Pediatric Nephrology

, Volume 27, Issue 5, pp 705–717

Monitoring and managing viral infections in pediatric renal transplant recipients



Viral infections remain a significant cause of morbidity and mortality following renal transplantation. The pediatric cohort is at high risk of developing virus-related complications due to immunological naiveté and the increased alloreactivity risk that requires maintaining a heavily immunosuppressive environment. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses may affect clinical outcome. Recent technological advances and novel antiviral therapy have allowed implementation of viral and immunological monitoring protocols and adoption of prophylactic or preemptive treatment approaches in high-risk groups. These strategies have led to improved viral infection management in the immunocompromised host, with significant impact on outcome. We review the major viral infections seen following kidney transplantation and discuss strategies for preventing and managing these pathogens.


Cytomegalovirus Polyomavirus BK Epstein-Barr virus Quantitative DNA assays Cellular immunity Kidney transplantation 


  1. 1.
    Fishman JA, Rubin RH (1998) Infection in organ-transplant recipients. N Engl J Med 338:1741–1751PubMedCrossRefGoogle Scholar
  2. 2.
    Dharnidharka VR, Stablein DM, Harmon WE (2004) Post-transplant infections now exceed acute rejection as cause for hospitalization: a report of the NAPRTCS. Am J Transplant 4:384–389PubMedCrossRefGoogle Scholar
  3. 3.
    Hirsch HH (2005) BK virus: opportunity makes a pathogen. Clin Infect Dis 41:354–360PubMedCrossRefGoogle Scholar
  4. 4.
    Fischer SA (2008) Emerging viruses in transplantation: there is more to infection after transplant than CMV and EBV. Transplantation 86:1327–1339PubMedCrossRefGoogle Scholar
  5. 5.
    Humar A, Michaels M (2006) American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant 6:262PubMedCrossRefGoogle Scholar
  6. 6.
    Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Snydman DR, Allen U, Humar A, Transplantation Society International CMV Consensus Group (2010) International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 89:779–795PubMedCrossRefGoogle Scholar
  7. 7.
    Baldanti F, Gatti M, Furione M, Paolucci S, Tinelli C, Comoli P, Merli P, Locatelli F (2008) Kinetics of Epstein-Barr virus DNA load in different blood compartments of pediatric recipients of T-cell depleted HLA-haploidentical stem cell transplantation. J Clin Microbiol 46:3672–3677PubMedCrossRefGoogle Scholar
  8. 8.
    Nickeleit V, Klimkait T, Binet IF Dalquen P, Del Zenero V, Thiel G, Mihatsch MJ, Hirsch HH (2000) Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. N Engl J Med 342:1309–1315PubMedCrossRefGoogle Scholar
  9. 9.
    Smets F, Latinne D, Bazin H, Reding R, Otte JB, Buts JP, Sokal EM (2002) Ratio between Epstein-Barr viral load and anti-Epstein-Barr virus specific T-cell response as a predictive marker of posttransplant lymphoproliferative disease. Transplantation 73:1603–1610PubMedCrossRefGoogle Scholar
  10. 10.
    Ginevri F, Hirsch HH, Comoli P (2008) Cellular immune responses to BK virus. Curr Opin Organ Transplant 13:569–574PubMedCrossRefGoogle Scholar
  11. 11.
    Rooney CM, Smith CA, Ng CY, Loftin S, Li C, Krance RA, Brenner MK, Heslop HE (1995) Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 345:9–12PubMedCrossRefGoogle Scholar
  12. 12.
    Choquet S, Leblond V, Herbrecht R, Socié G, Stoppa AM, Vandenberghe P, Fischer A, Morschhauser F, Salles G, Feremans W, Vilmer E, Peraldi MN, Lang P, Lebranchu Y, Oksenhendler E, Garnier JL, Lamy T, Jaccard A, Ferrant A, Offner F, Hermine O, Moreau A, Fafi-Kremer S, Morand P, Chatenoud L, Berriot-Varoqueaux N, Bergougnoux L, Milpied N (2006) Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood 107:3053–3057PubMedCrossRefGoogle Scholar
  13. 13.
    Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, Freeman R, Heaton N, Pescovitz MD, Valganciclovir Solid Organ Transplant Study Group (2004) Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 4:611–620PubMedCrossRefGoogle Scholar
  14. 14.
