Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Microbial Issues

Human parvoviruses B19, PARV4 and bocavirus in pediatric patients with allogeneic hematopoietic SCT

Abstract

Among the immunocompetent, infections with parvovirus B19 (B19V) and human bocavirus (HBoV) 1 range clinically from asymptomatic to severe, while following allogeneic hematopoietic SCT (HSCT) B19V can cause a persistent severe illness. The epidemiology and clinical impact of HBoV1 and the other emerging parvovirus 4 (PARV4) among immunocompromised patients have not been established. To determine the occurrence and clinical spectrum of B19V, PARV4 and HBoV1 infections, we performed a longitudinal molecular surveillance among 53 allogeneic HSCT recipients for pre- and post-HSCT DNAemias of these parvoviruses. Quantitative real-time PCR showed B19V DNA in sera of 16 (30%) patients, at mean levels of 4.6 × 103, 9.9 × 107, 1.1 × 1010 and 1.6 × 102 B19V DNA copies/mL pre-HSCT (9/53), and at 1 (6/53), 2 (4/53) and 3 months (1/25) post HSCT, respectively. However, no clinical manifestation correlated with the presence of B19V viremia. All B19V sequences were of genotype 1. None of the sera investigated contained PARV4 or HBoV1 DNAs. Our data demonstrate B19V viremia to be frequent among pediatric allogeneic HSCT recipients, yet without apparent clinical correlates. PARV4 or HBoV1 viremias were not seen in these immunocompromised patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Fisher SA . Emerging viruses in transplantation; there is more to infection after transplant than CMV and EBV. Transplantation 2008; 86: 1327–1339.

    Article  Google Scholar 

  2. Chatzidimitriou D, Gavriilaki E, Sakellari I, Diza E . Hematopoietic cell transplantation and emerging viral infections. J Med Virol 2010; 82: 528–538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Renaud C, Campbell AP . Changing epidemiology of respiratory viral infections in hematopoietic cell transplant recipients and solid organ transplant recipients. Curr Opin Infect Dis 2011; 24: 333–343.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Young NS, Brown KE . Parvovirus B19. N Engl J Med 2004; 350: 586–597.

    Article  CAS  PubMed  Google Scholar 

  5. Allander TM, Tammi T, Eriksson M, Bjerkner A, Tiveljung-Lindall A, Andersson B . Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci USA 2005; 102: 12891–12896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jones MS, Kapoor A, Lukashov VV, Simmonds P, Hecht F, Delwart E . New DNA viruses identified in patients with acute viral infection syndrome. J Virol 2005; 79: 8230–8236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Servant A, Laperche S, Lallemand F, Marinho V, De Saint Maur G, Meritet JF et al. Genetic diversity within human erythroviruses: identification of three genotypes. J Virol 2002; 76: 9124–9134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Norja P, Hokynar K, Aaltonen LM, Chen R, Ranki A, Partio EK et al. Bioportfolio: lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue. Proc Natl Acad Sci USA 2006; 103: 7450–7453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Allain JP, Stramer SL, Carneiro-Proietti ABF, Martins ML, Lopes da Silva SN, Proietti FA et al. Transfusion-transmitted infectious diseases. Biologicals 2009; 37: 71–77.

    Article  PubMed  Google Scholar 

  10. Beske F, Modrow S, Sörensen J, Schmidt H, Kriener S, Allwinn R et al. Parvovirus B19 pneumonia in a child undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 40: 89–91.

    Article  CAS  PubMed  Google Scholar 

  11. Klumpen H-J, Petersen EJ, Verdonck LF . Severe multiorgan failure after parvovirus B19 infection in an allogeneic stem cell transplant recipient. Bone Marrow Transplant 2004; 34: 469–470.

    Article  CAS  PubMed  Google Scholar 

  12. Muetherig A, Christopeit M, Muller LP, Grothe W, Weber T, Theurich S et al. Human parvovirus B19 infection with GvHD-like erythema in two allogeneic stem cell transplant recipients. Bone Marrow Transplant 2007; 39: 315–316.

    Article  CAS  PubMed  Google Scholar 

  13. Broliden K . Parvovirus B19 infection in pediatric solid-organ and bone marrow transplantation. Pediatr Transplant 2001; 5: 320–330.

    Article  CAS  PubMed  Google Scholar 

  14. Broliden K, Tolfvenstam T, Norbeck O . Clinical aspects of parvovirus B19 infection. J Intern Med 2006; 260: 285–304.

    Article  CAS  PubMed  Google Scholar 

  15. Lindblom A, Heyman M, Gustafsson I, Norbeck O, Kaldensjö T, Vernby Å et al. Parvovirus B19 infection in children with acute lymphoblastic leukemia is associated with cytopenia resulting in prolonged interruptions of chemotherapy. Clin Infect Dis 2008; 46: 528–536.

