eMedicine Specialties > Infectious Diseases > Viral Infections

Arenaviruses: Differential Diagnoses & Workup

Author: Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Contributor Information and Disclosures

Updated: May 15, 2009

Differential Diagnoses

Meningococcemia
Plague
Yellow Fever

Other Problems to Be Considered

Lymphocytic choriomeningitis virus infection

Influenza
Enterovirus meningitis
Enteric cytopathogenic human orphan virus meningitis
Coxsackievirus meningitis
Leptospirosis

Lassa virus hemorrhagic fever

Meningococcemia
Plague
Pneumococcemia
Filovirus infection (Ebola or Marburg)
Falciparum malaria
Yellow fever
Viral hepatitis
Congo-Crimean hemorrhagic fever
Leptospirosis
Dengue

South American Arenavirus hemorrhagic fevers

Meningococcemia
Plague
Pneumococcemia
Falciparum malaria
Yellow fever
Viral hepatitis
Leptospirosis
Dengue

Workup

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 LCM virus, 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 LCM virus, 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 infection with LCM virus, 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%.

More on Arenaviruses

Overview: Arenaviruses
Differential Diagnoses & Workup: Arenaviruses
Treatment & Medication: Arenaviruses
Follow-up: Arenaviruses
References
Further Reading
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References

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  2. Whitby LR, Lee AM, Kunz S, Oldstone MB, Boger DL. Characterization of lassa virus cell entry inhibitors: Determination of the active enantiomer by asymmetric synthesis. Bioorg Med Chem Lett. May 3 2009;[Medline].

  3. Fichet-Calvet E, Rogers DJ. Risk maps of lassa Fever in west Africa. PLoS Negl Trop Dis. 2009;3(3):e388. [Medline].

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Further Reading

Clinical guidelines

Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.
Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 2003 Jun 6. 42 pages. NGC:003059

Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings 2007. Standard precautions.
Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 1996 Jan (revised 2007 Jun). 17 pages. NGC:005766

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Keywords

arenaviruses, lymphocytic choriomeningitis virus, Lassa fever virus, Machupo virus, Junin virus, Guanarito virus, viral hemorrhagic fever

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Contributor Information and Disclosures

Author

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Daniel R Lucey, MD, MPH, Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences
Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center
Disclosure: BioMerieux Honoraria Review panel membership; Cubist Honoraria Review panel membership; Pfizer Honoraria Speaking and teaching; Merck Stock dividends stock holdings

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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