Norwalk Virus Shedding after Experimental Human Infection

Abstract

Noroviruses are the most common cause of viral gastroenteritis in the United States. To determine the magnitude and duration of virus shedding in feces, we evaluated persons who had been experimentally infected with Norwalk virus. Of 16 persons, clinical gastroenteritis (watery diarrhea and/or vomiting) developed in 11; symptomatic illness lasted 1-2 days. Virus shedding was fi rst detected by reverse transcription-PCR (RT-PCR) 18 hours after participant inoculation and lasted a median of 28 days after inoculation (range 13-56 days). The median peak amount of virus shedding was 95 × 10 9 (range 0.5-1,640 ×10 9 ) genomic copies/g feces as measured by quantitative RT-PCR. Virus shedding was fi rst detected by antigen ELISA ≈33 hours (median 42 hours) after inoculation and lasted 10 days (median 7 days) after inoculation. Understanding of the relevance of prolonged fecal norovirus excretion must await the development of sensitive methods to measure virus infectivity.

Prevalence and characteristics of asymptomatic norovirus infection in the community in England

“…A recent volunteer study showed that low norovirus viral loads, detectable by RT-PCR, are associated with asymptomatic infection (9). Consideration of viral load therefore provides the greatest diagnostic accuracy for identifying cases of norovirus-associated IID.…”

“…However, semiquantitative real-time RT-PCR testing has demonstrated a wide range of viral loads in norovirusinfected IID cases (8); many IID cases shed norovirus at the same concentration as healthy individuals, with no recent history of IID (8,9). It is therefore unlikely that all IID cases with norovirus infection detected by RT-PCR have disease caused by norovirus; another pathogen is probably causing illness in IID cases shedding norovirus at very low concentrations.…”

Risk factors for symptomatic and asymptomatic norovirus infection in the community

“…Norovirus infection has also been identified in a substantial proportion of individuals with no IID symptoms in several community-based studies, with prevelances of up to 16 % reported in high-income countries [1,[5][6][7]. Volunteer studies have demonstrated the occurrence of norovirus infection with no concurrent IID symptoms after experimental inoculation [8,9].…”

Norovirus vaccines: Correlates of protection, challenges and limitations

“…62 Predictive modeling of viral shedding classifies shedding into regular shedding with a mean of 14-16 d and long shedding with a mean ranging between 105 and 136 d 66 Recent studies suggest the lack of a significant difference of virus shedding between asymptomatic and symptomatic NoV infections despite the individual variation in virus peak levels detected in stool. 67,68 This study reported different viral shedding activities as compared to previous reports 7,69 whereby infected adults shed virus during a range of 15-56 d. The authors argued that the variable results in NoV shedding might be due to the use of different PCR techniques to detect the virus. Atmar et al 7 used NoV GI.1 which might have different shedding characteristics than the GII.4.…”

“…A number of factors contribute to the high communicability of NoV most importantly the low infectious dose of the virus (18-100 particles), 6 the high levels of virus shedding 7 (> 10 9 particles/ml of stool during the first days after infection) known to precede illness and to be prolonged in immunosuppressed persons, the stability of the virus at temperatures ranging between 0 C and 60 C, and finally the high rate of mutation and recombination leading to antigenic diversity. 8,9 Knowledge about the pathogenesis of NoVs emerged as a result of challenge studies showing a broadening and blunting of the intestinal villi, infiltration of the polymorphonuclear and mononuclear cells into the lamina propria, in addition to cytoplasmic vacuolization.…”