RESUMEN
BACKGROUND: The 2014 outbreak of the Ebola virus disease highlighted the importance of overhauling and transforming healthcare systems in West Africa to improve the ability of individual countries to deal with infectious diseases. As part of this effort, in November 2016 the West African Health Organization (WAHO) began the process of institutionalizing the One Health (OH) approach to health security across the Economic Community of West African States (ECOWAS). The lack of clear metrics and evaluation frameworks to measure the progress of OH implementation in West Africa has been reported as a challenge. Therefore, this study sought to assess and explore whether the existing metrics of global health security frameworks can measure the successful implementation of OH activities, evaluate the progress made since 2016, and identify key areas for improvement in the region. METHOD: The study employed predetermined keywords to select indicators from the International Health Regulations (IHR) Monitoring Frameworks, specifically the State Party Self-Assessment Annual Report (SPAR) and Joint External Evaluation (JEE), deemed relevant to the OH approach. In addition, the COVID-19 performance index scores (severity and recovery) for June 2022 were extracted from the Global COVID-19 Index (GCI). The GCI Recovery Index evaluated the major recovery parameters reported daily to indicate how a country performed on the path to recovery from the COVID-19 pandemic compared to other countries. National documents were also analyzed using categorical variables to assess the performance status of OH platforms across implementing countries. A quantitative analysis of these indicators was conducted and supplemented with qualitative data gathered through interviews with key stakeholders. Between March and April 2022, we conducted 18 key informant interviews with purposively selected representatives from regional governmental agencies and international multilateral agencies, including ECOWAS member states. Interviews were conducted online, transcribed, and analysed following the tenets of thematic analysis. RESULTS: Our quantitative analysis revealed no significant association between the implementation status of OH activities and any of the selected indicators from SPAR and JEE. The descriptive analysis of the JEE scores at the country level revealed that countries with existing OH platforms scored relatively higher on the selected JEE indicators than other countries in the pre-implementation stage. OH implementation status did not significantly affect COVID-19 recovery and severity indices. The qualitative findings with relevant stakeholders revealed noteworthy challenges related to insufficient human capacity, inadequate coordination, and a lack of government funding for the sustainability of OH initiatives. Nonetheless, countries in the ECOWAS region are making progress toward the integration of OH into their health security systems. CONCLUSION: Standardized metrics were used to assess the implementation and efficacy of OH systems in the ECOWAS region. Current indicators for monitoring global health security frameworks lack specificity and fail to comprehensively capture essential OH components, particularly at the sub-national level. To ensure consistency and effectiveness across countries, OH implementation metrics that align with global frameworks such as IHR should be developed.
Asunto(s)
Salud Global , Salud Única , Humanos , África Occidental , Fiebre Hemorrágica Ebola/epidemiología , COVID-19/epidemiología , Reglamento Sanitario Internacional , Investigación CualitativaRESUMEN
Filovirus-host interactions play important roles in all stages of the virus lifecycle. Here, we identify LATS1/2 kinases and YAP, key components of the Hippo pathway, as critical regulators of EBOV transcription and egress. Specifically, we find that when YAP is phosphorylated by LATS1/2, it localizes to the cytoplasm (Hippo "ON") where it sequesters VP40 to prevent egress. In contrast, when the Hippo pathway is "OFF", unphosphorylated YAP translocates to the nucleus where it transcriptionally activates host genes and promotes viral egress. Our data reveal that LATS2 indirectly modulates filoviral VP40-mediated egress through phosphorylation of AMOTp130, a positive regulator of viral egress, but more surprisingly that LATS1/2 kinases directly modulate EBOV transcription by phosphorylating VP30, an essential regulator of viral transcription. In sum, our findings highlight the potential to exploit the Hippo pathway/filovirus axis for the development of host-oriented countermeasures targeting EBOV and related filoviruses.