    Betts RF, Freeman RB, Douglas RG Jr, Talley TE (1977) Clinical manifestations of renal allograft derived primary cytomegalovirus infection. Am J Dis Child 131:759–763PubMedGoogle Scholar
  15. 15.
    Rubin RH (1989) The indirect effects of cytomegalovirus infection on the outcome of organ transplantation. JAMA 261:3607–3609PubMedCrossRefGoogle Scholar
  16. 16.
    Rubin RH (2007) The pathogenesis and clinical management of cytomegalovirus infection in the organ transplant recipient: the end of the ‘silo hypothesis’. Curr Opin Infect Dis 20:399–407PubMedCrossRefGoogle Scholar
  17. 17.
    Kranz B, Vester U, Wingen AM, Nadalin S, Paul A, Broelsch CE, Hoyer PF (2008) Acute rejection episodes in pediatric renal transplant recipients with cytomegalovirus infection. Pediatr Transplant 12:474–478PubMedCrossRefGoogle Scholar
  18. 18.
    Paya CV, Razonable RR (2003) Cytomegalovirus infection after organ transplantation. In:Bowden RA, Ljungman P, Paya CV, eds. Transplant Infections, 2nd Edn. Lippincott, Williams, and Wilkins, pp 298– 325Google Scholar
  19. 19.
    Preiksaitis JK, Brennan DC, Fishman J, Allen U (2005) Canadian society of transplantation consensus workshop on cytomegalovirus management in solid organ transplantation final report. Am J Transplant 5:218–227PubMedCrossRefGoogle Scholar
  20. 20.
    Paya CV, Wold AD, Smith TF (1987) Detection of cytomegalovirus infections in specimens other than urine by the shell vial assay and conventional tube cell cultures. J Clin Microbiol 25:755–757PubMedGoogle Scholar
  21. 21.
    van den Berg AP, Klompmaker IJ, Haagsma EB, Haagsma EB, Scholten-Sampson A, Bijleveld CM, Schirm J, van der Giessen M, Slooff MJ, The TH (1991) Antigenemia in the diagnosis and monitoring of active cytomegalovirus infection after liver transplantation. J Infect Dis 164:265–270PubMedCrossRefGoogle Scholar
  22. 22.
    Locatelli F, Percivalle E, Comoli P, Maccario R, Zecca M, Giorgiani G, De Stefano P, Gerna G (1994) Human cytomegalovirus (HCMV) infection in pediatric patients given allogeneic bone marrow transplantation: role of early antiviral treatment for HCMV antigenemia on patients’ outcome. Br J Haematol 88:64–71PubMedCrossRefGoogle Scholar
  23. 23.
    Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG (2005) Metaanalysis: The efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med 143:870–880PubMedGoogle Scholar
  24. 24.
    Smith JM, Corey L, Bittner R, Finn LS, Healey PJ, Davis CL, McDonald RA (2010) Subclinical viremia increases risk for chronic allograft injury in pediatric renal transplantation. J Am Soc Nephrol 21:1579–1586PubMedCrossRefGoogle Scholar
  25. 25.
    Khoury JA, Storch GA, Bohl DL, Schuessler RM, Torrence SM, Lockwood M, Gaudreault-Keener M, Koch MJ, Miller BW, Hardinger KL, Schnitzler MA, Brennan DC (2006) Prophylactic versus preemptive oral valganciclovir for the management of cytomegalovirus infection in adult renal transplant recipients. Am J Transplant 6:2134–2143PubMedCrossRefGoogle Scholar
  26. 26.
    Humar A, Lebranchu Y, Vincenti F, Blumberg E, Punch J, Limaye A, Abramowicz D, Jardine A, Voulgari A, Ives J, Hauser I, Peeters P (2010) The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high risk kidney transplant recipients. Am J Transplant 10:1228–1237PubMedCrossRefGoogle Scholar
  27. 27.
    San Juan R, Yebra M, Lumbreras C, López-Medrano F, Lizasoain M, Meneu JC, Delgado J, Andrés A, Aguado JM (2009) A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R-) solid organ transplant recipients. Clin Transplant 23:666–671PubMedCrossRefGoogle Scholar
  28. 28.
    Sanghavi SK, Abu-Elmagd K, Keightley MC, St George K, Lewandowski K, Boes SS, Bullotta A, Dare R, Lassak M, Husain S, Kwak EJ, Paterson DL, Rinaldo CR (2008) Relationship of cytomegalovirus load assessed by real-time PCR to pp 65 antigenemia in organ transplant recipients. J Clin Virol 42:335–342PubMedCrossRefGoogle Scholar
  29. 29.
