Parvovirus B19 is a common, ubiquitous human pathogen. It is a small, single-stranded linear, nonenveloped DNA virus classified into three different genotypes (genotype 1, Au and Wi strains; genotype 2, LaLi and A6 strains; and genotype 3, V9 strains). Its worldwide genetic variability is low, and there is no clear correlation between genotype and distinctive clinical manifestation. Parvovirus B19 replicates most efficiently and preferentially in human erythrocyte precursors; thus, the virus is classified as a member of the Erythrovirus genus of the Parvoviridae family. Most people are infected between the ages of 5 and 15 years; by adulthood, up to 80% are seropositive (1Kelly HA Siebert D Hammond R Leydon J Kiely P Maskill W The age-specific prevalence of human parvovirus immunity in Victoria, Australia compared with other parts of the world.Epidemiol Infect. 2000; 124: 449-457Crossref PubMed Scopus (111) Google Scholar). Infection appears to confer lifelong immunity to immunocompetent hosts, but reinfection is possible in a minority of cases (2Lehmann HW Von Landenberg P Modrow S Parvovirus B19 infection and autoimmune disease.Autoimmun Rev. 2003; 2: 218-223Crossref PubMed Scopus (125) Google Scholar). It has been hypothesized that Parvovirus B19 can persist in the bone marrow and other tissues (3Corcioli F Zakrzewska K Rinieri A et al.Tissue persistence of parvovirus B19 genotypes in asymptomatic persons.J Med Virol. 2008; 80: 2005-2011Crossref PubMed Scopus (71) Google Scholar), supporting possible reactivation rather than reinfection in certain seropositive patients. Parvovirus B19 infection can be either symptomatic or asymptomatic, depending on the age, hematologic and immunologic status of the host. While most patients recollect only nonspecific flu-like symptoms, distinctive clinical entities have been associated with Parvovirus B19 infection in both immunocompetent hosts (4Young NS Brown KE Parvovirus B19.N Engl J Med. 2004; 350: 586-597Crossref PubMed Scopus (730) Google Scholar) and solid organ transplant (SOT) recipients (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar). The most common clinical manifestations of Parvovirus B19 are summarized in Table 1.Table 1Manifestations of Parvovirus B19 in immunocompetent hosts and SOT recipientsImmunocompetent hostsErythema infectiosum (fifth disease)• Develops typically in primary school• Characteristic ‘slapped cheek’ rash with or without lacy erythematous exanthem• The ‘lace-like’ rashes on the limbs and torso can occasionally occur for several months and are worse after stress or heat exposure (22Musiani M Manaresi E Gallinella G Cricca M Zerbini M Recurrent erythema in patients with long-term parvovirus B19 infection.Clin Infect Dis. 2005; 40: e117-e119Crossref Scopus (13) Google Scholar)Hydrops fetalis• Occurs in pregnant women• Severe fetal anemia which can lead to miscarriage or intrauterine death• Risk of fetal loss: ~10% if the infection occurs before the 20th week of pregnancy (especially between weeks 14 and 20); minimal thereafter (23Ergaz Z Ornoy A Parvovirus B19 in pregnancy.Reprod Toxicol. 2006; 21: 421-435Crossref PubMed Scopus (89) Google Scholar)Polyarthropathy syndrome• Predominantly in adult womenTransient aplastic crisis• Arrest of erythropoiesis with extremely low or absent reticulocyte count• In patients with shortened red cell lifespan (e.g. sickle cell disease): infection can result in severe anemia (4Young NS Brown KE Parvovirus B19.N Engl J Med. 2004; 350: 586-597Crossref PubMed Scopus (730) Google Scholar)Immunocompromised Hosts (including SOT recipients)• Approximately 2/3 of PVB19 disease occurs within 3 months after transplantation (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar)• Longer viral replication periods leading to sustained or recurrent viremia (24Kurtzman GJ Cohen BJ Field AM Oseas R Blaese RM Young NS Immune response to B19 parvovirus and an antibody defect in persistent viral infection.J Clin Invest. 1989; 84: 1114-1123Crossref PubMed Scopus (292) Google Scholar)• Fulminant or protracted course of PVB19 disease is possible• Most common manifestation: anemia• Possible role in allograft dysfunction (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar)•Other manifestations: fever, skin rash; less frequently: pancytopenia, hepatitis, myocarditis, pneumonitis, neurological disease or vasculitis (25Laurenz M Winkelmann B Roigas J Zimmering M Querfeld U Muller D Severe parvovirus B19 encephalitis after renal transplantation.Pediatr Transplant. 2006; 10: 978-981Crossref PubMed Scopus (24) Google Scholar, 26Lee PC Hung CJ Lin YJ Wang JR Jan MS Lei HY A role for chronic parvovirus B19 infection in liver dysfunction in renal transplant recipients?.Transplantation. 