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Clinical manifestations and diagnosis of rotavirus infection

Miguel G O'Ryan, MD
David O Matson, MD, PhD
Section Editor
Morven S Edwards, MD
Deputy Editor
Mary M Torchia, MD


Rotaviruses were among the first viral agents identified as important causes of viral gastroenteritis, particularly in children between the ages of six months and two years.

The pathogenesis, epidemiology, clinical manifestations, and diagnosis of rotavirus gastroenteritis will be reviewed here. The prevention of rotavirus infection is discussed separately. (See "Rotavirus vaccines for infants".)

The management of rotavirus infection is as described for other types of viral gastroenteritis and is discussed separately. (See "Acute viral gastroenteritis in children in resource-rich countries: Management and prevention", section on 'Management' and "Acute viral gastroenteritis in adults", section on 'Treatment'.)


At least three factors are thought to play a role in the pathogenesis of rotavirus-induced diarrhea: loss of brush border enzymes, the direct effect of the rotavirus enterotoxin NSP4, and activation of the enteric nervous system.

Acute rotavirus infection is associated with decreased levels of intestinal brush border enzymes such as maltase, sucrase, and lactase [1], leading to malabsorption of D-xylose and lactose in the setting of acute infection [2-4]. Osmotic diarrhea likely occurs as a result of villous epithelial cell destruction with resulting brush border enzyme deficiency and complex sugar malabsorption [5,6]. The success of oral rehydration under these circumstances may reflect the patchy nature of mucosal involvement [4].

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Literature review current through: Nov 2017. | This topic last updated: Feb 27, 2017.
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  1. Bishop RF, Davidson GP, Holmes IH, Ruck BJ. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet 1973; 2:1281.
  2. Hyams JS, Krause PJ, Gleason PA. Lactose malabsorption following rotavirus infection in young children. J Pediatr 1981; 99:916.
  3. Mavromichalis J, Evans N, McNeish AS, et al. Intestinal damage in rotavirus and adenovirus gastroenteritis assessed by d-xylose malabsorption. Arch Dis Child 1977; 52:589.
  4. Sack DA, Rhoads M, Molla A, et al. Carbohydrate malabsorption in infants with rotavirus diarrhea. Am J Clin Nutr 1982; 36:1112.
  5. Davidson GP, Gall DG, Petric M, et al. Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport. J Clin Invest 1977; 60:1402.
  6. Graham DY, Sackman JW, Estes MK. Pathogenesis of rotavirus-induced diarrhea. Preliminary studies in miniature swine piglet. Dig Dis Sci 1984; 29:1028.
  7. Ball JM, Tian P, Zeng CQ, et al. Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein. Science 1996; 272:101.
  8. Johansen K, Hinkula J, Espinoza F, et al. Humoral and cell-mediated immune responses in humans to the NSP4 enterotoxin of rotavirus. J Med Virol 1999; 59:369.
  9. Ward RL, Mason BB, Bernstein DI, et al. Attenuation of a human rotavirus vaccine candidate did not correlate with mutations in the NSP4 protein gene. J Virol 1997; 71:6267.
  10. Lee CN, Wang YL, Kao CL, et al. NSP4 gene analysis of rotaviruses recovered from infected children with and without diarrhea. J Clin Microbiol 2000; 38:4471.
  11. González-Ochoa G, Menchaca GE, Hernández CE, et al. Mutation distribution in the NSP4 protein in rotaviruses isolated from Mexican children with moderate to severe gastroenteritis. Viruses 2013; 5:792.
  12. Greenberg HB, Estes MK. Rotaviruses: from pathogenesis to vaccination. Gastroenterology 2009; 136:1939.
  13. Lundgren O, Peregrin AT, Persson K, et al. Role of the enteric nervous system in the fluid and electrolyte secretion of rotavirus diarrhea. Science 2000; 287:491.
  14. Salazar-Lindo E, Santisteban-Ponce J, Chea-Woo E, Gutierrez M. Racecadotril in the treatment of acute watery diarrhea in children. N Engl J Med 2000; 343:463.
