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A major catastrophe hit Western Africa and we would like to put a definite end to that nightmare. Ever since in its initial identification in 1976, the Ebola virus is endemic in Zaire (currently, Democratic Republic of the Congo – DRC), where it has exerted devastating effects. For many years now, the virus has mercilessly attacked our fellow men, killing entire families overnight and leaving thousands of children orphan. The current, being the seventh epidemic of Ebola hemorrhagic fever (EHF) in the RDC, also broke out in West Africa - Guinea, Liberia, Sierra Leone Nigeria and Senegal. The World Health Organization (WHO) called specialists from several countries and concentrated efforts that might result in a practical contribution to the control of cases. It is worth to observe that the epidemic has caused more than 1,400 deaths in 2014, being the fatality rate 60 to 90%.

An attempt to summarize the data of available information materials on epidemiological aspects, the state and prospects of prevention and treatment of hemorrhagic fevers was. Hemorrhagic fevers of viral nature-zoonotic diseases caused by viruses containing ribonucleic acid are classified into 4 families: Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae. They are spread all over the world, and their pathogens are easily transmitted from person to person, thereby spreading quickly enough beyond the main focus of biological infection. That is why the causative agents of hemorrhagic fevers are regarded as highly contagious biological agents, and agents bioterrorism. Unfortunately, there are currently no effective means of specific prevention and treatment of these infections, and therapeutic measures are limited to the use of symptomatic means. In this regard, the search for substances with pronounced antiviral activity against pathogens of hemorrhagic fevers that can effectively protect against these infections, as well as prevent their occurrence and spread is one of the priority areas of research in modern Infectology, and with the involvement of modern achievements in the field of molecular Virology and genetic engineering. The data obtained in this regard allow a more in-depth understanding of the pathogenesis of hemorrhagic fevers, the mechanisms of interaction of the pathogen with the host at the cellular level, the mechanisms of intracellular replication of viruses, the formation of the hosts response to viral invasion and clinical manifestations of diseases.

In developed countries, it is said that "threats of infectious diseases are already thought as things of the past". However, as you can see in the case of Ebola hemorrhagic fever that occurred in West Africa, this is a big mistake. Among infectious diseases, only smallpox has been successfully eradicated worldwide. In addition to the three major infectious diseases of HIV/AIDS, tuberculosis, and malaria, there is another group called emerging and reemerging infectious diseases. Recently, neglected tropical diseases (NTDs) have been listed as threats by the WHO, as have drug-resistant bacteria. The spread of these pathogens is increasing due to an increase in global travel. Malaria and more than half of the NTDs are parasitic diseases, such as trypanosomiasis and soil-borne helminthiasis. These are caused by parasites, with eukaryotes similar to their host mammals. In the case of these NTDs, protective immune responses induced by differences between a pathogen and host do not work well, and there is no vaccine against parasites. As for drugs developed to treat these diseases, because the properties of enzymes and target receptors are very similar, and effective drugs simultaneously show efficacy against both the disease and the host, severe side effects often occur. Therefore, the search for targets specifically present in parasites, and screening for drugs that inhibit their physiological functions, is extremely important. Here, as an example of the development of antiparasitic drugs, I will introduce a study on malaria.

Ebola virus disease (EVD) is a deadly zoonotic disease caused by the Ebola virus. There is no specific treatment approved for EVD. Supportive care and management of complications are mainstays of treatment. Effective outbreak control requires a multidisciplinary team effort applying case management, infection prevention and control practices, surveillance and contact tracing, a good laboratory service, safe and dignified burials, and social and community mobilization. This article highlights the epidemiology, clinical features, diagnosis, management, and prevention of EVD. The emerging diagnostic technologies, rapid viral characterization, geospatial mapping of EVD transmission, and new treatments and vaccines are discussed.

The Ebola virus infection (EVI), generally known as Ebola hemorrhagic fever, is a major health concern. The occasional outbreaks of virus occur primarily in certain parts of Africa. Many researches have been devoted to the study of the Ebola virus disease. In this paper, we have taken susceptible-infected-recovered-deceased-environment (SIRDP) system to investigate the dynamics of Ebola virus infection. We adopted fractional operators for a better illustration of model dynamics and memory effects. Initially, the Ebola disease model is modified with Caputo–Fabrizio arbitrary operator in Caputo sense (CFC) and we employed the fixed-point results for the existence and uniqueness of the solution of the fractional system. Further, we adopted the arbitrary fractional conformable and [Formula: see text]-conformable derivatives to the alternative representation of the model. For the numerical approximation of the system, we show a numerical technique based on the fundamental theorem of fractional calculus for CFC derivative and a numerical scheme called the Adams–Moulton for conformable derivatives. Finally, for the validation of theoretical results, the numerical simulations are displayed.

