European data sources for computing burden of (potential) vaccine-preventable diseases in ageing adults.

BACKGROUND: To guide decision-making on immunisation programmes for ageing adults in Europe, one of the aims of the Vaccines and InfecTious diseases in the Ageing popuLation (IMI2-VITAL) project is to assess the burden of disease (BoD) of (potentially) vaccine-preventable diseases ((P)VPD). We aimed to identify the available data sources to calculate the BoD of (P)VPD in participating VITAL countries and to pinpoint data gaps. Based on epidemiological criteria and vaccine availability, we prioritized (P) VPD caused by Extra-intestinal pathogenic Escherichia coli (ExPEC), norovirus, respiratory syncytial virus, Staphylococcus aureus, and pneumococcal pneumonia. METHODS: We conducted a survey on available data (e.g. incidence, mortality, disability-adjusted life years (DALY), quality-adjusted life years (QALY), sequelae, antimicrobial resistance (AMR), etc.) among national experts from European countries, and carried out five pathogen-specific literature reviews by searching MEDLINE for peer-reviewed publications published between 2009 and 2019. RESULTS: Morbidity and mortality data were generally available for all five diseases, while summary BoD estimates were mostly lacking. Available data were not always stratified by age and risk group, which is especially important when calculating BoD for ageing adults. AMR data were available in several countries for S. aureus and ExPEC. CONCLUSION: This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD.

Epidemiologic challenges in norovirus vaccine development.

Norovirus is the leading cause of acute gastroenteritis (AGE) worldwide. In the United States norovirus is estimated to cause 19-21 million illnesses, 1.7-1.9 million outpatient visits, 56,000-71,000 hospitalizations, and 570-800 deaths annually. Through direct costs and loss of productivity, norovirus disease cost the US economy more than $5.5 billion annually. Due to the lack of available therapies to treat norovirus infections and their highly infectious nature, preventing norovirus illness through vaccination is an appealing strategy. Currently, several norovirus vaccines are in development, including five vaccines in preclinical trials, an oral monovalent vaccine (Vaxart, Inc.) that recently completed a phase IB clinical trial, and a bivalent intramuscular vaccine (Takeda Pharmaceutical Company Limited) in a phase IIB clinical trial. However, no norovirus vaccines are currently available on the market. In this commentary we aim to describe some of the barriers faced in norovirus vaccine development, particularly focusing on vaccine effectiveness and defining the target population.

Knowledge of Norovirus and Attitudes toward a Potential Norovirus Vaccine in Rural Guatemala: A Cross-Sectional Exploratory Survey.

Given limited data on norovirus vaccine acceptance, we performed an exploratory survey in a rural Guatemalan community on knowledge, interest, and willingness to pay (WTP) for a norovirus vaccine. Cluster-randomized households with children aged 6 weeks to 17 years were enrolled into one of two norovirus surveillance studies: 1) a prospective cohort (N = 207 households) and 2) two separate, community-based, cross-sectional surveys (N = 420 households). After completion of the surveillance study, vaccine surveys were completed by 564 (90%) of 627 households. Most households correctly answered questions regarding norovirus symptoms and transmission; 97% indicated interest in a hypothetical norovirus vaccine. Households with higher education had greater WTP for a vaccine (prevalence ratios = 2.2, 95% confidence interval: 1.2-3.1) and households with lower WTP were more likely to use pharmacies, the Ministry of Health, and radios for health care and information. These results suggest that a future norovirus vaccination program could be acceptable and feasible even in rural areas.

The incidence of medically-attended norovirus gastro-enteritis in Japan: Modelling using a medical care insurance claims database.