  15. Hagbom M, Istrate C, Engblom D, et al. Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting. PLoS Pathog 2011; 7:e1002115.
  16. Bishop RF, Davidson GP, Holmes IH, Ruck BJ. Letter: Evidence for viral gastroenteritis. N Engl J Med 1973; 289:1096.
  17. Barnes GL, Townley RR. Duodenal mucosal damage in 31 infants with gastroenteritis. Arch Dis Child 1973; 48:343.
  18. Davidson GP, Bishop RF, Townley RR, Holmes IH. Importance of a new virus in acute sporadic enteritis in children. Lancet 1975; 1:242.
  19. Bresee JS, Hummelman E, Nelson EA, Glass RI. Rotavirus in Asia: the value of surveillance for informing decisions about the introduction of new vaccines. J Infect Dis 2005; 192 Suppl 1:S1.
  20. Nakagomi T, Nakagomi O, Takahashi Y, et al. Incidence and burden of rotavirus gastroenteritis in Japan, as estimated from a prospective sentinel hospital study. J Infect Dis 2005; 192 Suppl 1:S106.
  21. Moe K, Hummelman EG, Oo WM, et al. Hospital-based surveillance for rotavirus diarrhea in children in Yangon, Myanmar. J Infect Dis 2005; 192 Suppl 1:S111.
  22. Van Man N, Luan le T, Trach DD, et al. Epidemiological profile and burden of rotavirus diarrhea in Vietnam: 5 years of sentinel hospital surveillance, 1998-2003. J Infect Dis 2005; 192 Suppl 1:S127.
  23. Grimwood K, Buttery JP. Clinical update: rotavirus gastroenteritis and its prevention. Lancet 2007; 370:302.
  24. O'Ryan M, Giaquinto C, Benninghoff B. Human rotavirus vaccine (Rotarix): focus on effectiveness and impact 6 years after first introduction in Africa. Expert Rev Vaccines 2015; 14:1099.
  25. Rha B, Tate JE, Payne DC, et al. Effectiveness and impact of rotavirus vaccines in the United States - 2006-2012. Expert Rev Vaccines 2014; 13:365.
  26. Elliott EJ. Acute gastroenteritis in children. BMJ 2007; 334:35.
  27. Parashar UD, Nelson EA, Kang G. Diagnosis, management, and prevention of rotavirus gastroenteritis in children. BMJ 2013; 347:f7204.
  28. Kapikian AZ, Kim HW, Wyatt RG, et al. Human reovirus-like agent as the major pathogen associated with "winter" gastroenteritis in hospitalized infants and young children. N Engl J Med 1976; 294:965.
  29. Blacklow NR, Greenberg HB. Viral gastroenteritis. N Engl J Med 1991; 325:252.
  30. Echeverria P, Blacklow NR, Cukor GG, et al. Rotavirus as a cause of severe gastroenteritis in adults. J Clin Microbiol 1983; 18:663.
  31. Velázquez FR, Matson DO, Calva JJ, et al. Rotavirus infection in infants as protection against subsequent infections. N Engl J Med 1996; 335:1022.
  32. Gladstone BP, Ramani S, Mukhopadhya I, et al. Protective effect of natural rotavirus infection in an Indian birth cohort. N Engl J Med 2011; 365:337.
  33. Richardson S, Grimwood K, Gorrell R, et al. Extended excretion of rotavirus after severe diarrhoea in young children. Lancet 1998; 351:1844.
  34. Musher DM, Musher BL. Contagious acute gastrointestinal infections. N Engl J Med 2004; 351:2417.
  35. Grinstein S, Gómez JA, Bercovich JA, Biscotti EL. Epidemiology of rotavirus infection and gastroenteritis in prospectively monitored Argentine families with young children. Am J Epidemiol 1989; 130:300.
  36. Gómez J, Bercovich A, Alvarez A, et al. [Seroepidemiology of human rotaviruses in a community of the Avellaneda district, Province of Buenos Aires]. Rev Argent Microbiol 1990; 22:182.
