title: Severe outcomes are associated with genogroup 2 genotype 4 norovirus outbreaks: a systematic literature review.
abstract: BACKGROUND
  Noroviruses (NoVs) are the most common cause of epidemic gastroenteritis; however, the relative impacts of individual factors underlying severe illness are poorly understood. This report reviews published NoV outbreak reports to quantify hospitalization and mortality rates and assess their relationship with outbreak setting, transmission route, and strain.
  
  
  METHODS
  Using a string of terms related to "norovirus" and "outbreak," we 2435 nonduplicate articles identified in PubMed, EMBASE, and Web of Knowledge published between January 1993 and June 2011. Inclusion criteria included outbreaks with a minimum of 2 ill persons with a common exposure and at least 1 reverse-transcription polymerase chain reaction-confirmed case of NoV disease. Univariate analyses were performed, and multivariable models were fitted to estimate the independent effect of each factor.
  
  
  RESULTS
  We analyzed 843 NoV outbreaks reported in 233 published articles from 45 countries. Based upon 71724 illnesses, 501 hospitalizations, and 45 deaths, overall hospitalization and mortality rates were 0.54% and 0.06%, respectively. In multivariate analysis, genogroup 2 genotype 4 (GII.4) NoV strains were associated with higher hospitalization (incidence rate ratio [IRR], 9.4; 95% confidence interval [CI], 6.1-14.4; P< .001) and mortality rates (IRR, 3.1; 95% CI, 1.3-7.6; P = .01). Deaths were much more likely to occur in outbreaks occurring in healthcare facilities (IRR, 60; 95% CI, 6-109; P = .01).
  
  
  CONCLUSIONS
  Our review suggests that hospitalizations and deaths were more likely in outbreaks associated with GII.4 viruses, independent of other factors, and underscores the importance of developing vaccines against GII.4 viruses to prevent severe disease outcomes.
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. rdesai1@cdc.gov
authors.forename: Rishi
authors.initials: R
authors.lastname: Desai
authors.forename: Christal D
authors.initials: CD
authors.lastname: Hembree
authors.forename: Andreas
authors.initials: A
authors.lastname: Handel
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Matthews
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Dickey
authors.forename: Sharla
authors.initials: S
authors.lastname: McDonald
authors.forename: Aron J
authors.initials: AJ
authors.lastname: Hall
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Parashar
authors.forename: Juan S
authors.initials: JS
authors.lastname: Leon
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lopman
mesh_terms: D017250:Caliciviridae Infections / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology* / Q000821:virology; D004196:Disease Outbreaks; D005759:Gastroenteritis / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology* / Q000821:virology; D005838:Genotype; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D029322:Norovirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D016019:Survival Analysis; D016896:Treatment Outcome