Emerging Transplant Infections pp 1-25 | Cite as
Transplant Adenovirus Infection: Clinical Syndromes, Diagnosis, and Management
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Abstract
Infections due to adenoviruses confer significant morbidity and mortality in immunocompromised hosts. Manifestations of disease in the setting of hematopoietic stem cell and solid organ transplantation may range from asymptomatic shedding or viremia to localized infection and disseminated disease. In solid organ transplant recipients, adenoviral disease often involves the allograft and can lead to graft dysfunction and/or graft loss. Several diagnostic methods are available for adenovirus infections, which include viral culture, direct antigen detection, molecular techniques, and histopathology. The cornerstone of treatment is the reduction of immunosuppression. Adjunct antiviral therapy is used if there is an inadequate clinical response to immunosuppression reduction. Immunotherapy is an option for those who fail to respond to established therapeutic options.
Keywords
Adenovirus Immunocompromised hosts Diagnosis TreatmentReferences
- 1.Echavarria M. Adenoviruses in immunocompromised hosts. Clin Microbiol Rev. 2008;21(4):704–15.PubMedPubMedCentralCrossRefGoogle Scholar
- 2.Ison MG. Adenovirus infections in transplant recipients. Clin Infect Dis. 2006;43(3):331–9.PubMedCrossRefGoogle Scholar
- 3.Hoffman JA. Adenovirus infections in solid organ transplant recipients. Curr Opin Organ Transplant. 2009;14(6):625–33.PubMedCrossRefGoogle Scholar
- 4.Lion T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin Microbiol Rev. 2014;27(3):441–62.PubMedPubMedCentralCrossRefGoogle Scholar
- 5.Dicks MD, Spencer AJ, Edwards NJ, Wadell G, Bojang K, Gilbert SC, et al. A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. PLoS One. 2012;7(7):e40385.PubMedPubMedCentralCrossRefGoogle Scholar
- 6.Sanchez-Prieto R, de Alava E, Palomino T, Guinea J, Fernandez V, Cebrian S, et al. An association between viral genes and human oncogenic alterations: the adenovirus E1A induces the Ewing tumor fusion transcript EWS-FLI1. Nat Med. 1999;5(9):1076–9.PubMedCrossRefGoogle Scholar
- 7.Kosulin K, Geiger E, Vecsei A, Huber WD, Rauch M, Brenner E, et al. Persistence and reactivation of human adenoviruses in the gastrointestinal tract. Clin Microbiol Infect. 2016;22(4):381 e1–8.CrossRefGoogle Scholar
- 8.Roy S, Calcedo R, Medina-Jaszek A, Keough M, Peng H, Wilson JM. Adenoviruses in lymphocytes of the human gastro-intestinal tract. PLoS One. 2011;6(9):e24859.PubMedPubMedCentralCrossRefGoogle Scholar
- 9.Garnett CT, Talekar G, Mahr JA, Huang W, Zhang Y, Ornelles DA, et al. Latent species C adenoviruses in human tonsil tissues. J Virol. 2009;83(6):2417–28.PubMedCrossRefGoogle Scholar
- 10.Lynch JP 3rd, Kajon AE. Adenovirus: epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Semin Respir Crit Care Med. 2016;37(4):586–602.PubMedCrossRefPubMedCentralGoogle Scholar
- 11.Matthes-Martin S, Boztug H, Lion T. Diagnosis and treatment of adenovirus infection in immunocompromised patients. Expert Rev Anti-Infect Ther. 2013;11(10):1017–28.PubMedCrossRefGoogle Scholar
- 12.Pettengill MA, Babu TM, Prasad P, Chuang S, Drage MG, Menegus M, et al. Probable donor-derived human adenovirus type 34 infection in 2 kidney transplant recipients from the same donor. Open Forum Infect Dis. 2019;6(3):ofy354.PubMedCrossRefGoogle Scholar
- 13.Huh K, Kim I, Jung J, Lee JE, Jhun BW, Gu SH, et al. Prolonged shedding of type 55 human adenovirus in immunocompetent adults with adenoviral respiratory infections. Eur J Clin Microbiol Infect Dis. 2019;38(4):793–800.PubMedCrossRefGoogle Scholar
- 14.Rutala WA, Peacock JE, Gergen MF, Sobsey MD, Weber DJ. Efficacy of hospital germicides against adenovirus 8, a common cause of epidemic keratoconjunctivitis in health care facilities. Antimicrob Agents Chemother. 2006;50(4):1419–24.PubMedPubMedCentralCrossRefGoogle Scholar