  37. LeBaron CW, Lew J, Glass RI, et al. Annual rotavirus epidemic patterns in North America. Results of a 5-year retrospective survey of 88 centers in Canada, Mexico, and the United States. Rotavirus Study Group. JAMA 1990; 264:983.
  38. Kovacs A, Chan L, Hotrakitya C, et al. Rotavirus gastroenteritis. Clinical and laboratory features and use of the Rotazyme test. Am J Dis Child 1987; 141:161.
  39. Tallett S, MacKenzie C, Middleton P, et al. Clinical, laboratory, and epidemiologic features of a viral gastroenteritis in infants and children. Pediatrics 1977; 60:217.
  40. Foldenauer A, Vossbeck S, Pohlandt F. Neonatal hypocalcaemia associated with rotavirus diarrhoea. Eur J Pediatr 1998; 157:838.
  41. Grimwood K, Coakley JC, Hudson IL, et al. Serum aspartate aminotransferase levels after rotavirus gastroenteritis. J Pediatr 1988; 112:597.
  42. Rodriguez WJ, Kim HW, Arrobio JO, et al. Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children. J Pediatr 1977; 91:188.
  43. Pryor WM, Bye WA, Curran DH, Grohmann GS. Acute diarrhoea in adults: a prospective study. Med J Aust 1987; 147:490.
  44. Hieber JP, Shelton S, Nelson JD, et al. Comparison of human rotavirus disease in tropical and temperate settings. Am J Dis Child 1978; 132:853.
  45. Caprioli A, Pezzella C, Morelli R, et al. Enteropathogens associated with childhood diarrhea in Italy. The Italian Study Group on Gastrointestinal Infections. Pediatr Infect Dis J 1996; 15:876.
  46. Konno T, Suzuki H, Imai A, et al. A long-term survey of rotavirus infection in Japanese children with acute gastroenteritis. J Infect Dis 1978; 138:569.
  47. Rodriguez WJ, Kim HW, Brandt CD, et al. Common exposure outbreak of gastroenteritis due to type 2 rotavirus with high secondary attack rate within families. J Infect Dis 1979; 140:353.
  48. Gurwith M, Wenman W, Hinde D, et al. A prospective study of rotavirus infection in infants and young children. J Infect Dis 1981; 144:218.
  49. Bhan MK, Raj P, Bhandari N, et al. Role of enteric adenoviruses and rotaviruses in mild and severe acute enteritis. Pediatr Infect Dis J 1988; 7:320.
  50. Carlson JA, Middleton PJ, Szymanski MT, et al. Fatal rotavirus gastroenteritis: an analysis of 21 cases. Am J Dis Child 1978; 132:477.
  51. Shukry S, Zaki AM, DuPont HL, et al. Detection of enteropathogens in fatal and potentially fatal diarrhea in Cairo, Egypt. J Clin Microbiol 1986; 24:959.
  52. Johansen K, Hedlund KO, Zweygberg-Wirgart B, Bennet R. Complications attributable to rotavirus-induced diarrhoea in a Swedish paediatric population: report from an 11-year surveillance. Scand J Infect Dis 2008; 40:958.
  53. Rodriguez WJ, Kim HW, Brandt CD, et al. Longitudinal study of rotavirus infection and gastroenteritis in families served by a pediatric medical practice: clinical and epidemiologic observations. Pediatr Infect Dis J 1987; 6:170.
  54. Brandt CD, Kim HW, Rodriguez WJ, et al. Simultaneous infections with different enteric and respiratory tract viruses. J Clin Microbiol 1986; 23:177.
  55. de Vries LS, Bearden D. Neurologic complications of rotavirus in neonates: More common than we thought? Neurology 2015; 84:13.
  56. Kawamura Y, Ohashi M, Ihira M, et al. Nationwide survey of rotavirus-associated encephalopathy and sudden unexpected death in Japan. Brain Dev 2014; 36:601.
  57. Hrdy DB. Epidemiology of rotaviral infection in adults. Rev Infect Dis 1987; 9:461.
  58. Cardemil CV, Cortese MM, Medina-Marino A, et al. Two rotavirus outbreaks caused by genotype G2P[4] at large retirement communities: cohort studies. Ann Intern Med 2012; 157:621.
