Norovirus Outbreaks Research Articles

Clinical and Epidemiologic Profiles for Identifying Norovirus in Acute Gastroenteritis Outbreak Investigations.

Noroviruses are the leading cause of acute gastroenteritis (AGE) outbreaks in the United States. However, outbreaks attributed to norovirus often lack confirmation by diagnostic testing. Clinical and epidemiologic profiles, such as the Kaplan criteria (vomiting in >50% cases, mean incubation period of 24-48 hours, mean duration of illness for 12-60 hours, and negative bacterial stool culture), have been used to distinguish norovirus outbreaks from those caused by bacteria. Kaplan criteria were evaluated among 10 023 outbreaks reported to the National Outbreak Reporting System (NORS) during 2009-2012. An alternate profile for distinguishing norovirus outbreaks from outbreaks caused by nonviral etiologies was identified using classification and regression tree (CART) modeling. Performance of the Kaplan criteria and alternate profile were compared among laboratory-confirmed outbreaks. The Kaplan criteria were 63.9% sensitive and 100% specific in discriminating norovirus from nonviral outbreaks, but only 3.3% of norovirus and 1.2% of nonviral outbreaks reported all criteria. Clinical and epidemiologic characteristics identified with CART modeling (ratio of proportion of cases with fever to the proportion of cases with vomiting <1, proportion of cases with bloody stool <0.1, proportion of cases with vomiting ≥0.26) were 85.7% sensitive and 92.4% specific for distinguishing norovirus from nonviral outbreaks and were applicable to more than 8 times as many outbreaks compared with the Kaplan criteria. Compared with the Kaplan criteria, the CART-derived profile had higher sensitivity and broader application in reported AGE outbreaks. Thus, this alternate profile may provide a more useful tool for identifying norovirus during outbreak investigations.

The influence of food matrices on aptamer selection by SELEX (systematic evolution of ligands by exponential enrichment) targeting the norovirus P-Domain

This study investigates the enrichment of aptamers targeting the norovirus protruding domain in the presence of foods often associated with norovirus outbreaks. The goal is to explore if and how the presence of food alters in vitro selection of aptamers and target binding of the enriched oligonucleotides. Our study demonstrates that the introduction of food to SELEX (systematic evolution of ligands by exponential enrichment) is either detrimental to enrichment of oligonucleotides with target-specific binding, or facilitates enrichment of non-target-specific oligonucleotides. Moreover, a relationship between target binding of enriched oligonucleotides in presence of food and their selection condition was not observed. Our findings also suggest that a pathogen specific aptamer with application in food does not need to be selected in presence of the particular food, but may require properties beyond high affinity and selectivity to be applied for pathogen extraction and detection in undiluted food matrices.

GII.4 norovirus recombinant causes gastroenteritis epidemic in Eastern Australia, winter 2017.

In Victoria, Australia, 160 gastroenteritis outbreaks were norovirus positive for the period January-September 2017. A distinctive peak in norovirus outbreaks was seen May-August, with 118 positive outbreaks occurring in the peak period. The peak was primarily due to the emergence of a GII.P4_NewOrleans_2009/GII.4_Sydney_2012 recombinant that had genetically changed sufficiently to escape herd immunity. This recombinant was also identified elsewhere in Australia, with highly similar sequences identified in Queensland during the same time period. The recombinant GII.P4_NewOrleans_2009/GII.4_Sydney_2012 has not been reported to cause norovirus epidemics outside Australia, suggesting regional factors play a role in determining norovirus genotype incidence.

The Epidemiology of Norovirus 2014-2017

The burden of disease can be detrimental to individuals, health systems and can be an overall burden on the public health system. While there have been efforts to educate the public on the prevention of the Norovirus, the emergence of outbreaks of Norovirus continue to increase across the United States. This purpose of this article is to present data on the outbreaks of Norovirus from years 2014-2017 and suggest additional options to help improve education of the general public in an effort to combat the disease.

Quantifying the relative effects of environmental and direct transmission of norovirus.

