Parvovirus B19

Classification

General Characteristics

Structure

• Family Parvoviridae
• Genus Erythroparvovirus
• Nonenveloped, icosahedral capsid, and linear single-stranded DNA genome
• Very small: approximately 22–24 nm in diameter

Basic features

• Discovered in 1974
• Unable to propagate virus in cell cultures
• Unique tropism for human erythroid progenitor cells

Epidemiology and Pathogenesis

Epidemiology

• Infection occurs at all ages, but it is more common in children 3–15 years of age.
• Outbreaks commonly occur in schools and childcare settings and are more frequent between late winter and early summer.
• 90% of patients ≥ 60 years old are seropositive.

Pathogenesis

• Reservoirs:
  • Parvoviruses commonly cause disease in animals and insects.
  • B19 is the only human parvovirus pathogen.
• Transmission:
  • Infected respiratory droplets
  • Bloodborne
  • The secondary attack risk for exposed household members is 50% and for classroom contacts 25%.
• Life cycle of B19: Virus binds to host cell receptors → endocytosis → translocation of genome to host nucleus → DNA replication → RNA transcription → assembly of capsid and packaging of genome → cell lysis with release of mature virions

Pathophysiology

• Initial infection with B19 at site of entry (usually upper respiratory tract) → spreads to rapidly dividing erythroid precursor cells in bone marrow, which express a P blood antigen
• Once inside host cell, viral DNA enters nucleus → virus is cytotoxic to cells →  ↓ erythrogenesis:
  • B19 requires P blood antigen receptor to enter cell.
  • Rare individuals who lack P antigen are immune.

Diseases Caused by Parvovirus B19

Healthy patients

• Erythema infectiosum (5th disease): biphasic disease that occurs mainly in children
  • Initial phase:
    • Reflecting lytic infection
    • Marked by nonspecific flu-like symptoms
    • ↓ Hemoglobin levels
  • Immune-mediated phase:
    • Begins 2–3 weeks later
    • Characterized by rash and arthralgia: “slapped cheek rash” appears first on face → spreads to arms and legs
  • Diagnosis is usually based on the clinical presentation; if diagnosis is unclear, IgG and IgM antibody testing by ELISA may be required.
  • Management: self-limited illness that requires only supportive treatment
• Polyarthropathy syndrome in adults may not be preceded by rash.
  • Acute, symmetric joint pain
  • Usually involves feet, knees, hands, and wrists
  • No lasting joint damage
  • Self-limiting illness; resolves in 3 weeks
  • Management: symptomatic analgesia (NSAIDs) for painful joints and supportive care

Immunocompromised patients

Pure red cell aplasia:

• Cannot clear parvovirus B19 infections → leads to aplasia of RBCs and their precursors
• May not have classic signs of infection
• Causes chronic anemia
• Can be life threatening
• Diagnosis: PCR for parvovirus B19 detects infection.
• Management: 
  • Aimed at reducing immunosuppression if possible (e.g., reduce chemotherapy dosage)  
  • Intravenous immunoglobulin (IVIG) treatment 
  • In severe cases, bone marrow transplantation

Patients with hemoglobinopathies

Transient aplastic crisis may result in those with hemoglobinopathies (e.g., sickle cell disease):

• Transient reticulocytopenia (7–10 days) leads to ↓ hemoglobin levels.
• Symptoms include:
  • Fever
  • Malaise
  • Itching
  • Chills
  • Possibly arthralgia
  • Maculopapular rash
• Anemia
• Generally resolves in weeks
• Management: transfusion for hemoglobin < 6 g/dl with few reticulocytes

Pregnant women

• Hydrops fetalis:
  • Defined as abnormal accumulation of fluid in fetal soft tissue
  • Thought to be due to acute anemia caused by virus: decrease in RBC numbers and increased need for circulating volume leads to fluid retention.
  • Associated with increased risk of fetal death
  • Management: 
    • Intrauterine transfusion
    • IVIG treatment 
    • Postnatal intubation/ventilation support and fluid management
• Fetal death in utero:
  • Risk ↑ the earlier the infection is contracted during gestation.
  • Immature fetal immune system is less capable of fighting infection.
• Congenital anemia:
  • Fetal RBC turnover is faster than that in postnatal life.
  • Makes fetus more susceptible to anemia
• Parvovirus involvement is usually identified via IgG and IgM antibody testing by ELISA.

Comparison of Common Childhood Rashes