Burden Of Norovirus Disease Research Articles

Vomiting as a Symptom and Transmission Risk in Norovirus Illness: Evidence from Human Challenge Studies.

BackgroundIn the US, noroviruses are estimated to cause 21 million cases annually with economic losses reaching $2 billion. Outbreak investigations frequently implicate vomiting as a major transmission risk. However, little is known about the characteristics of vomiting as a symptom or the amount of virus present in emesis.Methodology and Principal FindingsEmesis samples and symptomology data were obtained from previous norovirus human challenge studies with GI.1 Norwalk virus, GII.2 Snow Mountain virus, and a pilot study with GII.1 Hawaii virus. Viral titers in emesis were determined using strain-specific quantitative RT-PCR. In all four studies, vomiting was common with 40–100% of infected subjects vomiting at least once. However, only 45% of subjects with vomiting also had diarrhea. Most of the emesis samples had detectable virus and the mean viral titers were 8.0 x 105 and 3.9 x 104 genomic equivalent copies (GEC)/ml for GI and GII viruses, respectively (p = 0.02). Sample pH was correlated with GII.2 Snow Mountain virus detection.Conclusions and SignificanceHalf of all subjects with symptomatic infection experienced vomiting and the average subject shed 1.7 x 108 GEC in emesis. Unlike shedding through stool, vomiting is more likely to result in significant environmental contamination, leading to transmission through fomites and airborne droplets. This quantitative data will be critical for risk assessment studies to further understand norovirus transmission and develop effective control measures. The correlation between sample pH and virus detection is consistent with a single site of virus replication in the small intestine and stomach contents becoming contaminated by intestinal reflux. Additionally, the frequency of vomiting without concurrent diarrhea suggests that epidemiology studies that enroll subjects based on the presence of diarrhea may be significantly underestimating the true burden of norovirus disease.

Incidence of Norovirus and Other Viral Pathogens That Cause Acute Gastroenteritis (AGE) among Kaiser Permanente Member Populations in the United States, 2012-2013.

Noroviruses and other viral pathogens are increasingly recognized as frequent causes of acute gastroenteritis (AGE). However, few laboratory-based data are available on the incidence of AGE caused by viral pathogens in the U.S. This study examined stool specimens submitted for routine clinical diagnostics from patients enrolled in Kaiser Permanente (KP) health plans in metro Portland, OR, and the Maryland, District of Columbia, and northern Virginia geographic areas to estimate the incidence of viral enteropathogens in these populations. Over a one-year study period, participating laboratories randomly selected stools submitted for routine clinical diagnostics for inclusion in the study along with accompanying demographic and clinical data. Selected stools were tested for norovirus, rotavirus, sapovirus, and astrovirus using standardized real-time RT-PCR protocols. Each KP site provided administrative data which were used in conjunction with previously published data on healthcare utilization to extrapolate pathogen detection rates into population-based incidence rates. A total of 1,099 specimens collected during August 2012 to September 2013 were included. Mean age of patients providing stool specimens was 46 years (range: 0–98 years). Noroviruses were the most common viral pathogen identified among patients with AGE (n = 63 specimens, 6% of specimens tested). In addition, 22 (2%) of specimens were positive for rotavirus; 19 (2%) were positive for sapovirus; and 7 (1%) were positive for astrovirus. Incidence of norovirus-associated outpatient visits was 5.6 per 1,000 person-years; incidence of norovirus disease in the community was estimated to be 69.5 per 1,000 person-years. Norovirus incidence was highest among children <5 years of age (outpatient incidence = 25.6 per 1,000 person-years; community incidence = 152.2 per 1,000 person-years), followed by older adults aged >65 years (outpatient incidence = 7.8 per 1,000 person-years; community incidence = 75.8 per 1,000 person-years). Outpatient incidence rates of rotavirus, sapovirus, and astrovirus were 2.0, 1.6, 0.6 per 1,000 person-years, respectively; community incidence rates for these viruses were 23.4, 22.5, and 8.5 per 1,000 person-years, respectively. This study provides the first age-group specific laboratory-based community and outpatient incidence rates for norovirus AGE in the U.S. Norovirus was the most frequently detected viral enteropathogen across the age spectrum with the highest rates of norovirus disease observed among young children and, to a lesser extent, the elderly. These data provide a better understanding of the norovirus disease burden in the United States, including variations within different age groups, which can help inform the development, targeting, and future impacts of interventions, including vaccines.