Asunto(s)
Ebolavirus , Vía de Señalización Hippo , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Factores de Transcripción , Transcripción Genética , Liberación del Virus , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Fosforilación , Ebolavirus/fisiología , Ebolavirus/genética , Ebolavirus/metabolismo , Células HEK293 , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Señalizadoras YAP/metabolismo , Proteínas de la Matriz Viral/metabolismo , Proteínas de la Matriz Viral/genética , Fiebre Hemorrágica Ebola/virología , Fiebre Hemorrágica Ebola/metabolismo , Interacciones Huésped-Patógeno , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genéticaRESUMEN
Important policy questions during infections disease outbreaks include: i) How effective are particular interventions?; ii) When can resource-intensive interventions be removed? We used mathematical modelling to address these questions during the 2017 Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC). Eight cases occurred before 15 May 2017, when the Ebola Response Team (ERT; co-ordinated by the World Health Organisation and DRC Ministry of Health) was deployed to reduce transmission. We used a branching process model to estimate that, pre-ERT arrival, the reproduction number was R = 1.49 (95% credible interval ( 0.67, 2.81 ) ). The risk of further cases occurring without the ERT was estimated to be 0.97 (97%). However, no cases materialised, suggesting that the ERT's measures were effective. We also estimated the risk of withdrawing the ERT in real-time. By the actual ERT withdrawal date (2 July 2017), the risk of future cases without the ERT was only 0.01, indicating that the ERT withdrawal decision was safe. We evaluated the sensitivity of our results to the estimated R value and considered different criteria for determining the ERT withdrawal date. This research provides an extensible modelling framework that can be used to guide decisions about when to relax interventions during future outbreaks.
Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Humanos , Brotes de Enfermedades/prevención & control , República Democrática del Congo/epidemiología , Modelos Teóricos , EbolavirusRESUMEN
BACKGROUND: Ebola Virus Disease (EVD) is a rare but contagious disease caused by Ebola Virus (EBOV). The first Ebola outbreaks were reported in the Democratic Republic of Congo (DRC) before subsequent reported cases in Western and East African countries, including Uganda, which borders Tanzania. Proximity to EVD-infected countries raises the prospect of cross-border transmission, raising alarm in Tanzania. This study aimed to explore the cultural practices likely to prevent or escalate EVD transmission in the event of its outbreak in the country. METHODS: This rapid ethnographic assessment employed observation, interviews, and focus group discussions to collect data from people with diverse characteristics in five regions of Tanzania Mainland namely, Kagera, Kigoma, Mwanza and Songwe regions and Zanzibar Island. The qualitative data was then subjected to thematic analysis. FINDINGS: Cultural practices may escalate the transmission of EVD and hinder its prevention and control. These cultural practices include caring sick people at home, confirmation of death, mourning, and body preparation for burial. Communal life, ceremonies, and social gatherings were other aspects observed to have the potential for compounding EVD transmission and hindering its containment in case of an outbreak. CONCLUSION: Cultural practices may escalate EVD transmission as identified in the study settings. As such, Risk Communication and Community Engagement (RCCE) activities should be interventionist in transforming cultural practices that may escalate the spread of EVD as part of preparedness, prevention, and control efforts in the event of an outbreak.
Asunto(s)
Antropología Cultural , Brotes de Enfermedades , Grupos Focales , Fiebre Hemorrágica Ebola , Humanos , Fiebre Hemorrágica Ebola/epidemiología , Tanzanía/epidemiología , Masculino , Femenino , Adulto , Brotes de Enfermedades/prevención & control , Persona de Mediana Edad , Adulto Joven , Investigación Cualitativa , Adolescente , Entrevistas como AsuntoRESUMEN
The Ebola virus disease (EVD) has been endemic since 1976, and the case fatality rate is extremely high. EVD is spread by infected animals, symptomatic individuals, dead bodies, and contaminated environment. In this paper, we formulate an EVD model with four transmission modes and a time delay describing the incubation period. Through dynamical analysis, we verify the importance of blocking the infection source of infected animals. We get the basic reproduction number without considering the infection source of infected animals. And, it is proven that the model has a globally attractive disease-free equilibrium when the basic reproduction number is less than unity; the disease eventually becomes endemic when the basic reproduction number is greater than unity. Taking the EVD epidemic in Sierra Leone in 2014-2016 as an example, we complete the data fitting by combining the effect of the media to obtain the unknown parameters, the basic reproduction number and its time-varying reproduction number. It is shown by parameter sensitivity analysis that the contact rate and the removal rate of infected group have the greatest influence on the prevalence of the disease. And, the disease-controlling thresholds of these two parameters are obtained. In addition, according to the existing vaccination strategy, only the inoculation ratio in high-risk areas is greater than 0.4, the effective reproduction number can be less than unity. And, the earlier the vaccination time, the greater the inoculation ratio, and the faster the disease can be controlled.
