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      Estimating undetected Ebola spillovers

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          Abstract

          The preparedness of health systems to detect, treat, and prevent onward transmission of Ebola virus disease (EVD) is central to mitigating future outbreaks. Early detection of outbreaks is critical to timely response, but estimating detection rates is difficult because unreported spillover events and outbreaks do not generate data. Using three independent datasets available on the distributions of secondary infections during EVD outbreaks across West Africa, in a single district (Western Area) of Sierra Leone, and in the city of Conakry, Guinea, we simulated realistic outbreak size distributions and compared them to reported outbreak sizes. These three empirical distributions lead to estimates for the proportion of detected spillover events and small outbreaks of 26% (range 8–40%, based on the full outbreak data), 48% (range 39–62%, based on the Sierra Leone data), and 17% (range 11–24%, based on the Guinea data). We conclude that at least half of all spillover events have failed to be reported since EVD was first recognized. We also estimate the probability of detecting outbreaks of different sizes, which is likely less than 10% for single-case spillover events. Comparing models of the observation process also suggests the probability of detecting an outbreak is not simply the cumulative probability of independently detecting any one individual. Rather, we find that any individual’s probability of detection is highly dependent upon the size of the cluster of cases. These findings highlight the importance of primary health care and local case management to detect and contain undetected early stage outbreaks at source.

          Author summary

          Emerging infectious diseases are often not investigated in rural Africa unless outbreaks involve a sizeable number of cases. A number of different Ebola virus disease (EVD) outbreaks have been reported in the literature and in surveillance reports since its discovery in 1976. The majority of the reports are of large outbreaks. Given the low reported rate of transmission of Ebola, and the high frequency with which cases infect no one else, one might expect most outbreaks to be very small (<5 people). This is the first study to the authors’ knowledge that quantitatively estimates the number of undetected EVD outbreaks or probabilities of EVD outbreak detection by outbreak size. Although the total amount of evidence in this area is still limited, this study’s main result—that at least half of EVD outbreaks go undetected—is consistent under many different sets of assumptions. This is the most thorough estimation of EVD outbreak detection to date and corroborates the majority of more qualitative work on EVD surveillance, suggesting greater investment in primary health care and local surveillance will be important to detect EVD outbreaks early and consistently.

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          Most cited references 17

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          The evolution of Ebola virus: Insights from the 2013-2016 epidemic.

          The 2013-2016 epidemic of Ebola virus disease in West Africa was of unprecedented magnitude and changed our perspective on this lethal but sporadically emerging virus. This outbreak also marked the beginning of large-scale real-time molecular epidemiology. Here, we show how evolutionary analyses of Ebola virus genome sequences provided key insights into virus origins, evolution and spread during the epidemic. We provide basic scientists, epidemiologists, medical practitioners and other outbreak responders with an enhanced understanding of the utility and limitations of pathogen genomic sequencing. This will be crucially important in our attempts to track and control future infectious disease outbreaks.
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            Ebola hemorrhagic fever outbreaks in Gabon, 1994-1997: epidemiologic and health control issues.

            From the end of 1994 to the beginning of 1995, 49 patients with hemorrhagic symptoms were hospitalized in the Makokou General Hospital in northeastern Gabon. Yellow fever (YF) virus was first diagnosed in serum by use of polymerase chain reaction followed by blotting, and a vaccination campaign was immediately instituted. The epidemic, known as the fall 1994 epidemic, ended 6 weeks later. However, some aspects of this epidemic were atypical of YF infection, so a retrospective check for other etiologic agents was undertaken. Ebola (EBO) virus was found to be present concomitantly with YF virus in the epidemic. Two other epidemics (spring and fall 1996) occurred in the same province. GP and L genes of EBO virus isolates from all three epidemics were partially sequenced, which showed a difference of <0.1% in the base pairs. Sequencing also showed that all isolates were very similar to subtype Zaire EBO virus isolates from the Democratic Republic of the Congo.
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              After Ebola in West Africa — Unpredictable Risks, Preventable Epidemics

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                13 June 2019
                June 2019
                : 13
                : 6
                Affiliations
                Department of Veterinary Medicine, University of Cambridge, Cambridge United Kingdom
                Institute for Disease Modeling, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Article
                PNTD-D-18-01655
                10.1371/journal.pntd.0007428
                6563953
                31194734
                © 2019 Glennon et al

                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.

                Page count
                Figures: 3, Tables: 0, Pages: 10
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1144
                Award Recipient :
                Funded by: Medical Research Council (GB)
                Award ID: MR/P025226/1
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008288, Alborada Trust;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008288, Alborada Trust;
                Award Recipient :
                EEG is funded by the Gates-Cambridge Trust (Bill & Melinda Gates Foundation [OPP1144]). OR and JLNW are funded by the ALBORADA Trust. JLNW is funded by the Medical Research Council (MR/P025226/1). The funding bodies had no involvement in the design, writing, or decision to publish of this manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Medicine and Health Sciences
                Epidemiology
                Disease Surveillance
                Infectious Disease Surveillance
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Infectious Disease Surveillance
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Viral Hemorrhagic Fevers
                Ebola Hemorrhagic Fever
                Medicine and Health Sciences
                Infectious Diseases
                Viral Diseases
                Viral Hemorrhagic Fevers
                Ebola Hemorrhagic Fever
                Physical Sciences
                Mathematics
                Probability Theory
                Probability Distribution
                Medicine and Health Sciences
                Epidemiology
                Infectious Disease Epidemiology
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Epidemiology
                Physical Sciences
                Mathematics
                Probability Theory
                Statistical Distributions
                Statistical Dispersion
                People and places
                Geographical locations
                Africa
                Sierra Leone
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Filoviruses
                Ebola Virus
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Hemorrhagic Fever Viruses
                Ebola Virus
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Viral Pathogens
                Hemorrhagic Fever Viruses
                Ebola Virus
                Biology and Life Sciences
                Organisms
                Viruses
                Viral Pathogens
                Hemorrhagic Fever Viruses
                Ebola Virus
                Biology and Life Sciences
                Organisms
                Viruses
                Hemorrhagic Fever Viruses
                Ebola Virus
                Custom metadata
                All data and R code used in this analysis are publicly available at https://github.com/eeg31/evd-detection (doi: 10.5281/zenodo.2602105).

                Infectious disease & Microbiology

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