Query: norovirus classification

title: Updated classification of norovirus genogroups and genotypes.
abstract: Noroviruses are genetically diverse RNA viruses associated with acute gastroenteritis in mammalian hosts. Phylogenetically, they can be segregated into different genogroups as well as P (polymerase) groups and further into genotypes and P types based on amino acid diversity of the complete VP1 gene and nucleotide diversity of the RNA dependent RNA polymerase (RdRp) region of ORF1, respectively. In recent years, several new noroviruses have been reported that warrant an update of the existing classification scheme. Using previously described 2x standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI GX) and the number of genotypes to 49 (9 GI, 27 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX) Viruses for which currently only one sequence is available in public databases were classified into tentative new genogroups (GNA1 and GNA2) and genotypes (GII.NA1, GII.NA2 and GIV.NA1) with their definitive assignment awaiting additional related sequences. Based on nucleotide diversity in the RdRp region, noroviruses can be divided into 60 P types (14 GI, 37 GII, 2 GIII, 1 GIV, 2 GV, 2 GVI, 1 GVII and 1 GX) 2 tentative P groups and 14 tentative P types. Future classification and nomenclature updates will be based on complete genome sequences and will be coordinated and disseminated by the international norovirus classification working group.

title: Norovirus classification and proposed strain nomenclature.
abstract: Without a virus culture system, genetic analysis becomes the principal method to classify norovirus (NoV) strains. Currently, classification of NoV strains beneath the species level has been based on sequences from different regions of the viral genome. As a result, the phylogenetic insights of some virus were not appropriately interpreted, and no consensus has been reached to establish a uniform classification scheme. To provide a consistent and reliable scientific basis for classifying NoVs, we analyzed the amino acid sequences for the major capsid protein of 164 NoV strains by first using an alignment based on the predicted 3D structures. A Bayesian tree was generated, and the maximum likelihood pairwise distances of the aligned sequences were used to evaluate the results from the uncorrected pairwise distance method. Analyses of the pairwise distances demonstrated three clearly resolved peaks, suggesting that NoV strains beneath the species level can be classified at three levels: strain (S) cluster (C) and genogroup (G) The uncorrected pairwise distance ranges for S, C, and G were 0 14.1% 14.3 43.8% and 44.9 61.4% respectively. A scheme with 29 genetic clusters [8 in genogroup 1 (G1) 17 in G2, 2 in G3, and 1 each in G4 and G5] was defined on the basis of the tree topology with the standards provided and was supported by the distance analysis. Of these, five clusters in G2 and one in G1 are newly described. This analysis can serve as the basis for a standardized nomenclature to genetically describe NoV strains.

title: Norovirus Classification, Where are We Headed?

title: Norovirus Infections and Disease in Lower Middle and Low Income Countries, 1997 2018
abstract: Noroviruses are a major cause of viral gastroenteritis. The burden of the norovirus in low resource settings is not well established due to limited data. This study reviews the norovirus prevalence, epidemiology, and genotype diversity in lower middle income countries (LMIC) and in low income countries (LIC) PubMed was searched up to 14 January 2019 for norovirus studies from all LIC and LMIC (World Bank Classification) Studies that tested gastroenteritis cases and/or asymptomatic controls for norovirus by reverse transcription polymerase chain reaction (RT PCR) were included. Sixty four studies, the majority on children <5 years of age, were identified, and 14% (95% confidence interval; CI 14 15, 5158/36,288) of the gastroenteritis patients and 8% (95% CI 7 9, 423/5310) of healthy controls tested positive for norovirus. In LMIC, norovirus was detected in 15% (95% CI 15 16) of cases and 8% (95% CI 8 10) of healthy controls. In LIC, 11% (95% CI 10 12) of symptomatic cases and 9% (95% CI 8 10) of asymptomatic controls were norovirus positive. Norovirus genogroup II predominated overall. GII.4 was the predominant genotype in all settings, followed by GII.3 and GII.6. The most prevalent GI strain was GI.3. Norovirus causes a significant amount of gastroenteritis in low resource countries, albeit with high levels of asymptomatic infection in LIC and a high prevalence of coinfections.

title: Medical devices; immunology and microbiology devices; classification of norovirus serological reagents. Final rule.
abstract: The Food and Drug Administration (FDA) is classifying norovirus serological reagents into class II (special controls) The special control that will apply to these devices is the guidance document entitled `Class II Special Controls Guidance Document: Norovirus Serological Reagents. The Agency is classifying these devices into class II (special controls) because special controls, in addition to general controls, will provide a reasonable assurance of safety and effectiveness of these devices and there is sufficient information to establish special controls.

