Impact of prophylactic vaccination strategies on Ebola virus transmission: A modeling analysis

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Abstract

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.

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Ebola Virus Disease in Health Care Workers — Sierra Leone, 2014

Peter Kilmarx, Kevin R Clarke, Patricia Dietz … (2014)

Health care workers (HCWs) are at increased risk for infection in outbreaks of Ebola virus disease (Ebola) (1). To characterize Ebola in HCWs in Sierra Leone and guide prevention efforts, surveillance data from the national Viral Hemorrhagic Fever database were analyzed. In addition, site visits and interviews with HCWs and health facility administrators were conducted. As of October 31, 2014, a total of 199 (5.2%) of the total of 3,854 laboratory-confirmed Ebola cases reported from Sierra Leone were in HCWs, representing a much higher estimated cumulative incidence of confirmed Ebola in HCWs than in non-HCWs, based on national data on the number of HCW. The peak number of confirmed Ebola cases in HCWs was reported in August (65 cases), and the highest number and percentage of confirmed Ebola cases in HCWs was in Kenema District (65 cases, 12.9% of cases in Kenema), mostly from Kenema General Hospital. Confirmed Ebola cases in HCWs continued to be reported through October and were from 12 of 14 districts in Sierra Leone. A broad range of challenges were reported in implementing infection prevention and control measures. In response, the Ministry of Health and Sanitation and partners are developing standard operating procedures for multiple aspects of infection prevention, including patient isolation and safe burials; recruiting and training staff in infection prevention and control; procuring needed commodities and equipment, including personal protective equipment and vehicles for safe transport of Ebola patients and corpses; renovating and constructing Ebola care facilities designed to reduce risk for nosocomial transmission; monitoring and evaluating infection prevention and control practices; and investigating new cases of Ebola in HCWs as sentinel public health events to identify and address ongoing prevention failures. For this report of Ebola in HCWs in Sierra Leone, data were analyzed on laboratory-confirmed cases in the national Viral Hemorrhagic Fever database, which was created to capture and analyze data from the 2014 Ebola outbreak. Surveillance officers used a standardized case investigation form to collect information from patients with suspected or probable Ebola (2) and their family members. Information collected included age, sex, address, occupation, date of onset of symptoms, and potential exposures to other Ebola patients. “Health care worker” was one of the choices listed under a patient’s occupation and included clinicians such as doctors and nurses, as well as members of other cadres, including ambulance drivers, hospital cleaners, and burial team members. Vital status and laboratory information were entered into the patient’s case record as results were reported to the surveillance team in each health district. District data were merged at the national level. Whole blood from live patients and oral swab specimens from corpses were sent to one of several laboratories in Sierra Leone. Reverse transcription–polymerase chain reaction assays were used to confirm Ebolavirus infection. Select characteristics of HCW and non-HCW cases were compared using chi-square tests. P-values <0.05 were considered significant. To inform infection prevention and control efforts and surveillance of Ebola in HCWs, unstructured interviews concerning HCW infections were conducted with HCWs and health facility administrators in the course of site visits to health care facilities in eight districts during August–October 2014. During May 23 through October 31, 2014, there were 3,854 laboratory-confirmed cases of Ebola reported in Sierra Leone in the Viral Hemorrhagic Fever database, including 199 cases in HCWs (5.2%). Seven additional cases in HCWs and 949 cases in non-HCWs had dates of symptom onset that were missing or outside of May 23 (date of the first documented case) to October 31 and were excluded from analysis. According to the National Health Strategic Plan 2010–2015, published in 2009 (3), Sierra Leone had a total health workforce of 2,402 persons. Using this denominator, the cumulative confirmed Ebola incidence in HCWs was 8,285 per 100,000. This can be compared with the 2,806 confirmed Ebola cases in non-HCWs in a national population of 3.49 million persons aged ≥15 years, with a cumulative incidence in adult non-HCWs of 80.4 per 100,000 population. Therefore, the confirmed Ebola incidence was 103-fold higher in HCWs than that in the general population in Sierra Leone. Among confirmed cases in HCWs, 54.8% were in males, compared with 48.2% in non-HCWs (p=0.09). Of 183 (92%) confirmed Ebola cases in HCWs with recorded age, two (1.1%) were reportedly in persons aged <15 years, 82.0% were in persons aged 15–49 years, and 16.9% were in persons aged ≥50 years. There were no confirmed Ebola cases in HCWs reported in May. The number peaked at 65 cases in August and declined to 36 in September and 42 in October (Figure 1). The highest percentage of confirmed