Exanthem subitum (roseola infantum) with vesicular lesions.

We report a 7-month-old boy who developed vesicular lesions during the course of exanthem subitum. Human herpesvirus-6 (HHV-6) DNA was detected both in the skin lesions and in the throat, by polymerase chain reaction. IgG and IgM antibodies against HHV-6 were 1:10 and < 1:10, respectively on the tenth day of the illness, and > 1:640 and 1:10 on the twenty-second day, respectively. These results suggest that this was primary HHV-6 infection.

Human herpesvirus 7: another causal agent for roseola (exanthem subitum).

Human herpesvirus 7 (HHV-7) was isolated from peripheral blood mononuclear cells of two infants with typical exanthem subitum. The HindIII-, BamHI-, and EcoRI-digested DNA patterns of the isolated viruses were very similar to that of the prototype HHV-7 (RK strain), but different from that of human herpesvirus 6 (HHV-6). During the convalescent period of the first patient, the titer of antibody to HHV-7 rose from < 1:10 to 1:320 by an immunofluorescence antibody test, whereas the titer of antibody to HHV-6 remained < 1:10. In the second patient, who had two independent episodes of exanthem subitum during 2 months, both HHV-6 and HHV-7 were sequentially isolated; seroconversion to HHV-6 occurred during the first episode and to HHV-7 during the second episode. In addition, sera from another 15 children who had episodes of exanthem subitum were serologically tested for antibodies to HHV-6 and HHV-7 by immunofluorescence antibody test. Five of seven patients had seroconversion to HHV-7 just after having typical signs and symptoms of exanthem subitum. These results suggest that HHV-7 is one of the causative agents of exanthem subitum.

Molecular epidemiological studies of human herpesvirus 6 in families.

The mode of transmission of human herpesvirus 6 (HHV-6) was investigated by molecular epidemiological techniques in four families. HHV-6 was isolated from the peripheral blood of seven infants with exanthem subitum, including siblings, and from the saliva of two mothers. These isolates were examined for genetic relatedness by means of restriction enzymes analysis of purified DNA. While the profiles of the digestion patterns differed among families, they were very similar in a particular family. These results may suggest that HHV-6 is transmitted primarily from mother to child.

Laboratory testing in patients with morbilliform viral eruptions.

The explosion of immunologic testing capabilities over the past 20 years has enabled clinicians to accurately diagnose many conditions that previously were very difficult to identify solely on a clinical basis. Among these disorders are the viral exanthems. Infections with some of these viruses are of relatively little import (erythema infectiosum), whereas others have more significant consequences (HIV, cytomegalovirus). Clinical suspicions may be pursued more fully now, sometimes even in an office setting.

Clinical features of infants with primary human herpesvirus 6 infection (exanthem subitum, roseola infantum).

OBJECTIVE: To clarify clinical features of patients with primary human herpesvirus 6 (HHV-6) infection (roseola infantum, exanthem subitum) in a large-scale study. SUBJECTS AND METHODS: Clinical signs and symptoms were analyzed in 176 infants in whom exanthem subitum was initially suspected and primary HHV-6 infection was later confirmed. The infection was proved by isolation of the virus from blood, a significant increase in the neutralizing antibody titers to the virus, or both. RESULTS: The primary HHV-6 infection, which occurred throughout the year, was observed in 94 boys and 82 girls (mean age, 7.3 months). Fever developed in 98% (mean maximum fever, 39.4 degrees C) and lasted for 4.1 days. Macular or papular rashes appeared in 98%, on face, trunk, or both, mostly at the time of subsidence of the fever, and lasted for 3.8 days. Other clinical manifestations occurred as follows: mild diarrhea in 68%, edematous eyelids in 30%, erythematous papules in the pharynx in 65%, cough in 50%, and mild cervical lymph node swelling in 31%. Twenty-six percent had bulging of the anterior fontanelle and 8% had convulsions. CONCLUSIONS: Clinical features of patients with virologically confirmed exanthem subitum were comparable with those described before discovery of HHV-6.

Low-incidence latent infection with variant B or roseola type human herpesvirus 6 in leukocytes of healthy adults.

Nested primer-based polymerase chain reaction was employed to determine the frequency of latent infection with human herpesvirus 6 (HHV-6) among healthy adults from Bratislava, Slovak Republic. A 592-bp region, upstream from the gene encoding the putative large tegument protein of HHV-6, was amplified from DNA extracted from peripheral blood mononuclear cells (PBMC) of only one of 29 seropositive adults, suggesting that as few as 1 in 10(5) PBMC may be infected with the virus. Direct sequencing of the 592-bp fragment indicated that the virus harbored by the seropositive Slovak subject (designated B38) differed by only 3 nucleotides from an HHV-6 variant B strain (R-147) isolated from an American infant with a roseola-like illness and by 32 bases from the variant A strain GS isolated from a patient with lymphadenopathy (5.4% sequence divergence). None of these strains had a deoxyadenosine at base position 1251, when compared to the published sequence of strain GS clone pZVH14. Although this discrepancy did not affect the large tegument protein gene, it altered the predicted amino acid sequences of two putative proteins coded by open-reading frames 1 and 2 (ORF 1 and ORF 2) located upstream from this gene.

Clinical and virological analyses of 21 infants with exanthem subitum (roseola infantum) and central nervous system complications.

