Detection of norovirus infections in Denmark, 2011-2018.

Norovirus (NoV) infections occur very frequently yet are rarely diagnosed. In Denmark, NoV infections are not under surveillance. We aimed to collect and describe existing laboratory-based NoV data. National NoV laboratory data were collected for 2011-2018, including information on patient identification number, age and sex, requesting physician, analysis date and result. We defined positive patient-episodes by using a 30-day time window and performed descriptive and time series analysis. Diagnostic methods used were assessed through a survey. We identified 15 809 patient-episodes (11%) out of 142 648 tested patients with an increasing trend, 9366 in 2011 vs. 32 260 in 2018. This corresponded with a gradual introduction of polymerase chain reaction analysis in laboratories. The highest positivity rate was in patients aged <5 years (15%) or >85 years (17%). There was a large difference in test performance over five Danish geographical regions and a marked seasonal variation with peaks from December to February. This is the first analysis of national NoV laboratory data in Denmark. A future laboratory-based surveillance system may benefit public health measures by describing trend, burden and severity of seasons and possibly pinpoint hospital outbreaks.

Monitoring telehealth vomiting calls as a potential public health early warning system for seasonal norovirus activity in Ontario, Canada.

Norovirus is a predominant cause of infectious gastroenteritis in countries worldwide [1-5]. It accounts for approximately 50% of acute gastroenteritis (AGE) and >90% of viral gastroenteritis outbreaks [6, 7]. The incubation period ranges between 10 and 48 h and illness duration is generally 1-3 days with self-limiting symptoms; however, this duration is often longer (e.g. 4-6 days) in vulnerable populations such as hospital patients or young children [2, 8]. Symptomatic infection of norovirus presents as acute vomiting, diarrhoea, abdominal cramps and nausea, with severe vomiting and diarrhoea (non-bloody) being most common [2, 5, 9].

Norovirus epidemiology in South African children <5 years hospitalised for diarrhoeal illness between 2009 and 2013.

Public health interest in norovirus (NoV) has increased in recent years following improved diagnostics, global burden estimates and the development of NoV vaccine candidates. This study aimed to describe the detection rate, clinical characteristics and environmental features associated with NoV detection in hospitalized children <5 years with diarrhoea in South Africa (SA). Between 2009 and 2013, prospective diarrhoeal surveillance was conducted at four sites in SA. Stool specimens were collected and screened for NoVs and other enteric pathogens using molecular and serological assays. Epidemiological and clinical data were compared in patients with or without detection of NoV. The study detected NoV in 15% (452/3103) of hospitalized children <5 years with diarrhoea with the majority of disease in children <2 years (92%; 417/452). NoV-positive children were more likely to present with diarrhoea and vomiting (odds ratio (OR) 1·3; 95% confidence interval (CI) 1·1-1·7; P = 0·011) with none-to-mild dehydration (adjusted OR 0·5; 95% CI 0·3-0·7) compared with NoV-negative children. Amongst children testing NoV positive, HIV-infected children were more likely to have prolonged hospitalization and increased mortality compared with HIV-uninfected children. Continued surveillance will be important to consider the epidemic trends and estimate the burden and risk of NoV infection in SA.

A large outbreak of acute gastroenteritis in Shippensburg, Pennsylvania, 1972 revisited: evidence for common source exposure to a recombinant GII.Pg/GII.3 norovirus.

Historical outbreaks can be an important source of information in the understanding of norovirus evolution and epidemiology. Here, we revisit an outbreak of undiagnosed gastroenteritis that occurred in Shippensburg, Pennsylvania in 1972. Nearly 5000 people fell ill over the course of 10 days. Symptoms included diarrhea, vomiting, stomach cramps, and fever, lasting for a median of 24 h. Using current techniques, including next-generation sequencing of full-length viral genomic amplicons, we identified an unusual norovirus recombinant (GII.Pg/GII.3) in nine of 15 available stool samples from the outbreak. This particular recombinant virus has not been reported in recent decades, although GII.3 and GII.Pg genotypes have been detected individually in current epidemic strains. The consensus nucleotide sequences were nearly identical among the four viral genomes analysed, although each strain had three to seven positions in the genome with heterogenous non-synonymous nucleotide subpopulations. Two of these resulting amino acid polymorphisms were conserved in frequency among all four cases, consistent with common source exposure and successful transmission of a mixed viral population. Continued investigation of variant nucleotide populations and recombination events among ancestral norovirus strains such as the Shippensburg virus may provide unique insight into the origin of contemporary strains.

