Respiratory Syncytial Virus and Human Metapneumovirus Infection in Transplant Recipients

  • Christian Renaud
  • Janet Englund


Respiratory viral infections due to respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause infections in immunocompromised transplant patients ranging from mild upper respiratory infections to severe lower respiratory tract disease with respiratory failure. These viruses are more readily diagnosed due to improvements in sensitive molecular diagnostic methods. The epidemiology of RSV and hMPV is similarly becoming more readily appreciated in hematopoietic stem cell transplant (HSCT) patients of all ages as well as solid organ transplant (SOT) patients, with lung transplant recipients having evidence of more frequent and severe complications related to these viruses. RSV and hMPV infection typically but not always present with upper respiratory signs and symptoms that progress to lower respiratory tract disease. Treatment options for RSV are limited, with aerosolized, intravenous, and oral ribavirin all studied in HSCT and lung transplant patients. No antiviral therapy for the treatment of hMPV is available, although ribavirin has shown some effectiveness in vitro. New antiviral agents including RSV fusion inhibitors and nucleoside analogs are being developed, with some under clinical evaluation.


Respiratory syncytial virus Human metapneumovirus Ribavirin Antiviral therapy Immunocompromised Pneumonia 


  1. 1.
    Meyers JD, Flournoy N, Thomas ED. Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years’ experience. Rev Infect Dis. 1982;4:1119–32.PubMedCrossRefGoogle Scholar
  2. 2.
    Frank Jr JA, Warren RW, Tucker JA, Zeller J, Wilfert CM. Disseminated parainfluenza infection in a child with severe combined immunodeficiency. Am J Dis Child. 1983;137:1172–4.PubMedGoogle Scholar
  3. 3.
    Fishaut M, Tubergen D, McIntosh K. Cellular response to respiratory viruses with particular reference to children with disorders of cell-mediated immunity. J Pediatr. 1980;96:179–86.PubMedCrossRefGoogle Scholar
  4. 4.
    Delage G, Brochu P, Pelletier M, Jasmin G, Lapointe N. Giant-cell pneumonia caused by parainfluenza virus. J Pediatr. 1979;94:426–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Englund JA, Sullivan CJ, Jordan MC, Dehner LP, Vercellotti GM, Balfour Jr HH. Respiratory syncytial virus infection in immunocompromised adults. Ann Intern Med. 1988;109:203–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Hertz MI, Englund JA, Snover D, Bitterman PB, McGlave PB. Respiratory syncytial virus-induced acute lung injury in adult patients with bone marrow transplants: a clinical approach and review of the literature. Medicine (Baltimore). 1989;68:269–81.CrossRefGoogle Scholar
  7. 7.
    Glezen WP, Greenberg SB, Atmar RL, Piedra PA, Couch RB. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA. 2000;283:499–505.PubMedCrossRefGoogle Scholar
  8. 8.
    Whimbey E, Englund JA, Couch RB. Community respiratory virus infections in immunocompromised patients with cancer. Am J Med. 1997;102:10–8. discussion 25–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Whimbey E, Champlin RE, Couch RB, et al. Community respiratory virus infections among hospitalized adult bone marrow transplant recipients. Clin Infect Dis. 1996;22:778–82.PubMedCrossRefGoogle Scholar
  10. 10.
    Sable CA, Hayden FG. Orthomyxoviral and paramyxoviral infections in transplant patients. Infect Dis Clin North Am. 1995;9:987–1003.PubMedGoogle Scholar
  11. 11.
    Bowden RA. Respiratory virus infections after marrow transplant: the Fred Hutchinson Cancer Research Center experience. Am J Med. 1997;102:27–30. discussion 42–3.PubMedCrossRefGoogle Scholar
  12. 12.
    Whimbey E, Bodey GP. Viral pneumonia in the immunocompromised adult with neoplastic disease: the role of common community respiratory viruses. Semin Respir Infect. 1992;7:122–31.PubMedGoogle Scholar
  13. 13.
