Norovirus Season Research Articles

Predicting Dominant Genotypes in Norovirus Seasons in Japan.

Human noroviruses are an etiological agent of acute gastroenteritis. Since multiple genotypes co-circulate every season changing their proportions, it may be desirable to develop multivalent vaccines by formulating genotype composition of seed strains to match that of dominant strains. Here, performances of the models for predicting dominant genotypes, defined as the two most prevalent genotypes, were evaluated using observed genotype frequencies in Japan and genomic sequences for GI and GII strains. In the null model, genotype proportions in the target season were predicted to be the same as those in the immediately preceding season. In the fitness model, genotype proportions were predicted taking into account the acquisition of novel P-types through recombination and genotype-specific proliferation efficiency, as well as herd immunity to VP1 assuming the duration (d) of 0-10 years. The null model performed better in GII than in GI, apparently because dominant genotypes were more stable in the former than in the latter. Performance of the fitness model was similar to that of the null model irrespective of the assumed value of d. However, performance was improved when dominant genotypes were predicted as the union of those predicted with d = 0-10, suggesting that d may vary among individuals.

Predicting Norovirus in England Using Existing and Emerging Syndromic Data: Infodemiology Study.

Norovirus is associated with approximately 18% of the global burden of gastroenteritis and affects all age groups. There is currently no licensed vaccine or available antiviral treatment. However, well-designed early warning systems and forecasting can guide nonpharmaceutical approaches to norovirus infection prevention and control. This study evaluates the predictive power of existing syndromic surveillance data and emerging data sources, such as internet searches and Wikipedia page views, to predict norovirus activity across a range of age groups across England. We used existing syndromic surveillance and emerging syndromic data to predict laboratory data indicating norovirus activity. Two methods are used to evaluate the predictive potential of syndromic variables. First, the Granger causality framework was used to assess whether individual variables precede changes in norovirus laboratory reports in a given region or an age group. Then, we used random forest modeling to estimate the importance of each variable in the context of others with two methods: (1) change in the mean square error and (2) node purity. Finally, these results were combined into a visualization indicating the most influential predictors for norovirus laboratory reports in a specific age group and region. Our results suggest that syndromic surveillance data include valuable predictors for norovirus laboratory reports in England. However, Wikipedia page views are less likely to provide prediction improvements on top of Google Trends and Existing Syndromic Data. Predictors displayed varying relevance across age groups and regions. For example, the random forest modeling based on selected existing and emerging syndromic variables explained 60% variance in the ≥65 years age group, 42% in the East of England, but only 13% in the South West region. Emerging data sets highlighted relative search volumes, including "flu symptoms," "norovirus in pregnancy," and norovirus activity in specific years, such as "norovirus 2016." Symptoms of vomiting and gastroenteritis in multiple age groups were identified as important predictors within existing data sources. Existing and emerging data sources can help predict norovirus activity in England in some age groups and geographic regions, particularly, predictors concerning vomiting, gastroenteritis, and norovirus in the vulnerable populations and historical terms such as stomach flu. However, syndromic predictors were less relevant in some age groups and regions likely due to contrasting public health practices between regions and health information-seeking behavior between age groups. Additionally, predictors relevant to one norovirus season may not contribute to other seasons. Data biases, such as low spatial granularity in Google Trends and especially in Wikipedia data, also play a role in the results. Moreover, internet searches can provide insight into mental models, that is, an individual's conceptual understanding of norovirus infection and transmission, which could be used in public health communication strategies.

Spatiotemporal Trends in Norovirus Outbreaks in the United States, 2009-2019.

