A Flexible, Quantitative Plasmonic-Fluor Lateral Flow Assay for the Rapid Detection of Orthoebolavirus zairense and Orthoebolavirus sudanense.

Filoviruses comprise a family of single-stranded, negative-sense RNA viruses with a significant impact on human health. Given the risk for disease outbreaks, as highlighted by the recent outbreaks across Africa, there is an unmet need for flexible diagnostic technologies that can be deployed in resource-limited settings. Herein, we highlight the use of plasmonic-fluor lateral flow assays (PF-LFA) for the rapid, quantitative detection of an Ebolavirus-secreted glycoprotein, a marker for infection. Plasmonic fluors are a class of ultrabright reporter molecules that combine engineered nanorods with conventional fluorophores, resulting in improved analytical sensitivity. We have developed a PF-LFA for Orthoebolavirus zairense (EBOV) and Orthoebolavirus sudanense (SUDV) that provides estimated limits of detection as low as 0.446 and 0.641 ng/mL, respectively. Furthermore, our assay highlights a high degree of specificity between the two viral species while also maintaining a turnaround time as short as 30 min. To highlight the utility of our PF-LFA, we demonstrate the detection of EBOV infection in non-human primates. Our PF-LFA represents an enormous step forward in the development of a robust, field-deployable assay for filoviruses.

Case fatality rate for Ebola disease, 1976-2022: A meta-analysis of global data.

An up-to-date pooled case fatality rate (CFR) for Ebola disease (EBOD) at the global level is lacking. We abstracted EBOD data from 1976 to 2022 for 16 countries and 42 outbreaks to conduct a meta-analysis. The pooled CFR was 60.6% (95% confidence interval (CI) 51.6-69.4; 95% prediction interval 12.9-99.1). Of the four ebolaviruses, Zaire virus was the most lethal (CFR = 66.6%, 95% CI 55.9-76.8), then Sudan virus (CFR=48.5%, 95% CI 38.6-58.4), Bundibugyo virus (CFR=32.8%, 95% CI 25.8-40.2) and Tai Forest virus (CFR= 0%, 95% CI 0.0-97.5). The CFR in sub-Saharan Africa was 61.3% (95% CI 52.8-69.6) and for the rest of the world was 24.5% (95% CI 0.0-67.9%). CFR declined over time but stabilized at 61.0% (95% CI, 52.0-69.0) between 2014 and 2022. Overall, the EBOD CFR is still high and heterogeneous. Accordingly, early diagnosis, early treatment if available, and supportive care are important to prevent significant morbidity and mortality.

[Ebola and Marburg virus disease]. / Ebola-Virus- und Marburg-Viruserkrankung.

Viral hemorrhagic fevers (VHF) are serious, often fatal diseases that affect humans and non-human primates. The nomenclature of these diseases has changed in that they are now referred to as viral diseases because the previously named symptoms of fever or hemorrhages are not obligatory. In this article, the focus will be on the VHFs Ebola and Marburg viral disease with the potential for human-to-human transmission; these diseases are so-called high-consequence infectious diseases (HCID), some with considerable potential for epidemic spread and the risk of nosocomial transmission.

Cost-effectiveness of incorporating Ebola prediction score tools and rapid diagnostic tests into a screening algorithm: A decision analytic model.

