Arenaviruses Workup

Updated: May 12, 2019
  • Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Laboratory Studies

The diagnosis of acute illness with human Arenavirus is made using antigen and/or antibody measurements, virus isolation, and/or genomic detection by reverse transcriptase-polymerase chain reaction (RT-PCR). For Lassa and the South American hemorrhagic fever agents, laboratory samples from suspected cases should be handled under biosafety level 4 containment until treated chemically (10% hypochlorite, Lysol, formaldehyde, or peracetic acid) or with gamma irradiation.

Antigen/antibody detection

The serodiagnosis of Arenavirus can be made rapidly and with a high degree of sensitivity.

In Lassa fever, many acutely ill patients can be found to be immunoglobulin M (IgM) antibody–positive for the Lassa virus upon presentation. Indirect fluorescent antibody (IFA) assay or enzyme-linked immunoabsorbent assay (ELISA) methodology usually determines the IgM antibody. At least 50-75% of patients are IgM antibody–positive (ie, ≥ 1:4) by day 5 and 100% positive by days 12-14.

In ill patients, Lassa virus ELISA antigenemia has been detected by experimental technology. Antigen testing of liver biopsy specimens also has been accomplished.

In the South American hemorrhagic fevers, antibodies usually develop 1-2 weeks later than in Lassa or LCMV infections, appearing during the third week of illness. IFA assay and ELISA may not easily distinguish between the different agents (ie, all members of the Tacaribe complex), but plaque-reduction neutralization antibody testing can distinguish between the different agents.

Antigen-capture ELISA of blood or tissue may offer the earliest diagnostic test for the South American hemorrhagic fevers.

For LCMV infection, IgM ELISA appears to have replaced the IFA assay and other antibody assays for serological diagnosis. Antibodies also can be assessed using CSF.

Virus isolation

Lassa virus can be isolated easily (ie, in a biosafety level 4 laboratory) in tissue culture using the E6 clone of Vero cells or in suckling mice. Infected animals represent the highest risk of exposure to laboratory personnel.

Viremia can be high grade and sustained in Lassa fever with as many as 6-8 logs of median tissue culture infectious doses per milliliter. Low titers of virus can be found in throat swabs acutely and during convalescence at low titer in the urine. Viremias greater than 3 logs are associated with higher mortality.

In the South American hemorrhagic fevers, virus also can be isolated from blood or tissue samples using tissue culture or suckling mice. Cocultivation of peripheral blood mononuclear cells with Vero cells seems to increase sensitivity.

In human LCMV infection, the virus can be isolated from the blood early in the disease, and, in those who develop meningitis, the virus also can be isolated later from CSF.

Reverse transcriptase-polymerase chain reaction detection

Limited experience exists with RT-PCR.

Care must be taken to avoid false-positive results and to use appropriate primers.

RT-PCR assays detecting fragments of the S (glycoprotein) gene have been successful, and, after RNA extraction, minimal laboratory risk exists.

Serum aminotransferase testing in Lassa fever

Admission levels greater than 150 IU/L are associated with a 50% case fatality rate, and, when combined with high viremia, the mortality rate is approximately 80%.