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Journal of Clinical Microbiology, July 2007, p. 2205-2211, Vol. 45, No. 7
0095-1137/07/$08.00+0     doi:10.1128/JCM.02489-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Atypical Norovirus Epidemic in Hong Kong during Summer of 2006 Caused by a New Genogroup II/4 Variant

Eric C. M. Ho, Peter K. C. Cheng, Angela W. L. Lau, Ann H. Wong, and Wilina W. L. Lim^*

Virology Division, Public Health Laboratory Services Branch, Centre for Health Protection, Department of Health, Hong Kong SAR, China

Received 13 December 2006/ Returned for modification 21 March 2007/ Accepted 20 April 2007

Top ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
An atypically high level of norovirus activity was noticed in Hong Kong beginning in early May 2006. A study was carried out to investigate whether this was caused by a new norovirus variant. Epidemiological data including monthly positivity rates and the numbers of outbreaks per month from January to July 2006 were analyzed and compared to those from 2002 to 2005. In a comparison with the epidemiological data from 2001 to 2005, an atypical peak of norovirus-associated gastroenteritis outbreak was observed beginning in May 2006, concurring with a striking increase in norovirus activity. Most of the outbreaks (>60%) were located in homes for the elderly. Phylogenetic analysis for both RdRp and 5' capsid regions showed that this epidemic was caused by a new genogroup II/4 variant. This variant was genetically distinct from the predominant variants of 2002 and 2004 but was closely related to one of the 95/96-subset variants which caused an epidemic in Hong Kong in 2001, suggesting that the 95/96 subset may be starting to recirculate.

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Noroviruses (NoV) constitute a diverse group of nonenveloped RNA viruses belonging to the Caliciviridae family (8, 23). They are now recognized as a major cause of both outbreaks and sporadic cases of acute gastroenteritis worldwide (1, 7, 13, 19, 21, 24, 25, 29, 32). Transmission routes of NoV include ingestion of contaminated food (6) and water (22) and person-to-person spreads (15, 28). Phylogenetic analysis of the capsid region showed that NoV can be classified into five major genogroups (34), of which genogroups I and II are recognized as the major cause of NoV infections in human (30). Of special importance is genogroup II/4 (GII/4), also known as the Bristol or Lordsdale cluster, which was responsible for causing epidemics worldwide (16, 25), including the 95/96 subset, which was responsible for causing a pandemic between 1995 and 2001 (3, 19, 25), and two other variants, causing epidemics in 2002 (3, 12, 20) and 2004 (3, 26).

Surveillance of NoV in Hong Kong was started in 2001. Similar to reports from other countries, our surveillance data showed that NoV seasons usually started in early to mid-September and lasted till late March of the following year. However, we observed an atypical increase in both sporadic and outbreak cases beginning in May 2006. As a result, we compared the epidemiological data of 2006 to those of previous years to see if there were any significant changes in the seasonal pattern of NoV. In addition, we also studied the variant causing such an atypical pattern and its genetic diversity compared with other, previous predominant circulating variants in Hong Kong.

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Specimens. A total of 7,799 routine fecal specimens were collected from patients of all ages with acute gastroenteritis from hospitals and outpatient clinics and during the outbreak investigation from January to July 2006. Human ethics approval was not necessary, since the specimens were collected as part of diagnosis and surveillance activities. Data on the specimens collected from 2001 to 2005 were obtained from our previous study (11). In this study, an outbreak was defined as at least two patients having similar clinical symptoms that were related in place and time. At least one specimen from an individual outbreak was tested. A 10% (wt/vol) suspension was made by mixing 0.1 g of solid stool with 1.0 ml phosphate-buffered saline (pH 7.2). The suspensions were then centrifuged at 1,500 x g for 20 min, followed by collection of the supernatant fluids for viral RNA extraction.