- 15.Venard V, Carret A, Corsaro D, Bordigoni P, Le Faou A. Genotyping of adenoviruses isolated in an outbreak in a bone marrow transplant unit shows that diverse strains are involved. J Hosp Infect. 2000;44(1):71–4.PubMedCrossRefGoogle Scholar
- 16.Veltrop-Duits LA, van Vreeswijk T, Heemskerk B, Thijssen JC, El Seady R, Jol-van der Zijde EM, et al. High titers of pre-existing adenovirus serotype-specific neutralizing antibodies in the host predict viral reactivation after allogeneic stem cell transplantation in children. Clin Infect Dis. 2011;52(12):1405–13.PubMedCrossRefGoogle Scholar
- 17.Lion T, Kosulin K, Landlinger C, Rauch M, Preuner S, Jugovic D, et al. Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation. Leukemia. 2010;24(4):706–14.PubMedCrossRefGoogle Scholar
- 18.Baldwin A, Kingman H, Darville M, Foot AB, Grier D, Cornish JM, et al. Outcome and clinical course of 100 patients with adenovirus infection following bone marrow transplantation. Bone Marrow Transplant. 2000;26(12):1333–8.PubMedCrossRefGoogle Scholar
- 19.Runde V, Ross S, Trenschel R, Lagemann E, Basu O, Renzing-Kohler K, et al. Adenoviral infection after allogeneic stem cell transplantation (SCT): report on 130 patients from a single SCT unit involved in a prospective multi center surveillance study. Bone Marrow Transplant. 2001;28(1):51–7.PubMedCrossRefGoogle Scholar
- 20.Bruno B, Gooley T, Hackman RC, Davis C, Corey L, Boeckh M. Adenovirus infection in hematopoietic stem cell transplantation: effect of ganciclovir and impact on survival. Biol Blood Marrow Transplant. 2003;9(5):341–52.PubMedCrossRefGoogle Scholar
- 21.Avivi I, Chakrabarti S, Milligan DW, Waldmann H, Hale G, Osman H, et al. Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab. Biol Blood Marrow Transplant. 2004;10(3):186–94.PubMedCrossRefGoogle Scholar
- 22.Gustafson I, Lindblom A, Yun Z, Omar H, Engstrom L, Lewensohn-Fuchs I, et al. Quantification of adenovirus DNA in unrelated donor hematopoietic stem cell transplant recipients. J Clin Virol. 2008;43(1):79–85.PubMedCrossRefGoogle Scholar
- 23.La Rosa AM, Champlin RE, Mirza N, Gajewski J, Giralt S, Rolston KV, et al. Adenovirus infections in adult recipients of blood and marrow transplants. Clin Infect Dis. 2001;32(6):871–6.PubMedCrossRefGoogle Scholar
- 24.Ganzenmueller T, Buchholz S, Harste G, Dammann E, Trenschel R, Heim A. High lethality of human adenovirus disease in adult allogeneic stem cell transplant recipients with high adenoviral blood load. J Clin Virol. 2011;52(1):55–9.PubMedCrossRefGoogle Scholar
- 25.Watcharananan SP, Avery R, Ingsathit A, Malathum K, Chantratita W, Mavichak V, et al. Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery. Am J Transplant. 2011;11(6):1308–14.PubMedCrossRefGoogle Scholar
- 26.Humar A, Kumar D, Mazzulli T, Razonable RR, Moussa G, Paya CV, et al. A surveillance study of adenovirus infection in adult solid organ transplant recipients. Am J Transplant. 2005;5(10):2555–9.PubMedCrossRefGoogle Scholar
- 27.Humar A. Reactivation of viruses in solid organ transplant patients receiving cytomegalovirus prophylaxis. Transplantation. 2006;82(2 Suppl):S9–S14.PubMedCrossRefGoogle Scholar
- 28.Bridges ND, Spray TL, Collins MH, Bowles NE, Towbin JA. Adenovirus infection in the lung results in graft failure after lung transplantation. J Thorac Cardiovasc Surg. 1998;116(4):617–23.PubMedCrossRefGoogle Scholar
- 29.Florescu DF, Schaenman JM, Practice ASTIDCo. Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transpl. 2019;33:e13527.CrossRefGoogle Scholar
- 30.McGrath D, Falagas ME, Freeman R, Rohrer R, Fairchild R, Colbach C, et al. Adenovirus infection in adult orthotopic liver transplant recipients: incidence and clinical significance. J Infect Dis. 1998;177(2):459–62.PubMedCrossRefGoogle Scholar
- 31.Flomenberg P, Babbitt J, Drobyski WR, Ash RC, Carrigan DR, Sedmak GV, et al. Increasing incidence of adenovirus disease in bone marrow transplant recipients. J Infect Dis. 1994;169(4):775–81.PubMedCrossRefGoogle Scholar