    Emery VC, Sabin CA, Cope AV, Gor D, Hassan-Walker AF, Griffiths PD (2000) Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 355:2032–2036PubMedCrossRefGoogle Scholar
  30. 30.
    Pescovitz MD, Brook B, Jindal RM, Leapman SB, Milgram MG, Filo RS (1997) Oral ganciclovir in pediatric transplant recipients: A pharmacokinetic study. Clin Transplant 11:613–617PubMedGoogle Scholar
  31. 31.
    Vaudry W, Ettenger R, Jara P, Varela-Fascinetto G, Bouw MR, Ives J, Walker R, Valcyte WV16726 Study Group (2009) Valganciclovir dosing according to body surface area and renal function in pediatric solid organ transplant recipients. Am J Transplant 9:636–643PubMedCrossRefGoogle Scholar
  32. 32.
    Gerna G, Sarasini A, Lilleri D, Percivalle E, Torsellini M, Baldanti F, Revello MG (2003) In vitro model for the study of the dissociation of increasing antigenemia and decreasing DNAemia and viremia during treatment of human cytomegalovirus infection with ganciclovir in transplant recipients. J Infect Dis 188:1639–1647PubMedCrossRefGoogle Scholar
  33. 33.
    Limaye AP, Corey L, Koelle DM, Davis CL, Boeckh M (2000) Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants. Lancet 356:645–649PubMedCrossRefGoogle Scholar
  34. 34.
    Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, Mihatsch MJ, Nickeleit V, Ramos E, Randhawa P, Shapiro R, Steiger J, Suthanthiran M, Trofe J (2005) Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 79:1277–1286PubMedCrossRefGoogle Scholar
  35. 35.
    Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA, Cohen EP (2005) BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int 68:1834–1839PubMedCrossRefGoogle Scholar
  36. 36.
    Ramos E, Drachenberg CB, Papadimitriou JC, Hamze O, Fink JC, Klassen DK, Drachenberg RC, Wiland A, Wali R, Cangro CB, Schweitzer E, Bartlett ST, Weir MR (2002) Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol 13:2145–2151PubMedCrossRefGoogle Scholar
  37. 37.
    Schold JD, Rehman S, Kayle LK, Magliocca J, Srinivas TR, Meier-Kriesche HU (2009) Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States. Transpl Int 22:626–634PubMedCrossRefGoogle Scholar
  38. 38.
    Hirsch HH, Steiger J (2003) Polyomavirus BK. Lancet Infect Dis 3:611–623PubMedCrossRefGoogle Scholar
  39. 39.
    Funk GA, Steiger J, Hirsch HH (2006) Rapid dynamics of polyomavirus type BK in renal transplant recipients. J Infect Dis 193:80–87PubMedCrossRefGoogle Scholar
  40. 40.
    Randhawa PS, Finkelstein S, Scantlebury V, Shapiro R, Vivas C, Jordan M, Picken MM, Demetris AJ (1999) Human Polyoma virus-associated interstial nephritis in the allograft kidney. Transplantation 67:103–109PubMedCrossRefGoogle Scholar
  41. 41.
    Drachenberg CB, Papadimitriou JC, Hirsch HH, Wali R, Crowder C, Nogueira J, Cangro CB, Mendley S, Mian A, Ramos E (2004) Histological patterns of polyomavirus nephropathy: Correlation with graft outcome and viral load. Am J Transplantation 4:2082–2092CrossRefGoogle Scholar
  42. 42.
    Ginevri F, Hirsch HH (2008) Polyomavirus-associated nephropathy. In: Molony DA, Craig JC (eds) Evidence-Based Nephrology. John Wiley & Sons, LondonGoogle Scholar
  43. 43.
    Acott PD, Hirsch HH (2007) BK virus infection, replication, and diseases in pediatric kidney transplantation. Pediatr Nephrol 22:1243–1250PubMedCrossRefGoogle Scholar
  44. 44.
    Dharnidharka VR, Cherikh WS, Abbott KC (2009) An OPTN analysis of national registry data on treatment of BK virus allograft nephropathy in the United States. Transplantation 87:1019–1026PubMedCrossRefGoogle Scholar
  45. 45.
