Parvovirus B19

Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Other manifestations vary with the immunologic and hematologic status of the host due to the viral tropism for erythrocyte precursors. Diagnosis is primarily clinical and management is generally supportive.

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DNA virus classification flowchart

Identification of DNA viruses:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. Viruses with a DNA genome can be further characterized as single or double stranded. “Enveloped” viruses are covered by a thin coat of cell membrane, which is usually taken from the host cell. If the coat is absent, however, the viruses are called “naked” viruses. Some enveloped viruses translate DNA into RNA before incorporating into the genome of the host cell.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics


  • 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


  • 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.


  • 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
Human Parvovirus B19 pathogenesis

Human parvovirus B19 pathogenesis (replication cycle):
1. Virus binds to host cell.
2. Penetration/endocytosis
3. Shedding of viral capsid
4. Replication of DNA
5. Transcription of DNA into RNA
6. Translation of RNA into protein
7. Assembly into viral units
8. Cell lysis

Image by Lecturio. License: CC BY-NC-SA 4.0


  • 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
Fifth disease

“Slapped cheek rash”:
Also called erythema infectiosum, this characteristic rash is seen with parvovirus B19, or 5th disease, infections in immunocompetent individuals. The maculopapular rash is erythematous and pruritic; it starts in a malar distribution and often spreads to the extremities.

Image: “Slapped cheek” by Sandyjameslord. License: CC BY-SA 4.0

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
Giant pronormoblast in the bone marrow

Bone marrow histology during transient aplastic crisis in parvovirus B19 infection:
The image shows bone marrow cytology. Yellow arrow indicates a giant pronormoblast.

Image: “Cytology of bone marrow” by Department of Internal Medicine, Feng Yuan Hospital, No. 100, Ankang Road, Fengyuan District, Taichung City, 420, Taiwan. License: CC BY 4.0

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

Table: Comparison of common childhood rashes
NumberOther names for the diseaseEtiologySymptomsRash description
1st disease
  • Rubeola
  • Measles
  • 14-day measles
  • Morbilli
Measles virus
  • Cough, coryza, conjunctivitis
  • Koplik’s spots (blue-white spots with a red halo) on buccal membrane
  • Rash
Maculopapular rash begins on face and behind ears → spreads to trunk/extremities
2nd disease
  • Scarlet fever
  • Scarlatina
Streptococcus pyogenes
  • Strawberry tongue: coated white membrane through which swollen, red papillae protrude
  • Rash
  • Small sandpaper-feeling red bumps that begin on neck and groin → spread
  • Dark, hyperpigmented areas, especially in skin creases called Pastia’s lines
3rd disease
  • Rubella
  • German measles
  • 3-day measles
Rubella virus
  • Forscheimer spots: Pinpoint red macules and petechiae can be seen over soft palate/uvula.
  • Generalized tender lymphadenopathy
  • Rash
Discrete macules on face → spread to neck, trunk, and extremities
4th disease
  • Filatow–Dukes’ disease
  • Staphylococcal scalded skin syndrome
  • Ritter’s disease
  • Controversial existence
  • Due to Staphylococcus aureus strains that make epidermolytic (exfoliative) toxin
  • Starts with red diffuse rash
  • Nikolsky’s sign: Touching and moving finger over skin lesions while applying pressure results in skin sloughing.
  • Fluid-filled bullae or cutaneous blisters → break and desquamate
5th disease
  • Erythema infectiosum
Parvovirus (erythrovirus) B19Rash
  • Facial erythema (“slapped cheek rash”) that consist of red papules on cheeks
  • Net pattern erythema is unique → begins on extremities and extends to trunk/buttocks
6th disease
  • Exanthem subitum
  • Roseola infantum
  • Rose rash of infants
  • 3-day fever
Human herpesvirus 6B or human herpesvirus 7
  • Sudden onset of high fever
  • Rash
  • Rash begins as fever resolves (term exanthem subitum describes “surprise” of rash after fall of fever).
  • Numerous pale pink, almond-shaped macules on trunk and neck


  1. Heegaard, E., Brown, K. Human Parvovirus B19. Clin Microbiol Rev. 2002 Jul; 15(3): 485-505.
  2. Cherry, J.D., Schulte, D. J. Human Parvovirus B19. Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL, eds. Feigin & Cherry’s Textbook of Pediatric Infectious Diseases. 6th ed. Philadelphia, PA: Saunders Elsevier; 2009. Vol 2: 1902-1920.
  3. Cennimo, D. (2019). Parvovirus B19 Infection Differential Diagnoses. Emedicine. Retrieved February 3, 2021, from:
  4. Jordan, J. (2019). Clinical manifestations and diagnosis of parvovirus B19 infection. UpToDate. Retrieved February 2, 2021, from:
  5. Jordan, J. (2020) Treatment and prevention of parvovirus B19 infection. UpToDate. Retrieved February 2, 2021, from

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