Roseolavirus(HHV-6, HHV-7) Infection in Children
Introduction to Roseolavirus (HHV-6, HHV-7) Infection in Children
Roseolavirus infections, caused by Human Herpesvirus 6 (HHV-6) and Human Herpesvirus 7 (HHV-7), are common childhood illnesses. These viruses belong to the Betaherpesvirinae subfamily and are known for causing exanthem subitum, also called roseola infantum or sixth disease.
Key points:
- HHV-6 has two variants: HHV-6A and HHV-6B, with HHV-6B being the primary cause of roseola
- Primary infection usually occurs in infants and young children
- After primary infection, the virus establishes latency and can reactivate later in life
- Roseolavirus infections are generally mild but can cause complications in immunocompromised individuals
Etiology of Roseolavirus Infection
Roseolavirus infections are caused by Human Herpesvirus 6 (HHV-6) and Human Herpesvirus 7 (HHV-7).
Characteristics of HHV-6 and HHV-7:
- Enveloped, double-stranded DNA viruses
- Belong to the Betaherpesvirinae subfamily
- HHV-6 has two variants: HHV-6A and HHV-6B
- HHV-6B is the primary cause of roseola infantum
- HHV-7 can also cause roseola-like illness
Transmission:
- Primarily through saliva (horizontal transmission)
- Possible vertical transmission from mother to infant
- Incubation period: 5-15 days
Epidemiology of Roseolavirus Infection in Children
Roseolavirus infections are ubiquitous and typically occur in early childhood.
Key epidemiological features:
- Age of primary infection: 6 months to 3 years for HHV-6; slightly later for HHV-7
- Seroprevalence: >90% of adults have antibodies to HHV-6 and HHV-7
- No significant seasonal variation
- Global distribution
Risk factors:
- Young age (infants and toddlers)
- Attendance at daycare centers
- Immunocompromised status (for severe disease or reactivation)
Pathophysiology of Roseolavirus Infection
The pathophysiology of roseolavirus infection involves several stages:
- Viral entry and replication:
- Virus enters through the oropharyngeal route
- Replicates in salivary glands and lymphoid tissue
- Viremia:
- Virus spreads through the bloodstream
- Infects T lymphocytes (CD4+ cells)
- Fever production:
- Release of pyrogens during viral replication
- Activation of host immune response
- Rash development:
- Occurs as fever subsides
- Thought to be an immunologically mediated phenomenon
- Establishment of latency:
- Virus persists in various tissues, including salivary glands and brain
Immune response:
- Innate immunity: Initial control of viral replication
- Humoral immunity: Production of specific antibodies
- Cell-mediated immunity: Critical for long-term control and prevention of reactivation
Clinical Presentation of Roseolavirus Infection in Children
The classic presentation of roseolavirus infection, known as exanthem subitum or roseola infantum, typically follows a biphasic pattern:
- Febrile phase (3-5 days):
- High fever (often >39°C)
- Irritability
- Mild upper respiratory symptoms
- Possible febrile seizures
- Exanthem phase:
- Fever subsides abruptly
- Appearance of characteristic rash:
- Rose-pink, maculopapular
- Begins on trunk and spreads to neck and extremities
- Non-pruritic
- Lasts 1-2 days
Other clinical features:
- Cervical and/or occipital lymphadenopathy
- Mild gastrointestinal symptoms (diarrhea, vomiting)
- Bulging fontanelle in infants
Atypical presentations:
- Asymptomatic infection (common)
- Fever without rash
- Rash without preceding fever
Diagnosis of Roseolavirus Infection
Diagnosis of roseolavirus infection is primarily clinical, but laboratory tests can confirm the diagnosis when necessary.
Clinical diagnosis:
- Based on characteristic clinical presentation
- High fever followed by typical rash after fever subsides
Laboratory diagnosis:
- Polymerase Chain Reaction (PCR):
- Most sensitive and specific method
- Can detect viral DNA in blood, saliva, or cerebrospinal fluid
- Serology:
- IgM and IgG antibody detection
- Useful for confirming recent infection or determining immune status
- Viral culture:
- Less commonly used due to slow growth and specialized techniques required
- Antigen detection:
- Immunofluorescence assays for detecting viral antigens in infected cells
Differential diagnosis:
- Other viral exanthems (e.g., measles, rubella)
- Drug reactions
- Kawasaki disease
- Other causes of fever in young children
Treatment of Roseolavirus Infection in Children
Treatment for roseolavirus infection is primarily supportive, as the illness is generally self-limiting in immunocompetent children.
Supportive care:
- Fever management:
- Acetaminophen or ibuprofen for fever and discomfort
- Avoid aspirin due to risk of Reye's syndrome
- Adequate hydration
- Rest
- Monitoring for complications, especially febrile seizures
Antiviral therapy:
- Not routinely recommended for immunocompetent children
- May be considered in severe cases or immunocompromised patients:
- Ganciclovir or foscarnet for severe infections
- Cidofovir as an alternative
Management of complications:
- Febrile seizures: Supportive care, rarely require anticonvulsant therapy
- Encephalitis: Intensive supportive care, consider antiviral therapy
Complications of Roseolavirus Infection
While roseolavirus infections are generally mild, complications can occur, especially in certain high-risk groups.