    Ginevri F, De Santis R, Comoli P, Pastorino N, Rossi C, Botti G, Fontana I, Nocera A, Cardillo M, Ciardi MR, Locatelli F, Maccario R, Perfumo F, Azzi A (2003) Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches. Transplantation 75:1266–1270PubMedCrossRefGoogle Scholar
  46. 46.
    Haysom L, Rosenberg AR, Kainer G, Waliuzzaman ZM, Roberts J, Rawlinson WD, Mackie FE (2004) BK viral infection in an Australian pediatric renal transplant population. Pediatr Transplant 8:480–484PubMedCrossRefGoogle Scholar
  47. 47.
    Herman J, Van Ranst M, Snoeck R, Beuselinck K, Lerut E, Van Damme-Lombaerts R (2004) Polyomavirus infection in pediatric renal transplant recipients: evaluation using a quantitative real-time PCR technique. Pediatr Transplant 8:485–492PubMedCrossRefGoogle Scholar
  48. 48.
    Alexander RT, Langlois V, Tellier R, Robinson L, Hebert D (2006) The prevalence of BK viremia and urinary viral shedding in a pediatric renal transplant population: a single-center retrospective analysis. Pediatr Transplant 10:586–592PubMedCrossRefGoogle Scholar
  49. 49.
    Smith JM, Dharnidharka VR, Talley L, Martz K, McDonald RA (2007) BK virus nephropathy in pediatric renal transplant recipients: an analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry. Clin J Am Soc Nephrol 2:1037–1042PubMedCrossRefGoogle Scholar
  50. 50.
    KDIGO Guidelines (2009) Am J Transplant 9(Suppl 3):S44–S58Google Scholar
  51. 51.
    Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, Steiger J (2002) Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med 347:488–496PubMedCrossRefGoogle Scholar
  52. 52.
    Hirsch HH Randhawa P, AST Infectious Diseases Community of Practice (2009) BK virus in solid organ transplant recipients. Am J Transplant 9(Suppl 4):S136–S146CrossRefGoogle Scholar
  53. 53.
    Brennan DC, Agha I, Bohl DL, Schnitzler MA, Hardinger KL, Lockwood M, Torrence S, Schuessler R, Roby T, Gaudreault-Keener M, Storch GA (2005) Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 5:582–594PubMedCrossRefGoogle Scholar
  54. 54.
    Ginevri F, Azzi A, Hirsch HH, Basso S, Fontana I, Cioni M, Bodaghi S, Salotti V, Rinieri A, Botti G, Perfumo F, Locatelli F, Comoli P (2007) Prospective monitoring of polyomavirus BK replication and impact of pre-emptive intervention in pediatric kidney recipients. Am J Transplant 7:2727–2735PubMedCrossRefGoogle Scholar
  55. 55.
    Saad ER, Bresnahan BA, Cohen EP, Lu N, Orentas RJ, Vasudev B, Hariharan S (2008) Successful treatment of BK viremia using reduction in immunosuppression without antiviral therapy. Transplantation 85:850–854PubMedCrossRefGoogle Scholar
  56. 56.
    Vats A, Shapiro R, Singh Randhawa P, Scantlebury V, Tuzuner A, Saxena M, Moritz ML, Beattie TJ, Gonwa T, Green MD, Ellis D (2003) Quantitative viral load monitoring and cidofovir therapy for the management of BK virus associated nephropathy in children and adults. Transplantation 75:105–112PubMedCrossRefGoogle Scholar
  57. 57.
    Green M (2001) Management of Epstein-Barr virus-induced post-transplant lymphoproliferative disease in recipients of solid organ transplantation. Am J Transplant 1:103–108PubMedGoogle Scholar
  58. 58.
    Opelz G, Dohler B (2003) Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant 4:222–230CrossRefGoogle Scholar
  59. 59.
    Merlo A, Turrini R, Dolcetti R, Martorelli D, Muraro E, Comoli P, Rosato A (2010) The interplay between EBV and the immune system: a rationale for adoptive cell therapy of EBV-related disorders. Haematologica 95:1769–1777PubMedCrossRefGoogle Scholar
  60. 60.
    Dharnidharka VR, Harmon WE (2001) Management of pediatric postrenal transplantation infections. Semin Nephrol 21:521–531PubMedCrossRefGoogle Scholar
  61. 61.
    Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K (2005) Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 80:1233–1243PubMedCrossRefGoogle Scholar
  62. 62.