Ebola patients that were HCWs was in August (9.2%); this declined to 3.5% in October (Figure 1). The number of confirmed Ebola cases in HCW per district ranged from zero in two districts to 65 cases in Kenema District (Figure 2), which also had the highest percentage of all confirmed Ebola patients that were HCWs (12.9%). District of residence was missing in seven cases in HCWs (3.5%). The surveillance form included questions on potential sources of infection, specifically attendance at a funeral or contact with a person with known or suspected Ebola, with an ill person, or with a corpse in the month before onset of symptoms. Among 159 (80%) confirmed HCW Ebola cases with data on funeral attendance, 13.8% had attended a funeral, compared with 32.3% in non-HCW (p <0.001). Data on contact with a known or suspected Ebola patient or ill person or a corpse was available for 143 (72%) confirmed HCW Ebola cases; 18.2% were in persons who had contact with a person with known or suspected Ebola or an ill person, compared with 12.3% in non-HCWs (p = 0.05); 30.1% had contact with a corpse, compared with 34.3% in non-HCWs (p=0.3). Among confirmed HCW Ebola patients, 12.1% were dead at the time of surveillance recording, compared with 15.0% among non-HCW patients (p=0.3); other data on vital status, including numbers with missing data at time of surveillance recording and final outcome, are not consistently available in the Viral Hemorrhagic Fever data. Site visits and unstructured interviews with HCWs and health facility administrators revealed a broad range of circumstances potentially leading to Ebola in HCWs. These included a lack of standard operating procedures and clearly assigned responsibilities for infection prevention and control; overall staff shortages and lack of infection prevention specialists; limited availability of safe transport vehicles for patients and corpses; incorrect triage or recognition of potential Ebola in patients and corpses, including no reassessment of admitted patients to identify new symptoms of Ebola (especially children aged <5 years); delayed laboratory diagnosis of Ebola cases because of long turn-around time for specimen transport and reporting of results; inadequate control of Ebola patient or HCW movement within health facilities; and lack of delineation between high-risk and low-risk Ebola zones. Other findings included limited availability of appropriate personal protective equipment and hand washing facilities, including lack of water and sufficient chlorine supplies; no or inadequate training about and monitoring of personal protective equipment use and hand washing; lack of equipment and materials and no or inadequate training about and monitoring of decontamination of transport vehicles and care facility spaces; limited capacity and no or inadequate training about safe management of contaminated waste; and limited capacity and no or inadequate training about safe management and burial of corpses. Discussion Analysis of the national Viral Hemorrhagic Fever database found 199 cases of Ebola in the Sierra Leone health workforce. Using the number of HCWs reported in 2009 (3) as a denominator for HCWs and comparing with infection rates in the general population aged ≥15 years, the estimated confirmed Ebola incidence rate was approximately 100-fold higher in HCWs than in non-HCW adults in Sierra Leone. The number and proportion of all confirmed Ebola patients that were HCWs peaked in August. The subsequent reductions might be attributable to concurrent implementation of infection prevention and control measures, including training and availability of personal protective equipment, and could reflect a closure of many health facilities and reduction in availability of health care services and HCW exposure as the outbreak progressed. However, many Ebola cases in HCWs continued to be reported in October. The highest number of confirmed Ebola cases and the proportion of all confirmed Ebola case that were HCWs occurred in Kenema District. There were 43 Ebola cases in HCWs in Kenema District in July and August, mostly among Kenema General Hospital staff. Inquiries about breaches of infection prevention and control at Kenema General Hospital indicated, among other problems, challenges with overall site management and administrative controls, such as correct and consistent triage and isolation of Ebola patients. Although some districts, such as Kenema, were more heavily affected, confirmed Ebola cases in HCWs have been reported in 12 of 14 districts in Sierra Leone, including all districts that have reported more than 35 confirmed Ebola cases. Also, although most cases in HCWs occurred in facilities operated by the Ministry of Health and Sanitation, including both general care facilities and those designated for Ebola care, there were a small number of confirmed Ebola cases in HCWs at Ebola care facilities established and managed by international implementing partners. These findings underscore the widespread challenges with infection prevention and control in Sierra Leone. Compared with non-HCW patients, HCW patients were less likely to have attended a funeral and were more likely to have had contact with a live Ebola patient or ill person in the 30 days before symptom onset. However, a substantial proportion of both