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Background: To reduce the burden from the COVID-19 pandemic in the United States, federal and state local governments implemented restrictions such as limitations on gatherings, restaurant dining, and travel, and recommended non-pharmaceutical interventions including physical distancing, mask-wearing, surface disinfection, and increased hand hygiene. Resulting behavioral changes impacted other infectious diseases including enteropathogens such as norovirus and rotavirus, which had fairly regular seasonal patterns prior to the COVID-19 pandemic. The study objective was to project future incidence of norovirus and rotavirus gastroenteritis as contacts resumed and other NPIs are relaxed., Methods: We fitted compartmental mathematical models to pre-pandemic U.S. surveillance data (2012-2019) for norovirus and rotavirus using maximum likelihood estimation. Then, we projected incidence for 2022-2030 under scenarios where the number of contacts a person has per day varies from70%, 80%, 90%, and full resumption (100%) of pre-pandemic levels., Results: We found that the population susceptibility to both viruses increased between March 2020 and November 2021. The 70-90% contact resumption scenarios led to lower incidence than observed pre-pandemic for both viruses. However, we found a greater than two-fold increase in community incidence relative to the pre-pandemic period under the 100% contact scenarios for both viruses. With rotavirus, for which population immunity is driven partially by vaccination, patterns settled into a new steady state quickly in 2022 under the 70-90% scenarios. For norovirus, for which immunity is relatively short-lasting and only acquired through infection, surged under the 100% contact scenario projection., Conclusions: These results, which quantify the consequences of population susceptibility build-up, can help public health agencies prepare for potential resurgence of enteric viruses., (© 2023. The Author(s).)

Norovirus is the leading cause of acute gastroenteritis outbreaks in the United States. We estimated the basic (R 0 ) and effective (R e ) reproduction numbers for 7,094 norovirus outbreaks reported to the National Outbreak Reporting System (NORS) during 2009-2017 and used regression models to assess whether transmission varied by outbreak setting. The median R 0 was 2.75 (interquartile range [IQR] 2.38-3.65), and median R e was 1.29 (IQR 1.12-1.74). Long-term care and assisted living facilities had an R 0  of 3.35 (95% CI 3.26-3.45), but R 0 did not differ substantially for outbreaks in other settings, except for outbreaks in schools, colleges, and universities, which had an R 0  of 2.92 (95% CI 2.82-3.03). Seasonally, R 0 was lowest (3.11 [95% CI 2.97-3.25]) in summer and peaked in fall and winter. Overall, we saw little variability in transmission across different outbreaks settings in the United States.

We compared acute gastroenteritis (AGE)-related hospitalization rates among children <5 years of age during the pre-rotavirus vaccine (2000-2006) and post-rotavirus vaccine (2008-2013) periods to estimate national reductions in AGE-related hospitalizations and associated costs. We estimate that between 2008 and 2013, AGE-related hospitalizations declined by 382000, and $1.228 billion in medical costs were averted.

An estimated 179 million acute gastroenteritis (AGE) illnesses occur annually in the United States. The role of noroviruses in hospital-related AGE has not been well-documented in the U. S. We estimated the population incidence of community- acquired outpatient and inpatient norovirus AGE encounters, as well as hospital-acquired inpatient norovirus AGE among inpatients at four Veterans Affairs (VA) Medical Centers (VAMCs). Fifty (4%) of 1,160 stool specimens collected ≤7 days from symptom onset tested positive for norovirus. During a one year period, the estimated incidence of outpatient, community- and hospital-acquired inpatient norovirus AGE was 188 cases, 11 cases, and 54 cases/ 100,000 patients, respectively. This study demonstrates the incidence of outpatient and community- and hospital-acquired inpatient norovirus AGE among the VA population seeking care at these four VAMCs.

