Semin Respir Crit Care Med 2011; 32(4): 454-470
DOI: 10.1055/s-0031-1283285
© Thieme Medical Publishers

DNA Viruses (CMV, EBV, and the Herpesviruses)

Martin R. Zamora1
  • 1Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver Health Sciences Center, Aurora, Colorado
Further Information

Publication History

Publication Date:
19 August 2011 (online)

ABSTRACT

The human Herpesviridae family consists of eight members: cytomegalovirus (CMV), Epstein–Barr virus (EBV), herpes simplex virus 1 and 2 (HSV-1, -2), varicella-zoster virus (VZV), and human herpesvirus 6, 7, and 8 (HHV-6, -7, -8). Lifelong latency may develop in the host with reactivation during periods of relative immunosuppression that occurs in transplant recipients. These are pleiotropic viruses: in addition to their direct effects of tissue injury and clinical illness, they exhibit several indirect effects, including immunomodulation and effects on angiogenesis and tumorigenesis, which may result in long-term adverse sequelae in the lung allograft. CMV and HHV-6 and -7 are increasingly recognized as major causes of morbidity and mortality in lung transplant recipients. EBV and HHV-8 have proven oncogenic potential. HSV-1 and -2 and VZV are neurotropic, causing perioral fever blisters, genital ulcerations, and, rarely, encephalitis. This article discusses the individual pathogens, preventive strategies in the era of potent treatment regimens for established viral infection or disease and their potential impact on the indirect effects of these viruses on long-term allograft function, and the incidence, risk factors for, and impact of antiviral resistance.

REFERENCES

  • 1 Shah P D, McDyer J F. Viral infections in lung transplant recipients.  Semin Respir Crit Care Med. 2010;  31 (2) 243-254
  • 2 Costa C, Delsedime L, Solidoro P et al.. Herpesviruses detection by quantitative real-time polymerase chain reaction in bronchoalveolar lavage and transbronchial biopsy in lung transplant: viral infections and histopathological correlation.  Transplant Proc. 2010;  42 (4) 1270-1274
  • 3 Fishman J A, Rubin R H. Infection in organ-transplant recipients.  N Engl J Med. 1998;  338 (24) 1741-1751
  • 4 Paya C V, Razonable R R. Cytomegalovirus infection after solid organ transplantation. In: Bowden R A, Ljungman P, Paya C V, eds. Transplant Infections. 2nd ed. Philadelphia, PA: Lippincott, Williams and Wilkens; 2003
  • 5 Zamora M R. Cytomegalovirus and lung transplantation.  Am J Transplant. 2004;  4 (8) 1219-1226
  • 6 Zamora M R. Viral infections complicating lung and solid organ transplantation. In: Lynch III J P, Ross D J, eds. Lung and Heart–Lung Transplantation. New York: Taylor and Francis; 2006: 485-525
  • 7 Mitsani D, Nguyen M H, Kwak E J et al.. Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis.  J Heart Lung Transplant. 2010;  29 (9) 1014-1020
  • 8 Dunn H S, Haney D J, Ghanekar S A, Stepick-Biek P, Lewis D B, Maecker H T. Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors.  J Infect Dis. 2002;  186 (1) 15-22
  • 9 Zamora M R, Davis R D, Leonard C. CMV Advisory Board Expert Committee . Management of cytomegalovirus infection in lung transplant recipients: evidence-based recommendations.  Transplantation. 2005;  80 (2) 157-163
  • 10 Kotton C N, Kumar D, Caliendo A M Transplantation Society International CMV Consensus Group et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation.  Transplantation. 2010;  89 (7) 779-795
  • 11 Valantine H A. Prevention and treatment of cytomegalovirus disease in thoracic organ transplant patients: evidence for a beneficial effect of hyperimmune globulin.  Transplant Proc. 1995;  27 (5, Suppl 1) 49-57
  • 12 Balthesen M, Messerle M, Reddehase M J. Lungs are a major organ site of cytomegalovirus latency and recurrence.  J Virol. 1993;  67 (9) 5360-5366