Norovirus is a common cause of outbreaks of acute gastroenteritis in health- and child-care settings, with serial outbreaks also frequently observed aboard cruise ships. The relative contributions of environmental and direct person-to-person transmission of norovirus have hitherto not been quantified. We employ a novel mathematical model of norovirus transmission, and fit the model to daily incidence data from a major norovirus outbreak on a cruise ship, and examine the relative efficacy of potential control strategies aimed at reducing environmental and/or direct transmission. The reproduction number for environmental and direct transmission combined is [6.1,9.5], and of environmental transmission alone is [0.9,2.6]. Direct transmission is overwhelmingly due to passenger-to-passenger contacts, but crew can act as a reservoir of infection from cruise to cruise. This is the first quantification of the relative roles of environmental and direct transmission of norovirus. While environmental transmission has the potential to maintain a sustained series of outbreaks aboard a cruise ship in the absence of strict sanitation practices, direct transmission dominates. We find that intensive promotion of good hand washing practices may prevent outbreaks. Isolation of ill passengers and cleaning are beneficial, but appear to be less efficacious at outbreak control.

High transmissibility of norovirus among infants and school children during the 2016/17 season in Osaka, Japan.

The number of person-to-person transmitted norovirus cases (n = 4,712) in school children in Osaka, Japan, during 2016/17 was the largest since 2012/13. Norovirus outbreaks were reported by 101 schools including 53 nursery schools (1,927 cases), 18 kindergartens (1,086 cases) and 30 elementary schools (1,699 cases). The dominant genotype among outbreaks was GII.P16-GII.2 (57.4%; 58/101), followed by GII.P2-GII.2 (8.9%; 9/101) and GII.P7-GII.6 (5.9%; 6/101). GII.4 was not detected despite dominance in previous years.

Effect of the Shellfish Proteinase K Digestion Method on Norovirus Capsid Integrity.

Norovirus outbreaks are associated with the consumption of contaminated shellfish, and so efficient methods to recover and detect infectious norovirus in shellfish are important. The Proteinase K digestion method used to recover norovirus from shellfish, as described in the ISO 15216, would be a good candidate but its impact on the virus capsid integrity and thus infectivity was never examined. The aim of this study was to assess the impact of the Proteinase K digestion method, and of the heat treatment component of the method alone, on norovirus (genogroups I and II) and MS2 bacteriophage capsid integrity. A slightly modified version of the ISO method was used. RT-qPCR was used for virus detection following digestion of accessible viral RNA using RNases. MS2 phage infectivity was measured using a plaque assay. The effect of shellfish digestive glands (DG) on recovery was evaluated. In the presence of shellfish DG, a reduction in MS2 phage infectivity of about 1 log10 was observed after the Proteinase K digestion method and after heat treatment component alone. For norovirus GII and MS2 phage, there was no significant loss of genome following the Proteinase K digestion method but there was a significant 0.24 log10 loss of norovirus GI. In the absence of shellfish DG, the reduction in MS2 phage infectivity was about 2 log10, with the addition of RNases resulting in a significant loss of genome for all tested viruses following complete Proteinase K digestion method and the heat treatment alone. While some protective effect from the shellfish DG on viruses was observed, the impact on capsid integrity and infectivity suggests that this method, while suitable for norovirus genome detection, may not completely preserve virus infectivity.

Evolutionary dynamics of GII.17 norovirus.