Reverse transcription-PCR and DNA sequence analysis. Viral RNA was extracted from 200 or 220 µl of supernatant fluid using the MagNA Pure LC total nucleic acid isolation kit (Roche Applied Science) or the QiaAmp Virus BioRobot 9604 kit (QIAGEN), respectively, according to the manufacturer's instructions. Extracted RNA was reverse transcribed by murine leukemia virus reverse transcriptase (Applied Biosystems) and a random hexamer. A 155-bp amplicon of the RNA-dependent RNA polymerase (RdRp) gene was amplified using the primers as described by Green et al. (10). For the amplification of the 550-bp on the 5' capsid region of genogroup II NoV, COG2F (14) was used as the forward primer while CapIIb (9) was used as the reverse primer. Selected NoV-positive specimens were sequenced with the ABI Prism Big Dye Terminator cycle sequencing kit using ABI Prism 3100/3130xl DNA sequencers (Applied Biosystems). Specimen selection for sequencing was done on a monthly basis; a fixed percentage of specimens from each month were randomly selected for sequencing. The sequences obtained were aligned with reference norovirus strains. Phylogenetic analysis was carried out using MEGA 3.0 (17). All sequences obtained were then subjected to phylogenetic analysis with the exclusion of the primer region. Phylogenetic reconstructions were carried out using the neighbor-joining method with the Kimura 2-parameter model. Statistical confidence for the tree was assessed by bootstrap analysis (1,000 replicates).

Published norovirus sequences were included for alignments and phylogenetic analysis: Arg320 (accession no. AF190817; listed accession numbers refer to GenBank), Bristol Virus (accession no. X76716), Camberwell (accession no. AF145896), DOUG4770 (accession no. AY057918 for partial RdRp gene and AF406793 for complete capsid gene), Farmington Hills (accession no. AY502023), Hawaii (accession no. U07611), Lordsdale virus (accession no. X86557), Melksham (accession no. X81879), Pont de Roide 671 (accession no. AY682548), Snow Mountain (accession no. AY134748), Toronto (accession no. U02030), and White River/290 (accession no. AF414423). Norwalk (accession no. M87661) was used as the outgroup.

Statistical analysis. The chi-square test was performed using GraphPad Prism version 4.0 for Windows (GraphPad Software). A P value of <0.05 was considered statistically significant.

Nucleotide sequence accession numbers. The novel nucleotide sequences identified in this study were deposited in GenBank. Representative sequences from NoV variants isolated in Hong Kong in 2006 were deposited under accession numbers EF121839 and EF121840.

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Norovirus activity, January to July 2006. Our surveillance data on NoV activity showed that NoV seasons in Hong Kong usually started from early to mid-September and lasted till the end of March of the following year (Fig. 1). A similar seasonal pattern was also observed in the outbreak statistics (Fig. 2). However, unlike previous years, in 2006 we observed an atypical peak of NoV activity in June (Fig. 1). A similar pattern was observed for the NoV-associated gastroenteritis outbreak. While there were only 0 to 2 outbreaks that occurred in May and June from 2002 to 2005 (Fig. 2), a drastic increase in NoV-associated outbreaks was observed in 2006, with 24 and 42 outbreaks occurring in May and June, respectively (Fig. 2). Further investigation of the outbreaks in May to July showed that around 77% of the outbreaks occurred in homes for the elderly; detailed outbreak information was reported elsewhere (18, 33).

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FIG. 1. Monthly distribution of acute GE cases and NoV-positive cases in Hong Kong from January 2003 to July 2006.

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FIG. 2. Monthly distribution of NoV-associated outbreaks in Hong Kong from January 2003 to July 2006.

Statistical analysis of the NoV-positive rate showed that it was significantly higher in the epidemic years (2004 and 2006) than in the nonepidemic year (2005) (P < 0.0001, chi-square test). Even when comparing the epidemic years, the NoV-positive rate in 2006 was significantly higher than that in 2004 (P < 0.0001, chi-square test). Analysis of age group distribution showed that significantly high positivity rates were observed among all age groups compared with that in the nonepidemic year (P < 0.001, chi-square test) (Table 1). Analysis of age distribution in 2006 showed that the age distribution pattern was similar to that observed in 2004, with elderly people more than 60 years old having the highest positivity rate (50.83%), followed by infants and children below 4 years old (43.6%).

