Asymptomatic and Symptomatic Excretion of Noroviruses during a Hospital Outbreak of Gastroenteritis

Gallimore, Christopher; Cubitt, David; Plessis, Nelita du; Gray, Jim

doi:10.1128/jcm.42.5.2271-2274.2004

Cited by 115 publications

(90 citation statements)

References 18 publications

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“…A number of epidemiological reports on NV infection have shown that the GII genogroup is the predominant agent of NV-associated gastroenteritis (11,14,29,36). In this study, GII strains were also predominant in both sporadic cases and outbreaks.…”

Section: Discussionmentioning

confidence: 52%

“…They are one of the most common causes of gastroenteritis and have been detected in fecal samples from both humans (12,15,28) and animals (20,30,37). Human-associated NV outbreaks resulting from ingestion of contaminated water or food, such as oysters (4,5,18,23), and outbreaks in public places, particularly hospitals, schools, and cruise ships (9,11,22,36), pose an important public health problem.Reverse transcription-PCR (RT-PCR) and sequencing of the partial viral genome are the most popular and useful procedures for obtaining epidemiological and genetic information on NVs. Human NVs can be divided into two genogroups, genogroups GI and GII, by genetic analysis of the RNA polymerase and capsid regions (1, 15), with several genotype classifications having been reported independently (1,16,33).…”

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confidence: 99%

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Genetic Analysis of Noroviruses in Chiba Prefecture, Japan, between 1999 and 2004

et al. 2005

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Noroviruses (NVs) are common pathogens that consist of genetically divergent viruses that induce gastroenteritis in humans and animals. Between September 1999 and June 2004, 1,898 samples obtained from patients showing sporadic or outbreak gastroenteritis in Chiba Prefecture, Japan, were tested for NVs by reverse transcription-PCR. NVs were detected in 603 samples. Approximately 80% were positive for genogroup GII, 13% were positive for genogroup GI, and the remaining 7% were positive for both genogroups. Phylogenetic analysis showed that the GI and GII genogroups could be further divided into 13 and 16 genotypes (including new genotypes), respectively. The GII-4 genotype, which included five small genetic clusters (subtypes), was the most common in this study and was detected in approximately 40% of positive samples. The P2 regions of 10 strains belonging to each of the five GII-4 subtypes showed 5 to 18% amino acid diversity. The amino acid substitutions accumulated in the protruding (P) region during the 5-year study period. Our data suggest that highly variable NV strains are circulating in Chiba Prefecture, with a high rate of genetic change observed during the 5-year study period.The genus Norovirus is a member of the family Caliciviridae. Caliciviruses contain a positive-sense single-stranded RNA genome and include a further three genera, Vesivirus, Lagovirus, and Sapovirus (2,3,8). Noroviruses (NVs) have three major open reading frames (ORFs) that encode nonstructural, capsid, and minor structural proteins, respectively (8). They are one of the most common causes of gastroenteritis and have been detected in fecal samples from both humans (12,15,28) and animals (20,30,37). Human-associated NV outbreaks resulting from ingestion of contaminated water or food, such as oysters (4,5,18,23), and outbreaks in public places, particularly hospitals, schools, and cruise ships (9,11,22,36), pose an important public health problem.Reverse transcription-PCR (RT-PCR) and sequencing of the partial viral genome are the most popular and useful procedures for obtaining epidemiological and genetic information on NVs. Human NVs can be divided into two genogroups, genogroups GI and GII, by genetic analysis of the RNA polymerase and capsid regions (1, 15), with several genotype classifications having been reported independently (1,16,33). Recently, based on the genotype classification of Katayama et al. (16), Kageyama et al. (15) reported on a detailed scheme for the genotyping of NVs based on distribution analysis by using the pairwise distance of the capsid N-terminal/shell domain. They classified the GI and GII genogroups into 14 and 17 genotypes, respectively.During the winter of 2002-2003, an increase in NV outbreaks was reported in Europe and the United States (6, 21). Moreover, worldwide, the GII-4 genotype (Bristol virus-like genotype) has been shown to be the predominant strain of NV associated with gastroenteritis (13,21,(34)(35)(36). Changes in the phylogenetic and genetic characteristics of GII-4 genotype strains...

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Section: Discussionmentioning

confidence: 52%

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confidence: 99%

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confidence: 99%

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Genetic Analysis of Noroviruses in Chiba Prefecture, Japan, between 1999 and 2004

et al. 2005

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“…Nevertheless, taken as a whole, these results have shown that asymptomatic infections were widespread in the food-catering industry in Japan at the time of the study. Recently, excretion of norovirus by symptomatic and asymptomatic individuals during a hospital outbreak of gastroenteritis where a GII/4 strain was dominant has been described (6). At present, norovirus GII/4 strains are the most prevalent in many countries (4,8,27,28).…”