    Ljungman P, Gleaves CA, Meyers JD. Respiratory virus infection in immunocompromised patients. Bone Marrow Transplant. 1989;4:35–40.PubMedGoogle Scholar
  14. 14.
    Ljungman P. Respiratory virus infections in bone marrow transplant recipients: the European perspective. Am J Med. 1997;102:44–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Kim YJ, Boeckh M, Englund JA. Community respiratory virus infections in immunocompromised patients: hematopoietic stem cell and solid organ transplant recipients, and individuals with human immunodeficiency virus infection. Semin Respir Crit Care Med. 2007;28:222–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Peret TC, Boivin G, Li Y, et al. Characterization of human metapneumoviruses isolated from patients in North America. J Infect Dis. 2002;185:1660–3.PubMedCrossRefGoogle Scholar
  17. 17.
    Boivin G, Abed Y, Pelletier G, et al. Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups. J Infect Dis. 2002;186:1330–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Blount Jr RE, Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med. 1956;92:544–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Adams JM, Imagawa DT, Zike K. Epidemic bronchiolitis and pneumonitis related to respiratory syncytial virus. JAMA. 1961;176:1037–9.PubMedCrossRefGoogle Scholar
  20. 20.
    van den Hoogen BG, de Jong JC, Groen J, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. 2001;7:719–24.PubMedCrossRefGoogle Scholar
  21. 21.
    Papenburg J, Boivin G. The distinguishing features of human metapneumovirus and respiratory syncytial virus. Rev Med Virol. 2010;20:245–60.PubMedCrossRefGoogle Scholar
  22. 22.
    Englund JA. Diagnosis and epidemiology of community-acquired respiratory virus infections in the immunocompromised host. Biol Blood Marrow Transplant. 2001;7(Suppl):2S–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Peck AJ, Corey L, Boeckh M. Pretransplantation respiratory syncytial virus infection: impact of a strategy to delay transplantation. Clin Infect Dis. 2004;39:673–80.PubMedCrossRefGoogle Scholar
  24. 24.
    Campbell AP, Guthrie KA, Englund JA, et al. Clinical outcomes associated with respiratory virus detection before allogeneic hematopoietic stem cell transplant. Clin Infect Dis. 2015;61:192–202.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Barenfanger J, Drake C, Leon N, Mueller T, Troutt T. Clinical and financial benefits of rapid detection of respiratory viruses: an outcomes study. J Clin Microbiol. 2000;38:2824–8.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Vallieres E, Renaud C. Clinical and economical impact of multiplex respiratory virus assays. Diagn Microbiol Infect Dis. 2013;76:255–61.PubMedCrossRefGoogle Scholar
  27. 27.
    Walsh P, Overmyer CL, Pham K, et al. Comparison of respiratory virus detection rates for infants and toddlers by use of flocked swabs, saline aspirates, and saline aspirates mixed in universal transport medium for room temperature storage and shipping. J Clin Microbiol. 2008;46:2374–6.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Hernes SS, Quarsten H, Hagen E, et al. Swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs. Eur J Clin Microbiol Infect Dis. 2011;30:159–65.PubMedCrossRefGoogle Scholar
  29. 29.
    Esposito S, Molteni CG, Daleno C, et al. Comparison of nasopharyngeal nylon flocked swabs with universal transport medium and rayon-bud swabs with a sponge reservoir of viral transport medium in the diagnosis of paediatric influenza. J Med Microbiol. 2010;59:96–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Campbell AP, Kuypers J, Englund JA, Guthrie KA, Corey L, Boeckh M. Self-collection of foam nasal swabs for respiratory virus detection by PCR among immunocompetent subjects and hematopoietic cell transplant recipients. J Clin Microbiol. 2013;51:324–7.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Debyle C, Bulkow L, Miernyk K, et al. Comparison of nasopharyngeal flocked swabs and nasopharyngeal wash collection methods for respiratory virus detection in hospitalized children using real-time polymerase chain reaction. J Virol Methods. 2012;185:89–93.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Xu M, Qin X, Astion ML, et al. Implementation of filmarray respiratory viral panel in a core laboratory improves testing turnaround time and patient care. Am J Clin Pathol. 2013;139:118–23.PubMedCrossRefGoogle Scholar
  33. 33.