- 32.Matthes-Martin S, Feuchtinger T, Shaw PJ, Engelhard D, Hirsch HH, Cordonnier C, et al. European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL-4 (2011). Transpl Infect Dis. 2012;14(6):555–63.PubMedCrossRefGoogle Scholar
- 33.Keyes A, Mathias M, Boulad F, Lee YJ, Marchetti MA, Scaradavou A, et al. Cutaneous involvement of disseminated adenovirus infection in an allogeneic stem cell transplant recipient. Br J Dermatol. 2016;174(4):885–8.PubMedPubMedCentralCrossRefGoogle Scholar
- 34.Iyama S, Matsunaga T, Fujimi A, Murase K, Kuribayasi K, Sato T, et al. Successful treatment with oral ribavirin of adenovirus-associated hemophagocytic syndrome in a stem cell transplantation recipient. Rinsho Ketsueki. 2005;46(5):363–7.PubMedGoogle Scholar
- 35.Levy J, Wodell RA, August CS, Bayever E. Adenovirus-related hemophagocytic syndrome after bone marrow transplantation. Bone Marrow Transplant. 1990;6(5):349–52.PubMedGoogle Scholar
- 36.Yilmaz M, Chemaly RF, Han XY, Thall PF, Fox PS, Tarrand JJ, et al. Adenoviral infections in adult allogeneic hematopoietic SCT recipients: a single center experience. Bone Marrow Transplant. 2013;48(9):1218–23.PubMedPubMedCentralCrossRefGoogle Scholar
- 37.Ramsay ID, Attwood C, Irish D, Griffiths PD, Kyriakou C, Lowe DM. Disseminated adenovirus infection after allogeneic stem cell transplant and the potential role of brincidofovir – case series and 10 year experience of management in an adult transplant cohort. J Clin Virol. 2017;96:73–9.PubMedCrossRefGoogle Scholar
- 38.Hubmann M, Fritsch S, Zoellner AK, Prevalsek D, Engel N, Bucklein V, et al. Occurrence, risk factors and outcome of adenovirus infection in adult recipients of allogeneic hematopoietic stem cell transplantation. J Clin Virol. 2016;82:33–40.PubMedCrossRefGoogle Scholar
- 39.Howard DS, Phillips IG, Reece DE, Munn RK, Henslee-Downey J, Pittard M, et al. Adenovirus infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 1999;29(6):1494–501.PubMedCrossRefGoogle Scholar
- 40.Chakrabarti S, Mautner V, Osman H, Collingham KE, Fegan CD, Klapper PE, et al. Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppression, and immune recovery. Blood. 2002;100(5):1619–27.PubMedCrossRefGoogle Scholar
- 41.Lion T, Baumgartinger R, Watzinger F, Matthes-Martin S, Suda M, Preuner S, et al. Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease. Blood. 2003;102(3):1114–20.PubMedCrossRefGoogle Scholar
- 42.Omar H, Yun Z, Lewensohn-Fuchs I, Perez-Bercoff L, Orvell C, Engstrom L, et al. Poor outcome of adenovirus infections in adult hematopoietic stem cell transplant patients with sustained adenovirus viremia. Transpl Infect Dis. 2010;12(5):465–9.PubMedCrossRefGoogle Scholar
- 43.Michaels MG, Green M, Wald ER, Starzl TE. Adenovirus infection in pediatric liver transplant recipients. J Infect Dis. 1992;165(1):170–4.PubMedCrossRefGoogle Scholar
- 44.McLaughlin GE, Delis S, Kashimawo L, Cantwell GP, Mittal N, Cirocco RE, et al. Adenovirus infection in pediatric liver and intestinal transplant recipients: utility of DNA detection by PCR. Am J Transplant. 2003;3(2):224–8.PubMedCrossRefGoogle Scholar
- 45.Schaberg KB, Kambham N, Sibley RK, Higgins JPT. Adenovirus hepatitis: clinicopathologic analysis of 12 consecutive cases from a single institution. Am J Surg Pathol. 2017;41(6):810–9.PubMedCrossRefGoogle Scholar
- 46.Haas K, Longacre T, Castillo RO. Adenovirus hepatic abscess: a novel source of fever of unknown origin in a pediatric liver transplant recipient. Dig Dis Sci. 2017;62(4):871–3.PubMedPubMedCentralCrossRefGoogle Scholar
- 47.Mitchell SL, Kajon AE, Kaplan SL, Kim J, Cardenas AM. An unusual case of disseminated adenovirus infection in a cystic fibrosis, liver transplant patient. J Clin Virol. 2016;81:64–7.PubMedCrossRefGoogle Scholar
- 48.Majorant D, Qiu F, Kalil AC, Wilson N, Florescu DF. Adenovirus-A deadly disease in the solid organ transplant population: risk factors and outcomes. Transplant Proc. 2018;50(10):3769–74.PubMedCrossRefGoogle Scholar