  59. Wenman WM, Hinde D, Feltham S, Gurwith M. Rotavirus infection in adults. Results of a prospective family study. N Engl J Med 1979; 301:303.
  60. Vollet JJ, Ericsson CD, Gibson G, et al. Human rotavirus in an adult population with travelers' diarrhea and its relationship to the location of food consumption. J Med Virol 1979; 4:81.
  61. Echeverria P, Ramirez G, Blacklow NR, et al. Travelers' diarrhea among U.S. Army troops in South Korea. J Infect Dis 1979; 139:215.
  62. Keswick BH, Blacklow NR, Cukor GC, et al. Norwalk virus and rotavirus in travellers' diarrhoea in Mexico. Lancet 1982; 1:109.
  63. Centers for Disease Control and Prevention (CDC). Foodborne outbreak of Group A rotavirus gastroenteritis among college students--District of Columbia, March-April 2000. MMWR Morb Mortal Wkly Rep 2000; 49:1131.
  64. Marrie TJ, Lee SH, Faulkner RS, et al. Rotavirus infection in a geriatric population. Arch Intern Med 1982; 142:313.
  65. Rayani A, Bode U, Habas E, et al. Rotavirus infections in paediatric oncology patients: a matched-pairs analysis. Scand J Gastroenterol 2007; 42:81.
  66. Saulsbury FT, Winkelstein JA, Yolken RH. Chronic rotavirus infection in immunodeficiency. J Pediatr 1980; 97:61.
  67. Yolken RH, Bishop CA, Townsend TR, et al. Infectious gastroenteritis in bone-marrow-transplant recipients. N Engl J Med 1982; 306:1010.
  68. Willoughby RE, Wee SB, Yolken RH. Non-group A rotavirus infection associated with severe gastroenteritis in a bone marrow transplant patient. Pediatr Infect Dis J 1988; 7:133.
  69. Wood DJ, David TJ, Chrystie IL, Totterdell B. Chronic enteric virus infection in two T-cell immunodeficient children. J Med Virol 1988; 24:435.
  70. Gilger MA, Matson DO, Conner ME, et al. Extraintestinal rotavirus infections in children with immunodeficiency. J Pediatr 1992; 120:912.
  71. Fitts SW, Green M, Reyes J, et al. Clinical features of nosocomial rotavirus infection in pediatric liver transplant recipients. Clin Transplant 1995; 9:201.
  72. González GG, Pujol FH, Liprandi F, et al. Prevalence of enteric viruses in human immunodeficiency virus seropositive patients in Venezuela. J Med Virol 1998; 55:288.
  73. Grohmann GS, Glass RI, Pereira HG, et al. Enteric viruses and diarrhea in HIV-infected patients. Enteric Opportunistic Infections Working Group. N Engl J Med 1993; 329:14.
  74. Rotbart HA, Nelson WL, Glode MP, et al. Neonatal rotavirus-associated necrotizing enterocolitis: case control study and prospective surveillance during an outbreak. J Pediatr 1988; 112:87.
  75. Sızmaz E, Satar M, Ozlü F, et al. The coincidence of necrotizing enterocolitis and rotavirus infections and potential associations with cytokines. Can J Infect Dis Med Microbiol 2012; 23:e103.
  76. Nakagomi T. Rotavirus infection and intussusception: a view from retrospect. Microbiol Immunol 2000; 44:619.
  77. Konno T, Suzuki H, Kutsuzawa T, et al. Human rotavirus and intussusception. N Engl J Med 1977; 297:945.
  78. Konno T, Suzuki H, Kutsuzawa T, et al. Human rotavirus infection in infants and young children with intussusception. J Med Virol 1978; 2:265.
  79. Mulcahy DL, Kamath KR, de Silva LM, et al. A two-part study of the aetiological role of rotavirus in intussusception. J Med Virol 1982; 9:51.