An outbreak of norovirus GI-6 infection following a wedding in North West England.

In August 2015 a gastroenteritis outbreak occurred following a wedding. An outbreak investigation was undertaken and a cohort study was conducted using an online survey. Of 140 guests, 134 received the survey and 113 responded (84·3% response rate). Seventy respondents met the case definition of vomiting and/or diarrhoea within 72 h of the wedding (61·9% attack rate). Fifteen exposures were associated with illness; on stratification, all were confounded by the ham hock starter. Multivariable analysis showed a significant association with exposure to ham hock (risk ratio 6·62, 95% confidence interval 2·19-20·03). Eight guests and two catering staff submitted stool samples. All tested positive for norovirus GI-6 infection, including a food handler who had vomiting less than 48 h before the wedding. A single genotype was detected among all samples, suggesting a single source of contamination. The transmission pattern suggested point-source exposure. The most plausible cause of the outbreak was transmission from an infected food handler via contaminated food. This highlights the importance of appropriate exclusions for symptomatic food handlers. Additionally, the food handler's stool sample was submitted 7 days after symptom resolution. The potential for extended viral excretion, and the extremely low infective dose of norovirus, may mean that current exclusion guidelines are not of sufficient duration.

Norovirus gastroenteritis outbreak transmitted by food and vomit in a high school.

We investigated an outbreak of norovirus that affected students and teachers of a high school in Lleida, Spain through various transmission mechanisms. A case-control epidemiological study of the risk of disease and the relative importance of each mode of transmission was carried out. Cases and controls were selected from a systematic sample of students and teachers present at the school on 28 January. Faecal samples were taken from three food handlers and 16 cases. The influence of each factor was studied using the adjusted odds ratio (aOR) and the estimated population attributable risk (ePAR) with 95% confidence intervals (CI). We interviewed 210 people (42 cases, 168 controls). The proportion of symptoms in these individuals was nausea 78·6%, vomiting 59·5%, diarrhoea 45·2%, and fever 19·0%. The epidemic curve showed transmission for at least 4 days. The risk of disease was associated with exposure to food (aOR 5·8) in 66·1% of cases and vomit (aOR 4·7) in 24·8% of cases. Faecal samples from 11 patients and two food handlers were positive for norovirus GII.12 g. Vomit may co-exist with other modes of transmission in norovirus outbreaks and could explain a large number of cases.

A waterborne norovirus gastroenteritis outbreak in a school, eastern China.

In late 2014, a gastroenteritis outbreak occurred in a school in Shandong Province, eastern China. Hundreds of individuals developed the symptoms of diarrhoea and vomiting. Epidemiological investigation showed that food consumption was not linked to this outbreak, and unboiled direct drinking water was identified as the independent risk factor with a relative risk of 1·37 (95% confidence interval 1·03-1·83). Furthermore, examination of common bacterial and viral gastroenteritis pathogens was conducted on different specimens. Norovirus GI.1, GI.2, GI.6, GII.4, GII.6 and GII.13 were detected in clinical specimens and a water sample. GII.4 sequences between clinical specimens and the water sample displayed a close relationship and belonged to GII.4 variant Sydney 2012. These results indicate that direct drinking water contaminated by norovirus was responsible for this gastroenteritis outbreak. This study enriches our knowledge of waterborne norovirus outbreaks in China, and presents valuable prevention and control practices for policy-makers. In future, strengthened surveillance and supervision of direct drinking-water systems is needed.

Estimated hospitalizations attributed to norovirus and rotavirus infection in Canada, 2006-2010.

Enteric viruses including norovirus and rotavirus are leading causes of gastroenteritis in Canada. However, only a small number of clinical cases are actually tested for these pathogens leading to systematic underestimation of attributed hospitalizations in administrative databases. The objective of this analysis was to estimate the number of hospitalizations due to norovirus and rotavirus in Canada. Hospitalization records for acute gastroenteritis-associated discharges at all acute-care hospitals in Canada between 2006 and 2011 were analysed. Cause-unspecified gastroenteritis hospitalizations were modelled using age-specific negative binomial models with cause-specified gastroenteritis admissions as predictors. The coefficients from the models were used to estimate the number of norovirus and rotavirus admissions. The total annual hospitalizations for rotavirus were estimated to be between 4500 and 10 000. Total annual hospitalizations for norovirus were estimated to be between 4000 and 11 000. The mean total annual cost associated with these hospitalizations was estimated to be at least $16 million for rotavirus and $21 million for norovirus (all figures in Canadian dollars). This study is the first comprehensive analysis of norovirus and rotavirus hospitalizations in Canada. These estimates provide a more complete assessment of the burden and economic costs of these pathogens to the Canadian healthcare system.

