Ebola Virus Workup

  • Author: John W King, MD; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Apr 20, 2010
 

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.
  • Definitive diagnosis rests on isolation of the virus in tissue culture or RT-PCR. 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 indirect fluorescence antibody test (IFAT) is associated with false-positive results. Concerns over the sensitivity and utility of this test have resulted in the development of confirmatory tests. In infected patients who survive long enough to develop an immune response, the immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) tests may be useful in the diagnosis of Ebola infection (see below).
  • 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 ELISA, an IgM–capture ELISA using EBO-Z viral antigens harvested from infected Vero E6 cells, and an 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.[9]
  • 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.
  • Presently, an 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.
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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
  • RT-PCR - Converts Ebola RNA sequences to DNA, which is then detected by PCR
  • Viral culture - Requires BL-4 laboratory for safety
  • Electron microscopy - Not readily available in areas where Ebola is endemic
  • Immunohistochemical Identification - Can be performed on safely prepared and stored specimens gathered in the field and sent to a central laboratory
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Histologic Findings

Although capable of involving many tissues, Ebola 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, eosinophilic globules derived from focal necrosis of hepatic cells (Councilman-like bodies), 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.

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Contributor Information and Disclosures
Author

John W King, MD  Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks 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

Coauthor(s)

Rushdah Malik, MD  Fellow, Department of Infectious Diseases, Louisiana State University Health Science Center

Rushdah Malik, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Thomas M Kerkering, MD  Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia

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.

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.

References

  1. Sanchez A, Trappier SG, Mahy BW, Peters CJ, Nichol ST. The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A. Apr 16 1996;93(8):3602-7. [Medline].

  2. Leroy EM, Baize S, Volchkov VE, Fisher-Hoch SP, Georges-Courbot MC, Lansoud-Soukate J, et al. Human asymptomatic Ebola infection and strong inflammatory response. Lancet. Jun 24 2000;355(9222):2210-5. [Medline].

  3. Amblard J, Obiang P, Edzang S, Prehaud C, Bouloy M, Guenno BL. Identification of the Ebola virus in Gabon in 1994. Lancet. Jan 18 1997;349(9046):181-2. [Medline].

  4. Swanepoel R, Leman PA, Burt FJ, Zachariades NA, Braack LE, Ksiazek TG, et al. Experimental inoculation of plants and animals with Ebola virus. Emerg Infect Dis. Oct-Dec 1996;2(4):321-5. [Medline].

  5. Johnson E, Jaax N, White J, Jahrling P. Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus. Int J Exp Pathol. Aug 1995;76(4):227-36. [Medline].

  6. Allela L, Boury O, Pouillot R, Delicat A, Yaba P, Kumulungui B, et al. Ebola virus antibody prevalence in dogs and human risk. Emerg Infect Dis. Mar 2005;11(3):385-90. [Medline].

  7. Alsop Z. Ebola outbreak in Uganda "atypical", say experts. Lancet. Dec 22 2007;370(9605):2085. [Medline].

  8. Barrette RW, Metwally SA, Rowland JM, Xu L, Zaki SR, Nichol ST, et al. Discovery of swine as a host for the Reston ebolavirus. Science. Jul 10 2009;325(5937):204-6. [Medline].

  9. Geisbert TW, Jahrling PB. Differentiation of filoviruses by electron microscopy. Virus Res. Dec 1995;39(2-3):129-50. [Medline].

  10. Hensley LE, Stevens EL, Yan SB, Geisbert JB, Macias WL, Larsen T, et al. Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. J Infect Dis. Nov 15 2007;196 Suppl 2:S390-9. [Medline].

  11. Geisbert TW, Hensley LE, Jahrling PB, Larsen T, Geisbert JB, Paragas J, et al. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet. Dec 13 2003;362(9400):1953-8. [Medline].

  12. Huggins J, Zhang ZX, Bray M. Antiviral drug therapy of filovirus infections: S-adenosylhomocysteine hydrolase inhibitors inhibit Ebola virus in vitro and in a lethal mouse model. J Infect Dis. Feb 1999;179 Suppl 1:S240-7. [Medline].

  13. Geisbert TW, Hensley LE, Jahrling PB, Larsen T, Geisbert JB, Paragas J, et al. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet. Dec 13 2003;362(9400):1953-8. [Medline].

  14. Sullivan NJ, Sanchez A, Rollin PE, Yang ZY, Nabel GJ. Development of a preventive vaccine for Ebola virus infection in primates. Nature. Nov 30 2000;408(6812):605-9. [Medline].

  15. Geisbert TW, Pushko P, Anderson K, Smith J, Davis KJ, Jahrling PB. Evaluation in nonhuman primates of vaccines against Ebola virus. Emerg Infect Dis. May 2002;8(5):503-7. [Medline].

  16. Bausch DG, Feldmann H, Geisbert TW, Bray M, Sprecher AG, Boumandouki P. Outbreaks of filovirus hemorrhagic fever: time to refocus on the patient. J Infect Dis. Nov 15 2007;196 Suppl 2:S136-41. [Medline].

  17. Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y, et al. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis. Feb 1999;179 Suppl 1:S1-7. [Medline].

  18. Dowell SF. Ebola hemorrhagic fever: why were children spared?. Pediatr Infect Dis J. Mar 1996;15(3):189-91. [Medline].

  19. Feldmann H, Klenk HD, Sanchez A. Molecular biology and evolution of filoviruses. Arch Virol Suppl. 1993;7:81-100. [Medline].