title: Molecular epidemiology and temporal evolution of norovirus associated with acute gastroenteritis in Amazonas state, Brazil
abstract: BackgroundGlobally, Norovirus (NoV) is considered the most common cause of diarrheal episodes across all age groups. Despite its wide genetic diversity, the GII.4 strain is the most predominant and has been associated with epidemics worldwide. In this study, we characterized sporadic cases of diarrhea from NoV positive children, during a five year period (2010 2014).MethodsA total of 250 NoV positive samples identified by an enzyme immunoassay (EIA) were subjected to RT PCR and partial nucleotide sequencing for polymerase and capsid genes. Phylogenetic analysis was performed to identify NoV genotypes using the binary classification. In addition, sequences from the P2 subdomain (capsid) gene of GII 4 variants were characterized by evolutionary analyses, using the MCMC method implemented in the BEAST package. A 3D structure was built using protein modeling.ResultsPhylogenetic analysis demonstrated a predominance of genotype GII.4 (52.4% 99/189) variants New Orleans_2009 and Sydney_2012 followed by GII.P7/GII.6 with 6.3% (12/189) Amino acid analyses of the GII.4 strains showed several important amino acid changes. A higher evolutionary rate was found, 7.7 x 10 3 in the Sydney variant and 6.3 x 10 3 in the New Orleans. Based in evolutionary analysis the time to the most recent common ancestor (TMRCA) has been calculated as estimates of the population divergence time. Thus, TMRCA for New Orleans and Sydney variant were 2008.7 and 2010.7, respectively. Also, we observed a lineage of transition between New Orleans and Sydney.ConclusionThis study describes the different strains of norovirus isolated from Amazonas state in Brazil during a five year period. Considering that NoV are capable of changing their antigenic epitopes rapidly, a continuous surveillance is important to monitor the occurrence and changes of the NoV in the community through epidemiological studies. These results contribute to the understanding of NoV molecular epidemiology and its evolutionary dynamics in Amazonas state, Brazil.

title: Burden of Severe Norovirus Disease in Taiwan, 2003 2013
abstract: Despite the increasingly recognized role of norovirus in global acute gastroenteritis (AGE) specific estimates of the associated disease burden remain sparse, primarily due to limited availability of sensitive norovirus diagnostics in the clinical setting. We sought to estimate the incidence of norovirus associated hospitalizations by age group in Taiwan using a previously developed indirect regression method.  AGE related hospitalizations in Taiwan were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes abstracted from a national database; population data were provided from the Department of Household Registration Affairs. Population and hospitalizations were aggregated by month and year (July 2003 June 2013) and grouped by age: <5 years, 5 19 years, 20 64 years, and =65 years. Monthly counts of cause unspecified AGE hospitalizations were modeled as a function of counts of known causes, and the residuals were then analyzed to estimate norovirus associated hospitalizations.  Over the study period, an annual mean of 101400 gastroenteritis associated hospitalizations occurred in Taiwan (44 per 10000 person years) most of which (83% had no specified cause. The overall estimated rate of norovirus associated hospitalizations was 6.7 per 10000 person years, with the highest rates in children aged <5 years (63.7/10000 person years) Predicted norovirus peaked in 2006 2007 and 2012 2013.  Our study is one of the first to generate a population based estimate of severe norovirus disease incidence in Asia, and highlights the large burden of norovirus in Taiwan, particularly in children. Predicted peak norovirus seasons coincided with the emergence of new strains and resulting pandemics, supporting the validity of the estimates.

