Norovirus Genogroup II Gastroenteritis in Hospitalized Children in South India

The distribution of norovirus (NoV) genogroup II in children < 5 years of age admitted to a south Indian hospital with diarrhea was investigated. Viral RNA extracted from 282 stool samples were screened for NoV GII and positive amplicons sequenced. Twenty-eight (9.9%) had NoV GII infection with a median age of 6 months, with more severe episodes of diarrhea among infected (median Vesikari score 13, interquartile range [IQR] 10–15) than children without infection (median score 10, IQR 8–13, P = 0.002). The study documents NoV GII infections as an important cause of gastroenteritis and the genetic diversity of circulating strains.     

Detection of Norovirus in Saliva Samples from Acute Gastroenteritis Cases and Asymptomatic Subjects: Association with Age and Higher Shedding in Stool

Norovirus infections are a leading cause of acute gastroenteritis outbreaks worldwide and across all age groups, with two main genogroups (GI and GII) infecting humans. The aim of our study was to investigate the occurrence of norovirus in saliva samples from individuals involved in outbreaks of acute gastroenteritis in closed and semiclosed institutions, and its relationship with the virus strain, virus shedding in stool, the occurrence of symptoms, age, and the secretor status of the individual. Epidemiological and clinical information was gathered from norovirus outbreaks occurring in Catalonia, Spain during 2017–2018, and stool and saliva samples were collected from affected and exposed resident individuals and workers. A total of 347 saliva specimens from 25 outbreaks were analyzed. Further, 84% of individuals also provided a paired stool sample. For GII infections, norovirus was detected in 17.9% of saliva samples from symptomatic cases and 5.2% of asymptomatic individuals. Positivity in saliva occurred in both secretors and nonsecretors. None of the individuals infected by norovirus GI was positive for the virus in saliva. Saliva positivity did not correlate with any of the studied symptoms but did correlate with age ≥ 65 years old. Individuals who were positive in saliva showed higher levels of virus shedding in stool. Mean viral load in positive saliva was 3.16 ± 1.08 log₁₀ genome copies/mL, and the predominance of encapsidated genomes was confirmed by propidium monoazide (PMA)xx-viability RTqPCR assay. The detection of norovirus in saliva raises the possibility of oral-to-oral norovirus transmission during the symptomatic phase and, although to a lesser extent, even in cases of asymptomatic infections.     

Targeted Profiling of Immunological Genes during Norovirus Replication in Human Intestinal Enteroids

Norovirus is the leading cause of acute gastroenteritis worldwide. The pathogenesis of norovirus and the induced immune response remain poorly understood due to the lack of a robust virus culture system. The monolayers of two secretor-positive Chinese human intestinal enteroid (HIE) lines were challenged with two norovirus pandemic GII.4 Sydney strains. Norovirus RNA replication in supernatants and cell lysates were quantified by RT-qPCR. RNA expression levels of immune-related genes were profiled using PCR arrays. The secreted protein levels of shortlisted upregulated genes were measured in supernatants using analyte-specific enzyme-linked immunosorbent assay (ELISA). Productive norovirus replications were achieved in three (75%) out of four inoculations. The two most upregulated immune-related genes were CXCL10 (93-folds) and IFI44L (580-folds). Gene expressions of CXCL10 and IFI44L were positively correlated with the level of norovirus RNA replication (CXCL10: Spearman’s r = 0.779, p < 0.05; IFI44L: r = 0.881, p < 0.01). The higher level of secreted CXCL10 and IFI44L proteins confirmed their elevated gene expression. The two genes have been reported to be upregulated in norovirus volunteer challenges and natural human infections by other viruses. Our data suggested that HIE could mimic the innate immune response elicited in natural norovirus infection and, therefore, could serve as an experimental model for future virus-host interaction and antiviral studies.     

Burden of Norovirus and Rotavirus in Children after Rotavirus Vaccine Introduction,Cochabamba, Bolivia

The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5–24 months without AGE were recruited from an urban hospital serving Bolivia''s third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus.     

Quantification of Human Norovirus GII on Hands of Mothers with Children under the Age of Five Years in Bagamoyo,Tanzania

Human noroviruses are the most common cause of viral gastroenteritis worldwide and one of the leading causes of viral diarrhea in children under the age of 5 years. Hands have been shown to play an important role in norovirus transmission. Norovirus outbreaks tend to exhibit strong seasonality, most often occurring during cold, dry months, but recently have also been documented during hot, dry winter months in the southern hemisphere. Other research suggests that rainfall is an important factor in norovirus outbreaks. This study examines the prevalence and concentration of human norovirus GII on the hands of mothers in Bagamoyo, Tanzania, during the rainy and dry seasons. Norovirus GII was detected in approximately 5% of hand rinse samples during both the rainy and dry seasons. Fecal indicator bacteria levels, Escherichia coli and enterococci, in hand rinse samples were not associated with norovirus hand contamination. Turbidity of the hand rinses was found to be associated with norovirus presence on mothers'' hands; however, this relationship was only observed during the rainy season. The results suggest mothers'' hands serve as a source of norovirus exposure for young children in Tanzanian households, and further work is needed to determine better indicators of norovirus contamination in these environments.     

