title: Norovirus infection in primary immune deficiency.
abstract: Norovirus is acknowledged to be a leading cause of acute gastroenteritis worldwide, and its importance as a cause of chronic infection in immune deficient hosts is increasingly recognised. Current evidence suggests that a coordinated response of innate immune mechanisms, CD8+ cytotoxicity and a humoral response, with CD4+ orchestration, is necessary for norovirus clearance. We explain how primary immune deficiency impairs these host defences and predisposes to chronic infection, associated with protracted diarrhoea, weight loss, and requirement for parenteral nutrition. The mucosal villous atrophy frequently seen in norovirus infection appears to be immune mediated, suggesting that some functional immune response is required in order for chronic norovirus infection to become symptomatic in primary immune deficiency. We provide a comprehensive summary of published cases of norovirus infection in patients with primary immune deficiency. Spontaneous viral clearance has been described; however, the majority of reported cases have had prolonged and severe illness. Treatment strategies are discussed in detail. Approaches that have been tried in patients with primary immune deficiency include exclusion diets, enteral and intravenous immunoglobulins, breast milk, immunosuppressants, ribavirin, and nitazoxanide. To date, only ribavirin has been used with apparent success to achieve clearance of chronic norovirus in primary immune deficiency, and randomised controlled trials are needed to evaluate a number of promising therapies that are discussed.
authors.affiliation: Royal Free London NHS Foundation Trust, London, UK.
authors.forename: Li-An K
authors.identifier: http://orcid.org/0000-0002-8261-0288
authors.initials: LK
authors.lastname: Brown
authors.affiliation: Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Clark
authors.affiliation: Microbiology, Virology and Infection Control, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.|NIHR Biomedical Research Centre, Great Ormond Street Hospital for Children NHS Foundation Trust and University College, London, UK.
authors.forename: Julianne R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: Division of Infection and Immunity, University College London, London, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Breuer
authors.affiliation: Institute of Immunity and Transplantation, University College London, Royal Free Campus, London, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Lowe
keywords: immunodeficiency; norovirus; primary immune deficiency