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.

Keywords: infectious dose; norovirus; secretor; serology; virus shedding.

Figure 1.

Probability of infection based upon inoculum dosage. The infection frequency observed for secretor-positive (Se+) persons who were blood group O or A or any blood group (All Se+) is shown for each dosage group expressed as log₁₀ genomic equivalents, where 1 reverse transcription polymerase chain reaction unit is approximately 400 genomic equivalents. The open boxes represent the calculated 50% human infectious dose estimates, and the closed boxes represent observed infection frequencies.