Virological and Epidemiological Features of Norovirus Infections in Brazil, 2017–2018

Noroviruses are considered an important cause of acute gastroenteritis (AGE) across all age groups. Here, we investigated the incidence of norovirus, genotypes circulation, and norovirus shedding in AGE stool samples from outpatients in Brazil. During a two-year period, 1546 AGE stool samples from ten Brazilian states were analyzed by RT-qPCR to detect and quantify GI and GII noroviruses. Positive samples were genotyped by dual sequencing using the ORF1/2 junction region. Overall, we detected norovirus in 32.1% of samples, with a massive predominance of GII viruses (89.1%). We also observed a significant difference between the median viral load of norovirus GI (3.4×10⁵ GC/g of stool) and GII (1.9×10⁷ GC/g). The most affected age group was children aged between 6 and 24 m old, and norovirus infection was detected throughout the year without marked seasonality. Phylogenetic analysis of partial RdRp and VP1 regions identified six and 11 genotype combinations of GI and GII, respectively. GII.4 Sydney[P16] was by far the predominant genotype (47.6%), followed by GII.2[P16], GII.4 Sydney[P31], and GII.6[P7]. We detected, for the first time in Brazil, the intergenogroup recombinant genotype GIX.1[GII.P15]. Our study contributes to the knowledge of norovirus genotypes circulation at the national level, reinforcing the importance of molecular surveillance programs for future vaccine designs.     

Norovirus GII-4 causes a more severe gastroenteritis than other noroviruses in young children

Norovirus (NoV) GII-4 has emerged as the predominant NoV genotype in outbreaks of gastroenteritis worldwide. We determined clinical features of NoV GII-4 associated acute gastroenteritis (AGE) in comparison with AGE associated with other NoV types in infants during seasons 2001 and 2002. During the prospective follow-up period, 128 primary infections of AGE due to NoV were identified in 405 infants; of these, GII-4 was found in 40 cases (31%). NoV GII-4 was associated with longer duration of diarrhea and vomiting than other NoV genotypes, suggesting greater virulence of NoV GII-4.     

Oyster-associated outbreaks of Norovirus gastroenteritis in Singapore

Outbreaks of gastroenteritis associated with the consumption of raw imported half-shelled frozen oysters occurred in Singapore between 16 Dec 2003 and 04 Jan 2004. A total of 305 cases were reported with clinical symptoms of diarrhoea (94%), abdominal cramps (72%), vomiting (69%) and fever (54%). The median incubation period was 30.8 h and the duration of illness was 2–3 days. The overall relative risk of oyster consumption was 14.1 (95% CI: 8.3–24.0, P<0.001). Stool and oyster samples tested negative for common bacterial pathogens, including Vibrio parahaemolyticus. However, stool samples were positive for the presence of Norovirus group II RNA via RT PCR while oyster samples indicated the presence of Norovirus particles by electron microscopy. The clinical and epidemiological features were suggestive of Norovirus gastroenteritis and were subsequently confirmed by laboratory tests of stools and implicated oysters. Steps have been taken to ensure that food outlets do not thaw frozen oysters and serve them raw.     

Epidemiological and virological investigation of a Norovirus outbreak in a resort in Puglia,Italy

Background  

This paper describes the third large outbreak of Norovirus (NoV) gastroenteritis reported in the Southern Italy region of Puglia.     

诺如病毒感染宿主免疫应答的研究进展

诺如病毒是引起非细菌性急性感染性胃肠炎的主要病原体,常常引起严重的公共卫生与食品安全问题。诺如病毒疫苗的研发被越来越多的国家提上日程,疫苗的研制和应用依赖于对宿主和病毒相互关系的深入了解,依赖于宿主对病毒的免疫应答机制的了解。本文综述了诺如病毒国内外流行现状、诺如病毒感染与HBGAs受体关系和诺如病毒感染人或动物后机体的免疫应答研究现状。     

Swine Norovirus: Past,Present, and Future

Norovirus, an ssRNA + virus of the family Caliciviridae, is a leading disease burden in humans worldwide, causing an estimated 600 million cases of acute gastroenteritis every year. Since the discovery of norovirus in the faeces of swine in Japan in the 1990s, swine norovirus has been reported in several countries on several continents. The identification of the human-associated GII.4 genotype in swine has raised questions about this animal species as a reservoir of norovirus with zoonotic potential, even if species-specific P-types are usually detected in swine. This review summarises the available data regarding the geographic distribution of norovirus in swine, the years of detection, the genotype characterisation, and the prevalence in specific production groups. Furthermore, we discuss the major bottlenecks for the detection and characterisation of swine noroviruses.     

Identification of Norovirus as the Top Enteric Viruses Detected in Adult Cases with Acute Gastroenteritis

To elucidate the importance of the norovirus and other enteric viruses, and the difference of the genetic relatedness on norovirus between the outbreak and sporadic cases, a total of 557 stool samples, consisting of 503 sporadic cases and 54 samples of 4 outbreaks were collected and tested for norovirus and other enteric viruses in Beijing, China, July 2007–June 2008. The data showed norovirus, rotavirus, astrovirus, and sapovirus, were detected in 26.6%, 6.1%, 1.8%, and 0.5%, respectively. Norovirus was detected almost throughout the surveillance period, norovirus co-infecting with rotavirus, astrovirus, and sapovirus, respectively, were identified both in outbreak and the sporadic cases. GII.4/2006 was identified as the predominant strain circulating both in outbreak and sporadic cases. The results showed that norovirus was rather the important agent than other enteric viruses affected adults with acute gastroenteritis; no significant genetic relatedness of the dominant strains was found between the outbreak and sporadic cases.     

Norovirus outbreak among primary schoolchildren who had played in a recreational water fountain

BACKGROUND: A gastroenteritis outbreak was associated with playing in a norovirus-contaminated recreational fountain. OBJECTIVE AND STUDY DESIGN: A retrospective cohort study was performed to estimate the magnitude of the outbreak and identify its source. Epidemiological investigation included standardized questionnaires about sex, age, school, class, risk exposures, and illness characteristics. Stool samples and environmental water samples were analyzed for the presence of bacteria, viruses, and parasites. RESULTS: Questionnaires were returned for 191 schoolchildren (response rate, 83%) with a mean age of 9.2 years, of whom 47% were ill (diarrhea and/or vomiting). Children were more likely to have been ill if they had played in the recreational fountain (relative risk, 10.4). Norovirus (Birmingham) was detected in 22 (88%) stool specimens from ill children and in 6 (38%) specimens from healthy children. The water sample from the fountain contained a norovirus strain that was identical to the RNA sequence found in stools. CONCLUSIONS: Recreational water may be the source of gastroenteritis outbreaks. Adequate water treatment can prevent these types of outbreak.     

A Foodborne Norovirus Outbreak Due To Manually Prepared Salad, Austria 2006

Abstract Background: Norovirus is increasingly being recognized as a leading cause of foodborne disease. Nevertheless, welldocumented foodborne outbreaks due to norovirus are rarely found in the literature. Material and Methods: A retrospective cohort study was conducted for identifying the source of a gastroenteritis outbreak. A total of 325 persons were identified as the atrisk group. Results: The overall attack rate was 56% (182/325). Of the four working days of possible foodborne exposure to norovirus (Monday till Thursday), Wednesday (risk ratio [RR]: 18.82; 95%CI 11.82–29.96) and Thursday (RR 2.14; 95%CI 1.65–2.79) turned out to be the most likely days on which infections with norovirus occurred. The day-by-day food specific cohort analyses yielded consumption of salad on Wednesday (adjusted RR 2.82; 95%CI 1.0–7.94) to be associated with highest risk of illness. The most likely source of food contamination is a kitchen assistant having prepared salad manually. She fell ill with symptoms of gastroenteritis on Wednesday during the early working hours and continued working. Human stool samples obtained from five out of six outbreak cases, including the sick kitchen assistant, were RT-PCR positive for norovirus genotype GGII.7 (Leeds-like). Conclusion: This foodborne norovirus outbreak underlines the drastic consequences of neglecting the rules of basic kitchen hygiene. Food handlers working despite manifest diarrhea or vomiting – often in fear of job loss – are a common cause of foodborne norovirus outbreaks.     

Virus Etiology,Diversity and Clinical Characteristics in South African Children Hospitalised with Gastroenteritis

