Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Clinical manifestations and diagnosis of noroviruses and related viruses

David O Matson, MD, PhD
Miguel G O'Ryan, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Elinor L Baron, MD, DTMH


In developed countries (ie, those meeting modern standards of water and sewage handling), most cases of gastroenteritis are caused by viral infection. Viral etiologies of gastroenteritis include human caliciviruses (including noroviruses and sapoviruses), astroviruses, enteric adenoviruses, and rotaviruses (table 1).

Following introduction of rotavirus vaccination, norovirus has become the most common cause of gastroenteritis in adults and children. In the United States, norovirus causes 19 to 21 million illnesses, including 570 to 800 deaths, 56,000 to 71,000 hospitalizations, 400,000 emergency department visits, and 1.7 to 1.9 million outpatient visits [1].

The clinical manifestations and diagnosis of norovirus and related viruses will be reviewed here. The epidemiology and management of acute viral gastroenteritis in adults are discussed separately. (See "Epidemiology and pathogenesis of viral gastroenteritis in adults" and "Acute viral gastroenteritis in adults".)

Issues related to rotavirus are discussed separately. (See "Clinical manifestations and diagnosis of rotavirus infection" and "Rotavirus vaccines for infants".)


Norovirus and sapovirus — The human caliciviruses that cause acute gastroenteritis have a worldwide distribution and are divided into two genera, the noroviruses and the sapoviruses. Noroviruses were first identified as viral causes of gastroenteritis in an outbreak in Norwalk, Ohio, and were previously referred to as the Norwalk-like viruses [2]. Sapoviruses were first identified as viral causes of gastroenteritis in Japan and were previously referred to as the Sapporo virus [3].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Feb 2017. | This topic last updated: Fri Dec 02 00:00:00 GMT 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Hall AJ, Lopman BA, Payne DC, et al. Norovirus disease in the United States. Emerg Infect Dis 2013; 19:1198.
  2. Phillips G, Tam CC, Rodrigues LC, Lopman B. Prevalence and characteristics of asymptomatic norovirus infection in the community in England. Epidemiol Infect 2010; 138:1454.
  3. Oka T, Wang Q, Katayama K, Saif LJ. Comprehensive review of human sapoviruses. Clin Microbiol Rev 2015; 28:32.
  4. Lambden PR, Caul EO, Ashley CR, Clarke IN. Sequence and genome organization of a human small round-structured (Norwalk-like) virus. Science 1993; 259:516.
  5. Gibbs MJ, Weiller GF. Evidence that a plant virus switched hosts to infect a vertebrate and then recombined with a vertebrate-infecting virus. Proc Natl Acad Sci U S A 1999; 96:8022.
  6. Davidson I, Silva RF. Creation of diversity in the animal virus world by inter-species and intra-species recombinations: lessons learned from poultry viruses. Virus Genes 2008; 36:1.
  7. Hutson AM, Atmar RL, Estes MK. Norovirus disease: changing epidemiology and host susceptibility factors. Trends Microbiol 2004; 12:279.
  8. Vinjé J. Advances in laboratory methods for detection and typing of norovirus. J Clin Microbiol 2015; 53:373.
  9. Hardy ME, Kramer SF, Treanor JJ, Estes MK. Human calicivirus genogroup II capsid sequence diversity revealed by analyses of the prototype Snow Mountain agent. Arch Virol 1997; 142:1469.
  10. Jiang X, Espul C, Zhong WM, et al. Characterization of a novel human calicivirus that may be a naturally occurring recombinant. Arch Virol 1999; 144:2377.
  11. Matson DO. Calicivirus RNA Recombination. In: Viral Gastroenteritis: Perspectives in Medical Virology, Desselberger U, Gray J. (Eds), Elsevier, Amsterdam 2003. p.555.
  12. Siebenga JJ, Vennema H, Zheng DP, et al. Norovirus illness is a global problem: emergence and spread of norovirus GII.4 variants, 2001-2007. J Infect Dis 2009; 200:802.
  13. Desai R, Hembree CD, Handel A, et al. Severe outcomes are associated with genogroup 2 genotype 4 norovirus outbreaks: a systematic literature review. Clin Infect Dis 2012; 55:189.
  14. Widdowson MA, Cramer EH, Hadley L, et al. Outbreaks of acute gastroenteritis on cruise ships and on land: identification of a predominant circulating strain of norovirus--United States, 2002. J Infect Dis 2004; 190:27.
  15. Lopman B, Vennema H, Kohli E, et al. Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant. Lancet 2004; 363:682.
  16. Centers for Disease Control and Prevention (CDC). Norovirus activity--United States, 2006-2007. MMWR Morb Mortal Wkly Rep 2007; 56:842.
  17. Tu ET, Bull RA, Greening GE, et al. Epidemics of gastroenteritis during 2006 were associated with the spread of norovirus GII.4 variants 2006a and 2006b. Clin Infect Dis 2008; 46:413.
  18. Centers for Disease Control and Prevention (CDC). Emergence of new norovirus strain GII.4 Sydney--United States, 2012. MMWR Morb Mortal Wkly Rep 2013; 62:55.
  19. Saito M, Goel-Apaza S, Espetia S, et al. Multiple norovirus infections in a birth cohort in a Peruvian Periurban community. Clin Infect Dis 2014; 58:483.
  20. Matsushima Y, Ishikawa M, Shimizu T, et al. Genetic analyses of GII.17 norovirus strains in diarrheal disease outbreaks from December 2014 to March 2015 in Japan reveal a novel polymerase sequence and amino acid substitutions in the capsid region. Euro Surveill 2015; 20.
  21. de Graaf M, van Beek J, Vennema H, et al. Emergence of a novel GII.17 norovirus – End of the GII.4 era? Euro Surveill 2015; 20.
  22. Lu J, Sun L, Fang L, et al. Gastroenteritis Outbreaks Caused by Norovirus GII.17, Guangdong Province, China, 2014-2015. Emerg Infect Dis 2015; 21:1240.
  23. Lee CC, Feng Y, Chen SY, et al. Emerging norovirus GII.17 in Taiwan. Clin Infect Dis 2015; 61:1762.
  24. Katayama K, Miyoshi T, Uchino K, et al. Novel recombinant sapovirus. Emerg Infect Dis 2004; 10:1874.
  25. Wang QH, Han MG, Funk JA, et al. Genetic diversity and recombination of porcine sapoviruses. J Clin Microbiol 2005; 43:5963.
  26. Diez-Valcarce M. 6th International Calicivirus Conference, Oct 9-13, 2016. Savannah, GA, USA.
  27. Lee TW, Kurtz JB. Prevalence of human astrovirus serotypes in the Oxford region 1976-92, with evidence for two new serotypes. Epidemiol Infect 1994; 112:187.
  28. Noel JS, Lee TW, Kurtz JB, et al. Typing of human astroviruses from clinical isolates by enzyme immunoassay and nucleotide sequencing. J Clin Microbiol 1995; 33:797.
  29. Taylor MB, Walter J, Berke T, et al. Characterisation of a South African human astrovirus as type 8 by antigenic and genetic analyses. J Med Virol 2001; 64:256.
  30. Kurtz JB, Lee TW. Human astrovirus serotypes. Lancet 1984; 2:1405.
  31. Hudson RW, Herrmann JE, Blacklow NR. Plaque quantitation and virus neutralization assays for human astroviruses. Arch Virol 1989; 108:33.
  32. Herrmann JE, Hudson RW, Perron-Henry DM, et al. Antigenic characterization of cell-cultivated astrovirus serotypes and development of astrovirus-specific monoclonal antibodies. J Infect Dis 1988; 158:182.
  33. Dolin R, Treanor JJ, Madore HP. Novel agents of viral enteritis in humans. J Infect Dis 1987; 155:365.
  34. Estes MK, Prasad BV, Atmar RL. Noroviruses everywhere: has something changed? Curr Opin Infect Dis 2006; 19:467.
  35. Graham DY, Jiang X, Tanaka T, et al. Norwalk virus infection of volunteers: new insights based on improved assays. J Infect Dis 1994; 170:34.
  36. Ryder RW, Greenberg H, Singh N, et al. Seroepidemiology of heat-labile enterotoxigenic Escherichia coli and Norwalk virus infections in Panamanians, Canal Zone residents, Apache Indians, and United States Peace Corps volunteers. Infect Immun 1982; 37:903.
