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1.
BMC Med Ethics ; 25(1): 63, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778293

ABSTRACT

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


Subject(s)
COVID-19 , Emergencies , Pandemics , Public Health , SARS-CoV-2 , Humans , COVID-19/epidemiology , Public Health/ethics , Africa/epidemiology , Ethical Review , Betacoronavirus , Hemorrhagic Fever, Ebola/epidemiology , Coronavirus Infections/epidemiology , Ethics, Research
2.
Emerg Microbes Infect ; 13(1): 2352520, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38713593

ABSTRACT

Vaginal transmission from semen of male Ebola virus (EBOV) survivors has been implicated as a potential origin of Ebola virus disease (EVD) outbreaks. While EBOV in semen must traverse cervicovaginal mucus (CVM) to reach target cells, the behaviour of EBOV in CVM is poorly understood. CVM contains substantial quantities of IgG, and arrays of IgG bound to a virion can develop multiple Fc-mucin bonds, immobilizing the IgG/virion complex in mucus. Here, we measured the real-time mobility of fluorescent Ebola virus-like-particles (VLP) in 50 CVM specimens from 17 women, with and without ZMapp, a cocktail of 3 monoclonal IgGs against EBOV. ZMapp-mediated effective trapping of Ebola VLPs in CVM from a subset of women across the menstrual cycle, primarily those with Lactobacillus crispatus dominant microbiota. Our work underscores the influence of the vaginal microbiome on IgG-mucin crosslinking against EBOV and identifies bottlenecks in the sexual transmission of EBOV.


Subject(s)
Ebolavirus , Hemorrhagic Fever, Ebola , Vagina , Humans , Female , Ebolavirus/physiology , Vagina/virology , Hemorrhagic Fever, Ebola/virology , Hemorrhagic Fever, Ebola/transmission , Virion , Immunoglobulin G , Adult , Cervix Mucus/virology , Mucus/virology
3.
Nat Commun ; 15(1): 4171, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755147

ABSTRACT

Human Ebola virus (EBOV) outbreaks caused by persistent EBOV infection raises questions on the role of zoonotic spillover in filovirus epidemiology. To characterise filovirus zoonotic exposure, we collected cross-sectional serum samples from bushmeat hunters (n = 498) in Macenta Prefecture Guinea, adjacent to the index site of the 2013 EBOV-Makona spillover event. We identified distinct immune signatures (20/498, 4.0%) to multiple EBOV antigens (GP, NP, VP40) using stepwise ELISA and Western blot analysis and, live EBOV neutralisation (5/20; 25%). Using comparative serological data from PCR-confirmed survivors of the 2013-2016 EBOV outbreak, we demonstrated that most signatures (15/20) were not plausibly explained by prior EBOV-Makona exposure. Subsequent data-driven modelling of EBOV immunological outcomes to remote-sensing environmental data also revealed consistent associations with intact closed canopy forest. Together our findings suggest exposure to other closely related filoviruses prior to the 2013-2016 West Africa epidemic and highlight future surveillance priorities.


Subject(s)
Antibodies, Viral , Ebolavirus , Hemorrhagic Fever, Ebola , Humans , Animals , Guinea/epidemiology , Ebolavirus/immunology , Ebolavirus/isolation & purification , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/virology , Hemorrhagic Fever, Ebola/blood , Hemorrhagic Fever, Ebola/transmission , Adult , Male , Antibodies, Viral/blood , Antibodies, Viral/immunology , Middle Aged , Zoonoses/virology , Zoonoses/epidemiology , Zoonoses/transmission , Female , Cross-Sectional Studies , Disease Outbreaks , Young Adult , Aged , Enzyme-Linked Immunosorbent Assay , Viral Zoonoses/epidemiology , Viral Zoonoses/transmission , Viral Zoonoses/virology , Antigens, Viral/immunology
4.
Soc Sci Med ; 350: 116854, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38713978

