Human Herpesvirus 6 - HHV6

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

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 and sensitive than antibody testing
    • Use in patients with suspected meningitis – CSF sample
    • Quantitative PCR may help identify acute vs. previous disease
  • Antibody testing – traditional testing of paired acute and convalescent antibody testing samples
    • IFA, ELISA methodologies
    • Not as useful as PCR in immunocompromised diagnoses
  • Culture – not recommended due to difficulty and extended turnaround times

Differential Diagnosis

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
    • Types HHV6A and 6B
      • 6B – most common agent
      • 6A – may be responsible for neuromeningitis
  • 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 in children
    • Fever ≥40°C persisting for 3-5 days
    • Exanthem subitum (roseola infantum or sixth disease)
      • Develops on trunk and spreads to extremities
    • Diarrhea
    • Respiratory symptoms
  • Primary infection or reactivation in immunocompromised patients may cause the following (particularly in organ transplant patients)
    • Meningitis/encephalitis
      • Posttransplantation acute limbic encephalitis
    • Fulminant or chronic hepatitis, gastritis, colitis
    • Bone marrow suppression, hemophagocytosis syndrome
    • Pneumonitis
    • Organ transplant rejection
    • Arthritis
    • In transplant patient, increases risk for (Razonable, 2013)
      • Allograft dysfunction
      • CMV disease after kidney or liver transplantation
      • Fungal disease
      • Higher mortality
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.

Human Herpesvirus 6 (HHV-6A and HHV-6B) by Quantitative PCR 0060071
Method: Quantitative Polymerase Chain Reaction

Recommended Use 

Detect and quantify HHV6 subtypes A and B in immunocompromised patients

Limitations 

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 Antibody, IgG 2013423
Method: Quantitative Indirect Fluorescent Antibody

Recommended Use 

Can be used in conjunction with HHV6, IgM screen with reflex to titer for diagnosis of HHV6 disease in immunocompromised adults

Consider HHV6 (HHV6 A and HHV6 B) by PCR as an alternative, especially in cases of suspected meningitis

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

Recommended Use 

Can be used in conjunction with HHV6, IgG for diagnosis of HHV6 disease in immunocompromised adults

Consider HHV6 A and HHV6 B by PCR as an alternative, especially in cases of suspected meningitis

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

General References

Agut H, Bonnafous P, Gautheret-Dejean A. Laboratory and clinical aspects of human herpesvirus 6 infections. Clin Microbiol Rev. 2015; 28(2): 313-35. PubMed

Flamand L, Komaroff AL, Arbuckle JH, Medveczky PG, Ablashi DV. Review, part 1: Human herpesvirus-6-basic biology, diagnostic testing, and antiviral efficacy. J Med Virol. 2010; 82(9): 1560-8. PubMed

Prober CG. Human herpesvirus 6. Adv Exp Med Biol. 2011; 697: 87-90. PubMed

Razonable RR. Human herpesviruses 6, 7 and 8 in solid organ transplant recipients Am J Transplant. 2013; 13 Suppl 3: 67-77; quiz 77-8. PubMed

Tyler KL. Emerging viral infections of the central nervous system: part 1. Arch Neurol. 2009; 66(8): 939-48. PubMed

Yao K, Crawford JR, Komaroff AL, Ablashi DV, Jacobson S. Review part 2: Human herpesvirus-6 in central nervous system diseases. J Med Virol. 2010; 82(10): 1669-78. PubMed

Zamora MR. DNA viruses (CMV, EBV, and the herpesviruses). Semin Respir Crit Care Med. 2011; 32(4): 454-70. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Herrmann MG, Durtschi JD, Bromley K, Wittwer CT, Voelkerding KV. Amplicon DNA melting analysis for mutation scanning and genotyping: cross-platform comparison of instruments and dyes. Clin Chem. 2006; 52(3): 494-503. PubMed

Hymas W, Stevenson J, Taggart EW, Hillyard D. Use of lyophilized standards for the calibration of a newly developed real time PCR assay for human herpes type six (HHV6) variants A and B. J Virol Methods. 2005; 128(1-2): 143-50. PubMed

Rentz AC, Stevenson J, Hymas W, Hillyard D, Stoddard GJ, Taggart EW, Byington CL. Human herpesvirus 6 in the newborn intensive care unit. Eur J Clin Microbiol Infect Dis. 2007; 26(4): 297-9. PubMed

Medical Reviewers

Couturier, Marc Roger, PhD, D(ABMM), Medical Director, Microbial Immunology, Parasitology and Fecal Testing, and Infectious Disease Rapid Testing at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Hillyard, David R., MD, Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Professor of Clinical Pathology, Adjunct Professor of Biology, University of Utah

Last Update: September 2016