Human Parvovirus B19 in Solid Organ Transplantation: Human Parvovirus B19

The Parvoviridae family includes the genus erythrovirus with human parvovirus B19 being the classic type member. The virus is 25 nm in diameter, nonenveloped and consists of a single-strand linear DNA that is approximately 5 kb in length. The viral genome encodes three main proteins, a nonstructural protein (NS1) and two structural proteins (VP1 and VP2; Ref. 1Berns KP Colin R Parvoviridae.in: Knipe DHP Fields Virology.5th ed. Lippincott Williams and Wilkins, Philadelphia2007: 2438Google Scholar). The nonstructural protein is cytotoxic to host cells (2Moffatt S Yaegashi N Tada K Tanaka N Sugamura K. Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in erythroid lineage cells.J Virol. 1998; 72: 3018-3028Crossref PubMed Google Scholar,3Ozawa K Ayub J Kajigaya S Shimada T Young N The gene encoding the nonstructural protein of B19 (human) parvovirus may be lethal in transfected cells.J Virol. 1988; 62: 2884-2889Crossref PubMed Scopus (173) Google Scholar). Parvovirus B19 is classified into three different genotypes (genotype 1, 2, 3), but there is no definitive association of genotypes with specific clinical manifestations. Parvovirus B19 was first detected in a healthy blood donor’s serum in 1974 (4Cossart YE Field AM Cant B Widdows D Parvovirus-like particles in human sera.Lancet. 1975; 1: 72-73Abstract PubMed Scopus (773) Google Scholar). It was subsequently linked to disease in children with sickle cell anemia experiencing transient aplastic crisis (5Pattison JR Jones SE Hodgson J et al.Parvovirus infections and hypoplastic crisis in sickle-cell anaemia.Lancet. 1981; 1: 664-665Abstract PubMed Scopus (447) Google Scholar) and then in children with a contagious exanthem, called erythema infectiosum, or fifth disease (6Anderson MJ Lewis E Kidd IM Hall SM Cohen BJ An outbreak of erythema infectiosum associated with human parvovirus infection.J Hyg (Lond). 1984; 93: 85-93Crossref PubMed Scopus (271) Google Scholar). Parvovirus B19 has particular tropism for human erythroid progenitor cells, which is the natural host cell (7Mortimer PP Humphries RK Moore JG Purcell RH Young NS A human parvovirus-like virus inhibits haematopoietic colony formation in vitro.Nature. 1983; 302: 426-429Crossref PubMed Scopus (232) Google Scholar,8Potter CG Potter AC Hatton CS et al.Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19).J Clin Invest. 1987; 79: 1486-1492Crossref PubMed Scopus (136) Google Scholar). The cellular receptor is globoside (also called erythrocyte P antigen; Ref. 9Brown KE Anderson SM Young NS Erythrocyte P antigen: Cellular receptor for B19 parvovirus.Science. 1993; 262: 114-117Crossref PubMed Scopus (738) Google Scholar), which is found on erythroid cells, erythroid precursors and red cells of the placenta and fetal myocardium, fetal liver and some megakaryocytes and endothelial cells. Viral replication induces a distinctive cytopathic effect by light microscopy, represented by giant pronormoblasts (10Caul EO Usher MJ Burton PA Intrauterine infection with human parvovirus B19: A light and electron microscopy study.J Med Virol. 1988; 24: 55-66Crossref PubMed Scopus (63) Google Scholar), and productive infection has only been described in erythroid precursors (11Ozawa K Kurtzman G Young N Replication of the B19 parvovirus in human bone marrow cell cultures.Science. 1986; 233: 883-886Crossref PubMed Scopus (267) Google Scholar). Although P antigen receptors are found on nonerythroid cells, there is evidence that a region of the viral genome is responsible for inhibiting viral replication in nonpermissive cells (12Pallier C Greco A Le Junter J Saib A Vassias I Morinet F The 3’ untranslated region of the B19 parvovirus capsid protein mRNAs inhibits its own mRNA translation in nonpermissive cells.J Virol. 1997; 71: 9482-9489Crossref Scopus (49) Google Scholar). Parvovirus B19 is ubiquitous and a common illness of childhood so that half of the population have detectable IgG antibody by 15 years of age (13Risks associated with human parvovirus B19 infection.MMWR Morb Mortal Wkly Rep. 1989; 38 (93–97.): 81-88PubMed Google Scholar,14Anderson LJ Tsou C Parker RA et al.Detection of antibodies and antigens of human parvovirus B19 by enzyme-linked immunosorbent assay.J Clin Microbiol. 