Funder: Medizinischen Fakultät, Ludwig-Maximilians-Universität München; funder-id: http://dx.doi.org/10.13039/501100009401, Funder: Cambridge Commonwealth, European and International Trust; funder-id: http://dx.doi.org/10.13039/501100003343

Background The West African Ebola epidemic of 2013–2016 killed nearly 4,000 Sierra Leoneans and devastated health infrastructure across West Africa. Changes in health seeking behavior (HSB) during the outbreak resulted in dramatic underreporting and substantial declines in hospital presentations to public health facilities, resulting in an estimated tens of thousands of additional maternal, infant, and adult deaths per year. Sierra Leone’s Kenema District, a major Ebola hotspot, is also endemic for Lassa fever (LF), another often-fatal hemorrhagic disease. Here we assess the impact of the West African Ebola epidemic on health seeking behaviors with respect to presentations to the Kenema Government Hospital (KGH) Lassa Ward, which serves as the primary health care referral center for suspected Lassa fever cases in the Eastern Province of Sierra Leone. Methodology/Principal findings Presentation frequencies for suspected Lassa fever presenting to KGH or one of its referral centers from 2011–2019 were analyzed to consider the potential impact of the West African Ebola epidemic on presentation patterns. There was a significant decline in suspected LF cases presenting to KGH following the epidemic, and a lower percentage of subjects were admitted to the KGH Lassa Ward following the epidemic. To assess general HSB, a questionnaire was developed and administered to 200 residents from 8 villages in Kenema District. Among 194 completed interviews, 151 (78%) of respondents stated they felt hospitals were safer post-epidemic with no significant differences noted among subjects according to religious background, age, gender, or education. However, 37 (19%) subjects reported decreased attendance at hospitals since the epidemic, which suggests that trust in the healthcare system has not fully rebounded. Cost was identified as a major deterrent to seeking healthcare. Conclusions/Significance Analysis of patient demographic data suggests that fewer individuals sought care for Lassa fever and other febrile illnesses in Kenema District after the West African Ebola epidemic. Re-establishing trust in health care services will require efforts beyond rebuilding infrastructure and require concerted efforts to rebuild the trust of local residents who may be wary of seeking healthcare post epidemic., Author summary The West African Ebola epidemic of 2013–2016 killed nearly 4,000 Sierra Leoneans and devastated health infrastructure. There is limited information regarding the effects of the epidemic on health seeking behavior. Lassa fever is clinically similar to Ebola and is prevalent in Kenema District, located in the Eastern Province of Sierra Leone. There was a significant decline in the number of individuals seeking care for suspected Lassa fever following the epidemic. Responses to a questionnaire completed by 194 Sierra Leonean residents suggested that confidence in the healthcare system was not fully restored. Cost was identified as a major deterrent to seeking healthcare. Additional community sensitization is needed to convey the need, and importance, of seeking care for Lassa fever.

During an Ebola virus disease (EVD) outbreak, calculating the exposure window of a confirmed case can assist field investigators in identifying the source of infection and establishing chains of transmission. However, field investigators often have difficulty calculating this window. We developed a bilingual (English/French), smartphone-based field application to assist field investigators in determining the exposure window of an EVD case. The calculator only requires the reported date of symptoms onset and the type of symptoms present at onset or the date of death. Prior to the release of this application, there was no similar electronic capability to enable consistent calculation of EVD exposure windows for field investigators. The Democratic Republic of the Congo Ministry of Health endorsed the application and incorporated it into trainings for field staff. Available for Apple and Android devices, the calculator continues to be downloaded even as the eastern DRC outbreak resolved. We rapidly developed and implemented a smartphone application to estimate the exposure window for EVD cases in an outbreak setting

2020 saw the continuation of the second largest outbreak of Ebola virus disease (EVD) in history. Determining epidemiological links between cases is a key part of outbreak control. However, due to the large quantity of data and subsequent data entry errors, inconsistencies in potential epidemiological links are difficult to identify. We present chainchecker, an online and offline shiny application which visualises, curates and verifies transmission chain data. The application includes the calculation of exposure windows for individual cases of EVD based on user defined incubation periods and user specified symptom profiles. It has an upload function for viral hemorrhagic fever data and utility for additional entries. This data may then be visualised as a transmission tree with inconsistent links highlighted. Finally, there is utility for cluster analysis and the ability to highlight nosocomial transmission. chainchecker is a R shiny application which has an offline version for use with VHF (viral hemorrhagic fever) databases or linelists. The software is available at https://shiny.dide.imperial.ac.uk/chainchecker which is a web-based application that links to the desktop application available for download and the github repository, https://github.com/imperialebola2018/chainchecker.

Background Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone. Methods and findings In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%–82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%–34.2%), and at 360 days, 6.0% (95% CI 3.1%–10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%–19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose–response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26–35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%–50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness. Conclusions In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time., Author summary Why was this study done? Evidence of traces of Ebola virus in semen had been reported among survivors for a very long time after their disease. This study originated out of a need to expand understanding beyond single reported cases, to gain knowledge on how many male survivors have Ebola virus persistence in semen over time, and for how long on average. We also aimed to analyze factors associated with longer persistence that could provide information on hypotheses on why some men carry virus in their semen for a very long time after the acute disease. What did the researchers do and find? In this study, 220 men who had survived Ebola disease in Sierra Leone during 2015–2016 provided semen specimens, and all of those who had traces of Ebola virus detected were followed every other week until their specimen turned negative. Seventy-five percent of these men still had traces of Ebola virus in their semen specimen at 6 months after being discharged following acute EVD, and 50% at 204 days. We also found that longer persistence of virus was significantly associated with severe acute EVD and older age. What do these findings mean? We show there is an urgent need to organize a national semen testing program as part of Ebola epidemic preparedness and response. The findings also show that in addition to testing, targeted safe sex counseling and free access to condoms should be a priority from the start of an outbreak. While we show that most of the survivors had traces of virus in semen at 6 months, more research is needed to understand the impact of viral RNA in semen on transmission of Ebola virus.

