Ebola Virus Infection Workup

Updated: Oct 13, 2017
  • Author: John W King, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Workup

Approach Considerations

The US Food and Drug Administration (FDA) has granted emergency authorization for two new tests for detecting Ebola in humans. The tests, which can detect Ebola in blood or urine samples in 1 hour, can be performed on-site in hospitals with the proper lab equipment from the tests’ manufacturer, BioFire Defense. In other tests, samples must be sent from hospitals to be run in specialized labs and require 24-48 hours to produce results. Emergency use authorizations by the FDA permit the use of unapproved medical products in dealing with life-threatening illnesses when no approved or available alternatives exist. [18]

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Laboratory Studies

Basic blood tests

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.

Studies for isolating virus

Definitive diagnosis rests on isolation of the virus by means of tissue culture or reverse-transcription polymerase chain reaction (RT-PCR) assay. However, isolation of Ebola virus in tissue culture is a high-risk procedure that can be performed safely only in a few high-containment laboratories throughout the world.

Serologic testing for antibody and antigen

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 serologic 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 virus infection. Both ELISA tests have been demonstrated to be sensitive and specific.

IgM-capture ELISA uses Zaire ebolavirus antigens grown in Vero E6 cells to detect IgM antibodies to this strain. Results become positive in experimental primates within 6 days of infection but do not remain positive for extended periods. These qualities indicate that the IgM test may be used to document acute Ebola infection.

IgG-capture ELISA uses detergent-extracted viral antigens to detect IgG anti-Ebola antibodies. It is more specific than the IFAT, and it remains positive for long periods. Accordingly, this test appears to be superior for seroprevalence investigations.

An antigen detection ELISA test is available that identifies Ebola virus antigens.

Other studies

The risks in viral isolation have led to the development of various modalities that better lend themselves to laboratories with limited containment systems. Tests used to confirm the diagnosis of Ebola virus infection include an 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.

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. [19] It is not readily available in areas where Ebola virus is endemic.

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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 virus 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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