- 49.Engen RM, Huang ML, Park GE, Smith JM, Limaye AP. Prospective assessment of adenovirus infection in pediatric kidney transplant recipients. Transplantation. 2018;102(7):1165–71.PubMedPubMedCentralCrossRefGoogle Scholar
- 50.Hofland CA, Eron LJ, Washecka RM. Hemorrhagic adenovirus cystitis after renal transplantation. Transplant Proc. 2004;36(10):3025–7.PubMedCrossRefGoogle Scholar
- 51.Buchanan W, Bowman JS, Jaffers G. Adenoviral acute hemorrhagic cystitis following renal transplantation. Am J Nephrol. 1990;10(4):350–1.PubMedCrossRefGoogle Scholar
- 52.Satoh S, Tada H, Murakami M, Tsuchiya N, Inoue T, Togashi H, et al. The influence of mycophenolate mofetil versus azathioprine and mycophenolic acid pharmacokinetics on the incidence of acute rejection and infectious complications after renal transplantation. Transplant Proc. 2005;37(4):1751–3.PubMedCrossRefGoogle Scholar
- 53.Shindo K, Kitayama T, Ura T, Matsuya F, Kusaba Y, Kanetake H, et al. Acute hemorrhagic cystitis caused by adenovirus type 11 after renal transplantation. Urol Int. 1986;41(2):152–5.PubMedCrossRefGoogle Scholar
- 54.Shiramizu T, Satoh T, Jinushi K, Oka N, Inokuchi K. Renal allograft dysfunction with acute hemorrhagic cystitis caused by adenovirus in a recipient of a transplanted kidney. Tokai J Exp Clin Med. 1986;11(5):371–5.PubMedGoogle Scholar
- 55.Asim M, Chong-Lopez A, Nickeleit V. Adenovirus infection of a renal allograft. Am J Kidney Dis. 2003;41(3):696–701.PubMedCrossRefGoogle Scholar
- 56.Lim AK, Parsons S, Ierino F. Adenovirus tubulointerstitial nephritis presenting as a renal allograft space occupying lesion. Am J Transplant. 2005;5(8):2062–6.PubMedCrossRefGoogle Scholar
- 57.Alsaad KO, Tobar A, Belanger E, Ahmad M, Cattran DC, Herzenberg AM. Late-onset acute haemorrhagic necrotizing granulomatous adenovirus tubulointerstitial nephritis in a renal allograft. Nephrol Dial Transplant. 2007;22(4):1257–60.PubMedCrossRefGoogle Scholar
- 58.Hensley JL, Sifri CD, Cathro HP, Lobo P, Sawyer RG, Brayman KL, et al. Adenoviral graft-nephritis: case report and review of the literature. Transpl Int. 2009;22(6):672–7.PubMedCrossRefGoogle Scholar
- 59.Kolankiewicz LM, Pullman J, Raffeld M, Kopp JB, Glicklich D. Adenovirus nephritis and obstructive uropathy in a renal transplant recipient: case report and literature review. NDT Plus. 2010;3(4):388–92.PubMedPubMedCentralGoogle Scholar
- 60.Veer M, Abdulmassih R, Como J, Min Z, Bhanot N. Adenoviral nephritis in a renal transplant recipient: case report and literature review. Transpl Infect Dis. 2017;19:e12716.Google Scholar
- 61.Gaspert A, Luthi B, Mueller NJ, Bossart W, Heim A, Wuthrich RP, et al. Subacute allograft failure with dysuria and hematuria in a kidney transplant recipient. Am J Kidney Dis. 2009;54(1):154–8.PubMedCrossRefGoogle Scholar
- 62.Yagisawa T, Takahashi K, Yamaguchi Y, Teraoka S, Horita S, Toma H, et al. Adenovirus induced nephropathy in kidney transplant recipients. Transplant Proc. 1989;21(1 Pt 2):2097–9.PubMedGoogle Scholar
- 63.Keswani M, Moudgil A. Adenovirus-associated hemorrhagic cystitis in a pediatric renal transplant recipient. Pediatr Transplant. 2007;11(5):568–71.PubMedCrossRefGoogle Scholar
- 64.Keller EW, Rubin RH, Black PH, Hirsch MS, Hierholzer JC. Isolation of adenovirus type 34 from a renal transplant recipient with interstitial pneumonia. Transplantation. 1977;23(2):188–91.PubMedCrossRefGoogle Scholar
- 65.Stalder H, Hierholzer JC, Oxman MN. New human adenovirus (candidate adenovirus type 35) causing fatal disseminated infection in a renal transplant recipient. J Clin Microbiol. 1977;6(3):257–65.PubMedPubMedCentralGoogle Scholar
- 66.Hierholzer JC, Atuk NO, Gwaltney JM Jr. New human adenovirus isolated from a renal transplant recipient: description and characterization of candidate adenovirus type 34. J Clin Microbiol. 1975;1(4):366–76.PubMedPubMedCentralCrossRefGoogle Scholar
- 67.Rosario RF, Kimbrough RC, Van Buren DH, Laski ME. Fatal adenovirus serotype-5 in a deceased-donor renal transplant recipient. Transpl Infect Dis. 2006;8(1):54–7.PubMedCrossRefGoogle Scholar
