eMedicine Specialties > Infectious Diseases > Viral Infections

Ebola Virus: Differential Diagnoses & Workup

Author: John W King, MD, Professor of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center; Director, Viral Therapeutics Clinics for Hepatitis; Consulting Staff, Department of Infectious Diseases, Overton Brook Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Apr 2, 2008

Differential Diagnoses

Typhoid Fever

Other Problems to Be Considered

Acute surgical abdomen versus abdominal signs of Ebola hemorrhagic fever
Crimean-Congo hemorrhagic fever
Note: A main concern in dealing with Ebola viral infections is the potential for human-to-human spread of virus before the correct diagnosis is made. This risk includes all medical personnel in direct contact with the patient, the patient's blood, or other body fluids or tissues.

Workup

Laboratory Studies

  • The early phase of infection is characterized by thrombocytopenia, leukopenia, and a pronounced lymphopenia. Neutrophilia develops after several days, as do elevations in aspartate aminotransferase and alanine aminotransferase. Bilirubin may be normal or slightly elevated. With the onset of anuria, blood urea nitrogen and serum creatinine increase. Terminally ill patients may develop a metabolic acidosis that may contribute to the observation that these patients often have tachypnea, which may be an attempt at compensatory hyperventilation.
  • The most commonly used test to identify infection has been the indirect immunofluorescence test. Concern over the sensitivity and utility of this test has resulted in the development of confirmatory tests. Definitive diagnosis currently rests on isolation of the virus in tissue culture and serologic testing. However, isolation of Ebola virus in tissue culture is a high-risk procedure and can be performed safely only in a few high-containment laboratories throughout the world.
  • The risks in viral isolation have led to the development of other modalities that better lend themselves to laboratories with limited containment systems. Tests used to confirm the diagnosis of Ebola include a recently developed immunohistochemical test performed on formalin-fixed postmortem skin taken from patients who have died of Ebola hemorrhagic fever. This test is safe, sensitive, and specific, and it can be used for diagnosis and surveillance.  
    • Serologic testing includes an antigen detection enzyme-linked immunosorbent assay (ELISA), an immunoglobulin M–capture ELISA using EBO-Z viral antigens harvested from infected Vero E6 cells, and an immunoglobulin G (IgG) ELISA using detergent-extracted Ebola antigens.
    • Electron microscopy has been used to identify filoviruses in tissue but has obvious limitations as a diagnostic modality in the areas where human outbreaks have occurred.8
  • Ebola hemorrhagic fever should be considered in patients with recent travel to areas where Ebola has been reported or in patients with exposure to known cases and who exhibit signs and symptoms consistent with Ebola.
  • Diagnosis usually is confirmed by serologic testing. The most commonly used test in the past has been the indirect fluorescent antibody test (IFAT). However, concern over the specificity of the IFAT has led to the development and use of other tests, including ELISA, radioimmunoassay, radioimmunoprecipitation assay, and Western blot assay.
  • Presently, an immunoglobulin M (IgM) ELISA and an IgG ELISA have been demonstrated to be both sensitive and specific.  
    • The IgM ELISA becomes positive in experimental primates within 6 days of infection but does not remain positive for extended periods. These qualities indicate the IgM test may be used to document acute Ebola infection.
    • The IgG ELISA is more specific than the IFAT, and it remains positive for long periods. Thus, the IgG ELISA for Ebola appears to be a superior test for seroprevalence investigations.

Procedures

  • Antigen-detection ELISA - Identifies Ebola antigens
  • IgM-capture ELISA - Uses EBO-Z viral antigens grown in Vero E6 cells to detect anti-EBO-Z IgM antibodies
  • IgG-capture ELISA - Uses detergent-extracted viral antigens to detect IgG anti-Ebola antibodies

Histologic Findings

Although capable of involving many tissues, the virus has a predilection for endothelial cells, hepatocytes, and mononuclear phagocytes. Viral replication is associated with extensive focal necrosis and is most severe in the liver, spleen, lymph nodes, kidney, lung, and gonads. In the liver, councilmanlike bodies of focal necrosis similar to those seen in yellow fever are prevalent. However, the focal necrosis associated with Ebola replication results in a minimal effective inflammatory response. Late in the disease, the intestinal mucosa may separate from the lamina propria and slough.

More on Ebola Virus

Overview: Ebola Virus
Differential Diagnoses & Workup: Ebola Virus
Treatment & Medication: Ebola Virus
Follow-up: Ebola Virus
Multimedia: Ebola Virus
References
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Further Reading

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Keywords

Ebola virus, viral hemorrhagic fever syndrome, Arenaviridae, Bunyaviridae, Flaviviridae, Filoviridae, EBO-Z, Marburg virus, Ebola infection, Ebola virus Zaire, Ebola virus Sudan, EBO-S, African-derived Ebola virus, Ebola virus Côte-d'Ivoire, EBO-C, Ebola virus Reston, EBO-R

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Contributor Information and Disclosures

Author

John W King, MD, Professor of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center; Director, Viral Therapeutics Clinics for Hepatitis; Consulting Staff, Department of Infectious Diseases, Overton Brook Veterans Affairs Medical Center
John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi
Disclosure: emedicine $50.00 author of chapter

Medical Editor

Martin J Wood, MD †, Former Consulting Staff, Department of Infection and Tropical Medicine, Birmingham Heartlands Hospital, UK
Martin J Wood, MD † is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, American Society for Microbiology, Infectious Diseases Society of America, International Society for Infectious Diseases, and Royal College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Thomas M Kerkering, MD, Professor of Medicine and Microbiology, Department of Internal Medicine, Division of Infectious Disease, Brody School of Medicine at East Carolina University
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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