Globally, noroviruses cause infections year-round but have recognized winter seasonality in the Northern Hemisphere and yearly variations in incidence. With candidate norovirus vaccines in development, understanding temporal and geographic trends in norovirus disease is important to inform potential vaccination strategies and evaluate vaccine impact. We analyzed data from the National Outbreak Reporting System (NORS) and CaliciNet on single-state norovirus outbreaks that occurred during August 2009-July 2019 in the contiguous United States. We defined norovirus season onset and offset as the weeks by which 10% and 90% of norovirus outbreaks in a surveillance year occurred, respectively, and duration as the difference in weeks between onset and offset. We compared norovirus seasons across surveillance years and geographic regions. During August 2009-July 2019, 24 995 single-state norovirus outbreaks were reported to NORS and/or CaliciNet. Nationally, the median norovirus season duration was 24 weeks, with onset occurring between October and December and offset occurring between April and May. Across all years combined, we observed a west-to-east trend in seasonality, with the earliest onset (October) and latest offset (May) occurring in western regions and the latest onset (December) and earliest offset (April) occurring in northeastern regions. Timing and duration of the US norovirus season varied annually but generally occurred during October-May. Norovirus wintertime seasonality was less distinct in western regions and was progressively more pronounced moving east. Further understanding the drivers of spatiotemporal dynamics of norovirus could provide insights into factors that promote virus transmission and help guide future interventions.

Can cases and outbreaks of norovirus in children provide an early warning of seasonal norovirus infection: an analysis of nine seasons of surveillance data in England UK

BackgroundChildren are important transmitters of norovirus infection and there is evidence that laboratory reports in children increase earlier in the norovirus season than in adults. This raises the question as to whether cases and outbreaks in children could provide an early warning of seasonal norovirus before cases start increasing in older, more vulnerable age groups.MethodsThis study uses weekly national surveillance data on reported outbreaks within schools, care homes and hospitals, general practice (GP) consultations for infectious intestinal disease (IID), telehealth calls for diarrhoea and/or vomiting and laboratory norovirus reports from across England, UK for nine norovirus seasons (2010/11–2018/19). Lagged correlation analysis was undertaken to identify lead or lag times between cases in children and those in adults for each surveillance dataset. A partial correlation analysis explored whether school outbreaks provided a lead time ahead of other surveillance indicators, controlling for breaks in the data due to school holidays. A breakpoint analysis was used to identify which surveillance indicator and age group provided the earliest warning of the norovirus season each year.ResultsSchool outbreaks occurred 3-weeks before care home and hospital outbreaks, norovirus laboratory reports and NHS 111 calls for diarrhoea, and provided a 2-week lead time ahead of NHS 111 calls for vomiting. Children provided a lead time ahead of adults for norovirus laboratory reports (+ 1–2 weeks), NHS 111 calls for vomiting (+ 1 week) and NHS 111 calls for diarrhoea (+ 1 week) but occurred concurrently with adults for GP consultations. Breakpoint analysis revealed an earlier seasonal increase in cases among children compared to adults for laboratory, GP and NHS 111 data, with school outbreaks increasing earlier than other surveillance indicators in five out of nine surveillance years.ConclusionThese findings suggest that monitoring cases and outbreaks of norovirus in children could provide an early warning of seasonal norovirus infection. However, both school outbreak data and syndromic surveillance data are not norovirus specific and will also capture other causes of IID. The use of school outbreak data as an early warning indicator may be improved by enhancing sampling in community outbreaks to confirm the causative organism.

Effect of recombinations on changes in genotype proportions between norovirus seasons in Japan

BackgroundNorovirus (NoV) is an etiological agent of acute gastroenteritis in humans. Genomic recombinations in NoV occur mainly at the junction of the genes encoding the RNA-dependent RNA polymerase (RdRp) and the major capsid protein (viral protein 1, VP1), which may produce strains with novel combinations of VP1- and RdRp-genotypes. MethodsHere the effect of recombinations on changes in the proportions of VP1-genotypes was examined through analysis of the observed frequencies of VP1-genotypes in Japan from season 2006/2007 to 2019/2020 reported in the Infectious Agents Surveillance Report (IASR) and the nucleotide sequences for 2788 GI and 19,782 GII strains deposited in the International Nucleotide Sequence Database (INSD). ResultsPositive correlation was identified between the observed frequency in the IASR and the number of nucleotide sequences in the INSD for individual VP1-genotypes in each season. In addition, acquisition of novel RdRp-genotypes was associated with an increase in the observed proportion of VP1-genotypes. ConclusionsRecombinations creating strains with novel combinations of VP1- and RdRp-genotypes may be an adaptive mechanism for NoV.