  • 13 Mendez J C, Dockrell D H, Espy M J et al.. Human beta-herpesvirus interactions in solid organ transplant recipients.  J Infect Dis. 2001;  183 (2) 179-184
  • 14 Jamil B, Nicholls K M, Becker G J, Walker R G. Influence of anti-rejection therapy on the timing of cytomegalovirus disease and other infections in renal transplant recipients.  Clin Transplant. 2000;  14 (1) 14-18
  • 15 van der Meer J T, Drew W L, Bowden R A et al.. Summary of the international consensus symposium on advances in the diagnosis, treatment and prophylaxis and cytomegalovirus infection.  Antiviral Res. 1996;  32 (3) 119-140
  • 16 Duncan S R, Paradis I L, Yousem S A et al.. Sequelae of cytomegalovirus pulmonary infections in lung allograft recipients.  Am Rev Respir Dis. 1992;  146 (6) 1419-1425
  • 17 Snyder L D, Finlen-Copeland C A, Turbyfill W J, Howell D, Willner D A, Palmer S M. Cytomegalovirus pneumonitis is a risk for bronchiolitis obliterans syndrome in lung transplantation.  Am J Respir Crit Care Med. 2010;  181 (12) 1391-1396
  • 18 Snydman D R. Infection in solid organ transplantation.  Transpl Infect Dis. 1999;  1 (1) 21-28
  • 19 Singh N, Arnow P M, Bonham A et al.. Invasive aspergillosis in liver transplant recipients in the 1990s.  Transplantation. 1997;  64 (5) 716-720
  • 20 McCarthy J M, Karim M A, Krueger H, Keown P A. The cost impact of cytomegalovirus disease in renal transplant recipients.  Transplantation. 1993;  55 (6) 1277-1282
  • 21 Falagas M E, Arbo M, Ruthazer R et al.. Cytomegalovirus disease is associated with increased cost and hospital length of stay among orthotopic liver transplant recipients.  Transplantation. 1997;  63 (11) 1595-1601
  • 22 Kim W R, Badley A D, Wiesner R H et al.. The economic impact of cytomegalovirus infection after liver transplantation.  Transplantation. 2000;  69 (3) 357-361
  • 23 Tolkoff-Rubin N E, Fishman J A, Rubin R H. The bidirectional relationship between cytomegalovirus and allograft injury.  Transplant Proc. 2001;  33 (1-2) 1773-1775
  • 24 Beck S, Barrell B G. Human cytomegalovirus encodes a glycoprotein homologous to MHC class-I antigens.  Nature. 1988;  331 (6153) 269-272
  • 25 Winston D J, Antin J H, Wolff S N et al.. A multicenter, randomized, double-blind comparison of different doses of intravenous immunoglobulin for prevention of graft-versus-host disease and infection after allogeneic bone marrow transplantation.  Bone Marrow Transplant. 2001;  28 (2) 187-196
  • 26 Duncan S R, Grgurich W F, Iacono A T et al.. A comparison of ganciclovir and acyclovir to prevent cytomegalovirus after lung transplantation.  Am J Respir Crit Care Med. 1994;  150 (1) 146-152
  • 27 Schulman L L, Weinberg A D, McGregor C C, Suciu-Foca N M, Itescu S. Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation.  Am J Respir Crit Care Med. 2001;  163 (2) 437-442
  • 28 Ettinger N A, Bailey T C, Trulock E P Washington University Lung Transplant Group et al. Cytomegalovirus infection and pneumonitis: impact after isolated lung transplantation.  Am Rev Respir Dis. 1993;  147 (4) 1017-1023
  • 29 Sharples L D, Tamm M, McNeil K, Higenbottam T W, Stewart S, Wallwork J. Development of bronchiolitis obliterans syndrome in recipients of heart-lung transplantation—early risk factors.  Transplantation. 1996;  61 (4) 560-566
  • 30 Weseslindtner L, Nachbagauer R, Kundi M et al.. Human cytomegalovirus infection in lung transplant recipients triggers a CXCL-10 response.  Am J Transplant. 2011;  11 (3) 542-552
  • 31 Bowden R A, Slichter S J, Sayers M et al.. A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant.  Blood. 1995;  86 (9) 3598-3603
  • 32 Palmer S M, Limaye A P, Banks M et al.. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.  Ann Intern Med. 2010;  152 (12) 761-769