    Dharnidharka VR, Sullivan EK, Stablein DM, Tejani AH, Harmon WE (2001) Risk factors for posttransplant lymphoproliferative disorder (PTLD) in pediatric kidney transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation 71:1065–1068PubMedCrossRefGoogle Scholar
  63. 63.
    Kirk AD, Cherikh WS, Ring M, Burke G, Kaufman D, Knechtle SJ, Potdar S, Shapiro R, Dharnidharka VR, Kauffman HM (2007) Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab. Am J Transplant 7:2619–2625PubMedCrossRefGoogle Scholar
  64. 64.
    McDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P, Wyatt R, Arar M, Liereman D, Bridges N, Harmon W, CCTPT Study Group (2008) Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant 8:984–989PubMedCrossRefGoogle Scholar
  65. 65.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. IARC Press, Lyon, FranceGoogle Scholar
  66. 66.
    Cohen JI (2000) Epstein-Barr virus infection. N Engl J Med 343:481–492PubMedCrossRefGoogle Scholar
  67. 67.
    Nalesnik M, Jaffe R, Starzl TE, Demetris AJ, Porter K, Burnham JA, Makowka L, Ho M, Locker J (1988) The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporin A-prednisone immunosuppression. Am J Pathol 133:173–192PubMedGoogle Scholar
  68. 68.
    Baldanti F, Grossi P, Furione M, Simoncini L, Sarasini A, Comoli P, Maccario R, Fiocchi R, Gerna G (2000) High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders. J Clin Microbiol 38:613–619PubMedGoogle Scholar
  69. 69.
    Yang J, Tao Q, Flinn IW, Murray PG, Post LE, Ma H, Piantadosi S, Caligiuri MA, Ambinder RF (2000) Characterization of Epstein-Barr virus-infected B cells in patients with posttransplantation lymphoproliferative disease: disappearance after rituximab therapy does not predict clinical response. Blood 96:4055–4063PubMedGoogle Scholar
  70. 70.
    Rowe DT, Webber S, Schauer EM, Reyes J, Green M (2001) Epstein-Barr virus load monitoring: its role in the prevention and management of post-transplant lymphoproliferative disease. Transpl Infect Dis 3:79–87PubMedCrossRefGoogle Scholar
  71. 71.
    Comoli P, Maccario R, Locatelli F, Valente U, Basso S, Garaventa A, Tomà P, Botti G, Melioli G, Baldanti F, Nocera A, Perfumo F, Ginevri F (2005) Treatment of EBV-related post-renal transplant lymphoproliferative disease with a tailored regimen including EBV-specific T cells. Am J Transplant 5:1415–1422PubMedCrossRefGoogle Scholar
  72. 72.
    Comoli P, Rooney CM (2006) Treatment of Epstein-Barr virus infections. In: Jenson HB, Tselis A (eds) Epstein-Barr virus. Taylor & Francis, New York, pp 351–372Google Scholar
  73. 73.
    Swinnen LJ, Mullen GM, Carr TJ, Costanzo MR, Fisher RI (1995) Aggressive treatment for postcardiac transplant lymphoproliferation. Blood 86:3333–3340PubMedGoogle Scholar
  74. 74.
    Muti G, Cantoni S, Oreste P, Klersy C, Gini G, Rossi V, D'Avanzo G, Comoli P, Baldanti F, Montillo M, Nosari A, Morra E (2002) Post-transplant lymphoproliferative disorders: improved outcome after clinico-pathologically tailored treatment. Haematologica 87:67–77PubMedGoogle Scholar
  75. 75.
    Starzl TE, Porter KA, Iwatsuki JT, Rosenthal BW, Shaw RW Jr, Atchison MA, Nalesnik M Ho, Griffith BP, Hakala TR, Hardesty RL, Jaffe R, Bahnson HT (1984) Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1:583PubMedCrossRefGoogle Scholar
  76. 76.
    Porcu P, Eisenbeis CF, Pelletier RP, Davies EA, Baiocchi RA, Roychowdhury S, Vourganti S, Nuovo GJ, Marsh WL, Ferketich AK, Henry ML, Ferguson RM, Caligiuri MA (2002) Successful treatment of posttransplant lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8+ T-cell restoration. Blood 100:2341–2348PubMedCrossRefGoogle Scholar
  77. 77.