BackgroundDuring the winter of 2014–2015, a rarely reported norovirus (NoV) genotype GII.17 was found to have increased its frequency in norovirus outbreaks in East Asia, surpassing the GII.4 NoV infections. GII.17 genotype has been detected for over three decades in the world. The aim of this study is to examine the evolutionary dynamics of GII.17 over the last four decades.MethodsNoV GII.17 sequences with complete or nearly complete VP1 were downloaded from GenBank and the phylogenetic analyses were then conducted.ResultsThe maximum likelihood analysis showed that GII.17 genotype could be divided into four different clades (Clades A–D). The strains detected after 2012, which could be the cause of the outbreaks, were separated into Clades C–D with their mean amino acid distance being 4.5%. Bayesian Markov chain Monte Carlo analyses indicated that the rate of nucleotide substitution per sites was 1.68 × 10−3 nucleotide substitutions/site/year and the time of the most recent common ancestor was 1840. The P2 subdomain of GII.17 was highly variable with 44% (56/128) amino acids variations including two insertions at positions 295–296 and one deletion at position 385 (Clades C and D) and one insertion at position 375 (Clade D). Variations existed in Epitopes A, B and D corresponding to GII.4 and human histo-blood group antigens binding site I in P2 subdomain.ConclusionThe novel GII.17 strains that caused outbreaks in 2013–2015 may have two new variants. The evolvement of HBGAs binding site and epitopes in P2 subdomain might contribute to the novel GII.17 strains predominance in some regions.

Temporal Relationship Between Healthcare-Associated and Nonhealthcare-Associated Norovirus Outbreaks and Google Trends Data in the United States.

Healthcare-associated norovirus outbreaks increase later but have a more pronounced seasonality than nonhealthcare norovirus outbreaks. Healthcare-associated norovirus outbreaks had higher correlation with Google Trends activity than nonhealthcare outbreaks (R2=0.68 vs 0.39). Google Trends data may have the potential to supplement existing norovirus surveillance due to its real-time availability. Infect Control Hosp Epidemiol 2018;39:355-358.

Risk factors for hospital norovirus outbreaks: impact of vomiting, genotype, and multi-occupancy rooms

Norovirus is frequently introduced to the hospital and is a frequent cause of hospital outbreaks. Recognition of the factors that facilitate or impede norovirus transmission is an important step to effectively prevent hospital outbreaks. To investigate risk factors for norovirus outbreaks in hospital settings. Clinical data, ward setting, and norovirus genotype were collected from all 65 norovirus-positive index cases in outbreaks and all 186 sporadic norovirus cases at 192 wards in southern Sweden during 2010-2012 in a nested case-control study. Uni- and multivariate statistical analyses were conducted. Outbreak was independently associated with the number of patients sharing a room with the norovirus case (odds ratio (OR): 1.9 per additional patient in the room; P<0.01), vomiting (OR: 2.6; P=0.04), age >80 years (OR: 3.2; P<0.01), comorbidity (OR: 2.3; P=0.05), and onset of symptoms after admission to the ward (OR: 3.5; P<0.01) in the multivariate analysis. Infection with genotype GII.4 was found to be strongly associated with outbreak in the univariate analysis (OR: 5.7; P<0.01). Moreover, associations between GII.4 and vomiting (OR: 2.5; P=0.01) and old age (OR: 4.3: P<0.01) were found. This is the first study to investigate clinical, ward and genotype risk factors for norovirus hospital outbreaks. Recognition of these factors may help direct and prioritize infection control actions based on the outbreak risk. The results also suggest that the outbreak association with GII.4 partly may be explained by an enhanced ability to induce vomiting.

High Hand Contamination Rates During Norovirus Outbreaks in Long-Term Care Facilities.

We examined norovirus contamination on hands of ill patients during 12 norovirus outbreaks in 12 long-term care facilities (LTCFs). The higher frequency and norovirus titers on hands of residents compared to hands of heathcare workers highlights the importance of adhering to appropriate hand hygiene practices during norovirus outbreaks in LTCFs. Infect Control Hosp Epidemiol 2018;39:219-221.

Epidemiology of Foodborne Norovirus Outbreaks - United States, 2009-2015.