BACKGROUND: No distinctive clinical signs of Ebola virus disease (EVD) have prompted the development of rapid screening tools or called for a new approach to screening suspected Ebola cases. New screening approaches require evidence of clinical benefit and economic efficiency. As of now, no evidence or defined algorithm exists. OBJECTIVE: To evaluate, from a healthcare perspective, the efficiency of incorporating Ebola prediction scores and rapid diagnostic tests into the EVD screening algorithm during an outbreak. METHODS: We collected data on rapid diagnostic tests (RDTs) and prediction scores' accuracy measurements, e.g., sensitivity and specificity, and the cost of case management and RDT screening in EVD suspect cases. The overall cost of healthcare services (PPE, procedure time, and standard-of-care (SOC) costs) per suspected patient and diagnostic confirmation of EVD were calculated. We also collected the EVD prevalence among suspects from the literature. We created an analytical decision model to assess the efficiency of eight screening strategies: 1) Screening suspect cases with the WHO case definition for Ebola suspects, 2) Screening suspect cases with the ECPS at -3 points of cut-off, 3) Screening suspect cases with the ECPS as a joint test, 4) Screening suspect cases with the ECPS as a conditional test, 5) Screening suspect cases with the WHO case definition, then QuickNavi™-Ebola RDT, 6) Screening suspect cases with the ECPS at -3 points of cut-off and QuickNavi™-Ebola RDT, 7) Screening suspect cases with the ECPS as a conditional test and QuickNavi™-Ebola RDT, and 8) Screening suspect cases with the ECPS as a joint test and QuickNavi™-Ebola RDT. We performed a cost-effectiveness analysis to identify an algorithm that minimizes the cost per patient correctly classified. We performed a one-way and probabilistic sensitivity analysis to test the robustness of our findings. RESULTS: Our analysis found dual ECPS as a conditional test with the QuickNavi™-Ebola RDT algorithm to be the most cost-effective screening algorithm for EVD, with an effectiveness of 0.86. The cost-effectiveness ratio was 106.7 USD per patient correctly classified. The following algorithms, the ECPS as a conditional test with an effectiveness of 0.80 and an efficiency of 111.5 USD per patient correctly classified and the ECPS as a joint test with the QuickNavi™-Ebola RDT algorithm with an effectiveness of 0.81 and a cost-effectiveness ratio of 131.5 USD per patient correctly classified. These findings were sensitive to variations in the prevalence of EVD in suspected population and the sensitivity of the QuickNavi™-Ebola RDT. CONCLUSIONS: Findings from this study showed that prediction scores and RDT could improve Ebola screening. The use of the ECPS as a conditional test algorithm and the dual ECPS as a conditional test and then the QuickNavi™-Ebola RDT algorithm are the best screening choices because they are more efficient and lower the number of confirmation tests and overall care costs during an EBOV epidemic.

Evaluation of Ebola virus disease surveillance system capability to promptly detect a new outbreak in Liberia.

INTRODUCTION: Liberia was heavily affected by the 2014-2016 Ebola virus disease (EVD) outbreak. With substantial investments in interventions to combat future outbreaks, it is hoped that Liberia is well prepared for a new incursion. We assessed the performance of the current EVD surveillance system in Liberia, focusing on its ability to promptly detect a new EVD outbreak. METHODS: We integrated WHO and US Centers for Disease Control and Prevention guidelines for public health surveillance system evaluation and used standardised indicators to measure system performance. We conducted 23 key informant interviews, 150 health facility assessment surveys and a standardised patient (SP) study (19 visits) from January 2020 to January 2021. Data were summarised and a gap analysis conducted. RESULTS: We found basic competencies of case detection and reporting necessary for a functional surveillance system were in place. At the higher (national, county and district) levels, we found performance gaps in 2 of 6 indicators relating to surveillance system structure, 3 of 14 indicators related to core functions, 1 of 5 quality indicators and 2 of 8 indicators related to support functions. The health facility assessment found performance gaps in 9 of 10 indicators related to core functions, 5 of 6 indicators related to support functions and 3 of 7 indicators related to quality. The SP simulations revealed large gaps between expected and actual practice in managing a patient warranting investigation for EVD. Major challenges affecting the system's operations across all levels included limited access to resources to support surveillance activities, persistent stock out of sample collection materials and attrition of trained staff. CONCLUSION: The EVD surveillance system in Liberia may fail to promptly detect a new EVD outbreak. Specific improvements are required, and regular evaluations recommended. SP studies could be crucial in evaluating surveillance systems for rarely occurring diseases that are important to detect early.

Ebola virus disease: A narrative review.

