African Outbreak Research Articles

Priorities, Barriers, and Facilitators towards International Guidelines for the Delivery of Supportive Clinical Care during an Ebola Outbreak: A Cross-Sectional Survey.

During the Ebola outbreak, mortality reduction was attributed to multiple improvements in supportive care delivered in Ebola treatment units (ETUs). We aimed to identify high-priority supportive care measures, as well as perceived barriers and facilitators to their implementation, for patients with Ebola Virus Disease (EVD). We conducted a cross-sectional survey of key stakeholders involved in the response to the 2014–2016 West African EVD outbreak. Out of 57 email invitations, 44 responses were received, and 29 respondents completed the survey. The respondents listed insufficient numbers of health workers (23/29, 79%), improper tools for the documentation of clinical data (n = 22/28, 79%), insufficient material resources (n = 22/29, 76%), and unadapted personal protective equipment (n = 20/28, 71%) as the main barriers to the provision of supportive care in ETUs. Facilitators to the provision of supportive care included team camaraderie (n in agreement = 25/28, 89%), ability to speak the local language (22/28, 79%), and having treatment protocols in place (22/28, 79%). This survey highlights a consensus across various stakeholders involved in the response to the 2014–2016 EVD outbreak on a limited number of high-priority supportive care interventions for clinical practice guidelines. Identified barriers and facilitators further inform the application of guidelines.

Early transmission and case fatality of Ebola virus at the index site of the 2013–16 west African Ebola outbreak: a cross-sectional seroprevalence survey

SummaryBackgroundTo date, epidemiological studies at the index site of the 2013–16 west African Ebola outbreak in Meliandou, Guinea, have been restricted in their scope. We aimed to determine the occurrence of previously undocumented Ebola virus disease (EVD) cases and infections, and to reconstruct transmission events.MethodsThis cross-sectional seroprevalence survey of the adult population of Meliandou used a highly specific oral fluid test and detailed interviews of all households in the village and key informants. Each household was interviewed, with all members prompted to describe the events of the outbreak, any illness within the household, and possible contact with suspected cases. Information for deceased individuals was provided by relatives living in the same household. Symptoms were based on Ebola virus Makona variant EVD case definitions (focusing on fever, vomiting, and diarrhoea). For antibody testing, we used an Ebola virus glycoprotein IgG capture enzyme immunoassay developed from a previously validated assay. A maximum exposure level was assigned to every participant using a predetermined scale. We used a generalised linear model (logit function) to estimate odds ratios for the association of sociodemographic variables and exposure level with Ebola virus infection. We adjusted estimates for age and maximum exposure, as appropriate.FindingsBetween June 22, and July 9, 2017, we enrolled 237 participants from 27 households in Meliandou. Two households refused to participate and one was absent. All adults in participating households who were present for the interview provided an oral fluid swab for testing, of which 224 were suitable for analysis. In addition to the 11 EVD deaths described previously, on the basis of clinical description and oral fluid testing, we found two probable EVD deaths and eight previously unrecognised anti-Ebola virus IgG-positive survivors, including one who had mild symptoms and one who was asymptomatic, resulting in a case fatality of 55·6% (95% CI 30·8–78·5) for adults. Health-care work (adjusted odds ratio 6·64, 1·54–28·56; p=0·001) and level of exposure (odds ratio adjusted for linear trend across five levels 2·79, 1·59–4·883; p<0·0001) were independent risk factors for infection.InterpretationEbola virus infection was more widespread in this spillover population than previously recognised (21 vs 11 cases). We show the first serological evidence of survivors in this population (eight anti-Ebola virus IgG seropositive) and report a case fatality lower than previously reported (55·6% vs 100% in adults). These data show the high community coverage achievable by using a non-invasive test and, by accurately documenting the beginnings of the west African Ebola virus outbreak, reveal important insight into transmission dynamics and risk factors that underpin Ebola virus spillover events.FundingUS Food and Drug Administration, Wellcome Trust, and German Research Council.

Indirect Influence of African Swine Fever Outbreak on the Raven (Corvus corax) Population.