Asunto(s)
Número Básico de Reproducción , Ebolavirus , Fiebre Hemorrágica Ebola , Conceptos Matemáticos , Modelos Biológicos , Fiebre Hemorrágica Ebola/transmisión , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/epidemiología , Número Básico de Reproducción/estadística & datos numéricos , Humanos , Animales , Sierra Leona/epidemiología , Ebolavirus/patogenicidad , Ebolavirus/fisiología , Epidemias/estadística & datos numéricos , Epidemias/prevención & control , Simulación por Computador , Modelos Epidemiológicos , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricosRESUMEN
Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013-2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.
Asunto(s)
Amidas , Antivirales , Modelos Animales de Enfermedad , Ebolavirus , Fiebre Hemorrágica Ebola , Ratones Endogámicos BALB C , Pirazinas , Animales , Amidas/uso terapéutico , Amidas/administración & dosificación , Amidas/farmacología , Cobayas , Pirazinas/administración & dosificación , Pirazinas/uso terapéutico , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Ratones , Ebolavirus/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Femenino , Vías de Administración de Medicamentos , Esquema de MedicaciónRESUMEN
Following the apparent final case in an Ebola virus disease (EVD) outbreak, the decision to declare the outbreak over must balance societal benefits of relaxing interventions against the risk of resurgence. Estimates of the end-of-outbreak probability (the probability that no future cases will occur) provide quantitative evidence that can inform the timing of an end-of-outbreak declaration. An existing modeling approach for estimating the end-of-outbreak probability requires comprehensive contact tracing data describing who infected whom to be available, but such data are often unavailable or incomplete during outbreaks. Here, we develop a Markov chain Monte Carlo-based approach that extends the previous method and does not require contact tracing data. Considering data from two EVD outbreaks in the Democratic Republic of the Congo, we find that data describing who infected whom are not required to resolve uncertainty about when to declare an outbreak over.
Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , República Democrática del Congo/epidemiología , Humanos , Ebolavirus , Cadenas de Markov , Método de MontecarloRESUMEN
VP30 and VP40 proteins of Ebola and Marburg viruses have been recognized as potential targets for antiviral drug development due to their essential roles in the viral lifecycle. Targeting these proteins could disrupt key stages of the viral replication process, inhibiting the viruses' ability to propagate and cause disease. The current study aims to perform molecular docking and virtual screening on deep-sea fungal metabolites targeting Marburg virus VP40 Dimer, matrix protein VP40 from Ebola virus Sudan, Ebola VP35 Interferon Inhibitory Domain, and VP35 from Marburg virus. The top ten compounds for each protein target were chosen using the glide score. All the compounds obtained indicate a positive binding interaction. Furthermore, AdmetSAR was utilized to investigate the pharmacokinetics of the inhibitors chosen. Gliotoxin was used as a ligand with Marburg virus VP40 Dimer, Austinol with matrix protein VP40 from Ebola virus Sudan, Ozazino-cyclo-(2,3-dihydroxyl-trp-tyr) with Ebola VP35 Interferon Inhibitory Domain, and Dehydroaustinol with VP35 from Marburg virus. MD modeling and MMPBSA studies were used to provide a better understanding of binding behaviors. Pre-clinical experiments can assist validate our in-silico studies and assess whether the molecule can be employed as an anti-viral drug.
