1887

Abstract

Norovirus is the leading cause of viral gastroenteritis globally. Norovirus genotype GII.4 is responsible for the majority of outbreaks, but new variants are continuously emerging. The objective of the study was to delineate the clinical manifestations and complications associated with these new norovirus GII.4 variants in children. We investigated norovirus infections from the community outbreak in October 2011–September 2012 and an earlier outbreak in 2006–2007, in northern Taiwan. Norovirus genotypes and their variants were validated using molecular methods. A norovirus outbreak started in mid-2011 and continued through 2012 in northern Taiwan. Hospitalized children infected by norovirus in 2012 showed a significantly higher incidence of intestinal haemorrhage, as indicated by grossly bloody faeces ( = 0.012) and occult blood in faeces ( <0.001), and also presented with more high fever >39 °C ( <0.001), fever >38.5 °C ( <0.001) and fever of any temperature >38 °C ( <0.001), compared with children hospitalized in 2006–2007. Analysis of 20 near-full-length genome sequences indicated an emergence of GII.4 2012 variants in 2011–2012. Circulating noroviruses can be divided into two clusters: GII.4 2012a, which is identical to the newly reported strain GII.4 Sydney 2012, and GII.4 2012b, which is close to GII.4 2006b, the earlier predominant strain. The emerging new variants of norovirus GII.4 caused a distinct clinical syndrome of acute gastroenteritis with severe fever and a high rate of intestinal haemorrhage in children. The genetic diversity associated with changing clinical manifestations poses major obstacles to norovirus control.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000046
2015-05-01
2019-10-14
Loading full text...

Full text loading...

/deliver/fulltext/jmm/64/5/544.html?itemId=/content/journal/jmm/10.1099/jmm.0.000046&mimeType=html&fmt=ahah