  20. Feldmann H, Slenczka W, Klenk HD. Emerging and reemerging of filoviruses. Arch Virol Suppl. 1996;11:77-100. [Medline].

  21. Formenty P, Leroy EM, Epelboin A, Libama F, Lenzi M, Sudeck H, et al. Detection of Ebola virus in oral fluid specimens during outbreaks of Ebola virus hemorrhagic fever in the Republic of Congo. Clin Infect Dis. Jun 1 2006;42(11):1521-6. [Medline].

  22. Georges-Courbot MC, Lu CY, Lansoud-Soukate J, Leroy E, Baize S. Isolation and partial molecular characterisation of a strain of Ebola virus during a recent epidemic of viral haemorrhagic fever in Gabon. Lancet. Jan 18 1997;349(9046):181. [Medline].

  23. Gonzalez JP, Pourrut X, Leroy E. Ebolavirus and other filoviruses. Curr Top Microbiol Immunol. 2007;315:363-87. [Medline].

  24. Jaax NK, Davis KJ, Geisbert TJ, Vogel P, Jaax GP, Topper M, et al. Lethal experimental infection of rhesus monkeys with Ebola-Zaire (Mayinga) virus by the oral and conjunctival route of exposure. Arch Pathol Lab Med. Feb 1996;120(2):140-55. [Medline].

  25. Jahrling PB, Geisbert TW, Dalgard DW, Johnson ED, Ksiazek TG, Hall WC, et al. Preliminary report: isolation of Ebola virus from monkeys imported to USA. Lancet. Mar 3 1990;335(8688):502-5. [Medline].

  26. Kiley MP, Bowen ET, Eddy GA, Isaacson M, Johnson KM, McCormick JB, et al. Filoviridae: a taxonomic home for Marburg and Ebola viruses?. Intervirology. 1982;18(1-2):24-32. [Medline].

  27. Legrand J, Grais RF, Boelle PY, Valleron AJ, Flahault A. Understanding the dynamics of Ebola epidemics. Epidemiol Infect. May 2007;135(4):610-21. [Medline].

  28. Onyango CO, Opoka ML, Ksiazek TG, Formenty P, Ahmed A, Tukei PM. Laboratory diagnosis of Ebola hemorrhagic fever during an outbreak in Yambio, Sudan, 2004. J Infect Dis. Nov 15 2007;196 Suppl 2:S193-8. [Medline].

  29. Peters CJ. Ebola and hantaviruses. FEMS Immunol Med Microbiol. Aug 1997;18(4):281-9. [Medline].

  30. Peters CJ, Sanchez A, Feldmann A. Filoviruses as emerging pathogens. Semin Virol. 1994;5:147-54.

  31. Peterson AT, Bauer JT, Mills JN. Ecologic and geographic distribution of filovirus disease. Emerg Infect Dis. Jan 2004;10(1):40-7. [Medline].

  32. Professional journal. Viral haemorrhagic fever in imported monkeys. Wkly Epidemiol Rec. May 8 1992;67(19):142-3. [Medline].

  33. Sanchez A, Kiley MP, Holloway BP, Auperin DD. Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res. Sep 1993;29(3):215-40. [Medline].

  34. Takada A, Kawaoka Y. Pathogenesis of Ebola virus infection: recent insights. Trends Microbiol. Jul 1998;6(7):258-9. [Medline].

  35. Volchkov VE, Volchkova VA, Slenczka W, Klenk HD, Feldmann H. Release of viral glycoproteins during Ebola virus infection. Virology. May 25 1998;245(1):110-9. [Medline].

 
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Ebola virus. Courtesy of the US Centers for Disease Control and Prevention.
Table 1. History of Ebola Virus Sudan Outbreaksa
YearLocationReported Cases, No.Deaths, No. (%)
1976Sudan284151 (53)
1976Englandb10 (0)
1979Sudan3422 (65)
2000-2001Uganda425224 (53)
2004Sudan1717 (41)
Total761414 (54.4)
Table 2. History of Ebola Virus Zaire Outbreaksa
YearLocationReported Cases, No.Deaths, No. (%)
1976Zaire318280 (88)
1977Zaire11 (100)
1994Gabon5231 (60)
1995DRC315250 (81)
Jan 1996 to Apr 1996Gabon3721 (57)
Jul 1996 to Jan 1997Gabon6045 (74)
1996South Africa (acquired in Gabon)11 (100)
Oct 2001 to Mar 2002Gabon6553 (82)
Oct 2001 to Mar 2002DRC5944 (75)
Dec 2002 to Apr 2003DRC143128 (89)
Nov 2003 to Dec 2004DRC3529 (83)
2007DRC264187 (71)
Total1,3501,070 (79.3)
Table 3. History of Ebola Virus Côte-d’Ivoire Outbreaks (No Deaths Reported)a
YearLocationReported Cases, No.
1994Côte-d’Ivoire1
1995Liberia1
Total2
Table 4. History of Ebola Virus Reston Outbreaks (No Deaths Reported)a
YearLocationProven bCases Reported, No.
1989Virginia, Texas, Pennsylvania0
1990Virginia and Texas4
1989 -1990Philippines3
1992Italy0
1990Alice, Tex0
1996Philippines0
Nov 2008Philippinesc6
Total13
Table 5. History of Ebola Virus Bundibugyo Outbreaka
YearLocationReported Cases, No.Deaths, No. (%)
Dec 2007 to Jan 2008Uganda14937 (25)
Total14937 (25)
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