  37. Johnson PC, Mathewson JJ, DuPont HL, Greenberg HB. Multiple-challenge study of host susceptibility to Norwalk gastroenteritis in US adults. J Infect Dis 1990; 161:18.
  38. Zhu S, Regev D, Watanabe M, et al. Identification of immune and viral correlates of norovirus protective immunity through comparative study of intra-cluster norovirus strains. PLoS Pathog 2013; 9:e1003592.
  39. Robilotti E, Deresinski S, Pinsky BA. Norovirus. Clin Microbiol Rev 2015; 28:134.
  40. Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. Updated norovirus outbreak management and disease prevention guidelines. MMWR Recomm Rep 2011; 60:1.
  41. Goller JL, Dimitriadis A, Tan A, et al. Long-term features of norovirus gastroenteritis in the elderly. J Hosp Infect 2004; 58:286.
  42. Lopman BA, Reacher MH, Vipond IB, et al. Clinical manifestation of norovirus gastroenteritis in health care settings. Clin Infect Dis 2004; 39:318.
  43. Mattner F, Sohr D, Heim A, et al. Risk groups for clinical complications of norovirus infections: an outbreak investigation. Clin Microbiol Infect 2006; 12:69.
  44. Centers for Disease Control and Prevention (CDC). Outbreak of acute gastroenteritis associated with Norwalk-like viruses among British military personnel--Afghanistan, May 2002. MMWR Morb Mortal Wkly Rep 2002; 51:477.
  45. Porter CK, Faix DJ, Shiau D, et al. Postinfectious gastrointestinal disorders following norovirus outbreaks. Clin Infect Dis 2012; 55:915.
  46. Ghosh N, Malik FA, Daver RG, et al. Viral associated diarrhea in immunocompromised and cancer patients at a large comprehensive cancer center: a 10-year retrospective study. Infect Dis (Lond) 2017; 49:113.
  47. Echenique IA, Stosor V, Gallon L, et al. Prolonged norovirus infection after pancreas transplantation: a case report and review of chronic norovirus. Transpl Infect Dis 2016; 18:98.
  48. Karandikar UC, Crawford SE, Ajami NJ, et al. Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients. J Gen Virol 2016; 97:2291.
  49. Mai H, Gao Y, Cong X, et al. GII.4 Sydney_2012 norovirus infection in immunocompromised patients in Beijing and its rapid evolution in vivo. J Med Virol 2016; 88:224.
  50. Teunis PF, Sukhrie FH, Vennema H, et al. Shedding of norovirus in symptomatic and asymptomatic infections. Epidemiol Infect 2015; 143:1710.
  51. Rockx B, De Wit M, Vennema H, et al. Natural history of human calicivirus infection: a prospective cohort study. Clin Infect Dis 2002; 35:246.
  52. Vernacchio L, Vezina RM, Mitchell AA, et al. Diarrhea in American infants and young children in the community setting: incidence, clinical presentation and microbiology. Pediatr Infect Dis J 2006; 25:2.
  53. Rosenfeldt V, Vesikari T, Pang XL, et al. Viral etiology and incidence of acute gastroenteritis in young children attending day-care centers. Pediatr Infect Dis J 2005; 24:962.
  54. Marshall JA, Bruggink LD. Laboratory diagnosis of norovirus. Clin Lab 2006; 52:571.
  55. Jiang X, Wang J, Graham DY, Estes MK. Detection of Norwalk virus in stool by polymerase chain reaction. J Clin Microbiol 1992; 30:2529.
  56. Moe CL, Gentsch J, Ando T, et al. Application of PCR to detect Norwalk virus in fecal specimens from outbreaks of gastroenteritis. J Clin Microbiol 1994; 32:642.
  57. Schwab KJ, Estes MK, Neill FH, Atmar RL. Use of heat release and an internal RNA standard control in reverse transcription-PCR detection of Norwalk virus from stool samples. J Clin Microbiol 1997; 35:511.
  58. Ando T, Monroe SS, Noel JS, Glass RI. A one-tube method of reverse transcription-PCR to efficiently amplify a 3-kilobase region from the RNA polymerase gene to the poly(A) tail of small round-structured viruses (Norwalk-like viruses). J Clin Microbiol 1997; 35:570.
  59. Kundu S, Lockwood J, Depledge DP, et al. Next-generation whole genome sequencing identifies the direction of norovirus transmission in linked patients. Clin Infect Dis 2013; 57:407.
  60. Ando T, Monroe SS, Gentsch JR, et al. Detection and differentiation of antigenically distinct small round-structured viruses (Norwalk-like viruses) by reverse transcription-PCR and southern hybridization. J Clin Microbiol 1995; 33:64.
  61. Hutson AM, Atmar RL, Graham DY, Estes MK. Norwalk virus infection and disease is associated with ABO histo-blood group type. J Infect Dis 2002; 185:1335.
  62. Lindesmith L, Moe C, Marionneau S, et al. Human susceptibility and resistance to Norwalk virus infection. Nat Med 2003; 9:548.
  63. Atmar RL, Neill FH, Romalde JL, et al. Detection of Norwalk virus and hepatitis A virus in shellfish tissues with the PCR. Appl Environ Microbiol 1995; 61:3014.
  64. Atmar RL, Neill FH, Woodley CM, et al. Collaborative evaluation of a method for the detection of Norwalk virus in shellfish tissues by PCR. Appl Environ Microbiol 1996; 62:254.
  65. Atmar RL, Metcalf TG, Neill FH, Estes MK. Detection of enteric viruses in oysters by using the polymerase chain reaction. Appl Environ Microbiol 1993; 59:631.
  66. Beuret C. Simultaneous detection of enteric viruses by multiplex real-time RT-PCR. J Virol Methods 2004; 115:1.
  67. Patel MM, Widdowson MA, Glass RI, et al. Systematic literature review of role of noroviruses in sporadic gastroenteritis. Emerg Infect Dis 2008; 14:1224.
  68. de Bruin E, Duizer E, Vennema H, Koopmans MP. Diagnosis of Norovirus outbreaks by commercial ELISA or RT-PCR. J Virol Methods 2006; 137:259.
  69. González GG, Liprandi F, Ludert JE. Evaluation of a commercial enzyme immunoassay for the detection of norovirus antigen in fecal samples from children with sporadic acute gastroenteritis. J Virol Methods 2006; 136:289.
  70. Burton-MacLeod JA, Kane EM, Beard RS, et al. Evaluation and comparison of two commercial enzyme-linked immunosorbent assay kits for detection of antigenically diverse human noroviruses in stool samples. J Clin Microbiol 2004; 42:2587.
  71. Vinjé J, Vennema H, Maunula L, et al. International collaborative study to compare reverse transcriptase PCR assays for detection and genotyping of noroviruses. J Clin Microbiol 2003; 41:1423.
  72. Richards AF, Lopman B, Gunn A, et al. Evaluation of a commercial ELISA for detecting Norwalk-like virus antigen in faeces. J Clin Virol 2003; 26:109.
  73. Dimitriadis A, Bruggink LD, Marshall JA. Evaluation of the Dako IDEIA norovirus EIA assay for detection of norovirus using faecal specimens from Australian gastroenteritis outbreaks. Pathology 2006; 38:157.
  74. Dimitriadis A, Marshall JA. Evaluation of a commercial enzyme immunoassay for detection of norovirus in outbreak specimens. Eur J Clin Microbiol Infect Dis 2005; 24:615.
  75. Herrmann JE, Nowak NA, Perron-Henry DM, et al. Diagnosis of astrovirus gastroenteritis by antigen detection with monoclonal antibodies. J Infect Dis 1990; 161:226.
  76. Kapikian AZ, Wyatt RG, Dolin R, et al. Visualization by immune electron microscopy of a 27-nm particle associated with acute infectious nonbacterial gastroenteritis. J Virol 1972; 10:1075.
  77. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001; 32:331.
  78. O'Ryan ML, Peña A, Vergara R, et al. Prospective characterization of norovirus compared with rotavirus acute diarrhea episodes in chilean children. Pediatr Infect Dis J 2010; 29:855.
  79. Wikswo ME, Desai R, Edwards KM, et al. Clinical profile of children with norovirus disease in rotavirus vaccine era. Emerg Infect Dis 2013; 19:1691.
  80. O'Ryan ML, Lucero Y, Prado V, et al. Symptomatic and asymptomatic rotavirus and norovirus infections during infancy in a Chilean birth cohort. Pediatr Infect Dis J 2009; 28:879.