References

  1. Bok K., Green K. Y.. ( 2012; ). Norovirus gastroenteritis in immunocompromised patients. . N Engl J Med 367:, 2126–2132. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bok K., Abente E. J., Realpe-Quintero M., Mitra T., Sosnovtsev S. V., Kapikian A. Z., Green K. Y.. ( 2009; ). Evolutionary dynamics of GII.4 noroviruses over a 34-year period. . J Virol 83:, 11890–11901. [CrossRef] [PubMed]
    [Google Scholar]
  3. Boon D., Mahar J. E., Abente E. J., Kirkwood C. D., Purcell R. H., Kapikian A. Z., Green K. Y., Bok K.. ( 2011; ). Comparative evolution of GII.3 and GII.4 norovirus over a 31-year period. . J Virol 85:, 8656–8666. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bu W., Mamedova A., Tan M., Xia M., Jiang X., Hegde R. S.. ( 2008; ). Structural basis for the receptor binding specificity of Norwalk virus. . J Virol 82:, 5340–5347. [CrossRef] [PubMed]
    [Google Scholar]
  5. Bull R. A., White P. A.. ( 2011; ). Mechanisms of GII.4 norovirus evolution. . Trends Microbiol 19:, 233–240. [CrossRef] [PubMed]
    [Google Scholar]
  6. Centers for Disease Control and Prevention (CDC) ( 2013; ). Emergence of new norovirus strain GII.4 Sydney–United States, 2012. . MMWR Morb Mortal Wkly Rep 62:, 55.[PubMed]
    [Google Scholar]
  7. Chen S. Y., Chang Y. C., Lee Y. S., Chao H. C., Tsao K. C., Lin T. Y., Ko T. Y., Tsai C. N., Chiu C. H.. ( 2007; ). Molecular epidemiology and clinical manifestations of viral gastroenteritis in hospitalized pediatric patients in Northern Taiwan. . J Clin Microbiol 45:, 2054–2057. [CrossRef] [PubMed]
    [Google Scholar]
  8. Chen S. Y., Tsai C. N., Lai M. W., Chen C. Y., Lin K. L., Lin T. Y., Chiu C. H.. ( 2009; ). Norovirus infection as a cause of diarrhea-associated benign infantile seizures. . Clin Infect Dis 48:, 849–855. [CrossRef] [PubMed]
    [Google Scholar]
  9. Choi H., Choi Y. B., Hwang J. Y., Cheon D. S., Jeong H. S., Choe Y. H., Yoo K. H., Sung K. W., Koo H. H. et al. ( 2011; ). Clinical manifestations of norovirus infection in Korea pediatric cancer patients. . Korean J Pediatr Infect Dis 18:, 27–34.
    [Google Scholar]
  10. Eden J. S., Tanaka M. M., Boni M. F., Rawlinson W. D., White P. A.. ( 2013; ). Recombination within the pandemic norovirus GII.4 lineage. . J Virol 87:, 6270–6282. [CrossRef] [PubMed]
    [Google Scholar]
  11. Gallimore C. I., Green J., Richards A. F., Cotterill H., Curry A., Brown D. W., Gray J. J.. ( 2004; ). Methods for the detection and characterisation of noroviruses associated with outbreaks of gastroenteritis: outbreaks occurring in the north-west of England during two norovirus seasons. . J Med Virol 73:, 280–288. [CrossRef] [PubMed]
    [Google Scholar]
  12. Gallimore C. I., Iturriza-Gomara M., Xerry J., Adigwe J., Gray J. J.. ( 2007; ). Inter-seasonal diversity of norovirus genotypes: emergence and selection of virus variants. . Arch Virol 152:, 1295–1303. [CrossRef] [PubMed]
    [Google Scholar]
  13. Glass R. I., Parashar U. D., Estes M. K.. ( 2009; ). Norovirus gastroenteritis. . N Engl J Med 361:, 1776–1785. [CrossRef] [PubMed]
    [Google Scholar]
  14. Hoa Tran T. N., Trainor E., Nakagomi T., Cunliffe N. A., Nakagomi O.. ( 2013; ). Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: global distribution of genogroups, genotypes and GII.4 variants. . J Clin Virol 56:, 269–277. [CrossRef] [PubMed]
    [Google Scholar]
  15. Khan R. R., Lawson A. D., Minnich L. L., Martin K., Nasir A., Emmett M. K., Welch C. A., Udall J. N. Jr. ( 2009; ). Gastrointestinal norovirus infection associated with exacerbation of inflammatory bowel disease. . J Pediatr Gastroenterol Nutr 48:, 328–333. [CrossRef] [PubMed]
    [Google Scholar]
  16. Kim M. J., Kim Y. J., Lee J. H., Lee J. S., Kim J. H., Cheon D. S., Jeong H. S., Koo H. H., Sung K. W. et al. ( 2011; ). Norovirus: a possible cause of pneumatosis intestinalis. . J Pediatr Gastroenterol Nutr 52:, 314–318. [CrossRef] [PubMed]
    [Google Scholar]
  17. Lopman B., Vennema H., Kohli E., Pothier P., Sanchez A., Negredo A., Buesa J., Schreier E., Reacher M. et al. ( 2004; ). Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant. . Lancet 363:, 682–688. [CrossRef] [PubMed]
    [Google Scholar]
  18. Ludwig A., Adams O., Laws H. J., Schroten H., Tenenbaum T.. ( 2008; ). Quantitative detection of norovirus excretion in pediatric patients with cancer and prolonged gastroenteritis and shedding of norovirus. . J Med Virol 80:, 1461–1467. [CrossRef] [PubMed]
    [Google Scholar]
  19. Mattner F., Sohr D., Heim A., Gastmeier P., Vennema H., Koopmans M.. ( 2006; ). Risk groups for clinical complications of norovirus infections: an outbreak investigation. . Clin Microbiol Infect 12:, 69–74. [CrossRef] [PubMed]
    [Google Scholar]
  20. Motomura K., Yokoyama M., Ode H., Nakamura H., Mori H., Kanda T., Oka T., Katayama K., Noda M. et al. ( 2010; ). Divergent evolution of norovirus GII/4 by genome recombination from May 2006 to February 2009 in Japan. . J Virol 84:, 8085–8097. [CrossRef] [PubMed]
    [Google Scholar]
  21. Shanker S., Choi J. M., Sankaran B., Atmar R. L., Estes M. K., Prasad B. V.. ( 2011; ). Structural analysis of histo-blood group antigen binding specificity in a norovirus GII.4 epidemic variant: implications for epochal evolution. . J Virol 85:, 8635–8645. [CrossRef] [PubMed]
    [Google Scholar]
  22. Siebenga J. J., Vennema H., Zheng D. P., Vinjé J., Lee B. E., Pang X. L., Ho E. C., Lim W., Choudekar A. et al. ( 2009; ). Norovirus illness is a global problem: emergence and spread of norovirus GII.4 variants, 2001–2007. . J Infect Dis 200:, 802–812. [CrossRef] [PubMed]
    [Google Scholar]
  23. Simon A., Schildgen O., Maria Eis-Hübinger A., Hasan C., Bode U., Buderus S., Engelhart S., Fleischhack G.. ( 2006; ). Norovirus outbreak in a pediatric oncology unit. . Scand J Gastroenterol 41:, 693–699. [CrossRef] [PubMed]
    [Google Scholar]
  24. Tamura K., Peterson D., Peterson N., Stecher G., Nei M., Kumar S.. ( 2011; ). mega5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. . Mol Biol Evol 28:, 2731–2739. [CrossRef] [PubMed]
    [Google Scholar]
  25. Tu E. T., Bull R. A., Greening G. E., Hewitt J., Lyon M. J., Marshall J. A., McIver C. J., Rawlinson W. D., White P. A.. ( 2008; ). Epidemics of gastroenteritis during 2006 were associated with the spread of norovirus GII.4 variants 2006a and 2006b. . Clin Infect Dis 46:, 413–420. [CrossRef] [PubMed]
    [Google Scholar]
  26. Turcios-Ruiz R. M., Axelrod P., St John K., Bullitt E., Donahue J., Robinson N., Friss H. E.. ( 2008; ). Outbreak of necrotizing enterocolitis caused by norovirus in a neonatal intensive care unit. . J Pediatr 153:, 339–344. [CrossRef] [PubMed]
    [Google Scholar]
  27. van Beek J., Ambert-Balay K., Botteldoorn N., Eden J. S., Fonager J., Hewitt J., Iritani N., Kroneman A., Vennema H. et al. ( 2013; ). Indications for worldwide increased norovirus activity associated with emergence of a new variant of genotype II.4, late 2012. . Euro Surveill 18:, 8–9.[PubMed]
    [Google Scholar]
  28. Vesikari T., Rautanen T., Varis T., Beards G. M., Kapikian A. Z.. ( 1990; ). Rhesus Rotavirus candidate vaccine. Clinical trial in children vaccinated between 2 and 5 months of age. . Am J Dis Child 144:, 285–289. [CrossRef] [PubMed]
    [Google Scholar]
  29. Widerlite L., Trier J. S., Blacklow N. R., Schreiber D. S.. ( 1975; ). Structure of the gastric mucosa in acute infectious bacterial gastroenteritis. . Gastroenterology 68:, 425–430.[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000046
Loading
/content/journal/jmm/10.1099/jmm.0.000046
Loading

Data & Media loading...

Supplementary Data



PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error