title: PCR detection of adenovirus in a bone marrow transplant recipient: hemorrhagic cystitis as a presenting manifestation of disseminated disease.
abstract: Adenoviruses (AdV), causing fatal disseminated infections in bone marrow transplant (BMT) recipients, are associated not only with hemorrhagic cystitis (HC) but also with hepatitis, conjunctivitis, and viral interstitial pneumonia. The importance of this virus as a cause of disseminated disease, however, has remained underappreciated. AdV infection has been diagnosed primarily through the use of cell culture. The fact that cell culture is insensitive for detecting this virus has hindered recognition of the role that AdV may play in morbidity and mortality in BMT recipients. To emphasize these points, we describe a patient who presented with HC due to AdV serotype 11, genotype c, and died with disseminated infection. In addition to cell culture, this study used a newly developed PCR-based method, capable of detecting all AdV serotypes tested, including different genotypes of serotype 11. The PCR result was positive in all culture-positive samples, including samples of urine, conjunctiva, and bronchoalveolar lavage (BAL). Importantly, the PCR method provided evidence of urinary shedding of AdV in a pretransplant, culture-negative specimen and showed dissemination in a subset of culture-negative specimens, including BAL, blood, and bone marrow samples. The lack of widespread awareness of the fact that localized infections may presage dissemination, and the previous associated lack of rapid, sensitive diagnostic assays, has impaired recognition of AdV infections in patients undergoing BMT. Early detection may contribute to therapy modification and avoidance of unwarranted diagnostic procedures. It may also assist in epidemiologic control of this highly infectious pathogen and lead to a renewed interest in preventive and therapeutic approaches.
authors.affiliation: Division of Medical Microbiology, Department of Pathology, Division of Infectious Diseases, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Echavarria
authors.forename: S C
authors.initials: SC
authors.lastname: Ray
authors.forename: R
authors.initials: R
authors.lastname: Ambinder
authors.forename: J S
authors.initials: JS
authors.lastname: Dumler
authors.forename: P
authors.initials: P
authors.lastname: Charache
mesh_terms: D000258:Adenovirus Infections, Human / Q000175:diagnosis*; D000260:Adenoviruses, Human / Q000302:isolation & purification*; D000328:Adult; D001853:Bone Marrow / Q000821:virology; D016026:Bone Marrow Transplantation; D003228:Conjunctiva / Q000821:virology; D003231:Conjunctivitis / Q000821:virology; D003556:Cystitis / Q000821:virology; D017809:Fatal Outcome; D006470:Hemorrhage; D006801:Humans; D008168:Lung / Q000821:virology; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology / Q000628:therapy; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods