Norovirus Acute Gastroenteritis Research Articles

Norovirus outbreaks in german refugee camps in 2015

Purpose Refugees often live in confined housing conditions with shared kitchen and sanitary facilities, rendering susceptible to communicable diseases. We here describe the outbreak, spread and self-limiting nature of a norovirus outbreak in a German refugee camp in the winter of 2015. Methods During a norovirus outbreak, data on clinical symptoms, nationality and living conditions was obtained in a refugee camp in northern Germany in the winter of 2015. Furthermore secondary data on norovirus outbreaks in 2015 was assessed. Results Amongst n = 982 refugees, n = 36 patients (3.7 %) presented with acute norovirus gastroenteritis. The vast majority of cases were children, only the first patient was admitted to the hospital. Intensified hygiene measures were implemented on day 2 of the outbreak, but new cases peaked on day 21 and occurred until one month after the first case. Different cultural backgrounds, eating habits and hygiene standards amongst the refugees made it particularly challenging to implement stringent isolation and hygiene measures. Despite these predisposing factors, only minor norovirus outbreaks were reported in refugee camps in 2015. Conclusion Adults refugees had a low attack rate of symptomatic norovirus infection, while small children are at high risk. Infection spreads despite hygiene measures and camp sites and staff should be prepared for the particular challenges of such situations with a particular focus on cultural-background specific implementation of hygiene measures.

Incidence of Norovirus-Associated Acute Gastroenteritis in Four Veteran’s Affairs Medical Center Populations in the United States, 2011–2015

Abstract Background In the USA, norovirus is an important cause of epidemic acute gastroenteritis (AGE) as well as a leading cause of pediatric AGE. However, the burden of sporadic norovirus disease in US adults has not been well-documented. Our objective was to estimate the incidence of outpatient visits and hospitalizations for community-acquired norovirus AGE at four Veterans Affairs Medical Centers (VAMCs) and their associated outpatient clinics in Atlanta, GA; Bronx, New York; Houston, TX; and Los Angeles, CA. Methods From November 2011 to September 2015, stool specimens collected for clinician-requested diagnostic testing within 7 days of AGE symptom onset and with reported vomiting or diarrhea were tested for norovirus by real-time RT-PCR and positive samples were genotyped by Sanger sequencing. Incidence of norovirus-associated outpatient visits and hospitalizations were calculated by multiplying the prevalence of norovirus among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the unique patients served at each VAMC. Results 1,620 stool specimens were tested from all 4 sites. Seven percent of outpatient (n = 795) samples (annual range: 3%–10%; range by site: 3%–10%) and 6% of
(n = 825) samples from hospitalized patients tested positive for norovirus (annual range: 3%–8%; range by site: 3%–10%). Forty-four percent of norovirus-positive specimens were typed as GII.4 Sydney. Seventy-four percent of norovirus-positive specimens were collected between November and April. From 2011 to 2015, outpatient norovirus incidence was 250/100,000 population (annual range: 129 to 426/100,000; range by site: 87 to 428/100,000), and the incidence of norovirus hospitalizations was 28/100,000 population (annual range: 19 to 39/100,000; range by site: 14 to 57/100,000). By age group and setting, the highest incidence was observed among 45- to 64-year-old outpatients (370/100,000 population), and 85+-year-old inpatients (63/100,000 population). Conclusion This study provides estimates of the incidence of norovirus AGE outpatient visits and hospitalizations across multiple years among a geographically distributed VA population, highlighting the substantial burden of norovirus in US adults. Disclosures All authors: No reported disclosures.

Hospital-acquired rotavirus and norovirus acute gastroenteritis in a pediatric unit, in 2014-2015.