A “superspreader” refers to an unusually contagious organism infected with a disease. With respect to a human borne illnesses, a superspreader is someone who is more likely to infect other humans when compared to a typically infected person. The existence of human superspreaders is deeply entrenched in history; the most famous case being that of Typhoid Mary. Through contact tracing, epidemiologists have identified human superspreaders in measles, tuberculosis, rubella, monkeypox, smallpox, Ebola hemorrhagic fever, and SARS. The recent outbreak of Coronavirus disease (COVID-19) has shifted the focus back on the superspreaders. We herein present a case report of a COVID-19 superspreader with a hitherto unusually high number of infected contacts. The index case was a 33 year old male who resided in a low income settlement comprising of rehabilitated slum dwellers and worked as a healthcare worker (HCW) in a tertiary care hospital and had tested positive for COVID-19.On contact tracing, he had a total of 125 contacts, of which 49 COVID-19 infections had direct or indirect contact with the index case, qualifying him as a “superspreader.” This propagated infection led to an outbreak in the community. Contact tracing, testing and isolation of such superspreaders from the other members of the community is essential to stop the spread of this disease and contain the COVID-19 pandemic.

Lassa fever is an haemorrhagic fever caused by Lassa virus (LASV). There is no vaccine approved against LASV and the only recommended antiviral treatment relies on ribavirin, despite limited evidence of efficacy. Recently, the nucleotide analogue favipiravir showed a high antiviral efficacy, with 100% survival obtained in an otherwise fully lethal non-human primate (NHP) model of Lassa fever. However the mechanism of action of the drug is not known and the absence of pharmacokinetic data limits the translation of these results to the human setting. Here we aimed to better understand the antiviral effect of favipiravir by developping the first mathematical model recapitulating Lassa viral dynamics and treatment. We analyzed the viral dynamics in 24 NHPs left untreated or treated with ribavirin or favipiravir, and we put the results in perspective with those obtained with the same drugs in the context of Ebola infection. Our model estimates favipiravir EC50 in vivo to 2.89 μg.mL-1, which is much lower than what was found against Ebola virus. The main mechanism of action of favipiravir was to decrease virus infectivity, with an efficacy of 91% at the highest dose. Based on our knowledge acquired on the drug pharmacokinetics in humans, our model predicts that favipiravir doses larger than 1200 mg twice a day should have the capability to strongly reduce the production infectious virus and provide a milestone towards a future use in humans., Author summary Lassa virus is the etiological agent of Lassa fever, an haemorrhagic fever endemic that cause nearly 5000 deaths every year in West Africa. Here, we provide the first within-host mathematical model of the infection by Lassa virus in a macaque model and we analyze the antiviral effect of two candidate drugs, favipiravir or ribavirin. We show that both drugs act primarily by increasing mutagenesis in vivo. Both drugs had a strong antiviral efficacy in reducing the proportion of non infectious virus produced by infected cells, up to 91 and 40% for favipiravir and ribavirin, respectively. We bridge these predictions with our knowledge of the drugs pharmacokinetics to identify target concentrations having the capability to rapidly clear infectious virus from infected individuals.

Background. West Africa has witnessed the unprecedented outbreak of Ebola virus disease (EVD). The Ebola virus (EBOV) can cause Ebola hemorrhagic fever, which is documented as the most deadly viral hemorrhagic fever in the world. RT-PCR had been suggested to be employed in the detection of Ebola virus; however, this method has high requirements for laboratory equipment and takes a long time to determine Ebola infection. Although Xpert Ebola is a fast and simple instrument for the detection of Ebola virus, its effect is still unclear. This study is aimed at evaluating the accuracy of Xpert Ebola in diagnosing Ebola virus infection. Methods. Using the keywords “Xpert” and “Ebola virus”, relevant studies were retrieved from the database of PubMed, Embase, Web of Science, and Cochrane. RT-PCR was employed as a reference standard to evaluate whether the study is eligible to be included in the meta-analysis. Data from these included studies were extracted by two independent assessors and were then analyzed by the Meta-DiSc 1.4 software to produce the heterogeneity of sensitivity (SEN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) of the study. The results of pooled analysis were plotted, together with the summary receiver operating characteristic (SROC) curve plotted by calculating the area under the curve (AUC). Generated pooled summary estimates (95% CIs) were calculated for the evaluation of the overall accuracy of this study. Results. Five fourfold tables were made from the four studies that were included in the meta-analysis. The pooled sensitivity of Xpert Ebola was 0.98 (95% confidence interval (CI) (0.95, 0.99)), and the pooled specificity was 0.98 (95% CI (0.97, 0.99)). The pooled values of positive likelihood ratio was 53.91 (95% CI (12.82, 226.79)), with negative likelihood ratio being 0.04 (95% CI (0.02, 0.08)) and diagnostic odds ratio being 2649.45 (95% CI (629.61, 11149.02)). The AUC was 0.9961. Conclusions. Compared with RT-PCR, Xpert Ebola has high sensitivity and specificity. Therefore, it is a valued alternative method for the clinical diagnosis of Ebola virus infection. However, the Xpert Ebola test is a qualitative test that does not provide quantitative testing of EBOV concentration. Whether it can completely replace other methods or not calls for further evidences.