Outbreaks attributed to fresh leafy vegetables, United States, 1973-2012.

Leafy vegetables are an essential component of a healthy diet; however, they have been associated with high-profile outbreaks causing severe illnesses. We reviewed leafy vegetable-associated outbreaks reported to the Centers for Disease Control and Prevention between 1973 and 2012. During the study period, 606 leafy vegetable-associated outbreaks, with 20 003 associated illnesses, 1030 hospitalizations, and 19 deaths were reported. On average, leafy vegetable-associated outbreaks were larger than those attributed to other food types. The pathogens that most often caused leafy vegetable-associated outbreaks were norovirus (55% of outbreaks with confirmed aetiology), Shiga toxin-producing Escherichia coli (STEC) (18%), and Salmonella (11%). Most outbreaks were attributed to food prepared in a restaurant or catering facility (85%). An ill food worker was implicated as the source of contamination in 31% of outbreaks. Efforts by local, state, and federal agencies to control leafy vegetable contamination and outbreaks should span from the point of harvest to the point of preparation.

A norovirus oyster-related outbreak in a nursing home in France, January 2012.

The presence of norovirus in shellfish is a public health concern in Europe. Here, we report the results of an investigation into a norovirus gastroenteritis outbreak following a festive lunch which affected 84 (57%) residents and staff members of a nursing home in January 2012 in France. Individuals who had eaten oysters had a significantly higher risk of developing symptoms in the following 2·5 days than those who had not, the risk increasing with the amount eaten [relative risk 2·2 (1·0-4·6) and 3·3 (1·6-6·6) for 3-4 and 5-12 oysters, respectively]. In healthy individuals during those days, 29 (32%) subsequently became ill, most of whom were staff members performing activities in close contact with residents. Genogroup II noroviruses were detected in faecal samples, in a sample of uneaten oysters and in oysters from the production area. Identifying a norovirus's infectious dose may facilitate the health-related management of contaminated shellfish.

Association of host, agent and environment characteristics and the duration of incubation and symptomatic periods of norovirus gastroenteritis.

We analysed the reported duration of incubation and symptomatic periods of norovirus for a dataset of 1022 outbreaks, 64 of which reported data on the average incubation period and 87 on the average symptomatic period. We found the mean and median incubation periods for norovirus to be 32·8 [95% confidence interval (CI) 30·9-34·6] hours and 33·5 (95% CI 32·0-34·0) hours, respectively. For the symptomatic period we found the mean and median to be 44·2 (95% CI 38·9-50·7) hours and 43·0 (95% CI 36·0-48·0) hours, respectively. We further investigated how these average periods were associated with several reported host, agent and environmental characteristics. We did not find any strong, biologically meaningful associations between the duration of incubation or symptomatic periods and the reported host, pathogen and environmental characteristics. Overall, we found that the distributions of incubation and symptomatic periods for norovirus infections are fairly constant and showed little differences with regard to the host, pathogen and environmental characteristics we analysed.

Separate norovirus outbreaks linked to one source of imported frozen raspberries by molecular analysis, Denmark, 2010-2011.

Norovirus outbreaks occur frequently in Denmark and it can be difficult to establish whether apparently independent outbreaks have the same origin. Here we report on six outbreaks linked to frozen raspberries, investigated separately over a period of 3 months. Norovirus from stools were sequence-typed; including extended sequencing of 1138 bp encompassing the hypervariable P2 region of the capsid gene. Norovirus was detected in 27 stool samples. Genotyping showed genotype GI.Pb_GI.6 (polymerase/capsid) with 100% identical sequences. Samples from five outbreaks were furthermore identical over the variable capsid P2 region. In one outbreak at a hospital canteen, frozen raspberries was associated with illness by cohort investigation (relative risk 6·1, 95% confidence interval 3·2-11). Bags of raspberries suspected to be the source were positive for genogroup I and II noroviruses, one typable virus was genotype GI.6 (capsid). These molecular investigations showed that the apparently independent outbreaks were the result of one contamination event of frozen raspberries. The contaminated raspberries originated from a single producer in Serbia and were originally not considered to belong to the same batch. The outbreaks led to consultations and mutual visits between producers, investigators and authorities. Further, Danish legislation was changed to make heat-treatment of frozen raspberries compulsory in professional catering establishments.