Ebola virus disease (EVD), which is also referred to as Ebola hemorrhagic fever, is a highly contagious and frequently lethal sickness caused by the Ebola virus. In 1976, the disease emerged in two simultaneous outbreaks in Sudan and the Democratic Republic of Congo. Subsequently, it has caused intermittent outbreaks in several African nations. The virus is primarily spread via direct contact with the bodily fluids of an infected individual or animal. EVD is distinguished by symptoms such as fever, fatigue, muscle pain, headache, and hemorrhage. The outbreak of EVD in West Africa in 2014-2016 emphasized the need for effective control and prevention measures. Despite advancements and the identification of new treatments for EVD, the primary approach to treatment continues to be centered around providing supportive care. Early detection and supportive care can enhance the likelihood of survival. This includes intravenous fluids, electrolyte replacement, and treatment of secondary infections. Experimental therapies, for instance, monoclonal antibodies and antiviral drugs, have shown promising results in animal studies and some clinical trials. Some African countries have implemented the use of vaccines developed for EVD, but their effectiveness and long-term safety are still being studied. This article provides an overview of the history, transmission, symptoms, diagnosis, treatment, epidemiology, and Ebola coinfection, as well as highlights the ongoing research efforts to develop effective treatments and vaccines to combat this deadly virus.

Ebola virus disease: A review for the emergency medicine clinician.

INTRODUCTION: Ebolavirus, the causative agent of Ebola virus disease (EVD) has been responsible for sporadic outbreaks mainly in sub-Saharan Africa since 1976. EVD is associated with high risk of transmission, especially to healthcare workers during patient care. OBJECTIVE: The purpose of this review is to provide a concise review of EVD presentation, diagnosis, and management for emergency clinicians. DISCUSSION: EVD is spread through direct contact, including blood, bodily fluids or contact with a contaminated object. Patients may present with non-specific symptoms such as fevers, myalgias, vomiting, or diarrhea that overlap with other viral illnesses, but rash, bruising, and bleeding may also occur. Laboratory analysis may reveal transaminitis, coagulopathy, and disseminated intravascular coagulation. The average clinical course is approximately 8-10 days with an average case fatality rate of 50%. The mainstay of treatment is supportive care, with two U.S. Food and Drug Administration-approved monoclonal antibody treatments (Ebanga and Inmazeb). Survivors of the disease may have a complicated recovery, marked by long-term symptoms. CONCLUSION: EVD is a potentially deadly condition that can present with a wide range of signs and symptoms. Emergency clinicians must be aware of the presentation, evaluation, and management to optimize the care of these patients.

Head-to-head comparison of diagnostic accuracy of four Ebola virus disease rapid diagnostic tests versus GeneXpert® in eastern Democratic Republic of the Congo outbreaks: a prospective observational study.