ABSTRACT

Research, policy, and donor interest in health systems in conflict environments has grown rapidly in recent years. The 2018-20 Ebola outbreak in Democratic Republic of the Congo is a critical case of healthcare militarization. The first-ever such outbreak in an active conflict zone, it grew notorious for violence against response teams, with attacks aggravating the spread of disease. However, while medical responders observed physical attacks, the causes of the violence remained largely unknown. Drawing on interviews and participant observation, we contribute civilian vantages of the way health intervention grew militarized, or associated with conflict. The argument builds in two core steps. A first reconstructs civilian experiences of conflict prior to Ebola to trace how the response took on a political meaning. We find that relationships linking state forces with the health response inadvertently tethered Ebola to what civilians perceived as security threats and that by repeating government statements about conflict, response teams unintentionally endorsed a version of the truth that silenced local voices. A second step addresses a central paradox: residents communicated these concerns directly, repeatedly, and via official response channels, yet healthcare teams failed to apply these insights. We locate this gap in the knowledge structures, or frames, accompanying intervention. Medical emergencies in warzones operate with dual sets of frames casting conflict players as "non-state" and public health resistance as "ignorance." Both frames intersect in ways that amplify invisibilities in each, clouding understandings of the nature of conflict and humanitarians' role in it. We suggest this places intervention teams at heightened risk of mis-stepping on political fault lines-and not understanding why. The study advances work on community engagement by showing that instead of simply providing scientific knowledge, effective engagement requires adjusting socio-political lenses within the response. It contributes to studies on health intervention, humanitarian emergencies, and the limits of medical neutrality.


Subject(s)
Epidemics , Hemorrhagic Fever, Ebola , Politics , Public Health , Violence , Humans , Hemorrhagic Fever, Ebola/epidemiology , Democratic Republic of the Congo/epidemiology , Public Health/methods
5.
BMJ Glob Health ; 9(5)2024 May 23.
Article in English | MEDLINE | ID: mdl-38782464

ABSTRACT

BACKGROUND: The West African Ebola virus disease (EVD) epidemic resulted in >28 000 disease cases and >11 000 fatalities. The unprecedented number of survivors from this epidemic has raised questions about the long-term mental health impacts of EVD survivorship and the capacity to meet these needs. OBJECTIVES: Assess the frequency and factors associated with mental health consequences of EVD survivorship in Sierra Leone. METHODS: A cross-sectional study of 595 EVD survivors and 403 close contacts (n=998) from Sierra Leone assessed via in-person survey between November 2021 and March 2022. The assessment included validated mental health screening tools (Patient Health Questionnaire-9, PTSD Checklist-5, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test-20) to indicate the presence/absence of disorder. The frequency of each disorder and factors associated with each disorder were assessed. FINDINGS: EVD-associated post-traumatic stress disorder (PTSD) was reported by 45.7% (n=257) of EVD survivors. Moreover, 3.9% (n=22) and 12.0% (n=67) of EVD survivors reported major depression (MD) and substance use, respectively; all mental health outcomes were higher than baseline rates in the region (PTSD: 6%-16%, MD: 1.1%, substance use: 2.2%). PTSD among EVD survivors was associated with acute EVD duration of ≥21 days (adjusted OR, AOR 2.24, 95% CI 1.16 to 4.43), 35-44 years of age (AOR 3.31, 95% CI 1.33 to 8.24; AOR 2.99, 95% CI 1.09 to 8.24) and residential mobility (AOR 4.16, 95% CI 2.35 to 7.35). CONCLUSIONS: Concerningly, the levels of mental health disorders among EVD survivors in Sierra Leone remained elevated 6-8 years after recovery. CLINICAL IMPLICATIONS: Results can be used to inform policy efforts and target resources to address mental health in EVD survivors.


Subject(s)
Hemorrhagic Fever, Ebola , Mental Health , Stress Disorders, Post-Traumatic , Survivors , Humans , Sierra Leone/epidemiology , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/psychology , Cross-Sectional Studies , Male , Female , Adult , Survivors/psychology , Middle Aged , Young Adult , Stress Disorders, Post-Traumatic/epidemiology , Adolescent , Mental Disorders/epidemiology
6.
BMC Infect Dis ; 24(1): 520, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783244