Differences in epidemic spread patterns of norovirus and influenza seasons of Germany: an application of optical flow analysis in epidemiology

This analysis presents data from a new perspective offering key insights into the spread patterns of norovirus and influenza epidemic events. We utilize optic flow analysis to gain an informed overview of a wealth of statistical epidemiological data and identify trends in movement of influenza waves throughout Germany on the NUTS 3 level (413 locations) which maps municipalities on European level. We show that Influenza and norovirus seasonal outbreak events have a highly distinct pattern. We investigate the quantitative statistical properties of the epidemic patterns and find a shifted distribution in the time between influenza and norovirus seasonal peaks of reported infections over one decade. These findings align with key biological features of both pathogens as shown in the course of this analysis.

Predicting Directions of Changes in Genotype Proportions Between Norovirus Seasons in Japan.

The norovirus forecasting system (NOROCAST) has been developed for predicting directions of changes in genotype proportions between human norovirus (HuNoV) seasons in Japan through modeling herd immunity to structural protein 1 (VP1). Here 404 nearly complete genomic sequences of HuNoV were analyzed to examine whether the performance of NOROCAST could be improved by modeling herd immunity to VP2 and non-structural proteins (NS) in addition to VP1. It was found that the applicability of NOROCAST may be extended by compensating for unavailable sequence data and observed genotype proportions of 0 in each season. Incorporation of herd immunity to VP2 and NS did not appear to improve the performance of NOROCAST, suggesting that VP1 may be a suitable target of vaccines.

Hand hygiene education, an underutilized tool in preventing emerging, re-emerging infectious diseases and seasonal epidemics

Purpose: A common thread among most emerging infectious diseases is Hand Hygiene. So why isn’t more being done to introduce, educate and bring awareness of this improtant topic among our youngest members in the community. We created a fun scientific experiment with second and third grade students to see if education and intervention will bring about a positive behavioral change that will subsequently decrease the rate of illness during peak influenza and norovirus season. Methods & Materials: Ninety students cultured their “dirty” hands on a petri dish. Proper handwashing technique was demonstrate to all student. They were then divided equally into the hand washing group and the hand sanitizer group. All students then cultured their “clean” hands on a second petri dishes. The students observed, compared and documented their findings daily for a week. We then used a simulation germ that illuminates with black light to test the efficacy of their hand washing and see areas where they could improve. We followed the illumination along the classroom and each other to see how easily the “germ” spread. A light microscope, a microbiologist and slides of common pathogens were brought into the classroom for examination and discussion. Children were happy to share stories of infections they and their families have had.Results:1.91% of the students observed decreased microbial growth from “dirty” to “clean” hands.2.Education improved compliance as 89% had a favorable behaviorial change to clean their hands.3.There was a 71% decrease in incidence of illness related absences 30 days after the hand hygiene intervention.4.Three out of the five classes reported hand sanitizer was more effective when compared to hand washing. Conclusion: Hand Hygiene education is remarkable beneficial, especially in children who are at the greatest risk of illness. It is clearly effective in decreasing infectious disease risk, while teaching a valuable life-long habit. For the impact to be felt as a preventative strategy both for illness and emerging infectious diseses, its implementation into the elementary school curriculum is warranted. In the words of the Benjamin Franklin, “an ounce of prevention is worth a pound of cure”.

Burden of Severe Norovirus Disease in Taiwan, 2003-2013.