The occurrence of hospital-acquired acute gastroenteritis (AGE) is a major concern for public health. RotavirusA (RVA) and norovirus (NoV) are common causes of viral AGE in the pediatric population, and their role in nosocomial infections has been proven, remaining poorly investigated. To investigate RVA and NoV in hospital-acquired AGE, 55 stool samples from children with nosocomial AGE were collected between May 2014 and May 2015. To evaluate virus spreading routes, 51 environmental swabs were collected from staff and patients' rooms. Stools were tested for both RVA and NoV RNA by reverse-transcription-PCR. Nucleotide sequencing and phylogenetic analysis were performed to characterize the viruses. Forty-seven of 55 cases analyzed resulted positive for RVA. The predominant genotype was G4P[8] (18/55) followed by G1P[8] (14/55). Mixed RVA infections were also detected (7/55). Twenty-two samples were positive for NoV, and GII.4 was revealed to be the predominant genotype. Seventeen samples were positive for both RVA and NoV. This study aimed to evaluate the burden of norovirus and rotavirus nosocomial AGE, contributing to identify the environment source of infections and to activate effective strategies for intervention. The reduction in nosocomial AGE cases is an important aspect, considered the worsened disease course in transplant, cancer, and intensive care unit inpatients.

Norovirus in Latin America: Systematic Review and Meta-analysis.

Noroviruses are increasingly recognized as a major cause of sporadic and epidemic acute gastroenteritis (AGE). Although there have been multiple studies published on norovirus epidemiology in Latin America, no comprehensive assessment of the role of norovirus has been conducted in the region. We aim to estimate the role of norovirus in the Latin American region through a systematic review and meta-analysis of the existing literature. We carried out a literature search in MEDLINE, SciELO and LILACS. We included papers that provided information on the prevalence or incidence of norovirus (including seroprevalence studies and outbreaks), with a recruitment and/or follow-up period of at least 12 months and where the diagnosis of norovirus was confirmed by reverse transcription polymerase chain reaction. The data were pooled for meta-analysis to estimate the prevalence of norovirus AGE and norovirus asymptomatic infection with 95% confidence intervals (CIs). Thirty-eight studies were included in the review. Overall, the prevalence of norovirus among AGE cases was 15% (95% CI: 13-18). By location, it was 15% in the community (95% CI: 11%-21%), 14% in outpatient settings (95% CI: 10%-19%) and 16% in hospital locations (95% CI: 12%-21%). The prevalence of norovirus among asymptomatic subjects was 8% (95% CI: 4-13). Norovirus GII.4 strains were associated with 37%-100% of norovirus AGE cases, but only 7% of norovirus asymptomatic detections. Noroviruses are associated with almost 1 out of every 6 hospitalizations because of acute diarrhea in children younger than 5 years of age in Latin America.

Acute norovirus gastroenteritis in children in a highly rotavirus-vaccinated population in Northeast Brazil

BackgroundGastroenteritis is one of the most important causes of morbidity and mortality in children and an important etiological agent is norovirus. ObjectiveWe describe the occurrence and characteristics of norovirus diarrhoea in children from Sergipe, Northeast-Brazil, over two consecutive periods of three years following rotavirus vaccine introduction. Study designA cross sectional hospital-based survey conducted from October-2006 to September-2009 and from July-2011 to January-2013. Acute diarrhoea cases had a stool sample collected and tested for norovirus by RT-PCR and positive samples were sequenced. ResultsIn total 280 (19.6%) of 1432 samples were norovirus positive, including 204 (18.3%) of 1113 samples collected during the first period and 76 (23.9%) of 318 collected during the second period. The proportion of children with norovirus infection increased significantly through the second study period (χ2 for trend=6.7; p=0.009), was more frequent in rotavirus vaccinated and in younger children (p<0.001). Of 280 norovirus-positive specimens, 188 (67.1%) were sequenced. Of these, 12 were genogroup I and 176 genogroup II. The main genotype was GII.4 (149/188, 79.3%), followed by GII.2 (6, 3.2%) and GII.6 (5, 2.6%). ConclusionNorovirus annual detection rates increased over the study period. The detection of norovirus was higher among young children.

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.

Norovirus detection from sera of young children with acute norovirus gastroenteritis

BackgroundAntigenemia and viremia are common in rotavirus infection but only few studies have shown norovirus (NoV) RNA in the blood circulation. ObjectivesTo detect NoV RNA from serum of NoV-infected children and study if NoV RNAemia correlates with clinical severity of acute gastroenteritis. Study designSerum specimens were collected from 176 Finnish children with acute NoV gastroenteritis. Semi-nested PCR was optimized to detect NoV capsid RNA from sera. NoV positive samples were further analyzed by sequencing. ResultsNoV RNA was found in 11/176 (6.3%) of serum specimens. NoV GII.4 was found in 8 cases and GII.3, GII.6 and GII.7 in one case each. The genotypes detected in serum were identical to findings in stools in all cases. Most of the NoV RNA detections in serum were in young children less than 18 months of age. The clinical features of NoV serum-positive cases were not different from NoV serum-negative cases. ConclusionNoV RNA in serum is an uncommon finding limited to young children.