Noroviruses are the leading cause of acute gastroenteritis and foodborne disease in the United States (U.S.). About 1 in 5 reported norovirus outbreaks are spread through foodborne transmission, presenting opportunities for prevention. We describe the epidemiology of U.S. foodborne norovirus outbreaks reported to national surveillance systems, including differences between genotypes. Foodborne outbreaks that occurred during August 2009-July 2015 with norovirus reported as a single confirmed etiology to the National Outbreak Reporting System (NORS) were matched with outbreaks reported to CaliciNet, a U.S. laboratory norovirus outbreak surveillance network. We analyzed these matched outbreaks stratified by genotype for epidemiologic characteristics, including setting, size and duration, health outcomes of case-patients, implicated food, and outbreak contributing factors. Four hundred ninety-three confirmed foodborne norovirus outbreaks were reported in both NORS and CaliciNet. The most common norovirus genotypes reported were GII.4 (52%), GII.6 (9%), and GI.3 (8%). Compared to non-GII.4 outbreaks, GII.4 outbreaks had higher hospitalization rates (12.8 vs. 4.8 per 1,000 cases, P < 0.01). While contaminated foods were identified and reported in only 35% of outbreaks, molluscan shellfish (4% overall) were more often implicated in non-GII.4 outbreaks than in GII.4 outbreaks (7% vs. 1%, P = 0.04). Of the 240 outbreaks reporting at least one contributing factor, food workers were implicated as the source of contamination in 182 (76%), with no difference between GII.4 and non-GII.4 (73% vs 79%, P = 0.3). Foodborne norovirus outbreaks are frequently reported in the U.S., most of which are caused by GII.4 noroviruses. Viruses of this genotype are associated with higher rates of hospitalization; non-GII.4 noroviruses are more frequently associated with contaminated molluscan shellfish. These surveillance data highlight the diversity of noroviruses causing foodborne disease and can help guide appropriate food safety interventions, including worker hygiene, improved food handling and preparation, and further development of norovirus vaccines.

Series of Norovirus Outbreaks Caused by Consumption of Green Coral Lettuce, Denmark, April 2016.

Introduction: In early April 2016, an unusual high number of point-source outbreaks of gastrointestinal disease were reported to occur in Denmark.Methods: Outbreaks were individually investigated. Two analytical studies were performed. Patient stool samples collected and analysed; positive stool samples were sequenced over the polymerase and/or capsid gene areas. Implicated lettuce heads were collected and analysed for the presence of norovirus. Foods were traced-back and traced-forward and international alert systems applied.Results: A total of 23 linked point-source outbreaks occurred over the course of one week. Fresh green coral lettuce (Lollo Bionda lettuce) had been consumed in all settings. In a cohort study including 234 participants a dish containing green lettuce was associated with illness. Norovirus of Genogroup I (GI) was detected in samples from 28 patients comprising eight of the outbreaks. Sequencing showed GI.P2-GI.2. GI norovirus was detected in one of 20 examined lettuce heads. All lettuce consumed was supplied by the same packer who in turn had bought the lettuce from a wholesaler in France. The two lots of lettuce came from two different growers in different parts of France.Discussion: Green coral lettuce produced in France was found to have caused a large series of linked norovirus outbreaks in Denmark as established by a number of lines of evidence. A similar incidence occurred in 2010. Fresh lettuce increasingly appear to be a risk food for norovirus infections.

Foodborne Disease Outbreaks in the United States: A Historical Overview.

Understanding the epidemiology of foodborne disease outbreaks (FBDOs) is important for informing investigation, control, and prevention methods. We examined annual summary FBDO data in the United States from 1938 to 2015, to help understand the epidemiology of outbreaks over time. Due to changes in reporting procedures, before 1998, the mean number of annual outbreaks was 378, and after that, it was 1062. A mean of 42% had a known etiology during 1961-1998; since then the etiology has been identified in ∼65%, with a marked increase in the number of norovirus outbreaks. From 1967 to 1997, a mean of 41% of FBDOs occurred in restaurant settings, increasing to 60% in 1998-2015. Concurrently, the proportion of outbreaks occurring at a home decreased from 25% to 8%. The mean size of outbreaks has decreased over time, and the number of multistate outbreaks has increased. Many social, economic, environmental, technological, and regulatory changes have dramatically affected the epidemiology of foodborne disease over time.