The burden of norovirus disease in children in the European Union.

Noroviruses (NoVs) are the leading cause of acute gastroenteritis across all age groups. Because a vaccine is in clinical development, burden of disease data are required to guide the eventual introduction of this vaccine. In this study, we estimate the burden of NoV disease in children less than 5 years of age in the European Union (EU). We carried out a literature search using PubMed to identify studies providing incidence or prevalence data for NoV disease in the EU. We applied the pooled average NoV incidence and prevalence rates to the EU population less than 5 years of age to obtain the annual number of NoV illnesses, medical visits, hospitalizations and deaths occurring in the EU among children younger than 5 years. Data from 12 studies were included. We estimate that NoV infection may cause up to 5.7 million illnesses in the community, 800,000 medical visits, 53,000 hospitalizations and 102 deaths every year in children younger than 5 years in the EU. The burden of NoV disease in children in the EU is substantial, and will grow in relative importance as rotavirus (RV) vaccines are rolled out in the EU. This burden of disease is comparable with the burden of RV disease in the EU before RV vaccine introduction. More country-specific studies are needed to better assess this burden and guide the potential introduction of a vaccine against NoV at the national level.

Norovirus in healthcare settings.

Purpose of reviewTo provide an overview of the burden of norovirus disease in healthcare settings and the factors responsible for outbreaks in these institutions; to assess progress on interventions aimed at reducing the burden of norovirus disease.Recent findingsNorovirus outbreaks in healthcare settings are driven by confluence of viral diversity, the built environment, and host factors. Some of these characteristics may be modifiable and the target of successful interventions.SummaryMost norovirus outbreaks in hospital and residential care institutions are associated with a particular genotype, known as GII.4. The persistence of norovirus is associated with strain diversity, which is driven by immune evasion and viral adaptation to interaction with a variety of human histo-blood group antigens. The healthcare environment presents serious challenges for control, both because of the physical structure of the built space and the high levels of contact among patient populations who may have compromised hygiene. Increased vulnerability among the populations in healthcare institutions is likely to be multifactorial and may include the following: nutritional status, immunodeficiency or senescence, chronic inflammation, and microbiome alterations. Current control measures are based on general infection control principles, and treatment is mainly supportive and nonspecific. Vaccines and antiviral agents are being developed with promising results, but none are currently available.

The state of norovirus vaccines.

Noroviruses represent the most important cause of acute gastroenteritis worldwide; however, currently no licensed vaccine exists. Widespread vaccination that minimizes overall norovirus disease burden would benefit the entire population, but targeted vaccination of specific populations such as healthcare workers may further mitigate the risk of severe disease and death in vulnerable populations. While a few obstacles hinder the rapid development of efficacious vaccines, human trials for virus-like particle (VLP)-based vaccines show promise in both immune response and protection studies, with availability of vaccines being targeted over the next 5-10 years. Ongoing work including identification of important norovirus capsid antigenic sites, development of improved model systems, and continued studies in humans will allow improvement of future vaccines. In the meantime, a better understanding of norovirus disease course and transmission patterns can aid healthcare workers as they take steps to protect high-risk populations such as the elderly and immunocompromised individuals from chronic and severe disease.

