Essentials of Diagnosis
- Infant with high fever for several days; maculopapular rash after defervescence
- Can be isolated in cultures of monocytes but takes 10-30 days and may be false negative
- Detection of specific IgG and IgM by indirect immunofluorescence are diagnostic tests of choice
- Blood or saliva PCR for HHV-6 DNA may be positive, but diagnostic significance uncertain due to intermittent excretion in asymptomatic patients
- PCR positively in CSF diagnostic of encephalitis
General Considerations
In 1986 a human herpesvirus, now called human herpesvirus type 6 (HHV-6), was identified in cultures of peripheral blood lymphocytes from patients with lymphoproliferative diseases (Box 2). The virus, which is genetically distinct but morphologically similar to other herpesviruses, replicates in lymphoid tissue, especially CD4+ T lymphocytes, and has two distinct variants, A and B.
Initially it was thought that HHV-6 would grow only in freshly isolated B-lymphocytes, and the virus was referred to as the human B-lymphotropic virus (HBLV); now it is clear that the virus is preferentially tropic for CD4+ T lymphocytes. HHV-6 establishes a latent infection in T cells but may be activated to a productive lytic infection by mitogenic stimulation. Resting lymphocytes and lymphocytes from healthy immune individuals are resistant to HHV-6 infection. In vivo, HHV6 replication is controlled by cell-mediated immune factors. It appears to be capable of reactivating in immunosuppressed patients, but its clinical significance in this situation is unknown.
Serologic studies indicate that almost all children are infected by age 2. This makes HHV-6 the most communicable of all human herpesviruses. Most adults shed HHV-6 in saliva, and close personal contact is the most likely route of spread; vertical transmission also occurs.
Clinical Findings
Exanthem subitum occurs in infants and is characterized by fever, eg, 39 °C for several days followed by defervescence and a light maculopapular rash spreading from the trunk to the extremities. CNS complications may occur with febrile seizures, meningitis and encephalitis. HHV-6 may also be a cause of febrile episodes in transplant recipients.
Diagnosis
Virus infection is best documented by seroconversion. Active virus infection can be documented by culture, antigenemia, or DNAemia, but since reactivation or is common, it is very difficult to use these tools to diagnose HHV-6 as the cause of disease. Also, culture takes 10-30 days.
Treatment
HHV-6 appears to be susceptible in vitro to ganciclovir and foscarnet and less susceptible to acyclovir (INN: Aciclovir), but no clinical data are available.
Prevention & Control
Because HHV-6 infection is ubiquitous and almost all infants excrete the virus by 2 years of age, no preventative measure is practical. No vaccine is in development, and isolation is not practical owing to ubiquitous infection.