Virological studies were carried out on 3 to 36-month-old patients admitted to the Children's Hospital of the University of Modena with febrile syndrome from September 1990 to February 1991. Virological tests were carried out for human herpesvirus-6 (HHV-6), Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), adenoviruses, parainfluenza viruses 1, 2 and 3, respiratory syncytial virus (RSV) and influenza viruses A and B. Viral infections were confirmed in 60.7% patients: 39.6% were correlated with HHV-6, 5.4% with EBV, 5.4% with both HHV-6 and EBV, 5.4% with adenoviruses, 1.8% with HSV-1, 1.8% with CMV and 1.8% with an unidentified herpes-like lymphotropic virus. HHV-6 isolates were obtained from either peripheral blood lymphocytes (PBLs) or pharyngeal secretion of the infected children. HHV-6 infections included both primary infections (72%) and reactivations (28%). Among HHV-6 infected children, 40%, with exanthem subitum, had infections presenting serological evidence of primary infection and virus isolation from PBLs. The remaining cases of primary infection and the cases of reactivation were found in patients with febrile syndrome without rash (60%). HHV-6 isolates were obtained either from PBLs or pharyngeal secretions from these patients. Southern blot hybridization of the DNAs of 4 HHV-6 isolates showed that the circulating HHV-6 strains all appeared similar, but differed from the HHV-6 strain U1102 used as a positive control.

Most febrile convulsions (FC) in infants occur during a viral infection, particularly in children of less than 3 years of age; human herpesvirus 6 (HHV-6) has an important pathogenic role. To evaluate the link between this and other viruses and FC, a group of 65 children (mean age 18.46 months, SD +/- 9.19) with a first episode of simple FC (G1) was compared with 24 children (mean age 19.29 months, SD +/- 13.17) with a febrile syndrome but without FC (G2). Virological study showed the following infections: HHV-6 in 23/65 of G1 and in 12/24 of G2, adenoviruses (ADV) in 9/65 of G1 and in 0/24 of G2, syncytial respiratory virus (SRV) in 3/28 of G1 and in 0/2 of G2, HSV-1 in 6/65 of G1 and in 1/24 of G2, cytomegalovirus (CMV) in 2/65 of G1 and in 0/24 of G2 and HHV-7 in 1/42 of G1 and in 1/13 of G2. Children in G1, statistically compared with G2, were significantly more likely to have a family history of FC and circulating granulocytes, while IgM and alpha 2-globulin were less probable. Some cytokines (IL 1 beta, TNF beta and GM-CSF) were found in 24 children in G1 and 12 in G2; no differences were found between the two groups. In the light of our data and of the recent literature, the possibility that the cytokines may act on the nervous system cannot be excluded. Among the HHV-6-infected children, those suffering from convulsions were statistically more likely to have a family history of FC and IgM, while IgA were less likely. In G1, 57 cases were followed up over 2 years: 9 of them had a second episode of FC. Virological diagnosis at the first episode of FC revealed HHV-6 infection in 3 cases, 2 of these being due to viral reactivation. We underline the important role of HHV-6 infection in FC and postulate a relationship between family history and the immunity of the patient; this is confirmed by the loss of statistical significance in the reduction of IgM in G1 compared with G2 with no family history of FC. The reactivation of FC by HHV-6 is a possibility to be borne in mind; an increased number of cases would be needed to confirm this hypothesis.

Peripheral blood cultures from children showing symptoms of generic infectious disease have been examined for human herpesvirus-6 (HHV-6). Two HHV-6-related isolates have been obtained: one from a child for whom a clinical diagnosis of exanthema subitum has been made when a typical rash appeared, and one from a child in whom the infectious symptomatology has maintained the characters of nonspecific syndrome. All the syndrome diagnosed as exanthema subitum resulted as being associated with fresh infection by HHV-6-related virus.

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