  • 33 Baldanti F, Revello M G, Percivalle E, Gerna G. Use of the human cytomegalovirus (HCMV) antigenemia assay for diagnosis and monitoring of HCMV infections and detection of antiviral drug resistance in the immunocompromised.  J Clin Virol. 1998;  11 (1) 51-60
  • 34 Egan J J, Barber L, Lomax J et al.. Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.  Thorax. 1995;  50 (1) 9-13
  • 35 Bewig B, Haacke T C, Tiroke A et al.. Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells.  Respiration. 2000;  67 (2) 166-172
  • 36 Michaelides A, Liolios L, Glare E M et al.. Increased human cytomegalovirus (HCMV) DNA load in peripheral blood leukocytes after lung transplantation correlates with HCMV pneumonitis.  Transplantation. 2001;  72 (1) 141-147
  • 37 Guiver M, Fox A J, Mutton K, Mogulkoc N, Egan J. Evaluation of CMV viral load using TaqMan CMV quantitative PCR and comparison with CMV antigenemia in heart and lung transplant recipients.  Transplantation. 2001;  71 (11) 1609-1615
  • 38 Masaoka T, Hiraoka A, Ohta K et al.. Evaluation of the AMPLICOR CMV, COBAS AMPLICOR CMV monitor and antigenemia assay for cytomegalovirus disease.  Jpn J Infect Dis. 2001;  54 (1) 12-16
  • 39 Mazzulli T, Drew L W, 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 (4) 958-963
  • 40 Bhorade S M, Sandesara C, Garrity E R et al.. Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients.  J Heart Lung Transplant. 2001;  20 (9) 928-934
  • 41 Humar A, Paya C, Pescovitz M D et al.. Clinical utility of cytomegalovirus viral load testing for predicting CMV disease in D + /R − solid organ transplant recipients.  Am J Transplant. 2004;  4 (4) 644-649
  • 42 Chemaly R F, Yen-Lieberman B, Castilla E A et al.. Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry.  J Clin Microbiol. 2004;  42 (5) 2168-2172
  • 43 Humar A, Gregson D, Caliendo A M et al.. Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients.  Transplantation. 1999;  68 (9) 1305-1311
  • 44 Weinberg A, Hodges T N, Li S, Cai G, Zamora M R. Comparison of PCR, antigenemia assay, and rapid blood culture for detection and prevention of cytomegalovirus disease after lung transplantation.  J Clin Microbiol. 2000;  38 (2) 768-772
  • 45 Wreghitt T. Cytomegalovirus infections in heart and heart-lung transplant recipients.  J Antimicrob Chemother. 1989;  23 (Suppl E) 49-60
  • 46 Soghikian M V, Valentine V G, Berry G J, Patel H R, Robbins R C, Theodore J. Impact of ganciclovir prophylaxis on heart-lung and lung transplant recipients.  J Heart Lung Transplant. 1996;  15 (9) 881-887
  • 47 Duncan S R, Paradis I L, Dauber J H, Yousem S A, Hardesty R L, Griffith B P. Ganciclovir prophylaxis for cytomegalovirus infections in pulmonary allograft recipients.  Am Rev Respir Dis. 1992;  146 (5 Pt 1) 1213-1215
  • 48 Kelly J L, Albert R K, Wood D E, Raghu G. Efficacy of a 6-week prophylactic ganciclovir regimen and the role of serial cytomegalovirus antibody testing in lung transplant recipients.  Transplantation. 1995;  59 (8) 1144-1147
  • 49 Hertz M I, Jordan C, Savik S K et al.. Randomized trial of daily versus three-times-weekly prophylactic ganciclovir after lung and heart-lung transplantation.  J Heart Lung Transplant. 1998;  17 (9) 913-920
  • 50 Limaye A P, Raghu G, Koelle D M, Ferrenberg J, Huang M L, Boeckh M. High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy.  J Infect Dis. 2002;  185 (1) 20-27
  • 51 Paya C V. A randomized, double-blinded, double-dummy, active comparator controlled multicenter study of the efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of CMV in 372 high-risk (D + /R-) heart, liver and kidney recipients. [Abstract LB-4] In: Program and Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, September 27–30, 2002, San Diego, California. American Society for Microbiology Press, 2002. 
  • 52 Maurer J R, Snell G, deHoyos A, Kesten S, Winton T. Outcomes of lung transplantation using three different cytomegalovirus prophylactic regimens.  Transplant Proc. 1993;  25 (1 Pt 2) 1434-1435
  • 53 Gould F K, Freeman R, Taylor C E, Ashcroft T, Dark J H, Corris P A. Prophylaxis and management of cytomegalovirus pneumonitis after lung transplantation: a review of experience in one center.  J Heart Lung Transplant. 1993;  12 (4) 695-699
  • 54 Kruger R M, Paranjothi S, Storch G A, Lynch J P, Trulock E P. Impact of prophylaxis with cytogam alone on the incidence of CMV viremia in CMV-seropositive lung transplant recipients.  J Heart Lung Transplant. 2003;  22 (7) 754-763
  • 55 Bailey T C, Trulock E P, Ettinger N A, Storch G A, Cooper J D, Powderly W G. Failure of prophylactic ganciclovir to prevent cytomegalovirus disease in recipients of lung transplants.  J Infect Dis. 1992;  165 (3) 548-552
  • 56 Zamora M R. Use of cytomegalovirus immune globulin and ganciclovir for the prevention of cytomegalovirus disease in lung transplantation.  Transpl Infect Dis. 2001;  3 (Suppl 2) 49-56
  • 57 Valantine H A, Luikart H, Doyle R et al.. Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone.  Transplantation. 2001;  72 (10) 1647-1652
  • 58 Poirier C D, Doyle R L, Theodore J et al.. Comparison between CMV Hyperimmune globulin and GCV for CMV prophylaxis in heart-lung and lung transplant recipients.  J Heart Lung Transplant. 1998;  17 96
  • 59 Weill D, Lock B J, Wewers D L et al.. Combination prophylaxis with ganciclovir and cytomegalovirus (CMV) immune globulin after lung transplantation: effective CMV prevention following daclizumab induction.  Am J Transplant. 2003;  3 (4) 492-496
  • 60 Zamora M R, Nicolls M R, Hodges T N et al.. Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation.  Am J Transplant. 2004;  4 (10) 1635-1642
  • 61 Kelly J, Hurley D, Raghu G. Comparison of the efficacy and cost effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients.  J Heart Lung Transplant. 2000;  19 (4) 355-359
  • 62 Weill D, Zamora M R. Comparison of the efficacy and cost-effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients.  J Heart Lung Transplant. 2000;  19 (8) 815-816
  • 63 Zuk D M, Humar A, Weinkauf J G, Lien D C, Nador R G, Kumar D. An international survey of cytomegalovirus management practices in lung transplantation.  Transplantation. 2010;  90 (6) 672-676
  • 64 Asberg A, Humar A, Jardine A G VICTOR Study Group et al. Long-term outcomes of CMV disease treatment with valganciclovir versus IV ganciclovir in solid organ transplant recipients.  Am J Transplant. 2009;  9 (5) 1205-1213
  • 65 Rubin R H, Lynch P, Pasternack M S, Schoenfeld D, Medearis Jr D N. Combined antibody and ganciclovir treatment of murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice.  Antimicrob Agents Chemother. 1989;  33 (11) 1975-1979
  • 66 Goldfarb N S, Avery R K, Goormastic M et al.. Hypogammaglobulinemia in lung transplant recipients.  Transplantation. 2001;  71 (2) 242-246
  • 67 Yamani M H, Avery R K, Mawhorter S D et al.. Hypogammaglobulinemia following cardiac transplantation: a link between rejection and infection.  J Heart Lung Transplant. 2001;  20 (4) 425-430
  • 68 Rubin R H. Prevention and treatment of cytomegalovirus disease in heart transplant patients.  J Heart Lung Transplant. 2000;  19 (8) 731-735
  • 69 Turgeon N, Fishman J A, Doran M et al.. Prevention of recurrent cytomegalovirus disease in renal and liver transplant recipients: effect of oral ganciclovir.  Transpl Infect Dis. 2000;  2 (1) 2-10
  • 70 Nankivell B J, Malouf M A, Russ G R et al.. Maintenance therapy with oral ganciclovir after treatment of cytomegalovirus infection.  Clin Transplant. 1998;  12 (3) 270-273