    Article  PubMed  Google Scholar 

  16. Calvo C, Garcia-Garcia ML, Pozo F, Carvajal O, Perez-Brena P, Casas I . Clinical characteristics of human bocavirus infections compared with other respiratory viruses in Spanish children. Pediatr Infect Dis J 2008; 27: 677–680.

    Article  PubMed  Google Scholar 

  17. Pozo F, García-García ML, Calvo C, Cuesta I, Pérez-Breña P, Casas I . High incidence of human bocavirus infection in children in Spain. J Clin Virol 2007; 40: 224–228.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Franz A, Adams O, Willems R, Bonzel L, Neuhausen N, Schweizer-Krantz S et al. Correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection. J Clin Virol 2010; 48: 239–245.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Christensen A, Nordbø SA, Krokstad S, Rognlien AG, Døllner H . Human bocavirus commonly involved in multiple viral airway infections. J Clin Virol 2008; 41: 34–37.

    Article  CAS  PubMed  Google Scholar 

  20. Allander T, Jartti T, Gupta S, Niesters HG, Lehtinen P, Osterback R et al. Human bocavirus and acute wheezing in children. Clin Infect Dis 2007; 44: 904–910.

    Article  PubMed  Google Scholar 

  21. Wang K, Wang W, Yan H, Ren P, Zhang J, Shen J et al. Correlation between bocavirus infection and humoral response, and co-infection with other respiratory viruses in children with acute respiratory infection. J Clin Virol 2010; 47: 148–155.

    Article  CAS  PubMed  Google Scholar 

  22. Jartti T, Hedman K, Jartti L, Ruuskanen O, Allander T, Söderlund-Venermo M . Human bocavirus—the first 5 years. Rev Med Virol 2012; 22: 46–64.

    Article  PubMed  Google Scholar 

  23. Longtin J, Bastien M, Gilca R, Leblanc E, de Serres G, Bergelon MG et al. Human bocavirus infections in hospitalized children and adults. Emerg Infect Dis 2008; 14: 217–221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Martin ET, Fairhok MP, Kuypers J, Magaret A, Zerr DM, Wald A et al. Frequent and prolonged shedding of bocavirus in young children attending daycare. J Infect Dis 2010; 201: 1625–1632.

    Article  PubMed  Google Scholar 

  25. Lindner J, Karalar L, Zehentmeier S, Plentz A, Pfister H, Struffet W et al. Humoral immune response against human bocavirus VP2 virus-like particles. Viral Immunol 2008; 21: 443–449.

    Article  CAS  PubMed  Google Scholar 

  26. Christensen A, Nordbø SA, Krokstad S, Rognlien AG, Døllner H . Human bocavirus in children: mono-detection, high viral load and viraemia are associated with respiratory tract infection. J Clin Virol 2010; 49: 158–162.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Söderlund-Venermo M, Lahtinen A, Jartti T, Hedman L, Kemppainen K, Lehtinen P et al. Clinical assessment and improved diagnosis of bocavirus-induced wheezing in children, Finland. Emerg Infect Dis 2009; 15: 1423–1430.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Karalar L, Lindner J, Schimanski S, Kertai M, Segerer H, Modrow S . Prevalence and clinical aspects of human bocavirus infection in children. Clin Microbiol Infect 2010; 16: 633–639.

    Article  CAS  PubMed  Google Scholar 

  29. Tozer SJ, Stephen BL, Whiley DM, Bialasiewicz S, Lyon MJ, Nissen MD et al. Detection of human bocavirus in respiratory, fecal, and blood samples by real-time PCR. J Med Virol 2009; 81: 488–493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. De Vries JJC, Bredius RGM, van Rheenen PF, Smiers FJW, Schölvinck EH, Vossen ACTM et al. Human bocavirus in an immunocompromised child presenting with severe diarrhea. J Clin Microbiol 2009; 4: 1241–1243.

    Article  Google Scholar 

  31. Kainulainen K, Waris M, Söderlund-Venermo M, Allander T, Hedman K, Ruuskanen O . Hepatitis and human bocavirus primary infection in a child with T-cell deficiency. J Clin Microbiol 2008; 12: 4104–4105.

    Article  Google Scholar 

  32. Koskenvuo M, Möttönen M, Waris M, Allander T, Salmi TT, Ruuskanen O . Human bocavirus in children with acute lymphoblastic leukemia. Eur J Pediatr 2008; 167: 1011–1015.

    Article  PubMed  Google Scholar 

  33. Schenk T, Strahm B, Kontny U, Hufnagel M, Neumann-Haefelin D, Falcone V . Disseminated bocavirus infection after stem cell transplant. Emerg Infect Dis 2007; 9: 1425–1427.

