Shedding of norovirus in symptomatic and asymptomatic infections

Abstract

Norovirus is the most frequent cause of acute infectious gastroenteritis and it is difficult to control in crowded environments like hospitals and nursing homes. Transmission depends on oral intake of virus deposited in the environment by infectious subjects. Data from volunteer studies indicate that virus concentrations in stool are highly variable, but systematic studies of the time-course of shedding and its individual variation are lacking. This paper quantifies norovirus shedding in a large population of 102 subjects, including asymptomatic shedders, and uses a longitudinal model to generalize shedding patterns. Enhanced surveillance for studies of transmission of norovirus in hospital outbreaks has yielded a considerable number of faecal samples from symptomatic and asymptomatic shedders, both from patients and staff. Norovirus concentrations were determined by real-time PCR. A quantitative dynamic model was fitted to the shedding data, in a multilevel Bayesian framework, to study the time-course of shedding and its variation. The results indicate that shedding in asymptomatic subjects is similar to that in symptomatic infections, both showing considerable variation in peak levels (average 105-109 /g faeces) as well as duration of virus shedding (average 8-60 days). Patients appear to shed higher numbers of virus than staff, for slightly longer durations, but the differences are too small to be significant. Given equal shedding, the greater contribution of symptomatic cases to transmission must be caused by their higher efficiency in spreading these viruses. The results of this study will be helpful for risk studies that need to quantify the deposition of virus in the environment.

Keywords: virus infection.

Fig. 1.

Time-course of virus shedding in (a) symptomatic and (b) asymptomatic subjects. Median and 95% interval of the predicted virus concentration (log₁₀ numbers of viruses/g stool) are shown. Also shown are observed virus concentrations, as measured C_t values translated by means of the standard curve (Supplementary Fig. A1c). Multiple observations from the same subject are connected.

Fig. 2.

Characteristics of virus shedding for patients and staff: estimated means of (a) peak levels of shed virus (log₁₀ number of viruses/g stool), (b) time from onset of shedding to peak in virus shedding (days), (c) total duration of the shedding period (days) and (d) the estimated area under the shedding curve (log₁₀ numbers of viruses/g stool). Box plots [median, quartiles (box), 95% range (whiskers), and outliers (circles)] of means of Monte Carlo samples of (posterior) predicted values, for staff and patients, symptomatic and asymptomatic.

Fig. 3.

Characteristics of virus shedding vs. age of individuals: estimated individual (a) peak levels of shed virus (log₁₀ numbers of viruses/g stool), (b) time from onset of shedding to peak in virus shedding (days), (c) total duration of the shedding period (days) and (d) area under the shedding curve (log₁₀ numbers of viruses/g stool). Monte Carlo sample of (posterior) values with mean and uncertainty (95% credible intervals), for symptomatic (black) and asymptomatic (grey) subjects.