Despite the increasingly recognized role of norovirus in global acute gastroenteritis (AGE), specific estimates of the associated disease burden remain sparse, primarily due to limited availability of sensitive norovirus diagnostics in the clinical setting. We sought to estimate the incidence of norovirus-associated hospitalizations by age group in Taiwan using a previously developed indirect regression method. AGE-related hospitalizations in Taiwan were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes abstracted from a national database; population data were provided from the Department of Household Registration Affairs. Population and hospitalizations were aggregated by month and year (July 2003-June 2013) and grouped by age: <5 years, 5-19 years, 20-64 years, and ≥65 years. Monthly counts of cause-unspecified AGE hospitalizations were modeled as a function of counts of known causes, and the residuals were then analyzed to estimate norovirus-associated hospitalizations. Over the study period, an annual mean of 101400 gastroenteritis-associated hospitalizations occurred in Taiwan (44 per 10000 person-years), most of which (83%) had no specified cause. The overall estimated rate of norovirus-associated hospitalizations was 6.7 per 10000 person-years, with the highest rates in children aged <5 years (63.7/10000 person-years). Predicted norovirus peaked in 2006-2007 and 2012-2013. Our study is one of the first to generate a population-based estimate of severe norovirus disease incidence in Asia, and highlights the large burden of norovirus in Taiwan, particularly in children. Predicted peak norovirus seasons coincided with the emergence of new strains and resulting pandemics, supporting the validity of the estimates.

Molecular epidemiology of noroviruses detected in Vietnamese children with acute gastroenteritis from 2012 to 2015

Noroviruses, an important cause of diarrhoea in humans, are genetically diverse. The recent norovirus seasons recorded the emergence of new recombinants of the capsid and polymerase genotypes, with a global dominance of GII.Pe_GII.4 Sydney 2012 and GII.P17_GII.17 in Asian countries. However, the number of papers reporting the distribution of both polymerase and capsid genotypes circulating among children is scarce, with none from Vietnam. This study described both the polymerase and capsid genotypes of noroviruses circulating in Vietnamese children using stool specimens obtained under the World Health Organization rotavirus surveillance programme from 2012 to 2015. Of 350 specimens tested, noroviruses were detected in 90 (28 %) of 319 inpatient specimens and in 9 (29 %) of 31 outpatient specimens. The polymerase and capsid genotype combinations of GII.Pe_GII.4 Sydney 2012 and GII.P21_GII.3 were co-dominant (51 and 24 %, respectively), both of which were recombinants, contributing to a high proportion (87 %) of recombinants among circulating noroviruses. GII.4 variants evolved in the same fashion in Vietnam as in other countries, with amino acid substitutions in the putative variant-specific epitopes of the protruding domain. Unlike neighbouring countries where the predominance of GII.P17_GII.17 was reported, only one GII.P17_GII.17 strain was detected from an outpatient in 2015 in Vietnam. In conclusion, a substantial burden due to norovirus gastroenteritis hospitalizations among Vietnamese children was associated with circulating co-dominant GII.Pe_GII.4 Sydney 2012 and GII.P21_GII.3 strains. Continued surveillance is necessary to monitor infection caused by GII.4 variants and that of GII.P17_GII.17 noroviruses in paediatric patients in Vietnam.

Predicting genotype compositions in norovirus seasons in Japan.

Noroviruses cause acute gastroenteritis. Since multiple genotypes of norovirus co-circulate in humans, changing the genotype composition and eluding host immunity, development of a polyvalent vaccine against norovirus in which the genotypes of vaccine strains match the major strains in circulation in the target season is desirable. However, this would require prediction of changes in the genotype composition of circulating strains. A fitness model that predicts the proportion of a strain in the next season from that in the current season has been developed for influenza A virus. Here, such a fitness model that takes into account the fitness effect of herd immunity was used to predict genotype compositions in norovirus seasons in Japan. In the current study, a model that assumes a decline in the magnitude of cross immunity between norovirus strains according to an increase in the divergence of the major antigenic protein VP1 was found to be appropriate for predicting genotype composition. Although it is difficult to predict the proportions of genotypes accurately, the model is effective in predicting the direction of change in the proportions of genotypes. The model predicted that GII.3 and GII.4 may contract, whereas GII.17 may expand and predominate in the 2015-2016 season. The procedure of predicting genotype compositions in norovirus seasons described in the present study has been implemented in the norovirus forecasting system (NOROCAST).

Genome of Emerging Norovirus GII.17, United States, 2014.

To determine whether the norovirus strain GII.17 recently detected in Maryland, USA, (Hu/GII.17/Gaithersburg/2014/US) is spreading globally, we characterized the genome. High similarity with the norovirus GII.17 that caused recent outbreaks in Asia indicates that the same strain was present in the United States during the 2014–15 norovirus season (winter).