BACKGROUND: Ebola virus disease (EVD) outbreaks have emerged in Central and West Africa. EVD diagnosis relies principally on RT-PCR testing with GeneXpert®, which has logistical and cost restrictions at the peripheral level of the health system. Rapid diagnostic tests (RDTs) would offer a valuable alternative at the point-of-care to reduce the turn-around time, if they show good performance characteristics. We evaluated the performance of four EVD RDTs against the reference standard GeneXpert® on stored EVD positive and negative blood samples collected between 2018 and 2021 from outbreaks in eastern Democratic Republic of the Congo (DRC). METHODS: We conducted a prospective and observational study in the laboratory on QuickNavi-Ebola™, OraQuick® Ebola Rapid Antigen, Coris® EBOLA Ag K-SeT, and Standard® Q Ebola Zaïre Ag RDTs using left-over archived frozen EDTA whole blood samples. We randomly selected 450 positive and 450 negative samples from the EVD biorepositories in DRC, across a range of GeneXpert® cycle threshold values (Ct-values). RDT results were read by three persons and we considered an RDT result as "positive", when it was flagged as positive by at least two out of the three readers. We estimated the sensitivity and specificity through two independent generalized (logistic) linear mixed models (GLMM). FINDINGS: 476 (53%) of 900 samples had a positive GeneXpert Ebola result when retested. The QuickNavi-Ebola™ showed a sensitivity of 56.8% (95% CI 53.6-60.0) and a specificity of 97.5% (95% CI 96.2-98.4), the OraQuick® Ebola Rapid Antigen test displayed 61.6% (95% CI 57.0-65.9) sensitivity and 98.1% (95% CI 96.2-99.1) specificity, the Coris® EBOLA Ag K-SeT showed 25.0% (95% CI 22.3-27.9) sensitivity and 95.9% (95% CI 94.2-97.1) specificity, and the Standard® Q Ebola Zaïre Ag displayed 21.6% (95% CI 18.1-25.7) sensitivity and 99.1% (95% CI 97.4-99.7) specificity. INTERPRETATION: None of the RDTs evaluated approached the "desired or acceptable levels" for sensitivity set out in the WHO target product profile, while all of the tests met the "desired level" for specificity. Nevertheless, the QuickNavi-Ebola™ and OraQuick® Ebola Rapid Antigen Test demonstrated the most favorable profiles, and may be used as frontline tests for triage of suspected-cases while waiting for RT-qPCR confirmatory testing. FUNDING: Institute of Tropical Medicine Antwerp/EDCTP PEAU-EBOV-RDC project.

Development and Clinical Evaluation of a Rapid Point of Care Test for Ebola Virus Infection in Humans.

The genus Ebolavirus contains multiple species of viruses that are highly contagious and lethal, often causing severe hemorrhagic fever. To minimize the global threat from Ebola virus disease (EVD), sustainable, field-appropriate tools are needed to quickly screen and triage symptomatic patients and conduct rapid screening of cadavers to ensure proper handling of human remains. The OraQuick® Ebola Rapid Antigen Test is an in vitro diagnostic single-use immunoassay for the qualitative detection of Ebola virus antigens that detects all known species within the genus Ebolavirus. Here, we report the performance of the OraQuick® Ebola Rapid Antigen Test and provide a comparison of its performance with other rapid diagnostic tests (RDTs) for EVD. OraQuick® Ebola demonstrated clinical sensitivity of 84.0% in archived EVD patient venous whole-blood (WB) samples, 90.9% in Ebola virus-infected monkey fingerstick samples, and 97.1% in EVD patient cadaver buccal swabs, as well as clinical specificity of 98.0-100% in venous WB samples and 99.1-100% in contrived saliva samples. It is the only 510(k)-cleared Ebola rapid test, has analytical sensitivity as good as or better than all RDT comparators for EVD, and can detect the Sudan virus. Our data demonstrate that the OraQuick® Ebola Rapid Antigen Test is a sensitive and specific assay that can be used for rapid detection of EBOV in humans and could support efforts for EVD-specific interventions and control over outbreaks.

Investing in preparedness for rapid detection and control of epidemics: analysis of health system reforms and their effect on 2021 Ebola virus disease epidemic response in Guinea.

The 2014-2016 West Africa Ebola Virus Disease (EVD) Epidemic devastated Guinea's health system and constituted a public health emergency of international concern. Following the crisis, Guinea invested in the establishment of basic health system reforms and crucial legal instruments for strengthening national health security in line with the WHO's recommendations for ensuring better preparedness for (and, therefore, a response to) health emergencies. The investments included the scaling up of Integrated Disease Surveillance and Response; Joint External Evaluation of International Health Regulation capacities; National Action Plan for Health Security; Simulation Exercises; One Health platforms; creation of decentralised structures such as regional and prefectural Emergency Operation Centres; Risk assessment and hazard identification; Expanding human resources capacity; Early Warning Alert System and community preparedness. These investments were tested in the subsequent 2021 EVD outbreak and other epidemics. In this case, there was a timely declaration and response to the 2021 EVD epidemic, a lower-case burden and mortality rate, a shorter duration of the epidemic and a significant reduction in the cost of the response. Similarly, there was timely detection, response and containment of other epidemics including Lassa fever and Marburg virus disease. Findings suggest the utility of the preparedness activities for the early detection and efficient containment of outbreaks, which, therefore, underlines the need for all countries at risk of infectious disease epidemics to invest in similar reforms. Doing so promises to be not only cost-effective but also lifesaving.