Worldwide, noroviruses are a leading cause of gastroenteritis. They can be transmitted from person to person directly or indirectly through contaminated food, water, or environments. To estimate the proportion of foodborne infections caused by noroviruses on a global scale, we used norovirus transmission and genotyping information from multiple international outbreak surveillance systems (Noronet, CaliciNet, EpiSurv) and from a systematic review of peer-reviewed literature. The proportion of outbreaks caused by food was determined by genotype and/or genogroup. Analysis resulted in the following final global profiles: foodborne transmission is attributed to 10% (range 9%%-11%) of all genotype GII.4 outbreaks, 27% (25%-30%) of outbreaks caused by all other single genotypes, and 37% (24%%-52%) of outbreaks caused by mixtures of GII.4 and other noroviruses. When these profiles are applied to global outbreak surveillance data, results indicate that ≈14% of all norovirus outbreaks are attributed to food.

The pathogenicity of norovirus is definitively established. However, norovirus is frequently detected in the stool of healthy individuals. To gain understanding of the apparent high prevalence of asymptomatic infection, we analyzed a dynamic transmission model of norovirus infection, disease, and immunity. We simulated norovirus epidemiology in low- and high-transmission settings by varying the basic reproduction number (R0). We predicted annual disease incidence values in children aged 0-4 years of 25% with a low R0 and 29% with a high R0. However, the point prevalence of asymptomatic infection rose sharply from 3% to 48% from the low to high R0 settings. Among older children and adults, the models projected that incidence of disease would rise from 6% to 16% from the low to high R0 settings, whereas asymptomatic infection prevalence was lower in this age group. Asymptomatic prevalence of norovirus can change dramatically with small changes in R0. The ratio of prevalence in cases to controls could be high in a developed country and close to or even less than 1 in a high-exposure setting, despite similar disease incidence. These findings highlight an important limitation of case-control studies for pathogens for which there is suboptimal diagnostic specificity.

The duration of immunity to norovirus (NoV) gastroenteritis has been believed to be from 6 months to 2 years. However, several observations are inconsistent with this short period. To gain better estimates of the duration of immunity to NoV, we developed a mathematical model of community NoV transmission. The model was parameterized from the literature and also fit to age-specific incidence data from England and Wales by using maximum likelihood. We developed several scenarios to determine the effect of unknowns regarding transmission and immunity on estimates of the duration of immunity. In the various models, duration of immunity to NoV gastroenteritis was estimated at 4.1 (95% CI 3.2-5.1) to 8.7 (95% CI 6.8-11.3) years. Moreover, we calculated that children (<5 years) are much more infectious than older children and adults. If a vaccine can achieve protection for duration of natural immunity indicated by our results, its potential health and economic benefits could be substantial.

In October 2009, a new genogroup II, type 4 (GII.4) norovirus variant was identified in the United States. We collected norovirus outbreak data from 30 states to assess whether this new strain was associated with increased acute gastroenteritis activity. No increase in norovirus outbreaks was observed during the 2009-2010 winter.

Approximately 179 million cases of acute gastroenteritis (AGE) occur annually in the United States. However, lack of routine clinical testing for viruses limits understanding of their role among persons seeking medical care. Fecal specimens submitted for routine bacterial culture through a health maintenance organization in Georgia, USA, were tested with molecular diagnostic assays for norovirus, rotavirus, astrovirus, sapovirus, and adenovirus. Incidence was estimated by using national health care utilization rates. Routine clinical diagnostics identified a pathogen in 42 (7.3%) of 572 specimens; inclusion of molecular viral testing increased pathogen detection to 15.7%. Community AGE incidence was 41,000 cases/100,000 person-years and outpatient incidence was 5,400/100,000 person-years. Norovirus was the most common pathogen, accounting for 6,500 (16%) and 640 (12%) per 100,000 person-years of community and outpatient AGE episodes, respectively. This study demonstrates that noroviruses are leading causes of AGE among persons seeking medical care.