Asunto(s)
Antivirales , Ebolavirus , Marburgvirus , Simulación del Acoplamiento Molecular , Ebolavirus/efectos de los fármacos , Ebolavirus/metabolismo , Marburgvirus/efectos de los fármacos , Marburgvirus/metabolismo , Antivirales/farmacología , Antivirales/química , Proteínas de la Matriz Viral/metabolismo , Proteínas de la Matriz Viral/antagonistas & inhibidores , Proteínas de la Matriz Viral/química , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Fiebre Hemorrágica Ebola/virología , Humanos , Simulación por Computador , Simulación de Dinámica Molecular , Proteínas Reguladoras y Accesorias ViralesRESUMEN
Outbreaks of Ebolaviruses, such as Sudanvirus (SUDV) in Uganda in 2022, demonstrate that species other than the Zaire ebolavirus (EBOV), which is currently the sole virus represented in current licensed vaccines, remain a major threat to global health. There is a pressing need to develop effective pan-species vaccines and novel monoclonal antibody-based therapeutics for Ebolavirus disease. In response to recent outbreaks, the two dose, heterologous Ad26.ZEBOV/MVA-BN-Filo vaccine regimen was developed and was tested in a large phase II clinical trial (EBL2001) as part of the EBOVAC2 consortium. Here, we perform bulk sequencing of the variable heavy chain (VH) of B cell receptors (BCR) in forty participants from the EBL2001 trial in order to characterize the BCR repertoire in response to vaccination with Ad26.ZEBOV/MVA-BN-Filo. We develop a comprehensive database, EBOV-AbDab, of publicly available Ebolavirus-specific antibody sequences. We then use our database to predict the antigen-specific component of the vaccinee repertoires. Our results show striking convergence in VH germline gene usage across participants following the MVA-BN-Filo dose, and provide further evidence of the role of IGHV3-15 and IGHV3-13 antibodies in the B cell response to Ebolavirus glycoprotein. Furthermore, we found that previously described Ebola-specific mAb sequences present in EBOV-AbDab were sufficient to describe at least one of the ten most expanded BCR clonotypes in more than two thirds of our cohort of vaccinees following the boost, providing proof of principle for the utility of computational mining of immune repertoires.
Asunto(s)
Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Receptores de Antígenos de Linfocitos B , Vacunación , Humanos , Vacunas contra el Virus del Ébola/inmunología , Vacunas contra el Virus del Ébola/administración & dosificación , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Ebolavirus/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Receptores de Antígenos de Linfocitos B/genética , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Biología Computacional/métodos , Adulto , Masculino , Linfocitos B/inmunología , Femenino , Minería de DatosRESUMEN
BACKGROUND: Early detection of outbreaks requires robust surveillance and reporting at both community and health facility levels. Uganda implements Integrated Disease Surveillance and Response (IDSR) for priority diseases and uses the national District Health Information System (DHIS2) for reporting. However, investigations after the first case in the 2022 Uganda Sudan virus outbreak was confirmed on September 20, 2022 revealed many community deaths among persons with Ebola-like symptoms as far back as August. Most had sought care at private facilities. We explored possible gaps in surveillance that may have resulted in late detection of the Sudan virus disease (SVD) outbreak in Uganda. METHODS: Using a standardized tool, we evaluated core surveillance capacities at public and private health facilities at the hospital level and below in three sub-counties reporting the earliest SVD cases in the outbreak. Key informant interviews (KIIs) were conducted with 12 purposively-selected participants from the district local government. Focus group discussions (FGDs) were conducted with community members from six villages where early probable SVD cases were identified. KIIs and FGDs focused on experiences with SVD and Viral Hemorrhagic Fever (VHF) surveillance in the district. Thematic data analysis was used for qualitative data. RESULTS: Forty-six (85%) of 54 health facilities surveyed were privately-owned, among which 42 (91%) did not report to DHIS2 and 39 (85%) had no health worker trained on IDSR; both metrics were 100% in the eight public facilities. Weak community-based surveillance, poor private facility engagement, low suspicion index for VHF among health workers, inability of facilities to analyze and utilize surveillance data, lack of knowledge about to whom to report, funding constraints for surveillance activities, lack of IDSR training, and lack of all-cause mortality surveillance were identified as gaps potentially contributing to delayed outbreak detection. CONCLUSION: Both systemic and knowledge-related gaps in IDSR surveillance in SVD-affected districts contributed to the delayed detection of the 2022 Uganda SVD outbreak. Targeted interventions to address these gaps in both public and private facilities across Uganda could help avert similar situations in the future.