    Butt SA, Maceira VP, McCallen ME, Stellrecht KA. Comparison of three commercial RT-PCR systems for the detection of respiratory viruses. J Clin Virol. 2014;61:406–10.PubMedCrossRefGoogle Scholar
  34. 34.
    Kuypers J, Wright N, Morrow R. Evaluation of quantitative and type-specific real-time RT-PCR assays for detection of respiratory syncytial virus in respiratory specimens from children. J Clin Virol. 2004;31:123–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Kodani M, Yang G, Conklin LM, et al. Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens. J Clin Microbiol. 2011;49:2175–82.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Kuypers J, Wright N, Corey L, Morrow R. Detection and quantification of human metapneumovirus in pediatric specimens by real-time RT-PCR. J Clin Virol. 2005;33:299–305.PubMedCrossRefGoogle Scholar
  37. 37.
    Waghmare A, Campbell AP, Xie H, et al. Respiratory syncytial virus lower respiratory disease in hematopoietic cell transplant recipients: viral RNA detection in blood, antiviral treatment, and clinical outcomes. Clin Infect Dis. 2013;57:1731–41.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Fong CK, Lee MK, Griffith BP. Evaluation of R-Mix FreshCells in shell vials for detection of respiratory viruses. J Clin Microbiol. 2000;38:4660–2.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Matthey S, Nicholson D, Ruhs S, et al. Rapid detection of respiratory viruses by shell vial culture and direct staining by using pooled and individual monoclonal antibodies. J Clin Microbiol. 1992;30:540–4.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Hall CB, Douglas Jr RG. Clinically useful method for the isolation of respiratory syncytial virus. J Infect Dis. 1975;131:1–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Ebihara T, Endo R, Ma X, Ishiguro N, Kikuta H. Detection of human metapneumovirus antigens in nasopharyngeal secretions by an immunofluorescent-antibody test. J Clin Microbiol. 2005;43:1138–41.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Englund JA, Anderson LJ, Rhame FS. Nosocomial transmission of respiratory syncytial virus in immunocompromised adults. J Clin Microbiol. 1991;29:115–9.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Storch GA, Hall CB, Anderson LJ, Park CS, Dohner DE. Antigenic and nucleic acid analysis of nosocomial isolates of respiratory syncytial virus. J Infect Dis. 1993;167:562–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Machado AF, Sallum MA, Vilas Boas LS, Tateno AF, Machado CM. Molecular characterization of strains of respiratory syncytial virus identified in a hematopoietic stem cell transplant outpatient unit over 2 years: community or nosocomial infection? Biol Blood Marrow Transplant. 2008;14:1348–55.PubMedCrossRefGoogle Scholar
  45. 45.
    Chu HY, Renaud C, Ficken E, Thomson B, Kuypers J, Englund JA. Respiratory tract infections due to human metapneumovirus in immunocompromised children. J Pediatric Infect Dis Soc. 2014;3:286–93.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Couch RB, Englund JA, Whimbey E. Respiratory viral infections in immunocompetent and immunocompromised persons. Am J Med. 1997;102:2–9. discussion 25–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Wasserman R, August CS, Plotkin SA. Viral infections in pediatric bone marrow transplant patients. Pediatr Infect Dis J. 1988;7:109–15.PubMedCrossRefGoogle Scholar
  48. 48.
