Evaluation of the specificity and sensitivity of indirect immunofluorescence tests for IgG to human herpesviruses-6 and -7.

Sera from 118 children aged up to 4 years were tested by indirect immunofluorescence for human herpesvirus-6 and -7 (HHV-6 and HHV-7) antibodies. Antibody results were confirmed as true positives if the relevant viral DNA was detected in saliva or, in some cases of primary infection, by the finding of the relevant DNA in cerebrospinal fluid or serum. Results from samples taken from the 15 children less than 6 months old showed that HHV-6 and/or HHV-7 antibody was either absent or present at low titre suggesting persistent maternal antibody rather than true infection. The sensitivity, specificity, positive and negative predictive values of the HHV-6 IgG test were therefore based on the data from the 103 children older than 6 months and the results were 95, 84, 91 and 90%, respectively. Likewise, the sensitivity, specificity, positive and negative predictive values of the HHV-7 IgG test were 95, 76, 84 and 93%, respectively. There was limited cross-reactivity between HHV-6 and HHV-7 antibodies; where both HHV-6 and HHV-7 antibodies are detected, titres above 32 may be accepted as true positives but lower titres require confirmation by detection of the relevant viral DNA or, in the case of primary infection, by a rising antibody titre.

Use of immunoglobulin G antibody avidity for differentiation of primary human herpesvirus 6 and 7 infections.

A human herpesvirus 7 (HHV-7) indirect immunofluorescence antibody avidity test was developed and used with an existing human herpesvirus 6 (HHV-6) antibody avidity test to detect and distinguish low-avidity antibodies to HHV-6 and HHV-7 and hence the respective primary infections. With sera from 269 British children aged 0 to 179 weeks, the tests showed that most (10 of 98 serum samples [13%]) HHV-6 low-avidity antibody was found in the first year of life, whereas for HHV-7, most (18 of 101 serum samples [20%]) HHV-7 low-avidity antibody was found in the second year of life. Five children had low-avidity antibodies to both viruses. Of nine Japanese children with previously serologically proven primary HHV-6 or HHV-7 infections, eight had low-avidity antibody only to the relevant virus, but one child had low-avidity antibodies to HHV-6 and HHV-7. The avidity tests were applied to five British children and further proof of viral infection was sought by the detection of specific DNA in serum or plasma, and saliva or cerebrospinal fluid. In two children who had low-avidity antibody to HHV-7 but who were seronegative for HHV-6, only HHV-7 was found. Both viruses were detected in one child with low-avidity HHV-7 antibody and high-avidity HHV-6 antibody. In two children with low-avidity antibodies to both viruses, HHV-6 and HHV-7 DNAs were found, confirming dual primary infections and excluding antibody cross-reactivity.