- 68.Norris SH, Butler TC, Glass N, Tran R. Fatal hepatic necrosis caused by disseminated type 5 adenovirus infection in a renal transplant recipient. Am J Nephrol. 1989;9(2):101–5.PubMedCrossRefGoogle Scholar
- 69.Humar A, Doucette K, Kumar D, Pang XL, Lien D, Jackson K, et al. Assessment of adenovirus infection in adult lung transplant recipients using molecular surveillance. J Heart Lung Transplant. 2006;25(12):1441–6.PubMedCrossRefPubMedCentralGoogle Scholar
- 70.Ohori NP, Michaels MG, Jaffe R, Williams P, Yousem SA. Adenovirus pneumonia in lung transplant recipients. Hum Pathol. 1995;26(10):1073–9.PubMedCrossRefGoogle Scholar
- 71.Simsir A, Greenebaum E, Nuovo G, Schulman LL. Late fatal adenovirus pneumonitis in a lung transplant recipient. Transplantation. 1998;65(4):592–4.PubMedCrossRefGoogle Scholar
- 72.Shirali GS, Ni J, Chinnock RE, Johnston JK, Rosenthal GL, Bowles NE, et al. Association of viral genome with graft loss in children after cardiac transplantation. N Engl J Med. 2001;344(20):1498–503.PubMedCrossRefGoogle Scholar
- 73.Moulik M, Breinholt JP, Dreyer WJ, Kearney DL, Price JF, Clunie SK, et al. Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant recipients. J Am Coll Cardiol. 2010;56(7):582–92.PubMedPubMedCentralCrossRefGoogle Scholar
- 74.Schowengerdt KO, Ni J, Denfield SW, Gajarski RJ, Radovancevic B, Frazier HO, et al. Diagnosis, surveillance, and epidemiologic evaluation of viral infections in pediatric cardiac transplant recipients with the use of the polymerase chain reaction. J Heart Lung Transplant. 1996;15(2):111–23.PubMedGoogle Scholar
- 75.Bruminhent J, Athas DM, Hess BD, Flomenberg P. Disseminated adenovirus disease in heart transplant recipient presenting with conjunctivitis. Transpl Infect Dis. 2015;17(1):125–8.PubMedCrossRefGoogle Scholar
- 76.Gupta A, Philip A, Ranga K, Cappa J, Dougherty J, Lawlor M. An interesting case of adenoviral hepatitis in a cardiac transplant recipient. Transpl Infect Dis. 2010;12(1):84–6.PubMedCrossRefGoogle Scholar
- 77.Refaat M, McNamara D, Teuteberg J, Kormos R, McCurry K, Shullo M, et al. Successful cidofovir treatment in an adult heart transplant recipient with severe adenovirus pneumonia. J Heart Lung Transplant. 2008;27(6):699–700.PubMedCrossRefGoogle Scholar
- 78.Permpalung N, Mahoney MV, Alonso CD. Adjunctive use of cidofovir and intravenous immunoglobulin to treat invasive adenoviral disease in solid organ transplant recipients. Pharmacotherapy. 2018;38(12):1260–6.PubMedCrossRefGoogle Scholar
- 79.Pinchoff RJ, Kaufman SS, Magid MS, Erdman DD, Gondolesi GE, Mendelson MH, et al. Adenovirus infection in pediatric small bowel transplantation recipients. Transplantation. 2003;76(1):183–9.PubMedCrossRefGoogle Scholar
- 80.Ziring D, Tran R, Edelstein S, McDiarmid SV, Gajjar N, Cortina G, et al. Infectious enteritis after intestinal transplantation: incidence, timing, and outcome. Transplantation. 2005;79(6):702–9.PubMedCrossRefGoogle Scholar
- 81.Florescu DF, Islam MK, Mercer DF, Grant W, Langnas AN, Freifeld AG, et al. Adenovirus infections in pediatric small bowel transplant recipients. Transplantation. 2010;90(2):198–204.PubMedCrossRefGoogle Scholar
- 82.Lipson SM, Poshni IA, Ashley RL, Grady LJ, Ciamician Z, Teichberg S. Presumptive identification of common adenovirus serotypes by the development of differential cytopathic effects in the human lung carcinoma (A549) cell culture. FEMS Microbiol Lett. 1993;113(2):175–82.PubMedCrossRefGoogle Scholar
- 83.Van Doornum GJ, De Jong JC. Rapid shell vial culture technique for detection of enteroviruses and adenoviruses in fecal specimens: comparison with conventional virus isolation method. J Clin Microbiol. 1998;36(10):2865–8.PubMedPubMedCentralCrossRefGoogle Scholar
- 84.Florescu MC, Miles CD, Florescu DF. What do we know about adenovirus in renal transplantation? Nephrol Dial Transplant. 2013;28(8):2003–10.PubMedCrossRefGoogle Scholar
