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Clinical manifestations and diagnosis of Ebola virus disease

Authors
Mike Bray, MD, MPH
Daniel S Chertow, MD, MPH
Section Editor
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH

INTRODUCTION

The family Filoviridae consists of two genera, the Ebola and Marburg viruses, which are among the most virulent pathogens of humans [1]. The Zaire species of Ebola virus, discovered in an outbreak in Zaire (the present Democratic Republic of the Congo) in 1976, is the causative agent of the 2014-2016 epidemic in West Africa, where the case fatality rate is estimated to be as high as 70 percent [2]; rates in earlier outbreaks reached 80 to 90 percent [3].

Epidemics of Ebola virus disease are generally thought to begin when an individual becomes infected through contact with the body fluids of an infected animal. Once the individual becomes ill or dies, the virus spreads to others who come into direct contact with their blood or other body fluids. On rare occasions, Ebola virus disease has resulted from accidental laboratory infections [4], and there is concern that the virus might be used as an agent of bioterrorism.

The clinical manifestations and diagnosis of Ebola virus disease will be reviewed here. The epidemiology, pathogenesis, treatment, and prevention of this disease are discussed elsewhere. (See "Epidemiology and pathogenesis of Ebola virus disease" and "Treatment and prevention of Ebola virus disease".)

CLINICAL MANIFESTATIONS

During the nearly 40 years since the first recognized Ebola outbreaks in Zaire and Sudan in 1976, a number of publications have described the clinical and laboratory features of this disease [1,5,6]. That information is now being supplemented by a rapidly increasing number of case reports and large patient series from the epidemic in West Africa that describe the clinical manifestations and disease course of Ebola virus disease among those in West Africa, as well as those treated in American and European hospitals (table 1) [7-12].

Although most features of Ebola virus disease in West Africa match earlier descriptions, two aspects appear to differ:

                    