Twenty-one infants who had virologically confirmed exanthem subitum and central nervous system (CNS) complications were studied to elucidate the clinical features, laboratory and virological findings, and outcome. The primary infection with human herpesvirus 6 was confirmed by isolation of the virus from blood, a significant rise in the antibody titers to the virus, or both. All convulsive seizures (15 generalized and 6 focal) occurred during the pre-eruptive stage of exanthem subitum. Four infants with encephalitis/encephalopathy had more severe clinical features with abnormalities demonstrated on electroencephalograms and cerebral computed tomograms. All infants except those with encephalitis/encephalopathy recovered without any sequelae. One infant with encephalitis/encephalopathy developed epilepsy and another one died. Human herpesvirus 6 DNA amplified by the nested polymerase chain reaction method was detected in the cerebrospinal fluid of 6 infants, including 3 with encephalitis/encephalopathy, of 11 patients examined by the fifth day of the illness. These findings suggest that CNS complications including encephalitis/encephalopathy occur at the pre-eruptive stage of exanthem subitum, that human herpesvirus 6 invades the CNS in some patients, and that the outcome is not always benign.

Association of human herpesvirus 6 infection of the central nervous system with recurrence of febrile convulsions.

To determine the relationship of human herpesvirus-6 (HHV-6) infection to febrile convulsions, cerebrospinal fluid (CSF) from patients with a history of febrile convulsion were tested by polymerase chain reaction (PCR) amplification for HHV-6 DNA. HHV-6 DNA was detected in 9 of 10 samples from patients with exanthem subitum who showed neurologic symptoms. Also, 8 of 10 CSF samples from 8 patients who had three or more febrile convulsions and 1 of 7 CSF samples from patients who had a single febrile convulsion contained HHV-6 DNA. These data suggest that HHV-6 may invade the brain during the acute phase of exanthem subitum and that recurrence of febrile convulsions may be associated with reactivation of HHV-6.

Exanthema subitum and human herpesvirus 6 infection: clinical observations in fifty-seven cases.

Exanthema subitum had been speculated to be a viral disease although its pathogen is unknown. Human herpesvirus 6 (HHV-6), first isolated in 1986, was proved by Yamanishi et al. to be the causal agent of exanthema subitum. To evaluate the role of HHV-6 as the causal agent in clinically diagnosed exanthema subitum, we tested for HHV-6 antibody in 57 infants with clinical exanthema subitum and exanthema subitum-like rash without fever. Of the 53 patients with clinical exanthema subitum 43 showed seroconversion or a significant rise in antibody titer to HHV-6, 7 were seropositive without significant rise and 3 remained seronegative. The clinical manifestations of these 43 infants with serologically confirmed HHV-6 infection were consistent with the classical characteristics of exanthema subitum. The 4 patients with atypical exanthema subitum showed significant rises in antibody titer. Our results therefore show that the majority of cases with typical clinical manifestations of exanthema subitum had HHV-6 infection. Most cases with HHV-6 infection had the typical clinical course of exanthema subitum, and a few cases might show an afebrile exanthema subitum-like rash.

[Human herpesvirus 6. The etiological agent in exanthema subitum]. / Human herpesvirus 6. Det aetiologiske agens ved exanthema subitum.

Human Herpesvirus 6 (HHV-6) is the sixth human pathogenic Herpesvirus. It was isolated for the first time in 1986. The virus is isolated from blood and saliva and it is probable that it is latent in salivary glands and possibly also in blood. The most probable route of infection is droplet infection via saliva and thereafter possibly by blood. Sero-epidemiological investigations demonstrate that newly born infants are practically all passively immunised via maternal antibodies. At about the age of six months, HHV-6 antibody can be demonstrated in a minority of children. From the age of two years and until 50 years, HHV-6 antibody is present in 90-100% of the population. This is in agreement with the extensive HHV-6 infection in the age group from six months to two years. It is demonstrated that HHV-6 is the cause of exanthema subitum. It is uncertain whether HHV-6 is of pathogenetic significance for other diseases.

Human herpesvirus-6.

Human herpesvirus-6 (HHV-6), a mature T-cell lymphotropic virus, is a newly recognized member of the herpes virus family and shares limited homology with human cytomegalovirus. HHV-6 has been identified as the etiologic agent of the childhood illness exanthem subitum (roseola infantum). Widespread acquisition of this virus has been demonstrated to occur early in childhood, with fever as the most consistent manifestation of primary infection. Reactivation of latent infection has been postulated and may be associated with lymphoproliferative disorders or other diseases of immune function.

Acute obstructive respiratory diseases (ARD) and bacterial complications of ARD (pneumonia, sinusitis) in infants and children associated with human herpesvirus-6 infection.

The existence of catharreal respiratory symptoms (such as pharyngitis, tracheitis, bronchitis etc.) is established as the usual manifestation of "exanthema subitum" due to acute human herpesvirus-6 (HHV-6) infection. But so far pneumonia, purulent sinusitis, purulent otitis media and/or acute obstructive bronchitis (bronchiolitis) in infants and children have not been described. Here we report the results of observations of 2 children with bronchopneumonia/sinusitis maxillaris and severe bronchiolitis associated with an acute HHV-6 infection. Other respiratory viruses were excluded as agents causing the ARD.