HCW and non-HCW Ebola patients reported funeral attendance or contact with a corpse, highlighting the overall importance of transmission from corpses in this outbreak. HCW patients were not significantly less likely than non-HCW patients to be dead at the time their cases were recorded by the surveillance system. The finding that 12% of HCW patients were dead at the time of recording indicates shortcomings in contact tracing, early case identification, and access to medical care, even in HCWs, who might have been expected to have better awareness and access to health care. The findings in this report are subject to at least four limitations. First, public health surveillance data were incomplete, especially in the context of a health emergency in a resource-poor setting. It has been estimated that overall case numbers represent only one third to one half of all cases (4). Second, data on key information such as occupation was missing or might have been incorrect on many case investigation forms, and many cases were not included in the analysis because of missing or out-of-range dates of onset of symptoms. Third, members of some cadres, such as ambulance drivers, burial team members, and community health workers, might not have been consistently recorded as HCWs on case investigation forms or in the Ministry of Health and Sanitation 2009 report on the health workforce (3), and the number of health workers might have changed since 2009. As a result, these findings likely undercount the number of Ebolavirus-infected HCWs in Sierra Leone. However, Ebola reporting might be more complete for HCWs than non-HCWs, so the ratio of the Ebola cumulative incidence in HCWs compared with non-HCWs might be an overestimate. Finally, data on exposures are also likely to be incomplete. For example, the finding that contact with an Ebola patient or ill person was reported for only 19% of HCWs with Ebola is likely an underestimate. A broad range of potential problems with infection prevention and control were reported at both general care facilities and those designated for Ebola care. The Ministry of Health and Sanitation, together with Sierra Leonean and international partners, are implementing a wide range of interventions, including policies, training, procurement, renovation, construction, and monitoring and evaluation, in accordance with established recommendations (5). As is the case with prevention of nosocomial transmission of tuberculosis (6), many observed breaches of infection prevention and control practices appeared to be attributed to failures of administrative controls, such as incorrect triage, or infrastructure limitations of renovated facilities, such as lack of barriers separating Ebola wards, rather than personal protective equipment failures; particular attention to these issues is recommended in the control of Ebola. Cases of Ebola in HCWs are currently being investigated as sentinel public health events. An infection in an HCW might represent transmission from an Ebola patient in a health care facility, but might also be a signal for transmission to and from HCWs in the community, and for facility-based transmission from patient to patient and from HCWs to patients or to other HCWs. New, high-quality, dedicated Ebola treatment units are being established by international partners in Sierra Leone, but because the number of these beds does not meet the need in high-transmission areas, other, less well-resourced facilities, including Ebola care, holding, and isolation centers, are being established by the Ministry of Health and Sanitation. Given the high risk of nosocomial transmission of Ebolavirus (5), health authorities must be vigilant in implementation of strict infection prevention and control measures in all health care settings and alert to the possibility that less well-controlled settings might inadvertently act to propagate rather than interrupt transmission. Prevention of Ebola in HCWs is also critical to sustain the health workforce to address all causes of morbidity and mortality in Sierra Leone. What is already known on this topic? Health care workers (HCWs) are at increased risk for infection in outbreaks of Ebola virus disease (Ebola). Adherence to good infection prevention and control practices are required to prevent Ebola in HCWs. What is added by this report? As of October 31, 2014, of the total of 3,854 laboratory-confirmed Ebola cases reported from Sierra Leone, 199 (5.2%) were in HCWs. This was estimated to be a much higher cumulative incidence of confirmed Ebola in HCWs compared with non-HCWs. A broad range of breaches of good infection prevention and control practices were reported, and Ebola cases in HCW continued to be reported in October. What are the implications for public health practice? In Ebola outbreaks, comprehensive programs to reduce the risk for Ebola in HCWs in all health care settings are needed, including development of standard operating procedures (including safe triage), recruiting and training staff, procuring needed commodities and equipment, renovating and constructing safe Ebola care facilities, monitoring and evaluating infection prevention and control practices; and investigating new cases of Ebola in HCWs as sentinel public health events to identify and address ongoing prevention failures.

