Prolonged outbreak of adenovirus A31 in allogeneic stem cell transplant recipients L. Swartling, A. Allard, J. T€ orlen, P. Ljungman, J. Mattsson, E. Sparrelid. Prolonged outbreak of adenovirus A31 in allogeneic stem cell transplant recipients. Transpl Infect Dis 2015: 17: 785–794. All rights reserved Abstract: Background. An outbreak of human adenovirus (HAdV) A31 occurred from December 2011 to March 2012 at the Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital in Sweden. We analyzed the outbreak, the routes of transmission, and report the medical consequences. Methods. The medical records of all patients admitted to CAST during the outbreak period were studied. Phylogenetic analysis of the patient HAdV strains was performed by sequencing the hexon gene and the more variable E3 gene. Results. We identified 9 cases of HAdV A31. Hygiene measures were implemented, but transmission continued for 2 months. All 9 patients had been admitted to the ward, but 2 had no connection in time to other known HAdV A31 cases. DNA sequencing of the patient strains strongly suggested nosocomial transmission. Transplantation was postponed and then cancelled in 1 patient, and 5 patients were treated with cidofovir because of high levels of viremia. In 7 patients, concomitant graft-versus-host disease (GVHD) grade II–V complicated the clinical picture, as it was difficult to distinguish symptoms of GVHD from those of HAdV infection. Conclusion. An outbreak of HAdV in HSCT recipients can be difficult to control. Although none of the patients had severe disease, the medical consequences were significant. It is possible that unidentified cases with mild symptoms may have caused continuous transmission at the unit. Regular testing of all patients several weeks beyond the last case identified may be an important measure to control transmission. L. Swartling 1 , A. Allard 2 , J. T€ orlen 3 , P. Ljungman 3,4 , J. Mattsson 3, *, E. Sparrelid 1, * 1 Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, 2 Department of Virology, Ume  a University, Ume  a, Sweden, 3 Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, 4 Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Key words: adenovirus A31; stem cell transplantation; outbreak; phylogenetic analysis Correspondence to: Lisa Swartling, Division of Infectious Diseases, I 73, Karolinska University Hospital, Huddinge, Stockholm SE-141 86, Sweden Tel: +46 8 585 800 00 Fax: +46 8 585 819 16 E-mail: lisa.swartling@karolinska.se *These two authors share senior authorship. Received 19 February 2015, revised 2 June 2015, accepted for publication 2 August 2015 DOI: 10.1111/tid.12443 Transpl Infect Dis 2015: 17: 785–794 Human adenovirus (HAdV) infections are common, especially in young children, but the symptoms are usually mild. HAdV can persist in epithelial cells and lymphoid tissue in the gastrointestinal tract and the respiratory tract (1), and healthy children can excrete virus in stool for months to years after the primary infection (2–5). In allogeneic hematopoietic stem cell transplant (HSCT) recipients, HAdV can cause a range of symp- toms from mild localized gastrointestinal, urinary tract, or respiratory disease to disseminated disease with multiple organ involvement and very high mortality (6– 8). The incidence of HAdV infections following HSCT ranges from 11% to 41% depending on the age of the patient, the diagnostic method used, and the material tested. In recent screening studies for viremia, the incidence has varied between 2% and 42% (9, 10). Young children have the highest risk of both HAdV infection and disease (11, 12), especially if they undergo trans- plants with a high risk of prolonged immunodeficiency such as T-cell depleted unrelated or haploidentical transplants or cord blood grafts (7, 9, 13). In contrast, the risk is low in children who undergo human leukocyte antigen (HLA)-identical sibling transplants and in adults who undergo either HLA-identical sibling transplants or well-matched unrelated donor 785 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Transplant Infectious Disease, ISSN 1398-2273