  • 71 Erice A. Resistance of human cytomegalovirus to antiviral drugs.  Clin Microbiol Rev. 1999;  12 (2) 286-297
  • 72 Limaye A P, Corey L, Koelle D M, Davis C L, Boeckh M. Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants.  Lancet. 2000;  356 (9230) 645-649
  • 73 Kruger R M, Shannon W D, Arens M Q, Lynch J P, Storch G A, Trulock E P. The impact of ganciclovir-resistant cytomegalovirus infection after lung transplantation.  Transplantation. 1999;  68 (9) 1272-1279
  • 74 Alain S, Honderlick P, Grenet D et al.. Failure of ganciclovir treatment associated with selection of a ganciclovir-resistant cytomegalovirus strain in a lung transplant recipient.  Transplantation. 1997;  63 (10) 1533-1536
  • 75 Baldanti F, Simoncini L, Sarasini A et al.. Ganciclovir resistance as a result of oral ganciclovir in a heart transplant recipient with multiple human cytomegalovirus strains in blood.  Transplantation. 1998;  66 (3) 324-329
  • 76 Lurain N S, Ammons H C, Kapell K S, Yeldandi V V, Garrity E R, O'Keefe J P. Molecular analysis of human cytomegalovirus strains from two lung transplant recipients with the same donor.  Transplantation. 1996;  62 (4) 497-502
  • 77 Mylonakis E, Kallas W M, Fishman J A. Combination antiviral therapy for ganciclovir-resistant cytomegalovirus infection in solid-organ transplant recipients.  Clin Infect Dis. 2002;  34 (10) 1337-1341
  • 78 Chou S, Marousek G, Guentzel S et al.. Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease.  J Infect Dis. 1997;  176 (3) 786-789
  • 79 Waldman W J, Knight D A, Lurain N S et al.. Novel mechanism of inhibition of cytomegalovirus by the experimental immunosuppressive agent leflunomide.  Transplantation. 1999;  68 (6) 814-825
  • 80 Avery R K, Bolwell B J, Yen-Lieberman B et al.. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.  Bone Marrow Transplant. 2004;  34 (12) 1071-1075
  • 81 Avery R K, Mossad S B, Poggio E et al.. Utility of leflunomide in the treatment of complex cytomegalovirus syndromes.  Transplantation. 2010;  90 (4) 419-426
  • 82 Kumar D, Chernenko S, Moussa G et al.. Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients.  Am J Transplant. 2009;  9 (5) 1214-1222
  • 83 Yoshikawa T. Significance of human herpesviruses to transplant recipients.  Curr Opin Infect Dis. 2003;  16 (6) 601-606
  • 84 De Bolle L, Naesens L, De Clercq E. Update on human herpesvirus 6 biology, clinical features, and therapy.  Clin Microbiol Rev. 2005;  18 (1) 217-245
  • 85 Jacobs F, Knoop C, Brancart F Brussels Heart and Lung Transplantation Group et al. Human herpesvirus-6 infection after lung and heart-lung transplantation: a prospective longitudinal study.  Transplantation. 2003;  75 (12) 1996-2001
  • 86 Nash P J, Avery R K, Tang W H, Starling R C, Taege A J, Yamani M H. Encephalitis owing to human herpesvirus-6 after cardiac transplant.  Am J Transplant. 2004;  4 (7) 1200-1203
  • 87 Razonable R R, Rivero A, Brown R A et al.. Detection of simultaneous beta-herpesvirus infections in clinical syndromes due to defined cytomegalovirus infection.  Clin Transplant. 2003;  17 (2) 114-120
  • 88 Yoshida M, Yamada M, Tsukazaki T et al.. Comparison of antiviral compounds against human herpesvirus 6 and 7.  Antiviral Res. 1998;  40 (1-2) 73-84
  • 89 Ross D J, Chan R CK, Kubak B, Laks H, Nichols W S. Bronchiolitis obliterans with organizing pneumonia: possible association with human herpesvirus-7 infection after lung transplantation.  Transplant Proc. 2001;  33 (4) 2603-2606
