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. 2016 Apr 26;11(4):e0143759.
doi: 10.1371/journal.pone.0143759. eCollection 2016.

Vomiting as a Symptom and Transmission Risk in Norovirus Illness: Evidence from Human Challenge Studies

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Vomiting as a Symptom and Transmission Risk in Norovirus Illness: Evidence from Human Challenge Studies

Amy E Kirby et al. PLoS One. .

Abstract

Background: In the US, noroviruses are estimated to cause 21 million cases annually with economic losses reaching $2 billion. Outbreak investigations frequently implicate vomiting as a major transmission risk. However, little is known about the characteristics of vomiting as a symptom or the amount of virus present in emesis.

Methodology and principal findings: Emesis samples and symptomology data were obtained from previous norovirus human challenge studies with GI.1 Norwalk virus, GII.2 Snow Mountain virus, and a pilot study with GII.1 Hawaii virus. Viral titers in emesis were determined using strain-specific quantitative RT-PCR. In all four studies, vomiting was common with 40-100% of infected subjects vomiting at least once. However, only 45% of subjects with vomiting also had diarrhea. Most of the emesis samples had detectable virus and the mean viral titers were 8.0 x 105 and 3.9 x 104 genomic equivalent copies (GEC)/ml for GI and GII viruses, respectively (p = 0.02). Sample pH was correlated with GII.2 Snow Mountain virus detection.

Conclusions and significance: Half of all subjects with symptomatic infection experienced vomiting and the average subject shed 1.7 x 108 GEC in emesis. Unlike shedding through stool, vomiting is more likely to result in significant environmental contamination, leading to transmission through fomites and airborne droplets. This quantitative data will be critical for risk assessment studies to further understand norovirus transmission and develop effective control measures. The correlation between sample pH and virus detection is consistent with a single site of virus replication in the small intestine and stomach contents becoming contaminated by intestinal reflux. Additionally, the frequency of vomiting without concurrent diarrhea suggests that epidemiology studies that enroll subjects based on the presence of diarrhea may be significantly underestimating the true burden of norovirus disease.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Subjects With More Vomiting Events Have Higher Cumulative Virus Titers.
Cumulative virus titers are calculated by multiplying each sample’s virus titer by the sample volume and summing across all of the emesis samples from a subject. Vomiting events occurring within 15 minutes were considered a single event and the samples were combined for analysis. Each point represents a unique challenge subject, except at the baseline where multiple points overlap. Seven subjects vomited once and virus was not detected in any of those samples. Two subjects vomited twice and both samples were negative for virus.
Fig 2
Fig 2. Viral Titers in Emesis and Stool from Representative Challenge Subjects.
Selected subjects provided stool and emesis samples during the first 100 hours after challenge, allowing comparisons of stool and emesis viral titers in the same timeframe. Panels A and B are from subjects in study 1 infected with GI.1 Norwalk virus. Panel C is a subject in study 3 infected with GII.2 Snow Mountain virus. Panel D is a subject in study 4 infected with GII.1 Hawaii virus.
Fig 3
Fig 3. Correlation Between Sample pH and Detection of Virus.
GI positive samples are from studies 1 and 2, both GI.1 Norwalk virus. GII positive samples are from studies 3 and 4, GII.2 Snow Mountain virus and GII.1 Hawaii virus, respectively. Negative samples is a compilation of negative samples from all four studies.

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Grants and funding

This work was supported by the Agriculture and Food Research Initiative Competitive grant no. 2011-68003-30395 from the US Department of Agriculture, National Institute of Food and Agriculture through the NoroCORE project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.