Herpesvirus 6 - HHV6

Diagnosis

Indications for Testing

  • Immunocompromised patient with severe viral illness

Laboratory Testing

  • In young children, testing typically not performed; diagnosis based on clinical presentation
  • Suggest concurrent testing for other viral etiologies based on symptoms
  • PCR – more rapid than antibody testing
    • Use in patients with suspected meningitis
    • Quantitative PCR may help identify acute vs. previous disease
  • Antibody testing – traditional testing of paired acute and convalescent antibody testing samples
    • IFA, ELISA methodologies
  • Culture – not recommended due to difficulty and extended turnaround times

Differential Diagnosis

Clinical Background

Human herpesvirus 6 (HHV6), a member of the β-herpesvirus subfamily, exists as two closely related variants, HHV6 A and HHV6 B.

Epidemiology

  • Prevalence – most children >2 years are seropositive
  • Transmission

Organism

  • DNA virus – HHV6 and HHV7 together constitute Roseolovirus of the Herpesviridae family
  • Isolated in 1986 from patients with AIDS and lymphoproliferative disease
    • Virus originally named human B-lymphotropic virus; now identified as T-lymphotropic
  • Following primary infection, the virus becomes latent in lymphocytes and monocytes
    • May persist in various tissues with a low level of replication
  • Evidence suggests HHV6 may act as an opportunistic agent with reactivation found in the following
    • Immunodeficient patients – bone marrow or organ transplants
    • HIV-infected patients – as primary infection, reactivation of latent infection, or persistent infection

Clinical Presentation

  • Primary infection – fever ≥40° C persisting for 3-5 days
  • Primary infections in children – high fever followed by development of exanthem subitum, known as roseola infantum or sixth disease
    • Rash – develops on trunk and spreads to extremities
  • Primary infections in adults, though rare, may involve the following
  • Associated complications
    • Meningitis/encephalitis
      • May also occur in immunocompetent patients
      • Post transplantation acute limbic encephalitis
    • Fulminant or chronic hepatitis
    • Bone marrow suppression
    • Pneumonitis
    • Organ transplant rejection
    • Arthritis
    • Precipitation of graft-versus-host disease in transplant patient

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

May be helpful in differentiating bacterial from viral etiology

    
Electrolyte Panel 0020410
Method: Quantitative Ion-Selective Electrode/Enzymatic

Useful in assessing metabolic derangement as cause of altered consciousness

    
Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
Method: Stain/Culture/Identification

Identify organism causing meningitis

    
Glucose, CSF 0020515
Method: Enzymatic

May be helpful in differentiating bacterial from viral etiology

Usually low (<10mg/dL) in bacterial meningitis and tuberculous disease

    
Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Quantifies glucose to match CSF glucose values

    
Cell Count, CSF 0095018
Method: Cell Count/Differential

Aid in differentiating bacterial from viral meningitis

    
Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry

May be helpful in differentiating bacterial from viral etiology

    
Herpesvirus 6 (HHV6) (A and B), Quantitative PCR 0060071
Method: Quantitative Polymerase Chain Reaction

Detect and quantify HHV6 subtypes A and B

The limit of quantification for this DNA assay is 3.0 log copies/mL (1,000 copies/mL)

If no virus is detected, result will be reported as “<3.0 log copies/mL (<1,000 copies/mL)”; if assay detects the presence of the virus but is not able to accurately quantify the number of copies, result will be reported as “Not Quantified”

  
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Herpesvirus 6 (HHV-6) Antibody, IgG 0065288
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Herpesvirus 6 Antibody, IgM by IFA 2002829
Method: Immunofluorescence Assay
(Indirect Fluorescent Antibody)

Detect HHV6 IgM (indicative of acute infection)
Hepatitis Panel, Acute with Reflex to HBsAg Confirmation 0020457
Method: Qualitative Chemiluminescent Immunoassay

Order to evaluate viral etiology in patients with acute hepatitis

Panel includes HAV IgM, HBV core antibody IgM, HBV surface antigen, HCV antibody
Lymphocytic Choriomeningitis (LCM) Virus Antibodies, IgG & IgM 2001635
Method: Semi-Quantitative Indirect Fluorescent Antibody

Identify LCM as pathogen for meningitis
Arbovirus Antibodies, IgG and IgM, Serum 2001594
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Adenovirus, Qualitative PCR 2007473
Method: Qualitative Real-Time Polymerase Chain Reaction
Parvovirus B19 Antibodies, IgG and IgM 0065120
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Herpes Simplex Virus by PCR 0060041
Method: Qualitative Polymerase Chain Reaction

Preferred test for detecting herpes simplex virus (HSV) infection in CSF, neonates, or when rapid diagnostic test for suspected HSV infection is necessary

Highly sensitive and specific molecular method for detecting HSV

Failure to detect HSV does not indicate absence of infection (viral shedding is intermittent)

Does not provide information on HSV type
Heterophile Antibody (Infectious Mononucleosis) by Latex Agglutination, Qualitative 0050385
Method: Qualitative Latex Agglutination

Initial serologic test to detect acute Epstein-Barr virus infectious mononucleosis