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 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

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
  • 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

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

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 (HHV-6) Antibodies, IgG and IgM with  Reflex to IgM Titer (Temporary Referral as of 12/08/15) 2011721
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Limitations

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

Follow Up

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

Herpesvirus 6 (HHV-6) Antibody, IgG (Temporary Referral as of 12/08/15) 0065288
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Limitations

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

Limitations

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

Related Tests

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

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

Last Update: February 2016