ABSTRACT

BACKGROUND: On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this outbreak was 1.25. We described persons who were exposed to the virus, became infected, and they led to the infection of an unusually high number of cases during the outbreak. METHODS: In this descriptive cross-sectional study, we defined a super-spreader person (SSP) as any person with real-time polymerase chain reaction (RT-PCR) confirmed SVD linked to the infection of ≥ 13 other persons (10-fold the outbreak R). We reviewed illness narratives for SSPs collected through interviews. Whole-genome sequencing was used to support epidemiologic linkages between cases. RESULTS: Two SSPs (Patient A, a 33-year-old male, and Patient B, a 26-year-old male) were identified, and linked to the infection of one probable and 50 confirmed secondary cases. Both SSPs lived in the same parish and were likely infected by a single ill healthcare worker in early October while receiving healthcare. Both sought treatment at multiple health facilities, but neither was ever isolated at an Ebola Treatment Unit (ETU). In total, 18 secondary cases (17 confirmed, one probable), including three deaths (17%), were linked to Patient A; 33 secondary cases (all confirmed), including 14 (42%) deaths, were linked to Patient B. Secondary cases linked to Patient A included family members, neighbours, and contacts at health facilities, including healthcare workers. Those linked to Patient B included healthcare workers, friends, and family members who interacted with him throughout his illness, prayed over him while he was nearing death, or exhumed his body. Intensive community engagement and awareness-building were initiated based on narratives collected about patients A and B; 49 (96%) of the secondary cases were isolated in an ETU, a median of three days after onset. Only nine tertiary cases were linked to the 51 secondary cases. Sequencing suggested plausible direct transmission from the SSPs to 37 of 39 secondary cases with sequence data. CONCLUSION: Extended time in the community while ill, social interactions, cross-district travel for treatment, and religious practices contributed to SVD super-spreading. Intensive community engagement and awareness may have reduced the number of tertiary infections. Intensive follow-up of contacts of case-patients may help reduce the impact of super-spreading events.


Subject(s)
Disease Outbreaks , Humans , Uganda/epidemiology , Male , Cross-Sectional Studies , Adult , Female , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/virology , Whole Genome Sequencing , Ebolavirus/genetics , Ebolavirus/isolation & purification
7.
Commun Biol ; 7(1): 634, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796621

ABSTRACT

Ebola virus (EBOV) matrix protein VP40 can assemble and bud as virus-like particles (VLPs) when expressed alone in mammalian cells. Nucleoprotein (NP) could be recruited to VLPs as inclusion body (IB) when co-expressed, and increase VLP production. However, the mechanism behind it remains unclear. Here, we use a computational approach to study NP-VP40 interactions. Our simulations indicate that NP may enhance VLP production through stabilizing VP40 filaments and accelerating the VLP budding step. Further, both the relative timing and amount of NP expression compared to VP40 are important for the effective production of IB-containing VLPs. We predict that relative NP/VP40 expression ratio and time are important for efficient production of IB-containing VLPs. We conclude that disrupting the expression timing and amount of NP and VP40 could provide new avenues to treat EBOV infection. This work provides quantitative insights into EBOV proteins interactions and how virion generation and drug efficacy could be influenced.


Subject(s)
Ebolavirus , Viral Core Proteins , Ebolavirus/metabolism , Viral Core Proteins/metabolism , Viral Core Proteins/genetics , Humans , Virion/metabolism , Virion/genetics , Nucleoproteins/metabolism , Nucleoproteins/genetics , Viral Matrix Proteins/metabolism , Viral Matrix Proteins/genetics , Hemorrhagic Fever, Ebola/virology , Hemorrhagic Fever, Ebola/metabolism
8.
J Infect Dev Ctries ; 18(4): 556-564, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38728629

ABSTRACT

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.


Subject(s)
Health Personnel , Hemorrhagic Fever, Ebola , Hospitals, Private , Humans , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/epidemiology , Uganda/epidemiology , Cross-Sectional Studies , Health Personnel/statistics & numerical data , Adult , Hospitals, Private/statistics & numerical data , Male , Middle Aged , Female , Young Adult , Surveys and Questionnaires , Epidemics/prevention & control
9.
Sci Rep ; 14(1): 12147, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802461

ABSTRACT

The E/S (exposed/susceptible) ratio is analyzed in the SEIR model. The ratio plays a key role in understanding epidemic dynamics during the 2014-2016 Ebola outbreak in Sierra Leone and Guinea. The maximum value of the ratio occurs immediately before or after the time-dependent reproduction number (Rt) equals 1, depending on the initial susceptible population (S(0)). It is demonstrated that transmission rate curves corresponding to various incubation periods intersect at a single point referred to as the Cross Point (CP). At this point, the E/S ratio reaches an extremum, signifying a critical shift in transmission dynamics and aligning with the time when Rt approaches 1. By plotting transmission rate curves, ß(t), for any two arbitrary incubation periods and tracking their intersections, we can trace CP over time. CP serves as an indicator of epidemic status, especially when Rt is close to 1. It provides a practical means of monitoring epidemics without prior knowledge of the incubation period. Through a case study, we estimate the transmission rate and reproduction number, identifying CP and Rt = 1 while examining the E/S ratio across various values of S(0).