2002; 73: 1635-1639Crossref PubMed Scopus (14) Google Scholar, 27Liefeldt L Plentz A Klempa B et al.Recurrent high level parvovirus B19/genotype 2 viremia in a renal transplant recipient analyzed by real-time PCR for simultaneous detection of genotypes 1 to 3.J Med Virol. 2005; 75: 161-169Crossref PubMed Scopus (87) Google Scholar, 28Waldman M Kopp JB Parvovirus B19 and the kidney.Clin J Am Soc Nephrol. 2007; 2: S47-S56Crossref PubMed Scopus (93) Google Scholar)PVB19: parvovirus B 19; SOT: solid organ transplant recipients. Open table in a new tab PVB19: parvovirus B 19; SOT: solid organ transplant recipients. Although large, prospective surveillance studies are lacking, earlier studies reported an incidence of Parvovirus B19 disease of ~2% after transplantation (6Zolnourian ZR Curran MD Rima BK Coyle PV O’Neill HJ Middleton D Parvovirus B19 in kidney transplant patients.Transplantation. 2000; 69: 2198-2202Crossref PubMed Scopus (53) Google Scholar). However, more recently, it has been suggested that up to 30% of organ transplant recipients develop Parvovirus B19 viremia after transplantation and may present with clinical or subclinical infection (7Broliden K Parvovirus B19 infection in pediatric solid-organ and bone marrow transplantation.Pediatr Transplant. 2001; 5: 320-330Crossref PubMed Scopus (78) Google Scholar, 8Ki CS Kim IS Kim JW et al.Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients.Clin Transplant. 2005; 19: 751-755Crossref PubMed Scopus (45) Google Scholar). Rates may be higher in children because of their lower rates of preexisting immunity, but prospective data confirming this are lacking. The virus is primarily spread person-to-person by infected respiratory droplets in both immunocompetent and immunosuppressed patients (9Anderson MJ Higgins PG Davis LR et al.Experimental parvoviral infection in humans.J Infect Dis. 1985; 152: 257-265Crossref PubMed Scopus (620) Google Scholar) which led to nosocomial outbreaks in some transplant units (7Broliden K Parvovirus B19 infection in pediatric solid-organ and bone marrow transplantation.Pediatr Transplant. 2001; 5: 320-330Crossref PubMed Scopus (78) Google Scholar, 10Waldman M Kopp JB Parvovirus-B19-associated complications in renal transplant recipients.Nat Clin Pract Nephrol. 2007; 3: 540-550Crossref PubMed Scopus (61) Google Scholar). However, vertical transmission as well as transmission via blood products and organ transplantation has also been reported. Infected patients with normal immune system are contagious before becoming symptomatic (4–21 days after exposure), but probably not after. The secondary attack rate for exposed household members is around 50%. Typically, school-age children, day-care workers, teachers and mothers are most likely to be exposed to the virus. Individuals with Parvovirus B19 IgG antibodies are generally considered immune to repeated infection, but reinfection or reactivation may be possible in a minority of cases. Immunosuppression may lead to particularly prolonged shedding of the virus in respiratory secretions. For this reason, standard and droplet precautions are recommended for individuals caring for immunosuppressed patients with chronic Parvovirus B19 infection and those with unexplained anemia for the entire duration of their hospital stay. These patients should preferably be isolated in separate rooms to avoid cross transmission (11Siegel JD Rhinehart E Jackson M Chiarello L 2007 Guideline for Isolation Precautions: Preventing transmission of infectious agents in health care settings.Am J Infect Control. 2007; 35: S65-S164Abstract Full Text Full Text PDF PubMed Scopus (1399) Google Scholar). In SOT recipients, fever, arthralgia and rash were observed in 25%, 7% and 6% of patients with Parvovirus B19 infection, respectively. Anemia, however, was present in 99% of the patients (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar). Therefore, Parvovirus B19 infection should be specifically suspected in SOT recipients with otherwise unexplained anemia because the reported prevalence in this group of patients is relatively high (12Bertoni E Rosati A Zanazzi M et al.Aplastic anemia due to B19 parvovirus infection in cadaveric renal transplant recipients: An underestimated infectious disease in the immunocompromised host.J Nephrol. 1997; 10: 152-156PubMed Google Scholar). Parvovirus B19 infection can be diagnosed by serology or direct viral detection in clinical specimen, such as blood, bone marrow and other organs (i.e. liver, lung, kidney). In immunocompromised patients, Parvovirus B19 serology may not be reliable due to inadequate or delayed antibody-mediated immune response (7Broliden K Parvovirus B19 infection in pediatric solid-organ and bone marrow transplantation.Pediatr Transplant. 