BackgroundDuring health disaster events such as the current devastating havoc being inflicted on countries globally by the SARS-CoV-19 pandemic, mental health problems among survivors and frontline workers are likely concerns. However, during such health disaster events, stakeholders tend to give more precedence to the socio-economic and biomedical health consequences at the expense of mental health. Meanwhile, studies show that regardless of the kind of disaster/antecedent, all traumatic events trigger similar post-traumatic stress symptoms among survivors, families, and frontline workers. Thus, our study investigated the prevalence of anxiety, depression and insomnia symptoms among survivors of the 2014–2016 Ebola virus disease that plagued the West African sub-region.MethodsWe systematically retrieved peer-reviewed articles published between 1970 and 2019 from seven electronic databases, including Google Scholar, MEDLINE, PsychInfo, PubMed, Scopus, Springer Link, Web of Science on Ebola and post-traumatic stress disorder symptoms. A comprehensive hand search complemented this literature search. Of the 87 articles retrieved, only 13 met the inclusion criteria for this meta-analysis.ResultsAfter heterogeneity, influence, and publication bias analysis, our meta-analysis pooled proportion effects estimates showed a moderate to a high prevalence of anxiety (14%; 99% CI: 0.05–0.30), depression (15%; 99% CI: 0.11–0.21), and insomnia (22%; 99% CI: 0.13–0.36). Effect estimates ranging from (0.13; 99% CI: 0.05, 0.28) through to (0.11; 99% CI: 0.05–0.22), (0.15; 99% CI: 0.09–0.25) through to (0.13; 99% CI: 0.08–0.21) and (0.23; 99% CI: 0.11–0.41) to (0.23; 99% CI: 0.11–0.41) were respectively reported for anxiety, depression and insomnia symptoms. These findings suggest a significant amount of EVD survivors are struggling with anxiety, depression and insomnia symptoms.ConclusionOur study provided the first-ever meta-analysis evidence of anxiety, depression, and insomnia symptoms among EVD survivors, and suggest that the predominant biomedical health response to regional and global health disasters should be complemented with trauma-related mental health services.

Sexual transmission of Ebola virus (EBOV) is well established and has been implicated in multiple resurgences during the West African Ebola epidemic. Given the persistence of viral RNA in semen, guidelines from the World Health Organization (WHO) recommend abstinence or condom use for at least 1 year or until two semen PCR tests are negative. To better understand the impact of semen testing on sexual behavior, male EVD survivors were surveyed regarding their sexual behavior before and after semen testing. Of the 171 men who enrolled, 148 reported being sexually active following discharge from an ETU with 59% reporting episodes of condomless sex. At least one semen sample for testing was provided by 149 men and 13 of these men had EBOV RNA detected in their semen. When comparing sexual behaviors before and after semen testing, a positive semen test result had limited impact on behavior. Of those with seminal EBOV RNA detected, 61% reported no change in behavior pre- and post-semen testing with 46% engaging in condomless sex before and after testing and only 1 adopted safer sex behaviors following receipt of a positive result. Similarly, among men with undetectable EBOV in their semen, 66% reported no change in sexual behaviors with semen testing, with 55% forgoing condoms during sex. In only 11% was a negative semen result followed by abandoning condoms. There were no known sexual transmission events of Ebola virus in this cohort despite viral presence in semen during periods of condomless sex. This highlights the need to better understand the infectious potential of viral RNA persistence and determine what constitutes effective counseling for survivors and their partners., Author summary Ebola virus (EBOV) is established as a sexually transmitted infection, however there is limited information on the sexual behaviors of Ebola survivors. We surveyed a cohort of male Ebola survivors regarding sexual activity and condom use and offered semen testing to assess EBOV persistence in semen. We found that a large majority of men who were sexually active prior to contracting Ebola Virus Disease remained sexually active after their recovery with most reporting only intermittent condom use. Semen testing for the presence of Ebola virus had limited impact on sexual behaviors, with most continuing to report engaging in condomless sex whether EBOV was detected or not. This finding has implications for use of semen testing for outbreak control as well as counseling for Ebola survivors and their partners.