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TABLE 1. Age distribution for NoV-positive cases, January 2003 to July 2006

Genetic analysis of the 2006 positive samples. A total of 165 positive specimens between January and July 2006 were selected for sequencing of both the RdRp and 5' capsid regions (Table 2). A representative phylogenetic tree of the RdRp region is shown in Fig. 3a, while that of the 5' capsid region is shown in Fig. 3b. For the purpose of simplicity, only representative sequences from variants causing an epidemic in 2001 (2001a/HK and 2001b/HK), 2002 to 2003 (2002/HK), or 2004 (2004/HK) were incorporated. Similar phylogenetic tree topology was observed in both the RdRp and 5' capsid regions. Phylogenetic analysis of both regions showed that the epidemic we encountered in 2006 was caused by a new GII/4 variant. This new variant was first identified in March 2006 and became the predominant circulating strain from May 2006 onward (Table 2). One interesting point about this new variant is that it was phylogenetically distinct from 2002/HK and 2004/HK but relatively similar to 2001a/HK (Fig. 3b). Furthermore, phylogenetic analysis of the 5' capsid region showed that this variant can be further segregated into two strains, although they had 100% sequence homology in the RdRp region (Fig. 3a and b). This observation was further confirmed by sequence analysis, which showed that the new variant contained a polymorphic site (C/T) at position 5492 relative to Lordsdale/93/UK (X86557). At this position, C was observed in the strain detected in March 2006 (281/06), while T was identified in some sequences (733/06) since June 2006 (Fig. 4b, position D).

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TABLE 2. Monthly distribution of 2006 variant, January to July 2006a

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FIG. 3. Phylogenetic dendrogram of representative NoV specimens in Hong Kong, January to July 2006. (a) Phylogenetic dendrogram generated based on the partial sequence of the RdRp gene. (b) Phylogenetic dendrogram generated based on the 5' capsid gene. Numbers on the branches represent bootstrap values after resampling of 1,000 data sets. Norwalk virus (Norwalk/1968/US) was used as the outgroup.

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FIG. 4. (a) Sequence comparison of partial RdRp gene. A conserved motif, ANNNTG (the boxed sequence), was observed in all variants. (b) Sequence comparison of the 5' capsid region. Positions A and B refer to nucleotide signatures found only in previous epidemic variants but not in the 2006 variant. Position C refers to a unique nucleotide signature found only in the 2006 variant. Position D refers to a polymorphic site found in the 2006 variant identified in March and June 2006. Nucleotide positions are referenced to the Lordsdale/1993/UK sequence.

Sequence analysis showed that this new variant carried a signature at position 5372 relative to the Lordsdale/1993/UK sequence which was not found in previous epidemic strains (Fig. 4b, position C). In addition, certain unique signature nucleotides were present in both the new variant and 2001a/HK but not in 2002/HK and 2004/HK or vice versa. In the RdRp region, both 2001a/HK and the new variant showed a signature motif, AATTTG, starting at position 4547 relative to the Lordsdale/1993/UK sequence, which was different from the motifs observed in 2002/HK and 2004/HK (Fig. 4a). In the 5' capsid region, another signature was found at position 5276 relative to the Lordsdale/1993/UK sequence. At this position, C was found in 2001a/HK and the new variant, while T was found in 2002/HK and 2004/HK (Fig. 4b, position B). No nonsynonymous mutation was observed in the RdRp region of the new variant compared with the previous epidemic strains in Hong Kong. Unlike the case with the RdRp region, a nonsynonymous mutation was observed in the capsid region of this new variant in comparison with sequences from the previous epidemic strains in Hong Kong. This nucleotide change, from A to G at position 5127 relative to the Lordadale/1993/UK sequence, contributed to an amino acid change from threonine to alanine (Fig. 4b, position A).