Asunto(s)
Brotes de Enfermedades , Humanos , Uganda/epidemiología , Femenino , Masculino , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/diagnóstico , Adulto , Sudán/epidemiología , Vigilancia de la Población/métodos , Fiebres Hemorrágicas Virales/epidemiología , Fiebres Hemorrágicas Virales/diagnósticoRESUMEN
Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. At the same time, the role of the complement system remains unclear. Here, we compare complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of GP. Binding of GC-specific mAbs to GP induces complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs. In the mouse model of EBOV infection, depletion of the complement system leads to an impairment of protection exerted by one of the GC-specific, but not MPER-specific mAbs. Our data suggest that activation of the complement system represents an important mechanism of antiviral protection by GC antibodies.
Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , Ebolavirus , Fiebre Hemorrágica Ebola , Polisacáridos , Proteínas del Envoltorio Viral , Animales , Ebolavirus/inmunología , Anticuerpos Monoclonales/inmunología , Ratones , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/virología , Fiebre Hemorrágica Ebola/prevención & control , Polisacáridos/inmunología , Anticuerpos Antivirales/inmunología , Humanos , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/metabolismo , Activación de Complemento , Ratones Endogámicos BALB C , Femenino , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Glicoproteínas/inmunologíaRESUMEN
The 2013-2016 Ebola virus disease epidemic and the coronavirus disease 2019 pandemic galvanized tremendous growth in models for emerging zoonotic and vector-borne viruses. Therefore, we have reviewed the main goals and methods of models to guide scientists and decision-makers. The elements of models for emerging viruses vary across spectrums: from understanding the past to forecasting the future, using data across space and time, and using statistical versus mechanistic methods. Hybrid/ensemble models and artificial intelligence offer new opportunities for modeling. Despite this progress, challenges remain in translating models into actionable decisions, particularly in areas at highest risk for viral disease outbreaks. To address this issue, we must identify gaps in models for specific viruses, strengthen validation, and involve policymakers in model development.
Asunto(s)
Zoonosis , Animales , Humanos , Zoonosis/virología , Zoonosis/transmisión , Zoonosis/epidemiología , Enfermedades Transmitidas por Vectores/virología , Enfermedades Transmitidas por Vectores/epidemiología , Enfermedades Transmitidas por Vectores/transmisión , COVID-19/virología , COVID-19/epidemiología , COVID-19/transmisión , Virosis/virología , Virosis/transmisión , Virosis/epidemiología , Fiebre Hemorrágica Ebola/virología , Fiebre Hemorrágica Ebola/transmisión , Fiebre Hemorrágica Ebola/epidemiología , SARS-CoV-2 , Vectores de Enfermedades , Brotes de Enfermedades , Virus/patogenicidad , Virus/genéticaRESUMEN
Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4+ helper T (Th) cells induced by Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.
Asunto(s)
Anticuerpos Antivirales , Vacuna BCG , Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Animales , Ratones , Vacuna BCG/inmunología , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Vacunas contra el Virus del Ébola/inmunología , Vacunas contra el Virus del Ébola/administración & dosificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Linfocitos T Colaboradores-Inductores/inmunología , Vacunación/métodos , Ratones Endogámicos C57BL , Femenino , Humanos , Modelos Animales de Enfermedad , Receptores de IgG/inmunología , Desarrollo de Vacunas , Cambio de Clase de Inmunoglobulina , InmunizaciónRESUMEN
BACKGROUND: Dynamical mathematical models defined by a system of differential equations are typically not easily accessible to non-experts. However, forecasts based on these types of models can help gain insights into the mechanisms driving the process and may outcompete simpler phenomenological growth models. Here we introduce a friendly toolbox, SpatialWavePredict, to characterize and forecast the spatial wave sub-epidemic model, which captures diverse wave dynamics by aggregating multiple asynchronous growth processes and has outperformed simpler phenomenological growth models in short-term forecasts of various infectious diseases outbreaks including SARS, Ebola, and the early waves of the COVID-19 pandemic in the US. RESULTS: This tutorial-based primer introduces and illustrates a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using an ensemble spatial wave sub-epidemic model based on ordinary differential equations. Scientists, policymakers, and students can use the toolbox to conduct real-time short-term forecasts. The five-parameter epidemic wave model in the toolbox aggregates linked overlapping sub-epidemics and captures a rich spectrum of epidemic wave dynamics, including oscillatory wave behavior and plateaus. An ensemble strategy aims to improve forecasting performance by combining the resulting top-ranked models. The toolbox provides a tutorial for forecasting time-series trajectories, including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. CONCLUSIONS: We have developed the first comprehensive toolbox to characterize and forecast time-series data using an ensemble spatial wave sub-epidemic wave model. As an epidemic situation or contagion occurs, the tools presented in this tutorial can facilitate policymakers to guide the implementation of containment strategies and assess the impact of control interventions. We demonstrate the functionality of the toolbox with examples, including a tutorial video, and is illustrated using daily data on the COVID-19 pandemic in the USA.