BACKGROUND: The burden of medically-attended acute gastro-enteritis (MA-AGE) that can be attributed to norovirus is not well established in Japan. Using a nationwide database of medical care insurance claims, we estimated the incidence of medically-attended norovirus-attributable gastroenteritis (MA-NGE) in Japan. METHODS: The incidences of MA-NGE outpatient consultations or hospitalization in Japan were modelled on seasonal patterns of MA-AGE for unspecified causes derived from the Japan Medical Data Center (JMDC) database for the period July 2007 to June 2015. RESULTS: Mean age-adjusted annual incidence rates (per 10,000 person-years) of MA-NGE associated with outpatient care or hospitalization were 389 (95% CI 269-558) and 13 (95% CI 9-20), respectively. Highest rates were in children under 5 years of age: 1,569 (95% CI 1,325-1,792) for outpatient consultations and 48 (95% CI 39-56) for hospitalizations. Of all gastroenteritis episodes associated with outpatient care or hospitalization, 29% and 31% were attributed to norovirus, respectively. Norovirus was estimated to be responsible for 4,964,000 outpatient visits (95% CI 3,435,000-7,123,000) and 171,000 hospitalizations (95% CI 110,000-251,000) per year across Japan. CONCLUSIONS: Incidence rates of MA-AGE are high in Japan, and norovirus-attributable disease is at least as high as in some other developed countries.

Estimating the Hospital Burden of Norovirus-Associated Gastroenteritis in England and Its Opportunity Costs for Nonadmitted Patients.

Background: Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With several treatments and vaccines against norovirus in development, quantifying the expected economic burden is timely. Methods: The number of inpatients with norovirus-associated gastroenteritis in England was modeled using infectious and noninfectious gastrointestinal Hospital Episode Statistics codes and laboratory reports of gastrointestinal pathogens collected at Public Health England. The excess length of stay from norovirus was estimated with a multistate model and local outbreak data. Unoccupied bed-days and staff absences were estimated from national outbreak surveillance. The burden was valued conventionally using accounting expenditures and wages, which we contrasted to the opportunity costs from forgone patients using a novel methodology. Results: Between July 2013 and June 2016, 17.7% (95% confidence interval [CI], 15.6%‒21.6%) of primary and 23.8% (95% CI, 20.6%‒29.9%) of secondary gastrointestinal diagnoses were norovirus attributable. Annually, the estimated median 290000 (interquartile range, 282000‒297000) occupied and unoccupied bed-days used for norovirus displaced 57800 patients. Conventional costs for the National Health Service reached £107.6 million; the economic burden approximated to £297.7 million and a loss of 6300 quality-adjusted life-years annually. Conclusions: In England, norovirus is now the second-largest contributor of the gastrointestinal hospital burden. With the projected impact being greater than previously estimated, improved capture of relevant opportunity costs seems imperative for diseases such as norovirus.

Human norovirus transmission and evolution in a changing world.

Norovirus infections are a major cause of gastroenteritis, and outbreaks occur frequently. Several factors are currently increasing the challenge posed by norovirus infections to global health, notably the increasing number of infections in immunocompromised individuals, who are more susceptible to disease, and the globalization of the food industry, which enables large norovirus outbreaks to occur on an international scale. Furthermore, the rapid rate of the genetic and antigenic evolution of circulating noroviruses complicates the development of vaccines and therapies that are required to counter these challenges. In this Review, we describe recent advances in the study of the transmission, pathogenesis and evolution of human noroviruses, and consider the ongoing risk of norovirus outbreaks, together with the future prospects for therapeutics, in a rapidly changing world.

Global Economic Burden of Norovirus Gastroenteritis.