    Perrine SP, Hermine O, Small T, Suarez F, O'Reilly R, Boulad F, Fingeroth J, Askin M, Levy A, Mentzer SJ, Di Nicola M, Gianni AM, Klein C, Horwitz S, Faller DV (2007) A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood 109:2571–2578PubMedCrossRefGoogle Scholar
  78. 78.
    Gross TG, Bucuvalas JC, Park JR, Greiner TC, Hinrich SH, Kaufman SS, Langnas AN, McDonald RA, Ryckman FC, Shaw BW, Sudan DL, Lynch JC (2005) Low-dose chemotherapy for Epstein-Barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation. J Clin Oncol 23:6481–6488PubMedCrossRefGoogle Scholar
  79. 79.
    Savoie A, Perpete C, Carpentier L, Joncas J, Alfieri C (1994) Direct correlation between the load of Epstein-Barr virus-infected lymphocytes in the peripheral blood of pediatric transplant patients and risk of lymphoproliferative disease. Blood 83:2715–2722PubMedGoogle Scholar
  80. 80.
    Bingler MA, Feingold B, Miller SA, Quivers E, Michaels MG, Green M, Wadowsky RM, Rowe DT, Webber SA (2008) Chronic high Epstein-Barr viral load state and risk for late-onset posttransplant lymphoproliferative disease/lymphoma in children. Am J Transplant 8:442–5PubMedCrossRefGoogle Scholar
  81. 81.
    Lau AH, Soltys K, Sindhi RK, Bond G, Mazareigos G, Green M (2010) Chronic high Epstein-Barr viral load carriage in pediatric small bowel transplant recipients. Pediatr Transplant 14:549–553PubMedCrossRefGoogle Scholar
  82. 82.
    Green M, Soltys K, Rowe DT, Webber SA, Mazareigos G (2009) Chronic high Epstein-Barr viral load carriage in pediatric liver transplant recipients. Pediatr Transplant 13:319–323PubMedCrossRefGoogle Scholar
  83. 83.
    Ginevri F, Di Marco E, Parodi A, Gurrado A, Cirillo C, Botti G, Fontana I, Valente U, Locatelli F, Comoli P (2008) EBV viral load monitoring and reduction of immunosuppression do not successfully prevent PTLD after pediatric kidney transplantation. Am J Transplant 8(s2):477Google Scholar
  84. 84.
    Lee TC, Savoldo B, Rooney CM, Heslop HE, Gee AP, Caldwell Y, Barshes NR, Scott JD, Bristow LJ, O'Mahony CA, Goss JA (2005) Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients. Am J Transplant 5:2222–2228PubMedCrossRefGoogle Scholar
  85. 85.
    Kim Y, Boeckh M, Eglund JA (2007) 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 28:222–242PubMedCrossRefGoogle Scholar
  86. 86.
    Kuypers J, Wright N, Ferrenberg J, Huang ML, Cent A, Corey L, Morrow R (2006) Comparison of real-time PCR assays with fluorescent-antibody assays for diagnosis of respiratory virus infections in children. J Clin Microbiol 44:2382–2388PubMedCrossRefGoogle Scholar
  87. 87.
    Blanchard SS, Gerrek M, Siegel C, Czinn SJ (2006) Significant morbidity associated with RSV infection in immunosuppressed children following liver transplantation: case report and discussion regarding need of routine prophylaxis. Pediatr Transplant 10:826–829PubMedCrossRefGoogle Scholar
  88. 88.
    Apalsch AM, Green M, Ledesma-Medina J, Nour B, Wald ER (1995) Parainfluenza and influenza virus infections in pediatric organ transplant recipients. Clin Infect Dis 20:394–399PubMedCrossRefGoogle Scholar
  89. 89.
    Ardehall H, Volmar K, Roberts C, Huang ML, Cent A, Corey L, Morrow R (2000) Fatal disseminated adenoviral infection in a renal transplant patient. Transplantation 71:998CrossRefGoogle Scholar
  90. 90.
    Shirali GS, Ni J, Chinnock RE, Johnston JK, Rosenthal GL, Bowles NE, Towbin JA (2001) Association of viral genome with graft loss in children after cardiac transplantation. N Engl J Med 344:1498–1503PubMedCrossRefGoogle Scholar
  91. 91.
    Pelaez A, Lyon GM, Force SD, Ramirez AM, Neujahr DC, Foster M, Naik PM, Gal AA, Mitchell PO, Lawrence EC (2009) Efficacy of oral ribavirin in lung transplant patients with respiratory syncytial virus lower respiratory tract infection. J Heart Lung Transplant 28:67–71PubMedCrossRefGoogle Scholar
  92. 92.
