Determination of the 50% Human Infectious Dose for Norwalk Virus

• Published in: The Journal of infectious diseases Vol. 209; no. 7; pp. 1016 - 1022
• Main Authors: Atmar, Robert L., Opekun, Antone R., Gilger, Mark A., Estes, Mary K., Crawford, Sue E., Neill, Frederick H., Ramani, Sasirekha, Hill, Heather, Ferreira, Jennifer, Graham, David Y.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2014
• Subjects: Adult; Biological and medical sciences; Blood groups; Caliciviridae Infections - virology; Dosage; Feces - virology; Female; Fundamental and applied biological sciences. Psychology; Gastroenteritis; Gastroenteritis - virology; Humans; Infections; Infectious diseases; Inoculum; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Norovirus; Norwalk virus; Norwalk virus - pathogenicity; Placebos - administration & dosage; Reverse transcriptase polymerase chain reaction; Viral vaccines; Virology; Virus Shedding; Viruses; Young Adult; Virus; Human; Infection; Calicivirus; Human calicivirus; Caliciviridae; Norwalk virus; secretor; virus shedding; norovirus; infectious dose; serology
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jit620

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 secretorpositive 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 41000 gEq/mL. Conclusions. The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA viruses. Clinical TriaU Registration. NCT00138476.