Background: Viral gastroenteritis remains a major cause of hospitalisation in young children. This study aimed to determine the distribution and diversity of enteric viruses in children ≤5 years, hospitalised with gastroenteritis at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa, between July 2016 and December 2017. Methods: Stool specimens (n = 205) were screened for norovirus GI and GII, rotavirus, sapovirus, astrovirus and adenovirus by multiplex RT-PCR. HIV exposure and FUT2 secretor status were evaluated. Secretor status was determined by FUT2 genotyping. Results: At least one gastroenteritis virus was detected in 47% (96/205) of children. Rotavirus predominated (46/205), followed by norovirus (32/205), adenovirus (15/205), sapovirus (9/205) and astrovirus (3/205). Norovirus genotypes GI.3, GII.2, GII.3, GII.4, GII.7, GII.12, GII.21, and rotavirus strains G1P[8], G2P[4], G2P[6], G3P[4], G3P[8], G8P[4], G8P[6], G9P[6], G9P[8] and sapovirus genotypes GI.1, GI.2, GII.1, GII.4, GII.8 were detected; norovirus GII.4[P31] and rotavirus G3P[4] predominated. Asymptomatic norovirus infection (GI.3, GI.7, GII.4, GII.6, GII.13) was detected in 22% of 46 six-week follow up stools. HIV exposure (30%) was not associated with more frequent or severe viral gastroenteritis hospitalisations compared to unexposed children. Rotavirus preferentially infected secretor children (p = 0.143) and norovirus infected 78% secretors and 22% non-secretors. Conclusion: Rotavirus was still the leading cause of gastroenteritis hospitalisations, but norovirus caused more severe symptoms.     

GⅡ-4型诺如病毒体外结合唾液HBGAs受体的检测与分析

目的建立诺如病毒（Norovirus,NoV）结合唾液HBGAs受体的实验方法、验证2株GⅡ-4型NoV毒株与我国人群唾液HBGAs的结合方武。方法收集健康志愿者唾液标本,采用凝集抑制实验法检测唾液中HBGAs血型物质,用EIA法检测NoV VLPs、阳性毒株与HBGAs的结合情况。结果63份标本检出O型21例（占33．3％）,B型14例（占22．2％）,A型和非分泌型各13例（分别占20．6％）,AB型2例（占3．2％）。rVA387、2株GⅡ-4型毒株均能结合分泌型,与非分泌型唾液不反应。结论本研究成功建立了NoV结合唾液HBGAs受体的实验方法,通过NoV毒株与HBGAs相互作用的研究有助于了解NoV的宿主适应特性及病毒进化和流行规律;同时为筛选防治我国人群的抗NoV药物提供技术平台。     

Norovirus Epidemiology and Genetic Diversity in Leipzig,Germany during 2013–2017

Globally and in all age groups, noroviruses are a main cause of gastroenteritis. To assess their local epidemiology and genetic diversity, stool samples of 7509 inpatients with gastrointestinal complaints from all age groups were analyzed. After detection of norovirus genogroup I and II RNA by real-time RT-PCR, viral capsids were genotyped by partial nucleic acid sequencing. In the case of GII.2 strains, polymerase genotypes were also assessed. Between October 2013 and September 2017, presence of norovirus RNA was shown in 611 samples (8.1%), of which 610 (99.8%) were typed successfully. Norovirus positivity rate was higher in patients aged below five years (14.8%) than in older patients (5.7%). Among the 611 norovirus positive samples, GII.4 (56.6%) strains prevailed, followed by GII.6 (11.3%), GII.3 (11.0%) and GII.2 (9.5%). The most common genogroup I (GGI) genotype was GI.3 (3.6%). In addition, rare genotypes such as GII.13, GII.14 and GII.26 were detected. Interestingly, GII.3 infections were most common in children under the age of five years. Assessment of polymerase genotypes in GII.2 viruses showed a shift from P2 to P16, with higher diversity in P2 sequences. The varying distribution of norovirus genotypes depending on season, age and setting of infection highlights the importance of frequent genotyping as a basis for vaccine development and needful adjustments.     

Influenza Vaccine: Epidemiology of norovirus and viral gastroenteritis in Ontario,Canada, 2009–2014

BackgroundNorovirus is the most common cause of acute gastroenteritis in Canada. The illness causes great morbidity and high societal costs. The objective of this article is to describe the epidemiology of norovirus in the province of Ontario, Canada from 2009 to 2014.MethodsTo assess activity of norovirus and viral gastroenteritis (VGE) in Ontario, three datasets were acquired from the provincial government: two traditional surveillance datasets (outbreak and laboratory) and syndromic surveillance data (telehealth), all spanning 2009–2014. All outbreaks, laboratory submissions and telehealth calls were first assessed for total VGE. Norovirus and norovirus-like illness totals were calculated as a proportion of VGE to estimate agent-specific activity levels. Affected institution types, sexes and age groups were also analyzed.ResultsBetween 2009 and 2014, 41.5% of VGE outbreaks, 63.4% of VGE laboratory submissions and 36.6% of all acute gastroenteritis-related (not restricted to viral causes) telehealth calls were attributed to norovirus and norovirus-like illness in Ontario. The most commonly affected institution type was long-term care homes and the most commonly affected age groups were younger (younger than five years) and older (older than 65 years) individuals. Females were slightly more frequently affected than males.ConclusionNorovirus and norovirus-like illnesses were the leading cause of VGE in Ontario between 2009 and 2014. They comprised the greatest percentage of VGE when compared with all other VGE-associated viruses. Additional work is needed to determine all component costs and necessary public health actions to reduce the burden of disease.