APPENDIX 2 Human Parvovirus B19 Common Human Exposure Routes: Disease Agent: • Respiratory (droplet infection) • In utero (transplacental) from acutely infected • Human parvovirus B19 (B19V) mother Disease Agent Characteristics: Likelihood of Secondary Transmission: • High in day-care centers, schools, and household • Family: Parvoviridae; Genus: Erythrovirus; Species: contacts through the respiratory route human parvovirus B19 (B19V) • Virion morphology and size: Nonenveloped, icosahe- At-Risk Populations: dral nucleocapsid symmetry, spherical particles, 23-26 nm in diameter • Children (because of lack of immunity) • Nucleic acid: Linear, negative-sense, single-stranded • Populations at most risk for serious complications by DNA, ~5.6 kb in length transfusion route include patients who have short- • Physiochemical properties: Heat resistant (56°C for ened RBC survivals, patients who are immunocom- 60 min), relatively susceptible to inactivation by pas- promised, and women who are pregnant (because of teurization at 60°C for 10 hours and to dry heat in a transmission of infection to the fetus). freeze-dried state (1.5% moisture) at 80°C for 72 hours; stable in lipid solvents; acid stable at pH 3-9; Vector Involved: inactivated by other solvents • None Disease Name: Blood Phase: • Erythema infectiosum (fifth disease) in children • Virus is tropic for erythroid progenitor cells. • Extremely high-titer viremia (up to 1014 IU/mL) Priority Level: occurs approximately 1 week following infection and • Scientific/Epidemiologic evidence regarding blood persists for approximately 5 days. safety: Blood components: Very low/Low: In the US • IgM antibody develops 10-14 days postinfection and there is a higher level of concern for immunocompro- viremia subsequently declines rapidly, usually disap- mised patients, patients with chronic anemia (sickle pearing within weeks of IgM development. cell, thalassemia), and bone marrow transplant • IgM antibody becomes undetectable after several patients. A Low to Moderate rating is reasonable for months, but IgG persists long term and is thought to pooled plasma and fractionated products based on convey immunity to reinfection. variable implementation of NAT. • Infrequently, low-level B19V DNA in association with • Public perception and/or regulatory concern regard- IgG may persist for months, but transfusion transmis- ing blood safety: Very low in the US, with the excep- sion risk has not been established. tion of patients with hemophilia; concern exists for Survival/Persistence in Blood Products: immunocompromised individuals, patients with chronic anemia (sickle cell, thalassemia), and bone • Survives in blood components and frozen plasma marrow transplant patients; Low to Moderate in products several European countries with screening programs Transmission by Blood Transfusion: • Public concern regarding disease agent: Low • Rarely from blood components (four clinical cases Background: documented in literature); actual frequency of trans- mission not assessed prospectively. • Virus discovered in 1974 • Solvent-detergent (SD) treated plasma lots in the US • Clinical associations discovered in the early 1980s with B19V DNA titers of >107 IU per mL transmitted to (aplastic anemia, fifth disease, hydrops fetalis) patients and to seronegative volunteers; units with • Global and endemic infection <104 IU per mL of virus did not transmit. • Seasonal, with greater occurrence in late winter and • Commonly transmitted from Factor VIII and Factor IX spring concentrates prior to B19V DNA testing • Periodic focal outbreaks occurring at intervals of • Very rarely transmitted from intravenous immuno- several years are typical in temperate climates. globulin (IVIG) Volume 49, August 2009 Supplement TRANSFUSION 107S APPENDIX 2 Cases/Frequency in Population: • Other clinical syndromes are treated with supportive care. • Half of the population has been infected by late ado- lescence, with 70-80% infected by adult life. Agent-Specific Screening Question(s): • Annual incidence in women of childbearing age is • No specific question is in use. 1-1.5% (may be higher in periodic outbreaks). • Not indicated because of the rarity of transfusion • Seasonal epidemics generally occur in the late spring. transmission resulting in clinical disease Incubation Period: • No sensitive or specific question is feasible. • Approximately 5-6 days to viremia, peaking at days Laboratory Test(s) Available: 8-9; slightly longer time interval to disease symptoms • No FDA-licensed blood donor screening test exists. • NAT is available and can be used in a sensitive or Likelihood of Clinical Disease: insensitive fashion. • Most cases asymptomatic ᭺ Insensitive NAT (detection limit is currently at • Erythema infectiosum (fifth disease) in