Efficiency of Field Laboratories for Ebola Virus Disease Outbreak during Chronic Insecurity, Eastern Democratic Republic of the Congo, 2018-2020.

During the 10th outbreak of Ebola virus disease in the Democratic Republic of the Congo, the Institut National de Recherche Biomédicale strategically positioned 13 decentralized field laboratories with dedicated equipment to quickly detect cases as the outbreak evolved. The laboratories were operated by national staff, who quickly handed over competencies and skills to local persons to successfully manage future outbreaks. Laboratories analyzed ≈230,000 Ebola diagnostic samples under stringent biosafety measures, documentation, and database management. Field laboratories diversified their activities (diagnosis, chemistry and hematology, survivor follow-up, and genomic sequencing) and shipped 127,993 samples from the field to a biorepository in Kinshasa under good conditions. Deploying decentralized and well-equipped laboratories run by local personnel in at-risk countries for Ebola virus disease outbreaks is an efficient response; all activities are quickly conducted in the field.

A sequential test for assessing the effectiveness of response strategies during an emerging epidemic.

In epidemiology, the fatality rate is an important indicator of disease severity and has been used to evaluate the effects of new treatments. During an emerging epidemic with limited resources, monitoring the changes in fatality rate can also provide signals on the evaluation of government policies and healthcare quality, which helps to guide public health decision. A statistical test is developed in this paper to detect changes in fatality rate over time during the course of an emerging infectious disease. A major advantage of the proposed test is that it only requires the regularly reported numbers of deaths and recoveries, which meets the actual need as detailed surveillance data are hard to collect during the course of an emerging epidemic especially the deadly infectious diseases with large magnitude. In addition, with the sequential testing procedure, the effective measures can be detected at the earliest possible time to provide guidance to policymakers for swift action. Simulation studies showed that the proposed test performs well and is sensitive in picking up changes in the fatality rate. The test is applied to the 2014-2016 Ebola outbreak in Sierra Leone for illustration.

The diagnostic accuracy of rapid diagnostic tests for Ebola virus disease: a systematic review.

BACKGROUND: Ebola virus disease (EVD) is a dangerous condition that can cause an epidemic. Several rapid diagnostic tests (RDTs) have been developed to diagnose EVD. These RDTs promise to be quicker and easier to use than the current reference standard diagnostic test, PCR. OBJECTIVES: To assess the diagnostic accuracy of RDTs for EVD. METHODS: A systematic review of diagnostic accuracy studies. DATA SOURCES: The following bibliographic databases were searched from inception to present: MEDLINE (Ovid), Embase, Global Health, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus database, Web of Science, PROSPERO register of Systematic Reviews, and Clinical Trials.Gov. STUDY ELIGIBILITY CRITERIA: Diagnostic accuracy studies. PARTICIPANTS: Patients presenting to the Ebola treatment units with symptoms of EVD. INTERVENTIONS: RDTs; reference standard, RT-PCR. ASSESSMENT OF RISK OF BIAS: Quality Assessment of Diagnostic Accuracy Studies-2 tool. METHODS OF DATA SYNTHESIS: Summary estimates of diagnostic accuracy study were produced for each device type. Subgroup analyses were performed for RDT type and specimen material. A sensitivity analysis was performed to assess the effect of trial design and bias. RESULTS: We included 15 diagnostic accuracy studies. The summary estimate of sensitivity for lateral flow assays was 86.1% (95% CI, 86-86.2%), with specificity of 97% (95% CI, 96.1-97.9%). The summary estimate for rapid PCR devices was sensitivity of 96.2% (95% CI, 95.3-97.9%), with a specificity of 96.8% (95% CI, 95.3-97.9%). Pre-specified subgroup analyses demonstrated that RDTs were effective on a range of specimen material. Overall, the risk of bias throughout the included studies was low, but it was high in patient selection and uncertain in the flow and timing domains. CONCLUSIONS: RDTs possess both high sensitivity and specificity compared with RT-PCR among symptomatic patients presenting to the Ebola treatment units. Our findings support the use of RDTs as a 'rule in' test to expedite treatment and vaccination.