    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;24:333–43.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Renaud C, Xie H, Seo S, et al. Mortality rates of human metapneumovirus and respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation recipients. Biol Blood Marrow Transplant. 2013;19:1220–6.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Peck AJ, Englund JA, Kuypers J, et al. Respiratory virus infection among hematopoietic cell transplant recipients: evidence for asymptomatic parainfluenza virus infection. Blood. 2007;110:1681–8.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Pohl C, Green M, Wald ER, Ledesma-Medina J. Respiratory syncytial virus infections in pediatric liver transplant recipients. J Infect Dis. 1992;165:166–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Bridevaux PO, Aubert JD, Soccal PM, Mazza-Stalder J, Berutto C, Rochat T, et al. Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study. Thorax. 2014;69(1):32–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Lo MS, Lee GM, Gunawardane N, Burchett SK, Lachenauer CS, Lehmann LE. The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy. Pediatr Transplant. 2013;17(2):133–43.PubMedCrossRefGoogle Scholar
  54. 54.
    Larcher C, Geltner C, Fischer H, Nachbaur D, Muller LC, Huemer HP. Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology. J Heart Lung Transplant. 2005;24:1891–901.PubMedCrossRefGoogle Scholar
  55. 55.
    Martino R, Porras RP, Rabella N, et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant. 2005;11:781–96.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Raboni SM, Nogueira MB, Tsuchiya LR, et al. Respiratory tract viral infections in bone marrow transplant patients. Transplantation. 2003;76:142–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Garbino J, Soccal PM, Aubert JD, et al. Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in adults. Thorax. 2009;64:399–404.PubMedCrossRefGoogle Scholar
  58. 58.
    Wendt CH, Fox JM, Hertz MI. Paramyxovirus infection in lung transplant recipients. J Heart Lung Transplant. 1995;14:479–85.PubMedGoogle Scholar
  59. 59.
    Wendt CH. Community respiratory viruses: organ transplant recipients. Am J Med. 1997;102:31–6. discussion 42–3.PubMedCrossRefGoogle Scholar
  60. 60.
    Peigue-Lafeuille H, Gazuy N, Mignot P, Deteix P, Beytout D, Baguet JC. Severe respiratory syncytial virus pneumonia in an adult renal transplant recipient: successful treatment with ribavirin. Scand J Infect Dis. 1990;22:87–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Vicente D, Montes M, Cilla G, Perez-Yarza EG, Perez-Trallero E. Differences in clinical severity between genotype A and genotype B human metapneumovirus infection in children. Clin Infect Dis. 2006;42:e111–3.PubMedCrossRefGoogle Scholar
  62. 62.
    Papenburg J, Hamelin ME, Ouhoummane N, et al. Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children. J Infect Dis. 2012;206:178–89.PubMedCrossRefGoogle Scholar
  63. 63.
    Williams JV, Martino R, Rabella N, et al. A prospective study comparing human metapneumovirus with other respiratory viruses in adults with hematologic malignancies and respiratory tract infections. J Infect Dis. 2005;192:1061–5.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Englund JA, Boeckh M, Kuypers J, et al. Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients. Ann Intern Med. 2006;144:344–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Sumino KC, Agapov E, Pierce RA, et al. Detection of severe human metapneumovirus infection by real-time polymerase chain reaction and histopathological assessment. J Infect Dis. 2005;192:1052–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Debiaggi M, Canducci F, Sampaolo M, et al. Persistent symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients. J Infect Dis. 2006;194:474–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Oliveira R, Machado A, Tateno A, Boas LV, Pannuti C, Machado C. Frequency of human metapneumovirus infection in hematopoietic SCT recipients during 3 consecutive years. Bone Marrow Transplant. 2008;42:265–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Kamboj M, Gerbin M, Huang CK, et al. Clinical characterization of human metapneumovirus infection among patients with cancer. J Infect. 2008;57:464–71.PubMedCrossRefGoogle Scholar
  69. 69.