  • 90 Manuel O, Kumar D, Moussa G et al.. Lack of association between beta-herpesvirus infection and bronchiolitis obliterans syndrome in lung transplant recipients in the era of antiviral prophylaxis.  Transplantation. 2009;  87 (5) 719-725
  • 91 Brennan D C, Storch G A, Singer G G, Lee L, Rueda J, Schnitzler M A. The prevalence of human herpesvirus-7 in renal transplant recipients is unaffected by oral or intravenous ganciclovir.  J Infect Dis. 2000;  181 (5) 1557-1561
  • 92 Wang F Z, Dahl H, Linde A, Brytting M, Ehrnst A, Ljungman P. Lymphotropic herpesviruses in allogeneic bone marrow transplantation.  Blood. 1996;  88 (9) 3615-3620
  • 93 Collart F, Kerbaul F, Damaj G et al.. Visceral Kaposi's sarcoma associated with human herpesvirus 8 seroconversion in a heart transplant recipient.  Transplant Proc. 2004;  36 (10) 3173-3174
  • 94 Huang P M, Chang Y L, Chen J S et al.. Human herpesvirus-8 associated Kaposi's sarcoma after lung transplantation: a case report.  Transplant Proc. 2003;  35 (1) 447-449
  • 95 Preiksaitis J K, Cockfield S M. Epstein-Barr virus and lymphoproliferative disease after hematopoietic stem cell or solid organ transplantation. In: Bowden R A, Ljungman P, Paya C V, eds. Transplant Infections. 2nd ed. Philadelphia, PA: Lippincott-Williams and Wilkens; 2003: 326-349
  • 96 Gottschalk S, Rooney C M, Heslop H E. Post-transplant lymphoproliferative disorders.  Annu Rev Med. 2005;  56 29-44
  • 97 Preiksaitis J K. New developments in the diagnosis and management of posttransplantation lymphoproliferative disorders in solid organ transplant recipients.  Clin Infect Dis. 2004;  39 (7) 1016-1023
  • 98 Moss D J, Burrows S R, Silins S L, Misko I, Khanna R. The immunology of Epstein-Barr virus infection.  Philos Trans R Soc Lond B Biol Sci. 2001;  356 (1408) 475-488
  • 99 Rowe D T, Webber S, Schauer E M, Reyes J, Green M. Epstein-Barr virus load monitoring: its role in the prevention and management of post-transplant lymphoproliferative disease.  Transpl Infect Dis. 2001;  3 (2) 79-87
  • 100 Gärtner B C, Fischinger J, Schäfer H, Einsele H, Roemer K, Müller-Lantzsch N. Epstein-Barr viral load as a tool to diagnose and monitor post-transplant lymphoproliferative disease.  Recent Results Cancer Res. 2002;  159 49-54
  • 101 Schäfer H, Berger C, Aepinus C et al.. Molecular pathogenesis of Epstein-Barr virus associated posttransplant lymphomas: new insights through latent membrane protein 1 fingerprinting.  Transplantation. 2001;  72 (3) 492-496
  • 102 Reams B D, McAdams H P, Howell D N, Steele M P, Davis R D, Palmer S M. Posttransplant lymphoproliferative disorder: incidence, presentation, and response to treatment in lung transplant recipients.  Chest. 2003;  124 (4) 1242-1249
  • 103 Penn I. The changing pattern of posttransplant malignancies.  Transplant Proc. 1991;  23 (1 Pt 2) 1101-1103
  • 104 Cockfield S M, Preiksaitis J K, Jewell L D, Parfrey N A. Post-transplant lymphoproliferative disorder in renal allograft recipients: clinical experience and risk factor analysis in a single center.  Transplantation. 1993;  56 (1) 88-96
  • 105 Walker R C, Marshall W F, Strickler J G et al.. Pretransplantation assessment of the risk of lymphoproliferative disorder.  Clin Infect Dis. 1995;  20 (5) 1346-1353
  • 106 Swinnen L J, Costanzo-Nordin M R, Fisher S G et al.. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients.  N Engl J Med. 1990;  323 (25) 1723-1728
  • 107 Libertiny G, Watson C J, Gray D W, Welsh K I, Morris P J. Rising incidence of post-transplant lymphoproliferative disease in kidney transplant recipients.  Br J Surg. 2001;  88 (10) 1330-1334
  • 108 Dotti G, Fiocchi R, Motta T et al.. Primary effusion lymphoma after heart transplantation: a new entity associated with human herpesvirus-8.  Leukemia. 1999;  13 (5) 664-670
