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:

1. Viral entry and replication:
   • Virus enters through the oropharyngeal route
   • Replicates in salivary glands and lymphoid tissue
2. Viremia:
   • Virus spreads through the bloodstream
   • Infects T lymphocytes (CD4+ cells)
3. Fever production:
   • Release of pyrogens during viral replication
   • Activation of host immune response
4. Rash development:
   • Occurs as fever subsides
   • Thought to be an immunologically mediated phenomenon
5. 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:

1. Febrile phase (3-5 days):
   • High fever (often >39°C)
   • Irritability
   • Mild upper respiratory symptoms
   • Possible febrile seizures
2. 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:

1. Polymerase Chain Reaction (PCR):
   • Most sensitive and specific method
   • Can detect viral DNA in blood, saliva, or cerebrospinal fluid
2. Serology:
   • IgM and IgG antibody detection
   • Useful for confirming recent infection or determining immune status
3. Viral culture:
   • Less commonly used due to slow growth and specialized techniques required
4. 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