    Article  Google Scholar 

  34. Fryer JF, Delwart E, Bernardin F, Tuke PW, Lukashov VV, Baylis SA . Analysis of two human parvovirus PARV4 genotypes identified in human plasma for fractionation. J Gen Virol 2007; 88: 2162–2167.

    Article  CAS  PubMed  Google Scholar 

  35. Panning M, Kobbe R, Vollbach S, Drexler JF, Adjei S, Adjei O et al. Novel human parvovirus 4 genotype 3 in infants, Ghana. Emerg Infect Dis 2010; 16: 1143–1146.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Simmonds P, Douglas J, Bestetti G, Longhi E, Antinori S, Parravicini C et al. A third genotype of the human parvovirus PARV4 in sub-Saharan Africa. J Gen Virol 2008; 89: 2299–2302.

    Article  CAS  PubMed  Google Scholar 

  37. Manning A, Willey SJ, Bell JE, Simmonds P . Comparison of tissue distribution, persistence, and molecular epidemiology of parvovirus B19 and novel human parvoviruses PARV4 and human bocavirus. J Infect Dis 2007; 195: 1345–1352.

    Article  CAS  PubMed  Google Scholar 

  38. Longhi E, Bestetti G, Acquaviva V, Foschi A, Piolini R, Meroni L . Human parvovirus 4 in the bone marrow of Italian patients with AIDS. AIDS 2007; 21: 1481–1483.

    Article  PubMed  Google Scholar 

  39. Schneider B, Fryer JF, Reber U, Fischer HP, Tolba RH, Baylis SA et al. Persistence of novel human parvovirus PARV4 in liver tissue of adults. J Med Virol 2008; 80: 345–351.

    Article  CAS  PubMed  Google Scholar 

  40. Botto S, Bergallo M, Sidoti F, Terlizzi ME, Astegiano S, Ponti R et al. Detection of PARV4, genotypes 1 and 2, in healthy and pathological clinical specimens. New Microbiol 2009; 32: 189–192.

    CAS  PubMed  Google Scholar 

  41. Corcioli F, Zakrzewska K, Fanci R, De Giorgi V, Innocenti M, Rotellini M et al. Human PARV4 DNA in tissues from adult individuals: a comparison with human parvovirus B19 (B19V). Virol J 2011; 7: 272–276.

    Article  Google Scholar 

  42. Sharp CP, Lail A, Donfield S, Simmons R, Leen C, Klenerman P et al. High frequencies of exposure to the novel human parvovirus PARV4 in hemophiliacs and injection drug users, as detected by a serological assay for PARV4 antibodies. J Infect Dis 2009; 200: 1119–1125.

    Article  CAS  PubMed  Google Scholar 

  43. Simmonds P, Manning A, Kenneil R, Carnie FW, Bell JE . Parenteral transmission of the novel human parvovirus PARV4. Emerg Infect Dis 2007; 13: 1386–1388.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lahtinen A, Kivelä P, Hedman L, Kumar A, Kantele A, Lappalainen M et al. Serodiagnosis of primary infections with human parvovirus 4, Finland. Emerg Infect Dis 2011; 1: 79–82.

    Article  Google Scholar 

  45. Yu X, Zhang J, Hong L, Wang J, Yuan Z, Zhang X et al. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in Shanghai. PLoS One 2012; 7 (1): e29474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Vallerini D, Barozzi P, Quadrelli C, Bosco R, Potenza L, Riva G et al. Parvoviruses in blood donors and transplant patients, Italy. Emerg Infect Dis 2008; 14: 185–186.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Tolfvenstam T, Norbeck O, Ohrmalm L . No evidence of presence of parvovirus 4 in a Swedish cohort of severely immunocompromised children and adults. PLoS One 2012; 7 (9): e46430.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jartti T, Söderlund-Venermo M, Hedman K, Ruuskanen O, Mäkelä M . New molecular virus detection methods and their clinical value in lower respiratory tract infections in children. Paediatr Respir Rev 2013; 14: 38–45.

    Article  PubMed  Google Scholar 

  49. Söderlund M, von Essen R, Haapasaari J, Kiistala U, Kiviluoto O, Hedman K . Persistence of parvovirus B19 DNA in synovial membranes of young patients with and without chronic arthropathy. Lancet 1997; 349: 1063–1065.

    Article  PubMed  Google Scholar 

  50. Hokynar K, Norja P, Laitinen H, Palomäki P, Garbarg-Chenon A, Ranki A et al. Detection and differentiation of human parvovirus variants by commercial quantitative real-time PCR tests. J Clin Microbiol 2004; 42: 2013–2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kantola K, Sadeghi M, Antikainen J, Kirveskari J, Delwart E, Hedman K et al. Real-time quantitative PCR detection of four human bocaviruses. J Clin Microbiol 2010; 48: 4044–4050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Väisänen E, Lahtinen A, Hedman K, Söderlund-Venermo M Real-time PCR assay for detection, differentiation and quantification of three genotypes of human parvovirus 4 (submitted).

