Condition

Roseola Infantum

Editors: Zbigniew Fedorowicz PhD, MSc, DPH, BDS, LDSRCS; Scott A. Barron MD, FAAP

Next Section >

Background Information

Description

  • acute, benign childhood infection associated with high fever and macular or morbilliform rash in immunocompetent children
    1
    ,
    2
    ,
    4

Also Called

  • exanthem subitum
  • exanthema subitum
  • roseola subitum
  • roseola infantilis
  • sixth disease

Epidemiology

Who Is Most Affected

  • infants and young children (< 3 years old)
    1
    ,
    2
    ,
    3

Incidence/Prevalence

  • infection with herpesvirus 6 and 7 (HHV-6 and HHV-7), the causative agents of roseola infantum, is widespread among the general population
    1
    ,
    2
    ,
    3
  • in studies of the general population, reported 50%-60% are seropositive for HHV-6 by age 12 months, and nearly all children are seropositive by age 3 years
    1
  • only about 20% of primary HHV-6/HHV-7 infections present as roseola, whereas the remainder of infections are asymptomatic or present as mild-to-acute febrile illness
    1
  • reported peak age of primary infection
    1
    ,
    2
  • STUDY SUMMARY
    high seropositive rates for HHV-6 and HHV-7 in children by age 2 years, and seroprevalence rates range between 85% and 100% for both viruses in general population
    COHORT STUDY: Acta Paediatr 1997 Jun;86(6):604

  • STUDY SUMMARY
    roseola diagnosed in 23% of 81 children with well-defined time of HHV-6 infection identified by viral shedding in saliva
    COHORT STUDY: N Engl J Med 2005 Feb 24;352(8):768

  • STUDY SUMMARY
    roseola diagnosed in 17% of 160 children presenting to emergency department with acute febrile illness and confirmed HHV-6 infection
    COHORT STUDY: N Engl J Med 1994 Aug 18;331(7):432

Risk Factors

  • exposure to saliva of older siblings and parents in household
    2
    • STUDY SUMMARY
      presence of older sibling in household associated with increased risk for primary HHV-6 infection
      COHORT STUDY: N Engl J Med 2005 Feb 24;352(8):768

    • STUDY SUMMARY
      infants exposed to parents' saliva when kissed associated with increased risk of HHV-6 infection before age 1 year
      COHORT STUDY: J Infect 2007 Jun;54(6):623

Etiology and Pathogenesis

Pathogen

  • human herpesvirus 6 (HHV-6) is the primary agent, but roseola is also caused by human herpesvirus 7 (HHV-7)
    1
    ,
    2
    ,
    3
    • members of Betaherpesviridae subfamily
    • large, double-stranded DNA viruses
  • HHV-6 exists as 2 subtypes, HHV-6A and HHV-6B that share 90% sequence homology, but differ epidemiologically
    1
    ,
    2
    ,
    3
    • in North American, Europe, and Asia, HHV-6B is predominant infection and HHV-6A is rare
    • HHV-6A more prevalent in Sub-Saharan region of Africa
  • at birth, infants have protection from maternal antibodies until age 4-6 months
    1
  • similar to other herpesviruses, HHV-6 and HHV-7 establish lifelong latency in host
    1
    ,
    2
    ,
    3
    ,
    4
  • HHV-6 has unique ability to integrate into human chromosomal DNA, but no conclusive, associated pathology with this phenomenon
    1
    ,
    2
    ,
    3
    • 0.2%-3% of the population reported to harbor entire genome of either HHV-6A or HHV-6B integrated at different chromosomal locations
    • integrated HHV-6 can confound association between presence of HHV-6 DNA and active disease in these individuals

Transmission

  • modes of transmission for human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) are not definitively established
    1
    ,
    2
    • presumed to be transmitted primarily via saliva of asymptomatic adults and siblings
    • can be transmitted vertically from parent with chromosomally integrated HHV-6 (ciHHV-6), 0.86% of newborns are reported to have asymptomatic infections due to ciHHV-6

Pathogenesis

  • understanding of pathogenesis is incomplete
  • human herpesvirus 6 (HHV-6) infects cells by binding complement regulator receptor CD46, a receptor found on most cells
    1
    ,
    4
  • human herpesvirus 7 (HHV-7) binds CD4 receptors to infect T lymphocytes
    1
  • HHV-6 infects a range of cell types in vitro and has been found in brain, liver, tonsillar, salivary, and endothelial host samples
    4
  • during primary infection, HHV-6/HHV-7 are detected in peripheral mononuclear blood cells
    1
  • pathogen establishes latency after primary infection
    1
    ,
    2
    ,
    3
    ,
    4
    • mechanism uncertain, but thought to be episomal similar to other herpesviruses
    • chronic, low-level infection, evidenced by viral replication, occurs in salivary glands and brain tissue
    • latency without viral replication occurs in monocytes, peripheral blood mononuclear cells, and bone marrow progenitor cells
Next Section >

Published by EBSCO Information Services. Copyright © 2025, EBSCO Information Services. All rights reserved. No part of this may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission.

EBSCO Information Services accepts no liability for advice or information given herein or errors/omissions in the text. It is merely intended as a general informational overview of the subject for the healthcare professional.

DynaMed Levels of Evidence

Quickly find and determine the quality of the evidence.

DynaMed provides easy-to-interpret Level of Evidence labels so users can quickly find and determine the quality of the best available evidence. Evidence may be labeled in one of three levels:

1Level 1 (likely reliable) Evidence
Representing research results addressing clinical outcomes and meeting an extensive set of quality criteria which minimizes bias.
There are two types of conclusions which can earn a Level 1 label: levels of evidence for conclusions derived from individual studies and levels of evidence for conclusions regarding a body of evidence.
2Level 2 (mid-level) Evidence
Representing research results addressing clinical outcomes, and using some method of scientific investigation, but not meeting the quality criteria to achieve Level 1 evidence labeling.
3Level 3 (lacking direct) Evidence
Representing reports that are not based on scientific analysis of clinical outcomes. Examples include case series, case reports, expert opinion, and conclusions extrapolated indirectly from scientific studies.

Grades of Recommendation

Guideline producers are now frequently using classification approaches for their evidence and recommendations, and these classifications are recognized and requested by guideline users. When summarizing guideline recommendations for DynaMed users, the DynaMed Editors are using the guideline-specific classifications and providing guideline classification approach when this is done.

Download the full version of Levels of Evidence