We also compared the sequence of this new variant with the sequences of representative viruses causing epidemics in Europe in 2006 (2006a/EU and 2006b/EU) obtained from the FBVE network (http://www.rivm.nl/bnwww). Results showed that 2006a/EU was not found in any specimens analyzed; rather, it closely resembled 2004/HK, with the same signature motif, AACTTG, starting at position 4547 relative to the Lordsdale/93/UK sequence. 2006b/EU had a signature motif, AATTTG, starting at position 4547 relative to the Lordsdale/93/UK sequence (Fig. 4a). Besides, high sequence homology was also observed between the new variant and 2006b/EU, with 99% homology (96/97) in the RdRp region and 100% homology (282/282) in the 5' capsid region, respectively (Fig. 4a and b).

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Similar to those reported elsewhere (4, 31), NoV seasons in Hong Kong usually started in September and lasted till March of the following year. This phenomenon was observed from 2001 to 2005 with a slight deviation in 2004. Unlike the case in previous years, an atypically high NoV-positive rate caused by a new GII/4 variant was observed from May to July with a peak in June in 2006. This was reflected by an increase in the number of sporadic cases and outbreaks during the period compared with that of previous years. It should be noted that the number of specimens tested in the first seven months of 2006 was already 80% more than the total number of specimens tested in 2004, when the last epidemic occurred. Although the sample size was drastically increased, we observed the NoV-positive rate in 2006 was significantly higher than that in 2004, suggesting the scale of the 2006 epidemic was much larger than that of 2004. Similar to epidemics caused by other GII/4 variants (12, 31), most of the outbreaks occurred in health care settings including homes for the elderly (>60%) and hospitals (30%). Such a large scale for an epidemic occurring in summer raised suspicions that this new variant had a higher attack rate than other GII/4 variants reported before. This is supported by the drastic increase in positivity rates for all age groups except that of ages 5 to 14 years. Similar to the epidemic in 2004, elderly people over 60 years old and children below 4 years old were more susceptible to the new variant than the other age groups.

Since the International Committee on Taxonomy of Viruses has not yet come out with a classification scheme for NoV, we used the classification scheme proposed recently by Zheng et al. (34). Partial sequences from the major capsid (VP1) were used for phylogenetic analysis, and sequence alignment as shown in Fig. 4b is similar to that reported by Zheng et al. (34), suggesting it is reliable to use the 5' capsid region for genotyping of NoV. Since several studies reported recombinations in the ORF1-2 junction (2, 27), partial sequences from the RdRp and 5' capsid regions were thus analyzed to determine whether there was recombination in the ORF1-2 junction of the new variant. No sign of recombination was observed in this new variant, since the topologies of the phylogenetic trees of both the RdRp and 5' capsid regions were similar.

Results of sequence analysis for both the RdRp and 5' capsid regions showed that this new variant was distinct from the variants causing epidemics in previous years. Sequence analysis of specimens retrieved from March and June showed that a polymorphic site was present at position 5492 relative to the Lordsdale/1993/UK sequence in the 5' capsid region of the new variant, though the RdRp region showed 100% sequence homology. Since there was a 3-month time gap when this polymorphism was detected, this suggested that the polymorphic position was likely to be caused by sporadic point mutation. If such a high mutation rate was a unique phenomenon among GII/4 strains compared with other genogroup II clusters, this could partially explain why GII/4 strains are the predominant circulating strains over the last 10 years.

When we analyzed the signature motif reported by Lopman et al. (20), we found that the motif in the new variant was the same as that of 2001a/HK. Based on this observation, we postulated that this new variant evolved from 2001a/HK. This hypothesis is further supported by sequence analysis of the 5' capsid region. In this region, another nucleotide signature unique to 2001a/HK and the new variant was observed at position 5276 relative to the Lordsdale/93/UK sequence. It should be noted that compared to the original sequence of Lordsdale/93/UK, there is a nonsynonymous mutation from G to A at position 5127 present in all epidemic strains in Hong Kong from 2001 to 2004 but absent from this new variant. Since the 5' capsid region is highly conserved among the NoV genome (14) and is responsible for viral capsid assembly (5), it is not clear whether this nonsynonymous mutation would have a contributing effect on the assembly of viral capsid and thus result in changes in antigenicity.