  53. Zaki ME, Ashray RE . Clinical and haematological study for parvovirus b19 infection in children with acute leukemia. Int J Lab Hematol 2010; 32: 159–166.

    Article  CAS  PubMed  Google Scholar 

  54. Soliman O-S, Abd E-AHHM, El-Ashry R, Zaghloul MH, Kora B . Parvovirus B19 infection in pediatric oncology patients: diagnostic value of clinical and serologic parameters compared with nested PCR. J Pediatr Hematol Oncol 2009; 31: 173–176.

    Article  Google Scholar 

  55. Söderlund M, Ruutu P, Ruutu T, Asikainen K, Franssila R, Hedman K . Primary and secondary infections by human parvovirus B19 following bone marrow transplantation: characterization by PCR and B-cell molecular immunology. Scand J Infect Dis 1997; 29: 129–135.

    Article  PubMed  Google Scholar 

  56. Azzi A, Fanci R, Ciappi S, Zakrzewska K, Bosi A . Human parvovirus B19 infection in bone marrow transplantation patients. Am J Hematol 1993; 44: 207–209.

    Article  CAS  PubMed  Google Scholar 

  57. Eid AJ, Brown RA, Patel R, Razonable RR . Parvovirus B19 infection after transplantation: a review of 98 cases. Clin Infect Dis 2006; 43: 40–48.

    Article  PubMed  Google Scholar 

  58. Lindblom A, Isa A, Norbeck O, Wolf S, Johansson B, Broliden K et al. Slow clearance of human parvovirus B19 viremia following acute infection. Clin Infect Dis 2005; 41: 1201–1203.

    Article  PubMed  Google Scholar 

  59. Hayakawa F, Imada K, Towatari M, Saito H . Life-threatening human parvovirus B19 infection transmitted by intravenous immune globulin. Br J Haematol 2002; 118: 1187–1189.

    Article  PubMed  Google Scholar 

  60. Behre G, Christopeit M . Parvovirus B19 infection as trigger of graft vs host disease. Eur J Haematol 2008; 81: 404.

    PubMed  Google Scholar 

  61. Corcoran A, Doyle S . Advances in the biology, diagnosis and host-pathogen interactions of parvovirus B19. J Med Microbiol 2004; 53: 459–475.

    Article  CAS  PubMed  Google Scholar 

  62. Hourfar MK, Mayr-Wohlfart U, Themann A, Sireis W, Seifried E, Schrezenmeier M et al. Recipients potentially infected with parvovirus B19 by red blood cell products. Transfusion 2011; 50: 129–136.

    Article  Google Scholar 

  63. Foot AB, Potter MN, Donaldson C, Cornish JM, Wallington TB, Oakhill A et al. Immune reconstitution after BMT in children. Bone Marrow Transplant 1993; 11: 7–13.

    CAS  PubMed  Google Scholar 

  64. Meriluoto M, Hedman L, Tanner L, Simell V, Mäkinen M, Simell S et al. Association of human bocavirus 1 infection with respiratory disease in childhood follow-up study, Finland. Emerg Infect Dis 2012; 18: 264–271.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Schildgen O, Müller A, Allander T, Mackay IM, Völz S, Kupfer B et al. Human bocavirus: passenger or pathogen in acute respiratory tract infections. Clin Microbiol Rev 2008; 21: 291–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. von Linstow ML, Høgh M, Høgh B . Clinical and epidemiologic characteristics of human bocavirus in Danish infants: results from a prospective birth cohort study. Pediatr Infect Dis J 2008; 27: 897–902.

    Article  PubMed  Google Scholar 

  67. Brieu N, Guyon G, Rodiére M, Segondy M, Foulongne V . Human bocavirus infection in children with respiratory tract disease. Pediatr Infect Dis J 2008; 27: 969–973.

    Article  PubMed  Google Scholar 

  68. Lehtoranta L, Söderlund-Venermo M, Nokso-Koivisto J, Toivola H, Blomgren K, Hatakka K et al. Human bocavirus in the nasopharynx of otitis-prone children. Int J Pediatr Otorhinolaryngol 2012; 76: 206–211.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Foundation for Pediatric Research, the Nona and Kullervo Väre Foundation, the University of Helsinki Research Fund, and the Turku University Foundation, the Sigrid Jusélius Foundation, the Finnish Medical Foundation (FLS), and the Academy of Finland (Grant No. 1257964).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J Rahiala.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rahiala, J., Koskenvuo, M., Norja, P. et al. Human parvoviruses B19, PARV4 and bocavirus in pediatric patients with allogeneic hematopoietic SCT. Bone Marrow Transplant 48, 1308–1312 (2013). https://doi.org/10.1038/bmt.2013.63

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2013.63

Keywords

This article is cited by

Search

Quick links