BACKGROUND: Despite accounting for approximately one fifth of all acute gastroenteritis illnesses, norovirus has received comparatively less attention than other infectious pathogens. With several candidate vaccines under development, characterizing the global economic burden of norovirus could help funders, policy makers, public health officials, and product developers determine how much attention and resources to allocate to advancing these technologies to prevent and control norovirus. METHODS: We developed a computational simulation model to estimate the economic burden of norovirus in every country/area (233 total) stratified by WHO region and globally, from the health system and societal perspectives. We considered direct costs of illness (e.g., clinic visits and hospitalization) and productivity losses. RESULTS: Globally, norovirus resulted in a total of $4.2 billion (95% UI: $3.2-5.7 billion) in direct health system costs and $60.3 billion (95% UI: $44.4-83.4 billion) in societal costs per year. Disease amongst children <5 years cost society $39.8 billion, compared to $20.4 billion for all other age groups combined. Costs per norovirus illness varied by both region and age and was highest among adults ≥55 years. Productivity losses represented 84-99% of total costs varying by region. While low and middle income countries and high income countries had similar disease incidence (10,148 vs. 9,935 illness per 100,000 persons), high income countries generated 62% of global health system costs. In sensitivity analysis, the probability of hospitalization had the largest impact on health system cost estimates ($2.8 billion globally, assuming no hospitalization costs), while the probability of missing productive days had the largest impact on societal cost estimates ($35.9 billion globally, with a 25% probability of missing productive days). CONCLUSIONS: The total economic burden is greatest in young children but the highest cost per illness is among older age groups in some regions. These large costs overwhelmingly are from productivity losses resulting from acute illness. Low, middle, and high income countries all have a considerable economic burden, suggesting that norovirus gastroenteritis is a truly global economic problem. Our findings can help identify which age group(s) and/or geographic regions may benefit the most from interventions.

Lessons learned from a prolonged and costly norovirus outbreak at a Scottish medicine of the elderly hospital: case study.

BACKGROUND: Norovirus outbreaks are a major burden for healthcare facilities globally. AIM: Lessons learned to inform an action plan to improve facilities as well as responses to norovirus within the medicine of the elderly (MoE) hospital as well as other NHS (National Health Service) Lothian facilities. METHODS: This study investigated the impact of a prolonged outbreak at an MoE hospital in one of the 14 Scottish health boards between February and March 2013. FINDINGS: In all, 143 patients (14.80 cases per 1000 inpatient bed-days) and 30 healthcare staff (3.10 cases per 1000 inpatient bed-days) were affected clinically and 63 patients were confirmed virologically. Restricting new admissions to affected units resulted in 1192 lost bed-days. The cost due to lost bed-days in addition to staff absence and management of the outbreak was estimated at £341,534 for this incident alone. At certain points during the outbreak, the whole facility was closed with resulting major impact on the health board's acute care hospitals. CONCLUSION: Due to the outbreak, new measures were implemented for the first time within NHS Lothian that included floor-by-floor (instead of individual) ward closures, enhanced cleaning with chlorine-based products throughout the hospital, reduction in bed capacity with enhanced bed-spacing and interruption to direct admissions from the Board's general practice surgeries, and temporary suspension of visitors to affected areas. Together with regular communication to staff, patients, relatives, and the public throughout the outbreak and good engagement of staff groups in management of the incident, the outbreak was gradually brought under control.

Economic Cost of Campylobacter, Norovirus and Rotavirus Disease in the United Kingdom.

OBJECTIVES: To estimate the annual cost to patients, the health service and society of infectious intestinal disease (IID) from Campylobacter, norovirus and rotavirus. DESIGN: Secondary data analysis. SETTING: The United Kingdom population, 2008-9. MAIN OUTCOME MEASURES: Cases and frequency of health services usage due to these three pathogens; associated healthcare costs; direct, out-of-pocket expenses; indirect costs to patients and caregivers. RESULTS: The median estimated costs to patients and the health service at 2008-9 prices were: Campylobacter £50 million (95% CI: £33m-£75m), norovirus £81 million (95% CI: £63m-£106m), rotavirus £25m (95% CI: £18m-£35m). The costs per case were approximately £30 for norovirus and rotavirus, and £85 for Campylobacter. This was mostly borne by patients and caregivers through lost income or out-of-pocket expenditure. The cost of Campylobacter-related Guillain-Barré syndrome hospitalisation was £1.26 million (95% CI: £0.4m-£4.2m). CONCLUSIONS: Norovirus causes greater economic burden than Campylobacter and rotavirus combined. Efforts to control IID must prioritise norovirus. For Campylobacter, estimated costs should be considered in the context of expenditure to control this pathogen in agriculture, food production and retail. Our estimates, prior to routine rotavirus immunisation in the UK, provide a baseline vaccine cost-effectiveness analyses.