1986; 24: 522-526Crossref PubMed Scopus (239) Google Scholar). Most infections occur in the spring in temperate climates with small epidemics regularly occurring several years apart (15Human parvovirus B19 infections in United Kingdom 1984–86.Lancet. 1987; 1: 738-739Abstract Scopus (60) Google Scholar). The incidence of parvovirus infection in solid organ transplant patients is unknown because of the lack of surveillance studies. Based on detection of parvovirus DNA in peripheral blood, one study reported a single institution incidence of 12% in kidney transplant patients who had anemia (16Ki 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 (49) Google Scholar). Transmission of parvovirus B19 appears to be via respiratory secretions (6Anderson MJ Lewis E Kidd IM Hall SM Cohen BJ An outbreak of erythema infectiosum associated with human parvovirus infection.J Hyg (Lond). 1984; 93: 85-93Crossref PubMed Scopus (271) Google Scholar,17Serjeant GR Topley JM Mason K et al.Outbreak of aplastic crises in sickle cell anaemia associated with parvovirus-like agent.Lancet. 1981; 2: 595-597Abstract Scopus (313) Google Scholar). Direct intranasal inoculation of parvovirus B19 into healthy volunteers resulted in viremia and clinical manifestations (18Anderson MJ Higgins PG Davis LR et al.Experimental parvoviral infection in humans.J Infect Dis. 1985; 152: 257-265Crossref PubMed Scopus (624) Google Scholar). Transmission can also occur to the fetus via transplacental infection and rarely through blood products (19Anand A Gray ES Brown T Clewley JP Cohen BJ Human parvovirus infection in pregnancy and hydrops fetalis.N Engl J Med. 1987; 316: 183-186Crossref PubMed Scopus (361) Google Scholar,20Parsyan A Candotti D Human erythrovirus B19 and blood transfusion—an update.Transfus Med. 2007; 17: 263-278Crossref PubMed Scopus (66) Google Scholar). No FDA approved test is available for parvovirus B19 screening in blood donors. However, nucleic acid testing (NAT) is available for plasma units in process of being fractionated (21Stramer SL Hollinger FB Katz LM et al.Emerging infectious disease agents and their potential threat to transfusion safety.Transfusion. 2009; 49: 1S-29SCrossref PubMed Scopus (303) Google Scholar). There is evidence that transmission of parvovirus B19 infection may occur at the time of transplantation (22Barzon L Murer L Pacenti M et al.Detection of viral DNA in kidney graft preservation and washing solutions is predictive of posttransplant infections in pediatric recipients.J Infect Dis. 2009; 200: 1425-1433Crossref Scopus (16) Google Scholar, 23Heegaard ED Laub Petersen B Parvovirus B19 transmitted by bone marrow.Br J Haematol. 2000; 111: 659-661Crossref PubMed Scopus (48) Google Scholar, 24Yango Jr., A Morrissey P Gohh R Wahbeh A Donor-transmitted parvovirus infection in a kidney transplant recipient presenting as pancytopenia and allograft dysfunction.Transpl Infect Dis. 2002; 4: 163-166Crossref PubMed Scopus (49) Google Scholar). Barzon et al. showed that in the majority of 10 pediatric kidney transplant patients (pretransplant parvovirus serology D+/R−), positive detection of parvovirus B19 DNA in the allograft kidney biopsy sample, preservation solution or washing solution (which contain circulating donor cells and resident kidney cells) was associated with posttransplant detection of parvovirus DNA in the blood of the recipient (22Barzon L Murer L Pacenti M et al.Detection of viral DNA in kidney graft preservation and washing solutions is predictive of posttransplant infections in pediatric recipients.J Infect Dis. 2009; 200: 1425-1433Crossref Scopus (16) Google Scholar). The incubation period ranges from 4–14 days, and individuals with erythema infectiosum are contagious before onset of rash but rarely afterwards. Individuals with aplastic crisis can be contagious before symptoms until about one week after onset of symptoms (25Bell LM Naides SJ Stoffman P Hodinka RL Plotkin SA Human parvovirus B19 infection among hospital staff members after contact with infected patients.N Engl J Med. 1989; 321: 485-491Crossref PubMed Scopus (156) Google Scholar). Secondary infection rates are 50% for susceptible household members (26Chorba T Coccia P Holman RC et al.The role of parvovirus B19 in aplastic crisis and erythema infectiosum (fifth disease).J