Viral Infections in Transplant Patients

  • Andrea Ferreira-Gonzalez
  • Angela M. Caliendo


Viruses are particularly problematic pathogens in transplant recipients. Viral infections not only can cause disease but also can enhance susceptibility to opportunistic infections by both causing tissue injury and contributing to systemic immunosuppression. Such infections have been shown to increase the rate of graft rejection and increase the risk of cancer. The outcome of viral infections in the transplant setting is the result of a balance among infection in tissues, host antiviral immune function, and the level of immunosuppression required to maintain graft function. Diagnosis of viral infections in immunocompromised patients remains a challenge due to the need to differentiate asymptomatic infection from clinically relevant disease.


Viral Load Hemorrhagic Cystitis Preemptive Therapy Quantitative Polymerase Chain Reaction Assay Peripheral Blood Lympho 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Rubin RH. The direct and indirect effects of infection in liver transplantation: pathogenesis, impact, and clinical management. Curr Clin Top Infect Dis. 2002;22:125–154.PubMedGoogle Scholar
  2. 2.
    Ljungman P. Beta-herpesvirus challenges in the transplant recipient. J Infect Dis. 2002;186(suppl 1):S99–S109.PubMedCrossRefGoogle Scholar
  3. 3.
    Sissons JG, Carmichael AJ. Clinical aspects and management of cytomegalovirus infection. J Infect. 2002;44:78–83.PubMedCrossRefGoogle Scholar
  4. 4.
    Rubin RH. Cytomegalovirus in solid organ transplantation. Transpl Infect Dis. 2001;3(suppl 2):1–5.Google Scholar
  5. 5.
    Aitken C, Barrett-Muir W, Millar C, et al. Use of molecular assays in diagnosis and monitoring of cytomegalovirus disease following renal transplantation. J Clin Microbiol. 1999;37:2804–2807.PubMedGoogle Scholar
  6. 6.
    Caliendo AM, Schuurman R, Yen-Lieberman B, et al. Comparison of quantitative and qualitative PCR assays for cytomegalovirus DNA in plasma. J Clin Microbiol. 2001;39:1334–1338.PubMedCrossRefGoogle Scholar
  7. 7.
    Caliendo AM, St George K, Allega J, et al. Distinguishing cytomegalovirus (CMV) infection and disease with CMV nucleic acid assays. J Clin Microbiol. 2002;40:1581–1586.PubMedCrossRefGoogle Scholar
  8. 8.
    Mazzulli T, Drew LW, Yen-Lieberman B, et al. Multicenter comparison of the digene hybrid capture CMV DNA assay (version 2.0), the pp65 antigenemia assay, and cell culture for detection of cytomegalovirus viremia. J Clin Microbiol. 1999;37:958–963.PubMedGoogle Scholar
  9. 9.
    Gerna G, Baldanti F, Middeldorp JM, et al. Clinical significance of expression of human cytomegalovirus pp67 late transcript in heart, lung, and bone marrow transplant recipients as determined by nucleic acid sequence-based amplification. J Clin Microbiol. 1999;37:902–911.PubMedGoogle Scholar
  10. 10.
    Razonable RR, Brown RA, Wilson J, et al. The clinical use of various blood compartments for cytomegalovirus (CMV) DNA quantitation in transplant recipients with CMV disease. Transplantation. 2002;73:968–973.PubMedCrossRefGoogle Scholar
  11. 11.
    Middeldorp J, Sillekens P, Lunenberg J. Diagnosis of active HCMV infection: the mRNA approach. Organs and Tissue. 2000;2:99–107.Google Scholar
  12. 12.
    Weinberg A, Hodges TN, Li S, et al. Comparison of PCR, antigenemia assay, and rapid blood culture for detection and prevention of cytomegalovirus disease after lung transplantation. J Clin Microbiol. 2000;38:768–772.PubMedGoogle Scholar
  13. 13.
    Caliendo AM, St George K, Kao SY, et al. Comparison of quantitative cytomegalovirus (CMV) PCR in plasma and CMV antigenemia assay: clinical utility of the prototype AMPLICOR CMV MONITOR test in transplant recipients. J Clin Microbiol. 2000;38:2122–2127.PubMedGoogle Scholar
  14. 14.