    Debur MC, Vidal LR, Stroparo E, et al. Human metapneumovirus infection in hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2010;12:173–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Weigt SS, Gregson AL, Deng JC, Lynch 3rd JP, Belperio JA. Respiratory viral infections in hematopoietic stem cell and solid organ transplant recipients. Semin Respir Crit Care Med. 2011;32:471–93.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Hughes JH. Physical and chemical methods for enhancing rapid detection of viruses and other agents. Clin Microbiol Rev. 1993;6:150–75.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Espy MJ, Hierholzer JC, Smith TF. The effect of centrifugation on the rapid detection of adenovirus in shell vials. Am J Clin Pathol. 1987;88:358–60.PubMedCrossRefGoogle Scholar
  73. 73.
    Weinberg A, Lyu DM, Li S, Marquesen J, Zamora MR. Incidence and morbidity of human metapneumovirus and other community-acquired respiratory viruses in lung transplant recipients. Transpl Infect Dis. 2010;12:330–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Kumar D, Husain S, Chen MH, et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation. 2010;89:1028–33.PubMedCrossRefGoogle Scholar
  75. 75.
    Kisch AL, Johnson KM, Chanock RM. Immunofluorescence with respiratory syncytial virus. Virology. 1962;16:177–89.PubMedCrossRefGoogle Scholar
  76. 76.
    Daley P, Castriciano S, Chernesky M, Smieja M. Comparison of flocked and rayon swabs for collection of respiratory epithelial cells from uninfected volunteers and symptomatic patients. J Clin Microbiol. 2006;44:2265–7.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Dosanjh A. Respiratory metapneumoviral infection without co-infection in association with acute and chronic lung allograft dysfunction. J Inflamm Res. 2015;8:79–82.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Feldman S, Webster RG, Sugg M. Influenza in children and young adults with cancer: 20 cases. Cancer. 1977;39:350–3.PubMedCrossRefGoogle Scholar
  79. 79.
    Whimbey E, Couch RB, Englund JA, et al. Respiratory syncytial virus pneumonia in hospitalized adult patients with leukemia. Clin Infect Dis. 1995;21:376–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Ljungman P, Ward KN, Crooks BN, et al. Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2001;28:479–84.PubMedCrossRefGoogle Scholar
  81. 81.
    Nichols WG, Gooley T, Boeckh M. Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: the Fred Hutchinson Cancer Research Center experience. Biol Blood Marrow Transplant. 2001;7(Suppl):11S–5.PubMedCrossRefGoogle Scholar
  82. 82.
    Chemaly RF, Ghosh S, Bodey GP, et al. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore). 2006;85:278–87.CrossRefGoogle Scholar
  83. 83.
    Seo S, Campbell AP, Xie H, et al. Outcome of respiratory syncytial virus lower respiratory tract disease in hematopoietic cell transplant recipients receiving aerosolized ribavirin: significance of stem cell source and oxygen requirement. Biol Blood Marrow Transplant. 2013;19:589–96.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Kim YJ, Guthrie KA, Waghmare A, et al. Respiratory syncytial virus in hematopoietic cell transplant recipients: factors determining progression to lower respiratory tract disease. J Infect Dis. 2014;209:1195–204.PubMedCrossRefGoogle Scholar
  85. 85.
    Debiaggi M, Canducci F, Terulla C, et al. Long-term study on symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients. New Microbiol. 2007;30:255–8.PubMedGoogle Scholar
  86. 86.
    Kanne JP, Godwin JD, Franquet T, Escuissato DL, Muller NL. Viral pneumonia after hematopoietic stem cell transplantation: high-resolution CT findings. J Thorac Imaging. 2007;22:292–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Franquet T, Muller NL, Lee KS, Gimenez A, Flint JD. High-resolution CT and pathologic findings of noninfectious pulmonary complications after hematopoietic stem cell transplantation. AJR Am J Roentgenol. 2005;184:629–37.PubMedCrossRefGoogle Scholar
  88. 88.