Subject(s)
Epidemics , Hemorrhagic Fever, Ebola , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/transmission , Humans , Sierra Leone/epidemiology , Guinea/epidemiology , Disease Outbreaks , Africa, Western/epidemiology , Basic Reproduction Number
10.
Glob Health Action ; 17(1): 2331291, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38666727

ABSTRACT

BACKGROUND: There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high. OBJECTIVES: The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak. METHODS: We analysed the outputs of two independent population-based surveys conducted at the end of the 2014-2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design. RESULTS: Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23-0.52) and 0.12/10,000 person-days (95%CI: 0.05-0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area. CONCLUSION: Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.


Main findings: For humanitarian organizations it is imperative to document the methodological limitations of cluster surveys and discuss the utility.Added knowledge: This paper adds new knowledge on cluster surveys for highly clustered data such us in Ebola virus disease.Global health impact of policy and action: We provided empirical estimates and discuss design improvements to inform future study.


Subject(s)
Disease Outbreaks , Hemorrhagic Fever, Ebola , Humans , Sierra Leone/epidemiology , Hemorrhagic Fever, Ebola/mortality , Hemorrhagic Fever, Ebola/epidemiology , Retrospective Studies , Adult , Female , Adolescent , Child, Preschool , Male , Middle Aged , Young Adult , Cluster Analysis , Child , Infant , Rural Population/statistics & numerical data , Urban Population , Surveys and Questionnaires
11.
Genes (Basel) ; 15(4)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38674337

ABSTRACT

Ebola virus (EBOV) is a highly pathogenic virus that causes a severe illness called Ebola virus disease (EVD). EVD has a high mortality rate and remains a significant threat to public health. Research on EVD pathogenesis has traditionally focused on host transcriptional responses. Limited recent studies, however, have revealed some information on the significance of cellular microRNAs (miRNAs) in EBOV infection and pathogenic mechanisms, but further studies are needed. Thus, this study aimed to identify and validate additional known and novel human miRNAs in EBOV-infected adult retinal pigment epithelial (ARPE) cells and predict their potential roles in EBOV infection and pathogenic mechanisms. We analyzed previously available small RNA-Seq data obtained from ARPE cells and identified 23 upregulated and seven downregulated miRNAs in the EBOV-infected cells; these included two novel miRNAs and 17 additional known miRNAs not previously identified in ARPE cells. In addition to pathways previously identified by others, these miRNAs are associated with pathways and biological processes that include WNT, FoxO, and phosphatidylinositol signaling; these pathways were not identified in the original study. This study thus confirms and expands on the previous study using the same datasets and demonstrates further the importance of human miRNAs in the host response and EVD pathogenesis during infection.


Subject(s)
Ebolavirus , Hemorrhagic Fever, Ebola , MicroRNAs , Retinal Pigment Epithelium , Humans , MicroRNAs/genetics , Hemorrhagic Fever, Ebola/genetics , Hemorrhagic Fever, Ebola/virology , Ebolavirus/genetics , Ebolavirus/pathogenicity , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/virology , Retinal Pigment Epithelium/pathology , Cell Line
13.
ACS Infect Dis ; 10(5): 1590-1601, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38684073

ABSTRACT

Ebola virus (EBOV) is an enveloped virus that must fuse with the host cell membrane in order to release its genome and initiate infection. This process requires the action of the EBOV envelope glycoprotein (GP), encoded by the virus, which resides in the viral envelope and consists of a receptor binding subunit, GP1, and a membrane fusion subunit, GP2. Despite extensive research, a mechanistic understanding of the viral fusion process is incomplete. To investigate GP-membrane association, a key step in the fusion process, we used two approaches: high-throughput measurements of single-particle diffusion and single-molecule measurements with optical tweezers. Using these methods, we show that the presence of the endosomal Niemann-Pick C1 (NPC1) receptor is not required for primed GP-membrane binding. In addition, we demonstrate this binding is very strong, likely attributed to the interaction between the GP fusion loop and the membrane's hydrophobic core. Our results also align with previously reported findings, emphasizing the significance of acidic pH in the protein-membrane interaction. Beyond Ebola virus research, our approach provides a powerful toolkit for studying other protein-membrane interactions, opening new avenues for a better understanding of protein-mediated membrane fusion events.


