Prospective study of persistence and excretion of human herpesvirus-6 in patients with exanthem subitum and their parents

Objective. To elucidate persistence of human herpesvirus-6 (HHV-6) in the blood and excretion of the virus into several body fluids of patients with exanthem subitum (ES), and to examine serologic and virologic findings of the parents caring for the patients in the family setting. Materials and Methods. During a 15-month period, 20 infants from 20 families (11 boys and 9 girls; mean age, 7.7 months; range, 4-11 months) with primary HHV-6 infection and a typical clinical course of ES, and 15 parents from the 20 families (2 males and 13 females; mean age, 28.2 years; range, 21-34 years) were enrolled in the study and examined clinically and virologically. Primary infection with HHV-6 was confirmed by isolation of the virus from peripheral blood mononuclear cells (MNCs), and seroconversion or a significant increase in the antibody titers to HHV-6 by a neutralization test. Viral persistence or excretion was examined by amplifying the viral deoxyribonucleic acid (DNA) in serially collected peripheral blood MNCs, plasma, saliva, stool, and urine samples with a nested polymerase chain reaction method. Data on saliva from the parents were compared with those of 21 age-matched controls. Results. Twenty infants with virologically confirmed ES had HHV-6 DNA in MNCs persistently during and after the disease but in plasma only in the first 5 days of ES. The viral DNA was also detected persistently or intermittently in saliva and stool during and after the disease but rarely in urine. On the other hand, the 15 parents examined of the 20 infants had no HHV-6 viremia nor viral DNA in peripheral blood MNCs and plasma except 1, but half of them excreted viral DNA in saliva during and after ES. The frequency of excretion of viral DNA into saliva was not significantly different from that of 21 control parents. Only 1 of the 15 showed a fourfold increase in antibody titers to HHV-6 after possible exposure from their children. Conclusions. After systemic replication of HHV-6 in the blood of patients with ES during the first 5 days of the disease, the virus is excreted into saliva and stool persistently or intermittently but rarely into urine. The presence of HHV-6 DNA in plasma suggested active infection with the virus. Excretion of the virus into the saliva of infants with ES and their parents suggests the source and transmission route of infection with HHV-6.