Apart from Hong Kong, NoV epidemics were also reported in various countries, including Australia, Canada, United Kingdom and several European countries, in early 2006; we obtained the sequences of the epidemic strains in Europe from the FBVE website and compared them with our local epidemic sequences. The sequences were aligned and analyzed. The result showed that the new variant was almost identical to 2006b/EU, while 2006a/EU was not found in any specimen analyzed. This is the first time we observed a discrepancy between the epidemic strains reported in Hong Kong and Europe.

In this report, we showed that there was an atypical NoV epidemic in Hong Kong during the summer of 2006. The new variant causing the epidemic is phylogenetically different from the previous epidemic strains but closely resembles the 2001a/HK strain and is related to the 95/96 subsets. It is certain that the large-scale epidemic occurring in 2006 was the result of a change in the antigenicity of the new variant compared with that of previous predominant circulating strains. Since we started the strain surveillance in 2001, we have witnessed the emergence of new variants in 2002, 2004, and 2006. With such an enormous capacity for genetic change, it is expected there will be more new variants emerging in the coming years.

 
We thank the staff at the Virology Division, Public Health Laboratory Services Branch, Centre for Health Protection, for their technical assistance.

 
* Corresponding author. Mailing address: Virology Division, Public Health Laboratory Centre, 382 Nam Cheong Street, Shek Kip Mei, Kowloon, Hong Kong. Phone: (852) 2319 8252. Fax: (852) 2319 5989. E-mail: wllim{at}pacific.net.hk

Published ahead of print on 2 May 2007.

