Effect of Norovirus Dose on Virus Shedding and Symptoms

In This Article

Abstract and Introduction

Abstract

The effect of norovirus dose on outcomes such as virus shedding and symptoms after initial infection is not well understood. We performed a secondary analysis of a human challenge study by using Bayesian mixed-effects models. As the dose increased from 4.8 to 4,800 reverse transcription PCR units, the total amount of shed virus in feces increased from 4.5 × 10¹¹ to 3.4 × 10¹² genomic equivalent copies; in vomit, virus increased from 6.4 × 10⁵ to 3.0 × 10⁷ genomic equivalent copies. Onset time of viral shedding in feces decreased from 1.4 to 0.8 days, and time of peak viral shedding decreased from 2.3 to 1.5 days. Time to symptom onset decreased from 1.5 to 0.8 days. One type of symptom score increased. An increase in norovirus dose was associated with more rapid shedding and symptom onset and possibly increased severity. However, the effect on virus load and shedding was inconclusive.

Introduction

Norovirus is a major cause of foodborne disease and causes a large number of cases, hospitalizations, and deaths in the United States and globally.^[1–4] Specific treatments are not available, and vaccines are still under development.^[4,5] Generic infection control measures are the best approaches to minimizing disease burden.^[6–10]

An increase in exposure dose (number of virus particles) is associated with an increased risk for infection; this principle applies to norovirus^[11–14] and many other pathogens.^[15,16] Less is known about the possible effect of dose on infection outcomes after infection has occurred. For acute infections such as influenza, infectious bronchitis virus, and parainfluenza virus, animal studies and models suggest that dose influences the virus load kinetics.^[17–19] For norovirus, some evidence from experimental challenge studies suggests that dose is associated with more rapid onset of symptoms.^[20] To further elucidate the effect of inoculum dose on infection outcomes such as virus shedding and symptom severity, we performed a secondary analysis of data from a human norovirus challenge study.^[20]

Table. Selected characteristics of patients in in study of the effect of norovirus inoculum dose on virus kinetics, shedding, and symptoms*
Characteristic	Dose, RT-PCR units
Characteristic	0.48	4.8	48	4,800
No. participants	1	6	7	6
Age, y, median (range)	24 (24–24)	30 (21–39)	24 (22–34)	28 (22–47)
Sex
F	1 (100)	2 (33)	4 (57)	2 (33)
M	0	4 (67)	3 (43)	4 (67)
Blood type group
A	0	2 (33)	2 (29)	3 (50)
O	1 (100)	4 (67)	5 (71)	3 (50)