children ~105 IU/mL) is used for in-process screening of • Arthopathy (acute and chronic; more common in plasma units intended for fractionation into adult females) plasma derivatives. • Transient aplastic crisis in patients with shortened ᭺ More sensitive testing (detection limit at RBC survival or hemolytic anemias ~103 IU/mL) is used in Germany to make avail- • Pure RBC aplasia or pancytopenia in immunocom- able, upon request, B19V-safe blood components promised patients for categories of patients susceptible to severe • Myocarditis rarely reported clinical outcomes of infection. • Hydrops fetalis • B19V antigen tests are available but are not sensitive enough for donor screening. Primary Disease Symptoms: • IgG and IgM antibody tests are commercially avail- • Acute biphasic illness with fever, chills, headache, and able and licensed in the US for diagnostic testing. myalgia, followed subsequently by classic fifth • In the Netherlands, donors with two positive IgG tests > disease symptoms associated with the appearance of at an interval of 6 months are considered B19V-safe, IgM antibodies (generalized erythematous eruption and their components are available for particular cat- and joint inflammation) indicative of immune egories of susceptible patients upon request. complex formation. Currently Recommended Donor Deferral Period: Severity of Clinical Disease: • No FDA Guidance or AABB Standard exists. • Prudent practice would be to defer a donor with B19V • Transient aplastic crisis can cause significant morbid- disease signs and symptoms until they resolve. ity and occasionally be fatal. • Seronegative pregnant women are at risk for adverse Impact on Blood Availability: outcomes of pregnancy including giving birth to • Agent-specific screening question(s): Not applicable infants with congenital anemia or for fetal demise due • Laboratory test(s) available: Impact could be rela- to hydrops fetalis (vertical transmission rate of 33%). tively high if sensitive NAT were used (donor DNA Mortality: positivity rates of 0.2%-0.9%) and perhaps higher in communities experiencing epidemics; low if insensi- • 5-9% risk of fetal mortality in transplacental infection tive NAT used (donor DNA positivity rates of Chronic Carriage: 0.03%-0.1%) • Chronicity is presumably rare in immunocompetent Impact on Blood Safety: patients, but virus-specific nucleic acid has been • Agent-specific screening question(s): Not applicable documented to persist in plasma for a year or longer • Laboratory test(s) available: NAT screening could at low concentrations as DNA assays have improved. decrease transmission rate by removal of viremic • More common in immunocompromised patients units. Extent of clinical disease because of transfusion who cannot make antibody transmission is unknown but thought to be very low; therefore, benefits of screening may be minimal. Treatment Available/Efficacious: However, outcomes could theoretically be severe in • Pure RBC aplasia is often effectively treated by IVIG. particular populations of transfusion recipients (e.g., • Hydrops fetalis may respond to high dose IVIG. patients with hemolytic anemias, immunosup- 108S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 pressed patients). These recipients might benefit 5. Corcoran A, Doyle S. Advances in the biology, diagno- from B19V-safe components. sis and host-pathogen interactions of parvovirus B19. J Med Microbiol 2004;53:459-75. Leukoreduction Efficacy: 6. Heegaard ED, Brown KE. Human parvovirus B19. Clin • None, because virus has tropism for RBCs and RBC Microbiol Rev 2002;15:485-505. precursors. 7. Jordan JA, Tiangco B, Kiss J, Koch W. Prevalence of human parvovirus B19 DNA in a blood donor popu- Pathogen Reduction Efficacy for Plasma Derivatives: lation. Vox Sang 1998;75:97-102. • Only partially inactivated by heat and solvent- 8. Koenigbauer UF, Eastlund T, Day JW. Clinical illness detergent treatment due to parvovirus B19 infection after infusion of • Inactivation appears to be effective if titer of plasma solvent/detergent-treated pooled plasma. Transfu- pool is below 104-105 IU per mL. sion 2000;40:1203-6. 9. Roberts PL, El Hana C, Saldana J. Inactivation of par- Other Prevention Measures: vovirus B19 and model viruses in factor VIII by dry • None heat treatment at 80°C. Transfusion 2006;46:1648-50. 10. Thomas I, Di Giambattista M, Gerard C, Mathys E, Suggested Reading: Hougardy V, Latour B, Branckaert T, Laub R. Preva- 1. Azzi A, Ciappi S, Zakvrzewska K, Morfini M, Mariani lence of human erythrovirus B19 DNA in healthy G, Mannucci PM. Human parvovirus B19 infection in Belgian blood donors and correlation with specific hemophiliacs first infused with two high-purity, antibodies against structural and non-structural viral virally attenuated factor VIII