Background: Diarrhea remains an important cause of morbidity, but until the mid 1990s, hospital admissions for diarrhea in the US adult population were declining. We aimed to describe recent trends in gastroenteritis hospitalizations and to determine the contribution of norovirus., Methods: We analyzed all gastroenteritis-associated hospital discharges during 1996-2007 from a nationally representative data set of hospital inpatient stays. Annual rates of discharges by age were calculated. Time-series regression models were fitted using cause-specified discharges as explanatory variables; model residuals were analyzed to estimate norovirus- and rotavirus-associated discharges. We then calculated the annual hospital charges for norovirus-associated discharges., Results: Sixty-nine percent of all gastroenteritis discharges were cause-unspecified and rates increased by ≥ 50% in all adult and elderly age groups (≥ 18 years of age) from 1996 through 2007. We estimate an annual mean of 71,000 norovirus-associated hospitalizations, costing $493 million per year, with surges to nearly 110,000 hospitalizations per year in epidemic seasons. We also estimate 24,000 rotavirus hospitalizations annually among individuals aged ≥ 5 years., Conclusions: Gastroenteritis hospitalizations are increasing, and we estimate that norovirus is the cause of 10% of cause-unspecified and 7% of all-cause gastroenteritis discharges. Norovirus should be routinely considered as a cause of gastroenteritis hospitalization.

Existing estimates of the incidence of infectious intestinal disease (IID) caused by norovirus are based on electron microscopy or reverse transcription-polymerase chain reaction (RT-PCR). Neither method accurately represents norovirus disease burden: Electron microscopy has poor diagnostic sensitivity, and RT-PCR has poor diagnostic specificity. In this study, viral load measurements were used to identify cases of norovirus-associated IID and to produce new incidence estimates for England. IID cases were ascertained in the Study of Infectious Intestinal Disease in England (1993-1996), and stool specimens were tested by semiquantitative real-time RT-PCR for norovirus. The age-adjusted community incidence of norovirus-associated IID was 4.5/100 person-years (95% credibility interval: 3.8, 5.2), equating to 2 million episodes/year. Among children aged less than 5 years, the community incidence was 21.4/100 person-years (95% credibility interval: 15.9, 27.7), and the incidence of consultations to general practitioners for norovirus-associated IID was 3.2/100 person-years (95% credibility interval: 2.6, 3.8), with 100,000 children visiting their general practitioner for norovirus-associated IID each year. Norovirus is the most common cause of IID in the community in England and is responsible for a similar number of pediatric primary care consultations as rotavirus.

Norovirus generally causes a mild illness in the community. However, modeling routine hospital admission statistics, we estimate that approximately 3000 norovirus admissions to English hospitals occur per year, accounting for 0.3% and 0.1% of emergency admissions among elderly and adult patients, respectively, at times of peak activity. These admissions pose a risk for subsequent nosocomial infection outbreaks.

Unlabelled: Norovirus, the most commonly identified cause of both sporadic cases and outbreaks of infectious diarrhoea in developed countries, exhibits a complex epidemiology and has a strong wintertime seasonality. Viral populations are dynamic and evolve under positive selection pressure., Methods: Time series-adapted Poisson regression models were fitted to daily counts of laboratory reports of norovirus in England and Wales from 1993 to 2006., Findings: Inverse linear associations with daily temperature over the previous seven weeks (rate ratio (RR) = 0.85; 95% CI: 0.83 to 0.86 for every 1 degrees C increase) and relative humidity over the previous five weeks (RR = 0.980; 95% CI: 0.973 to 0.987 for every 1% increase) were found, with temperature having a greater overall effect. The emergence of new norovirus variants (RR = 1.16; 95% CI: 1.10 to 1.22) and low population immunity were also associated with heightened norovirus activity. Temperature and humidity, which may be localised, had highly consistent effects in each region of England and Wales., Conclusions: These results point to a complex interplay between host, viral and climatic factors driving norovirus epidemic patterns. Increases in norovirus are associated with cold, dry temperature, low population immunity and the emergence of novel genogroup 2 type 4 antigenic variants.