Mapping Investments and Published Outputs in Norovirus Research: A Systematic Analysis of Research Funded in the United States and United Kingdom During 1997-2013.

BACKGROUND: Norovirus accounts for a considerable portion of the global disease burden. Mapping national or international investments relating to norovirus research is limited. METHODS: We analyzed the focus and type of norovirus research funding awarded to institutions in the United States and United Kingdom during 1997-2013. Data were obtained from key public and philanthropic funders across both countries, and norovirus-related research was identified from study titles and abstracts. Included studies were further categorized by the type of scientific investigation, and awards related to vaccine, diagnostic, and therapeutic research were identified. Norovirus publication trends are also described using data from Scopus. RESULTS: In total, US and United Kingdom funding investment for norovirus research was £97.6 million across 349 awards; 326 awards (amount, £84.9 million) were received by US institutions, and 23 awards (£12.6 million) were received by United Kingdom institutions. Combined, £81.2 million of the funding (83.2%) was for preclinical research, and £16.4 million (16.8%) was for translational science. Investments increased from £1.7 million in 1997 to £11.8 million in 2013. Publication trends showed a consistent temporal increase from 48 in 1997 to 182 in 2013. CONCLUSIONS: Despite increases over time, trends in US and United Kingdom funding for norovirus research clearly demonstrate insufficient translational research and limited investment in diagnostics, therapeutics, or vaccine research.

Economic costs of outbreaks of acute viral gastroenteritis due to norovirus in Catalonia (Spain), 2010-2011.

BACKGROUND: To determine the direct and indirect costs of outbreaks of acute viral gastroenteritis (AVG) due to norovirus in closed institutions (hospitals, social health centers or nursing homes) and the community in Catalonia in 2010-11. METHODS: Information on outbreaks were gathered from the reports made by epidemiological surveillance units. Direct costs (medical visits, hospital stays, drug treatment, sample processing, transport, diagnostic tests, monitoring and control of the outbreaks investigated) and indirect costs (lost productivity due to work absenteeism, caregivers time and working hours lost due to medical visits) were calculated. RESULTS: Twenty-seven outbreaks affecting 816 people in closed institutions and 74 outbreaks affecting 1,940 people in the community were detected. The direct and indirect costs of outbreaks were € 131,997.36 (€ 4,888.79 per outbreak) in closed institutions and € 260,557.16 (€ 3,521.04 per outbreak) in community outbreaks. The cost per case was € 161.76 in outbreaks in closed institutions and € 134.31 in community outbreaks. The main costs were surveillance unit monitoring (€ 116,652.93), laboratory diagnoses (€ 119,950.95), transport of samples (€ 69,970.90), medical visits (€ 25,250.50) and hospitalization (€ 13,400.00). CONCLUSIONS: The cost of outbreaks of acute viral gastroenteritis due to norovirus obtained in this study was influenced by the number of people affected and the severity of the outbreak, which determined hospitalizations and work absenteeism. Urgent reporting of outbreaks would allow the implementation of control measures that could reduce the numbers affected and the duration of the illness and thus the costs derived from them.

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.

Cost-effectiveness of norovirus vaccination in children in Peru.