Asunto(s)
COVID-19 , Predicción , Humanos , COVID-19/epidemiología , Predicción/métodos , SARS-CoV-2 , Epidemias/estadística & datos numéricos , Pandemias , Modelos Teóricos , Fiebre Hemorrágica Ebola/epidemiología , Modelos EstadísticosRESUMEN
Ebolavirus disease (EVD) is an often-lethal disease caused by the genus Ebolavirus (EBOV). Although vaccines are being developed and recently used, outbreak control still relies on a combination of various factors, including rapid identification of EVD cases. This allows rapid patient isolation and control measure implementation. Ebolavirus diagnosis is performed in treatment centers or reference laboratories, which usually takes a few hours to days to confirm the outbreak or deliver a clear result. A fast and field-deployable molecular detection method, such as the isothermal amplification recombinase-aided amplification (RAA), could significantly reduce sample-to-result time. In this study, a RT-RAA assay was evaluated for EBOV detection. Various primer and probe combinations were screened; analytical sensitivity and cross-specificity were tested. A total of 40 archived samples from the 2014 to 2016 Ebola outbreak in West Africa were tested with both the reference method real-time RT-PCR and the established RT-RAA assay. The assay could detect down to 22.6 molecular copies per microliter. No other pathogens were detected with the Ebolavirus RT-RAA assay. Testing 40 samples yield clinical sensitivity and specificity of 100% each. This rapid isothermal RT-RAA assay can replace the previous RT-RPA and continue to offer rapid EBOV diagnostics.
Asunto(s)
Ebolavirus , Fiebre Hemorrágica Ebola , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , Recombinasas , Sensibilidad y Especificidad , Ebolavirus/genética , Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/virología , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , Recombinasas/metabolismo , Técnicas de Diagnóstico Molecular/métodos , África Occidental/epidemiología , Brotes de Enfermedades , ARN Viral/genética , Cartilla de ADN/genéticaRESUMEN
Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model.
Asunto(s)
Ebolavirus , Fiebre Hemorrágica Ebola , Fiebre de Lassa , Virus Lassa , Enfermedad del Virus de Marburg , Marburgvirus , Animales , Ratones , Ebolavirus/inmunología , Virus Lassa/inmunología , Marburgvirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Fiebre de Lassa/inmunología , Fiebre de Lassa/prevención & control , Enfermedad del Virus de Marburg/inmunología , Enfermedad del Virus de Marburg/prevención & control , Vacunas Virales/inmunología , Humanos , Vacunación , Femenino , Anticuerpos Antivirales/inmunología , Inmunogenicidad Vacunal , Vacunas contra el Virus del Ébola/inmunologíaRESUMEN
The 2014 West Africa Ebola virus disease outbreak prompted the deployment to Sierra Leone of non-governmental organisations and the UK Joint Inter-Agency Taskforce including personnel from the UK Defence Medical Services (DMS). Some of these military personnel partnered with the Republic of Sierra Leone Armed Forces (RSLAF) as an example of Defence Healthcare Engagement (DHE).UK DMS mentors assisted RSLAF to plan and upscale Ebola treatment units. Use of military analysis and planning tools facilitated robust and flexible plans to be produced while under significant time and resource constraints. Macrosimulation exercises enabled large numbers to be trained and standard operating procedures to be developed.Fundamental to success was a mutual respect between the DHE partners while maintaining host nation primacy throughout. DHE in this example offered advantages over non-governmental organisations. Transferable lessons for future DHE from the RSLAF-UK DMS partnership are described in this paper.