Infect Dis. 1986; 154: 383-393Crossref PubMed Scopus (194) Google Scholar) and 20% for school and childcare personnel (27Gillespie SM Cartter ML Asch S et al.Occupational risk of human parvovirus B19 infection for school and day-care personnel during an outbreak of erythema infectiosum.JAMA. 1990; 263: 2061-2065Crossref PubMed Scopus (133) Google Scholar). Transmission to hospital personnel can occur. The clinical manifestations of parvovirus B19 infection in immunocompromised patients are atypical (Table 1). Among 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 (28Eid 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 (167) Google Scholar). Therefore, parvovirus B19 infection should be suspected in SOT recipients with erythropoietin-resistant anemia since the reported incidence in this group of patients is relatively high (29Bertoni E Rosati A Zanazzi M et al.Unusual incidence of aplastic anaemia due to B-19 parvovirus infection in renal transplant recipients.Transplant Proc. 1997; 29: 818-819Crossref Scopus (24) Google Scholar).Table 1:Clinical manifestations of parvovirus B19 in immunocompromised hostsPersistent anemiaSevere anemia• Lack of reticulocyte response• Lack of response to erythropoietinFever• Observed in 25% of solid organ transplant patients.Lacy skin rash• Not always present because of lack of antigen-antibody complexes (30Young NS Brown KE Parvovirus B19.N Engl J Med. 2004; 350: 586-597Crossref PubMed Scopus (739) Google Scholar,33Kurtzman 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 (294) Google Scholar)Arthropathy• Not always present because of lack of antigen-antibody complexes (30Young NS Brown KE Parvovirus B19.N Engl J Med. 2004; 350: 586-597Crossref PubMed Scopus (739) Google Scholar,33Kurtzman 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 (294) Google Scholar)Pancytopenia• A subset of patients will manifest concomitant leukopenia or thrombocytopenia with the anemia (8Potter CG Potter AC Hatton CS et al.Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19).J Clin Invest. 1987; 79: 1486-1492Crossref PubMed Scopus (136) Google Scholar,18Anderson MJ Higgins PG Davis LR et al.Experimental parvoviral infection in humans.J Infect Dis. 1985; 152: 257-265Crossref PubMed Scopus (624) Google Scholar,51Saunders PW Reid MM Cohen BJ Human parvovirus induced cytopenias: A report of five cases.Br J Haematol. 1986; 63: 407-4010Crossref PubMed Scopus (61) Google Scholar).• The pathogenesis is speculated to be non-specific cytopathic effects in the bone marrow (8Potter CG Potter AC Hatton CS et al.Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19).J Clin Invest. 1987; 79: 1486-1492Crossref PubMed Scopus (136) Google Scholar) or restricted non-structural protein expression in megakaryocytes, which leads to cytotoxicity but not viral progeny (52Srivastava A Bruno E Briddell R et al.Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro.Blood. 1990; 76: 1997-2004Crossref PubMed Google Scholar). Open table in a new tab Many clinical manifestations have been associated with parvovirus B19 (30Young NS Brown KE Parvovirus B19.N Engl J Med. 2004; 350: 586-597Crossref PubMed Scopus (739) Google Scholar). However, the association with parvovirus is predominantly based on finding DNA in tissue, which may not be proof of causation. Parvovirus DNA has been found persistently in a number of tissues including bone marrow, synovium, heart tissue and skin from individuals who are asymptomatic (31Corcioli 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 (72) Google Scholar). The reason for the persistence is unclear but may be related to inhibition of viral replication in nonpermissive cells. Furthermore, normal healthy blood donors have been found to have circulating parvovirus B19 DNA in peripheral blood (32Kooistra K Mesman HJ de Waal M Koppelman MH Zaaijer HL Epidemiology of high-level parvovirus B19 viraemia among Dutch blood donors, 2003–2009.Vox Sang. 2011; 100: 261-266Crossref PubMed Scopus (41) Google Scholar). Antibody response to parvovirus B19 appears to confer life-long protective immunity for the individual. Lack of an antibody response is observed in patients with persistent infection (33Kurtzman 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 (294) Google Scholar). “Recurrences” of parvovirus B19 infection may be more related to poor initial neutralizing antibody production in immunocompetent and immunocompromised hosts. T cell responses to parvovirus B19 have been detected (34Tolfvenstam T Oxenius A Price DA et al.Direct ex vivo measurement of CD8(+) T-lymphocyte responses to human parvovirus B19.J Virol. 