Subject(s)
Ebolavirus , Viral Envelope Proteins , Ebolavirus/metabolism , Ebolavirus/physiology , Ebolavirus/genetics , Ebolavirus/chemistry , Viral Envelope Proteins/metabolism , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/genetics , Humans , Protein Binding , Virus Internalization , Niemann-Pick C1 Protein/metabolism , Cell Membrane/metabolism , Cell Membrane/virology , Hemorrhagic Fever, Ebola/virology , Hydrogen-Ion Concentration
14.
MMWR Morb Mortal Wkly Rep ; 73(16): 360-364, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662631

ABSTRACT

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.


Subject(s)
Disease Outbreaks , Ebola Vaccines , Global Health , Hemorrhagic Fever, Ebola , Humans , Ebola Vaccines/administration & dosage , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/epidemiology , Disease Outbreaks/prevention & control , Strategic Stockpile , Adult , Child , Adolescent
15.
PLoS Negl Trop Dis ; 18(4): e0011500, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38603720

ABSTRACT

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.


Subject(s)
Antibodies, Viral , Ebola Vaccines , Hemorrhagic Fever, Ebola , Adolescent , Adult , Animals , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Africa , Antibodies, Helminth/blood , Antibodies, Viral/blood , Cytokines/immunology , Ebola Vaccines/immunology , Ebola Vaccines/administration & dosage , Ebolavirus/immunology , Ebolavirus/genetics , Enzyme-Linked Immunosorbent Assay , Helminthiasis/immunology , Helminthiasis/prevention & control , Helminths/immunology , Helminths/genetics , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/immunology , Immunoglobulin G/blood , Aged
16.
Protein Sci ; 33(5): e4978, 2024 May.
Article in English | MEDLINE | ID: mdl-38591637

ABSTRACT

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.


Subject(s)
Ebolavirus , Hemorrhagic Fever, Ebola , Humans , Ebolavirus/genetics , Ebolavirus/metabolism , Hemorrhagic Fever, Ebola/metabolism , Cell Membrane/metabolism , Molecular Dynamics Simulation , Amino Acids/metabolism , Viral Matrix Proteins/genetics , Viral Matrix Proteins/chemistry , Viral Matrix Proteins/metabolism
19.
Antiviral Res ; 226: 105873, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38580170

ABSTRACT

In the 1990s, monoclonal antibodies (mAbs) progressed from scientific tools to advanced therapeutics, particularly for the treatment of cancers and autoimmune and inflammatory disorders. In the arena of infectious disease, the inauguration of mAbs as a post-exposure treatment in humans against Ebola virus (EBOV) occurred in response to the 2013-2016 West Africa outbreak. This review recounts the history of a candidate mAb treatment, ZMapp, beginning with its emergency use in the 2013-2016 outbreak and advancing to randomized controlled trials into the 2018-2020 African outbreak. We end with a brief discussion of the hurdles and promise toward mAb therapeutic use against infectious disease.


Subject(s)
Antibodies, Monoclonal , Antibodies, Viral , Ebolavirus , Hemorrhagic Fever, Ebola , Hemorrhagic Fever, Ebola/drug therapy , Hemorrhagic Fever, Ebola/immunology , Humans , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/immunology , Ebolavirus/immunology , Ebolavirus/drug effects , Antibodies, Viral/therapeutic use , Antibodies, Viral/immunology , Animals , Disease Outbreaks , Antibodies, Neutralizing/therapeutic use , Antibodies, Neutralizing/immunology , Africa, Western/epidemiology
20.
Glob Public Health ; 19(1): 2334887, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38625999

ABSTRACT

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 .


Subject(s)
Ebola Vaccines , Hemorrhagic Fever, Ebola , Humans , Sierra Leone/epidemiology , Pandemics , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Focus Groups
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