2001; 5: 320-330Crossref PubMed Scopus (78) Google Scholar, 13Kurtzman GJ Ozawa K Cohen B Hanson G Oseas R Young NS Chronic bone marrow failure due to persistent B19 parvovirus infection.N Engl J Med. 1987; 317: 287-294Crossref PubMed Scopus (394) Google Scholar). Parvovirus B19 IgM antibody was present in only 75% of SOT recipients at the time of disease onset. The detection of Parvovirus B19 IgG antibody alone is suggestive of remote infection and is uncommonly seen (7% of patients) in transplant recipients with Parvovirus B19 infection (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar). The current use of polymerase chain reaction (PCR) assays significantly improved the detection of viral DNA (14Manaresi E Gallinella G Zuffi E Bonvicini F Zerbini M Musiani M Diagnosis and quantitative evaluation of parvovirus B19 infections by real-time PCR in the clinical laboratory.J Med Virol. 2002; 67: 275-281Crossref PubMed Scopus (59) Google Scholar). However, some PCR assays are unable to detect non-B19 strains (genotypes 2 and 3) (15Baylis SA Shah N Minor PD Evaluation of different assays for the detection of parvovirus B19 DNA in human plasma.J Virol Methods. 2004; 121: 7-16Crossref PubMed Scopus (72) Google Scholar, 16Harder TC Hufnagel M Zahn K et al.New LightCycler PCR for rapid and sensitive quantification of parvovirus B19 DNA guides therapeutic decision-making in relapsing infections.J Clin Microbiol. 2001; 39: 4413-4419Crossref PubMed Scopus (42) Google Scholar). Furthermore, Parvovirus B19 DNA can be detected by PCR in the serum of some patients for long time after the acute phase of infection (17Cassinotti P Siegl G Quantitative evidence for persistence of human parvovirus B19 DNA in an immunocompetent individual.Eur J Clin Microbiol Infect Dis. 2000; 19: 886-887Crossref PubMed Scopus (65) Google Scholar). Thus, a positive PCR for Parvovirus B19 must be carefully interpreted in the context of the clinical setting and other laboratory data. However, the positive predictive value of positive PCR in an immunocompromised host with red cell aplasia is high. Bone marrow examination with in situ hybridization or immunohistochemical staining is very helpful in establishing the diagnosis when the clinical presentation is strongly suggestive of Parvovirus B19 infection but the blood PCR and serology are negative (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar). Typical bone marrow findings include overall hypercellularity and the presence of giant pronormoblasts with finely granulated cytoplasm and glassy intranuclear inclusions with a clear central halo (lantern cells), and absent late normoblasts. Recommendations: 1Parvovirus B19 infection should be suspected in SOT recipients with(a)otherwise-unexplained anemia(b)Pancytopenia(c)clinical syndromes including(i)Fever, arthralgia or rash(ii)Organ-specific disease such as hepatitis, myocarditis, pneumonitis, neurological disease or vasculitis (III).2.The initial work-up for possible Parvovirus B19 infection should include Parvovirus B19 serology (IgG and IgM) and serum/whole blood Parvovirus B19 PCR (III).3.Bone marrow examination should be considered when Parvovirus B19 infection is strongly suspected and the serology and serum PCR results are negative. In addition, in situ hybridization or immunohistochemical staining should be performed (III). Antiviral drugs are not available for the treatment of Parvovirus B19 infection. However, intravenous immunoglobulin (IVIG) has been shown to be beneficial in a large number of SOT recipients with Parvovirus B19 infection (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar, 18Bergen GA Sakalosky PE Sinnott JT Transient aplastic anemia caused by parvovirus B19 infection in a heart transplant recipient.J Heart Lung Transplant. 1996; 15: 843-845PubMed Google Scholar). On the other hand some patients have resolution of infection without IVIG therapy (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar). In addition, the optimal dosing regimen and duration of IVIG therapy for Parvovirus B19 infection has not been established. Most patients are treated with 400 mg/kg day for 5 days, even though a much higher dose has been used. In one review, the rate of relapse was not different among transplant recipients who received a total dose of ≤2 g/kg or >2 g/kg (5Eid AJ Brown RA Patel R Razonable RR Parvovirus B19 infection after transplantation: a review of 98 cases.Clin Infect Dis. 2006; 43: 40-48Crossref PubMed Scopus (163) Google Scholar). Unfortunately, in the same case series up to 28% of SOT recipients experienced relapse after receiving IVIG. The value of PCR use to monitor the response to therapy is not known, especially since persistent viremia for months