Description

• 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)

Epidemiology

• Predominant age
  • HHV-6
    • Infants and very young children (<2 years old) (3)
    • 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 26 months
    • >90% population with HHV-7 by 10 years (1)
• Predominant sex: male = female (1)
• No seasonal variance

Incidence
Common—accounts for 20% ED visits for febrile illness among children 6 to 8 months (4)

Prevalence

• Peak prevalence is between 9 and 21 months (3).
• Nearly 100% population carrying HHV-6 by 3 years (1)
• Approximately 20% patients with primary HHV-6 have roseola (4).

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 (4).

Genetics
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 (3)
• Having older siblings (3)
• At-risk adults: immunocompromised (5)
  • Renal, liver, other solid organ, and bone marrow transplant (BMT) (3)
  • HHV-6 reactivation can occur in 1st week posttransplant (5). HHV-6 viremia occurs in 30–45% of BMT within the first several weeks after transplantation (4).
    • Usually asymptomatic (4)
    • Up to 82% of HHV-6 reactivation/reinfection in solid organ transplant (5)
• Nonrisk factors (3)
  • Child care attendance
  • Method of delivery
  • Breastfeeding (HHV does not appear to pass through breast milk.)
  • Maternal age
  • Season