  81. Krajden M, Brown M, Petrasek A, Middleton PJ. Clinical features of adenovirus enteritis: a review of 127 cases. Pediatr Infect Dis J 1990; 9:636.
  82. Lew JF, Moe CL, Monroe SS, et al. Astrovirus and adenovirus associated with diarrhea in children in day care settings. J Infect Dis 1991; 164:673.
  83. Moe CL, Allen JR, Monroe SS, et al. Detection of astrovirus in pediatric stool samples by immunoassay and RNA probe. J Clin Microbiol 1991; 29:2390.
  84. Glass RI, Noel J, Mitchell D, et al. The changing epidemiology of astrovirus-associated gastroenteritis: a review. Arch Virol Suppl 1996; 12:287.
  85. Kurtz JB, Lee TW, Craig JW, Reed SE. Astrovirus infection in volunteers. J Med Virol 1979; 3:221.
  86. Midthun K, Greenberg HB, Kurtz JB, et al. Characterization and seroepidemiology of a type 5 astrovirus associated with an outbreak of gastroenteritis in Marin County, California. J Clin Microbiol 1993; 31:955.
  87. Caul EO, Paver WK, Clarke SK. Letter: Coronavirus particles in faeces from patients with gastroenteritis. Lancet 1975; 1:1192.
  88. Jevšnik M, Steyer A, Zrim T, et al. Detection of human coronaviruses in simultaneously collected stool samples and nasopharyngeal swabs from hospitalized children with acute gastroenteritis. Virol J 2013; 10:46.
  89. Hyypiä T, Horsnell C, Maaronen M, et al. A distinct picornavirus group identified by sequence analysis. Proc Natl Acad Sci U S A 1992; 89:8847.
  90. Stanway G, Kalkkinen N, Roivainen M, et al. Molecular and biological characteristics of echovirus 22, a representative of a new picornavirus group. J Virol 1994; 68:8232.
  91. Wildenbeest JG, Benschop KS, Minnaar RP, et al. Clinical relevance of positive human parechovirus type 1 and 3 PCR in stool samples. Clin Microbiol Infect 2014; 20:O640.
  92. Ludert JE, Hidalgo M, Gil F, Liprandi F. Identification in porcine faeces of a novel virus with a bisegmented double stranded RNA genome. Arch Virol 1991; 117:97.
  93. Ganesh B, Bányai K, Martella V, et al. Picobirnavirus infections: viral persistence and zoonotic potential. Rev Med Virol 2012; 22:245.
  94. Allander T, Tammi MT, Eriksson M, et al. Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci U S A 2005; 102:12891.
  95. Jin Y, Cheng WX, Xu ZQ, et al. High prevalence of human bocavirus 2 and its role in childhood acute gastroenteritis in China. J Clin Virol 2011; 52:251.
  96. Yamashita T, Kobayashi S, Sakae K, et al. Isolation of cytopathic small round viruses with BS-C-1 cells from patients with gastroenteritis. J Infect Dis 1991; 164:954.
  97. Saikruang W, Khamrin P, Suantai B, et al. Molecular detection and characterization of Aichivirus A in adult patients with diarrhea in Thailand. J Med Virol 2014; 86:983.
  98. Iritani N, Kaida A, Abe N, et al. Detection and genetic characterization of human enteric viruses in oyster-associated gastroenteritis outbreaks between 2001 and 2012 in Osaka City, Japan. J Med Virol 2014; 86:2019.
  99. Levican J, Navas E, Orizola J, et al. Human bocavirus in children with acute gastroenteritis, Chile, 1985-2010. Emerg Infect Dis 2013; 19:1877.
  100. Rovida F, Campanini G, Piralla A, et al. Molecular detection of gastrointestinal viral infections in hospitalized patients. Diagn Microbiol Infect Dis 2013; 77:231.
  101. Chhabra P, Payne DC, Szilagyi PG, et al. Etiology of viral gastroenteritis in children <5 years of age in the United States, 2008-2009. J Infect Dis 2013; 208:790.
  102. Stanway G, Joki-Korpela P, Hyypiä T. Human parechoviruses--biology and clinical significance. Rev Med Virol 2000; 10:57.