Testing for Human Norovirus and Recovery of Process Control in Outbreak-Associated Produce Items

The development of rapid and sensitive detection methods for human noroviruses (HuNoV) in produce items is critical, especially with the recent rise in outbreaks associated with this food commodity. In this study, 50-g portions of various produce items linked to a norovirus outbreak (celery, cucumber, lettuce, grapes, and radish) were artificially inoculated with murine norovirus (MNV-1) and concentrated either by ultracentrifugation or polyethylene glycol (PEG) precipitation after elution with an alkaline Tris-glycine-beef extract buffer supplemented with pectinase. As a viral concentration step following virus elution and clarification, ultracentrifugation yielded a faster method (<8 h, including reverse transcription quantitative PCR), with MNV-1 recoveries similar to or better, than those obtained with PEG precipitation. The addition of polyvinylpyrrolidone to the elution buffer, to remove polyphenolic inhibitors, improved MNV-1 recoveries by over two- and fivefold for cucumber and grapes, respectively. However, despite MNV-1 recoveries ranging from 10 to 38% as calculated with 10-fold diluted RNA, contaminating HuNoV was not detected in any of the outbreak-associated samples tested. For store-bought produce samples, the limit of detection for artificially seeded HuNoV GII.4 was determined to be 103 copies per 50 g, with reproducible detection achieved in grapes, radish, and celery. The results support the use of ultracentrifugation as an alternative approach to PEG precipitation to concentrate norovirus from a variety of produce items.

Antigenic Characterization of a Novel Recombinant GII.P16-GII.4 Sydney Norovirus Strain With Minor Sequence Variation Leading to Antibody Escape.

Human noroviruses are the leading cause of acute gastroenteritis. Strains of the GII.4 genotype cause pandemic waves associated with viral evolution and subsequent antigenic drift and ligand-binding modulation. In November 2015, a novel GII.4 Sydney recombinant variant (GII.P16-GII.4 Sydney) emerged and replaced GII.Pe-GII.4 Sydney as the predominant cause of acute gastroenteritis in the 2016-2017 season in the United States. Virus-like particles of GII.4 2012 and GII.4 2015 were compared for ligand binding and antibody reactivity, using a surrogate neutralization assay. Residue changes in the capsid between GII.4 2012 and GII.4 2015 decreased the potency of human polyclonal sera and monoclonal antibodies. A change in epitope A resulted in the complete loss of reactivity of a class of blockade antibodies and reduced levels of a second antibody class. Epitope D changes modulated monoclonal antibody potency and ligand-binding patterns. Substitutions in blockade antibody epitopes between GII.4 2012 and GII.4 2015 influenced antigenicity and ligand-binding properties. Although the impact of polymerases on fitness remains uncertain, antigenic variation resulting in decreased potency of antibodies to epitope A, coupled with altered ligand binding, likely contributed significantly to the spread of GII.4 2015 and its replacement of GII.4 2012 as the predominant norovirus outbreak strain.

Development of artificial intelligence approach to forecasting oyster norovirus outbreaks along Gulf of Mexico coast

This paper presents an artificial intelligence-based model, called ANN-2Day model, for forecasting, managing and ultimately eliminating the growing risk of oyster norovirus outbreaks. The ANN-2Day model was developed using Artificial Neural Network (ANN) Toolbox in MATLAB Program and 15-years of epidemiological and environmental data for six independent environmental predictors including water temperature, solar radiation, gage height, salinity, wind, and rainfall. It was found that oyster norovirus outbreaks can be forecasted with two-day lead time using the ANN-2Day model and daily data of the six environmental predictors. Forecasting results of the ANN-2Day model indicated that the model was capable of reproducing 19years of historical oyster norovirus outbreaks along the Northern Gulf of Mexico coast with the positive predictive value of 76.82%, the negative predictive value of 100.00%, the sensitivity of 100.00%, the specificity of 99.84%, and the overall accuracy of 99.83%, respectively, demonstrating the efficacy of the ANN-2Day model in predicting the risk of norovirus outbreaks to human health. The 2-day lead time enables public health agencies and oyster harvesters to plan for management interventions and thus makes it possible to achieve a paradigm shift of their daily management and operation from primarily reacting to epidemic incidents of norovirus infection after they have occurred to eliminating (or at least reducing) the risk of costly incidents.

