title: High prevalence of prolonged norovirus shedding and illness among hospitalized patients: a model for in vivo molecular evolution.
abstract: During a 2-year survey in an academic hospital, 8 (8.4%) of all norovirus (NoV)-positive patients showed prolonged norovirus illness and shedding (duration, 21-182 days). All patients had underlying illnesses, resulting in some level of immunodeficiency in 5. Four patients were admitted to the hospital with gastroenteritis, 2 acquired norovirus while hospitalized, and 2 were outpatients. Genotypes GII.4 and GIIb-GII.3 were found. Reinfection occurred in 3 patients. Full capsid sequences were determined from strains detected in sequentially collected stool specimens to study evolution. The greatest number of amino acid mutations in a given patient was 11; they were detected in NoV isolates recovered over a 119-day period and were mapped to positions at or near putative antigenic sites. In the patient with most severe immune dysfunction, only 5 amino acids mutated over 182 days, suggesting immune-driven selection. The severe impact on patients and hospitals and the potential role of prolonged shedders as a reservoir for viral antigenic variants lead us to stress the importance of confinement of outbreaks of NoV infection that occur in hospitals.
authors.affiliation: National Institute for Public Health and the Environment, The Netherlands. Joukje.Siebenga@RIVM.nl
authors.forename: J Joukje
authors.initials: JJ
authors.lastname: Siebenga
authors.forename: Mathias F C
authors.initials: MF
authors.lastname: Beersma
authors.forename: Harry
authors.initials: H
authors.lastname: Vennema
authors.forename: Paula
authors.initials: P
authors.lastname: van Biezen
authors.forename: Nico J
authors.initials: NJ
authors.lastname: Hartwig
authors.forename: Marion
authors.initials: M
authors.lastname: Koopmans
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D017250:Caliciviridae Infections / Q000276:immunology / Q000821:virology*; D036022:Capsid Proteins / Q000737:chemistry; D002675:Child, Preschool; D003428:Cross Infection / Q000276:immunology / Q000821:virology*; D019143:Evolution, Molecular; D005243:Feces / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000821:virology; D006760:Hospitalization; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D029322:Norovirus / Q000235:genetics / Q000302:isolation & purification*; D017201:Virus Shedding
chemical_list: D036022:Capsid Proteins