Introduction In public health emergencies, local media are important sources of information for the public. Not much is known about the professional and personal roles and experiences of Sierra Leonean journalists during the Ebola virus disease (EVD) outbreak between 2014–2015. Methods/Principal findings This qualitative study is based on semi-structured interviews with 13 Sierra Leonean journalists based in urban Freetown and rural Waterloo in February and March 2016. The majority of the journalists worked for radio stations. The mostly male journalists represented national, regional and local radio stations. Transcripts of the interviews were analysed using thematic analysis. The analysis was inspired by previously reported journalist roles and agenda-setting theory, which state that the media filter what is happening, making a few core issues more salient. Sierra Leonean journalists shifted from being sceptical monitors in the beginning of the outbreak, to collaborative instructors towards the end. While they adapted to different roles, journalists struggled with their own fears for the virus, which hampered their work. They indicated that the training they received about Ebola helped them overcome their fear. Being trained gave a sense of security that helped them carry out their jobs. By turning into instructors, journalists stepped away from their journalistic professional detachment–potentially exacerbated by their personal experiences. Conclusion/Significance The first months of the outbreak were marked by passive agenda-setting roles of Sierra Leonean journalists. It took several months before the outbreak became a core issue in local media. In health emergencies, efforts should be made to partner with local media to use their platforms for local, trusted journalists and leaders to disseminate public health messages. Whereas this might hamper journalists’ credibility and can be challenging in areas with problematic press freedom, Sierra Leonean journalists experienced the outbreak as a driver of necessary change in their profession., Author summary Local media are important sources of information for the public during a health emergency. However, not much is known about the roles and experiences of local journalists who have to report under extraordinary circumstances. In this qualitative study, we interviewed Sierra Leonean journalists who reported during the 2014–2015 Ebola outbreak. The thematic analysis shows that the journalists adapted different roles over the course of the outbreak. They went from being sceptical about the existence of an outbreak at the start to changing into instructors at the end of the outbreak. Journalists struggled with their own fear for the virus, which they could overcome through targeted training, that helped them identify safe practices of reporting in the field. Our results show that it is possible to effectively partner with local media to disseminate public health messages. This might be challenging in settings with problematic press freedom, but Sierra Leonean journalists actually felt that the outbreak helped improve their practices.

Ebola epidemics constitute serious public health emergencies. Multiple vaccines are under development to prevent these epidemics and avoid the associated morbidity and mortality. Assessing the potential impact of these vaccines on morbidity and mortality of Ebola is essential for devising prevention strategies. A mean-field compartmental stochastic model was developed for this purpose and validated by simulating the 2014 Sierra Leone epidemic. We assessed the impacts of prophylactic vaccination of healthcare workers (HCW) both alone and in combination with the vaccination of the general population (entire susceptible population other than HCW). The model simulated 8,706 (95% confidence intervals [CI]: 478-21,942) cases and 3,575 (95%CI: 179-9,031) deaths in Sierra Leone, in line with WHO-reported statistics for the 2014 epidemic (8,704 cases and 3,587 deaths). Relative to this base case, the model then estimated that prophylactic vaccination of only 10% of HCW will avert 12% (95% CI: 6%-14%) of overall cases and deaths, while vaccination of 30% of HCW will avert 34% of overall cases (95% CI: 30%-64%) and deaths (95% CI: 30%-65%). Prophylactic vaccination of 1% and 5% of the general population in addition to vaccinating 30% of HCW was estimated to result in reduction in cases by 44% (95% CI: 39%-61%) and 72% (95% CI: 68%-84%) respectively, and deaths by 45% (95% CI: 40%-61%) and 74% (95% CI: 70%-85%) respectively. Prophylactic vaccination of even small proportions of HCW is estimated to significantly reduce incidence of Ebola and associated mortality. The effect is greatly enhanced by the additional vaccination even of small percentages of the general population. These findings could be used to inform the planning of prevention strategies.

During the initial phase of the 2014-2016 Ebola virus disease (EVD) outbreak in Monrovia, Liberia, all hospitals' isolation capacities were overwhelmed by the sheer caseload. As a stop-gap measure to halt transmission, Medecins sans Frontieres (MSF) distributed household disinfection kits to those who were at high risk of EVD contamination. The kit contained chlorine and personal protective materials to be used for the care of a sick person or the handling of a dead body. This intervention was novel and controversial for MSF. This paper shed the light on this experience of distribution in Monrovia and assess if kits were properly used by recipients. Targeted distribution was conducted to those at high risk of EVD (relatives of confirmed EVD cases) and health staff. Mass distributions were also conducted to households in the most EVD affected urban districts. A health promotion strategy focused on the purpose and use of the kit was integrated into the distribution. Follow-up phone calls to recipients were conducted to enquire about the use of the kit. Overall, 65,609 kits were distributed between September and November 2014. A total of 1,386 recipients were reached by phone. A total of 60 cases of sickness and/or death occurred in households who received a kit. The majority of these (46, 10%) were in households of relatives of confirmed EVD cases. Overall, usage of the kits was documented in 56 out of 60 affected households. Out of the 1322 households that did not experience sickness and/or death after the distribution, 583 (44%) made use of elements of the kit, mainly (94%) chlorine for hand-washing. At the peak of an EVD outbreak, the distribution of household disinfection kits was feasible and kits were appropriately used by the majority of recipients. In similar circumstances in the future, the intervention should be considered.

Summary Ebola virus, for which we lack effective countermeasures, causes hemorrhagic fever in humans, with significant case fatality rates. Lack of experimental human models for Ebola hemorrhagic fever is a major obstacle that hinders the development of treatment strategies. Here, we model the Ebola hemorrhagic syndrome in a microvessel-on-a-chip system and demonstrate its applicability to drug studies. Luminal infusion of Ebola virus-like particles leads to albumin leakage from the engineered vessels. The process is mediated by the Rho/ROCK pathway and is associated with cytoskeleton remodeling. Infusion of Ebola glycoprotein (GP1,2) generates a similar phenotype, indicating the key role of GP1,2 in this process. Finally, we measured the potency of a recently developed experimental drug FX06 and a novel drug candidate, melatonin, in phenotypic rescue. Our study confirms the effects of FX06 and identifies melatonin as an effective, safe, inexpensive therapeutic option that is worth investigating in animal models and human trials., Graphical Abstract, Highlights • We developed the first chip-based model for Ebola hemorrhagic shock syndrome • The engineered model recapitulates the disease-associated alteration in signaling • The “disease severity” depends on the viral load and glycoprotein concentration • We identified melatonin as an effective, safe, and inexpensive therapeutic option, Virology; Screening in Health Technology; Biological Sciences Research Methodologies