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Literature review current through: Nov 2016. | This topic last updated: Fri Nov 18 00:00:00 GMT+00:00 2016.
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References
Top
  1. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet 2011; 377:849.
  2. WHO Ebola Response Team. Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections. N Engl J Med 2014; 371:1481.
  3. Bray M, Murphy FA. Filovirus research: knowledge expands to meet a growing threat. J Infect Dis 2007; 196 Suppl 2:S438.
  4. Emond RT, Evans B, Bowen ET, Lloyd G. A case of Ebola virus infection. Br Med J 1977; 2:541.
  5. Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis 2011; 204 Suppl 3:S810.
  6. Bwaka MA, Bonnet MJ, Calain P, et al. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis 1999; 179 Suppl 1:S1.
  7. Schieffelin JS, Shaffer JG, Goba A, et al. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med 2014; 371:2092.
  8. Chertow DS, Kleine C, Edwards JK, et al. Ebola virus disease in West Africa--clinical manifestations and management. N Engl J Med 2014; 371:2054.
  9. Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med 2015; 372:40.
  10. Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med 2014; 371:2394.
  11. Lyon GM, Mehta AK, Varkey JB, et al. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med 2014; 371:2402.
  12. Uyeki TM, Mehta AK, Davey RT Jr, et al. Clinical Management of Ebola Virus Disease in the United States and Europe. N Engl J Med 2016; 374:636.
  13. Centers for Disease Control and Prevention. Ebola virus disease information for clinicians in U.S. healthcare settings http://www.cdc.gov/vhf/ebola/hcp/clinician-information-us-healthcare-settings.html (Accessed on October 17, 2014).
  14. World Health Organziation. Travel and transport risk assessment: Recommendations for public health authorities and transport sector. http://www.who.int/ith/updates/20140421/en/ (Accessed on August 12, 2014).
  15. Peters CJ, Jahrling PB, Khan AS. Patients infected with high-hazard viruses: scientific basis for infection control. Arch Virol Suppl 1996; 11:141.
  16. Parra JM, Salmerón OJ, Velasco M. The first case of Ebola virus disease acquired outside Africa. N Engl J Med 2014; 371:2439.
  17. Ansumana R, Jacobsen KH, Sahr F, et al. Ebola in Freetown area, Sierra Leone--a case study of 581 patients. N Engl J Med 2015; 372:587.
  18. Formenty P, Hatz C, Le Guenno B, et al. Human infection due to Ebola virus, subtype Côte d'Ivoire: clinical and biologic presentation. J Infect Dis 1999; 179 Suppl 1:S48.
  19. Martini GA. Marburg agent disease: in man. Trans R Soc Trop Med Hyg 1969; 63:295.
  20. Piot P, Breman JG, Heymann DL, et al. Clinical aspects of Ebola virus infection in Yambuku area, Zaire, 1976. In: Ebola Virus Haemorrhagic Fever, Pattyn S (Ed), Elsevier/North-Holland, Amsterdam 1978. p.17.
  21. Isaacson M, Sureau P, Courteille G, Pattyn SR. Clinical aspects of Ebola virus disease at the Ngaliema Hospital, Kinshasa, Zaire. In: Ebola Virus Haemorrhagic Fever, Pattyn S (Ed), Elsevier/North-Holland, Amsterdam 1978. p.22.
  22. Jamieson DJ, Uyeki TM, Callaghan WM, et al. What obstetrician-gynecologists should know about Ebola: a perspective from the Centers for Disease Control and Prevention. Obstet Gynecol 2014; 124:1005.
  23. Chertow DS, Nath A, Suffredini AF, et al. Severe Meningoencephalitis in a Case of Ebola Virus Disease: A Case Report. Ann Intern Med 2016; 165:301.
  24. de Greslan T, Billhot M, Rousseau C, et al. Ebola Virus-Related Encephalitis. Clin Infect Dis 2016; 63:1076.
  25. Kibadi K, Mupapa K, Kuvula K, et al. Late ophthalmologic manifestations in survivors of the 1995 Ebola virus epidemic in Kikwit, Democratic Republic of the Congo. J Infect Dis 1999; 179 Suppl 1:S13.
  26. Bellan S, et al. Ebola control: effect of asymptomatic infection and acquired immunity. Lancet 2014; 384:1499.
  27. Leroy EM, Baize S, Volchkov VE, et al. Human asymptomatic Ebola infection and strong inflammatory response. Lancet 2000; 355:2210.
  28. Heffernan RT, Pambo B, Hatchett RJ, et al. Low seroprevalence of IgG antibodies to Ebola virus in an epidemic zone: Ogooué-Ivindo region, Northeastern Gabon, 1997. J Infect Dis 2005; 191:964.
  29. Rowe AK, Bertolli J, Khan AS, et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis 1999; 179 Suppl 1:S28.
  30. Dean NE, Halloran ME, Yang Y, Longini IM. Transmissibility and Pathogenicity of Ebola Virus: A Systematic Review and Meta-analysis of Household Secondary Attack Rate and Asymptomatic Infection. Clin Infect Dis 2016; 62:1277.
