various fractional orders by using real data. Our findings highlight the importance of fractional operators in enhancing the accuracy of the model in capturing the intricate dynamics of the disease. This research contributes to a deeper understanding of Ebola virus dynamics and provides valuable insights for improving disease modeling and public health strategies.

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.

Geographic Disparities in Domestic Pig Population Exposure to Ebola Viruses, Guinea, 2017-2019.

Although pigs are naturally susceptible to Reston virus and experimentally to Ebola virus (EBOV), their role in Orthoebolavirus ecology remains unknown. We tested 888 serum samples collected from pigs in Guinea during 2017-2019 (between the 2013-16 epidemic and its resurgence in 2021) by indirect ELISA against the EBOV nucleoprotein. We identified 2 hotspots of possible pig exposure by IgG titer levels: the northern coast had 48.7% of positive serum samples (37/76), and Forest Guinea, bordering Sierra Leone and Liberia, where the virus emerged and reemerged, had 50% of positive serum samples (98/196). The multitarget Luminex approach confirms ELISA results against Ebola nucleoprotein and highlights cross-reactivities to glycoprotein of EBOV, Reston virus, and Bundibugyo virus. Those results are consistent with previous observations of the circulation of Orthoebolavirus species in pig farming regions in Sierra Leone and Ghana, suggesting potential risk for Ebola virus disease in humans, especially in Forest Guinea.

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.

Scalable gradients enable Hamiltonian Monte Carlo sampling for phylodynamic inference under episodic birth-death-sampling models.

Birth-death models play a key role in phylodynamic analysis for their interpretation in terms of key epidemiological parameters. In particular, models with piecewise-constant rates varying at different epochs in time, to which we refer as episodic birth-death-sampling (EBDS) models, are valuable for their reflection of changing transmission dynamics over time. A challenge, however, that persists with current time-varying model inference procedures is their lack of computational efficiency. This limitation hinders the full utilization of these models in large-scale phylodynamic analyses, especially when dealing with high-dimensional parameter vectors that exhibit strong correlations. We present here a linear-time algorithm to compute the gradient of the birth-death model sampling density with respect to all time-varying parameters, and we implement this algorithm within a gradient-based Hamiltonian Monte Carlo (HMC) sampler to alleviate the computational burden of conducting inference under a wide variety of structures of, as well as priors for, EBDS processes. We assess this approach using three different real world data examples, including the HIV epidemic in Odesa, Ukraine, seasonal influenza A/H3N2 virus dynamics in New York state, America, and Ebola outbreak in West Africa. HMC sampling exhibits a substantial efficiency boost, delivering a 10- to 200-fold increase in minimum effective sample size per unit-time, in comparison to a Metropolis-Hastings-based approach. Additionally, we show the robustness of our implementation in both allowing for flexible prior choices and in modeling the transmission dynamics of various pathogens by accurately capturing the changing trend of viral effective reproductive number.

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.

An oral antiviral for Ebola disease.

For those exposed to filovirus, such as Sudan virus and Ebola virus, a new study offers hope.

Exploring equity in global health collaborations: a qualitative study of donor and recipient power dynamics in Liberia.

IntroductionGlobal health collaborations between individuals from high-resource and low-resource settings are complex and often built on hierarchical structures and power differentials that are difficult to change. There have been many calls and frameworks developed to facilitate more equity within these collaborations, yet little is known about the lived experiences of global health donors and recipients working within such collaborations and how those experiences can facilitate more equitable collaboration. Liberia, a postconflict, post-Ebola country, provides an ideal setting to study lived experiences of global health collaborations.MethodsOur qualitative analysis used key informant interviews representing the perspectives of those working on behalf of the Liberian government, Liberian academics, foreign donors and non-governmental organisations and implementing partners. Thematic analysis guided this analysis to explore topics such as financial control, accountability and decision making.ResultsThe first phase of the analysis mapped the existing patterns of priority setting. Priority-setting power was most strongly held by those with financial control (donors), and implementation plans tended to be built on metrics that aim to meet donor expectations. The second phase of the analysis explored the interplay between underlying factors that we identified in our data associated with driving collaborative inequity: history of prior of engagement, level of transparency and patterns of accountability.ConclusionsOur findings highlight that global health collaborations in Liberia are structured to hinder equitable partnerships. The power structure tied to financial ownership offers little space for recipients to have an equitable role in collaborations, which maintains dependence on external aid and ensures that weak systems remain weak. While our study is limited to Liberia, we anticipate that these dynamics are common elsewhere and reinforce the importance of intentional efforts to ensure equitable decision making and power structures in similar settings worldwide.