Asunto(s)
Fiebre Hemorrágica Ebola , Humanos , Fiebre Hemorrágica Ebola/terapia , Fiebre Hemorrágica Ebola/epidemiología , Sierra Leona/epidemiología , Reino Unido , Personal Militar/estadística & datos numéricos , Brotes de Enfermedades/prevención & control , Medicina Militar/métodosRESUMEN
INTRODUCTION: Clear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic Republic of the Congo and formulate policy recommendations. METHODS: To evaluate the AC policy, we performed a longitudinal cohort study, nested in an open-label, single-centre, randomised Ebola vaccine trial conducted among healthcare personnel. Participants' demographic information, residence distance to the study site and details on the financial and/or medical support provided for any (serious) adverse events ((S)AE) were combined and analysed. To assess the feasibility of the AC policy, an expenditure analysis of the costs related to AC support outcomes was performed. RESULTS: Enrolment in this evaluation study started on 29 November 2021. The study lasted 11 months and included 655 participants from the Ebola vaccine trial. In total, 393 participants used the AC policy, mostly for AE management (703 AE and 94 SAE) via medication provided by the study pharmacy (75.3%). Men had a 35.2% (95% CI 4.0% to 56.6%) lower likelihood of reporting AE compared with women. Likewise, this was 32.3% lower (95% CI 5.8% to 51.4%) for facility-based compared with community-based healthcare providers. The daily AE reporting was 78.8% lower during the passive vs the active trial stage, and 97.4% lower during unscheduled vs scheduled visits (p<0.001). Participants living further than 10 km from the trial site more frequently reported the travel distance as a reason for not using the policy (p<0.04). In practice, only 1.1% of the operational trial budget was used for AC policy support. CONCLUSION: The trial design, study population and local health system impacted the use of the AC policy. Nonetheless, the AC policy implementation in this remote and resource-constrained setting was feasible, had negligible budgetary implications and contributed to participants' healthcare options and well-being.
Asunto(s)
Vacunas contra el Virus del Ébola , Humanos , Masculino , Femenino , Vacunas contra el Virus del Ébola/economía , Adulto , República Democrática del Congo , Estudios Longitudinales , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/economía , Política de Salud , Persona de Mediana Edad , Personal de SaludRESUMEN
BACKGROUND: Many Ebola virus disease (EVD) survivors have reported somatic and neuropsychological symptoms after discharge from the Ebola Treatment Unit (ETU). Since the 2014-2016 Ebola epidemic in West Africa, various studies have investigated and identified these symptoms. Evidence on somatic symptoms is widely available in the literature, however, there is no concise overview of the prevalence across different time intervals. METHODS: This meta-analysis was conducted following the (PRISMA) guidelines. A database search was conducted to identify original studies that reported the prevalence of symptoms. The primary outcome measure was the prevalence rate of several somatic symptoms. Results were pooled, and prevalence rates were assessed over time, to elucidate any particular trends. RESULTS: We included 23 studies (5,714 participants). The pooled prevalence was: arthralgia 50% (95% CI: 41%-59%); headache 44% (95% CI: 36%-52%); myalgia 32% (95% CI: 26%-38%); abdominal pain 27% (95% CI: 15%-39%); fatigue 25% (95% CI: 19%-31%); numbness of feet 16% (95% CI: 14%-18%); numbness of hands 12% (95% CI: 10%-14%) and hearing loss 9% (95% CI: 5%-12%). Prevalence across different time intervals revealed significant patterns. All the symptoms persisted for more than 2 years after discharge except for abdominal pain. CONCLUSION: The pooled prevalence rates of somatic symptoms are notably high. Arthralgia and headache are the most prevalent of the symptoms, with hearing loss and numbness in hands and feet being the least. We found that arthralgia, myalgia, and abdominal pain decreased over time. However, headache, fatigue, numbness of hands and feet, and hearing loss increased over time.
Asunto(s)
Fiebre Hemorrágica Ebola , Sobrevivientes , Humanos , Fiebre Hemorrágica Ebola/epidemiología , Prevalencia , Sobrevivientes/estadística & datos numéricos , Sobrevivientes/psicología , Síntomas sin Explicación Médica , Artralgia/epidemiología , Cefalea/epidemiología , África Occidental/epidemiología , Fatiga/epidemiología , África/epidemiologíaRESUMEN
BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.