Incidence of Medically-Attended Norovirus-Associated Acute Gastroenteritis in Four Veteran's Affairs Medical Center Populations in the United States, 2011-2012.

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.

Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population.

Norovirus is a leading cause of acute gastroenteritis (AGE). Noroviruses bind to gut histo-blood group antigens (HBGAs), but only 70%-80% of individuals have a functional copy of the FUT2 ("secretor") gene required for gut HBGA expression; these individuals are known as "secretors." Susceptibility to some noroviruses depends on FUT2 secretor status, but the population impact of this association is not established. From December 2011 to November 2012, active AGE surveillance was performed at 6 geographically diverse pediatric sites in the United States. Case patients aged <5 years were recruited from emergency departments and inpatient units; age-matched healthy controls were recruited at well-child visits. Salivary DNA was collected to determine secretor status and genetic ancestry. Stool was tested for norovirus by real-time reverse transcription polymerase chain reaction. Norovirus genotype was then determined by sequencing. Norovirus was detected in 302 of 1465 (21%) AGE cases and 52 of 826 (6%) healthy controls. Norovirus AGE cases were 2.8-fold more likely than norovirus-negative controls to be secretors (P < .001) in a logistic regression model adjusted for ancestry, age, site, and health insurance. Secretors comprised all 155 cases and 21 asymptomatic infections with the most prevalent norovirus, GII.4. Control children of Meso-American ancestry were more likely than children of European or African ancestry to be secretors (96% vs 74%; P < .001). FUT2 status is associated with norovirus infection and varies by ancestry. GII.4 norovirus exclusively infected secretors. These findings are important to norovirus vaccine trials and design of agents that may block norovirus-HBGA binding.

Noroviruses: Epidemiology, Immunity and Prospects for Prevention

In recent years, noroviruses have become recognized as an important cause of both sporadic and epidemic acute gastroenteritis (AGE), largely due to the improved availability of broadly reactive real-time RT-PCR (TaqMan-based RT-PCR) assays. While there is substantial diversity among noroviruses, one specific genotype, GII.4, is the most common etiology in sporadic and epidemic AGE. Outbreaks of norovirus AGE most commonly occur in healthcare facilities and restaurants and result in significant morbidity and mortality and substantial healthcare costs. Norovirus vaccine development is progressing, and Phase I and II human trials have shown proof-of-principle that norovirus vaccines can reduce illness and infection.

An outbreak of acute norovirus gastroenteritis in a boarding school in Shanghai: a retrospective cohort study

BackgroundMore than 200 students and teachers at a boarding school in Shanghai developed acute gastroenteritis in December, 2012. The transmission mode remained largely unknown. An immediate epidemiological investigation was conducted to identify it.MethodsUsing a retrospective cohort design, we investigated demographic characteristics, school environment, and previous contacts with people who had diarrhea and/or vomiting, drinking water conditions, recalls of food consumption in the school cafeteria, hand-washing habits and eating habits. Rectal swabs of the new cases and food handlers as well as water and food samples were collected to test potential bacteria and viruses. Norovirus was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR).ResultsA total of 278 cases developed gastrointestinal symptoms in this outbreak, and the overall attack rate was 13.9%. The main symptoms included vomiting (50.0%), abdominal cramps (40.3%), nausea (27.0%), diarrhea (6.8%) and fever (6.8%). Twenty rectal swab samples were detected as Norovirus–positive, including 11 from student cases and 9 from asymptomatic food handlers (non-cases). Among environmental surface samples from the kitchen, 8 samples were also detected as Norovirus-positive. The genotypes of viral strains were the same (GII) in patients, asymptomatic food handlers and environmental surfaces. Other samples, including rectal swabs, water samples and food samples were negative for any bacteria and other tested viruses. Asymptomatic food handlers may have contaminated the cooked food during the food preparation.ConclusionThe study detected that the outbreak was caused by Norovirus and should be controlled by thorough disinfection and excluding asymptomatic food handlers from food preparation. Early identification of the predominant mode of transmission in this outbreak was necessary to prevent new cases. Furthermore, good hygiene practices such as regular hand washing and efficient daily disinfection should be promoted to prevent such infection and outbreaks.