- 85.Weidner AS, Panarelli NC, Rennert H, Jessurun J, Yantiss RK. Immunohistochemistry improves the detection of adenovirus in gastrointestinal biopsy specimens from hematopoietic stem cell transplant recipients. Am J Clin Pathol. 2016;146(5):627–31.PubMedCrossRefGoogle Scholar
- 86.Levent F, Greer JM, Snider M, Demmler-Harrison GJ. Performance of a new immunochromatographic assay for detection of adenoviruses in children. J Clin Virol. 2009;44(2):173–5.PubMedCrossRefGoogle Scholar
- 87.Sambursky R, Trattler W, Tauber S, Starr C, Friedberg M, Boland T, et al. Sensitivity and specificity of the AdenoPlus test for diagnosing adenoviral conjunctivitis. JAMA Ophthalmol. 2013;131(1):17–22.PubMedCrossRefGoogle Scholar
- 88.Landry ML, Ferguson D. SimulFluor respiratory screen for rapid detection of multiple respiratory viruses in clinical specimens by immunofluorescence staining. J Clin Microbiol. 2000;38(2):708–11.PubMedPubMedCentralCrossRefGoogle Scholar
- 89.Kuypers J, Campbell AP, Cent A, Corey L, Boeckh M. Comparison of conventional and molecular detection of respiratory viruses in hematopoietic cell transplant recipients. Transpl Infect Dis. 2009;11(4):298–303.PubMedPubMedCentralCrossRefGoogle Scholar
- 90.Ebner K, Suda M, Watzinger F, Lion T. Molecular detection and quantitative analysis of the entire spectrum of human adenoviruses by a two-reaction real-time PCR assay. J Clin Microbiol. 2005;43(7):3049–53.PubMedPubMedCentralCrossRefGoogle Scholar
- 91.Mackay IM, Arden KE, Nitsche A. Real-time PCR in virology. Nucleic Acids Res. 2002;30(6):1292–305.PubMedPubMedCentralCrossRefGoogle Scholar
- 92.Fryer JF, Hockley JG, Govind S, Morris CL and the Collaborative Study Group. Collaborative study to evaluate the proposed 1st WHO International Standard for Human Adenovirus (HAdV) DNA for nucleic acid amplification techniques (NAT). WHO ECBS Report 2018; WHO/BS/2018.2346.Google Scholar
- 93.Doern CD, Lacey D, Huang R, Haag C. Evaluation and implementation of FilmArray version 1.7 for improved detection of adenovirus respiratory tract infection. J Clin Microbiol. 2013;51(12):4036–9.PubMedPubMedCentralCrossRefGoogle Scholar
- 94.Song E, Wang H, Salamon D, Jaggi P, Leber A. Performance characteristics of FilmArray Respiratory Panel v1.7 for detection of adenovirus in a large cohort of pediatric nasopharyngeal samples: one test may not fit all. J Clin Microbiol. 2016;54(6):1479–86.PubMedPubMedCentralCrossRefGoogle Scholar
- 95.McMillen T, Lee YJ, Kamboj M, Babady NE. Limited diagnostic value of a multiplexed gastrointestinal pathogen panel for the detection of adenovirus infection in an oncology patient population. J Clin Virol. 2017;94:37–41.PubMedCrossRefGoogle Scholar
- 96.Zou X, Fan Y, Zhang W, Lu B, Liu Y, Cao B, et al. Metagenomics facilitated complete genome sequencing of adenovirus untyped by real-time PCR. J Infect. 2018;77(2):158–64.PubMedCrossRefGoogle Scholar
- 97.Haddad-Boubaker S, Joffret ML, Perot P, Bessaud M, Meddeb Z, Touzi H, et al. Metagenomic analysis identifies human adenovirus 31 in children with acute flaccid paralysis in Tunisia. Arch Virol. 2019;164(3):747–55.PubMedCrossRefGoogle Scholar
- 98.Morfin F, Dupuis-Girod S, Mundweiler S, Falcon D, Carrington D, Sedlacek P, et al. In vitro susceptibility of adenovirus to antiviral drugs is species-dependent. Antivir Ther. 2005;10(2):225–9.PubMedGoogle Scholar
- 99.Naesens L, Lenaerts L, Andrei G, Snoeck R, Van Beers D, Holy A, et al. Antiadenovirus activities of several classes of nucleoside and nucleotide analogues. Antimicrob Agents Chemother. 2005;49(3):1010–6.PubMedPubMedCentralCrossRefGoogle Scholar
- 100.Chen FE, Liang RH, Lo JY, Yuen KY, Chan TK, Peiris M. Treatment of adenovirus-associated haemorrhagic cystitis with ganciclovir. Bone Marrow Transplant. 1997;20(11):997–9.PubMedCrossRefGoogle Scholar
- 101.Nakazawa Y, Suzuki T, Fukuyama T, Katsuyama Y, Tanaka M, Yanagisawa R, et al. Urinary excretion of ganciclovir contributes to improvement of adenovirus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation. Pediatr Transplant. 2009;13(5):632–5.PubMedCrossRefGoogle Scholar