title: 1624. Primary Care Physician Knowledge, Attitudes, and Diagnostic Testing Practices for Norovirus and Acute Gastroenteritis
abstract: Norovirus is a leading cause of acute gastroenteritis (AGE) across the age spectrum; candidate vaccines are in clinical trials. While norovirus diagnostic testing is increasingly available, stool testing may not be performed routinely, which can hamper surveillance and burden of disease estimates. Our objectives were to understand physicians' stool testing practices in outpatients with AGE, and physician knowledge of norovirus, in order to improve surveillance and prepare for vaccine introduction.  Internet and mail survey on AGE and norovirus conducted January to March 2018 among national networks of primary care pediatricians (Peds) family practice (FP) and general internal medicine (GIM) physicians.  The response rate was 59% (820/1,383) During peak AGE season, physicians estimated they ordered stool tests for a median of 15% (interquartile range: 5 33% of their outpatients with AGE. Stool tests were more often available for ova and parasites, Clostridioides difficile, and bacterial culture >95% for all specialties) than for norovirus (6 33% across specialties) even when available, norovirus specific tests were infrequently ordered. Most providers were unaware that norovirus is a leading cause of AGE across all age groups (Peds 80% FP 86% GIM 89% or that alcohol based hand sanitizers are ineffective against norovirus (Peds 51% FP 66% GIM 62%  Physicians infrequently order stool tests for outpatients with AGE, and have knowledge gaps on norovirus prevalence and hand hygiene for prevention. Understanding the limitations of surveillance that relies on physician ordered stool diagnostics, and closing physician knowledge gaps, can help support norovirus vaccine introduction.  No reported disclosures.

title: Clinical and Epidemiologic Profiles for Identifying Norovirus in Acute Gastroenteritis Outbreak Investigations
abstract: Noroviruses are the leading cause of acute gastroenteritis (AGE) outbreaks in the United States. However, outbreaks attributed to norovirus often lack confirmation by diagnostic testing. Clinical and epidemiologic profiles, such as the Kaplan criteria (vomiting in >50% cases, mean incubation period of 24 48 hours, mean duration of illness for 12 60 hours, and negative bacterial stool culture) have been used to distinguish norovirus outbreaks from those caused by bacteria.  Kaplan criteria were evaluated among 10 023 outbreaks reported to the National Outbreak Reporting System (NORS) during 2009 2012. An alternate profile for distinguishing norovirus outbreaks from outbreaks caused by nonviral etiologies was identified using classification and regression tree (CART) modeling. Performance of the Kaplan criteria and alternate profile were compared among laboratory confirmed outbreaks.  The Kaplan criteria were 63.9% sensitive and 100% specific in discriminating norovirus from nonviral outbreaks, but only 3.3% of norovirus and 1.2% of nonviral outbreaks reported all criteria. Clinical and epidemiologic characteristics identified with CART modeling (ratio of proportion of cases with fever to the proportion of cases with vomiting <1, proportion of cases with bloody stool <0.1, proportion of cases with vomiting =0.26) were 85.7% sensitive and 92.4% specific for distinguishing norovirus from nonviral outbreaks and were applicable to more than 8 times as many outbreaks compared with the Kaplan criteria.  Compared with the Kaplan criteria, the CART derived profile had higher sensitivity and broader application in reported AGE outbreaks. Thus, this alternate profile may provide a more useful tool for identifying norovirus during outbreak investigations.

title: Evaluation of the protection against norovirus afforded by E. coli monitoring of shellfish production areas under EU regulations.
abstract: EC Regulation 854/2004 requires the classification of bivalve mollusc harvesting areas according to the faecal pollution status of sites. It has been reported that determination of Escherichia coli in bivalve shellfish is a poor predictor of norovirus (NoV) contamination in individual samples. We explore the correlation of shellfish E. coli data with norovirus presence using data from studies across 88 UK sites (1,184 paired samples) We investigate whether current E. coli legislative standards could be refined to reduce NoV infection risk. A significant relationship between E. coli and NoV was found in the winter months (October to February) using data from sites with at least 10 data pairs (51 sites) We found that the ratio of arithmetic means (log10 E. coli to log10 NoV) at these sites ranged from 0.6 to 1.4. The lower ratios (towards 0.6) might typically indicate situations where the contribution from UV disinfected sewage discharges was more significant. Conversely, higher ratios (towards 1.4) might indicate a prevalence of animal sources of pollution; however, this relationship did not always hold true and so further work is required to fully elucidate the factors of relevance. Reducing the current class B maximum (allowed in 10% of samples) from 46,000 E. coli per 100 g (corresponding NoV value of 75750 103) to 18,000 E. coli per 100 g (corresponding NoV value of 29365 69) reduces maximum levels of NoV by a factor of 2.6 to 1; reducing the upper class B limit to 100% compliance with 4,600 E. coli per 100 g (corresponding NoV value of 7403 39) reduces maximum levels of NoV by a factor of 10.2 to 1. We found using the UK filtered winter dataset that a maximum of 200 NoV corresponded to a maximum of 128 7 E. coli per 100 g. A maximum of 1,000 NoV corresponded to a maximum of 631 14 E. coli per 100 g.