  31. Hunt L, Gupta-Wright A, Simms V, et al. Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study. Lancet Infect Dis 2015; 15:1292.
  32. Janvier F, Foissaud V, Cotte J, et al. Monitoring of Prognostic Laboratory Markers in Ebola Virus Disease. J Infect Dis 2016; 213:1049.
  33. Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet 2015; 385:1428.
  34. West TE, von Saint André-von Arnim A. Clinical presentation and management of severe Ebola virus disease. Ann Am Thorac Soc 2014; 11:1341.
  35. Clark DV, Kibuuka H, Millard M, et al. Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study. Lancet Infect Dis 2015; 15:905.
  36. Mahanty S, Bray M. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis 2004; 4:487.
  37. Varkey JB, Shantha JG, Crozier I, et al. Persistence of Ebola Virus in Ocular Fluid during Convalescence. N Engl J Med 2015; 372:2423.
  38. Mattia JG, Vandy MJ, Chang JC, et al. Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study. Lancet Infect Dis 2016; 16:331.
  39. Wendo C. Caring for the survivors of Uganda's Ebola epidemic one year on. Lancet 2001; 358:1350.
  40. Scott JT, Sesay FR, Massaquoi TA, et al. Post-Ebola Syndrome, Sierra Leone. Emerg Infect Dis 2016; 22:641.
  41. Jacobs M, Rodger A, Bell DJ, et al. Late Ebola virus relapse causing meningoencephalitis: a case report. Lancet 2016; 388:498.
  42. Centers for Disease Control and Prevention. Interim guidance for management of survivors of Ebola virus disease in U.S. healthcare settings. http://www.cdc.gov/vhf/ebola/healthcare-us/evaluating-patients/guidance-for-management-of-survivors-ebola.html (Accessed on March 24, 2016).
  43. Chancellor JR, Padmanabhan SP, Greenough TC, et al. Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease. Emerg Infect Dis 2016; 22:295.
  44. Akerlund E, Prescott J, Tampellini L. Shedding of Ebola Virus in an Asymptomatic Pregnant Woman. N Engl J Med 2015; 372:2467.
  45. Baggi FM, Taybi A, Kurth A, et al. Management of pregnant women infected with Ebola virus in a treatment centre in Guinea, June 2014. Euro Surveill 2014; 19.
  46. Centers for Disease Control and Prevention. Ebola virus disease: algorithm for evaluation of the returned traveler. http://www.cdc.gov/vhf/ebola/pdf/ebola-algorithm.pdf (Accessed on October 17, 2014).
  47. Centers for Disease Control and Prevention. Identify, isolate, inform: emergency department evaluation and management for patients who present with possible Ebola virus. Disease http://www.cdc.gov/vhf/ebola/hcp/ed-management-patients-possible-ebola.html (Accessed on October 27, 2014).
  48. Centers for Disease Control and Prevention. Interim Guidance for Monitoring and Movement of Persons with Ebola Virus Disease Exposure. http://www.cdc.gov/vhf/ebola/hcp/monitoring-and-movement-of-persons-with-exposure.html (Accessed on October 09, 2015).
  49. Centers for Disease Control and Prevention. Safe management of patients with Ebola virus disease (EVD) in U.S. hospitals. http://www.cdc.gov/vhf/ebola/hcp/patient-management-us-hospitals.html (Accessed on October 22, 2014).
  50. Centers for Disease Control and Prevention. When caring for suspect or confirmed patients with Ebola. http://www.cdc.gov/vhf/ebola/hcp/caring-for-ebola-suspects.html (Accessed on October 20, 2014).
  51. Wu HM, Fairley JK, Steinberg J, Kozarsky P. The potential Ebola-infected patient in the ambulatory care setting: preparing for the worst without compromising care. Ann Intern Med 2015; 162:66.
  52. The Centers for Disease Control and Prevention. Identify, isolate, inform: ambulatory care evaluation of patients with possible Ebola virus disease (Ebola). http://www.cdc.gov/vhf/ebola/pdf/ambulatory-care-evaluation-of-patients-with-possible-ebola.pdf (Accessed on November 03, 2014).
  53. Centers for Disease Control and Prevention. For general healthcare settings in West Africa: managing patient flow during triage, isolation, and care of patients with confirmed or suspected Ebola. http://www.cdc.gov/vhf/ebola/hcp/international/managing-patient-flow.html (Accessed on December 01, 2014).
  54. Centers for Disease Control and Prevention. Determining risk of Ebola transmission in healthcare and community settings. http://www.cdc.gov/vhf/ebola/hcp/international/determining-risk.html (Accessed on December 01, 2014).
  55. Isakov A, Jamison A, Miles W, Ribner B. Safe management of patients with serious communicable diseases: recent experience with Ebola virus. Ann Intern Med 2014; 161:829.
  56. Cummings KJ, Choi MJ, Esswein EJ, et al. Addressing Infection Prevention and Control in the First U.S. Community Hospital to Care for Patients With Ebola Virus Disease: Context for National Recommendations and Future Strategies. Ann Intern Med 2016.