Common complications:
- Febrile seizures (most common complication)
- Encephalitis or meningoencephalitis
- Hepatitis
Less common complications:
- Hemophagocytic lymphohistiocytosis
- Myocarditis
- Pneumonitis
- Thrombocytopenia
Complications in specific populations:
- Immunocompromised patients:
- Prolonged fever and rash
- Pneumonitis
- Encephalitis
- Bone marrow suppression
- Transplant recipients:
- Graft rejection
- Delayed engraftment
Long-term sequelae:
- Possible association with certain autoimmune diseases
- Potential role in chronic fatigue syndrome (controversial)
Prevention of Roseolavirus Infection
Prevention of roseolavirus infection is challenging due to the ubiquitous nature of the viruses and the lack of a vaccine.
General preventive measures:
- Good hygiene practices:
- Regular handwashing
- Avoiding sharing personal items (e.g., utensils, towels)
- Limiting exposure of young infants to individuals with active infection
Prevention in healthcare settings:
- Standard precautions for all patients
- Contact precautions for patients with suspected or confirmed infection
- Proper disinfection of surfaces and medical equipment
Prevention in transplant recipients:
- Screening donors and recipients for HHV-6 and HHV-7
- Prophylactic or preemptive antiviral therapy in high-risk patients
- Close monitoring for viral reactivation
Future directions:
- Ongoing research into potential vaccines
- Development of more effective antiviral therapies
Roseolavirus (HHV-6, HHV-7) Infection in Children
- What is the taxonomic classification of Human Herpesvirus 6 (HHV-6) and Human Herpesvirus 7 (HHV-7)?
Betaherpesvirinae subfamily of Herpesviridae - How many variants of HHV-6 are known?
Two (HHV-6A and HHV-6B) - Which variant of HHV-6 is most commonly associated with roseola infantum?
HHV-6B - What is the primary mode of transmission for HHV-6 and HHV-7?
Saliva (horizontal transmission) - At what age do most primary HHV-6 infections occur?
6-24 months - What is the common name for the clinical syndrome caused by primary HHV-6 infection?
Roseola infantum (exanthema subitum) - Which of the following is NOT a typical feature of roseola infantum?
Rash appearing before fever onset - What is the typical duration of fever in roseola infantum?
3-5 days - Which of the following best describes the rash in roseola infantum?
Rose-pink, maculopapular, blanching rash appearing as fever subsides - What percentage of HHV-6 infections in infants are symptomatic?
Approximately 20% - Which of the following is a potential complication of HHV-6 infection in young children?
Febrile seizures - What is the term for the presence of HHV-6 DNA integrated into human chromosomes?
Chromosomally integrated HHV-6 (ciHHV-6) - Approximately what percentage of the population has chromosomally integrated HHV-6?
1% - Which organ system is most commonly affected in severe HHV-6 infections in immunocompromised patients?
Central nervous system - What is the name of the neurological complication associated with HHV-6 reactivation in hematopoietic stem cell transplant recipients?
Post-transplant acute limbic encephalitis - Which of the following is NOT a typical manifestation of primary HHV-7 infection?
Mononucleosis-like syndrome - What is the recommended diagnostic test for acute HHV-6 infection?
PCR of blood or CSF - Which antiviral drug is most commonly used to treat severe HHV-6 infections?
Ganciclovir - What is the typical incubation period for primary HHV-6 infection?
5-15 days - Which of the following is NOT a typical laboratory finding in acute HHV-6 infection?
Leukocytosis - What is the term for the reactivation of latent HHV-6 infection?
HHV-6 reactivation - Which cell type serves as the primary reservoir for latent HHV-6?
CD4+ T lymphocytes - What is the recommended treatment for uncomplicated roseola infantum?
Supportive care (no specific antiviral treatment) - Which of the following is NOT a risk factor for severe HHV-6 infection?
Breastfeeding - What is the name of the protein expressed on the surface of HHV-6 infected cells that facilitates cell-to-cell fusion?
Glycoprotein complex gH-gL-gQ1-gQ2 - Which of the following best describes the relationship between HHV-6 and HHV-7?
HHV-7 can reactivate latent HHV-6 - What is the recommended isolation precaution for hospitalized children with suspected HHV-6 or HHV-7 infection?
Standard precautions - Which of the following is NOT a potential long-term complication of HHV-6 infection?
Chronic fatigue syndrome - What is the term for the presence of HHV-6 DNA in CSF without evidence of active CNS infection?
HHV-6 CSF positivity - Which of the following best describes the immune response to primary HHV-6 infection?
Initial IgM response followed by lifelong IgG antibodies - What is the estimated seroprevalence of HHV-6 in adults worldwide?
Over 90%