  • 109 Kapelushnik J, Ariad S, Benharroch D et al.. Post renal transplantation human herpesvirus 8-associated lymphoproliferative disorder and Kaposi's sarcoma.  Br J Haematol. 2001;  113 (2) 425-428
  • 110 McLaughlin K, Wajstaub S, Marotta P et al.. Increased risk for posttransplant lymphoproliferative disease in recipients of liver transplants with hepatitis C.  Liver Transpl. 2000;  6 (5) 570-574
  • 111 Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients.  Lancet. 1993;  342 (8886–8887) 1514-1516
  • 112 Funch D P, Brady J, Ko H H, Dreyer N A, Walker A M. Methods and objectives of a large US multicenter case-control study of post-transplant lymphoproliferative disorder in renal transplant patients.  Recent Results Cancer Res. 2002;  159 81-88
  • 113 Ghobrial I M, Habermann T M, Macon W R et al.. Differences between early and late posttransplant lymphoproliferative disorders in solid organ transplant patients: are they two different diseases?.  Transplantation. 2005;  79 (2) 244-247
  • 114 Harris N L, Ferry J A, Swerdlow S H. Posttransplant lymphoproliferative disorders: summary of Society for Hematopathology Workshop.  Semin Diagn Pathol. 1997;  14 (1) 8-14
  • 115 Harris N L, Swerdlow S H, Frizerra G et al.. Posttransplant lymphoproliferative disorders. In: Jaffe E S, Harris N L, Stein H, Vardiman J W, eds. Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tumours: WHO Classification of Tumours. Lyons, France: IARC Press; 2001: 264-269
  • 116 Gulley M L, Swinnen L J, Plaisance Jr K T, Schnell C, Grogan T M, Schneider B G. Southwest Oncology Group . Tumor origin and CD20 expression in posttransplant lymphoproliferative disorder occurring in solid organ transplant recipients: implications for immune-based therapy.  Transplantation. 2003;  76 (6) 959-964
  • 117 Nelson B P, Nalesnik M A, Bahler D W, Locker J, Fung J J, Swerdlow S H. Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity?.  Am J Surg Pathol. 2000;  24 (3) 375-385
  • 118 Green M, Cacciarelli T V, Mazariegos G V et al.. Serial measurement of Epstein-Barr viral load in peripheral blood in pediatric liver transplant recipients during treatment for posttransplant lymphoproliferative disease.  Transplantation. 1998;  66 (12) 1641-1644
  • 119 Straathof K C, Savoldo B, Heslop H E, Rooney C M. Immunotherapy for post-transplant lymphoproliferative disease.  Br J Haematol. 2002;  118 (3) 728-740
  • 120 Leung E, Shenton B K, Green K et al.. Dynamic EBV gene loads in renal, hepatic, and cardiothoracic transplant recipients as determined by real-time PCR light cycler.  Transpl Infect Dis. 2004;  6 (4) 156-164
  • 121 Khanna R, Bell S, Sherritt M et al.. Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease.  Proc Natl Acad Sci U S A. 1999;  96 (18) 10391-10396
  • 122 Davis C L. Interferon and cytotoxic chemotherapy for the treatment of post-transplant lymphoproliferative disorder.  Transpl Infect Dis. 2001;  3 (2) 108-118
  • 123 Paya C V, Fung J J, Nalesnik M A et al.. Epstein-Barr virus-induced post-transplant lymphoproliferative disorders. ASTS/ASTP EBV-PTLD Task Force and The Mayo Clinic Organized International Consensus Development Meeting.  Transplantation. 1999;  68 1517-1525
  • 124 Gross T G. Low-dose chemotherapy for children with post-transplant lymphoproliferative disease.  Recent Results Cancer Res. 2002;  159 96-103
  • 125 Milpied N, Vasseur B, Parquet N et al.. Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: a retrospective analysis on 32 patients.  Ann Oncol. 2000;  11 (Suppl 1) 113-116