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Ebola virus vaccines: an overview of current approaches.

Andrea Marzi, Heinz Feldmann (2014)

Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible.

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Ebola Viral Disease Outbreak — West Africa, 2014

Meredith G Dixon, Ilana Schafer (2014)

On March 21, 2014, the Guinea Ministry of Health reported the outbreak of an illness characterized by fever, severe diarrhea, vomiting, and a high case-fatality rate (59%) among 49 persons (1). Specimens from 15 of 20 persons tested at Institut Pasteur in Lyon, France, were positive for an Ebola virus by polymerase chain reaction (2). Viral sequencing identified Ebola virus (species Zaïre ebolavirus), one of five viruses in the genus Ebolavirus, as the cause (2). Cases of Ebola viral disease (EVD) were initially reported in three southeastern districts (Gueckedou, Macenta, and Kissidougou) of Guinea and in the capital city of Conakry. By March 30, cases had been reported in Foya district in neighboring Liberia (1), and in May, the first cases identified in Sierra Leone were reported. As of June 18, the outbreak was the largest EVD outbreak ever documented, with a combined total of 528 cases (including laboratory-confirmed, probable, and suspected cases) and 337 deaths (case-fatality rate = 64%) reported in the three countries. The largest previous outbreak occurred in Uganda during 2000–2001, when 425 cases were reported with 224 deaths (case-fatality rate = 53%) (3). The current outbreak also represents the first outbreak of EVD in West Africa (a single case caused by Taï Forest virus was reported in Côte d’Ivoire in 1994 [3]) and marks the first time that Ebola virus transmission has been reported in a capital city. Characteristics of EVD EVD is characterized by the sudden onset of fever and malaise, accompanied by other nonspecific signs and symptoms such as myalgia, headache, vomiting, and diarrhea. Among EVD patients, 30%–50% experience hemorrhagic symptoms (4). In severe and fatal forms, multiorgan dysfunction, including hepatic damage, renal failure, and central nervous system involvement occur, leading to shock and death. The first two Ebolavirus species were initially recognized in 1976 during simultaneous outbreaks in Sudan (Sudan ebolavirus) and Zaïre (now Democratic Republic of the Congo) (Zaïre ebolavirus) (5). Since 1976, there have been more than 20 EVD outbreaks across Central Africa, with the majority caused by Ebola virus (species Zaïre ebolavirus), which historically has demonstrated the highest case-fatality rate (up to 90%) (3). The wildlife reservoir has not been definitively ascertained; however, evidence supports fruit bats as one reservoir (6). The virus initially is spread to the human population after contact with infected wildlife and is then spread person-to-person through direct contact with body fluids such as, but not limited to, blood, urine, sweat, semen, and breast milk. The incubation period is 2–21 days. Patients can transmit the virus while febrile and through later stages of disease, as well as postmortem, when persons contact the body during funeral preparations. Additionally, the virus has been isolated in semen for as many as 61 days after illness onset. Diagnosis is made most commonly through detection of Ebola virus RNA or Ebola virus antibodies in blood (5). Testing in this outbreak is being performed by Institut Pasteur, the European Mobile Laboratory, and CDC in Guinea; by the Kenema Government Hospital Viral Hemorrhagic Fever Laboratory in Sierra Leone; and by the Liberia Institute of Biomedical Research. Patient care is supportive; there is no approved treatment known to be effective against Ebola virus. Clinical support consists of aggressive volume and electrolyte management, oral and intravenous nutrition, and medications to control fever and gastrointestinal distress, as well as to treat pain, anxiety, and agitation (4,5). Diagnosis and treatment of concomitant infections and superinfections, including malaria and typhoid, also are important aspects of patient care (4). Keys to controlling EVD outbreaks include 1) active case identification and isolation of patients from the community to prevent continued virus spread; 2) identifying contacts of ill or deceased