2001; 75: 540-543Crossref PubMed Scopus (39) Google Scholar) but their role in protective immunity is not clear (35Isa A Norbeck O Hirbod T et al.Aberrant cellular immune responses in humans infected persistently with parvovirus B19.J Med Virol. 2006; 78: 129-133Crossref PubMed Scopus (24) 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 highly viremic patients following acute parvovirus B19 infection, serology might be falsely negative because antibodies could be complexed by viral particles (36Bredl S Plentz A Wenzel JJ Pfister H Most J Modrow S False-negative serology in patients with acute parvovirus B19 infection.J Clin Virol. 2011; 51: 115-120Crossref PubMed Scopus (39) Google Scholar). In addition, parvovirus B19 serology is not reliable in immunocompromised patients due to inadequate or delayed antibody-mediated immune response (37Broliden K Parvovirus B19 infection in pediatric solid-organ and bone marrow transplantation.Pediatr Transplant. 2001; 5: 320-330Crossref PubMed Scopus (82) Google Scholar,38Kurtzman 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 (396) 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) among transplant recipients with parvovirus B19 infection (28Eid 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 (167) Google Scholar). The current use of polymerase chain reaction (PCR) assays significantly improved the detection of viral DNA (39Manaresi 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, one should keep in mind that some PCR assays are unable to detect non-B19 strains (genotypes 2 and 3; Refs. 40Baylis SA Buchheit KH A proficiency testing study to evaluate laboratory performance for the detection of different genotypes of parvovirus B19.Vox Sang. 2009; 97: 13-20Crossref PubMed Scopus (12) Google Scholar, 41Baylis 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 (73) Google Scholar, 42Harder 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), and real-time PCR can be falsely negative in case of high-level viremia (43Grabarczyk P Kalinska A Kara M et al.Identification and characterization of acute infection with parvovirus B19 genotype 2 in immunocompromised patients in Poland.J Med Virol. 2011; 83: 142-149Crossref PubMed Scopus (25) 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 (44Cassinotti 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 (66) Google Scholar). Thus, a positive PCR for parvovirus B19 does not necessarily indicate acute infection. However, the positive predictive value of positive PCR in an immunocompromised host with red cell aplasia is high. Bone marrow examination associated with in situ hybridization or immunohistochemical staining could be very helpful in establishing the diagnosis when the clinical presentation is strongly suggestive of parvovirus B19 infection but the PCR and serology are negative (28Eid 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 (167) 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:(1)Parvovirus B19 infection should be suspected in SOT recipients with:(a)Erythropoietin-resistant anemia or anemia with inappropriate reticulocyte response with or without:(i)Fever, arthralgia or rash(ii)Organ-invasive disease such as hepatitis, myocarditis, pneumonitis, neurological disease or vasculitis (III).(b)Pancytopenia(2)The initial work-up for suspected parvovirus B19 infection should include serology (IgG and IgM) and serum/whole blood PCR for parvovirus B19 (III).(3)If not done earlier, bone marrow examination should be performed when parvovirus B19 infection is strongly suspected and the serology and serum PCR 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 appeared to be beneficial in a large number of SOT recipients with parvovirus B19 infection (28Eid 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 (167) Google Scholar,45Bergen 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,46Jordan SC Toyoda M Kahwaji J Vo AA Clinical aspects of intravenous immunoglobulin use in solid organ transplant recipients.Am J Transplant. 