    Patel R, Smith TF, Espy M, et al. A prospective comparison of molecular diagnostic techniques for the early detection of cytomegalovirus in liver transplant recipients [comment]. J Infect Dis. 1995;171:1010–1014.PubMedGoogle Scholar
  15. 15.
    Humar A, Gregson D, Caliendo AM, et al. Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients. Transplantation. 1999;68:1305–1311.PubMedCrossRefGoogle Scholar
  16. 16.
    Ferreira-Gonzalez A, Fisher RA, Weymouth LA, et al. Clinical utility of a quantitative polymerase chain reaction for diagnosis of cytomegalovirus disease in solid organ transplant patients. Transplantation. 1999;68:991–996.PubMedCrossRefGoogle Scholar
  17. 17.
    Cope AV, Sabin C, Burroughs A, et al. Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donorrecipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation. J Infect Dis. 1997;176:1484–1490.PubMedCrossRefGoogle Scholar
  18. 18.
    Oldenburg N, Lam KM, Khan MA, et al. Evaluation of human cytomegalovirus gene expression in thoracic organ transplant recipients using nucleic acid sequence-based amplification. Transplantation. 2000;70:1209–1215.PubMedCrossRefGoogle Scholar
  19. 19.
    Razonable RR, Brown RA, Espy MJ, et al. Comparative quantitation of cytomegalovirus (CMV) DNA in solid organ transplant recipients with CMV infection by using two high-throughput automated systems. J Clin Microbiol. 2001;39:4472–4476.PubMedCrossRefGoogle Scholar
  20. 20.
    Norris S, Kosar Y, Donaldson N, et al. Cytomegalovirus infection after liver transplantation: viral load as a guide to treating clinical infection. Transplantation. 2002;74:527–531.PubMedCrossRefGoogle Scholar
  21. 21.
    Razonable RR, van Cruijsen H, Brown RA, et al. Dynamics of cytomegalovirus replication during preemptive therapy with oral ganciclovir. J Infect Dis. 2003;187:1801–1808.PubMedCrossRefGoogle Scholar
  22. 22.
    Hebart H, Rudolph T, Loeffler J, et al. Evaluation of the NucliSens CMV pp67 assay for detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation. Bone Marrow Transplant. 2002;30:181–187.PubMedCrossRefGoogle Scholar
  23. 23.
    Li H, Dummer JS, Estes WR, et al. Measurement of human cytomegalovirus loads by quantitative real-time PCR for monitoring clinical intervention in transplant recipients. J Clin Microbiol. 2003;41:187–191.PubMedCrossRefGoogle Scholar
  24. 24.
    Sia IG, Wilson JA, Groettum CM, et al. Cytomegalovirus (CMV) DNA load predicts relapsing CMV infection after solid organ transplantation. J Infect Dis. 2000;181:717–720.PubMedCrossRefGoogle Scholar
  25. 25.
    Humar A, Kumar D, Boivin G, et al. Cytomegalovirus (CMV) virus load kinetics to predict recurrent disease in solid-organ transplant patients with CMV disease. J Infect Dis. 2002;186:829–833.PubMedCrossRefGoogle Scholar
  26. 26.
    Fisher RA, Saggi BH, Ferreira-Gonzalez A, et al. Prospective validation of quantitative polymerase chain reaction for management of cytomegalovirus disease in solid-organ transplant patients. Transplantation. 2002;74:573–576.PubMedCrossRefGoogle Scholar
  27. 27.
    Chou S. Antiviral drug resistance in human cytomegalovirus. Transpl Infect Dis. 1999;1:105–114.PubMedCrossRefGoogle Scholar
  28. 28.
    Chou S, Erice A, Jordan MC, et al. Analysis of the UL97 phosphotransferase coding sequence in clinical cytomegalovirus isolates and identification of mutations conferring ganciclovir resistance. J Infect Dis. 1995;171:576–583.PubMedGoogle Scholar
  29. 29.
    Chou S, Guentzel S, Michels KR, et al. Frequency of UL97 phosphotransferase mutations related to ganciclovir resistance in clinical cytomegalovirus isolates. J Infect Dis. 1995;172:239–242.PubMedGoogle Scholar
  30. 30.
