Classification
DNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will either have a genome formed by DNA or RNA. Viruses with a DNA genome can be further characterized by whether that DNA is single or double stranded. If the viruses are covered by a thin coat of cell membrane (usually taken from the host cell), they are called “enveloped” viruses. If that coat is absent, however, the viruses are called “naked” viruses. Some of the enveloped viruses translate their DNA into RNA before it is incorporated into the host cell’s genome.
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
Human parvovirus B19 pathogenesis (replication cycle):
1: virus binding 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
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
- Initial phase:
- 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
“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.
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
Bone marrow histology during transient aplastic crisis in parvovirus B19 infection:
The image shows bone marrow cytology. Yellow arrow indicates a giant pronormoblast.
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
| Number | Other names for the disease | Etiology | Symptoms | Rash description |
|---|---|---|---|---|
| 1st disease |
| Measles virus |
| Maculopapular rash begins on face and behind ears → spreads to trunk/extremities |
| 2nd disease |
| Streptococcus pyogenes |
|
|
| 3rd disease |
| Rubella virus |
| Discrete macules on face → spread to neck, trunk, and extremities |
| 4th disease |
|
| Rash |
|
| 5th disease |
| Parvovirus (erythrovirus) B19 | Rash |
|
| 6th disease |
| Human herpesvirus 6B or human herpesvirus 7 |
|
|
References
- Heegaard, E., Brown, K. Human Parvovirus B19. Clin Microbiol Rev. 2002 Jul; 15(3): 485-505.
- 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.
- Cennimo, D. (2019). Parvovirus B19 Infection Differential Diagnoses. Emedicine. Retrieved February 3, 2021, from: https://emedicine.medscape.com/article/961063-differential
- Jordan, J. (2019). Clinical manifestations and diagnosis of parvovirus B19 infection. UpToDate. Retrieved February 2, 2021, from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-parvovirus-b19-infection
- Jordan, J. (2020) Treatment and prevention of parvovirus B19 infection. UpToDate. Retrieved February 2, 2021, from https://www.uptodate.com/contents/treatment-and-prevention-of-parvovirus-b19-infection