Characterizing dynamic transmission of contaminants on a surface touch network

Our understanding of the fomite transmission route of diseases remains at an empirical level. There are no data on how surface contamination is propagated by human touching. We designed a novel and effective benchtop experiment to investigate the dynamic transmission of contaminants on multiple environmental surfaces due to touching. The benchtop experiment setting design was based on an inflight norovirus outbreak. Hundreds of representative environmental surfaces in the plane were scaled down, and fluorescent particles were used as surrogate indicators of virus-laden aerosols. The fluorescent particles were initially carried by six index “patients” and then transmitted to other surfaces through the touching behavior of one hundred and twenty-four “passengers.” The distributions of fluorescent particles were photographed by cameras when exposed to UV light and the acquired photos were processed using fluorescence imaging techniques to quantify fluorescent particles on each surface. The temporal diffusion of contaminated surfaces was found to follow an S-shaped logistic curve. The aisle seats were found to be more contaminated, which was consistent with the reported higher attack rates in passengers seating along the aisle in the outbreak. This study confirmed the findings of the logistic growth from the multi-agent simulations, and provided a possible mechanism for the role played by environmental surfaces in the fomite route of diseases.

The unwelcome houseguest: secondary household transmission of norovirus.

Norovirus is the leading cause of acute gastroenteritis in the USA. Although secondary household transmission of norovirus is frequently reported in outbreaks, little is known about specific risk factors for susceptibility and infectiousness in the household. Three norovirus outbreaks were investigated and data were collected on individuals exposed in the primary outbreak setting and their household members. Potential individual- and household-level risk factors for susceptibility and infectiousness were assessed using univariate and multivariate generalised linear mixed models. In the univariate models, the secondary attack rate (SAR) was significantly higher when living in a household with two or more primary cases (incidence rate ratio (IRR) = 2·1; 95% confidence interval (CI) 1·37-3·29), more than one primary case with vomiting (IRR = 1·9; CI 1·11-3·37), and at least one primary case with diarrhoea (IRR = 3·0; CI 1·46-6·01). After controlling for other risk factors in the multivariate models, the SAR was significantly higher among those living in a household with two or more primary cases (adjusted IRR = 2·0; CI 1·17-3·47) and at least one primary case with diarrhoea (adjusted IRR = 2·8; CI 1·35-5·93). These findings underscore the importance of maintaining proper hygiene and isolating ill household members to prevent norovirus transmission in the household.

Airborne or Fomite Transmission for Norovirus? A Case Study Revisited.

Norovirus infection, a highly prevalent condition associated with a high rate of morbidity, comprises a significant health issue. Although norovirus transmission mainly occurs via the fecal-oral and vomit-oral routes, airborne transmission has been proposed in recent decades. This paper re-examines a previously described norovirus outbreak in a hotel restaurant wherein airborne transmission was originally inferred. Specifically, the original evidence that suggested airborne transmission was re-analyzed by exploring an alternative hypothesis: could this outbreak instead have occurred via fomite transmission? This re-analysis was based on whether fomite transmission could have yielded similar attack rate distribution patterns. Seven representative serving pathways used by waiters were considered, and the infection risk distributions of the alternative fomite transmission routes were predicted using a multi-agent model. These distributions were compared to the reported attack rate distribution in the original study using a least square methods approach. The results show that with some reasonable assumptions of human behavior patterns and parameter values, the attack rate distribution corresponded well with that of the infection risk via the fomite route. This finding offers an alternative interpretation of the transmission routes that underlay this particular norovirus outbreak and an important consideration in the development of infection control guidelines and the investigation of similar norovirus outbreaks in future.