    Chou S, Lurain NS, Thompson KD, et al. Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus. J Infect Dis. 2003;188:32–39.PubMedCrossRefGoogle Scholar
  31. 31.
    Chou S, Miner RC, Drew WL. A deletion mutation in region V of the cytomegalovirus DNA polymerase sequence confers multidrug resistance. J Infect Dis. 2000;182:1765–1768.PubMedCrossRefGoogle Scholar
  32. 32.
    Chou S, Waldemer RH, Senters AE, et al. Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir. J Infect Dis. 2002;185:162–169.PubMedCrossRefGoogle Scholar
  33. 33.
    Hamprecht K, Eckle T, Prix L, et al. Ganciclovir-resistant cytomegalovirus disease after allogeneic stem cell transplantation: pitfalls of phenotypic diagnosis by in vitro selection of an UL97 mutant strain. J Infect Dis. 2003;187:139–143.PubMedCrossRefGoogle Scholar
  34. 34.
    Kwak EJ, Vilchez RA, Randhawa P, et al. Pathogenesis and management of polyomavirus infection in transplant recipients. Clin Infect Dis. 2002;35:1081–1087.PubMedCrossRefGoogle Scholar
  35. 35.
    Lin PL, Vats AN, Green M. BK virus infection in renal transplant recipients. Pediatr Transplant. 2001;5:398–405.PubMedCrossRefGoogle Scholar
  36. 36.
    Boubenider S, Hiesse C, Marchand S, et al. Post-transplantation polyomavirus infections. J Nephrol. 1999;12:24–29.PubMedGoogle Scholar
  37. 37.
    Vats A, Shapiro R, Singh Randhawa P, et al. Quantitative viral load monitoring and cidofovir therapy for the management of BK virusassociated nephropathy in children and adults. Transplantation. 2003;75:105–112.PubMedCrossRefGoogle Scholar
  38. 38.
    Randhawa PS, Finkelstein S, Scantlebury V, et al. Human polyoma virus-associated interstitial nephritis in the allograft kidney. Transplantation. 1999;67:103–109.PubMedCrossRefGoogle Scholar
  39. 39.
    Hirsch HH, Knowles W, Dickenmann M, et al. Prospective study of polyomavirus type BK replication and nephropathy in renaltransplant recipients [comment]. N Engl J Med. 2002;347:488–496.PubMedCrossRefGoogle Scholar
  40. 40.
    Limaye AP, Jerome KR, Kuhr CS, et al. Quantitation of BK virus load in serum for the diagnosis of BK virus-associated nephropathy in renal transplant recipients [comment]. J Infect Dis. 2001;183:1669–1672.PubMedCrossRefGoogle Scholar
  41. 41.
    Ginevri F, De Santis R, Comoli P, et al. Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches. Transplantation. 2003;75:1266–1270.PubMedCrossRefGoogle Scholar
  42. 42.
    Leung AY, Chan M, Tang SC, et al. Real-time quantitative analysis of polyoma BK viremia and viruria in renal allograft recipients. J Virol Methods. 2002;103:51–56.PubMedCrossRefGoogle Scholar
  43. 43.
    Azzi A, Cesaro S, Laszlo D, et al. Human polyomavirus BK (BKV) load and haemorrhagic cystitis in bone marrow transplantation patients. J Clin Virol. 1999;14:79–86.PubMedCrossRefGoogle Scholar
  44. 44.
    Iwamoto S, Azuma E, Hori H, et al. BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation. Pediatr Hematol Oncol. 2002;19:255–261.PubMedCrossRefGoogle Scholar
  45. 45.
    Leung AY, Suen CK, Lie AK, et al. Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. Blood. 2001;98:1971–1978.PubMedCrossRefGoogle Scholar
  46. 46.
    Gretch D. Standardization of hepatitis C virus—RNA quantification: advances and unfinished business [comment]. Hepatology. 2000;31:788–789.PubMedCrossRefGoogle Scholar
  47. 47.
    Chan SE, Rosen HR. Outcome and management of hepatitis C in liver transplant recipients. Clin Infect Dis. 2003;37:807–812.PubMedCrossRefGoogle Scholar
  48. 48.
