Cytomegalovirus and Lung Transplantation

Cytomegalovirus (CMV) infection remains a serious problem in lung transplant recipients. Development of potent oral antiviral agents, molecular techniques for the detection of infection and its response to therapy and the emergence of isolates with antiviral resistance have had significant impacts on the approach to CMV in these patients. This article discusses the following issues as part of a comprehensive CMV management strategy in lung transplant recipients: ( 1) Prevention strategies in the era of potent oral antiviral agents, ( 2) the role of new diagnostic techniques in the management of CMV, ( 3) treatment regimens for established CMV infection or disease, ( 4) the potential impact of treatment of CMV on the indirect effects on long‐term allograft function, and ( 5) the incidence, risk factors for and impact of ganciclovir resistance following lung transplantation.

[1]  M. Zamora Use of cytomegalovirus immune globulin and ganciclovir for the prevention of cytomegalovirus disease in lung transplantation , 2001, Transplant infectious disease : an official journal of the Transplantation Society.

[2]  S. Chou,et al.  Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease. , 1997, The Journal of infectious diseases.

[3]  M. Messerle,et al.  Lungs are a major organ site of cytomegalovirus latency and recurrence , 1993, Journal of virology.

[4]  J. Cooper,et al.  Failure of prophylactic ganciclovir to prevent cytomegalovirus disease in recipients of lung transplants. , 1992, The Journal of infectious diseases.

[5]  S. Walmsley,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 , 1999, Journal of Clinical Microbiology.

[6]  N. Lurain,et al.  Molecular analysis of human cytomegalovirus strains from two lung transplant recipients with the same donor. , 1996, Transplantation.

[7]  Thomas F. Smith,et al.  Human β-Herpesvirus Interactions in Solid Organ Transplant Recipients , 2001 .

[8]  N. Smedira,et al.  HYPOGAMMAGLOBULINEMIA IN LUNG TRANSPLANT RECIPIENTS , 2001, Transplantation.

[9]  H. Krueger,et al.  THE COST IMPACT OF CYTOMEGALOVIRUS DISEASE IN RENAL TRANSPLANT RECIPIENTS , 1993, Transplantation.

[10]  G. Snell,et al.  Increased human cytomegalovirus (HCMV) DNA load in peripheral blood leukocytes after lung transplantation correlates with HCMV pneumonitis. , 2001, Transplantation.

[11]  M. Stern,et al.  Failure of ganciclovir treatment associated with selection of a ganciclovir-resistant cytomegalovirus strain in a lung transplant recipient. , 1997, Transplantation.

[12]  R. Rubin,et al.  Infection in organ-transplant recipients. , 1998, The New England journal of medicine.

[13]  R. Rubin,et al.  Combined antibody and ganciclovir treatment of murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice , 1989, Antimicrobial Agents and Chemotherapy.

[14]  G. Schoch,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. , 1995, Blood.

[15]  J. Egan,et al.  Evaluation of CMV viral load using TaqMan CMV quantitative PCR and comparison with CMV antigenemia in heart and lung transplant recipients. , 2001, Transplantation.

[16]  Nina Singh,et al.  Invasive aspergillosis in liver transplant recipients in the 1990s. , 1997, Transplantation.

[17]  B. Griffith,et al.  Ganciclovir prophylaxis for cytomegalovirus infections in pulmonary allograft recipients. , 1992, The American review of respiratory disease.

[18]  G. Raghu,et al.  EFFICACY OF A 6‐WEEK PROPHYLACTIC GANCICLOVIR REGIMEN AND THE ROLE OF SERIAL CYTOMEGALOVIRUS ANTIBODY TESTING IN LUNG TRANSPLANT RECIPIENTS , 1995, Transplantation.

[19]  A. Caliendo,et al.  Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients. , 1999, Transplantation.

[20]  K. Ohta,et al.  Evaluation of the AMPLICOR CMV, COBAS AMPLICOR CMV monitor and antigenemia assay for cytomegalovirus disease. , 2001, Japanese journal of infectious diseases (Print).

[21]  E. Trulock,et al.  The impact of ganciclovir-resistant cytomegalovirus infection after lung transplantation. , 1999, Transplantation.

[22]  M. Zamora,et al.  Comparison of the efficacy and cost-effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients. , 2000, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[23]  F. Baldanti,et al.  Use of the human cytomegalovirus (HCMV) antigenemia assay for diagnosis and monitoring of HCMV infections and detection of antiviral drug resistance in the immunocompromised. , 1998, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[24]  R. Rubin,et al.  The bidirectional relationship between cytomegalovirus and allograft injury. , 2001, Transplantation proceedings.

[25]  B. Griffith,et al.  A comparison of ganciclovir and acyclovir to prevent cytomegalovirus after lung transplantation. , 1994, American journal of respiratory and critical care medicine.