    Dare R, Sanghavi S, Bullotta A, et al. Diagnosis of human metapneumovirus infection in immunosuppressed lung transplant recipients and children evaluated for pertussis. J Clin Microbiol. 2007;45:548–52.PubMedCrossRefGoogle Scholar
  89. 89.
    Harrington RD, Hooton TM, Hackman RC, et al. An outbreak of respiratory syncytial virus in a bone marrow transplant center. J Infect Dis. 1992;165:987–93.PubMedCrossRefGoogle Scholar
  90. 90.
    Kassis C, Champlin RE, Hachem RY, et al. Detection and control of a nosocomial respiratory syncytial virus outbreak in a stem cell transplantation unit: the role of palivizumab. Biol Blood Marrow Transplant. 2010;16:1265–71.PubMedCrossRefGoogle Scholar
  91. 91.
    Chu HY, Englund JA, Podczervinski S, et al. Nosocomial transmission of respiratory syncytial virus in an outpatient cancer center. Biol Blood Marrow Transplant. 2014;20:844–51.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Hoellein A, Hecker J, Hoffmann D, et al. Serious outbreak of human metapneumovirus in patients with hematologic malignancies. Leuk Lymphoma. 2015:1–5.Google Scholar
  93. 93.
    Englund JA, Piedra PA, Jefferson LS, Wilson SZ, Taber LH, Gilbert BE. High-dose, short-duration ribavirin aerosol therapy in children with suspected respiratory syncytial virus infection. J Pediatr. 1990;117:313–20.PubMedCrossRefGoogle Scholar
  94. 94.
    Hirsch HH, Martino R, Ward KN, Boeckh M, Einsele H, Ljungman P. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis. 2013;56:258–66.PubMedCrossRefGoogle Scholar
  95. 95.
    Chemaly RF, Shah DP, Boeckh MJ. Management of respiratory viral infections in hematopoietic cell transplant recipients and patients with hematologic malignancies. Clin Infect Dis. 2014;59 Suppl 5:S344–51.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Chemaly RF, Torres HA, Munsell MF, et al. An adaptive randomized trial of an intermittent dosing schedule of aerosolized ribavirin in patients with cancer and respiratory syncytial virus infection. J Infect Dis. 2012;206:1367–71.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Boeckh M, Englund J, Li Y, et al. Randomized controlled multicenter trial of aerosolized ribavirin for respiratory syncytial virus upper respiratory tract infection in hematopoietic cell transplant recipients. Clin Infect Dis. 2007;44:245–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Whimbey E, Champlin RE, Englund JA, et al. Combination therapy with aerosolized ribavirin and intravenous immunoglobulin for respiratory syncytial virus disease in adult bone marrow transplant recipients. Bone Marrow Transplant. 1995;16:393–9.PubMedGoogle Scholar
  99. 99.
    Shah DP, Ghantoji SS, Shah JN, et al. Impact of aerosolized ribavirin on mortality in 280 allogeneic haematopoietic stem cell transplant recipients with respiratory syncytial virus infections. J Antimicrob Chemother. 2013;68:1872–80.PubMedCrossRefGoogle Scholar
  100. 100.
    Marcelin JR, Wilson JW, Razonable RR, Mayo Clinic HO and Transplant Infectious Diseases S. Oral ribavirin therapy for respiratory syncytial virus infections in moderately to severely immunocompromised patients. Transpl Infect Dis. 2014;16:242–50.Google Scholar
  101. 101.
    Li L, Avery R, Budev M, Mossad S, Danziger-Isakov L. Oral versus inhaled ribavirin therapy for respiratory syncytial virus infection after lung transplantation. J Heart Lung Transplant. 2012;31:839–44.PubMedCrossRefGoogle Scholar
  102. 102.
    Burrows FS, Carlos LM, Benzimra M, et al. Oral ribavirin for respiratory syncytial virus infection after lung transplantation: efficacy and cost-efficiency. J Heart Lung Transplant. 2015;34:958–62.PubMedCrossRefGoogle Scholar
  103. 103.