    Wali MH, Heydtmann M, Harrison RF, et al. Outcome of liver transplantation for patients infected by hepatitis C, including those infected by genotype 4. Liver Transpl. 2003;9:796–804.PubMedCrossRefGoogle Scholar
  49. 49.
    Alonso O, Loinaz C, Abradelo M, et al. Changes in the incidence and severity of recurrent hepatitis C after liver transplantation over 1990–1999. Transplant Proc. 2003;35:1836–1847.PubMedCrossRefGoogle Scholar
  50. 50.
    Berenguer M. Natural history of recurrent hepatitis C. Liver Transpl. 2002;8(suppl 1):S14–S18.PubMedCrossRefGoogle Scholar
  51. 51.
    Firpi RJ, Abdelmalek MF, Soldevila-Pico C, et al. Combination of interferon alfa-2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C. Liver Transpl. 2002;8:1000–1006.PubMedCrossRefGoogle Scholar
  52. 52.
    McCaughan GW, Zekry A. Pathogenesis of hepatitis C virus recurrence in the liver allograft. Liver Transpl. 2002;8(suppl 1):S7–S13.PubMedCrossRefGoogle Scholar
  53. 53.
    Costes V, Durand L, Pageaux GP, et al. Hepatitis C virus genotypes and quantification of serum hepatitis C RNA in liver transplant recipients. Relationship with histologic outcome of recurrent hepatitis C. Am J Clin Pathol. 1999;111:252–258.PubMedGoogle Scholar
  54. 54.
    Nuovo GJ, Holly A, Wakely P Jr, et al. Correlation of histology, viral load, and in situ viral detection in hepatic biopsies from patients with liver transplants secondary to hepatitis C infection. Hum Pathol. 2002;33:277–284.PubMedCrossRefGoogle Scholar
  55. 55.
    Gigou M, Roque-Afonso AM, Falissard B, et al. Genetic clustering of hepatitis C virus strains and severity of recurrent hepatitis after liver transplantation. J Virol. 2001;75:11292–11297.PubMedCrossRefGoogle Scholar
  56. 56.
    Feray C, Caccamo L, Alexander GJ, et al. European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group. Gastroenterology. 1999;117:619–625.PubMedCrossRefGoogle Scholar
  57. 57.
    Charlton M, Seaberg E, Wiesner R, et al. Predictors of patient and graft survival following liver transplantation for hepatitis C. Hepatology. 1998;28:823–830.PubMedCrossRefGoogle Scholar
  58. 58.
    Zhou S, Terrault NA, Ferrell L, et al. Severity of liver disease in liver transplantation recipients with hepatitis C virus infection: relationship to genotype and level of viremia. Hepatology. 1996;24:1041–1046.PubMedCrossRefGoogle Scholar
  59. 59.
    Holmes RD, Sokol RJ. Epstein-Barr virus and post-transplant lymphoproliferative disease. Pediatr Transplant. 2002;6:456–464.PubMedCrossRefGoogle Scholar
  60. 60.
    Muti G, Cantoni S, Oreste P, et al. Post-transplant lymphoproliferative disorders: improved outcome after clinico-pathologically tailored treatment. Haematologica. 2002;87:67–77.PubMedGoogle Scholar
  61. 61.
    Ho M. Risk factors and pathogenesis of posttransplant lymphoproliferative disorders. Transplant Proc. 1995;27(suppl 1):38–40.PubMedGoogle Scholar
  62. 62.
    Ho M, Miller G, Atchison RW, et al. Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: the role of primary infection. J Infect Dis. 1985;152:876–886.PubMedGoogle Scholar
  63. 63.
    Matsukura T, Yokoi A, Egawa H, et al. Significance of serial real-time PCR monitoring of EBV genome load in living donor liver transplantation. Clin Transplant. 2002;16:107–112.PubMedCrossRefGoogle Scholar
  64. 64.
    Merlino C, Cavallo R, Bergallo M, et al. Epstein Barr viral load monitoring by quantitative PCR in renal transplant patients. New Microbiol. 2003;26:141–149.PubMedGoogle Scholar
  65. 65.