Simple SummaryThe persecution of ravens ceased in the middle of the 20th century, and consequently their abundance started to rise in most European countries. Ravens are food opportunists that can eat plants, prey on animals, and feed on garbage dumps. However, carrion plays a crucial role in their diet. In Central Poland, the carrion of farm animals (disposed of illegally) was thought to be the main food source for ravens. This changed radically in February 2014, after the first case of African swine fever (ASF) in Poland, and the introduction of strict procedures for the utilization of pig and wild boar carcasses to stop the spread of the virus. This decrease in carrion availability influenced the raven population; ravens changed their diet, i.e., instead of feeding on the carrion of pigs (previously their main dietary component), they ate (among others) the carrion of domestic dogs and cats, and also preyed on small vertebrates. Consequently, the number of breeding raven pairs decreased, and birds produced fewer fledglings. This research showed how certain human activities influence wildlife. The illegal disposal of dead animals, motivated by the desire to save money, resulted in abundant food sources for ravens and an increase in population size.Carrion plays a crucial role in the raven’s diet. In the past, domestic pig carrion was widely available in Poland. This changed with an African swine fever (ASF) outbreak and the introduction of strict procedures aimed at stopping the virus from spreading. We compared data from Central Poland (field and forest mosaic, study area of 105 km2) for two periods, i.e., before (2011–2014) and after the ASF outbreak (2015–2018). In breeding seasons, nests of ravens were found, juveniles were counted, and the time when juveniles left their nests was recorded. Diet composition data were based on pellet analysis and direct observations of feeding birds. The number of breeding pairs dropped from 12.3 to 7.5 in the second period. Breeding parameters were similar. However, birds in the second period had fewer fledglings per successful pair. Domestic pig carrion was found to be an important food item, and with its limited supply, ravens changed their diet, i.e., they fed on the carrion of dogs and cats or preyed on small vertebrates more often. Overall, our study points to a crucial role of the availability of the carrion of big farm animals (i.e., domestic pig) in maintaining the high density of breeding raven populations.

Epidemiological characteristics, clinical manifestations, and treatment outcome of 139 paediatric Ebola patients treated at a Sierra Leone Ebola treatment center

BackgroundThe West Africa Ebola Virus Disease (EVD) outbreak in 2014–2016 was declared by the World Health Organization (WHO) a public health emergency of international concern. Most of the previous studies done in Sierra Leone relating to the clinical and epidemiological features of EVD during the 2014–2016 West African outbreak focused on adult EVD patients. There have been conflicting reports about the effects of EVD on children during previous outbreaks.MethodsThis is an observational retrospective analysis of medical data of all laboratory confirmed paediatric EVD patients below 15 years of age who were admitted at the 34 Military Hospital Ebola Treatment Center (ETC) in Wilberforce, Sierra Leone between June 2014 to April 2015. We analyzed the sociodemographic and clinical characteristics of paediatric EVD cases contained in case report forms that were collected by Ebola surveillance officers and clinicians at the 34 Military Hospital ETC. Both univariate and multivariate logistic regression models were used to determine the sociodemographic and clinical characteristics of paediatric EVD patients that were associated with EVD facility-based mortality.ResultsThe majority of the paediatric EVD cases in this study were female (56.1%), pupils (51.1%), and 43.2% belonged to the age group between 10 years and below 15 years. The median age of the paediatric EVD cases was 9 years (interquartile range = 4 to 11 years). Adjusting for other covariates in the model, male paediatric EVD patient (AOR = 13.4, 95% CI = [2.07–156-18], p < 0.05), EVD patient with abdominal pain (AOR = 11.0, 95% CI = [1.30–161.81], p < 0.05), vomiting (AOR = 35.7, 95% CI = [3.43–833.73], p < 0.05), signs of conjunctivitis (AOR = 17.4, 95% CI = [1.53–342.21], p < 0.05) and difficulty in breathing (AOR = 23.3, 95% CI = [1.92–713.01], p < 0.05) at the time of admission had increased odds of dying during EVD treatment.ConclusionsWe recommend the adoption of case definitions currently in vigour to cater for specific characteristics of paediatric patients. Subgroups that can be identified by applying the model developed in this study may require special attention and intensified care.