persons and tracking the contacts daily for the entire incubation period of 21 days; 3) investigation of retrospective and current cases to document all historic and ongoing chains of virus transmission; 4) identifying deaths in the community and using safe burial practices; and 5) daily reporting of cases (4,7,8). Education of health-care workers regarding safe infection-control practices, including appropriate use of personal protective equipment, is essential to protect them and their patients because health-care–associated transmission has played a part in transmission during previous outbreaks (4,9). Efforts to Control the Current Outbreak To implement prevention and control measures in both Guinea and Liberia, ministries of health with assistance from Médecins Sans Frontières, the World Health Organization, and others, put in place Ebola treatment centers to provide better patient care and interrupt virus transmission. Teams from CDC traveled to Guinea and Liberia at the end of March as part of a response by the Global Outbreak Alert and Response Network to assist the respective ministries of health in characterizing and controlling the outbreak through collection of case reports, interviewing of patients and family members, coordination of contact tracing, and consolidation of data into centralized databases. Cases are categorized into one of three case definitions: suspected (alive or dead person with fever and at least three additional symptoms, or fever and a history of contact with a person with hemorrhagic fever or a dead or sick animal, or unexplained bleeding); probable (meets the suspected case definition and has an epidemiologic link to a confirmed or probable case); confirmed (suspected or probable case that also has laboratory confirmation).* In late April, it appeared that the outbreak was slowing when Liberia did not report new cases for several weeks after April 9, and the number of new reported cases in Guinea decreased to nine for the week of April 27 (Figure 1). Since then, however, the EVD outbreak has resurged, with neighboring Sierra Leone reporting its first laboratory-confirmed case on May 24, Liberia reporting a new case on May 29 that originated in Sierra Leone, and Guinea reporting a new high of 38 cases for the week of May 25. As of June 18, the total EVD case count reported for all three countries combined was 528, including 364 laboratory-confirmed, 99 probable, and 65 suspected cases, with 337 deaths (case-fatality rate = 64%). Guinea had reported 398 cases (254 laboratory-confirmed, 88 probable, and 56 suspected) with 264 deaths (case-fatality rate = 66%) across nine districts (Figure 1). Sierra Leone had reported 97 cases (92 laboratory-confirmed, three probable, and two suspected) with 49 deaths (case-fatality rate = 51%) across five districts and the capital, Freetown. Liberia had reported 33 cases (18 confirmed, eight probable, and seven suspected) with 24 deaths (case-fatality rate = 73%) across four districts. Major challenges faced by all partners in the efforts to control the outbreak include its wide geographic spread (Figure 2), weak health-care infrastructures, and community mistrust and resistance (10). Retrospective case investigation has indicated that the first case of EVD might have occurred as early as December 2013 (Figure 1) (2). To control the outbreak, additional strategies such as involving community leaders in response efforts are needed to alleviate concerns of hesitant and fearful populations so that health-care workers can care for patients in treatment centers and thorough contact tracing can be performed. Enhancing communication across borders with respect to disease surveillance will assist in the control and prevention of more cases in this EVD outbreak. In June 2014, the World Health Organization, via the Global Outbreak Alert and Response Network, requested additional support from CDC and other partners, necessitating the deployment of additional staff members to Guinea and Sierra Leone to further coordinate efforts aimed at halting and preventing virus transmission. Persistence of the outbreak necessitates high-level, regional and international coordination to bolster response efforts among involved and neighboring nations and other response partners in order to expeditiously end this outbreak.