  57. Centers for Disease Control and Prevention. Questions and answers: infection control in general healthcare settings in countries with widespread Ebola Transmission (Guinea, Liberia, and Sierra Leone) http://www.cdc.gov/vhf/ebola/hcp/qa-infection-control-general-healthcare-widespread-ebola-transmission.html (Accessed on November 03, 2014).
  58. Centers for Disease Control and Prevention. Identify, isolate, inform: emergency department evaluation and management for patients who present with possible Ebola virus. http://www.cdc.gov/vhf/ebola/pdf/ed-algorithm-management-patients-possible-ebola.pdf (Accessed on October 27, 2014).
  59. Centers for Disease Control and Prevention. Guidance on personal protective equipment (PPE) to be used by healthcare workers during management of patients with confirmed Ebola or persons under investigation (PUIs) for Ebola who are clinically unstable or have bleeding, vomiting, or diarrhea in U.S. Hospitals, including procedures for donning and doffing PPE. http://www.cdc.gov/vhf/ebola/healthcare-us/ppe/guidance.html (Accessed on August 31, 2015).
  60. Centers for Disease Control and Prevention. For US healthcare settings: donning and doffing personal protective equipment (PPE) for evaluating persons under investigation (PUIs) for Ebola who are clinically stable and do not have bleeding, vomiting, or diarrhea http://www.cdc.gov/vhf/ebola/healthcare-us/ppe/guidance-clinically-stable-puis.html (Accessed on August 31, 2015).
  61. Centers for Disease Control and Prevention. Case Definition for Ebola Virus Disease (EVD). http://www.cdc.gov/vhf/ebola/hcp/case-definition.html. (Accessed on October 28, 2014).
  62. World Heatlh Organization: Travel and transport risk assessment: interim guidance for public health authorities and the transport sector. http://www.who.int/csr/resources/publications/ebola/travel-guidance/en/ (Accessed on October 23, 2014).
  63. World Health Organization.Ebola and Marburg virus disease epidemics: preparedness, alert, control,and evaluation. http://apps.who.int/iris/bitstream/10665/130160/1/WHO_HSE_PED_CED_2014.05_eng.pdf?ua=1 (Accessed on August 14, 2014).
  64. World Health Organizaiton. Case definition recommendations for Ebola or Marburg Virus Diseases . http://who.int/csr/resources/publications/ebola/ebola-case-definition-contact-en.pdf (Accessed on August 18, 2014).
  65. Public Health Agency of Canada. Ebola clinical care guidelines: A guide for clincians in Canada. http://www.ammi.ca/media/73235/Ebola%20Clinical%20Care%20Guidelines%20v2%2028%20Oct%202014.pdf (Accessed on November 03, 2014).
  66. European Centre for Disease Prevention and Control. Critical aspects of the safe use of personal protective equipment. http://www.ecdc.europa.eu/en/publications/Publications/safe-use-of-ppe.pdf (Accessed on November 03, 2014).
  67. World Health Organization. Implementation and management of contact tracing for Ebola virus disease. http://apps.who.int/iris/bitstream/10665/185258/1/WHO_EVD_Guidance_Contact_15.1_eng.pdf?ua=1.
  68. Centers for Disease Control and Prevention. Epidemiologic risk factors to consider when evaluating a person for exposure to Ebola virus. http://www.cdc.gov/vhf/ebola/exposure/risk-factors-when-evaluating-person-for-exposure.html (Accessed on February 02, 2015).
  69. Centers for Disease Control and Prevention. Checklist for patients being evaluated for Ebola virus disease (EVD) in the United States http://www.cdc.gov/vhf/ebola/pdf/checklist-patients-evaluated-us-evd.pdf (Accessed on October 24, 2014).
  70. Centers for Disease Control. Assessment of persons under investigation having low (but not zero) risk of exposure to Ebola. http://www.cdc.gov/vhf/ebola/healthcare-us/evaluating-patients/persons-under-investigation-low-exposure-ebola.html (Accessed on July 01, 2015).
  71. Centers for Disease Control and Prevention. Interim guidance for U.S. hospital preparedness for patients with possible or confirmed Ebola virus disease: a framework for a tiered approach. http://www.cdc.gov/vhf/ebola/hcp/us-hospital-preparedness.html (Accessed on December 03, 2014).
  72. Koonin LM, Jamieson DJ, Jernigan JA, et al. Systems for rapidly detecting and treating persons with ebola virus disease--United States. MMWR Morb Mortal Wkly Rep 2015; 64:222.
  73. Centers for Disease Control and Prevention. Ebola update: updated CDC guidance monitoring symptoms and controlling movement to stop spread of Ebola. http://www.cdc.gov/media/releases/2014/fs1027-monitoring-symptoms-controlling-movement.pdf (Accessed on October 28, 2014).
