A population-based study of primary human herpesvirus 6 infection

N Engl J Med. 2005 Feb 24;352(8):768-76. doi: 10.1056/NEJMoa042207.


Background: Serologic studies indicate that human herpesvirus 6 (HHV-6) infects 90 percent of children by two years of age. Little is known about the acquisition, virologic course, and clinical manifestations of HHV-6 infection.

Methods: We prospectively studied a cohort of 277 children from birth through the first two years of life to define the pattern of acquisition of HHV-6. The children's saliva was tested weekly for HHV-6 DNA with the use of the polymerase chain reaction. Parents maintained a daily log of signs and symptoms of illness in their children.

Results: Primary HHV-6 infection occurred in 130 children, with cumulative percentages of 40 percent by the age of 12 months and 77 percent by the age of 24 months. The peak age of acquisition was between 9 and 21 months. The acquisition of HHV-6 was associated with female sex (adjusted hazard ratio, 1.7; 95 percent confidence interval, 1.2 to 2.4) and having older siblings (adjusted hazard ratio, 2.1; 95 percent confidence interval, 1.4 to 2.9). Among 81 children with a well-defined time of acquisition of HHV-6, 93 percent had symptoms, and 38 percent were seen by a physician. None had seizures. As compared with children who had other illnesses, those with primary HHV-6 infection were more likely to have fever (P=0.003), fussiness (P=0.02), diarrhea (P=0.03), rash (P=0.003), and roseola (P=0.002) and were more likely to visit a physician (P=0.003).

Conclusions: The acquisition of HHV-6 in infancy is usually symptomatic and often results in medical evaluation. Roseola occurs in a minority of patients, and febrile seizures are infrequently associated with primary HHV-6 infection. Older siblings appear to serve as a source of HHV-6 transmission.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Viral / blood
  • Child, Preschool
  • DNA, Viral / analysis
  • Exanthema Subitum / diagnosis
  • Exanthema Subitum / epidemiology
  • Female
  • Fever / etiology
  • Herpesvirus 6, Human* / genetics
  • Herpesvirus 6, Human* / immunology
  • Herpesvirus 6, Human* / isolation & purification
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Incidence
  • Infant
  • Infant, Newborn
  • Male
  • Polymerase Chain Reaction
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Roseolovirus Infections / complications
  • Roseolovirus Infections / diagnosis
  • Roseolovirus Infections / epidemiology*
  • Saliva / virology
  • Sex Factors
  • Survival Analysis


  • Antibodies, Viral
  • DNA, Viral
  • Immunoglobulin G
  • Immunoglobulin M