Use of Immunoglobulin G Antibody Avidity for Differentiation of Primary Human Herpesvirus 6 and 7 Infections

Abstract

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.

Human herpesvirus-7 infection of the CNS with acute myelitis in an adult bone marrow recipient

“…Indeed, the patient was already infected with HHV-7 prior to transplant as indicated by specific IgG antibodies of high avidity. 11 In any event the finding of HHV-7 DNA in the CSF of an immunosuppressed adult is unique as there have been no previously published reports; HHV-7 DNA was not detected in the CSF of 22 cases of neurological disease after allogeneic bone marrow transplant 18 and we have not detected HHV-7 DNA in the CSF of 55 other immunocompromised adults with various neurological illnesses (unpublished).…”

“…A serum specimen taken before bone marrow transplant contained high avidity IgG to HHV-7 (titre 128) indicating prior HHV-7 infection. 11 All other screens for infectious agents were negative. The patient was seronegative for CMV antibodies before transplant and there had been no evidence of CMV infection upon regular screening of his blood for CMV DNA using a nested PCR.…”

Human Herpesvirus 6 DNA Levels in Cerebrospinal Fluid Due to Primary Infection Differ from Those Due to Chromosomal Viral Integration and Have Implications for Diagnosis of Encephalitis

“…(i) Primary HHV-6 infection. Validated tests for HHV-6 antibody avidity (42,45,48) and DNA (47) were used. As described elsewhere (41,47), the diagnosis of primary HHV-6 infection was based on seroconversion to HHV-6 immunoglobulin G between acute-and convalescent-phase sera and/or PCR to detect low level HHV-6 DNA, i.e., concentration of Ͻ3.0 log 10 copies/ml in an acute seronegative serum.…”

Precision and Accuracy of a Procedure for Detecting Recent Human Immunodeficiency Virus Infections by Calculating the Antibody Avidity Index by an Automated Immunoassay-Based Method

“…The AI is a marker of recent primary infection and is routinely used for several infectious diseases, including toxoplasmosis, rubella, and cytomegalovirus infection (1,5,9). Moreover, it has been applied for a number of other infectious agents, such as hepatitis C virus, hepatitis B virus, human herpes viruses 6 and 7, and varicella-zoster virus (6,17,18,19). The AI is based on the rationale that antibodies produced in the early phase of infection show a low avidity for the antigen.…”