Sequence analysis of the capsid gene during a genotype II.4 dominated norovirus season in one university hospital: identification of possible transmission routes.

Norovirus (NoV) is a leading cause of gastroenteritis and genotype II.4 (GII.4) is responsible for the majority of nosocomial NoV infections. Our objective was to examine whether sequencing of the capsid gene might be a useful tool for the hospital outbreak investigation to define possible transmission routes. All NoV positive samples submitted from one university hospital during the 2007/8 season were selected. Genotyping of selected samples by partial polymerase gene sequencing had shown that the majority belonged to the GII.4 variant Den Haag 2006b and had identical polymerase sequences. Sequences of the capsid gene (1412 nucleotides) were obtained from the first available sample from 55 patients. From six immunocompromised patients with persistent infections a second sample was also included. As a control for a point-source outbreak, five samples from a foodborne outbreak caused by the same GII.4 variant were analyzed. Forty-seven of the inpatients (85%) were infected with the GII.4 variant Den Haag 2006b. Phylogenetic analysis of the Den Haag 2006b sequences identified four distinct outbreaks in different departments and a fifth outbreak with possible inter-department spread. In addition, a more heterogeneous cluster with evidence of repeated introductions from the community, but also possible inter-department spread was observed. In all six patients with paired sequences, evidence for in vivo evolution of the virus was found. Capsid gene sequencing showed substantial sequence variation among NoV GII.4 variant Den Haag 2006b strains from one single institution during a nine months’ period. This method proved useful to understand the local epidemiology and, when used promptly, has the potential to make infection control measures more targeted.

Detecting the norovirus season in Sweden using search engine data--meeting the needs of hospital infection control teams.

Norovirus outbreaks severely disrupt healthcare systems. We evaluated whether Websök, an internet-based surveillance system using search engine data, improved norovirus surveillance and response in Sweden. We compared Websök users' characteristics with the general population, cross-correlated weekly Websök searches with laboratory notifications between 2006 and 2013, compared the time Websök and laboratory data crossed the epidemic threshold and surveyed infection control teams about their perception and use of Websök. Users of Websök were not representative of the general population. Websök correlated with laboratory data (b = 0.88-0.89) and gave an earlier signal to the onset of the norovirus season compared with laboratory-based surveillance. 17/21 (81%) infection control teams answered the survey, of which 11 (65%) believed Websök could help with infection control plans. Websök is a low-resource, easily replicable system that detects the norovirus season as reliably as laboratory data, but earlier. Using Websök in routine surveillance can help infection control teams prepare for the yearly norovirus season.

A Systematic Review and Meta-Analysis of the Global Seasonality of Norovirus

BackgroundNoroviruses are the most common cause of acute gastroenteritis across all ages worldwide. These pathogens are generally understood to exhibit a wintertime seasonality, though a systematic assessment of seasonal patterns has not been conducted in the era of modern diagnostics.MethodsWe conducted a systematic review of the Pubmed Medline database for articles published between 1997 and 2011 to identify and extract data from articles reporting on monthly counts of norovirus. We conducted a descriptive analysis to document seasonal patterns of norovirus disease, and we also constructed multivariate linear models to identify factors associated with the strength of norovirus seasonality.ResultsThe searched identified 293 unique articles, yielding 38 case and 29 outbreak data series. Within these data series, 52.7% of cases and 41.2% of outbreaks occurred in winter months, and 78.9% of cases and 71.0% of outbreaks occurred in cool months. Both case and outbreak studies showed an earlier peak in season-year 2002-03, but not in season-year 2006-07, years when new genogroup II type 4 variants emerged. For outbreaks, norovirus season strength was positively associated with average rainfall in the wettest month, and inversely associated with crude birth rate in both bivariate and multivariate analyses. For cases, none of the covariates examined was associated with season strength. When case and outbreaks were combined, average rainfall in the wettest month was positively associated with season strength.ConclusionsNorovirus is a wintertime phenomenon, at least in the temperate northern hemisphere where most data are available. Our results point to possible associations of season strength with rain in the wettest month and crude birth rate.