BACKGROUND: With candidate norovirus (NV) vaccines in a rapid phase of development, assessment of the potential economic value of vaccine implementation will be necessary to aid health officials in vaccine implementation decisions. To date, no evaluations have been performed to evaluate the benefit of adopting NV vaccines for use in the childhood immunization programs of low- and middle-income countries. METHODS: We used a Markov decision model to evaluate the cost-effectiveness of adding a two-dose NV vaccine to Peru's routine childhood immunization schedule using two recent estimates of NV incidence, one for a peri-urban region and one for a jungle region of the country. RESULTS: Using the peri-urban NV incidence estimate, the annual cost of vaccination would be $13.0 million, offset by $2.6 million in treatment savings. Overall, this would result in 473 total DALYs averted; 526,245 diarrhea cases averted;153,735 outpatient visits averted; and 414 hospitalizations averted between birth and the fifth year of life. The incremental cost-effectiveness ratio would be $21,415 per DALY averted; $19.86 per diarrhea case; $68.23 per outpatient visit; and $26,298 per hospitalization. Using the higher jungle NV incidence rates provided a lower cost per DALY of $10,135. The incremental cost per DALY with per-urban NV incidence is greater than three times the 2012 GDP per capita of Peru but the estimate drops below this threshold using the incidence from the jungle setting. In addition to the impact of incidence, sensitivity analysis showed that vaccine price and efficacy play a strong role in determining the level of cost-effectiveness. CONCLUSIONS: The introduction of a NV vaccine would prevent many healthcare outcomes in the Peru and potentially be cost-effective in scenarios with high NV incidence. The vaccine cost-effectiveness model could also be applied to the evaluation of NV vaccine cost-effectiveness in other countries. In resource-poor settings, where NV incidence rates are expected to be higher.

Cost-of-illness and disease burden of food-related pathogens in the Netherlands, 2011.

To inform risk management decisions on control and prevention of food-related disease, both the disease burden expressed in Disability Adjusted Life Years (DALY) and the cost-of-illness of food-related pathogens are estimated and presented. Disease burden of fourteen pathogens that can be transmitted by food, the environment, animals and humans was previously estimated by Havelaar et al. (2012). In this paper we complement these by cost-of-illness estimates. Together, these present a complete picture of the societal burden of food-related diseases. Using incidence estimates for 2011, community-acquired non-consulting cases, patients consulting their general practitioner, hospitalized patients and the incidence of sequelae and fatal cases, estimates were obtained for DALYs, direct healthcare costs (e.g. costs for doctor's fees, hospitalizations and medicines), direct non-healthcare costs (e.g. travel costs to and from the doctor), indirect non-healthcare costs (e.g. productivity loss, special education) and total costs. The updated disease burden for 2011 was equal to 13,940 DALY/year (undiscounted) or 12,650 DALY/year (discounted at 1.5%), and was of the same magnitude as previous estimates. At the population-level thermophilic Campylobacter spp., Toxoplasma gondii and rotavirus were associated with the highest disease burden. Perinatal listeriosis infection was associated with the highest DALY per symptomatic case. The total cost-of-illness in 2011 of fourteen food-related pathogens and associated sequelae was estimated at € 468 million/year, if undiscounted, and at € 416 million/year if discounted by 4%. Direct healthcare costs accounted for 24% of total costs, direct non-healthcare costs for 2% and indirect non-healthcare costs for 74% of total costs. At the population-level, norovirus had the highest total cost-of-illness in 2011 with € 106 million/year, followed by thermophilic Campylobacter spp. (€ 76 million/year) and rotavirus (€ 73 million/year). Cost-of-illness per infected case varied from € 150 for Clostridium perfringens intoxications to € 275,000 for perinatal listeriosis. Both incident cases and fatal cases are more strongly correlated with COI/year than with DALY/year. More than 40% of all cost-of-illness and DALYs can be attributed to food, in total € 168 million/year and 5,150 DALY/year for 2011. Beef, lamb, pork and poultry meat alone accounted for 39% of these costs. Products of animal origin accounted for € 86 million/year (or 51% of the costs attributed to food) and 3,320 DALY/year (or 64% of the disease burden attributed to food). Among the pathogens studied Staphylococcus aureus intoxications accounted for the highest share of costs attributed to food (€ 47.1 million/year), followed by Campylobacter spp. (€ 32.0 million/year) and norovirus (€ 17.7 million/year).

The burden of norovirus gastroenteritis: an important foodborne and healthcare-related infection.

