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...e outbreaks. Clinical and epidemiologic criteria can help attribute gastroenteritis outbreaks to NoV disease [13]. However, commercial NoV PCR testing has become more widely available in recent years =-=[14]-=-, and there is now a Food and Drug Table 1. Univariate and Multivariate Analysis of Hospitalization and Death Rates by Setting, Transmission Type, and Strain Univariate Analysis Multivariate Analysis ...

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... However, severe outcomes, including hospitalization and death, have been reported in more vulnerable populations, such as young children, immunocompromised persons, and the institutionalized elderly =-=[3, 4]-=-. The relative impact of individual factors underlying severe illness is poorly understood and difficult to tease apart in individual outbreaks or across a small number of outbreaks. For example, seve...

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...e and distinct strains have emerged every 2–4 years over the last decade [18–20]. At least 2 GII.4 variants have escaped population immunity and were associated with large global outbreaks of disease =-=[19, 20]-=-. Currently there is no licensed NoV vaccine. Efforts to reduce NoV disease burden have been focused on effective disease surveillance and limiting disease transmission. We have again highlighted the ...

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...transmission identified in our data. However, broad-based surveillance studies as well as expert elicitation suggest that the majority of NoV outbreaks primarily involve person-to-person transmission =-=[1, 11, 12]-=-, suggesting a publication bias favoring reports of foodborne and waterborne transmission. Fortunately, this bias would not affect our estimates of the association between mode of transmission and sev...

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...e expect that estimates of severe disease frequency in these specific populations would have been even higher. Studies have demonstrated that rates of severe NoV disease are highest among the elderly =-=[9]-=-, whereas overall NoV rates are highest in younger age groups [10], making advanced age a risk factor for higher NoV-associated hospitalization and fatality rates. Because age was not reported in the ...

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...hs may also be more likely to be investigated and subsequently published in the peer-reviewed literature. Indeed, passive surveillance systems have estimated lower hospitalization and mortality rates =-=[6]-=-. Many NoV outbreaks likely go unrecognized, and among those that get reported to local public health authorities, the majority are not systematically investigated or well documented [7]. Additionally...

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...e and distinct strains have emerged every 2–4 years over the last decade [18–20]. At least 2 GII.4 variants have escaped population immunity and were associated with large global outbreaks of disease =-=[19, 20]-=-. Currently there is no licensed NoV vaccine. Efforts to reduce NoV disease burden have been focused on effective disease surveillance and limiting disease transmission. We have again highlighted the ...

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...kely to occur. In addition, NoV vaccines are under development, and it has been demonstrated that, in principle at least, it is possible to immunize using a GI.1 vaccine against a homotypic challenge =-=[21]-=-. Our analysis highlights the importance of developing vaccines against GII.4 viruses that are safe and effective, particularly for vulnerable populations who suffer severe disease outcomes, including...

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... However, severe outcomes, including hospitalization and death, have been reported in more vulnerable populations, such as young children, immunocompromised persons, and the institutionalized elderly =-=[3, 4]-=-. The relative impact of individual factors underlying severe illness is poorly understood and difficult to tease apart in individual outbreaks or across a small number of outbreaks. For example, seve...

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...ntified. It is possible that transmission route may have been misclassified in some of these outbreaks. Clinical and epidemiologic criteria can help attribute gastroenteritis outbreaks to NoV disease =-=[13]-=-. However, commercial NoV PCR testing has become more widely available in recent years [14], and there is now a Food and Drug Table 1. Univariate and Multivariate Analysis of Hospitalization and Death...

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...ific populations would have been even higher. Studies have demonstrated that rates of severe NoV disease are highest among the elderly [9], whereas overall NoV rates are highest in younger age groups =-=[10]-=-, making advanced age a risk factor for higher NoV-associated hospitalization and fatality rates. Because age was not reported in the many outbreak reports, this unmeasured covariate could have confou...

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...rtance of developing vaccines against GII.4 viruses to prevent severe disease outcomes. Noroviruses (NoVs) are the most common cause of epidemic gastroenteritis and a major cause of foodborne illness =-=[1]-=-. Noroviruses are responsible for approximately 50% of all reported gastroenteritis outbreaks in the United States and European countries (range, 36%–59%) [2]. In otherwise healthy adults, NoV gastroe...

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...a striking difference in mortality rate and hospitalization rate, suggesting that this genotype may be responsible for severe disease. Previous observations that GII strains are shed at higher levels =-=[15]-=-, are more likely to induce vomiting, and cause more severe disease in children [16, 17], when taken in the context of this study, demonstrate a consistent pattern. Noroviruses rapidly evolve and dist...

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...is genotype may be responsible for severe disease. Previous observations that GII strains are shed at higher levels [15], are more likely to induce vomiting, and cause more severe disease in children =-=[16, 17]-=-, when taken in the context of this study, demonstrate a consistent pattern. Noroviruses rapidly evolve and distinct strains have emerged every 2–4 years over the last decade [18–20]. At least 2 GII.4...

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...is genotype may be responsible for severe disease. Previous observations that GII strains are shed at higher levels [15], are more likely to induce vomiting, and cause more severe disease in children =-=[16, 17]-=-, when taken in the context of this study, demonstrate a consistent pattern. Noroviruses rapidly evolve and distinct strains have emerged every 2–4 years over the last decade [18–20]. At least 2 GII.4...

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...rtality rates [6]. Many NoV outbreaks likely go unrecognized, and among those that get reported to local public health authorities, the majority are not systematically investigated or well documented =-=[7]-=-. Additionally, the only outbreaks in this analysis that were reported from a low(Afghanistan) or low-middle–income income (Iraq) setting occurred among US and UK military forces; however, it is thoug...

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...transmission identified in our data. However, broad-based surveillance studies as well as expert elicitation suggest that the majority of NoV outbreaks primarily involve person-to-person transmission =-=[1, 11, 12]-=-, suggesting a publication bias favoring reports of foodborne and waterborne transmission. Fortunately, this bias would not affect our estimates of the association between mode of transmission and sev...

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...is and a major cause of foodborne illness [1]. Noroviruses are responsible for approximately 50% of all reported gastroenteritis outbreaks in the United States and European countries (range, 36%–59%) =-=[2]-=-. In otherwise healthy adults, NoV gastroenteritis is typically mild and resolves without medical intervention. However, severe outcomes, including hospitalization and death, have been reported in mor...

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...inition on the articles, we adopted each author’s case definition. Outbreaks reported in multiple publications were only recorded once. A range of data was extracted and is reported in full elsewhere =-=[5]-=-; here, we consider outbreak setting, route of transmission, and NoV strain. Data Abstraction Once eligibility was determined, 2 reviewers independently extracted data from selected articles using a s...

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...are settings underscores the vulnerability of populations affected by outbreaks in these settings. Norovirus infection often causes prolonged symptoms in frail, elderly patients with limited mobility =-=[8]-=-. Due to limitations in the published outbreak data, it was not possible to assess whether healthcare settings may have been a proxy for intrinsic factors for patient vulnerability, such as age or com...