    Gruber WC, Wilson SZ, Throop BJ, Wyde PR. Immunoglobulin administration and ribavirin therapy: efficacy in respiratory syncytial virus infection of the cotton rat. Pediatr Res. 1987;21:270–4.PubMedCrossRefGoogle Scholar
  104. 104.
    Hemming VG, Rodriguez W, Kim HW, et al. Intravenous immunoglobulin treatment of respiratory syncytial virus infections in infants and young children. Antimicrob Agents Chemother. 1987;31:1882–6.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    De Vincenzo JP, Leombruno D, Soiffer RJ, Siber GR. Immunotherapy of respiratory syncytial virus pneumonia following bone marrow transplantation. Bone Marrow Transplant. 1996;17:1051–6.PubMedGoogle Scholar
  106. 106.
    Rodriguez WJ, Gruber WC, Groothuis JR, et al. Respiratory syncytial virus immune globulin treatment of RSV lower respiratory tract infection in previously healthy children. Pediatrics. 1997;100:937–42.PubMedCrossRefGoogle Scholar
  107. 107.
    Martin MA, Bock MJ, Pfaller MA, Wenzel RP. Respiratory syncytial virus infections in adult bone marrow transplant recipients. Lancet. 1988;1:1396–7.PubMedCrossRefGoogle Scholar
  108. 108.
    Avetisyan G, Mattsson J, Sparrelid E, Ljungman P. Respiratory syncytial virus infection in recipients of allogeneic stem-cell transplantation: a retrospective study of the incidence, clinical features, and outcome. Transplantation. 2009;88:1222–6.PubMedCrossRefGoogle Scholar
  109. 109.
    DeVincenzo J, Lambkin-Williams R, Wilkinson T, et al. A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci U S A. 2010;107:8800–5.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Lewinsohn DM, Bowden RA, Mattson D, Crawford SW. Phase I study of intravenous ribavirin treatment of respiratory syncytial virus pneumonia after marrow transplantation. Antimicrob Agents Chemother. 1996;40:2555–7.PubMedPubMedCentralGoogle Scholar
  111. 111.
    Englund JA, Piedra PA, Whimbey E. Prevention and treatment of respiratory syncytial virus and parainfluenza viruses in immunocompromised patients. Am J Med. 1997;102:61–70. discussion 5–6.PubMedCrossRefGoogle Scholar
  112. 112.
    Sparrelid E, Ljungman P, Ekelof-Andstrom E, et al. Ribavirin therapy in bone marrow transplant recipients with viral respiratory tract infections. Bone Marrow Transplant. 1997;19:905–8.PubMedCrossRefGoogle Scholar
  113. 113.
    McCormick JB, King IJ, Webb PA, et al. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986;314:20–6.PubMedCrossRefGoogle Scholar
  114. 114.
    Huggins JW, Hsiang CM, Cosgriff TM, et al. Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome. J Infect Dis. 1991;164:1119–27.PubMedCrossRefGoogle Scholar
  115. 115.
    Ghosh S, Champlin RE, Englund J, et al. Respiratory syncytial virus upper respiratory tract illnesses in adult blood and marrow transplant recipients: combination therapy with aerosolized ribavirin and intravenous immunoglobulin. Bone Marrow Transplant. 2000;25:751–5.PubMedCrossRefGoogle Scholar
  116. 116.
    Wyde PR, Chetty SN, Jewell AM, Boivin G, Piedra PA. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro. Antiviral Res. 2003;60:51–9.PubMedCrossRefGoogle Scholar
  117. 117.