Identifying Paucisymptomatic or Asymptomatic and Unrecognized Ebola Virus Disease Among Close Contacts Based on Exposure Risk Assessments and Screening Algorithms.

BACKGROUND: There is limited evidence to evaluate screening algorithms with rapid antigen testing and exposure assessments as identification strategies for paucisymptomatic or asymptomatic Ebola virus (EBOV) infection and unrecognized EBOV disease (EVD). METHODS: We used serostatus and self-reported postexposure symptoms from a cohort study to classify contact-participants as having no infection, paucisymptomatic or asymptomatic infection, or unrecognized EVD. Exposure risk was categorized as low, intermediate, or high. We created hypothetical scenarios to evaluate the World Health Organization (WHO) case definition with or without rapid diagnostic testing (RDT) or exposure assessments. RESULTS: This analysis included 990 EVD survivors and 1909 contacts, of whom 115 (6%) had paucisymptomatic or asymptomatic EBOV infection, 107 (6%) had unrecognized EVD, and 1687 (88%) were uninfected. High-risk exposures were drivers of unrecognized EVD (adjusted odds ratio, 3.5 [95% confidence interval, 2.4-4.9]). To identify contacts with unrecognized EVD who test negative by the WHO case definition, the sensitivity was 96% with RDT (95% confidence interval, 91%-99%), 87% with high-risk exposure (82%-92%), and 97% with intermediate- to high-risk exposures (93%-99%). The proportion of false-positives was 2% with RDT and 53%-93% with intermediate- and/or high-risk exposures. CONCLUSION: We demonstrated the utility and trade-offs of sequential screening algorithms with RDT or exposure risk assessments as identification strategies for contacts with unrecognized EVD.

Identifying the scope of ethical challenges caused by the Ebola epidemic 2014-2016 in West Africa: a qualitative study.

BACKGROUND: The West African Ebola virus epidemic from 2014 to 2016 is unprecedented in its scale, surpassing all previous and subsequent Ebola outbreaks since 1976. This epidemic provoked a humanitarian emergency that extended to different spheres of life, making visible ethical challenges in addition to medical, economic, and social ones. The present article aims to identify and differentiate the scope of ethical issues associated with the Ebola epidemic. METHODS: An online media analysis was performed on articles published from March 2014 to September 2015 in ten preselected academic journals (scientific press) and two online newspapers (lay press). Two methodological approaches were combined: a systematic literature search and a qualitative content analysis. An additional keyword search was conducted on the PubMed database for the period after the end of the Ebola epidemic (2016-2020) to obtain an overview of research dealing with medical ethics due to the epidemic and to compare these results with the identified ethical challenges. RESULTS: A total of 389 articles dealing with the subject fields "Ebola epidemic" and "ethics" were researched. For qualitative content analysis, the time span with the highest article density was selected and a total of 64 articles were included (15 scientific articles, 49 popular articles). Five core ethical challenges of the Ebola epidemic emerged: 1. Responsibility and Accountability, 2. Spillover Effects, 3. Research and Development, 4. Health Communication, and 5. Resource Allocation. Articles in academic journals were dominated by the discussion of normative aspects in the area of "research and development", while newspaper articles focused on aspects of "responsibility and accountability". CONCLUSION: An ethical discussion of the Ebola epidemic requires an examination of as many of the ethical dimensions involved as possible. The presented investigation of the two types of media with regard to the Ebola epidemic offers this possibility of a more comprehensive insight into this diversity as a basis for ethical discussions.

