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      Clinical Manifestations and Modes of Death among Patients with Ebola Virus Disease, Monrovia, Liberia, 2014

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          Abstract.

          Although the high case fatality rate (CFR) associated with Ebola virus disease (EVD) is well documented, there are limited data on the actual modes of death. We conducted a retrospective, observational cohort study among patients with laboratory-confirmed EVD. The patients were all seen at the Eternal Love Winning Africa Ebola Treatment Unit in Monrovia, Liberia, from June to August 2014. Our primary objective was to describe the modes of death of our patients and to determine predictors of mortality. Data were available for 53 patients with laboratory-confirmed EVD, with a median age of 35 years. The most frequent presenting symptoms were weakness (91%), fever (81%), and diarrhea (78%). Visible hemorrhage was noted in 25% of the cases. The CFR was 79%. Odds of death were higher in patients with diarrhea (odds ratio = 26.1, P < 0.01). All patients with hemorrhagic signs died ( P < 0.01). Among the 18 fatal cases for which clinical information was available, three distinct modes of death were observed: sudden death after a moderate disease process (44%), profuse hemorrhage (33%), and encephalopathy (22%). We found that these modes of death varied by age ( P = 0.04), maximum temperature ( P = 0.43), heart rate on admission ( P = 0.04), time to death from symptom onset ( P = 0.13), and duration of hospitalization ( P = 0.04). Although further study is required, our findings provide a foundation for developing treatment strategies that factor in patients with specific disease phenotypes (which often require the use of aggressive hydration). These findings provide insights into underlying pathogenic mechanisms resulting in severe EVD and suggest direction for future research and development of effective treatment options.

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          Most cited references12

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          Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients.

          During the 1995 outbreak of Ebola hemorrhagic fever in the Democratic Republic of the Congo, a series of 103 cases (one-third of the total number of cases) had clinical symptoms and signs accurately recorded by medical workers, mainly in the setting of the urban hospital in Kikwit. Clinical diagnosis was confirmed retrospectively in cases for which serum samples were available (n = 63, 61% of the cases). The disease began unspecifically with fever, asthenia, diarrhea, headaches, myalgia, arthralgia, vomiting, and abdominal pain. Early inconsistent signs and symptoms included conjunctival injection, sore throat, and rash. Overall, bleeding signs were observed in <45% of the cases. Typically, terminally ill patients presented with obtundation, anuria, shock, tachypnea, and normothermia. Late manifestations, most frequently arthralgia and ocular diseases, occurred in convalescent patients. This series is the most extensive number of cases of Ebola hemorrhagic fever observed during an outbreak.
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            Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days

            We report on an Ebola virus disease (EVD) survivor who showed Ebola virus in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia.
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              An outbreak of Ebola in Uganda.

              An outbreak of Ebola disease was reported from Gulu district, Uganda, on 8 October 2000. The outbreak was characterized by fever and haemorrhagic manifestations, and affected health workers and the general population of Rwot-Obillo, a village 14 km north of Gulu town. Later, the outbreak spread to other parts of the country including Mbarara and Masindi districts. Response measures included surveillance, community mobilization, case and logistics management. Three coordination committees were formed: National Task Force (NTF), a District Task Force (DTF) and an Interministerial Task Force (IMTF). The NTF and DTF were responsible for coordination and follow-up of implementation of activities at the national and district levels, respectively, while the IMTF provided political direction and handled sensitive issues related to stigma, trade, tourism and international relations. The international response was coordinated by the World Health Organization (WHO) under the umbrella organization of the Global Outbreak and Alert Response Network. A WHO/CDC case definition for Ebola was adapted and used to capture four categories of cases, namely, the 'alert', 'suspected', 'probable' and 'confirmed cases'. Guidelines for identification and management of cases were developed and disseminated to all persons responsible for surveillance, case management, contact tracing and Information Education Communication (IEC). For the duration of the epidemic that lasted up to 16 January 2001, a total of 425 cases with 224 deaths were reported countrywide. The case fatality rate was 53%. The attack rate (AR) was highest in women. The average AR for Gulu district was 12.6 cases/10 000 inhabitants when the contacts of all cases were considered and was 4.5 cases/10 000 if limited only to contacts of laboratory confirmed cases. The secondary AR was 2.5% when nearly 5000 contacts were followed up for 21 days. Uganda was finally declared Ebola free on 27 February 2001, 42 days after the last case was reported. The Government's role in coordination of both local and international support was vital. The NTF and the corresponding district committees harmonized implementation of a mutually agreed programme. Community mobilization using community-based resource persons and political organs, such as Members of Parliament was effective in getting information to the public. This was critical in controlling the epidemic. Past experience in epidemic management has shown that in the absence of regular provision of information to the public, there are bound to be deleterious rumours. Consequently rumour was managed by frank and open discussion of the epidemic, providing daily updates, fact sheets and press releases. Information was regularly disseminated to communities through mass media and press conferences. Thus all levels of the community spontaneously demonstrated solidarity and response to public health interventions. Even in areas of relative insecurity, rebel abductions diminished considerably.
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                Author and article information