    Chávez-Bueno S, Mejías A, Merryman RA, Ahmad N, Jafri HS, Ramilo O (2007) Intravenous palivizumab and ribavirin combination for respiratory syncytial virus disease in high-risk pediatric patients. Pediatr Infect Dis J 26:1089–1093PubMedCrossRefGoogle Scholar
  93. 93.
    McCurdy LH, Milstone A, Dummer S (2003) Clinical features and outcomes of paramyxoviral infection in lung transplant recipients treated with ribavirin. J Heart Lung Transplant 22:745–753PubMedCrossRefGoogle Scholar
  94. 94.
    Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, Mills RG, Ward P (2001) Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 20:127–133PubMedCrossRefGoogle Scholar
  95. 95.
    Carter BA, Karpen SJ, Quiros-Tejeira RE, Chang IF, Clark BS, Demmler GJ, Heslop HE, Scott JD, Seu P, Goss JA (2002) Intravenous cidofovir therapy for disseminated adenovirus in a pediatric liver transplant recipient. Transplantation 74:1050–1052PubMedCrossRefGoogle Scholar
  96. 96.
    Thomas NJ, Hollenbeck CS, Ceneviva GD, Geskey JM, Young MJ (2007) Palivizumab prophylaxis to prevent respiratory syncytial virus mortality after pediatric bone marrow transplantation: A decision analysis model. J Pediatr Hematol/Oncol 29:227–232CrossRefGoogle Scholar
  97. 97.
    Scharpé J, Evenepoel P, Maes B, Bammens B, Claes K, Osterhaus AD, Vanrenterghem Y, Peetermans WE (2008) Influenza vaccination is efficacious and safe in renal transplant recipients. Am J Transplant 8:332–337PubMedCrossRefGoogle Scholar
  98. 98.
    Clark DA, Griffiths PD (2003) Human herpesvirus 6: relevance of infection in the immunocompromised host. Br J Haematol 120:384–395PubMedCrossRefGoogle Scholar
  99. 99.
    Abdel Massih RC, Razonable RR (2009) Human herpesvirus 6 infections after liver transplantation. World J Gastroenterol 15:2561–2569PubMedCrossRefGoogle Scholar
  100. 100.
    Mendez JC, Dockrell DH, Espy MJ, Smith TF, Wilson JA, Harmsen WS, Ilstrup D, Paya CV (2001) Human beta-herpesvirus interactions in solid organ transplant recipients. J Infect Dis 183:179–184PubMedCrossRefGoogle Scholar
  101. 101.
    Razonable RR, Brown RA, Humar A, Covington E, Alecock E, Paya CV (2005) Herpesvirus infections in solid organ transplant patients at high risk of primary cytomegalovirus disease. J Infect Dis 192:1331–1339PubMedCrossRefGoogle Scholar
  102. 102.
    Gupta M, Diaz-Mitoma F, Feber J, Shaw L, Forget C, Filler G (2003) Tissue HHV6 and 7 determination in pediatric solid organ recipients: a pilot study. Pediatr Transplant 7:458–463PubMedCrossRefGoogle Scholar
  103. 103.
    Singh N, Carrigan DR (1996) Human Herpesvirus-6 in transplantation: An emerging pathogen. Ann Intern Med 124:1065–1071PubMedGoogle Scholar
  104. 104.
    Nash PJ, Avery RK, Tang WH, Starling RC, Taege AJ, Yamani MH (2004) Encephalitis owing to human herpesvirus-6 after cardiac transplant. Am J Transplant 4:1200–1203PubMedCrossRefGoogle Scholar
  105. 105.
    Montejo M, Ramon Fernandez J, Testillano M, Valdivieso A, Aguirrebengoa K, Varas C, Olaizola A, De Urbina JO (2002) Encephalitis caused by human herpesvirus-6 in a liver transplant recipient. Eur Neurol 48:234–235PubMedCrossRefGoogle Scholar
  106. 106.
    Takahashi K, Suzuki M, Iwata Y, Shigeta S, Yamanishi K, De Clercq E (1997) Selective activity of various nucleoside and nucleotide analogues against human herpesvirus 6 and 7. Antivir Chem Chemother 8:24–31Google Scholar
  107. 107.