    Hamelin ME, Prince GA, Boivin G. Effect of ribavirin and glucocorticoid treatment in a mouse model of human metapneumovirus infection. Antimicrob Agents Chemother. 2006;50:774–7.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Raad I, Abbas J, Whimbey E. Infection control of nosocomial respiratory viral disease in the immunocompromised host. Am J Med. 1997;102:48–52. discussion 3–4.PubMedCrossRefGoogle Scholar
  119. 119.
    Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children—diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:1003–32.PubMedCrossRefGoogle Scholar
  120. 120.
    Centers for Disease C, Prevention, Infectious Disease Society of A, American Society of B and Marrow T. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Recomm Rep. 2000;49:1–125, CE1–7.Google Scholar
  121. 121.
    American Academy of Pediatrics Committee on Infectious D and American Academy of Pediatrics Bronchiolitis Guidelines C. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134:415–20.Google Scholar
  122. 122.
    Cortez K, Murphy BR, Almeida KN, et al. Immune-globulin prophylaxis of respiratory syncytial virus infection in patients undergoing stem-cell transplantation. J Infect Dis. 2002;186:834–8.PubMedCrossRefGoogle Scholar
  123. 123.
    Boeckh M, Berrey MM, Bowden RA, Crawford SW, Balsley J, Corey L. Phase 1 evaluation of the respiratory syncytial virus-specific monoclonal antibody palivizumab in recipients of hematopoietic stem cell transplants. J Infect Dis. 2001;184:350–4.PubMedCrossRefGoogle Scholar
  124. 124.
    Schuster JE, Cox RG, Hastings AK, et al. A broadly neutralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus. J Infect Dis. 2015;211:216–25.PubMedCrossRefGoogle Scholar
  125. 125.
    Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15:1143–238.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    DeVincenzo JP, Whitley RJ, Mackman RL, et al. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med. 2014;371:711–22.PubMedCrossRefGoogle Scholar
  127. 127.
    De Clercq E. Chemotherapy of respiratory syncytial virus infections: the final breakthrough. Int J Antimicrob Agents. 2015;45:234–7.PubMedCrossRefGoogle Scholar
  128. 128.
    Murray J, Saxena S, Sharland M. Preventing severe respiratory syncytial virus disease: passive, active immunisation and new antivirals. Arch Dis Child. 2014;99:469–73.PubMedCrossRefGoogle Scholar
  129. 129.
    McLellan JS, Chen M, Kim A, Yang Y, Graham BS, Kwong PD. Structural basis of respiratory syncytial virus neutralization by motavizumab. Nat Struct Mol Biol. 2010;17:248–50.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Polack FP. The changing landscape of respiratory syncytial virus. Vaccine. 2015.Google Scholar
  131. 131.
    Karron RA, Buchholz UJ, Collins PL. Live-attenuated respiratory syncytial virus vaccines. Curr Top Microbiol Immunol. 2013;372:259–84.PubMedPubMedCentralGoogle Scholar
  132. 132.
    Green CA, Scarselli E, Sande CJ, et al. Chimpanzee adenovirus- and MVA-vectored respiratory syncytial virus vaccine is safe and immunogenic in adults. Sci Transl Med. 2015;7:300ra126.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Bernstein DI, Malkin E, Abughali N, et al. Phase 1 study of the safety and immunogenicity of a live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine in seronegative children. Pediatr Infect Dis J. 2012;31:109–14.PubMedCrossRefGoogle Scholar
  134. 134.
    Mackow N, Amaro-Carambot E, Liang B, et al. Attenuated human parainfluenza virus type 1 (HPIV1) expressing the fusion glycoprotein of human respiratory syncytial virus (RSV) as a bivalent HPIV1/RSV vaccine. J Virol. 2015;89:10319–32.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Wen SC, Williams JV. New approaches for immunization and therapy against human metapneumovirus. Clin Vaccine Immunol. 2015;22:858–66.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Open Access This chapter is distributed under the terms of the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyCentre Hospitalier Universitaire Sainte-JustineMontrealCanada
  2. 2.Department of PediatricsSeattle Children’s HospitalSeattleUSA

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