[26]  P. Corris,et al.  Prophylaxis and management of cytomegalovirus pneumonitis after lung transplantation: a review of experience in one center. , 1993, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[27]  H. Valantine Prevention and treatment of cytomegalovirus disease in thoracic organ transplant patients: evidence for a beneficial effect of hyperimmune globulin. , 1995, Transplantation proceedings.

[28]  T. Wreghitt Cytomegalovirus infections in heart and heart-lung transplant recipients. , 1989, The Journal of antimicrobial chemotherapy.

[29]  A. Limaye,et al.  Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants , 2000, The Lancet.

[30]  G. Raghu,et al.  High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. , 2002, The Journal of infectious diseases.

[31]  E. Trulock,et al.  Impact of prophylaxis with cytogam alone on the incidence of CMV viremia in CMV-seropositive lung transplant recipients. , 2003, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[32]  A. Haverich,et al.  Detection of CMV Pneumonitis after Lung Transplantation Using PCR of DNA from Bronchoalveolar Lavage Cells , 2000, Respiration.

[33]  R. Walker,et al.  Influence of anti‐rejection therapy on the timing of cytomegalovirus disease and other infections in renal transplant recipients , 2000, Clinical transplantation.

[34]  S. Hunt,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 , 2001, Transplantation.

[35]  J. Griffith,et al.  Cytomegalovirus disease is associated with increased cost and hospital length of stay among orthotopic liver transplant recipients. , 1997, Transplantation.

[36]  S. Beck,et al.  Human cytomegalovirus encodes a glycoprotein homologous to MHC class-I antigens , 1988, Nature.

[37]  R. Bolman,et al.  Randomized trial of daily versus three-times-weekly prophylactic ganciclovir after lung and heart-lung transplantation. , 1998, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[38]  G. Raghu,et al.  Comparison of the efficacy and cost effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients. , 2000, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[39]  N. Smedira,et al.  Hypogammaglobulinemia following cardiac transplantation: a link between rejection and infection. , 2001, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[40]  R. Rubin,et al.  Prevention dof recurrent cytomegalovirus disease in renal and liver transplant recipients: effect of oral ganciclovir , 2000 .

[41]  B. Griffith,et al.  Sequelae of cytomegalovirus pulmonary infections in lung allograft recipients. , 1992, The American review of respiratory disease.

[42]  L L Schulman,et al.  Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation. , 2001, American journal of respiratory and critical care medicine.

[43]  W. Harmsen,et al.  Human beta-herpesvirus interactions in solid organ transplant recipients. , 2001, The Journal of infectious diseases.

[44]  C. S. Campbell,et al.  Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients. , 1995, Thorax.

[45]  R. Rubin Prevention and treatment of cytomegalovirus disease in heart transplant patients. , 2000, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[46]  G. Berry,et al.  Impact of ganciclovir prophylaxis on heart-lung and lung transplant recipients. , 1996, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[47]  F. Baldanti,et al.  Ganciclovir resistance as a result of oral ganciclovir in a heart transplant recipient with multiple human cytomegalovirus strains in blood. , 1998, Transplantation.

[48]  A. Husain,et al.  Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients. , 2001, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[49]  A. Erice Resistance of Human Cytomegalovirus to Antiviral Drugs , 1999, Clinical Microbiology Reviews.

[50]  D. Knight,et al.  Novel mechanism of inhibition of cytomegalovirus by the experimental immunosuppressive agent leflunomide. , 1999, Transplantation.

[51]  E. Spitznagel,et al.  Cytomegalovirus Infection and Pneumonitis: Impact after Isolated Lung Transplantation , 1993 .

[52]  L. Sharples,et al.  Development of bronchiolitis obliterans syndrome in recipients of heart-lung transplantation--early risk factors. , 1996, Transplantation.

[53]  W. Kim,et al.  The economic impact of cytomegalovirus infection after liver transplantation. , 2000, Transplantation.

[54]  J. Maurer,et al.  Outcomes of lung transplantation using three different cytomegalovirus prophylactic regimens. , 1993, Transplantation proceedings.

[55]  T. Small,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 , 2001, Bone Marrow Transplantation.

[56]  D. Snydman Infection in solid organ transplantation , 1999, Transplant infectious disease : an official journal of the Transplantation Society.

[57]  E. Mylonakis,et al.  Combination antiviral therapy for ganciclovir-resistant cytomegalovirus infection in solid-organ transplant recipients. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[58]  D. McGiffin,et al.  Combination Prophylaxis with Ganciclovir and Cytomegalovirus (CMV) Immune Globulin After Lung Transplantation: Effective CMV Prevention Following Daclizumab Induction , 2003, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[59]  M. Zamora,et al.  Comparison of PCR, Antigenemia Assay, and Rapid Blood Culture for Detection and Prevention of Cytomegalovirus Disease after Lung Transplantation , 2000, Journal of Clinical Microbiology.

[60]  R. Rubin,et al.  Prevention of recurrent cytomegalovirus disease in renal and liver transplant recipients: effect of oral ganciclovir. , 1999, Transplant infectious disease : an official journal of the Transplantation Society.