Omnipresent infection occurring in infancy and childhood; majority of cases are caused by human herpesvirus 6 (HHV-6); may be associated with other diseases including encephalitis


  • Acute infection of infants or very young children (1)
  • Causes a high fever followed by a skin eruption as the fever resolves (1)
  • Transmission via contact with salivary secretions or respiratory droplet (1)
  • Incubation period of 9 to 10 days (1)
  • System(s) affected: skin/exocrine, metabolic, gastrointestinal, respiratory, neurologic
  • Synonym(s): roseola infantum, exanthem subitum; pseudorubella; sixth disease; 3-day fever (1)

Pediatric Considerations
A disease of infants and very young children (2)


  • Predominant age
    • HHV-6
      • Infants and very young children (<2 years old)
      • Peak age infection 6 to 9 months, rarely congenital or perinatal infection (1)
      • 95% of children have been infected with HHV-6 by 2 years of life.
    • HHV-7
      • Later childhood
      • Mean age of infection is 26 months.
      • >90% population with HHV-7 by 10 years (1)
  • Predominant sex: male = female (1)
  • No seasonal variance

Common—accounts for 20% ED visits for febrile illness among children aged 6 to 8 months


  • Peak prevalence is between 9 and 21 months.
  • Nearly 100% population carrying HHV-6 by 3 years (1)
  • Approximately 20% patients with primary HHV-6 have roseola.

Etiology and Pathophysiology

  • HHV-6 and HHV-7 (2)
  • Majority of cases (60–74%) due to HHV-6
    • HHV-6B > HHV-6A (2)
    • HHV-6A seen in children in Africa
    • HHV-6 binds to CD46 receptors on all nucleated cells (2).
  • Primary infection typically through respiratory droplets or saliva
  • Congenital infection/vertical transmission occurs in 1% of cases (1).
    • Transplacental transmission
    • Chromosomal integration (clinical significance unknown)
  • Lifelong latent or persistent asymptomatic infection occurs after primary infection (1).
    • 80–90% of population intermittently sheds HHV-6/HHV-7 in saliva (2).
    • Patients are viremic from 2 days prior to fever until defervescence and onset of rash.
    • HHV-6 latency is also implicated in CSF.

HHV-6 is integrated into the chromosomes of 0.2–3.0% of the population. This leads to vertical transmission of the virus. Clinical significance of this is unknown (1).

Risk Factors

  • Female gender
  • Having older siblings
  • At-risk adults: immunocompromised
    • Renal, liver, other solid organ, and bone marrow transplant (BMT)
    • HHV-6 reactivation can occur in 1st week posttransplant. HHV-6 viremia occurs in 30–45% of BMT within the first several weeks after transplantation.
      • Usually asymptomatic
      • Up to 82% of HHV-6 reactivation/reinfection in solid organ transplant
  • Nonrisk factors
    • Child care attendance
    • Method of delivery
    • Breastfeeding (HHV does not appear to pass through breast milk.)
    • Maternal age
    • Season

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