title: Determination of the 50% human infectious dose for Norwalk virus.
abstract: BACKGROUND
  Noroviruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these viruses is important for risk assessment studies.
  
  
  METHODS
  Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of virus in vomitus was also assessed.
  
  
  RESULTS
  Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of virus shedding was higher for persons with gastroenteritis. Norwalk virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL.
  
  
  CONCLUSIONS
  The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA viruses. Clinical Trials Registration NCT00138476.
authors.affiliation: Department of Medicine.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.forename: Antone R
authors.initials: AR
authors.lastname: Opekun
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gilger
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
authors.forename: Sue E
authors.initials: SE
authors.lastname: Crawford
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Neill
authors.forename: Sasirekha
authors.initials: S
authors.lastname: Ramani
authors.forename: Heather
authors.initials: H
authors.lastname: Hill
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ferreira
authors.forename: David Y
authors.initials: DY
authors.lastname: Graham
mesh_terms: D000328:Adult; D017250:Caliciviridae Infections / Q000821:virology*; D005243:Feces / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009663:Norwalk virus / Q000472:pathogenicity*; D010919:Placebos / Q000008:administration & dosage; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D010919:Placebos
keywords: infectious dose; norovirus; secretor; serology; virus shedding