Emergency Department Visit Data for Rapid Detection and Monitoring of Norovirus Activity, United States

Noroviruses are the leading cause of gastroenteritis in the United States, but timely measures of disease are lacking. BioSense, a national-level electronic surveillance system, assigns data on chief complaints (patient symptoms) collected during emergency department (ED) visits to 78 subsyndromes in near real-time. In a series of linear regression models, BioSense visits mapped by chief complaints of diarrhea and nausea/vomiting subsyndromes as a monthly proportion of all visits correlated strongly with reported norovirus outbreaks from 6 states during 2007–2010. Higher correlations were seen for diarrhea (R = 0.828–0.926) than for nausea/vomiting (R = 0.729–0.866) across multiple age groups. Diarrhea ED visit proportions exhibited winter seasonality attributable to norovirus; rotavirus contributed substantially for children <5 years of age. Diarrhea ED visit data estimated the onset, peak, and end of norovirus season within 4 weeks of observed dates and could be reliable, timely indicators of norovirus activity.

Epidemiology of norovirus gastroenteritis in Germany 2001–2009: eight seasons of routine surveillance

We analysed data on laboratory or epidemiologically confirmed cases (n = 856,539) and on outbreaks (n = 31,644) notified during week 31 (2001) to week 30 (2009), and performed molecular typing of specimens from 665 outbreaks. We aimed at identifying demographic and molecular characteristics to inform on potential additional approaches to prevent disease spread in the population. The mean incidence by norovirus season (week 31 in one year to week 30 in the following year) was 130 (range 19-300) cases/100,000 population and was highest in persons aged <5 years (430/100,000) and ≥ 75 years (593/100,000). The proportion hospitalized in community-acquired cases was 8-19% per season. The mean norovirus-associated mortality was 0.05/100,000 per season and 0.5/100,000 in the ≥ 75 years age group. Most outbreaks with known setting (75%) occurred in hospitals (32%), nursing homes (28%), households (24%) and childcare facilities (10%). GII strains dominated in the outbreak specimens. GII.4 strains were found in 82% of nursing home outbreaks, 85% of hospital outbreaks, and 33% of childcare facility and school outbreaks. Cases in younger individuals were notified earlier during the season than adult cases, and outbreaks in childcare facilities and schools preceded those in nursing/residential homes, hospitals and private households. We suggest future studies to investigate more closely potential transmission patterns between children and adults.

Rapid emergence and antigenic diversification of the norovirus 2012 Sydney variant in Denmark, October to December, 2012

The norovirus (NoV) season in Denmark in late 2012 was characterised by an increase in the number of NoV infections caused mainly by the 2012 Sydney variant, but also by the 2009 New Orleans variant. Analysis of approximately 85% of the capsid gene from 10 Sydney 2012 and 9 New Orleans 2009 isolates showed rapid antigenic diversification of the Sydney 2012 variant shortly after its emergence. We also present new primers useful for transmission tracking.

Increased norovirus activity in Scotland in 2012 is associated with the emergence of a new norovirus GII.4 variant

To the editor: Since late 2012, Scotland has seen a significant increase in norovirus activity and the norovirus season began earlier than usual [1]. The article by van Beek et al. published in last week’s issue of Eurosurveillance described the emergence of a new variant of norovirus GII.4 (Sydney strain) in a number of countries [2]. To examine whether this was also the case in Scotland, we examined representative samples from norovirus outbreaks in hospitals submitted to the West of Scotland Specialist Virology Centre (WoSSVC) in Glasgow between 8 and 20 November 2012. This time period was chosen as it was after the point when the increased norovirus activity was first reported by Health Protection Scotland [1].

Indications for worldwide increased norovirus activity associated with emergence of a new variant of genotype II.4, late 2012

Globally, surveillance systems showed an increasein norovirus activity in late 2012. Molecular datashared through the NoroNet network suggest thatthis increase is related to the emergence of a newnorovirus genotype II.4 variant, termed Sydney 2012.Healthcare institutions are advised to be prepared fora severe norovirus season.