Human norovirus (NoV) is now recognized as one of the most important causative agents of gastroenteritis in all age groups worldwide. During the course of NoV infection, symptoms are usually mild and disappear within 48 h after onset. The incidence of NoV infection is high, with hundreds of cases per 10 000 of the population, although the number of infections is still underestimated. Epidemiological surveys conducted in Europe and North America have shown that NoV infections constitute a major disease burden, especially for young children and the elderly, in whom NoV infection leads to high rates of hospitalization and mortality. NoV infections are also of concern in hospitals, where viral infections can be persistent in immunocompromised patients. Although the cost of NoV infection in the hospital community has not yet been clearly established, it appears that NoV infections could cost hundreds of thousands of euros in terms of unit closure, and NoV-related sickness in patients and health workers. Besides their clinical burden, NoVs, as foodborne pathogens, also cause to millions of dollars of losses for the healthcare system and the food industry. Recent estimates in the USA showed that, annually, NoV illness cost $2 billion and led to a loss of approximately 5000 quality-adjusted life-years, making NoV one of the top five pathogens causing enteric illnesses. The highest cost among 14 foodborne pathogens is also attributed to human NoV in The Netherlands. This accumulation of evidence underlines the enormous impact of NoV on populations.

Burden of acute gastroenteritis, norovirus and rotavirus in a managed care population.

This study assessed and described the episode rate, duration of illness, and health care utilization and costs associated with acute gastroenteritis (AGE), norovirus gastroenteritis (NVGE), and rotavirus gastroenteritis (RVGE) in physician office, emergency department (ED), and inpatient care settings in the United States (US). The retrospective analysis was conducted using an administrative insurance claims database (2006-2011). AGE episode rates were assessed using medical (ICD-9-CM) codes for AGE; whereas a previously published "indirect" method was used in assessing estimated episode rates of NVGE and RVGE. We calculated per-patient, per-episode and total costs incurred in three care settings for the three diseases over five seasons. For each season, we extrapolated the total economic burden associated with the diseases to the US population. The overall AGE episode rate in the physician office care setting declined by 15% during the study period; whereas the AGE episode rate remained stable in the inpatient care setting. AGE-related total costs (inflation-adjusted) per 100 000 plan members increased by 28% during the 2010-2011 season, compared with the 2006-2007 season ($832,849 vs. $1 068 116) primarily due to increase in AGE-related inpatient costs. On average, the duration of illness for NVGE and RVGE was 1 day longer than the duration of illness for AGE (mean: 2 days). Nationally, the average AGE-related estimated total cost was $3.88 billion; NVGE and RVGE each accounted for 7% of this total. The episodes of RVGE among pediatric populations have declined; however, NVGE, RVGE and AGE continue to pose a substantial burden among managed care enrollees. In conclusion, the study further reaffirms that RVGE has continued to decline in pediatric population post-launch of the rotavirus vaccination program and provides RVGE- and NVGE-related costs and utilization estimates which can serve as a resource for researchers and policy makers to conduct cost-effectiveness studies for prevention programs.

Systematic analysis of funding awarded for norovirus research to institutions in the United Kingdom, 1997-2010.

OBJECTIVES: Norovirus infections pose great economic and disease burden to health systems around the world. This study quantifies the investments in norovirus research awarded to UK institutions over a 14-year time period. DESIGN: A systematic analysis of public and philanthropic infectious disease research investments awarded to UK institutions between 1997 and 2010. PARTICIPANTS: None SETTING: UK institutions carrying out infectious disease research. MAIN OUTCOME MEASURES: Total funding for infectious disease research, total funding for norovirus research, position of norovirus research along the R&D value chain. RESULTS: The total dataset consisted of 6165 studies with sum funding of £2.6 billion. Twelve norovirus studies were identified with a total funding of £5.1 million, 0.2% of the total dataset. Of these, eight were categorized as pre-clinical, three as intervention studies and one as implementation research. Median funding was £200,620. CONCLUSIONS: Research funding for norovirus infections in the UK appears to be unacceptably low, given the burden of disease and disability produced by these infections. There is a clear need for new research initiatives along the R&D value chain: from pre-clinical through to implementation research, including trials to assess cost-effectiveness of infection control policies as well as clinical, public health and environmental interventions in hospitals, congregate settings and in the community.