Development of Ebola virus disease prediction scores: Screening tools for Ebola suspects at the triage-point during an outbreak.

BACKGROUND: The control of Ebola virus disease (EVD) outbreaks relies on rapid diagnosis and prompt action, a daunting task in limited-resource contexts. This study develops prediction scores that can help healthcare workers improve their decision-making at the triage-point of EVD suspect-cases during EVD outbreaks. METHODS: We computed accuracy measurements of EVD predictors to assess their diagnosing ability compared with the reference standard GeneXpert® results, during the eastern DRC EVD outbreak. We developed predictive scores using the Spiegelhalter-Knill-Jones approach and constructed a clinical prediction score (CPS) and an extended clinical prediction score (ECPS). We plotted the receiver operating characteristic curves (ROCs), estimated the area under the ROC (AUROC) to assess the performance of scores, and computed net benefits (NB) to assess the clinical utility (decision-making ability) of the scores at a given cut-off. We performed decision curve analysis (DCA) to compare, at a range of threshold probabilities, prediction scores' decision-making ability and to quantify the number of unnecessary isolation. RESULTS: The analysis was done on data from 10432 subjects, including 651 EVD cases. The EVD prevalence was 6.2% in the whole dataset, 14.8% in the subgroup of suspects who fitted the WHO Ebola case definition, and 3.2% for the set of suspects who did not fit this case definition. The WHO clinical definition yielded 61.6% sensitivity and 76.4% specificity. Fatigue, difficulty in swallowing, red eyes, gingival bleeding, hematemesis, confusion, hemoptysis, and a history of contact with an EVD case were predictors of EVD. The AUROC for ECPS was 0.88 (95%CI: 0.86-0.89), significantly greater than this for CPS, 0.71 (95%CI: 0.69-0.73) (p < 0.0001). At -1 point of score, the CPS yielded a sensitivity of 85.4% and specificity of 42.3%, and the ECPS yielded sensitivity of 78.8% and specificity of 81.4%. The diagnostic performance of the scores varied in the three disease contexts (the whole, fitting or not fitting the WHO case definition data sets). At 10% of threshold probability, e.g. in disease-adverse context, ECPS gave an NB of 0.033 and a net reduction of unnecessary isolation of 67.1%. Using ECPS as a joint approach to isolate EVD suspects reduces the number of unnecessary isolations by 65.7%. CONCLUSION: The scores developed in our study showed a good performance as EVD case predictors since their use improved the net benefit, i.e., their clinical utility. These rapid and low-cost tools can help in decision-making to isolate EVD-suspicious cases at the triage point during an outbreak. However, these tools still require external validation and cost-effectiveness evaluation before being used on a large scale.

Innovative approach to monitor performance of integrated disease surveillance and response after the Ebola outbreak in Sierra Leone: lessons from the field.

BACKGROUND: Supervision of healthcare workers improves performance if done in a supportive and objective manner. Regular supervision is a support function of Integrated Disease Surveillance and Response (IDSR) strategy and allows systematic monitoring of IDSR implementation. Starting 2015, WHO and other development partners supported the Ministry of Health and Sanitation (MoHS) to revitalize IDSR in Sierra Leone and to monitor progress through supportive supervision assessments. We report on the findings of these assessments. METHODS: This was a cross-sectional study where six longitudinal assessments were conducted in randomly selected health facilities. Health facilities assessed were 71 in February 2016, 99 in July 2016, 101 in May 2017, 126 in August 2018, 139 in February 2019 and 156 in August 2021. An electronic checklist based on selected core functions of IDSR was developed and uploaded onto tablets using the Open Data Kit (ODK) platform. Supervision teams interviewed health care workers, reviewed documents and made observations in health facilities. Supervision books were used to record feedback and corrective actions. Data from the supervisory visits was downloaded from ODK platform, cleaned and analysed. Categorical data was summarized using frequencies and proportions while means and medians were used for continuous variables. Z test was used to test for differences in proportions. RESULTS: Completeness of IDSR reporting improved from 84.5% in 2016 to 96% in 2021 (11.5% points; 95% CI 3.6, 21.9; P-value 0.003). Timeliness of IDSR reports improved from 80.3 to 92% (11.7% points; 95% CI 2.4, 22.9; P-value 0.01). There was significant improvement in health worker knowledge of IDSR concepts and tools, in availability of IDSR standard case definition posters and reporting tools and in data analysis practices. Availability of vaccines and temperature monitoring tools in health facilities also improved significantly but some indicators dropped such as availability of IDSR technical guidelines and malaria testing kits and drugs. CONCLUSION: Supervision using electronic tool contributed to health systems strengthening through longitudinal tracking of core IDSR indicators and other program indicators such as essential malaria commodities and availability and status of routine vaccines. Supervision using electronic tools should be extended to other programs.