- 102.Duggan JM, Farrehi J, Duderstadt S, Turner NJ, Fekety R. Treatment with ganciclovir of adenovirus pneumonia in a cardiac transplant patient. Am J Med. 1997;103(5):439–40.PubMedCrossRefGoogle Scholar
- 103.Gavin PJ, Katz BZ. Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children. Pediatrics. 2002;110(1 Pt 1):e9.PubMedCrossRefGoogle Scholar
- 104.Lankester AC, Heemskerk B, Claas EC, Schilham MW, Beersma MF, Bredius RG, et al. Effect of ribavirin on the plasma viral DNA load in patients with disseminating adenovirus infection. Clin Infect Dis. 2004;38(11):1521–5.PubMedCrossRefGoogle Scholar
- 105.Lea AP, Bryson HM. Cidofovir. Drugs. 1996;52(2):225–30; discussion 31.PubMedCrossRefGoogle Scholar
- 106.Ljungman P, Ribaud P, Eyrich M, Matthes-Martin S, Einsele H, Bleakley M, et al. Cidofovir for adenovirus infections after allogeneic hematopoietic stem cell transplantation: a survey by the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2003;31(6):481–6.PubMedCrossRefGoogle Scholar
- 107.Yusuf U, Hale GA, Carr J, Gu Z, Benaim E, Woodard P, et al. Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation. 2006;81(10):1398–404.PubMedCrossRefGoogle Scholar
- 108.Muller WJ, Levin MJ, Shin YK, Robinson C, Quinones R, Malcolm J, et al. Clinical and in vitro evaluation of cidofovir for treatment of adenovirus infection in pediatric hematopoietic stem cell transplant recipients. Clin Infect Dis. 2005;41(12):1812–6.PubMedCrossRefGoogle Scholar
- 109.Vittecoq D, Dumitrescu L, Beaufils H, Deray G. Fanconi syndrome associated with cidofovir therapy. Antimicrob Agents Chemother. 1997;41(8):1846.PubMedPubMedCentralCrossRefGoogle Scholar
- 110.Neau D, Renaud-Rougier MB, Viallard JE, Dutronc H, Cazorla C, Ragnaud JM, et al. Intravenous cidofovir-induced iritis. Clin Infect Dis. 1999;28(1):156–7.PubMedCrossRefGoogle Scholar
- 111.Akler ME, Johnson DW, Burman WJ, Johnson SC. Anterior uveitis and hypotony after intravenous cidofovir for the treatment of cytomegalovirus retinitis. Ophthalmology. 1998;105(4):651–7.PubMedCrossRefGoogle Scholar
- 112.Scott RA, Pavesio C. Ocular side-effects from systemic HPMPC (Cidofovir) for a non-ocular cytomegalovirus infection. Am J Ophthalmol. 2000;130(1):126–7.PubMedCrossRefGoogle Scholar
- 113.Lacy SA, Hitchcock MJ, Lee WA, Tellier P, Cundy KC. Effect of oral probenecid coadministration on the chronic toxicity and pharmacokinetics of intravenous cidofovir in cynomolgus monkeys. Toxicol Sci. 1998;44(2):97–106.PubMedCrossRefGoogle Scholar
- 114.Hoffman JA, Shah AJ, Ross LA, Kapoor N. Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7(7):388–94.PubMedCrossRefGoogle Scholar
- 115.Bhadri VA, Lee-Horn L, Shaw PJ. Safety and tolerability of cidofovir in high-risk pediatric patients. Transpl Infect Dis. 2009;11(4):373–9.PubMedCrossRefGoogle Scholar
- 116.Leruez-Ville M, Minard V, Lacaille F, Buzyn A, Abachin E, Blanche S, et al. Real-time blood plasma polymerase chain reaction for management of disseminated adenovirus infection. Clin Infect Dis. 2004;38(1):45–52.PubMedCrossRefGoogle Scholar
- 117.Seidemann K, Heim A, Pfister ED, Koditz H, Beilken A, Sander A, et al. Monitoring of adenovirus infection in pediatric transplant recipients by quantitative PCR: report of six cases and review of the literature. Am J Transplant. 2004;4(12):2102–8.PubMedCrossRefGoogle Scholar
- 118.Painter W, Robertson A, Trost LC, Godkin S, Lampert B, Painter G. First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob Agents Chemother. 2012;56(5):2726–34.PubMedPubMedCentralCrossRefGoogle Scholar
- 119.Toth K, Spencer JF, Dhar D, Sagartz JE, Buller RM, Painter GR, et al. Hexadecyloxypropyl-cidofovir, CMX001, prevents adenovirus-induced mortality in a permissive, immunosuppressed animal model. Proc Natl Acad Sci U S A. 2008;105(20):7293–7.PubMedPubMedCentralCrossRefGoogle Scholar
- 120.Florescu DF, Keck MA. Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses. Expert Rev Anti-Infect Ther. 2014;12(10):1171–8.PubMedCrossRefGoogle Scholar