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1
1. Buesa, J., B. Collado, P. Lopez-Andujar, R. bu-Mallouh, D. J. Rodriguez, D. A. Garcia, J. Prat, S. Guix, T. Llovet, G. Prats, and A. Bosch. 2002. Molecular epidemiology of caliciviruses causing outbreaks and sporadic cases of acute gastroenteritis in Spain. J. Clin. Microbiol. 40:2854-2859.[Abstract/Free Full Text]
2
2. Bull, R. A., G. S. Hansman, L. E. Clancy, M. M. Tanaka, W. D. Rawlinson, and P. A. White. 2005. Norovirus recombination in ORF1/ORF2 overlap. Emerg. Infect. Dis. 11:1079-1085.[Medline]
3
3. Bull, R. A., E. T. Tu, C. J. McIver, W. D. Rawlinson, and P. A. White. 2006. Emergence of a new norovirus genotype II.4 variant associated with global outbreaks of gastroenteritis. J. Clin. Microbiol. 44:327-333.[Abstract/Free Full Text]
4
4. Centers for Disease Control and Prevention. 2003. Norovirus activity—United States, 2002. Morb. Mortal. Wkly. Rep. 52:41-45.[Medline]
5
5. Chakravarty, S., A. M. Hutson, M. K. Estes, and B. V. Prasad. 2005. Evolutionary trace residues in noroviruses: importance in receptor binding, antigenicity, virion assembly, and strain diversity. J. Virol. 79:554-568.[Abstract/Free Full Text]
6
6. Cheng, P. K., D. K. Wong, T. W. Chung, and W. W. Lim. 2005. Norovirus contamination found in oysters worldwide. J. Med. Virol. 76:593-597.[CrossRef][Medline]
7
7. Fankhauser, R. L., J. S. Noel, S. S. Monroe, T. Ando, and R. I. Glass. 1998. Molecular epidemiology of "Norwalk-like viruses" in outbreaks of gastroenteritis in the United States. J. Infect. Dis. 178:1571-1578.[CrossRef][Medline]
8
8. Green, K. Y., T. Ando, M. S. Balayan, T. Berke, I. N. Clarke, M. K. Estes, D. O. Matson, S. Nakata, J. D. Neill, M. J. Studdert, and H. J. Thiel. 2000. Taxonomy of the caliciviruses. J. Infect. Dis. 181(Suppl. 2):S322-S330.[CrossRef][Medline]
9
9. Green, S. M., P. R. Lambden, E. O. Caul, and I. N. Clarke. 1997. Capsid sequence diversity in small round structured viruses from recent UK outbreaks of gastroenteritis. J. Med. Virol. 52:14-19.[CrossRef][Medline]
10
10. Green, S. M., P. R. Lambden, Y. Deng, J. A. Lowes, S. Lineham, J. Bushell, J. Rogers, E. O. Caul, C. R. Ashley, and I. N. Clarke. 1995. Polymerase chain reaction detection of small round-structured viruses from two related hospital outbreaks of gastroenteritis using inosine-containing primers. J. Med. Virol. 45:197-202.[Medline]
11
11. Ho, E. C., P. K. Cheng, D. A. Wong, A. W. Lau, and W. W. Lim. 2006. Correlation of norovirus variants with epidemics of acute viral gastroenteritis in Hong Kong. J. Med. Virol. 78:1473-1479.[CrossRef][Medline]
12
12. Ike, A. C., S. O. Brockmann, K. Hartelt, R. E. Marschang, M. Contzen, and R. M. Oehme. 2006. Molecular epidemiology of norovirus in outbreaks of gastroenteritis in southwest Germany from 2001 to 2004. J. Clin. Microbiol. 44:1262-1267.[Abstract/Free Full Text]
13
13. Inouye, S., K. Yamashita, S. Yamadera, M. Yoshikawa, N. Kato, and N. Okabe. 2000. Surveillance of viral gastroenteritis in Japan: pediatric cases and outbreak incidents. J. Infect. Dis. 181(Suppl. 2):S270-S274.[CrossRef][Medline]
14
14. Kageyama, T., S. Kojima, M. Shinohara, K. Uchida, S. Fukushi, F. B. Hoshino, N. Takeda, and K. Katayama. 2003. Broadly reactive and highly sensitive assay for Norwalk-like viruses based on real-time quantitative reverse transcription-PCR. J. Clin. Microbiol. 41:1548-1557.[Abstract/Free Full Text]
15
15. Kobayashi, S., T. Morishita, T. Yamashita, K. Sakae, O. Nishio, T. Miyake, Y. Ishihara, and S. Isomura. 1991. A large outbreak of gastroenteritis associated with a small round structured virus among schoolchildren and teachers in Japan. Epidemiol. Infect. 107:81-86.[Medline]
16
16. Koopmans, M., J. Vinje, M. de Wit, I. Leenen, W. van der Poel, and Y. van Duynhoven. 2000. Molecular epidemiology of human enteric caliciviruses in The Netherlands. J. Infect. Dis. 181(Suppl. 2):S262-S269.[CrossRef][Medline]
17
17. Kumar, S., K. Tamura, I. B. Jakobsen, and M. Nei. 2001. MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17:1244-1245.[Abstract/Free Full Text]