High serum levels of norovirus genotype-specific blocking antibodies correlate with protection from infection in children.

Norovirus is a common cause of acute gastroenteritis in children. Serum immunoglobulin G (IgG) antibodies have been implicated in protection against norovirus-associated gastroenteritis, but the level, specificity, and functionality necessary for protection remain to be elucidated. Norovirus-specific IgG antibodies to genogroup II (GII)-4-2010 New Orleans (NO), GII-4-1999, GII-12-1998, GI-1-2001, and GI-3-2002 virus-like particles (VLPs) were determined by enzyme-linked immunosorbent assay in serum samples collected from children who presented to the hospital because of acute norovirus gastroenteritis in 2009-2011. The blocking activity of the antibodies was tested in a surrogate neutralization assay. Most norovirus infections (62.8%) in the study population were caused by a GII-4 NO variant. Children who acquired GII-4 NO infection had a low preexisting type-specific IgG level and blocking activity of the sera, in contrast to children infected with other GII genotypes. Following GII-4 NO infection, genotype-specific seroconversion and a corresponding increase in blocking antibody potential was observed. Although seroconversion to the heterologous GII-4-1999 variant was observed, there was no corresponding increase in the specific blocking antibody titer. There was no concomitant seroconversion against GI VLPs, indicating a highly genogroup-specific antibody response. High preexisting norovirus genotype-specific serum IgG titers and blocking activity in children indicate protection from norovirus infection in a strain-specific manner.

Clinical Profile of Children with Norovirus Disease in Rotavirus Vaccine Era

Clinical Profile of Children with Norovirus Disease in Rotavirus Vaccine Era

High prevalence of community-acquired norovirus gastroenteritis among hospitalized children: a prospective study

Acute gastroenteritis (AGE) causes significant morbidity, especially in young children, and frequently requires hospitalization even in developed countries. Surveillance studies of AGE are important to determine the prevalence and variety of bacterial and viral pathogens, to initiate targeted preventive measures, such as vaccine programmes, and to monitor its impact. A prospective study was conducted in children <5 years old, admitted with AGE between April 2006 and April 2007 to the Virgen del Rocío University Hospital, Seville, Spain. Demographic and clinical data were collected and patients followed-up after hospital discharge. A stool sample from each child was screened for enteropathogenic bacteria and tested by reverse transcription polymerase chain reaction for rotavirus, astrovirus, noroviru and sapovirus and by the immunochromatographic method for enteric adenoviruses. Norovirus was the most common pathogen in hospitalized children, being detected in 27%, followed by rotavirus 21%. Mixed infection occurred in nearly 20% of all norovirus infections and was most commonly associated with Salmonella spp. Rotavirus infection was associated with an overall higher severe clinical score compared with norovirus infection. Lactose intolerance was observed in 29 children (7.5%) and most commonly due to rotavirus infection (p <0.001). Seizures were reported in four children. Norovirus was the commonest cause of AGE in hospitalized children <5 years during 2006–2007 in Seville, Spain. The use of these molecular techniques should be included routinely for the surveillance of sporadic cases and outbreaks of norovirus AGE in children attending hospitals as well as healthcare centres.

Norovirus gastroenteritis successfully treated with nitazoxanide

Infectious diarrhea is a common occurrence in the immunosuppressed population. We present a 43-year-old individual with large-volume stool output Norovirus acute gastroenteritis in the setting of relapsed refractory acute myelogenous leukemia, hematopoietic stem cell transplantation, and biopsy-proven cutaneous and pulmonary graft-versus-host disease. Therapeutic options such as intravenous immunoglobulin or reduction of immunosuppressants were not a feasible choice. A prompt clinical cure was achieved with nitazoxanide, a broad-spectrum antimicrobial agent. Nitazoxanide may be a safe therapeutic alternative, in which a reduction in immunosuppression may not be a viable option.