  • 126 Ghobrial I M, Habermann T M, Ristow K M et al.. Prognostic factors in patients with post-transplant lymphoproliferative disorders (PTLD) in the rituximab era.  Leuk Lymphoma. 2005;  46 (2) 191-196
  • 127 Suzan F, Ammor M, Ribrag V. Fatal reactivation of cytomegalovirus infection after use of rituximab for a post-transplantation lymphoproliferative disorder.  N Engl J Med. 2001;  345 (13) 1000
  • 128 Leblond V, Dhedin N, Mamzer Bruneel M F et al.. Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders.  J Clin Oncol. 2001;  19 (3) 772-778
  • 129 Manuel O, Kumar D, Singer L G, Cobos I, Humar A. Incidence and clinical characteristics of herpes zoster after lung transplantation.  J Heart Lung Transplant. 2008;  27 (1) 11-16
  • 130 Fuks L, Shitrit D, Fox B D et al.. Herpes zoster after lung transplantation: incidence, timing, and outcome.  Ann Thorac Surg. 2009;  87 (2) 423-426
  • 131 Corey L, Spear P G. Infections with herpes simplex viruses (1).  N Engl J Med. 1986;  314 (11) 686-691
  • 132 Dummer J S, Armstrong J, Somers J et al.. Transmission of infection with herpes simplex virus by renal transplantation.  J Infect Dis. 1987;  155 (2) 202-206
  • 133 Holland H K, Wingard J R, Saral R. Herpesvirus and enteric viral infections in bone marrow transplantation: clinical presentations, pathogenesis, and therapeutic strategies.  Cancer Invest. 1990;  8 (5) 509-521
  • 134 Singh N, Dummer J S, Kusne S et al.. Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT3 antibodies.  J Infect Dis. 1988;  158 (1) 124-131
  • 135 Smyth R L, Higenbottam T W, Scott J P et al.. Herpes simplex virus infection in heart-lung transplant recipients.  Transplantation. 1990;  49 (4) 735-739
  • 136 Taylor R J, Saul S H, Dowling J N, Hakala T R, Peel R L, Ho M. Primary disseminated herpes simplex infection with fulminant hepatitis following renal transplantation.  Arch Intern Med. 1981;  141 (11) 1519-1521
  • 137 Lakeman F D, Whitley R J. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group . Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease.  J Infect Dis. 1995;  171 (4) 857-863
  • 138 Gnann Jr J W. Herpes simplex and Varicella Zoster infection after hemopoietic stem cell or solid organ transplantation. In: Bowden R A, Ljungman P, Paya C V, eds. Transplant Infections. 2nd ed. Philadelphia: Lippincott-Williams and Wilkens; 2003: 350-366
  • 139 Perry C M, Faulds D. Valaciclovir: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections.  Drugs. 1996;  52 (5) 754-772
  • 140 Gäbel H, Flamholc L, Ahlfors K. Herpes simplex virus hepatitis in a renal transplant recipient: successful treatment with acyclovir.  Scand J Infect Dis. 1988;  20 (4) 435-438
  • 141 Gnann Jr J W, Whitley R J. Clinical practice: herpes zoster.  N Engl J Med. 2002;  347 (5) 340-346
  • 142 Locksley R M, Flournoy N, Sullivan K M, Meyers J D. Infection with varicella-zoster virus after marrow transplantation.  J Infect Dis. 1985;  152 (6) 1172-1181
  • 143 Liesegang T J. Varicella zoster viral disease.  Mayo Clin Proc. 1999;  74 (10) 983-998
  • 144 Zaia J A, Levin M J, Preblud S R et al.. Evaluation of varicella-zoster immune globulin: protection of immunosuppressed children after household exposure to varicella.  J Infect Dis. 1983;  147 (4) 737-743
  • 145 Broyer M, Tete M J, Guest G, Gagnadoux M F, Rouzioux C. Varicella and zoster in children after kidney transplantation: long-term results of vaccination.  Pediatrics. 1997;  99 (1) 35-39

Martin R ZamoraM.D. 

Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver Health Sciences Center

Mail Stop F749, 1635 Aurora Court, Rm. 7082, Aurora, CO 80045

Email: Marty.Zamora@ucdenver.edu

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