ORIGINAL ARTICLE Description of an adenovirus A31 outbreak in a paediatric haematology unit M Leruez-Ville 1 , M Chardin-Ouache´e 2 , B Neven 2 , C Picard 2 , I Le Guinche 2 , A Fischer 2 , C Rouzioux 1 and S Blanche 2 1 Laboratoire de Virologie, EA 3620 Universite´Paris V, Hoˆpital Necker-Enfants Malades AP-HP, Paris, France; and 2 Service d’Immunologie-He´matologie Pe´diatrique, Universite´Paris-Descartes, Faculte´de Me´decine, Hoˆpital Necker-Enfants Malades AP-HP, Paris, France Adenovirus infections result in significant morbidity and mortality in allogeneic haematopoietic stem cell trans- planted (hSCT) children. Adenovirus from species C and B account for more than 90% of adenoviruses recovered after hSCT. However, infections due to adenovirus A31 have been increasingly reported in recent years. Between April 2002 and April 2005, blood samples obtained every 2 weeks from 58 hSCT children were screened for adenovirus species A to C by quantitative real-time PCR. Phylogenetic analysis was realized after amplifica- tion and sequencing of the entire hexon gene. Fifteen cases of adenovirus infection with viraemia were recovered during this 3 years period. During spring/summer 2003, seven cases occurred and were due to an adenovirus species A. Phylogenetic analysis of the seven strains showed that they belonged to the A31 genotype and shared 100% homology. Clinical features of the seven HSCT children with A31 adenovirus viraemia are described. We describe here an epidemic spread of adenovirus genotype A31 in a paediatric haematology unit. Timing, location and hexon gene genotyping results highly suggested a nosocomial origin to this epidemic. The burden of adenovirus A31 infection needs to be further assessed in this context. Bone Marrow Transplantation (2006) 38, 23–28. doi:10.1038/sj.bmt.1705389; published online 15 May 2006 Keywords: adenovirus genotype A31; stem cell trans- plantation; children; nosocomial infection; cidofovir Introduction Adenovirus infections have an incidence of over 20% in paediatric bone marrow transplanted recipients and result in significant morbidity and mortality. 1 Most haemato- poietic stem cell transplanted (hSCT) children with adenovirus infection develop related local symptoms and around 20% of them will further develop a severe disseminated disease, which could eventually lead to death. 1 Adenoviruses from C and B species represent more than 90% of reported cases of adenoviruses infections occurring after hSCT in children, and the vast majority of fatal cases of disseminated adenovirus infection described in the literature are due to adenoviruses of C species. 2–6 In recent years, cases of adenovirus A31 infection have also been reported as another cause of adenovirus infection in hSCT children. However, the origin and the particularities of adenovirus infection with A31 strains in this context have not been specifically studied. 4,5,7 The paediatric haematology unit of Necker hospital specializes in hematopoietic stem cell transplantation for children with underlying congenital immunodeficiency syndrome, haematological disease or metabolic disorders. Bone marrow protocol often includes T-cell depletion for recipients of hSCT from human lymphocyte antigen partially identical donors, and therefore a high number of those hSCT children are at a high risk for the development of adenovirus infection owing to slow immune reconstitu- tion. Recent data suggested that a positive adenovirus DNA detection in blood plasma or serum has a good specific predictive value for the occurrence of adenovirus disseminated disease in allogeneic stem cell paediatric recipients. 8–10 Moreover, we demonstrated that adenovirus quantitative real-time PCR in blood plasma was effective for accurate monitoring of adenovirus-disseminated infec- tion treatment. 11 Based on these data, surveillance for adenovirus viraemia was implemented for hSCT children from April 2002. Between April 2002 and April 2005, 58 hSCT children were screened for adenovirus viraemia by PCR. Within the first 11 months (April 2002 to February 2003), after implementation of our screening programme, three cases of adenovirus infection with positive viraemia were diagnosed among the children hospitalized in Necker hospital bone marrow transplant unit. Then, between February 2003 and August 2003, eight cases of adenovirus infection were reported in the unit: one child was infected with an adenovirus from C species but the other seven were infected with an adenovirus from A species. This alarming high rate of adenovirus A detection suggested the occurrence of an epidemic. Genotyping analysis showed that this epidemic was due to an adenovirus type 31 strain. Received 15 December 2005; revised 27 February 2006; accepted 9 April 2006; published online 15 May 2006 Correspondence: Dr M Leruez-Ville, Laboratoire de Virologie, CHU Necker-Enfants Malades, 149 rue de Se`vres, 75015 Paris, France. E-mail: marianne.leruez@nck.ap-hop-paris.fr Bone Marrow Transplantation (2006) 38, 23–28 & 2006 Nature Publishing Group All rights reserved 0268-3369/06 $30.00 www.nature.com/bmt