Norovirus and medically attended gastroenteritis in U.S. children.

BACKGROUND: Cases of rotavirus-associated acute gastroenteritis have declined since the introduction of rotavirus vaccines, but the burden of norovirus-associated acute gastroenteritis in children remains to be assessed. METHODS: We conducted active surveillance for laboratory-confirmed cases of norovirus among children younger than 5 years of age with acute gastroenteritis in hospitals, emergency departments, and outpatient clinical settings. The children resided in one of three U.S. counties during the years 2009 and 2010. Fecal specimens were tested for norovirus and rotavirus. We calculated population-based rates of norovirus-associated acute gastroenteritis and reviewed billing records to determine medical costs; these data were extrapolated to the U.S. population of children younger than 5 years of age. RESULTS: Norovirus was detected in 21% of young children (278 of 1295) seeking medical attention for acute gastroenteritis in 2009 and 2010, with norovirus detected in 22% (165 of 742) in 2009 and 20% (113 of 553) in 2010 (P=0.43). The virus was also detected in 4% of healthy controls (19 of 493) in 2009. Rotavirus was identified in 12% of children with acute gastroenteritis (152 of 1295) in 2009 and 2010. The respective rates of hospitalization, emergency department visits, and outpatient visits for the norovirus were 8.6, 146.7, and 367.7 per 10,000 children younger than 5 years of age in 2009 and 5.8, 134.3, and 260.1 per 10,000 in 2010, with an estimated cost per episode of $3,918, $435, and $151, respectively, in 2009. Nationally, we estimate that the average numbers of annual hospitalizations, emergency department visits, and outpatient visits due to norovirus infection in 2009 and 2010 among U.S. children in this age group exceeded 14,000, 281,000, and 627,000, respectively, with more than $273 million in treatment costs each year. CONCLUSIONS: Since the introduction of rotavirus vaccines, norovirus has become the leading cause of medically attended acute gastroenteritis in U.S. children and is associated with nearly 1 million health care visits annually. (Funded by the Centers for Disease Control and Prevention.).

The potential economic value of a human norovirus vaccine for the United States.

Vaccines against human norovirus are currently under development. We developed a simulation model to determine their potential economic value. Vaccination prevented 100-6125 norovirus gastroenteritis cases per 10,000 vaccinees. Low vaccine cost (≤$50) garnered cost-savings and a more expensive vaccine led to costs per case averted comparable to other vaccines. In the US, vaccination could avert approximately 1.0-2.2 million cases (efficacy 50%, 12 month duration), costing an additional $400 million to $1.0 billion, but could save ≤$2.1 billion (48 month duration). Human norovirus vaccination can offer economic value while averting clinical outcomes, depending on price, efficacy, and protection duration.

Epidemiology and costs associated with norovirus outbreaks in NHS Lothian, Scotland 2007-2009.

Healthcare-associated gastroenteritis outbreaks are becoming more common and are recognized challenges in hospital and community settings. In Edinburgh [NHS (National Health Service) Lothian], all the hospitals and the community were actively monitored for outbreaks of gastroenteritis from September 2007 to June 2009. In total, 1732 patients and 599 healthcare staff were affected in 192 unit outbreaks. In the acute sector, 1368 patients (0.99 cases/1000 inpatient bed-days) and 406 healthcare staff (0.29 cases/1000 inpatient bed-days) were affected in 155 unit outbreaks (0.23 unit outbreaks/day). Noroviruses were detected in 142 outbreaks (74%); 50 were not laboratory confirmed but were presumed to be noroviruses on epidemiological grounds. The closure of affected units to new admissions resulted in the loss of 3678 bed-days. By extrapolation, lost bed-days and staff absence due to gastroenteritis outbreaks cost NHS Lothian £1.2 million for the two norovirus seasons. Outbreaks in which the affected unit was closed within the first three days of recognizing the index case were contained in a mean of six days, and outbreaks in units that were closed later persisted for a mean of seven days; this difference was not statistically significant. Rapid implementation of control measures was effective in the control of outbreaks.