despite adequate clinical response to therapy is not uncommon (19Kumar J Shaver MJ Abul-Ezz S Long-term remission of recurrent parvovirus-B associated anemia in a renal transplant recipient induced by treatment with immunoglobulin and positive seroconversion.Transpl Infect Dis. 2005; 7: 30-33Crossref PubMed Scopus (25) Google Scholar). Therefore, it may be reasonable to simply follow serial hemoglobin measurement and consider obtaining Parvovirus B19 PCR in case of recurrence of anemia. Patients with recurrence of Parvovirus B19 infection have been successfully treated with additional courses of IVIG (19Kumar J Shaver MJ Abul-Ezz S Long-term remission of recurrent parvovirus-B associated anemia in a renal transplant recipient induced by treatment with immunoglobulin and positive seroconversion.Transpl Infect Dis. 2005; 7: 30-33Crossref PubMed Scopus (25) Google Scholar). The side effects of IVIG treatment may include fever, chills, headache, myalgias, nausea, hypertension, chest pain and renal failure. A reduction in immunosuppression has been suggested to contribute to the resolution of infection; however, the timing of such an intervention (i.e. prior to or after IVIG therapy) and the degree of dose reduction for specific agent(s) are not defined. Recommendations: 1.Patients with symptomatic Parvovirus B19 infection should be treated with 400 mg/(kg day) of IVIG for 5 days (III).2.Reduction of immunosuppression should be considered at the time of diagnosis (III).3.In case of nonresponse to the first IVIG course or in case of relapse another course of IVIG (400 mg/(kg day) for 5 days) may be given (III). In the SOT population, no proven specific preventive strategy against Parvovirus B19 infection is available. Routine screening of donor and recipient serostatus for Parvovirus B19 is not recommended. Recommendations specifically aimed at avoiding exposure of transplant recipients to children or adults with Parvovirus B19 have not been offered by any advisory group because symptomatic patients are usually no longer contagious. In addition, the relative rarity of this diagnosis in transplant recipients, particularly among pediatric transplant recipients, does not support the introduction of such a policy. To avoid nosocomial transmission, standard and droplet precautions should be implemented when a patient has an active disease. Anecdotal data in bone marrow transplant recipients have demonstrated the absence of Parvovirus B19 disease in cohorts of patients who received prophylactic IVIG for other reasons (20Azzi A Fanci R Ciappi S Zakrzewska K Bosi A Human parvovirus B19 infection in bone marrow transplantation patients.Am J Hematol. 1993; 44: 207-209Crossref PubMed Scopus (46) Google Scholar). However, studies comparing the incidence of Parvovirus infection among bone marrow transplant recipients who received IVIG and those who did not are not available. Furthermore, the lack of evidence of efficacy in the SOT population, the relative low incidence of symptomatic Parvovirus B19 infection and the prohibitive cost and significant toxicity associated with IVIG therapy do not favor its prophylactic use. Finally, the development of recombinant human Parvovirus B19 vaccine composed of VP1 and VP2 capsid proteins is underway. All 24 volunteers who received either 2.5 or 25 μg of Parvovirus B19 recombinant vaccine (MEDI-491) formulated with the adjuvant MF59C.1 at 0, 1 and 6 months developed neutralizing antibody titers that peaked after the third immunization and were sustained through study day 364 (21Ballou WR Reed JL Noble W Young NS Koenig S Safety and immunogenicity of a recombinant parvovirus B19 vaccine formulated with MF59C.1.J Infect Dis. 2003; 187: 675-678Crossref PubMed Scopus (107) Google Scholar). A phase I/II randomized, placebo-controlled, double-blind clinical trial of the immunogenicity and safety of 2 dose levels of a recombinant human Parvovirus B19 vaccine (VAI-VP705) is currently being conducted by the National Institute of Allergy and Infectious Diseases. Hopefully, a vaccine will be available in the near future for clinical use in high-risk populations. However, further studies will be required in order to specifically define its use in the SOT population. Recommendations: 1No specific recommendations are issued regarding Parvovirus B19 prevention. Future studies should evaluate the need for Parvovirus B19 monitoring in SOT candidates and recipients. Large, prospective, multicenter studies are needed in order to investigate current and novel therapeutic options for Parvovirus B19 disease. Finally, future studies should explore the benefits of immunization of SOT candidates with the new Parvovirus B19 vaccine when available. The authors have nothing to disclose.