18
18. Lam, M., and R. Ho. 2006. Declining trend of gastroenteritis outbreaks caused by norovirus in institutions. Commun. Dis. Watch 3:65-66.
19
19. Lau, C. S., D. A. Wong, L. K. Tong, J. Y. Lo, A. M. Ma, P. K. Cheng, and W. W. Lim. 2004. High rate and changing molecular epidemiology pattern of norovirus infections in sporadic cases and outbreaks of gastroenteritis in Hong Kong. J. Med. Virol. 73:113-117.[CrossRef][Medline]
20
20. Lopman, B., H. Vennema, E. Kohli, P. Pothier, A. Sanchez, A. Negredo, J. Buesa, E. Schreier, M. Reacher, D. Brown, J. Gray, M. Iturriza, C. Gallimore, B. Bottiger, K. O. Hedlund, M. Torven, C. H. von Bonsdorff, L. Maunula, M. Poljsak-Prijatelj, J. Zimsek, G. Reuter, G. Szucs, B. Melegh, L. Svennson, D. Y. van, and M. Koopmans. 2004. Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant. Lancet 363:682-688.[CrossRef][Medline]
21
21. Martinez, N., C. Espul, H. Cuello, W. Zhong, X. Jiang, D. O. Matson, and T. Berke. 2002. Sequence diversity of human caliciviruses recovered from children with diarrhea in Mendoza, Argentina, 1995-1998. J. Med. Virol. 67:289-298.[CrossRef][Medline]
22
22. Maunula, L., I. T. Miettinen, and C. H. von Bonsdorff. 2005. Norovirus outbreaks from drinking water. Emerg. Infect. Dis. 11:1716-1721.[Medline]
23
23. Mayo, M. A. 2002. A summary of taxonomic changes recently approved by ICTV. Arch. Virol. 147:1655-1663.[CrossRef][Medline]
24
24. Monroe, S. S., T. Ando, and R. I. Glass. 2000. Introduction: human enteric caliciviruses—an emerging pathogen whose time has come. J. Infect. Dis. 181(Suppl. 2):S249-S251.[CrossRef][Medline]
25
25. Noel, J. S., R. L. Fankhauser, T. Ando, S. S. Monroe, and R. I. Glass. 1999. Identification of a distinct common strain of "Norwalk-like viruses" having a global distribution. J. Infect. Dis. 179:1334-1344.[CrossRef][Medline]
26
26. Okada, M., T. Tanaka, M. Oseto, N. Takeda, and K. Shinozaki. 2006. Genetic analysis of noroviruses associated with fatalities in healthcare facilities. Arch. Virol. 151:1635-1641.[CrossRef][Medline]
27
27. Phan, T. G., T. Kuroiwa, K. Kaneshi, Y. Ueda, S. Nakaya, S. Nishimura, A. Yamamoto, K. Sugita, T. Nishimura, F. Yagyu, S. Okitsu, W. E. Muller, N. Maneekarn, and H. Ushijima. 2006. Changing distribution of norovirus genotypes and genetic analysis of recombinant GIIb among infants and children with diarrhea in Japan. J. Med. Virol. 78:971-978.[CrossRef][Medline]
28
28. Riordan, T. 1991. Norwalk-like viruses and winter vomiting disease, p. 61-94. In P. Morgan-Capner (ed.), Current topics in clinical virology. Public Health Laboratory Service, London, United Kingdom.
29
29. Subekti, D. S., P. Tjaniadi, M. Lesmana, C. Simanjuntak, S. Komalarini, H. Digdowirogo, B. Setiawan, A. L. Corwin, J. R. Campbell, K. R. Porter, and B. A. Oyofo. 2002. Characterization of Norwalk-like virus associated with gastroenteritis in Indonesia. J. Med. Virol. 67:253-258.[CrossRef][Medline]
30
30. Vinje, J., H. Vennema, L. Maunula, C. H. von Bonsdorff, M. Hoehne, E. Schreier, A. Richards, J. Green, D. Brown, S. S. Beard, S. S. Monroe, B. E. de, L. Svensson, and M. P. Koopmans. 2003. International collaborative study to compare reverse transcriptase PCR assays for detection and genotyping of noroviruses. J. Clin. Microbiol. 41:1423-1433.[Abstract/Free Full Text]
31
31. Vipond, I. B., E. O. Caul, D. Hirst, B. Carmen, A. Curry, B. A. Lopman, P. Pead, M. A. Pickett, P. R. Lambden, and I. N. Clarke. 2004. National epidemic of Lordsdale Norovirus in the UK. J. Clin. Virol. 30:243-247.[Medline]
32
32. White, P. A., G. S. Hansman, A. Li, J. Dable, M. Isaacs, M. Ferson, C. J. McIver, and W. D. Rawlinson. 2002. Norwalk-like virus 95/96-US strain is a major cause of gastroenteritis outbreaks in Australia. J. Med. Virol. 68:113-118.[CrossRef][Medline]
33
33. Yung, R., R. Ho, and M. Lam. 2006. Update on norovirus activity. Commun. Dis. Watch 3:53-55.
34
34. Zheng, D. P., T. Ando, R. L. Fankhauser, R. S. Beard, R. I. Glass, and S. S. Monroe. 2006. Norovirus classification and proposed strain nomenclature. Virology 346:312-323.[CrossRef][Medline]