Section: Discussionmentioning

confidence: 99%

Norovirus Infections in Symptomatic and Asymptomatic Food Handlers in Japan

Ozawa¹,

et al. 2007

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Noroviruses are the leading cause of outbreaks of gastroenteritis in the world. At present, norovirus genogroup II, genotype 4 (GII/4), strains are the most prevalent in many countries. In this study we investigated 55 outbreaks and 35 sporadic cases of norovirus-associated gastroenteritis in food handlers in foodcatering settings between 10 November 2005 and 9 December 2006 in Japan. Stool specimens were collected from both symptomatic and asymptomatic individuals and were examined for norovirus by real-time reverse transcription-PCR; the results were then confirmed by sequence analysis. Norovirus was detected in 449 of 2,376 (19%) specimens. Four genogroup I (GI) genotypes and 12 GII genotypes, including one new GII genotype, were detected. The GII/4 sequences were predominant, accounting for 19 of 55 (35%) outbreaks and 16 of 35 (46%) sporadic cases. Our results also showed that a large number of asymptomatic food handlers were infected with norovirus GII/4 strains. Norovirus GII had a slightly higher mean viral load (1 log unit higher) than norovirus GI, i.e., 3.81 ؋ 10 8 versus 2.79 ؋ 10 7 copies/g of stool. Among norovirus GI strains, GI/4 had the highest mean viral load, whereas among GII strains, GII/4 had the highest mean viral load (2.02 ؋ 10 8 and 7.96 ؋ 10 9 copies/g of stool, respectively). Importantly, we found that asymptomatic individuals had mean viral loads similar to those of symptomatic individuals, which may account for the increased number of infections and the predominance of an asymptomatic transmission route.The positive-sense polyadenylated single-stranded RNA virus family Caliciviridae contains four genera: Norovirus, Sapovirus, Lagovirus, and Vesivirus (1). The prototype strain of human norovirus is the Norwalk virus (NV/Human/US/1968), which was first discovered in an outbreak of gastroenteritis in an elementary school in Norwalk, OH, in 1968 (15). Noroviruses are the leading cause of outbreaks of gastroenteritis in the world; they cause outbreaks in various settings, including hospitals, cruise ships, schools, and restaurants (2,9,12,15,23,24,29). In addition, noroviruses have been detected in environmental samples (e.g., treated and untreated sewage) as well as in contaminated foods such as oysters, shellfish, sandwiches, salads, raspberries, and even ice (7,18,19,26). Numerous molecular epidemiological studies have revealed a global distribution of these viruses (25,27,31).The most widely used method of detecting noroviruses is reverse transcription-PCR (RT-PCR), which has high sensitivity; also, the products can be used for further genetic analysis. Real-time RT-PCR assays have also been developed; they are sensitive, broadly reactive, and rapid for the detection of human noroviruses in clinical stool specimens and environmental samples (13,14,21).As the detection methods become more and more sensitive, the numbers of genogroups and genotypes are expected to increase. One emerging characteristic is that strains have been found to persist in one geographical region, only to disapp...

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“…Usually in exposed individuals, histologic lesions correlate with diarrhea, but in one report, lesions in volunteers who did not show clinical symptoms were described (42). There are also numerous reports of asymptomatic individuals who were infected with HuNoVs and shed virus in the feces (11,28).…”

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Pathogenesis of a Genogroup II Human Norovirus in Gnotobiotic Pigs

Cheetham

Souza

Meulia

et al. 2006

J Virol

257

264

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Human noroviruses (HuNoVs) are a major cause of foodborne gastroenteritis worldwide. Because they do not grow in cell culture and there is no animal model for HuNoVs, pathogenesis studies have been hampered. Thus, little is known about their replication strategies or induction of neutralizing antibodies.The limited information on their pathogenesis is from human volunteer studies of HuNoV infections in which villus atrophy in duodenal biopsies and presence of malabsorptive diarrhea were described (1,7,8). No information is available on lesions in other portions of the intestines of these volunteers (9). Intestinal transplant pediatric patients that were diagnosed with HuNoV infection developed secretory or osmotic diarrhea (19,20,31). These patients had prolonged diarrhea (17 to 326 days) due to immunosuppressive therapy. The detection of HuNoV RNA and the clinical symptoms remitted after reduction of the immunosuppressive therapy. Usually in exposed individuals, histologic lesions correlate with diarrhea, but in one report, lesions in volunteers who did not show clinical symptoms were described (42). There are also numerous reports of asymptomatic individuals who were infected with HuNoVs and shed virus in the feces (11, 28).Most past attempts to study these viruses in an animal model may have failed because (i) the human strains that were used were not closely related to the host animal NoV strains, (ii) sensitive detection techniques were lacking, and finally (iii) the role of histo-blood group antigen (HBGA) phenotypes in differential susceptibility of the host was unrecognized. Our goal was to adapt a HuNoV strain to replicate in the gnotobiotic (Gn) pig to develop an animal model for the study of HuNoV pathogenesis. Gnotobiotic pigs are good models for human enteric diseases (40) because pigs resemble humans in their gastrointestinal anatomy, physiology, and immune responses. The Gn pigs are immunocompetent at birth, but they lack maternal antibodies and previous or ongoing exposure to microbial agents, including caliciviruses.Recently, viral RNA genetically similar to that of human NoV GII (65 to 71% amino acid sequence identity in the capsid gene) was detected in pigs in Japan (46, 47) and Europe (22,48). In U.S. swine, our laboratory detected both viral RNA and virus particles similar to GII HuNoV (70% sequence identity in the capsid region) which were infectious for Gn pigs (50). Our approach to infect Gn pigs with a HuNoV was to use a GII strain that is closely related genetically to the identified GII porcine NoVs and that has a broad HBGA binding pattern because little information or reagents are available for pig HBGA. Additionally, we used sensitive assays and reagents including reverse transcription (RT)-PCR to detect fecal shedding, virus-like particles (VLPs) for serological assays, and antisera to these VLPs for antigen enzyme-linked immunosor-

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Asymptomatic and Symptomatic Excretion of Noroviruses during a Hospital Outbreak of Gastroenteritis

Cited by 115 publications

References 18 publications

Genetic Analysis of Noroviruses in Chiba Prefecture, Japan, between 1999 and 2004

Genetic Analysis of Noroviruses in Chiba Prefecture, Japan, between 1999 and 2004

Norovirus Infections in Symptomatic and Asymptomatic Food Handlers in Japan

Pathogenesis of a Genogroup II Human Norovirus in Gnotobiotic Pigs

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