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Contributors

Ravi Potluri:

ORCID: http://orcid.org/0000-0002-0509-2659

Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing

Amit Kumar: Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing

Vikalp Maheshwari: Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Charlie Smith: Role: ConceptualizationRole: InvestigationRole: ValidationRole: Writing – review & editing

Valerie Oriol Mathieu: Role: ConceptualizationRole: InvestigationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Kerstin Luhn: Role: ConceptualizationRole: InvestigationRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Benoit Callendret: Role: Formal analysisRole: InvestigationRole: Writing – original draftRole: Writing – review & editing

Hitesh Bhandari: Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing

Malaya Kumar Sahoo: Role: Editor

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Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 27 April 2020

Publication date Collection: 2020

Volume: 15

Issue: 4

Electronic Location Identifier: e0230406

Affiliations

[1 ] SmartAnalyst Inc., New York, New York, United States of America

[2 ] SmartAnalyst India Pvt. Ltd., Gurgaon, India

[3 ] Janssen Vaccines & Prevention, Raritan, New Jersey, United States of America

[4 ] Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

Stanford University School of Medicine, UNITED STATES

Author notes

Competing Interests: The study was commissioned and funded by Janssen Vaccines & Prevention of Johnson and Johnson. At the time of conducting the study, Charlie Smith, Valerie Oriol Mathieu, Kerstin Luhn and Benoit Callendret were full-time employees and potential stockholders of Janssen Pharmaceuticals Inc. or its affiliates, and Ravi Potluri, Amit Kumar, Vikalp Maheshwari and Hitesh Bhandari were full-time employees of SmartAnalyst Inc. or its affiliate. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

* E-mail: rpotluri@ 123456smartanalyst.com

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Ravi Potluri http://orcid.org/0000-0002-0509-2659

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Publisher ID: PONE-D-19-17366

DOI: 10.1371/journal.pone.0230406

PMC ID: 7185698

PubMed ID: 32339195

SO-VID: 47bc8c17-a518-4903-9147-d49221735bb8

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Date received : 19 June 2019

Date accepted : 1 March 2020

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Figures: 7, Tables: 3, Pages: 17

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Funded by: Janssen Vaccines & Prevention

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ORCID: http://orcid.org/0000-0002-0509-2659

Ravi Potluri

The study was commissioned and funded by Janssen Vaccines & Prevention of Johnson and Johnson. The funders had no role in model design, data collection and analysis, decision to publish, or preparation of the manuscript. At the time of writing this manuscript, CS was employed by Janssen Vaccines & Prevention, Raritan, NJ, USA, and VOM, KL and BC were employed by Janssen Vaccines & Prevention B.V., Leiden, The Netherlands and RP, AK, VM and HB were employed by SmartAnalyst Inc, New York, NY, USA or its subsidiaries. While Janssen Vaccines & Prevention and Janssen Vaccines & Prevention B.V. provided support in the form of salaries to authors CS, VOM, KL and BC, they did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section. Additionally, assistance in the preparation of this manuscript was provided by Asclepius Medical Communications LLC, Ridgewood, NJ.

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Impact of prophylactic vaccination strategies on Ebola virus transmission: A modeling analysis

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Ebola Virus Disease in Health Care Workers — Sierra Leone, 2014

Ebola virus vaccines: an overview of current approaches.

Ebola Viral Disease Outbreak — West Africa, 2014

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