International audience; No abstract available

Hemorrhagic fever outbreaks are difficult to diagnose and control in part because of a lack of low-cost and easily accessible diagnostic structures in countries where etiologic agents are present. Furthermore, initial clinical symptoms are common and shared with other endemic diseases such as malaria or typhoid fever. Current molecular diagnostic methods such as polymerase chain reaction require trained personnel and laboratory infrastructure, hindering diagnostics at the point of need, particularly in outbreak settings. Therefore, rapid diagnostic tests such as lateral flow can be broadly deployed and are typically well-suited to rapidly diagnose hemorrhagic fever viruses, such as Ebola virus. Early detection and control of Ebola outbreaks require simple, easy-to-use assays that can detect very low amount of virus in blood. Here, we developed and characterized an immunoassay test based on immunochromatography coupled to silver amplification technology to detect the secreted glycoprotein of EBOV. The glycoprotein is among the first viral proteins to be detected in blood. This strategy aims at identifying infected patients early following onset of symptoms by detecting low amount of sGP protein in blood samples. The limit of detection achieved by this sGP-targeted kit is 2.2 x 104 genome copies/ml in plasma as assayed in a monkey analytical cohort. Clinical performance evaluation showed a specificity of 100% and a sensitivity of 85.7% when evaluated with plasma samples from healthy controls and patients infected with Zaire Ebola virus from Macenta, Guinea. This rapid and accurate diagnostic test could therefore be used in endemic countries for early detection of infected individuals in point of care settings. Moreover, it could also support efficient clinical triage in hospitals or clinical centers and thus reducing transmission rates to prevent and better manage future severe outbreaks., Author summary Ebola virus disease is a severe disease caused by Ebola virus, a member of the filovirus family, which occurs in humans and other primates. Ebola is believed to be zoonotic, however the natural reservoir is unknown. Overlapping symptoms with other endemic diseases, such as malaria and cholera, make accurate diagnostic challenging. Outbreaks of Ebola have been widespread as the consequence of the absence of available rapid, sensitive, specific, robust, and affordable licensed diagnostic test in remote areas, where outbreaks usually start. Here we have established and validated a rapid diagnostic test, which is fast, sensitive, specific, efficient, affordable, and user-friendly. Its analytical characteristics make it suitable for clinical management during Ebola virus outbreaks in remote areas. Of interest, this rapid diagnostic test detects the presence of an early viral antigen, the secreted glycoprotein, found in blood of patients shortly after infection, suggesting that it could be used to identify infected patients shortly after onset of symptoms.

Understanding the behavior of emerging disease outbreaks in, or ahead of, real-time could help healthcare officials better design interventions to mitigate impacts on affected populations. Most healthcare-based disease surveillance systems, however, have significant inherent reporting delays due to data collection, aggregation, and distribution processes. Recent work has shown that machine learning methods leveraging a combination of traditionally collected epidemiological information and novel Internet-based data sources, such as disease-related Internet search activity, can produce meaningful “nowcasts” of disease incidence ahead of healthcare-based estimates, with most successful case studies focusing on endemic and seasonal diseases such as influenza and dengue. Here, we apply similar computational methods to emerging outbreaks in geographic regions where no historical presence of the disease of interest has been observed. By combining limited available historical epidemiological data available with disease-related Internet search activity, we retrospectively estimate disease activity in five recent outbreaks weeks ahead of traditional surveillance methods. We find that the proposed computational methods frequently provide useful real-time incidence estimates that can help fill temporal data gaps resulting from surveillance reporting delays. However, the proposed methods are limited by issues of sample bias and skew in search query volumes, perhaps as a result of media coverage., Author summary Public health officials regularly make choices about treatment and prevention in disease outbreaks that have the potential to impact entire affected populations. Often these decisions are based on incomplete or unreliable information due to inherent reporting delays in healthcare-based disease surveillance systems. This issue of public health decision-making based on limited data is even more salient in emerging outbreaks, which are typically characterized by uncertain disease dynamics and limited surveillance capacity. We demonstrate the potential for using digital trace data—in this case, Internet-based information from Google search trends—for estimating disease activity in emerging outbreaks in the absence of accurate real-time healthcare-based data sources. We evaluate how data-driven methods leveraging search trend data would have performed in real-time in five recent outbreaks (yellow fever in Angola, Zika in Colombia, Ebola in the DRC, plague in Madagascar, and cholera in Yemen), and find that the methods frequently provide useful signals of disease activity ahead of standard healthcare-based surveillance methods.