Epidemiological Analysis of Norovirus Infection between March 2007 and February 2010

Norovirus is a common cause of non-bacterial acute gastroenteritis worldwide, and norovirus infection shows symptoms such as vomiting and diarrhea in patients of all age groups. Mass outbreaks of norovirus infection have been recently reported in Korea. Herein, we investigated the epidemiological characteristics of acute norovirus gastroenteritis. We analyzed 11,219 fecal specimens of patients with acute gastroenteritis symptoms from the 5 participating hospitals for 3 yr (March 2007-February 2010) to determine positive rates of detection using RIDASCREEN Norovirus ELISA (R-Biopharm AG, Germany) kit by year, prevalence season, sex, age, and region. Norovirus infection was prevalent during autumn and winter, and 13.0% specimens were positive for the infection. The positive rates of norovirus detection were 16.2%, 13.8%, and 9.9% in 2007, 2008, and 2009, respectively, and they tended to decrease every year. In 2007 and 2008, the epidemicity of norovirus started from October, reached its peak in November, and lasted until January. However, in 2009, it started from December, reached its peak in January, and lasted until February. Most patients were 0-3 yr old and this patient group had the highest positive rate. There was no significant inter-regional difference among the subjects. We performed epidemiological analysis of norovirus infection using ELISA assay. Reverse transcription-PCR indicated higher prevalence of norovirus infection as compared with that reported before 2007. Further studies are warranted to examine the changes observed in the epidemic period of 2009.

Chronic norovirus infection in an HIV-positive patient with persistent diarrhoea: A novel cause

Environmental surfaces are a potential vehicle for the transmission of norovirus outbreaks in closed and semi-closed settings. Testing of environmental samples may help control outbreaks.To assess the level of environmental contamination by norovirus in acute gastroenteritis outbreaks in closed or semi-closed settings (nursing homes, schools, kindergartens, youth accommodations, hospitals and social health centres) in the Barcelona region between January 2017 and March 2019.A prospective surveillance study was carried out. Environmental samples (529) were collected in 46 of the 50 outbreaks of acute norovirus gastroenteritis from environmental surfaces of common areas, bathrooms and kitchens in closed and semi-closed settings when the outbreak was notified and 10 days later. Instructions for taking environmental samples were distributed to public health inspectors. Norovirus was detected by reverse transcription polymerase chain reaction.Environmental samples were positive for norovirus in 31 (67.4%) outbreaks. Norovirus was most frequently detected on elevator buttons (4/17, 24%), toilet handles (16/66, 24%) and handrail bars (7/34, 21%). Positive samples from the first sampling were mainly found in bathrooms and greater viral persistence in the second sampling was found on elevator buttons and TV remote controls. Nursing homes were the setting with the most types of environmental surfaces contaminated (82% in first samples and 55% in second samples).The probability of virus detection is independent of the time between notification of the outbreak or symptom onset and sample collection. Our results suggest possible defects in cleaning protocols and disinfection in closed and semi-closed settings.

A foodborne outbreak of norovirus gastroenteritis associated with a Christmas dinner in Porto, Portugal, December 2008

An outbreak of acute norovirus gastroenteritis was detected and epidemiologically linked to a Christmas dinner reunion of 22 recent graduate students in a restaurant in Porto, Portugal, in December 2008. A retrospective cohort study was carried out using online standardised questionnaires. Sixteen primary and three secondary cases were identified and the risk ratios with 95% confidence intervals for each food item were calculated. The response rate to the online questionnaires was 96%. The outbreak met all four Kaplan s criteria and the attack rate was 73%. Norovirus GII.4 2006b was detected in stools and emesis samples of two primary cases. The ingestion of soup and lettuce salad was considered a risk factor for this norovirus outbreak, as determined by statistical analysis. Our investigation demonstrated two routes of transmission of norovirus starting with foodborne exposure followed by secondary person-to-person spread. To our knowledge this is the first study identifying norovirus as the causative agent of a foodborne outbreak in Portugal.