Background: Reverse transcription-polymerase chain reaction (RT-PCR) is the main method for laboratory diagnosis of norovirus-associated infectious intestinal disease (IID). However, up to 16% of healthy individuals in the community, with no recent history of IID, may be RT-PCR positive; so it is unclear whether norovirus is actually the cause of illness in an IID case when they are RT-PCR positive. It is important to identify the pathogen causing illness in sporadic IID cases, for clinical management and for community based incidence studies. The aim of this study was to investigate how faecal viral load can be used to determine when norovirus is the most likely cause of illness in an IID case., Methods: Real-time RT-PCR was used to determine the viral load in faecal specimens collected from 589 IID cases and 159 healthy controls, who were infected with genogroup II noroviruses. Cycle threshold (Ct) values from the real-time RT-PCR were used as a proxy measure of viral load. Receiver-operating characteristic (ROC) analysis was used to identify a cut-off in viral load for attributing illness to norovirus in IID cases., Results: One hundred and sixty-nine IID cases and 159 controls met the inclusion criteria for the ROC analysis. The optimal Ct value cut-off for attributing IID to norovirus was 31. The same cut-off was selected when using healthy controls, or IID cases who were positive by culture for bacterial pathogens, as the reference negative group. This alternative reference negative group can be identified amongst specimens routinely received in clinical virology laboratories., Conclusion: We demonstrated that ROC analysis can be used to select a cut-off for a norovirus real time RT-PCR assay, to aid clinical interpretation and diagnose when norovirus is the cause of IID. Specimens routinely received for diagnosis in clinical virology laboratories can be used to select an appropriate cut-off. Individual laboratories can use this method to define in-house cut-offs for their assays, to provide the best possible diagnostic service to clinicians and public health workers. Other clinical and epidemiological information should also be considered for patients with Ct values close to the cut-off, for the most accurate diagnosis of IID aetiology.

The number of deaths in England and Wales associated with gastrointestinal pathogens, norovirus in particular, in persons >or=65 years was estimated for 2001-2006. Regression analysis was used to model monthly counts of gastrointestinal pathogens in fecal samples from infected patients against monthly counts of deaths from infectious and noninfectious intestinal diseases. Data came from the Office of National Statistics (death registrations from local registrars) and from the Health Protection Agency (laboratory results). Model results suggest that 20% (13.3%-26.8%) of deaths in persons >or=65 years of age caused by infectious intestinal disease other than Clostridium difficile were associated with norovirus infection in this period and that 13% (7.5%-18.5%) of deaths caused by noninfectious intestinal disease were associated with norovirus. An estimated 80 deaths each year in this age group may be associated with norovirus infection.

Background: Noroviruses are highly infectious pathogens that cause gastroenteritis in the community and in semi-closed institutions such as hospitals. During outbreaks, multiple units within a hospital are often affected, and a major question for control programs is: are the affected units part of the same outbreak or are they unrelated transmission events? In practice, investigators often assume a transmission link based on epidemiological observations, rather than a systematic approach to tracing transmission.Here, we present a combined molecular and statistical method for assessing:1) whether observed clusters provide evidence of local transmission and2) the probability that anecdotally|linked outbreaks truly shared a transmission event., Methods: 76 healthcare associated outbreaks were observed in an active and prospective surveillance scheme of 15 hospitals in the county of Avon, England from April 2002 to March 2003. Viral RNA from 64 out of 76 specimens from distinct outbreaks was amplified by reverse transcription-PCR and was sequenced in the polymerase (ORF 1) and capsid (ORF 2) regions. The genetic diversity, at the nucleotide level, was analysed in relation to the epidemiological patterns., Results: Two out of four genetic and epidemiological clusters of outbreaks were unlikely to have occurred by chance alone, thus suggesting local transmission. There was anecdotal epidemiological evidence of a transmission link among 5 outbreaks pairs. By combining this epidemiological observation with viral sequence data, the evidence of a link remained convincing in 3 of these pairs. These results are sensitive to prior beliefs of the strength of epidemiological evidence especially when the outbreak strains are common in the background population., Conclusion: The evidence suggests that transmission between hospitals units does occur. Using the proposed criteria, certain hypothesized transmission links between outbreaks were supported while others were refuted. The combined molecular/epidemiologic approach presented here could be applied to other viral populations and potentially to other pathogens for a more thorough view of transmission.