Ebola Virus Disease - clinical manifestations, management and future therapies

AbstractThe largest epidemic of Ebola Virus Disease in recorded human history occurred in West Africa in 2014 and resulted in significant morbidity and mortality. The causative pathogen, Ebola virus, is readily transmitted through contact with the body fluids of infected individuals and from the bodies of those who have died from the disease. In its early stages, the illness is characterised by non-specific symptoms that mimic many other endemic infectious diseases in countries with limited healthcare resources. These factors contributed to the rapid spread of the outbreak, which required an international response in which the UK Armed Forces played an important role. This review describes the clinical presentation, lessons learned from managing the West African outbreak, and potential future treatments.

Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial

Introduction/HypothesisRecruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014–2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study. MethodsAn online survey which included participants’ prior experience with clinical trials, motivations to participate (including financial incentives), and demographic information was developed to examine the motivations of healthy participants in two phase 1 clinical vaccine trials conducted at the Canadian Center for Vaccinology in Halifax, Nova Scotia. Participants were invited via email to complete the online survey. Readability and clarity were assessed through pilot testing. ResultsA total of 49 (55.7%) of 88 participants of the two studies completed the survey (22 [55%] of 40 participants from the Ebola vaccine study and 27 [56.3%] of 48 from the adjuvanted influenza vaccine study). Motivations that were most frequently ranked among participants' top three in both trials were (1) wanting to contribute to the health of others, (2) wanting to participate in something important, (3) wanting to contribute to the advancement of science, and (4) wanting to receive an incentive such as money or a tablet. Conclusions/RecommendationsAlthough media attention and financial compensation were more often cited by Ebola vaccine trial participants as a reason to participate, both altruistic and self-interested factors were important motivations for participants in their decision to participate in a phase 1 vaccine clinical trial.

A field investigation of an African horse sickness outbreak in the controlled area of South Africa in 2016.

An outbreak of African horse sickness (AHS) caused by AHS virus type 1 occurred within the South African AHS surveillance zone during April and May 2016. The index case was detected by a private veterinarian through passive surveillance. There were 21 cases in total, which is relatively low compared to case totals during prior AHS outbreaks in the same region (and of the same AHS virus type) in 2004, 2011 and 2014. The affected proportion of horses on affected properties was 0.07 (95% CI 0.04, 0.11). Weather conditions were conducive to high midge activity immediately prior to the outbreak but midge numbers decreased rapidly with the advent of winter. The outbreak was localized, with 18 of the 21 cases occurring within 8km of the index property and the three remaining cases on two properties within 21km of the index property, with direction of spread consistent with wind-borne dispersion of infected midges. Control measures included implementation of a containment zone with movement restrictions on equids. The outbreak was attributed to a reversion to virulence of a live attenuated vaccine used extensively in South Africa. Outbreaks in the AHS control zones have a major detrimental impact on the direct export of horses from South Africa, notably to the European Union.

Determining the Efficacy, Safety and Suitability of Disinfectants to Prevent Emerging Infectious Disease Transmission

The scale of the 2014–2017 West African Ebola Virus Disease outbreak overwhelmed the international response capacity. This has led to inconsistencies in international guidance documents, particularly around chlorine disinfection of surfaces and hands to prevent transmission. To provide evidence for the disinfection recommendations, three research strands were conducted: (1) impacts of chlorine chemistry; (2) efficacy of surface cleaning recommendations; and (3) safety and efficacy of handwashing recommendations. Strand 1 research found that the compound chemistry of the chlorine source has an impact on the chlorine solution shelf-life (&lt;1 day–30 days), with testing of chlorine solutions recommended to ensure accuracy. Strand 2 research found that surface cleaning with 0.5% chlorine solutions with a 15-min exposure time is efficacious in reducing transmission risk. Strand 3 research found that community handwashing with chlorine solutions is as safe and efficacious as handwashing with soap and water or sanitizer, which offers a benefit of reducing pathogens in the rinsing water. Using calcium hypochlorite as the chlorine source compound provided a particularly good performance in chemistry and handwashing studies. The research was successful at providing information to align with the inconsistent international guidelines. Further research is needed to proactively establish the efficacy, safety and suitability of disinfection for the seven viral pathogens that are considered likely to cause severe outbreaks with few/no medical countermeasures.