                Journal
                Am J Trop Med Hyg
                Am. J. Trop. Med. Hyg
                tpmd
                tropmed
                The American Journal of Tropical Medicine and Hygiene
                The American Society of Tropical Medicine and Hygiene
                0002-9637
                1476-1645
                April 2018
                05 February 2018
                05 February 2018
                : 98
                : 4
                : 1186-1193
                Affiliations
                [1 ]Disaster Response Unit, Samaritan’s Purse, Boone, North Carolina;
                [2 ]Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland;
                [3 ]Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland;
                [4 ]Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom;
                [5 ]Eternal Love Winning Africa (ELWA) Hospital, Monrovia, Liberia;
                [6 ]SIM, Monrovia, Liberia
                Author notes
                [* ]Address correspondence to Linda M. Mobula, 600 N. Wolfe St, Baltimore, MD 21287. E-mail: mmobula1@ 123456jhmi.edu
                [†]

                These authors contributed equally to this work.

                Financial support: L. M. M. receives funding from the Bill & Melinda Gates Foundation. N. M. receives funding from the Wellcome Trust. C. H. receives funding from the EU FP7. L.A.C. is supported by a grant from the National Heart, Lung, and Blood Institute (K24HL83113).

                Authors’ addresses: Linda M. Mobula, Disaster Response Unit, Samaritan’s Purse, Boone, NC, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, and Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, E-mail: mmobula1@ 123456jhmi.edu . Nathalie MacDermott, Disaster Response Unit, Samaritan’s Purse, Boone, NC, and Department of Medicine, Imperial College London, London, United Kingdom, E-mail: n.macdermott@ 123456imperial.ac.uk . Clive Hoggart, Department of Medicine, Imperial College London, London, United Kingdom, E-mail: c.hoggart@ 123456imperial.ac.uk . Kent Brantly and William Plyler, Disaster Response Unit, Samaritan’s Purse, Boone, NC, E-mails: kentbrantly@ 123456gmail.com and lplyler@ 123456samaritan.org . Jerry Brown, Department of Medicine, ELWA Hospital, Monrovia, Liberia, E-mail: fahnloe@ 123456yahoo.com . Bev Kauffeldt, Disaster Response Unit, Samaritan’s Purse Canada, Calgary, Canada, E-mail: bkauffeldt@ 123456samaritan.org . Deborah Eisenhut, Department of Surgery, SIM, Monrovia, Liberia, E-mail: deborah.eisenhut@ 123456sim.org . Lisa A. Cooper, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, and Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, E-mail: lisa.cooper@ 123456jhmi.edu . John Fankhauser, Department of Family Medicine, SIM, Monrovia, Liberia, and Samaritan’s Purse, ELWA Hospital, Monrovia, Liberia, E-mail: john.fankhauser@ 123456samaritan.org .

                Article
                tpmd170090
                10.4269/ajtmh.17-0090
                5928808
                29405115
                25cb78d6-4bcd-46d5-b9b1-8251d9488ec0
                © The American Society of Tropical Medicine and Hygiene

                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.

                History
                : 06 February 2017
                : 17 November 2017
                Page count
                Pages: 8
                Categories
                Articles

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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