  74. Centers for Disease Control and Prevention. Interim guidance for specimen collection, transport, testing, and submission for patients with suspected infection with Ebola virusvdisease http://www.cdc.gov/vhf/ebola/pdf/ebola-lab-guidance.pdf (Accessed on October 24, 2014).
  75. Considerations for discharging persons under investigation (PUI) for Ebola virus disease. http://www.cdc.gov/vhf/ebola/hcp/considerations-discharging-pui.html (Accessed on November 03, 2014).
  76. Erickson BR, Sealy TK, Flietstra T, et al. Ebola Virus Disease Diagnostics, Sierra Leone: Analysis of Real-time Reverse Transcription-Polymerase Chain Reaction Values for Clinical Blood and Oral Swab Specimens. J Infect Dis 2016; 214:S258.
  77. Su S, Wong G, Qiu X, et al. Diagnostic strategies for Ebola virus detection. Lancet Infect Dis 2016; 16:294.
  78. Gire SK, Goba A, Andersen KG, et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. http://www.sciencemag.org/content/early/2014/08/27/science.1259657.full.pdf (Accessed on October 17, 2014).
  79. World Health Organization. First antigen rapid test for Ebola through emergency assessment and eligible for procurement. http://www.who.int/medicines/ebola-treatment/1st_antigen_RT_Ebola/en/ (Accessed on September 03, 2015).
  80. Boisen ML, Cross RW, Hartnett JN, et al. Field Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection. J Infect Dis 2016; 214:S203.
  81. Cross RW, Boisen ML, Millett MM, et al. Analytical Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection. J Infect Dis 2016; 214:S210.
  82. Centers for Disease Control and Prevention. Guidance for U.S. laboratories for managing and testing routine clinical specimens when there is a concern about Ebola virus disease http://www.cdc.gov/vhf/ebola/healthcare-us/laboratories/safe-specimen-management.html (Accessed on February 02, 2015).
  83. Centers for Disease Control and Prevention. Interim guidance regarding compliance with select agent regulations for laboratories handling patient specimens that are known or suspected to contain Ebola virus. http://www.cdc.gov/vhf/ebola/hcp/select-agent-regulations.html (Accessed on September 12, 2014).
  84. Centers for Disease Control and Prevention. Interim Guidance for Specimen Collection, Transport, Testing, and Submission for Patients with Suspected Infection with Ebola Virus Disease http://www.cdc.gov/vhf/ebola/hcp/interim-guidance-specimen-collection-submission-patients-suspected-infection-ebola.html (Accessed on August 11, 2014).
  85. Centers for Disease Control and Prevention. Specimen Submission Information. http://www.cdc.gov/ncezid/dhcpp/vspb/specimens.html (Accessed on August 12, 2014).
  86. World Health Organization.How to safely collect blood samples from persons suspected to be infected with highly infectious blood-borne pathogens (e.g. Ebola). http://www.who.int/csr/resources/publications/ebola/blood-collect-en.pdf?ua=1.
  87. World Health Organization.In-Country shipment : How to safely ship human blood samples from suspected Ebola cases within a country by road, rail and sea. http://www.who.int/csr/resources/publications/ebola/blood-shipment-en.pdf?ua=1.
  88. World Health Organization.Laboratory guidance for the diagnosis of Ebola virus disease, interim recommendations. http://apps.who.int/iris/bitstream/10665/134009/1/WHO_EVD_GUIDANCE_LAB_14.1_eng.pdf (Accessed on October 03, 2014).
  89. Boggild AK, Esposito DH, Kozarsky PE, et al. Differential diagnosis of illness in travelers arriving from Sierra Leone, Liberia, or Guinea: a cross-sectional study from the GeoSentinel Surveillance Network. Ann Intern Med 2015; 162:757.
  90. Peacock G, Uyeki TM, Rasmussen SA. Ebola virus disease and children: what pediatric health care professionals need to know. JAMA Pediatr 2014; 168:1087.
  91. Centers for Disease Control and Prevention. Interim recommendations for Influenza vaccination and post-exposure hemoprophylaxis to prevent Influenza virus. Infection in People Being Actively Monitored for Potential Ebola Virus Exposure. http://www.cdc.gov/vhf/ebola/exposure/flu.html (Accessed on February 10, 2015).
  92. Takahashi S, Metcalf CJ, Ferrari MJ, et al. Reduced vaccination and the risk of measles and other childhood infections post-Ebola. Science 2015; 347:1240.
  93. The Centers for Disease Control and Prevention. Lassa fever. http://www.cdc.gov/vhf/lassa/ (Accessed on November 04, 2014).
  94. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA 1997; 278:399.
  95. Rotz LD, Khan AS, Lillibridge SR, et al. Public health assessment of potential biological terrorism agents. Emerg Infect Dis 2002; 8:225.