Using next generation matrices to estimate the proportion of infections that are not detected in an outbreak.

Contact tracing, where exposed individuals are followed up to break ongoing transmission chains, is a key pillar of outbreak response for infectious disease outbreaks. Unfortunately, these systems are not fully effective, and infections can still go undetected as people may not remember all their contacts or contacts may not be traced successfully. A large proportion of undetected infections suggests poor contact tracing and surveillance systems, which could be a potential area of improvement for a disease response. In this paper, we present a method for estimating the proportion of infections that are not detected during an outbreak. Our method uses next generation matrices that are parameterized by linked contact tracing data and case line-lists. We validate the method using simulated data from an individual-based model and then investigate two case studies: the proportion of undetected infections in the SARS-CoV-2 outbreak in New Zealand during 2020 and the Ebola epidemic in Guinea during 2014. We estimate that only 5.26% of SARS-CoV-2 infections were not detected in New Zealand during 2020 (95% credible interval: 0.243 - 16.0%) if 80% of contacts were under active surveillance but depending on assumptions about the ratio of contacts not under active surveillance versus contacts under active surveillance 39.0% or 37.7% of Ebola infections were not detected in Guinea (95% credible intervals: 1.69 - 87.0% or 1.70 - 80.9%).

Providing On-Site Laboratory and Biosafety Just-In-Time Training Inside a Box-Based Laboratory during the West Africa Ebola Outbreak: Supporting Better Preparedness for Future Health Emergencies.

The Biological Light Fieldable Laboratory for Emergencies (B-LiFE) is a box-based modular laboratory with the capacity to quickly deploy on-site in cases of uncontrolled spread of infectious disease. During the 2014-2015 West Africa Ebola outbreak, this tent laboratory provided diagnostic support to the N'Zerekore Ebola Treatment Center (ETC), Guinea, for three months. One of the objectives of B-LiFE deployment was to contribute, as much as possible, to national capacity building by training local scientists. Two Guinean biologists were selected according to their basic biological knowledge and laboratory skills among 50 candidate trainees, and were integrated into the team through "just-in-time training" (JiTT), which helped the biologists acquire knowledge and laboratory skills beyond their expertise. The JiTT program was conducted according to standard laboratory procedures, in line with international biosafety guidelines adapted to field conditions. Supervised acquisition of field-laboratory practices mainly focused on biochemical testing and Ebola viral load quantification using routine PCR-based detection, including the Biofire FilmArray® system (BFA), a novel, as yet non-validated, automated assay for diagnostic testing of Ebola virus disease at the time of B-LiFE deployment. During the JiTT, the two biologists were closely involved in all laboratory activities, including BFA validation and biosafety procedures. Meanwhile, this successful JiTT enhanced the B-LiFE in-field operational capacity and contributed to national capacity building. A post-training evaluation and contacts were organised to assess the evolution and technical skills gained by the two researchers during the B-LiFE mission. At the end of the B-LiFE mission, both biologists were enrolled in follow-on programmes to curb the epidemic spreading in Africa. These results demonstrate that during infectious disease outbreaks or major crises, the JiTT approach can rapidly expand access to critical diagnostic testing and train local staff to do so.