2011; 11: 196-202Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar). The optimal dosing regimen and duration of IVIG therapy for parvovirus B19 infection has not been established and some patients have been reported to have long-lasting resolution of the infection without IVIG therapy (28Eid 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 (167) Google Scholar). Most patients are treated with 400 mg/kg/day for 5 days, although higher doses have been used for shorter periods of time. 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 (28Eid 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 (167) 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 that persistent low grade viremia for months despite adequate clinical response to therapy is not uncommon (47Kumar 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 would 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 (47Kumar 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). Yet, there is a wide variation in the clinical practice in terms of dose and duration of therapy. The side effects of IVIG treatment include fever, chills, headache, myalgia, nausea, hypertension, chest pain and renal failure. The reduction of immunosuppression is believed to contribute to the resolution of infection; however, the timing of such an intervention (i.e. before or after IVIG therapy) is a subject of debate. Recommendations:(1)Patients with parvovirus B19 infection may be treated with 400 mg/kg/day of IVIG for 5 consecutive days (III).(2)Reduction of immunosuppression should be attempted if at all possible 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. In one study, donor and recipient serostatus and more importantly the detection of viral DNA in renal allograft tissue, preservation solution or washing solution were useful to predict the risk of posttransplant viremia (22Barzon L Murer L Pacenti M et al.Detection of viral DNA in kidney graft preservation and washing solutions is predictive of posttransplant infections in pediatric recipients.J Infect Dis. 2009; 200: 1425-1433Crossref Scopus (16) Google Scholar). However, only a few patients developed clinically significant disease in this study, which raises the question of cost-effectiveness of such method. Furthermore, strategies to prevent symptomatic parvovirus B19 infection are yet to be defined. Recommendations 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 (48Azzi 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 high cost and potential 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 (49Ballou 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 (111) 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) conducted by the National Institute of Allergy and Infectious Diseases was halted because of three unexplained cutaneous events. After the second dose of the vaccine, most vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19 (50Bernstein DI El Sahly HM Keitel WA et al.Safety and immunogenicity of a candidate parvovirus B19 vaccine.Vaccine. 2011; 29: 7357-7363Crossref PubMed Scopus (66) Google Scholar). Hopefully a vaccine will be available in the near future for clinical use in high-risk populations. However, studies will be required to specifically define its use in the SOT population. Recommendations:(1)To avoid nosocomial transmission, standard and droplet precautions should be implemented when a patient has an active disease. Future studies should further evaluate the utility of parvovirus B19 monitoring in SOT recipients. The significance of parvovirus B19 DNA detection in the blood or tissue samples obtained from immunocompetent patients and SOT recipients should be determined. Large, prospective, multicenter studies are needed in order to investigate current and novel therapeutic options for parvovirus B19 disease. Finally, future studies are needed to investigate new parvovirus B19 vaccines and the benefit of their use among SOT candidates and recipients. This manuscript was modified from a previous guideline written by AJ Eid, KM Posfay-Barbe published in American Journal of Transplantation 2009; 9(Suppl 4): S147–S150 and endorsed by the American Society of Transplantation/Canadian Society of Transplantation. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.