Resumen Introducción. El virus del Ébola, antes llamado fiebre hemorrágica del Ébola, es una enfermedad altamente contagiosa con mortalidad entre 50% y 90%, para la cual existen prometedoras opciones de tratamiento que se encuentran en fase de evaluación y uso compasional. Objetivos. Revisar la mejor evidencia médica publicada y analizar el comportamiento de las epidemias por virus del Ébola, sus manifestaciones clínicas, sus complicaciones, los elementos más significativos para su diagnóstico y las nuevas opciones terapéuticas disponibles, para así aprender y aplicar estas experiencias en nuevos brotes. Materiales y métodos. Se realizó una búsqueda sistemática en las bases de datos PubMed, ProQuest, Embase, Redalyc, Ovid, Medline, DynaMed y ClinicalKey durante el periodo 2009-2017 en el contexto internacional, regional y local. Resultados. La revisión sistemática de artículos aportó un total de 51 430 registros, de los cuales 772 eran elegibles; de estos, 722 no eran relevantes, por lo que quedaron incluidos 50. A punto de partida se pudieron precisar los aspectos objeto de esta revisión. Conclusión. La enfermedad causada por el virus del Ébola, a pesar de su alta mortalidad, puede ser prevenida, diagnosticada oportunamente y tratada con efectividad, lo cual permite evaluar su impacto epidemiológico en las áreas endémicas y a nivel mundial. Existe un potencial arsenal terapéutico en fase de experimentación con resultados prometedores. Abstract Introduction: The Ebola virus, also known as Ebola hemorrhagic fever, is a highly contagious disease with mortality rates that range between 50% and 90%. There are promising treatment options that are currently under evaluation and compassionate use. Objectives: To review the best published medical material and analyze the behavior of Ebola virus outbreaks, clinical manifestations, complications, the most significant elements for diagnosis and new therapeutic options available, in order to learn and apply these experiences during new outbreaks. Materials and methods: A systematic search was carried out in the PubMed, ProQuest, Embase, Redalyc, Ovid, Medline, DynaMed and ClinicalKey databases during the 2009-2017 period in the international, regional and local context. Results: The systematic review yielded a total of 51 430 documents, of which 772 were eligible; of these, 722 were not relevant, and only 50 were included. Conclusion: Ebola virus disease, despite its high mortality, can be prevented, diagnosed promptly and treated effectively, which allows evaluating its epidemiological impact in endemic areas and worldwide. There are potential therapeutic tools under experimentation with promising results.

Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever (EHF), is often a severe and fatal disease. The objective of this study is to identify the psychological and social problems as well as the needs of people cured of Ebola. This work is a prospective, cross-sectional, descriptive study done within a period of three months, from 16 November 2014 to 15 February 2015. The population of this research consists of those who were infected by and cured of Ebola; they were 18 years and above and were both males and females. They have received treatment at Donka (CET) and are members of those affected and healed in Guinea (A.PE.GU.AEG); they were in Conakry during the study period and gave their consent to participate in our study. Of a total of 72 members, 55 (76.39%) met the inclusion criteria of this study. The average age was 29.9 ± 11.33 years [18-66 years] with a male predominance, sex ratio = 1.2. The average duration of isolation was 16 days with extremes of 6 and 25 days. The main psychological disorders experienced by people healed of Ebola are: fear, 85.45%; revivability, 43.64%; nightmare, 63.64%; stress, 56.36%; anxiety, 49.10%; insomnia, 45.45%; withdrawal, 43.63%; insomnia, 45.45%; distrust, 41.82%; discouragement, 41.82%; and those that want to die, 41.82%. On the social level, stigmatization from the neighborhood was 90.91% and distrust 58.18%. This study shows that people infected by and cured of Ebola suffer many psychological and behavioral disorders. Stigma and distrust are the major social problems. Key words: Ebola, psychosocial lived, Donka, Conakry.

Ebola virus disease has known as Ebola hemorrhagic fever (EHF) is an acute viral syndrome characterized by fever and bleeding witha high mortality rate in humans and non human (primates). The current outbreak inWestern Africa is the largest ebola outbreak since theebola virus was first discovered in 1976. The first EHF case that reemerged back in Africa occurred in March 2014 and in Desember 29th2014 had been revealed 20,153 cases and 7,883 deaths. The virus is transmitted from wild animals and spread in the human populationthrough human –to -human transmission. Ebola virus infection is characterized by immunosuppression and systemic inflammatoryresponse. Both condition cause the damage of blood vessels, coagulation and disorders of the immune system, leading to multiple organfailure and shock. Until now there are no ebola standards treatment guidelines. However, the life survival increased with early supportivecare such as rehydration and symptomatic treatment.

