Does a positive Human Herpesvirus 6 (HHV-6) antibody titer indicate active Herpes infection in an adolescent?

Interpretation of Positive HHV-6 Antibody Titer in Adolescents

A positive HHV-6 antibody with a titer of 1:40 alone does not indicate active herpes infection in an adolescent, as this finding is consistent with past infection which is present in approximately 85-90% of the adolescent population. 1

Understanding HHV-6 Antibody Testing

HHV-6 infection is nearly universal, with approximately:

• 90% of children infected before age 1
• 100% infected by age 3
• 85% of healthy adults showing evidence of past infection 1, 2

Interpretation of Antibody Results

The presence of HHV-6 antibodies must be interpreted carefully:

1. Single positive titer (1:40):

   • Indicates past exposure to HHV-6
   • Cannot distinguish between latent (clinically silent) and active infection 3, 4
   • Expected finding in most adolescents due to childhood infection

2. Diagnostic criteria for active infection:

   • A fourfold or greater rise in antibody titer between acute and convalescent samples 1, 2
   • Detection of HHV-6 DNA in cell-free plasma by PCR (indicates active viral replication) 1
   • Viral isolation (most reliable method for confirming active infection) 4

Clinical Relevance in Adolescents

HHV-6 is primarily known for causing:

• Exanthem subitum (roseola) in infants
• Febrile seizures in young children 2, 5

In adolescents:

• Primary infection is rare (most are already infected)
• Reactivation can occur but is generally clinically insignificant in immunocompetent individuals
• Active infection is more concerning in immunocompromised patients 1, 5

Diagnostic Algorithm for Suspected Active HHV-6 Infection

1. Initial positive antibody test (like 1:40 titer):

   • Obtain convalescent serum in 2-4 weeks to look for fourfold rise in titer
   • Consider PCR testing of cell-free plasma (not whole blood) if clinically indicated

2. When to suspect active infection:

   • Unexplained fever with compatible clinical syndrome
   • Neurological manifestations (encephalitis, seizures)
   • Immunocompromised status with compatible symptoms

3. Confirmatory testing:

   • PCR of cell-free plasma (not whole blood, which may detect latent virus)
   • Viral culture (gold standard but less available)

Common Pitfalls in HHV-6 Diagnosis

1. Misinterpreting single positive antibody results as active infection (most common error)
2. Cross-reactivity with other herpesviruses, particularly during acute EBV or CMV infections 6, 7
3. PCR of whole blood can detect latent virus and lead to false positives for active infection
4. IgM detection in adults is unreliable as it can be present during reactivation 1

In conclusion, a single positive HHV-6 antibody titer of 1:40 in an adolescent most likely represents past infection and should not be interpreted as evidence of active herpes infection without additional supporting clinical and laboratory evidence.