A probabilistic quantitative microbial risk assessment model of norovirus disease burden from wastewater irrigation of vegetables in Shepparton, Australia

Wastewater can be an important resource for water-scarce regions of the world, but a major barrier to its use is the associated health risk. Quantitative microbial risk assessment (QMRA) is a probabilistic modeling technique used to determine the health risks from wastewater reuse, but only a handful of QMRA studies have examined the norovirus health risks from consumption of vegetables irrigated with human wastewater, even though norovirus is a, if not the most, significant microbial cause of diarrheal disease world-wide. Furthermore, the majority of these studies have focused only on risks from lettuce consumption. To meet the knowledge gap in health risks for other vegetables, a QMRA model was constructed for agricultural wastewater irrigation in the regional city of Shepparton, Australia, using fecal shedding rates to estimate norovirus concentration in raw sewage. Annual norovirus disease burden was estimated for the consumption of lettuce, broccoli, cabbage, Asian vegetables, and cucumber after irrigation with treated wastewater. Results indicate that the waste stabilization pond treatment did not have sufficient virus removal to meet the World Health Organization (WHO) threshold for acceptable level of risk for wastewater reuse, but addition of disinfection treatments provided acceptable results for consumption of cucumber and broccoli. This is the first QMRA study to incorporate virus accumulation from previous wastewater irrigation events.

The Epidemiology of Noroviruses in Ghana: A Case Study of Norovirus Detection

Diarrheal diseases cause significant morbidity and mortality worldwide, particularly in children under age five. Most of the 2.5 million annual diarrhea-related deaths occur in developing countries, where access to treatment is limited by geographic, cultural and knowledge-based factors. Noroviruses, the leading cause of diarrhea in adults, are the second leading viral etiology of diarrhea in children behind rotaviruses, causing a roughly estimated 218,000 child deaths a year. The recent introduction of rotavirus vaccines throughout the world may open a path for noroviruses to take over as the leading viral etiology of diarrhea in children. However, while norovirus vaccines are still currently in development, the burden of norovirus disease in many developing nations has yet to be established. Through the analysis of 152 stool specimens collected from Ghanaian children presenting with diarrhea from 3 sites, this study demonstrates that noroviruses are a significant contributor to the childhood diarrheal disease burden in Ghana, responsible for at least 16.4% of all cases. The results help establish the baseline norovirus prevalence in this developing nation prior to the introduction of rotavirus vaccines and explore the potential for future interventions against this major viral etiology of childhood diarrhea. Moreover, a survey of the disparities in norovirus studies around the world leads to a call for standardized detection protocols.

A probabilistic model of norovirus disease burden associated with greywater irrigation of home-produced lettuce in Melbourne, Australia

The reuse of domestic greywater has become common in Australia, especially during periods of extreme drought. Greywater is typically used in a raw, untreated form, primarily for landscape irrigation, but more than a quarter of greywater users irrigate vegetable gardens with the water, despite government advice against this practice. Greywater can be contaminated with enteric pathogens and may therefore pose a health risk if irrigated produce is consumed raw. A quantitative microbial risk assessment (QMRA) model was constructed to estimate the norovirus disease burden associated with consumption of greywater-irrigated lettuce. The annual disease burdens (95th percentile; DALYs per person) attributed to greywater irrigation ranged from 2 × 10−8 to 5 × 10−4, depending on the source of greywater and the existence of produce washing within households. Accounting for the prevalence of produce-washing behaviours across Melbourne, the model predicted annual disease burdens ranging from 4 × 10−9 for bathroom water use only to 3 × 10−6 for laundry water use only, and accounting for the proportionate use of each greywater type, the annual disease burden was 2 × 10−6. We recommend the preferential use of bathroom water over laundry water where possible as this would reduce the annual burden of disease to align with the current Australian recycled water guidelines, which recommend a threshold of 10−6 DALYs per person. It is also important to consider other exposure pathways, particularly considering the high secondary attack rate of norovirus, as it is highly likely that the estimated norovirus disease burden associated with greywater irrigation of vegetables is negligible relative to household contact with an infected individual.