The Democratic Republic of the Congo (DRC) declared an Ebola virus disease (EVD) outbreak in North Kivu in August 2018. By June 2019, the outbreak had spread to 26 health zones in northeastern DRC, causing >2,000 reported cases and >1,000 deaths. On June 10, 2019, three members of a Congolese family with EVD-like symptoms traveled to western Uganda’s Kasese District to seek medical care. Shortly thereafter, the Viral Hemorrhagic Fever Surveillance and Laboratory Program (VHF program) at the Uganda Virus Research Institute (UVRI) confirmed that all three patients had EVD. The Ugandan Ministry of Health declared an outbreak of EVD in Uganda’s Kasese District, notified the World Health Organization, and initiated a rapid response to contain the outbreak. As part of this response, UVRI and the United States Centers for Disease Control and Prevention, with the support of Uganda’s Public Health Emergency Operations Center, the Kasese District Health Team, the Superintendent of Bwera General Hospital, the United States Department of Defense’s Makerere University Walter Reed Project, and the United States Mission to Kampala’s Global Health Security Technical Working Group, jointly established an Ebola Field Laboratory in Kasese District at Bwera General Hospital, proximal to an Ebola Treatment Unit (ETU). The laboratory consisted of a rapid containment kit for viral inactivation of patient specimens and a GeneXpert Instrument for performing Xpert Ebola assays. Laboratory staff tested 76 specimens from alert and suspect cases of EVD; the majority were admitted to the ETU (89.3%) and reported recent travel to the DRC (58.9%). Although no EVD cases were detected by the field laboratory, it played an important role in patient management and epidemiological surveillance by providing diagnostic results in, Author summary Following an imported outbreak of Ebola virus disease in Uganda’s western Kasese District, the Uganda Virus Research Institute and the United States Centers for Disease Control and Prevention jointly established a frontline field laboratory to test specimens collected from alert and suspect cases for Ebola virus disease. Using a single room equipped with a rapid containment kit to safely inactivate patient specimens and a GeneXpert to perform the Xpert Ebola Assay, the field laboratory rapidly ruled-out Ebola virus disease as the cause of illness in 76 patients during its 46 operational days. All specimens were also referred to Uganda Virus Research Institute (Entebbe) for confirmatory Ebola virus testing and testing against a panel of viruses known to cause hemorrhagic fever in Uganda, in line with the National Viral Hemorrhagic Fever Program’s testing protocol and mandate. The Ebola field laboratory served as a valuable asset in the outbreak response by supporting patient management and epidemiological surveillance.

Swiftly growing viruses are a major intimidation to human health. Such viruses are extremely pathogenic like Ebola virus, influenza virus, HIV virus, Zika virus etc . Ebola virus, a type of Filovirus, is an extremely infectious, single-stranded ribonucleic acid virus that infects both humans and apes, prompting acute fever with hemorrhagic syndrome. The high infectivity, severity and mortality of Ebola has plagued the world for the past fifty years with its first outbreak in 1976 in Marburg, Germany, and Frankfurt along with Belgrade and Serbia. The world has perceived about 28,000 cases and over 11,000 losses. The high lethality of Ebola makes it a candidate for use in bioterrorism thereby arising more concern. New guidelines have been framed for providing best possible care to the patients suffering from Ebola virus i.e Grading of Recommendation Assessment, Development And Evaluation (GRADE) methodology to develop evidence-based strategy for the treatment in future outbreak of Ebola virus. No drugs have been approved, while many potent drugs like rVSV-EBOV, Favipiravir, ZMapp are on clinical test for human safety. In this review we will discover and discuss perspective aspects that lead to the evolution of different Ebola variants as well as advances in various drugs and vaccines for treatment of the disease.

Background Ebola virus (EBOV) is a zoonotic filovirus spread through exposure to infected bodily fluids of a human or animal. Though EBOV is capable of causing severe disease, referred to as Ebola Virus Disease (EVD), individuals who have never been diagnosed with confirmed, probable or suspected EVD can have detectable EBOV antigen-specific antibodies in their blood. This study aims to identify risk factors associated with detectable antibody levels in the absence of an EVD diagnosis. Methodology Data was collected from September 2015 to August 2017 from 1,366 consenting individuals across four study sites in the DRC (Boende, Kabondo-Dianda, Kikwit, and Yambuku). Seroreactivity was determined to EBOV GP IgG using Zaire Ebola Virus Glycoprotein (EBOV GP antigen) ELISA kits (Alpha Diagnostic International, Inc.) in Kinshasa, DRC; any result above 4.7 units/mL was considered seroreactive. Among the respondents, 113 (8.3%) were considered seroreactive. Several zoonotic exposures were associated with EBOV seroreactivity after controlling for age, sex, healthcare worker status, location, and history of contact with an EVD case, namely: ever having contact with bats, ever having contact with rodents, and ever eating non-human primate meat. Contact with monkeys or non-human primates was not associated with seroreactivity. Conclusions This analysis suggests that some zoonotic exposures that have been linked to EVD outbreaks can also be associated with EBOV GP seroreactivity in the absence of diagnosed EVD. Future investigations should seek to clarify the relationships between zoonotic exposures, seroreactivity, asymptomatic infection, and EVD., Author summary Ebola virus (EBOV) is spread through exposure to infected bodily fluids of a human or animal. While EBOV can lead to a severe disease, Ebola Virus Disease (EVD), it is possible for individuals to have anti-EBOV antibodies without ever getting sick with EVD. Seroreactivity (the detection of antigen-specific antibodies) suggests that that person has been exposed to EBOV or a similar virus in the past. Our study looked for seroreactive individuals who have never received an EVD diagnosis in four sites across the Democratic Republic of the Congo. Then we checked if animal exposures previously linked to EVD were more common among seroreactive individuals than non-seroreactive individuals. Among respondents from all four sites, 113 (8.3%) were seroreactive to EBOV. Additionally, contact with bats, rodents, and eating non-human primate meat were associated with seroreactivity, indicating these factors may be predictors of undocumented EBOV exposure events. These findings show that some EVD risk factors may be associated with EBOV seroreactivity without EVD diagnosis. Future research is needed to clarify the relationships between zoonotic exposures, seroreactivity, asymptomatic infection, and EVD.