    Orentas RJ, Schauer DWJ, Ellis FW, et al. Monitoring and modulation of Epstein-Barr virus loads in pediatric transplant patients. Pediatr Transplant. 2003;7:305–314.PubMedCrossRefGoogle Scholar
  66. 66.
    Limaye AP, Huang ML, Atienza EE, et al. Detection of Epstein-Barr virus DNA in sera from transplant recipients with lymphoproliferative disorders [comment]. J Clin Microbiol. 1999;37:1113–1116.PubMedGoogle Scholar
  67. 67.
    Riddler SA, Breinig MC, McKnight JL. Increased levels of circulating Epstein-Barr virus (EBV)-infected lymphocytes and decreased EBV nuclear antigen antibody responses are associated with the development of posttransplant lymphoproliferative disease in solid-organ transplant recipients. Blood. 1994;84:972–984.PubMedGoogle Scholar
  68. 68.
    Gartner BC, Schafer H, Marggraff K, et al. Evaluation of use of Epstein-Barr viral load in patients after allogeneic stem cell transplantation to diagnose and monitor posttransplant lymphoproliferative disease [erratum appears in J Clin Microbiol. 2002;40:2316]. J Clin Microbiol. 2002;40:351–358.PubMedCrossRefGoogle Scholar
  69. 69.
    Campe H, Jaeger G, Abou-Ajram C, et al. Serial detection of Epstein-Barr virus DNA in sera and peripheral blood leukocyte samples of pediatric renal allograft recipients with persistent mononucleosislike symptoms defines patients at risk to develop post-transplant lymphoproliferative disease. Pediatr Transplant. 2003;7:46–52.PubMedCrossRefGoogle Scholar
  70. 70.
    Kogan-Liberman D, Burroughs M, Emre S, et al. The role of quantitative Epstein-Barr virus polymerase chain reaction and preemptive immunosuppression reduction in pediatric liver transplantation: a preliminary experience [comment]. J Pediatr Gastroenterol Nutr. 2001;33:445–449.PubMedCrossRefGoogle Scholar
  71. 71.
    Griffiths PD, Clark DA, Emery VC. Betaherpesviruses in transplant recipients. J Antimicrob Chemother. 2000;45(suppl T3):29–34.PubMedCrossRefGoogle Scholar
  72. 72.
    Boutolleau D, Fernandez C, Andre E, et al. Human herpesvirus (HHV)-6 and HHV-7: two closely related viruses with different infection profiles in stem cell transplantation recipients. J Infect Dis. 2003;187:179–186.PubMedCrossRefGoogle Scholar
  73. 73.
    Kidd IM, Clark DA, Sabin CA, et al. Prospective study of human betaherpesviruses after renal transplantation: association of human herpesvirus 7 and cytomegalovirus co-infection with cytomegalovirus disease and increased rejection. Transplantation. 2000;69:2400–2404.PubMedCrossRefGoogle Scholar
  74. 74.
    Humar A, Kumar D, Caliendo AM, et al. Clinical impact of human herpesvirus 6 infection after liver transplantation. Transplantation. 2002;73:599–604.PubMedCrossRefGoogle Scholar
  75. 75.
    Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, et al. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J Virol Methods. 2002;100:27–35.PubMedCrossRefGoogle Scholar
  76. 76.
    Ljungman P, Wang FZ, Clark DA, et al. High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients. Br J Haematol. 2000;111:774–781.PubMedCrossRefGoogle Scholar
  77. 77.
    Nitsche A, Muller CW, Radonic A, et al. Human herpesvirus 6A DNA Is detected frequently in plasma but rarely in peripheral blood leukocytes of patients after bone marrow transplantation. J Infect Dis. 2001;183:130–133.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Andrea Ferreira-Gonzalez
    • 1
    • 2
  • Angela M. Caliendo
    • 3
  1. 1.Department of PathologyVirginia Commonwealth UniversityRichmondUSA
  2. 2.Department of Molecular Diagnostics Laboratory, Molecular DiagnosticsVirginia Commonwealth UniversityRichmondUSA
  3. 3.Department of Pathology and Laboratory MedicineEmory University HospitalAtlantaUSA

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