Rotavirus
Epidemiology
- single most important viral cause of severe gastroenteritis in children worldwide
- Rotavirus predominantly infects children, but infection also occurs in adults.
- Immunosuppressed hosts, including children, appear to develop a more severe and protracted infection.
- Cases in adults are typically mild and seen in families of affected children [35,44]. In addition, rotavirus has been implicated in traveler's diarrhea [45-47], and in outbreaks of gastroenteritis in colleges [48], nursing homes [49], or other institutions.
- rotavirus yearly:
- 2.1-3.2 million episodes of diarrhea
- 410-600 K outpt visits, 160000 ED visits
- 50-70K hospitalizations, 20-70 deaths, among children < 5yo.
- (Pediatrics Vol 122, No. 5, Nov 2008)
- Rotavirus does not appear to be a common cause of severe or persistent diarrhea in individuals with human immunodeficiency virus (HIV) infection [57,58].
Clinical
- vomiting, non-bloody diarrhea, and fever [8,31-33]
- Disease manifestations in hospitalized children have lasted an average of eight days [32], although protracted episodes have been noted on occasion.
- Stools: watery or yellow or green without mucus or blood. Minimal to moderate numbers of fecal leukocytes are seen in approximately one-third of samples [34,41,42].
- Labs: WBC usually normal in uncomplicated cases. Mild elevations AST have been reported during acute illness without other evidence of hepatic injury [40], and these elevations may reflect damage to intestinal epithelial cells.
- Although the vast majority of children recover from rotavirus gastroenteritis completely, some children continue to have protracted diarrhea or other gastrointestinal disturbances such as persistent gastroparesis and diarrhea [74,75]. Carbohydrate intolerance or lactase intolerance may persist after resolution of diarrhea [76]. Epidemiologic studies have suggested that rotavirus does not increase the risk for subsequent persistent diarrhea in childhood [77].
Diagnosis
- Rotavirus can be isolated in culture, but direct immune-based assays of stool and polymerase chain reaction (PCR) techniques have been employed most frequently to make the diagnosis.
Pathogenesis
- jejunal and duodenal mucosa appear to have patchy irregularities, which consist of shortening and blunting of villi, and increased infiltration of the lamina propria with mononuclear cells. EM reveals numerous rotavirus particles in the epithelial cells. The success of oral rehydration under these circumstances may reflect the patchy nature of the mucosal abnormality [18].
- Causes of diarrhea:
- loss of brush border enzymes -> complex sugar malabsorption -> osmotic diarrhea. decreased levels of intestinal brush border enzymes such as maltase, sucrase, and lactase [15], causes lactose and D-xylose malabsorption in acutely infected children [16-18] and the presence of reducing substances in diarrheal stool [18].
- the direct effect of the rotavirus enterotoxin NSP4 (rotavirus nonstructural protein NSP4, the product of gene segment 10, has been shown to have direct toxic effects on the gastrointestinal mucosa [21], and antibody to this protein may be associated with protection from rotavirus induced diarrhea [22]. However, this protein is not the sole cause of diarrhea in this infection because significant sequence variation in the gene for NSP4 does not always correlate with differences in virulence among strains [23,24].)
- activation of the enteric nervous system (resulting in net intestinal fluid and electrolyte secretion [25]. The effectiveness of the drug racecadotril, an inhibitor of enteric enkephalinase, in treatment of rotavirus diarrhea [26], supports the hypothesis that the enteric nervous system plays a role in rotavirus diarrhea in humans.)
Transmission
- Virus can be detected:
- coincident with or slightly before the onset of illness [8,9],
- in 94 percent of specimens 1 to 4 days
- in 76 percent 4 to 8 days after onset.
- occasionally, in stool two weeks or longer after illness [8,10],
- more severe episodes of diarrhea may be associated with shedding of rotavirus in stools for as long as 25 to 30 days [11].
- Asymptomatic excretion of rotaviruses in stool has been described in both adults and children and may play a role in transmission, particularly in nosocomial settings [12].
Abridged from UpToDate.com in February 2009.
Clinical presentation and diagnosis of rotavirus infection
Author
John J Treanor, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Barbara H McGovern, MD
Last literature review version 16.3: October 2008 | This topic last updated: May 30, 2008
- 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.
- 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.
- 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.
- Man, NV, 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.
- Bishop, RF, Davidson, GP, Holmes, IH, Ruck, BJ. Letter: Evidence for viral gastroenteritis. N Engl J Med 1973; 289:1096.
- Barnes, GL, Townley, RR. Duodenal mucosal damage in 31 infants with gastroenteritis. Arch Dis Child 1973; 48:343.
- Davidson, GP, Bishop, RF, Townlee, RRW, et al. Importance of a new virus in acute sporadic enteritis in children. Lancet 1975; 1:242.