Epidemiological analysis of the 2015–2017 African swine fever outbreaks in Estonia

African swine fever (ASF) was first detected in the Estonian wild boar population in September 2014, while the first domestic pig farm was affected in July 2015. In the present study, we aimed to analyse, retrospectively, the epidemiology of the disease in all 26 outbreaks in domestic pig herds that occurred in Estonia during the period 2015–2017. Formal interviews were conducted to estimate the high-risk period for every farm, and to identify the possible origin of the ASF virus and the mode of virus introduction. Furthermore, the clinical manifestation of the disease as well as the course of the disease within the farm were investigated. Survival analysis was used to calculate herd incidence and to estimate outbreak risk. A hierarchical Bayesian space–time model was used to analyse the associations between outbreaks and ASF occurrence in wild boar. The spatial and temporal distribution of outbreaks was analysed to characterise the ASF epidemic in the Estonian domestic pig population from 2015 to 2017.The estimated high-risk period varied from seven to 20 days with a median of 11 days. On most of the affected farms, the first clinical signs were mild and not specific to ASF despite the high virulence of the circulating virus. Morbidity and mortality were often limited to a single pen or unit of the farm. The highest mortality (29.7%) was seen on backyard farms with 1–10 pigs and the lowest (0.7%) on large commercial farms (>1000 pigs). The spread of the virus within affected farms has been slow and the contagiousness of the virus has been relatively low. Farms of all sizes and types have been at risk, including large commercial farms operating at a high biosecurity level. In none of the affected farms could the specific route of introduction be verified. However, the findings suggested that virus introduction occurred via indirect transmission routes due to insufficient biosecurity. The total herd incidence of outbreaks was similar across all three years, being 2.4% in 2015 and 2016, and 2.0% in 2017. All outbreaks occurred from June to September, during the warmest period of the year. The results suggest that the increase in ASF cases in local wild boar populations is the main risk factor leading to the infection of farms; 88% of outbreaks occurred in areas where ASF virus was detected in wild boar prior to the outbreak, within a radius of 15 km from the outbreak farm.

Mannoside Glycolipid Conjugates Display Antiviral Activity Against Ebola Virus.

The West African outbreak of Ebola virus (EBOV) infection during 2013-2016 highlighted the need for development of field-applicable therapeutic drugs for this infection. Here we report that mannoside glycolipid conjugates (MGCs) consisting of a trimannose head and a lipophilic chain assembled by a linker inhibit EBOV infection not only of human monocyte-derived dendritic cells and macrophages, but also of a number of susceptible cells. Analysis of the mode of action leads us to conclude that MGCs act directly on cells, notably by preventing virus endocytosis.

Assessment of knowledge, attitudes and perceptions regarding Ebola disease in healthcare workers from a tertiary care hospital in Romania.

ObjectivesThe National Institute for Infectious Diseases ‘Prof. Dr. Matei Balș’ was the designated centre for managing Ebola alerts in Romania during the 2014 African outbreak. We surveyed Ebola knowledge, attitudes and perceptions (KAP) among the institute's healthcare workers.Study designThis was a cross-sectional survey.MethodsThe study consisted of a self-administered paper-based anonymous questionnaire that included 24 closed-item questions and two scales of personal concern.ResultsRespondents were generally well informed; compared to nurses, doctors recorded a 1.9-fold higher rate of correct responses regarding Ebola transmission (P < 0.001), but both nurses and doctors correctly identified Ebola's aetiological agent. Nurses perceived higher personal (P = 0.008) and family (P < 0.001) risk than doctors. Respondents reporting high perceived risks were more likely to be less informed about Ebola (P = 0.019) and its prevention options (P = 0.033). Males were 6.7-fold more likely to volunteer than females (P = 0.001) and so were graduates of higher rather than lower education (1.5-fold more likely, P = 0.017) and doctors than nurses (1.7-fold more likely, P = 0.018). The institute ranked first among sources of information on Ebola; respondents who had received Ebola training in the institute 2 years previously were 1.2–1.3 times more likely to correctly identify transmission routes.ConclusionsWe have characterised KAP on Ebola disease among Romanian healthcare workers from a tertiary care hospital in Bucharest. Nurses, specialist physicians and laboratory personnel may need more frequent retraining than residents and senior physicians.