  80. Nicolas JC, Ingrand D, Fortier B, Bricout F. A one-year virological survey of acute intussusception in childhood. J Med Virol 1982; 9:267.
  81. Minney-Smith CA, Levy A, Hodge M, et al. Intussusception is associated with the detection of adenovirus C, enterovirus B and rotavirus in a rotavirus vaccinated population. J Clin Virol 2014; 61:579.
  82. Hertel PM, Estes MK. Rotavirus and biliary atresia: can causation be proven? Curr Opin Gastroenterol 2012; 28:10.
  83. Riepenhoff-Talty M, Gouvea V, Evans MJ, et al. Detection of group C rotavirus in infants with extrahepatic biliary atresia. J Infect Dis 1996; 174:8.
  84. Bobo L, Ojeh C, Chiu D, et al. Lack of evidence for rotavirus by polymerase chain reaction/enzyme immunoassay of hepatobiliary samples from children with biliary atresia. Pediatr Res 1997; 41:229.
  85. Clemente MG, Patton JT, Yolken R, et al. Prevalence of groups A and C rotavirus antibodies in infants with biliary atresia and cholestatic controls. J Pediatr 2015; 166:79.
  86. Takahashi S, Oki J, Miyamoto A, et al. Encephalopathy associated with haemophagocytic lymphohistiocytosis following rotavirus infection. Eur J Pediatr 1999; 158:133.
  87. Riedel F, Kroener T, Stein K, et al. Rotavirus infection and bradycardia-apnoea-episodes in the neonate. Eur J Pediatr 1996; 155:36.
  88. Komori H, Wada M, Eto M, et al. Benign convulsions with mild gastroenteritis: a report of 10 recent cases detailing clinical varieties. Brain Dev 1995; 17:334.
  89. Iyadurai S, Troester M, Harmala J, Bodensteiner J. Benign afebrile seizures in acute gastroenteritis: is rotavirus the culprit? J Child Neurol 2007; 22:887.
  90. Payne DC, Baggs J, Zerr DM, et al. Protective association between rotavirus vaccination and childhood seizures in the year following vaccination in US children. Clin Infect Dis 2014; 58:173.
  91. Hongou K, Konishi T, Yagi S, et al. Rotavirus encephalitis mimicking afebrile benign convulsions in infants. Pediatr Neurol 1998; 18:354.
  92. Makino M, Tanabe Y, Shinozaki K, et al. Haemorrhagic shock and encephalopathy associated with rotavirus infection. Acta Paediatr 1996; 85:632.
  93. Lynch M, Lee B, Azimi P, et al. Rotavirus and central nervous system symptoms: cause or contaminant? Case reports and review. Clin Infect Dis 2001; 33:932.
  94. Yeom JS, Kim YS, Seo JH, et al. Distinctive pattern of white matter injury in neonates with rotavirus infection. Neurology 2015; 84:21.
  95. Sigurdsson L, Flores A, Putnam PE, et al. Postviral gastroparesis: presentation, treatment, and outcome. J Pediatr 1997; 131:751.
  96. Guarino A, Spagnuolo MI, Russo S, et al. Etiology and risk factors of severe and protracted diarrhea. J Pediatr Gastroenterol Nutr 1995; 20:173.
  97. Bhardwaj A, Aggarwal V, Chakravarty A, Mittal SK. Does Rota virus infection cause persistent diarrhoea in childhood? Trop Gastroenterol 1996; 17:18.
  98. Szajewska H, Kantecki M, Albrecht P, Antoniewicz J. Carbohydrate intolerance after acute gastroenteritis--a disappearing problem in Polish children. Acta Paediatr 1997; 86:347.
  99. Cromien JL, Himmelreich CA, Glass RI, Storch GA. Evaluation of new commercial enzyme immunoassay for rotavirus detection. J Clin Microbiol 1987; 25:2359.
  100. Hornsleth A, Jankowski M. Sensitive enzyme immunoassay for the rapid diagnosis of influenza A virus infections in clinical specimens. Res Virol 1990; 141:373.