Healthcare-associated outbreaks of gastroenteritis are an increasingly recognized problem, but detailed knowledge of the epidemiology of these events is lacking. We actively monitored three hospital systems in England for outbreaks of gastroenteritis in 2002 to 2003. A total of 2,154 patients (2.21 cases/1,000-hospital-days) and 1,360 healthcare staff (0.47 cases/1,000-hospital-days) were affected in 227 unit outbreaks (1.33 outbreaks/unit-year). Norovirus, detected in 63% of outbreaks, was the predominant etiologic agent. Restricting new admissions to affected units resulted in 5,443 lost bed-days. The cost of bed-days lost plus staff absence was calculated to be 635,000 pounds sterling (US. 1.01 million dollars) per 1,000 beds. By our extrapolation, gastroenteritis outbreaks likely cost the English National Health Service 115 million pounds sterling (US 184 million dollars) in 2002 to 2003. Outbreaks were contained faster (7.9 vs. 15.4 days, p = 0.0023) when units were rapidly closed to new admissions (<4 days). Implementing control measures rapidly may be effective in controlling outbreaks.

Noroviruses are generally believed to cause relatively mild gastroenteritis of short duration in otherwise healthy adults. However, outbreaks in health care settings are common and affect vulnerable populations. During 2002-2003, a total of 4 major hospitals, 11 community hospitals, and 135 nursing homes in the county of Avon, England, were prospectively monitored for outbreaks of gastroenteritis. For 482 hospital staff, 166 nursing home staff, and 266 nursing home residents, the median duration of norovirus gastroenteritis was 2 days, with 75% achieving complete recovery within 3 days. The median duration of norovirus gastroenteritis for 730 hospital patients was 3 days (75% of the patients achieved complete recovery within 5 days), which was significantly longer than that for all other groups (P<.001). Therefore, infection in hospitalized persons may be more severe than that in other groups in the community at large. This increased duration of acute illness should be considered when implementing measures to prevent transmission in hospital settings.

Background: Noroviruses are the most common cause of gastroenteritis outbreaks in industrialised countries. Gastroenteritis caused by Norovirus infection has been described as a highly seasonal syndrome, often referred to as "winter vomiting disease"., Methods: The Public Health Laboratory Service Communicable Disease Surveillance Centre has systematically collected reports of laboratory confirmed cases of Norovirus-gastroenteritis since 1995. We analysed these data for annual and seasonal trends and age distribution., Results: A mid-summer peak in reported cases of Norovirus was observed in 2002, unlike all six previous years when there was a marked summer decline. Total reports from 2002 have also been higher than all previous years. From the first 10 months of 2002, a total of 3029 Norovirus diagnoses were reported compared the previous peak in 1996 of 2437 diagnoses for the whole 12-month period. The increase in 2002 was most marked in the 65 and older age group., Conclusion: This surveillance data challenges the view that Noroviruses infections exclusively have wintertime seasonality.

To gain understanding of surveillance and epidemiology of viral gastroenteritis outbreaks in Europe, we compiled data from 10 surveillance systems in the Foodborne Viruses in Europe network. Established surveillance systems found Norovirus to be responsible for >85% (N =3,714) of all nonbacterial outbreaks of gastroenteritis reported from 1995 to 2000. However, the absolute number and population-based rates of viral gastroenteritis outbreaks differed markedly among European surveillance systems. A wide range of estimates of the importance of foodborne transmission were also found. We review these differences within the context of the sources of outbreak surveillance information, clinical definitions, and structures of the outbreak surveillance systems.

