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Human herpesvirus-6 infection in children. A prospective study of complications and reactivation
C B Hall1, C E Long, K C Schnabel
1Department of Pediatrics, University of Rochester School of Medicine and Dentistry, NY.
Insights
Human herpesvirus-6 (HHV-6) is a significant cause of febrile illnesses and seizures in young children, leading to emergency department visits and hospitalizations. This study highlights the prevalence and potential long-term presence of HHV-6 in this age group.
Area of Science:
- Pediatric Infectious Diseases
- Virology
- Immunology
Background:
- Human herpesvirus-6 (HHV-6) infection is nearly universal in infants and young children.
- The clinical course, complications, persistence, and reactivation patterns of HHV-6 remain incompletely understood.
Purpose of the Study:
- To investigate the incidence and clinical significance of primary HHV-6 infection in infants and young children presenting with acute illnesses.
- To determine the frequency of HHV-6 related hospitalizations and seizures.
- To assess the persistence and reactivation of HHV-6 in blood mononuclear cells post-infection.
Main Methods:
- Studied infants and children under three years with acute illnesses, including febrile and non-febrile conditions, and healthy controls.
- Utilized blood-mononuclear-cell culture, serologic testing, and polymerase chain reaction (PCR) to identify HHV-6 infection.
- Conducted follow-up studies for up to two years to monitor viral genome persistence and reactivation.
Main Results:
- Primary HHV-6 infection was identified in 9.7% of infants and young children with acute febrile illnesses, particularly those aged 6-12 months.
- HHV-6 infections were associated with 13% hospitalization rates and 13% incidence of seizures, accounting for one-third of all febrile seizures in children up to two years.
- The HHV-6 genome persisted in 66% of children one to two years post-infection, with evidence of reactivation in 16% and viral presence in 29% of healthy newborns.
Conclusions:
- HHV-6 infection is a primary driver of emergency department visits, febrile seizures, and hospitalizations in infants and young children.
- Perinatal transmission of HHV-6 can occur, potentially leading to asymptomatic, transient, or persistent neonatal infections.
- The high rate of viral genome persistence and reactivation underscores the long-term implications of HHV-6 infection in early childhood.
Background:
Infection with human herpesvirus-6 (HHV-6) is nearly universal in infancy or early childhood. However, the course of this infection, its complications, and its potential for persistence or reactivation remain unclear.
Methods:
We studied infants and children under the age of three years who presented to our emergency department with acute illnesses. Infants and young children without acute illness were studied as controls. HHV-6 infection was identified by blood-mononuclear-cell culture, serologic testing, and the polymerase chain reaction (PCR).
Results:
No primary HHV-6 infection was found among 582 infants and young children with acute nonfebrile illnesses or among 352 controls without acute illness. Of 1653 infants and young children with acute febrile illnesses, 160 (9.7 percent) had primary HHV-6 infection, as documented by viremia and seroconversion. They ranged in age from 2 weeks to 25 months; 23 percent were under the age of 6 months. HHV-6 infections accounted for 20 percent of 365 visits to the emergency department for febrile illnesses among children 6 to 12 months old. Of the 160 infants and young children with acute HHV-6 infections, 21 (13 percent) were hospitalized, and 21 had seizures. Often the seizures appeared late and were prolonged or recurrent. HHV-6 infections accounted for one third of all febrile seizures in children up to the age of two years. In follow-up studies over a period of one to two years, the HHV-6 genome persisted in blood mononuclear cells after primary infection in 37 of 56 children (66 percent). Reactivation, sometimes with febrile illnesses, was suggested by subsequent increases in antibody titers in 16 percent (30 of 187) and by PCR in 6 percent (17 of 278). No recurrent viremia was detected. Of 41 healthy newborns studied, 12 (29 percent) had the HHV-6 genome in their blood mononuclear cells; nevertheless, 6 of these newborns subsequently had primary HHV-6 infections.
Conclusions:
In infants and young children HHV-6 infection is a major cause of visits to the emergency department, febrile seizures, and hospitalizations. Perinatal transmission may occur, with possible asymptomatic, transient, or persistent neonatal infection.