- 121.Florescu DF, Pergam SA, Neely MN, Qiu F, Johnston C, Way S, et al. Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients. Biol Blood Marrow Transplant. 2012;18(5):731–8.PubMedCrossRefGoogle Scholar
- 122.Grimley MS, Chemaly RF, Englund JA, Kurtzberg J, Chittick G, Brundage TM, et al. Brincidofovir for asymptomatic adenovirus viremia in pediatric and adult allogeneic hematopoietic cell transplant recipients: a randomized placebo-controlled phase II trial. Biol Blood Marrow Transplant. 2017;23(3):512–21.PubMedCrossRefGoogle Scholar
- 123.Feuchtinger T, Lucke J, Hamprecht K, Richard C, Handgretinger R, Schumm M, et al. Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation. Br J Haematol. 2005;128(4):503–9.PubMedCrossRefGoogle Scholar
- 124.Heemskerk B, Lankester AC, van Vreeswijk T, Beersma MF, Claas EC, Veltrop-Duits LA, et al. Immune reconstitution and clearance of human adenovirus viremia in pediatric stem-cell recipients. J Infect Dis. 2005;191(4):520–30.PubMedCrossRefGoogle Scholar
- 125.van Tol MJ, Claas EC, Heemskerk B, Veltrop-Duits LA, de Brouwer CS, van Vreeswijk T, et al. Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity. Bone Marrow Transplant. 2005;35(Suppl 1):S73–6.PubMedGoogle Scholar
- 126.Feuchtinger T, Matthes-Martin S, Richard C, Lion T, Fuhrer M, Hamprecht K, et al. Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation. Br J Haematol. 2006;134(1):64–76.PubMedCrossRefGoogle Scholar
- 127.Leen AM, Christin A, Myers GD, Liu H, Cruz CR, Hanley PJ, et al. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood. 2009;114(19):4283–92.PubMedPubMedCentralCrossRefGoogle Scholar
- 128.Amrolia PJ, Muccioli-Casadei G, Huls H, Adams S, Durett A, Gee A, et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. Blood. 2006;108(6):1797–808.PubMedPubMedCentralCrossRefGoogle Scholar
- 129.Leen AM, Bollard CM, Mendizabal AM, Shpall EJ, Szabolcs P, Antin JH, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013;121(26):5113–23.PubMedPubMedCentralCrossRefGoogle Scholar
- 130.Gerdemann U, Katari UL, Papadopoulou A, Keirnan JM, Craddock JA, Liu H, et al. Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Mol Ther. 2013;21(11):2113–21.PubMedPubMedCentralCrossRefGoogle Scholar
- 131.Sili U, Leen AM, Vera JF, Gee AP, Huls H, Heslop HE, et al. Production of good manufacturing practice-grade cytotoxic T lymphocytes specific for Epstein-Barr virus, cytomegalovirus and adenovirus to prevent or treat viral infections post-allogeneic hematopoietic stem cell transplant. Cytotherapy. 2012;14(1):7–11.PubMedPubMedCentralCrossRefGoogle Scholar
- 132.Saquib R, Melton LB, Chandrakantan A, Rice KM, Spak CW, Saad RD, et al. Disseminated adenovirus infection in renal transplant recipients: the role of cidofovir and intravenous immunoglobulin. Transpl Infect Dis. 2010;12(1):77–83.PubMedCrossRefGoogle Scholar
- 133.Emovon OE, Lin A, Howell DN, Afzal F, Baillie M, Rogers J, et al. Refractory adenovirus infection after simultaneous kidney-pancreas transplantation: successful treatment with intravenous ribavirin and pooled human intravenous immunoglobulin. Nephrol Dial Transplant. 2003;18(11):2436–8.PubMedCrossRefGoogle Scholar
- 134.Park UJ, Hyun SK, Kim HT, Cho WH, Han SY. Successful treatment of disseminated adenovirus infection with ribavirin and intravenous immunoglobulin in an adult renal transplant recipient: a case report. Transplant Proc. 2015;47(3):791–3.PubMedCrossRefGoogle Scholar
- 135.Mawhorter S, Yamani MH. Hypogammaglobulinemia and infection risk in solid organ transplant recipients. Curr Opin Organ Transplant. 2008;13(6):581–5.PubMedGoogle Scholar
- 136.Lindemans CA, Leen AM, Boelens JJ. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood. 2010;116(25):5476–85.PubMedPubMedCentralCrossRefGoogle Scholar
- 137.Anderson EJ, Guzman-Cottrill JA, Kletzel M, Thormann K, Sullivan C, Zheng X, et al. High-risk adenovirus-infected pediatric allogeneic hematopoietic progenitor cell transplant recipients and preemptive cidofovir therapy. Pediatr Transplant. 2008;12(2):219–27.PubMedCrossRefGoogle Scholar