Background While prior studies have suggested a role for norovirus gastroenteritis in contributing to severe morbidity and mortality, the importance of norovirus as a causal pathogen for hospitalization and mortality remains poorly understood. We estimated the effect of laboratory-confirmed norovirus infection on hospitalization and mortality among a national cohort of veterans who sought care within the Veterans Affairs health care system. Methods We analyzed electronic health record data from a cohort study of adults who were tested for norovirus within the Veterans Affairs system between 1 January 2010 and 31 December 2018. Adjusted risk ratios (aRRs) for hospitalization and mortality were estimated using log-binomial regression models, adjusting for age, Clostridioides difficile , underlying medical conditions, and nursing home residence. Results In total, 23 196 veterans had 25 668 stool samples tested for norovirus; 2156 samples (8.4%) tested positive. Testing positive for norovirus infection, compared with testing negative, was associated with a slight increased risk of hospitalization (aRR, 1.13 [95% confidence interval, 1.06–1.21]) and a significant increased risk of mortality within 3 days after the norovirus test (2.14 [1.10–4.14]). The mortality aRR within 1 week and 1 month were reduced to 1.40 (95% confidence interval,.84–2.34) and 0.97 (.70–1.35), respectively. Conclusions Older veterans with multiple comorbid conditions were at a slight increased risk of hospitalization and significant increased risk of mortality in the 3 days after a norovirus-positive test, compared with those testing negative. Clinicians should be aware of these risks and can use these data to inform clinical management for veterans with norovirus. [ABSTRACT FROM AUTHOR]

The article discusses a study which examines the resistance and susceptibility of humans to norovirus infection, which is recognized as the leading cause of gastroenteritis in children and adults. Topics include the intermediary factors that affect susceptibility including secretor status affecting gut microbiota composition, the interaction of noroviruses with secretor status and the diverse secretor and non-secretor human histo-blood group antigens that increased susceptibility.

Although recognized as the leading cause of epidemic acute gastroenteritis across all age groups, norovirus has remained poorly characterized with respect to its endemic disease incidence. Use of different methods, including attributable proportion extrapolation, population-based surveillance, and indirect modeling, in several recent studies has considerably improved norovirus disease incidence estimates for the United States. Norovirus causes an average of 570--800 deaths, 56,000--71,000 hospitalizations, 400,000 emergency department visits, 1.7--1.9 million outpatient visits, and 19--21 million total illnesses per year. Persons ≥65 years of age are at greatest risk for norovirus-associated death, and children <5 years of age have the highest rates of norovirus-associated medical care visits. Endemic norovirus disease occurs year round but exhibits a pronounced winter peak and increases by ≤50% during years in which pandemic strains emerge. These findings support continued development and targeting of appropriate interventions, including vaccines, for norovirus disease. [ABSTRACT FROM AUTHOR]

Noroviruses are a common cause of gastroenteritis worldwide, but outbreaks appear to be more common in industrialized countries than in developing countries, possibly reflecting differences in exposure and immunity. In this study, age-stratified sera from India and UK populations were analysed for the presence of norovirus-genogroup II specific IgG by a time resolved immunofluorescence assay and relative levels of antibodies in the two populations were compared. Antibody levels were higher among all age groups in India than in UK and increased with age in India, whereas in the UK, levels of antibody decreased in adulthood. These results indicate different patterns of exposure to noroviruses in the two countries. [ABSTRACT FROM AUTHOR]

Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of norovirus outbreaks are caused by genogroup II.4 (GII.4). Novel GII.4 strains emerge every 2 to 4 years and replace older variants as the dominant norovirus. Novel variants emerge through a combination of recombination, genetic drift, and selection driven by population immunity, but the exact mechanism of how or where is not known. We detected two previously unknown novel GII.4 variants, termed GII.4 UNK1 and GII.4 UNK2, and a diverse norovirus population in fecal specimens from immunocompromised individuals with diarrhea after they had undergone bone marrow transplantation. We hypothesized that immunocompromised individuals can serve as reservoirs for novel norovirus variants. To test our hypothesis, metagenomic analysis of viral RNA populations was combined with a full-genome bioinformatic analysis of publicly available GII.4 norovirus sequences from 1974 to 2014 to identify converging sites. Variable sites were proportionally more likely to be within two amino acids (P<0.05) of positively selected sites. Further analysis using a hypergeometric distribution indicated that polymorphic site distribution was random and its proximity to positively selected sites was dependent on the size of the norovirus genome and the number of positively selected sites. In conclusion, random mutations may have a positive impact on driving norovirus evolution, and immunocompromised individuals could serve as potential reservoirs for novel GII.4 strains. [ABSTRACT FROM AUTHOR]