Human Herpesvirus-6, Molecular Detection, PCR, Plasma
As an adjunct in the rapid diagnosis of human herpesvirus-6 infection in plasma specimens
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Herpesvirus-6 (HHV-6) is a member of the Herpesviridae family. These viruses contain DNA surrounded by a lipid envelope. Among members of this group, this virus is most closely related to cytomegalovirus (CMV) and HHV-7. As with other members of the herpesvirus group (herpes simplex virus [HSV] 1, HSV 2, varicella zoster virus [VZV], CMV, Epstein-Barr virus [EBV], HHV-7, HHV-8), HHV-6 may cause primary and reactivated infections subsequent to latent association with cells.(1) Infection with HHV-6 occurs early in childhood. Most adults (80%-90%) have been infected with this virus.
HHV-6 was first linked with exanthem subitum (roseola infantum) in 1998; since then, the virus has been associated with central nervous system disease almost exclusively in immunocompromised patients.(1) HHV-6 is commonly detected in patients posttransplantation. Clinical symptoms associated with this viral infection include febrile illness, pneumonitis, hepatitis, encephalitis, and bone marrow suppression. However, the majority of HHV-6 infections are asymptomatic.(2) The incidence of HHV-7 infection and its clinical manifestations posttransplantation are less well characterized.
HHV-6 is designated as variant A (HHV-6A) or variant B (HH6-B) depending on restriction enzyme digestion patterns and on its reaction with monoclonal antibodies. Generally, variant B has been associated with exanthem subitum, whereas variant A has been found in many immunosuppressed patients.(3)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
A positive result indicates the presence of specific DNA from human herpesvirus-6 (HHV-6) and supports the diagnosis of infection with this virus.
A negative result indicates the absence of detectable DNA from HHV-6 in the specimen, but it does not negate the presence of the virus or active or recent disease.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The sensitivity of the assay is very dependent upon the quality of the specimen submitted.
A negative test does not exclude infection with human herpesvirus-6 (HHV-6) virus. Therefore, the results obtained should be used in conjunction with clinical findings to make an accurate diagnosis.
This assay detects nucleic acid, and therefore, cannot distinguish between viable and nonviable virus. Test performance depends on viral load in the specimen and may not correlate with cell culture performed on the same specimen.
A total of 32 plasma specimens and 30 cerebrospinal fluid (CSF) specimens were spiked with human herpesvirus-6 (HHV-6) plasmid control at the limit of detection (LoD) (25-50 copies/mcL). The 62 spiked specimens were run in a blinded manner along with 28 negative (nonspiked) plasma and 30 negative (nonspiked) CSF specimens. Of the spiked specimens, 100% were positive; of the nonspiked specimens, 100% were negative.
The lower LoD of this assay is 25 to 50 DNA target copies per mcL (in plasma).
No PCR signal was obtained from extracts of 25 viral, bacterial, and fungal isolates that can cause similar symptoms as HHV-6 infection.
Interassay precision was 100% and intra-assay precision was 100%.
Although the reference range is typically "negative" for this assay, this assay may detect viremia in asymptomatic individuals. However, this assay is only to be used for patients with a clinical history and symptoms consistent with HHV-6 infection, and must be interpreted in the context of the clinical picture. This test should not be used to screen asymptomatic patients.
This is a qualitative assay and results are reported either as negative or positive for targeted HHV-6 DNA.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. De Bolle L, Naesens L, De Clercq E: Update on human herpesvirus 6 biology, clinical features, and therapy. Clin Microbiol Rev 2005 Jan;18(1):217-245
2. Dockrell DH, Paya CV: Human herpesvirus-6 and -7 in transplantation. Rev Med Virol 2001 Jan-Feb;11(1):23-36
3. Abdel-Haq NM, Asmar BI: Human herpesvirus 6 (HHV6) infection. Indian J Pediatr 2004 Jan;71(1):89-96
4. Dockrell DH, Smith TF, Paya CV: Human herpesvirus 6. Mayo Clin Proc 1999 Feb;74(2):163-170