    Yang J, Lemas VM, Flinn IW, Krone C, Ambinder RF (2000) Application of the ELISPOT assay to the characterization of CD8+ responses to Epstein-Barr virus antigens. Blood 95:241–248PubMedGoogle Scholar
  108. 108.
    Comoli P, Azzi A, Maccario R, Basso S, Botti G, Basile G, Fontana I, Labirio M, Cometa A, Poli F, Perfumo F, Locatelli F, Ginevri F (2004) Polyomavirus BK-specific immunity after kidney transplantation. Transplantation 78:1229–1232PubMedCrossRefGoogle Scholar
  109. 109.
    Mattes FM, Vargas A, Kopycinski J, Hainsworth EG, Sweny P, Nebbia G, Bazeos A, Lowdell M, Klenerman P, Phillips RE, Griffiths PD, Emery VC (2008) Functional Impairment of Cytomegalovirus Specific CD8 T Cells Predicts High-Level Replication After Renal Transplantation. Am J Transplant 8:990–999PubMedCrossRefGoogle Scholar
  110. 110.
    Kumar D, Chernenko S, Moussa G, Cobos I, Manuel O, Preiksaitis J, Venkataraman S, Humar A (2009) Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients. Am J Transplant 9:1214–1222PubMedCrossRefGoogle Scholar
  111. 111.
    Savoldo B, Rooney CM, Quiros-Tejeira RE, Caldwell Y, Wagner HJ, Lee T, Finegold MJ, Dotti G, Heslop HE, Goss JA (2005) Cellular immunity to Epstein-Barr virus in liver transplant recipients treated with rituximab for post-transplant lymphoproliferative disease. Am J Transplant 5:566–572PubMedCrossRefGoogle Scholar
  112. 112.
    Sester U, Presser D, Dirks J, Gartner BC, Kohler H, Sester M (2008) PD-1 expression and IL-2 loss of cytomegalovirus- specific T cells correlates with viremia and reversible functional anergy. Am J Transplant 8:1486–1497PubMedCrossRefGoogle Scholar
  113. 113.
    Binggeli S, Egli A, Schaub S, Binet I, Mayr M, Steiger J, Hirsch HH (2007) Polyomavirus BK-specific cellular immune response to VP1 and Large T-antigen in kidney transplant recipients. Am J Transplant 7:1131–1139PubMedCrossRefGoogle Scholar
  114. 114.
    Prosser SE, Orentas RJ, Jurgens L, Cohen EP, Hariharan S (2008) Recovery of BK virus Large-T-antigen-specific cellular immune response correlates with resolution of BK virus nephropathy. Transplantation 85:185–192PubMedCrossRefGoogle Scholar
  115. 115.
    Bunde T, Kirchner A, Hoffmeister B, Habedank D, Hetzer R, Cherepnev G, Proesch S, Reinke P, Volk HD, Lehmkuhl H, Kern F (2005) Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells. J Exp Med 201:1031–1036PubMedCrossRefGoogle Scholar
  116. 116.
    Heslop HE, Slobod KS, Pule MA, Hale GA, Rousseau A, Smith CA, Bollard CM, Liu H, Wu MF, Rochester RJ, Amrolia PJ, Hurwitz JL, Brenner MK, Rooney CM (2010) Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood 115:925–935PubMedCrossRefGoogle Scholar
  117. 117.
    Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR (1995) Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med 333:1038–1044PubMedCrossRefGoogle Scholar
  118. 118.
    Feuchtinger T, Opherk K, Bethge WA, Topp MS, Schuster FR, Weissinger EM, Mohty M, Or R, Maschan M, Schumm M, Hamprecht K, Handgretinger R, Lang P, Einsele H (2010) Adoptive transfer of pp 65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood 116:4360–4367PubMedCrossRefGoogle Scholar
  119. 119.
    Comoli P, Locatelli F, Ginevri F, Maccario R (2002) Cellular immunotherapy for viral infections in solid organ transplant recipients. Curr Opin Organ Transplant 7:314–319CrossRefGoogle Scholar

Copyright information

© IPNA 2011

Authors and Affiliations

  1. 1.Pediatric Hematology/Oncology and Research LaboratoriesPaviaItaly
  2. 2.Clinical and Experimental Kidney Transplantation UnitGenovaItaly
  3. 3.UOS Medicina Clinica e Sperimentale dei Trapianti d’Organo, Unità Operativa di NefrologiaIstituto G. GasliniGenovaItaly

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