  101. Thomas EE, Puterman ML, Kawano E, Curran M. Evaluation of seven immunoassays for detection of rotavirus in pediatric stool samples. J Clin Microbiol 1988; 26:1189.
  102. Brandt CD, Arndt CW, Evans GL, et al. Evaluation of a latex test for rotavirus detection. J Clin Microbiol 1987; 25:1800.
  103. Sanekata T, Okada H. Human rotavirus detection by agglutination of antibody-coated erythrocytes. J Clin Microbiol 1983; 17:1141.
  104. Sanders RC, Campbell AD, Jenkins MF. Routine detection of human rotavirus by latex agglutination: comparison with enzyme-linked immunosorbent assay, electron microscopy and polyacrylamide gel electrophoresis. J Virol Methods 1986; 13:285.
  105. Wilde J, Yolken R, Willoughby R, Eiden J. Improved detection of rotavirus shedding by polymerase chain reaction. Lancet 1991; 337:323.
  106. Wolffs PF, Bruggeman CA, van Well GT, van Loo IH. Replacing traditional diagnostics of fecal viral pathogens by a comprehensive panel of real-time PCRs. J Clin Microbiol 2011; 49:1926.
  107. Konno T, Suzuki H, Imai A, Ishida N. Reovirus-like agent in acute epidemic gastroenteritis in Japanese infants: fecal shedding and serologic response. J Infect Dis 1977; 135:259.
  108. Pickering LK, Bartlett AV 3rd, Reves RR, Morrow A. Asymptomatic excretion of rotavirus before and after rotavirus diarrhea in children in day care centers. J Pediatr 1988; 112:361.
  109. Fischer TK, Ashley D, Kerin T, et al. Rotavirus antigenemia in patients with acute gastroenteritis. J Infect Dis 2005; 192:913.
  110. Ray P, Fenaux M, Sharma S, et al. Quantitative evaluation of rotaviral antigenemia in children with acute rotaviral diarrhea. J Infect Dis 2006; 194:588.
  111. Blutt SE, Matson DO, Crawford SE, et al. Rotavirus antigenemia in children is associated with viremia. PLoS Med 2007; 4:e121.
  112. Hemming M, Huhti L, Räsänen S, et al. Rotavirus antigenemia in children is associated with more severe clinical manifestations of acute gastroenteritis. Pediatr Infect Dis J 2014; 33:366.
  113. Husain M, Seth P, Broor S. Detection of group A rotavirus by reverse transcriptase and polymerase chain reaction in feces from children with acute gastroenteritis. Arch Virol 1995; 140:1225.
  114. Champsaur H, Questiaux E, Prevot J, et al. Rotavirus carriage, asymptomatic infection, and disease in the first two years of life. I. Virus shedding. J Infect Dis 1984; 149:667.
  115. Champsaur H, Henry-Amar M, Goldszmidt D, et al. Rotavirus carriage, asymptomatic infection, and disease in the first two years of life. II. Serological response. J Infect Dis 1984; 149:675.
  116. Barnes GL, Callaghan SL, Kirkwood CD, et al. Excretion of serotype G1 rotavirus strains by asymptomatic staff: a possible source of nosocomial infection. J Pediatr 2003; 142:722.
  117. Sato K, Inaba Y, Shinozaki T, et al. Isolation of human rotavirus in cell cultures: brief report. Arch Virol 1981; 69:155.
  118. Wyatt RG, James HD Jr, Pittman AL, et al. Direct isolation in cell culture of human rotaviruses and their characterization into four serotypes. J Clin Microbiol 1983; 18:310.
  119. Taniguchi K, Urasawa S, Urasawa T. Electrophoretic analysis of RNA segments of human rotaviruses cultivated in cell culture. J Gen Virol 1982; 60:171.
  120. Urasawa T, Urasawa S, Taniguchi K. Sequential passages of human rotavirus in MA-104 cells. Microbiol Immunol 1981; 25:1025.
  121. Urasawa S, Urasawa T, Taniguchi K. Three human rotavirus serotypes demonstrated by plaque neutralization of isolated strains. Infect Immun 1982; 38:781.