DNA-launched RNA replicon vaccines induce potent anti-Ebolavirus immune responses that can be further improved by a recombinant MVA boost

There are currently no licensed therapeutic treatment or preventive vaccines against Ebolavirus disease, and the 2013–2016 West African outbreak of Ebolavirus disease spread rapidly and resulted in almost 30,000 cases and more than 11,000 deaths. However, the devastating outbreak has spurred the development of novel Ebolavirus vaccines. Here, we demonstrate that alphavirus-based DNA-launched self-replicating RNA replicon vaccines (DREP) encoding either the glycoprotein (GP) gene or co-expressing the GP and VP40 genes of Sudan or Zaire Ebolavirus are immunogenic in mice inducing both binding and neutralizing antibodies as well as CD8 T cell responses. In addition, antibodies were cross-reactive against another Ebolavirus, although the specificity was higher for the vaccination antigen. DREP vaccines were more immunogenic than recombinant MVA vaccines expressing the same Ebolavirus antigens. However, a DREP prime followed by an MVA boost immunization regimen improved vaccine immunogenicity as compared to DREP and MVA homologous prime-boost immunizations. Moreover, we show that a bivalent approach targeting both Sudan and Zaire Ebolavirus can be employed without significant loss of immunity. This opens for further investigation of a pan-Ebolavirus or even a pan-filovirus vaccine.

Persistence of Ebola virus after the end of widespread transmission in Liberia: an outbreak report

Outbreak response efforts for the 2014-15 Ebola virus disease epidemic in west Africa brought widespread transmission to an end. However, subsequent clusters of infection have occurred in the region. An Ebola virus disease cluster in Liberia in November, 2015, that was identified after a 15-year-old boy tested positive for Ebola virus infection in Monrovia, raised the possibility of transmission from a persistently infected individual. Case investigations were done to ascertain previous contact with cases of Ebola virus disease or infection with Ebola virus. Molecular investigations on blood samples explored a potential linkage between Ebola virus isolated from cases in this November, 2015, cluster and epidemiologically linked cases from the 2014-15 west African outbreak, according to the national case database. The cluster investigated was the family of the index case (mother, father, three siblings). Ebola virus genomes assembled from two cases in the November, 2015, cluster, and an epidemiologically linked Ebola virus disease case in July, 2014, were phylogenetically related within the LB5 sublineage that circulated in Liberia starting around August, 2014. Partial genomes from two additional individuals, one from each cluster, were also consistent with placement in the LB5 sublineage. Sequencing data indicate infection with a lineage of the virus from a former transmission chain in the country. Based on serology and epidemiological and genomic data, the most plausible scenario is that a female case in the November, 2015, cluster survived Ebola virus disease in 2014, had viral persistence or recurrent disease, and transmitted the virus to three family members a year later. Investigation of the source of infection for the November, 2015, cluster provides evidence of Ebola virus persistence and highlights the risk for outbreaks after interruption of active transmission. These findings underscore the need for focused prevention efforts among survivors and sustained capacity to rapidly detect and respond to new Ebola virus disease cases to prevent recurrence of a widespread outbreak. US Centers for Disease Control and Prevention, Defense Threat Reduction Agency, and WHO.

Phylodynamic assessment of intervention strategies for the West African Ebola virus outbreak

Genetic analyses have provided important insights into Ebola virus spread during the recent West African outbreak, but their implications for specific intervention scenarios remain unclear. Here, we address this issue using a collection of phylodynamic approaches. We show that long-distance dispersal events were not crucial for epidemic expansion and that preventing viral lineage movement to any given administrative area would, in most cases, have had little impact. However, major urban areas were critical in attracting and disseminating the virus: preventing viral lineage movement to all three capitals simultaneously would have contained epidemic size to one-third. We also show that announcements of border closures were followed by a significant but transient effect on international virus dispersal. By quantifying the hypothetical impact of different intervention strategies, as well as the impact of barriers on dispersal frequency, our study illustrates how phylodynamic analyses can help to address specific epidemiological and outbreak control questions.

Serological Evidence of Ebola Virus Infection in Rural Guinea before the 2014 West African Epidemic Outbreak.

Questions remain as to whether an unnoticed Ebola outbreak occurred in Guinea before the 2014-2016 epidemic. To address this, we used a highly sensitive and specific Luminex-based assay for Ebola virus (EBOV) antibody detection to screen blood samples collected in the framework of the Demographic Health Survey performed in 2012 in Guinea. One sample (GF069) of 1,483 tested was positive at very high immunoglobulin G titer to Zaire EBOV in Guinée Forestière. Thus, at least 2 years before the 2014 EVD outbreak in Guinea, Zaire EBOV was circulating in rural areas of this country.

