Human Herpesvirus 6 - HHV6


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.


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


  • DNA virus – HHV6 and HHV7 together constitute Roseolovirus of the Herpesviridae family
    • Types HHV6A and 6B
  • 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
    • Other immunosuppressed patients

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 (rare) may involve the following
  • Primary infection or reactivation may cause the following
    • Meningitis/encephalitis
      • 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
Human Herpesvirus 6 (HHV-6A and HHV-6B) by Quantitative PCR 0060071
Method: Quantitative Polymerase Chain Reaction

Detect and quantify HHV6 subtypes A and B in immunocompromised patients

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”

Herpesvirus 6 (HHV-6) Antibodies, IgG and IgM with  Reflex to IgM Titer 2011721
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Detect acute HHV6 disease

Reflex pattern – if HHV6 IgM is detected at 1:10, an IgM titer will be added

Specimens containing IgM antibodies to cytomegalovirus and adenovirus may have falsely reactive results

Convalescent titers 10-14 days after initial testing may be necessary to confirm disease

Herpesvirus 6 (HHV-6) Antibody, IgG 0065288
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Not a preferred test for HHV6 antibody testing for acute infection; refer to HHV-6 IgG and IgM antibody panel 

Specimens containing IgM antibodies to cytomegalovirus and adenovirus may have falsely reactive results

Herpesvirus 6 Antibody, IgM Screen with Reflex to Titer by IFA 2011420
Method: Semi-Quantitative Immunofluorescence

For HHV6 antibody testing, the panel test is generally preferred; refer to HHV-6 IgG and IgM antibody panel 

Reflex pattern – if HHV6 IgM is detected at 1:10, an IgM titer will be added

Specimens containing IgM antibodies to cytomegalovirus and adenovirus may have falsely reactive results

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
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

Panel includes sodium, serum or plasma; potassium, serum or plasma; chloride, serum or plasma; carbon dioxide, serum or plasma; anion gap

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

Hepatitis Panel, Acute with Reflex to HBsAg Confirmation 0020457
Method: Qualitative Chemiluminescent Immunoassay

Order to evaluate viral etiology in patients with acute hepatitis

Not recommended for screening asymptomatic patients

Panel includes HAV IgM, HBV core antibody IgM, HBV surface antigen, HCV antibody

Reflex pattern – if results for HBsAg are repeatedly reactive with an index value between 1.00 and 50.00, then HBsAg Confirmation will be added

Lymphocytic Choriomeningitis (LCM) Virus Antibodies, IgG & IgM 2001635
Method: Semi-Quantitative Indirect Fluorescent Antibody

Identify LCM as pathogen for meningitis

Adenovirus by 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

Preferred initial serologic test to detect acute Epstein-Barr virus infectious mononucleosis

West Nile Virus Antibodies, IgG and IgM by ELISA, Serum 0050226
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Detect presence of IgG and IgM antibodies in individuals with a clinical suspicion of West Nile Virus