Abstract
Adenovirus infection remains an important cause of mortality after bone marrow transplantation (BMT). Currently no efficient antiviral treatment is known. Thus, testing new modalities of early diagnosis and treatment is a crucial objective. Adenovirus infection is defined by the combination of symptoms and the isolation of virus from the source of clinical symptoms. The involvement of two or more organs and the presence of virus in blood cultures define disseminated disease. Seven children with a median age of 7 years received bone marrow transplantation for leukemia. All received an unrelated graft without T cell depletion. Adenovirus was sought in blood, urine and biopsy specimens using PCR and culture. Analysis of biopsy specimens included systematic immunohistochemistry. Cidofovir treatment was initiated as soon as biopsy revealed the histopathological signs of adenovirus. Cidofovir was given at 5 mg/kg once weekly for 3 weeks then every 2 weeks. Six patients had diarrhoea and one patient had cystitis. Adenovirus infection and disseminated disease were diagnosed in four cases and three cases, respectively. In six cases, serotype A31 was isolated from gastrointestinal biopsy and in two cases serotypes B2 and C6 were detected in blood and urine. Cidofovir treatment was associated with clinical improvement of diarrhoea, cystitis and fever in five patients, in whom the virus became undetectable in cultures and PCR analyses despite the persistence of immunodeficiency. The median follow-up was 360 days after BMT (240–570). One child died of invasive aspergillosis and another of disseminated adenovirus after interruption of cidofovir therapy. Further studies in immunocompromised patients will be needed to extend these promising results concerning the role of cidofovir in adenovirus infection. Bone Marrow Transplantation (2001) 27, 621–626.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hierholzer JC . Adenoviruses in the immunocompromised host Clin Microbiol 1992 5: 262–274
Flomenberg P, Babbitt J, Drobyski WR et al. Increasing incidence of adenovirus disease in bone marrow transplant recipients Infect Dis 1994 169: 775–781
Hale GA, Heslop HE, Krance RA et al. Adenovirus infection after pediatric bone marrow transplantation Bone Marrow Transplant 1999 23: 277–282
Shields AF, Hackman RC, Fife KH et al. Adenovirus infections in patients undergoing bone-marrow transplantation New Engl J Med 1985 312: 529–533
Cherry JD . Adenoviral infections. In: Feigin RD, Cherry JD (eds) Textbook of Pediatric Infectious Diseases WB Saunders Co: Philadelphia 1992 pp 1670–1687
Cox JG, Matusi SM, Lo RS et al. Etiology and outcome of diarrhea after marrow transplantation: a prospective study Gastroenterology 1994 107: 1398–1407
Dalapathy S, Lily TK, Roy S et al. Development and use of nested polymerase chain reaction (PCR) for the detection of adenovirus from conjunctivitis specimens J Clin Virol 1998 11: 77–84
Hierholzer JC, Halonen PE, Dahlen PO et al. Detection of adenovirus in clinical specimens by polymerase chain reaction and liquid-phase hybridization quantitated by time-resolved fluorimetry J Clin Microbiol 1993 31: 1886–1891
Larousserie F, Berrebi D, Florentin A et al. Down-regulation of CD95 (Fas/Apo-1) in the epithelia of adenovirus-infected appendices Histopathology 1997 31: 342–346
Studies of ocular complications of AIDS Research Group in collaboration with AIDS Clinical Trial Group . A randomized controlled trial. Parenteral Cidofovir for CMV retinitis in patients with AIDS: the HPMPC peripheral CMV retinitis trial Ann Intern Med 1997 126: 264–274
Jacob P, Lalezari JP, Robert J et al. Intravenous cidofovir for peripheral CMV retinitis in patients with AIDS Ann Intern Med 1997 126: 257–263
De Oliveira CB, Stevenson D, LaBree L et al. Evaluation of cidofovir (HPMPC, GS-504) against adenovirus type 5 infection in vitro and in a New Zealand rabbit ocular model Antiviral Res 1996 31: 165–172
Freymuth F, Vabret A, Galateau-Salle F et al. Detection of respiratory syncytial virus, parainfluenza virus 3, adenovirus and rhinovirus in respiratory tract of infants by PCR and hybridization Clin Diagn Virol 1997 8: 31–40
Kidd AH, Jonsson M, Garwicz D et al. Rapid subgenus identification of human adenovirus isolates by a general PCR J Clin Microbiol 1996 34: 622–627
Masereeuw R, van Pelt AP, van Os SH et al. Probenecid interferes with renal oxidative metabolism: a potential pitfall in its use as an inhibitor of drug transport Br J Pharmacol 2000 131: 57–62
Cundy KC, Li ZH, Lee WA . Effect of probenecid on the distribution, metabolism, and excretion of cidofovir in rabbits Drug Metab Dispos 1996 24: 315–321
Chen FE, Liang RH, Lo JY et al. Treatment of adenovirus-associated haemorrhagic cystitis with ganciclovir Bone Marrow Transplant 1997 20: 997–999
Sabroe I, McHale J, Tait DR et al. Treatment of adenoviral pneumonitis with intravenous ribavirin and immunoglobulin Thorax 1995 50: 1219–1220
Maslo C, Girard PM, Urban T et al. Ribavirin therapy for adenovirus pneumonia in an AIDS patient Am J Respir Crit Care Med 1997 156: 1263–1264
Kawakami M, Ueda S, Maeda T et al. Vidarabine therapy for virus-associated cystitis after allogenic bone marrow transplantation Bone Marrow Transplant 1997 20: 485–490
Mann D, Moreb J, Smith S et al. Failure of intravenous ribavirin in the treatment of invasive adenovirus infection following allogenic bone marrow transplantation: a case report J Infect 1998 36: 227–228
Ribaud P, Scieux C, Freymuth F et al. Successful treatment of adenovirus disease with intravenous cidofovir in an unrelated stem-cell transplant recipient Clin Infect Dis 1999 28: 690–691
Hedderwick SA, Greenson JK, McGaughy VR et al. Adenovirus cholecystitis in a patient with AIDS Clin Infect Dis 1998 26: 997–999
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Legrand, F., Berrebi, D., Houhou, N. et al. Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children. Bone Marrow Transplant 27, 621–626 (2001). https://doi.org/10.1038/sj.bmt.1702820
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1702820
Keywords
This article is cited by
-
Experience with Cidofovir as an adjunctive therapy in a patient of adenovirus-induced macrophage activation syndrome in systemic arthritis
Clinical Rheumatology (2020)
-
Navigating the jungles of tropical infectious gastrointestinal pathology: a pattern-based approach to the endoscopic biopsy
Virchows Archiv (2018)
-
The Role of Adenovirus in Respiratory Tract Infections
Current Infectious Disease Reports (2010)