Ebola vaccine offers lasting protection

In promising news for the infectious disease world, Merck & Co.’s Ebola vaccine appears to offer protection for at least two years after inoculation. The results, reported recently in The Lancet, offer hope that doctors will have a new tool to deploy in a future Ebola virus outbreak. A consortium of researchers has been tracking levels of Ebola-neutralizing antibodies in people who had received the vaccine as part of three Phase I clinical trials. Of the 217 participants across the three studies, 90 people who agreed to be followed over time submitted blood samples two years after receiving the vaccine. Those being followed included people who had received low and high doses of the vaccine; antibodies persisted in both groups.Merck licensed rVSV-ZEBOV from NewLink Genetics in late 2014, near the peak of the West African Ebola virus outbreak that eventually killed more than 11,000 people. rVSV-ZEBOV is one of several

A52 Ebola virus phylogenetic analysis during the 2014–2016 West African outbreak

A52 Ebola virus phylogenetic analysis during the 2014–2016 West African outbreak

Fractional-Dose Yellow Fever Vaccine Appears Effective

Efforts to control an African outbreak of yellow fever that began in 2015 have severely depleted the worldwide supply of yellow fever vaccine. With

Active Monitoring of Travelers for Ebola Virus Disease-New York City, October 25, 2014-December 29, 2015.

The CDC recommended active monitoring of travelers potentially exposed to Ebola virus during the 2014 West African Ebola virus disease outbreak, which involved daily contact between travelers and health authorities to ascertain the presence of fever or symptoms for 21 days after the travelers' last potential Ebola virus exposure. From October 25, 2014, to December 29, 2015, the New York City Department of Health and Mental Hygiene (DOHMH) monitored 5,359 persons for Ebola virus disease, corresponding to 5,793 active monitoring events. Most active monitoring events were in travelers classified as low (but not zero) risk (n = 5,778; 99%). There were no gaps in contact with DOHMH of ≥2 days during 95% of active monitoring events. Instances of not making any contact with travelers decreased after CDC began distributing mobile telephones at the airport. Ebola virus disease-like symptoms or a temperature ≥100.0°F were reported in 122 (2%) active monitoring events. In the final month of active monitoring, an optional health insurance enrollment referral was offered for interested travelers, through which 8 travelers are known to have received coverage. Because it is possible that active monitoring will be used again for an infectious threat, the experience we describe might help to inform future such efforts.

Single-Dose Trivalent VesiculoVax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge.

Previous studies demonstrated that a single intramuscular (i.m.) dose of an attenuated recombinant vesicular stomatitis virus (rVSV) vector (VesiculoVax vector platform; rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHPs) from lethal challenge with EBOV strains Kikwit and Makona. Here, we studied the immunogenicities of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies, an optimal attenuated trivalent rVSV vector formulation was identified that included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV), and the Angola strain of Marburg marburgvirus (MARV) GPs. NHPs were vaccinated with a single dose of the trivalent formulation, followed by lethal challenge 28 days later with each of the three corresponding filoviruses. At day 14 postvaccination, a serum IgG response specific for all three GPs was detected in all the vaccinated macaques. A modest and balanced cell-mediated immune response specific for each GP was also detected in a majority of the vaccinated macaques. No matter the level of total GP-specific immune response detected postvaccination, all the vaccinated macaques were protected from disease and death following lethal challenge with each of the three filoviruses. These findings indicate that vaccination with a single dose of attenuated rVSV-N4CT1 vectors each expressing a single filovirus GP may provide protection against the filoviruses most commonly responsible for outbreaks of hemorrhagic fever in sub-Saharan Africa.IMPORTANCE The West African Ebola virus Zaire outbreak in 2013 showed that the disease was not only a regional concern, but a worldwide problem, and highlighted the need for a safe and efficacious vaccine to be administered to the populace. However, other endemic pathogens, like Ebola virus Sudan and Marburg, also pose an important health risk to the public and therefore require development of a vaccine prior to the occurrence of an outbreak. The significance of our research was the development of a blended trivalent filovirus vaccine that elicited a balanced immune response when administered as a single dose and provided complete protection against a lethal challenge with all three filovirus pathogens.