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Journal of Clinical Microbiology, July 2007, p. 2205-2211, Vol. 45, No. 7
0095-1137/07/$08.00+0     doi:10.1128/JCM.02489-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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• Aw, T. G., Gin, K. Y.-H., Ean Oon, L. L., Chen, E. X., Woo, C. H. (2009). Prevalence and Genotypes of Human Noroviruses in Tropical Urban Surface Waters and Clinical Samples in Singapore. Appl. Environ. Microbiol. 75: 4984-4992 [Abstract] [Full Text]  
• Iwai, M., Hasegawa, S., Obara, M., Nakamura, K., Horimoto, E., Takizawa, T., Kurata, T., Sogen, S.-i., Shiraki, K. (2009). Continuous Presence of Noroviruses and Sapoviruses in Raw Sewage Reflects Infections among Inhabitants of Toyama, Japan (2006 to 2008). Appl. Environ. Microbiol. 75: 1264-1270 [Abstract] [Full Text]  
• Sdiri-Loulizi, K., Ambert-Balay, K., Gharbi-Khelifi, H., Sakly, N., Hassine, M., Chouchane, S., Guediche, M. N., Pothier, P., Aouni, M. (2009). Molecular Epidemiology of Norovirus Gastroenteritis Investigated Using Samples Collected from Children in Tunisia during a Four-Year Period: Detection of the Norovirus Variant GGII.4 Hunter as Early as January 2003. J. Clin. Microbiol. 47: 421-429 [Abstract] [Full Text]  
• Motomura, K., Oka, T., Yokoyama, M., Nakamura, H., Mori, H., Ode, H., Hansman, G. S., Katayama, K., Kanda, T., Tanaka, T., Takeda, N., Sato, H., and the Norovirus Surveillance Group of Japan, (2008). Identification of Monomorphic and Divergent Haplotypes in the 2006-2007 Norovirus GII/4 Epidemic Population by Genomewide Tracing of Evolutionary History. J. Virol. 82: 11247-11262 [Abstract] [Full Text]  
• Kroneman, A., Verhoef, L., Harris, J., Vennema, H., Duizer, E., van Duynhoven, Y., Gray, J., Iturriza, M., Bottiger, B., Falkenhorst, G., Johnsen, C., von Bonsdorff, C.-H., Maunula, L., Kuusi, M., Pothier, P., Gallay, A., Schreier, E., Hohne, M., Koch, J., Szucs, G., Reuter, G., Krisztalovics, K., Lynch, M., McKeown, P., Foley, B., Coughlan, S., Ruggeri, F. M., Di Bartolo, I., Vainio, K., Isakbaeva, E., Poljsak-Prijatelj, M., Grom, A. H., Mijovski, J. Z., Bosch, A., Buesa, J., Fauquier, A. S., Hernandez-Pezzi, G., Hedlund, K.-O., Koopmans, M. (2008). Analysis of Integrated Virological and Epidemiological Reports of Norovirus Outbreaks Collected within the Foodborne Viruses in Europe Network from 1 July 2001 to 30 June 2006. J. Clin. Microbiol. 46: 2959-2965 [Abstract] [Full Text]  
• Tu, E. T.-V., Bull, R. A., Kim, M.-J., McIver, C. J., Heron, L., Rawlinson, W. D., White, P. A. (2008). Norovirus Excretion in an Aged-Care Setting. J. Clin. Microbiol. 46: 2119-2121 [Abstract] [Full Text]  
• Kroneman, A., Harris, J., Vennema, H., Duizer, E., van Duynhoven, Y., Gray, J., Iturriza, M., Bottiger, B., Falkenhorst, G., Johnsen, C., von Bonsdorff, C.-H., Maunula, L., Kuusi, M., Pothier, P., Gallay, A., Schreier, E., Koch, J., Szucs, G., Reuter, G., Krisztalovics, K., Lynch, M., McKeown, P., Foley, B., Coughlan, S., Ruggeri, F. M., Di Bartolo, I., Vainio, K., Isakbaeva, E., Poljsak-Prijatelj, M., Grom, A. H., Bosch, A., Buesa, J., Fauquier, A. S., Hernandez-Pezzi, G., Hedlund, K.-O., Koopmans, M. (2008). Data quality of 5 years of central norovirus outbreak reporting in the European Network for food-borne viruses. J Public Health (Oxf) 30: 82-90 [Abstract] [Full Text]  

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