The estimated disease burden of norovirus in The Netherlands

Noroviruses are an important cause of acute gastroenteritis in humans. We incorporated new insights gained over the past decade in an updated estimate of the disease burden of (foodborne) norovirus illness in The Netherlands in 2009. The disease outcomes - non-consulting cases, visiting a general practitioner, hospitalization and mortality - and the foodborne proportion were derived from cohort studies, surveillance data and literature. Age-specific incidence estimates were applied to the population age distribution in The Netherlands in 2009. The general population incidence was 3800/100 000 (95% CI 2670–5460), including 0.4 fatal cases/100 000,resulting in 1622 (95% CI 966–2650) disability-adjusted life-years in a population of 16.5 million [corrected].The updated burden of norovirus is over twofold higher than previously estimated, due in particular to the new insights in case-fatality ratios. Results suggest that the burden of norovirus institutional outbreaks is relatively small compared to the burden of community-acquired norovirus infections.

Noroviruses: The Perfect Human Pathogens?

Noroviruses: The Perfect Human Pathogens?

The Emerging Importance of Norovirus as the Etiology of Pediatric Gastroenteritis in Taipei

Rotavirus is a major causative agent of pediatric gastroenteritis throughout the world. However, other viruses such as norovirus also play an important role, but have seldom been studied in Taipei, Taiwan. The aim of this study was to survey the prevalence and clinical manifestations of different types of viral gastroenteritis in Taipei, focusing especially on the disease burden of norovirus. Between November 2004 and April 2005, stool samples were collected from hospitalized pediatric patients with a diagnosis of acute gastroenteritis. Clinical manifestations, laboratory data, and hospitalization course of the patients were all analyzed. Stool cultures for bacteria and rotavirus antigens were performed. All samples were tested for norovirus, enteric adenovirus, and astrovirus using enzyme-linked immunosorbent assays. A total of 75 stool specimens were collected during the 6-month period. Fifteen (20.0%) were positive for norovirus (3 genogroup I and 12 genogroup II). Three (4.0%) were positive for enteric adeno-virus, and one (1.3%) for astrovirus. Nine (12.0%) patients had positive rotavirus antigen tests. Bacterial pathogens were found in 12 patients (16.0%), including seven cases of Salmonella, and five of Campylobacter. The patients with norovirus gastroenteritis were aged between 1.5-7.5 years old (median 20 months old). Fever was found in six patients (40.0%), and bloody, mucoid stools in three (20.0%). The mean hospitalization time was 3.3 days. None of them had complications. During the study period, norovirus was the most common pathogen causing hospitalized pediatric gastroenteritis in our hospital. Genogroup II was the predominant type (80.0%). Clinicians in Taipei should, therefore, be aware of the emergence of norovirus infections.

Community Incidence of Norovirus-associated Infectious Intestinal Disease in England: Improved Estimates Using Viral Load for Norovirus Diagnosis

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.

Molecular epidemiology of norovirus infections in sporadic cases of viral gastroenteritis among children in Northern Italy

Surveillance of norovirus infections in sporadic cases of pediatric gastroenteritis admitted to a main hospital in Northern Italy during a full-year period (2002) showed that noroviruses (10.4%) were the second most common causative viral agent, following rotaviruses (21.1%), and noroviruses (81%) were mostly implicated in mixed infections. The epidemic period of norovirus was September-December, with September and November as months of major prevalence (33.3 and 38.5%, respectively). Six distinct norovirus genotypes were detected (GI.7, GII.1, GII.2, GII.4, GII.7, GII, not assigned named GIIb), and the predominant genotype was GII.4. A "new GII.4 2002 variant" accounted for 82.9% of total strains. Since the severity of norovirus symptoms does not usually require admission to hospital, the burden of norovirus disease in the general children population may be much higher than that suggested by the present hospital-based investigation.