Ebola virus disease sequelae and viral persistence in animal models: Implications for the future.

Ebola virus disease (EVD), caused by infection with Ebola virus, results in severe, acute illness with a high mortality rate. As the incidence of outbreaks of EVD increases and with the development and approval of medical countermeasures (MCMs) against the acute disease, late phases of EVD, including sequelae, recrudescence, and viral persistence, are occuring more frequently and are now a focus of ongoing research. Existing animal disease models recapitulate acute EVD but are not suitable to investigate the mechanisms of these late disease phenomena. Although there are challenges in establishing such a late disease model, the filovirus research community has begun to call for the development of an EBOV persistence model to address late disease concerns. Ultimately, this will aid the development of MCMs against late disease and benefit survivors of future EVD and filovirus outbreaks.

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.

Critical perspective on infodemic and infodemic management in previous Ebola outbreaks in Uganda.

This research investigates the complex dynamics of Uganda's recent Ebola outbreaks, emphasizing the interplay between disease spread, misinformation, and existing societal vulnerabilities. Highlighting poverty as a core element, it delves into how socioeconomic factors exacerbate health crises. The study scrutinizes the role of political economy, medical pluralism, health systems, and informal networks in spreading misinformation, further complicating response efforts. Through a comprehensive analysis, this study aims to shed light on the multifaceted challenges faced in combating epidemics in resource-limited settings. It calls for integrated strategies that address not only the biological aspects of the disease but also the socioeconomic and informational ecosystems that influence public health outcomes. This perspective research contributes to a better understanding of how poverty, medical pluralism, political economy, misinformation, and health emergencies intersect, offering insights for future preparedness and response initiatives.

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.

Broad antibody and T cell responses to Ebola, Sudan, and Bundibugyo ebolaviruses using mono- and multi-valent adjuvanted glycoprotein vaccines.

Currently, there are two approved vaccine regimens designed to prevent Ebola virus (EBOV) disease (EVD). Both are virus-vectored, and concerns about cold-chain storage and pre-existing immunity to the vectors warrant investigating additional vaccine strategies. Here, we have explored the utility of adjuvanted recombinant glycoproteins (GPs) from ebolaviruses Zaire (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) for inducing antibody (Ab) and T cell cross-reactivity. Glycoproteins expressed in insect cells were administered to C57BL/6 mice as free protein or bound to the surface of liposomes, and formulated with toll-like receptor agonists CpG and MPLA (agonists for TLR 9 and 4, respectively), with or without the emulsions AddaVax or TiterMax. The magnitude of Ab cross-reactivity in binding and neutralization assays, and T cell cross-reactivity in antigen recall assays, correlated with phylogenetic relatedness. While most adjuvants screened induced IgG responses, a combination of CpG, MPLA and AddaVax emulsion ("IVAX-1") was the most potent and polarized in an IgG2c (Th1) direction. Breadth was also achieved by combining GPs into a trivalent (Tri-GP) cocktail with IVAX-1, which did not compromise antibody responses to individual components in binding and neutralizing assays. Th1 signature cytokines in T cell recall assays were undetectable after Tri-GP/IVAX-1 administration, despite a robust IgG2c response, although administration of Tri-GP on lipid nanoparticles in IVAX-1 elevated Th1 cytokines to detectable levels. Overall, the data indicate an adjuvanted trivalent recombinant GP approach may represent a path toward a broadly reactive, deployable vaccine against EVD.

Two-way pharmacodynamic modeling of drug combinations and its application to pairs of repurposed Ebola and SARS-CoV-2 agents.

Existing pharmacodynamic (PD) mathematical models for drug combinations discriminate antagonistic, additive, multiplicative, and synergistic effects, but fail to consider how concentration-dependent drug interaction effects may vary across an entire dose-response matrix. We developed a two-way pharmacodynamic (TWPD) model to capture the PD of two-drug combinations. TWPD captures interactions between upstream and downstream drugs that act on different stages of viral replication, by quantifying upstream drug efficacy and concentration-dependent effects on downstream drug pharmacodynamic parameters. We applied TWPD to previously published in vitro drug matrixes for repurposed potential anti-Ebola and anti-SARS-CoV-2 drug pairs. Depending on the drug pairing, the model recapitulated combined efficacies as or more accurately than existing models and can be used to infer efficacy at untested drug concentrations. TWPD fits the data slightly better in one direction for all drug pairs, meaning that we can tentatively infer the upstream drug. Based on its high accuracy, TWPD could be used in concert with PK models to estimate the therapeutic effects of drug pairs in vivo.

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.