L Helena Gutierrez Sanchez1, Henry Shiau1, Julia M Baker1, Stephanie Saaybi1, Markus Buchfellner1, William Britt1, Veronica Sanchez1, Jennifer L Potter1, L Amanda Ingram1, David Kelly1, Xiaoyan Lu1, Stephanie Ayers-Millsap1, Wesley G Willeford1, Negar Rassaei1, Julu Bhatnagar1, Hannah Bullock1, Sarah Reagan-Steiner1, Ali Martin1, Michael E Rogers1, Anna M Banc-Husu1, Sanjiv Harpavat1, Daniel H Leung1, Elizabeth A Moulton1, Daryl M Lamson1, Kirsten St George1, Aron J Hall1, Umesh Parashar1, Adam MacNeil1, Jacqueline E Tate1, Hannah L Kirking1. 1. From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition (L.H.G.S., H.S., S.S.) and the Division of Pediatric Infectious Diseases, (M.B., W.B., V.S., J.L.P.), Department of Pediatrics, and the Department of Pathology (D.K.), University of Alabama at Birmingham, Children's of Alabama (L.H.G.S., H.S., S.S., M.B., D.K.), and Jefferson County Department of Health (S.A.-M., W.G.W.), Birmingham, and the Alabama Department of Public Health, Montgomery (L.A.I., A. Martin) - all in Alabama; the Division of Viral Diseases (J.M.B., X.L., A.J.H., U.P., A. MacNeil, J.E.T., H.L.K.), the Epidemic Intelligence Service (J.M.B.), and the Division of High-Consequence Pathogens and Pathology (N.R., J.B., H.B., S.R.-S.), Centers for Disease Control and Prevention, Atlanta, and Synergy America, Duluth (H.B.) - both in Georgia; the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (M.E.R.), and the Department of Pediatrics, University of Cincinnati College of Medicine (M.E.R.) - both in Cincinnati; the Division of Pediatric Gastroenterology, Hepatology and Nutrition (A.M.B.-H., S.H., D.H.L.) and the Division of Pediatric Infectious Diseases (E.A.M.), Texas Children's Hospital, and the Department of Pediatrics, Baylor College of Medicine (A.M.B.H., S.H., D.H.L., E.A.M.) - both in Houston; and the Wadsworth Center, New York State Department of Health (D.M.L., K.S.G.), and the Department of Biomedical Sciences, University at Albany (K.S.G.) - both in Albany.
Abstract
BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).
BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).
Authors: Temitope O C Faleye; Peter Skidmore; Amir Elyaderani; Sangeet Adhikari; Nicole Kaiser; Abriana Smith; Allan Yanez; Tyler Perleberg; Erin M Driver; Rolf U Halden; Arvind Varsani; Matthew Scotch Journal: medRxiv Date: 2022-09-26