- Konno, T, Suzuki, H, Imai, A, et al. A long term serosurvey of rotavirus infection in Japanese children with acute gastroenteritis. J Infect Dis 1978; 138:569.
- 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.
- Pickering, LK, Bartlett, AV, Reves, RR et, al. Asymptomatic excretion of rotavirus before and after rotavirsu diarrhea in children in day care center. J Pediatr 1988; 112:361.
- Richardson, S, Grimwood, K, Gorrell, R, et al. Extended excretion of rotavirus after severe diarrhoea in young children. Lancet 1998; 351:1844.
- 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.
- Fischer, TK, Ashley, D, Kerin, T, et al. Rotavirus antigenemia in patients with acute gastroenteritis. J Infect Dis 2005; 192:913.
- 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.
- Bishop, RF, Davidson, GP, Holmes, IH, Ruck, BJ. Virus particles in epithelial cells of duodenal mucosa from children with acute gastroenteritis. Lancet 1973; 2:1281.
- Hyams, JS, Krause, PJ, Gleason, PA. Lactose malabsorption following rotavirus infection in young children. J Pediatr 1981; 99:916.
- 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.
- Sack, DA, Rhoads, M, Molla, A, et al. Carbohydrate malabsorption in infants with rotavirus diarrhea. Am J Clin Nutr 1982; 36:1112.
- Davidson, GP, Gall, DG, Petric, M. Human rotavirus enteritis induced in conventional piglets. J Clin Invest 1977; 60:1402.
- Graham, DY, Sackman, JW, Estes, MK. Pathogenesis of rotavirus induced diarrhea. Dig Dis Sci 1984; 29:1028.
- Ball, JM, Tian, P, Zieng, CQ-Y, et al. Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein. Science 1996; 272:101.
- 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.
- 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.
- 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.
- Lundgren, O, Peregrin, AT, Persson, K, et al. Role of the enteric nervous system in the fluid and electolyte secretion of rotavirus diarrhea. Science 2000; 287:491.
- 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.
- 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.
- Champsaur, H, Henry-Amar, M, Goldszmidt, D, et al. Rotavirus carriage, asymptomatic infection, and disease in the first two years of life II serologic response. J Infect Dis 1984; 149:675.
- Carlson, JAK, Middleton, PJ, MT. Fatal rotavirus gastroenteritis. Am J Dis Child 1978; 132:477.
- 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.
- Rodriguez, WJ, Kim, HW, Brandt, CD, et al. Common exposure outbreak of gastroenteritis due to type 2 rotavirus with high secondary attack rates within families. J Infect Dis 1979; 140:353.
- 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.
- Bhan, MK, Bhandari, N, Wvensson, L, et al. Role of enteric adenoviruses and rotaviruses in mild and severe acute enteritis. Pediatr Infect Dis J 1988; 7:320.
- 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.
- 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.
- Brandt, CD, Kim, HW, Rodriguez, WJ, et al. Simultaneous infections with different enteric and respiratory tract viruses. J Clin Microbiol 1986; 23:177.
- 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.
- 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.
- Foldenauer, A, Vossbeck, S, Pohlandt, F. Neonatal hypocalcaemia associated with rotavirus diarrhoea. Eur J Pediatr 1998; 157:838.
- Grimwood, K, Coakley, JC, Hudson, IL, et al. Serum aspartate aminotransferase levels after rotavirus gastroenteritis. J Pediatr 1988; 112:597.
- Pryor, WM, Bye, WA, Curran, DH, Grohmann, GS. Acute diarrhoea in adults: a prospective study. Med J Aust 1987; 147:490.
- Hieber, JP, Shelton, S, Nelson, JD. Comparison of human rotavirus disease in tropical and temperate settings. Am J Dis Child 1978; 132:853.
- Hrdy, DB. Epidemiology of rotaviral infection in adults. Rev Infect Dis 1987; 9:461.
- 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.
- 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.
- Echeverria, P, Ramirez, G, Blacklow, NR, et al. Traveler's diarrhea among US Army troops in South Korea. J Infect Dis 1979; 139:215.
- Keswick, GH, Blacklow, NR, Cukor, GC, et al. Norwalk virus and rotavirus in travelers'diarrhea in Mexico. Lancet 1982; 1:109.
- Foodborne outbreak of Group A rotavirus gastroenteritis among college students--District of Columbia, March-April 2000. MMWR Morb Mortal Wkly Rep 2000; 49:1131.
- Marrie, TJ, Lee, SH, Faulkner, RS, et al. Rotavirus infection in a geriatric population. Arch Intern Med 1982; 142:313.
- Echeverria, P, Blacklow, NR, Cukor, GG, et al. Rotavirus as a cause of severe gastroenteritis in adults. J Clin Microbiol 1983; 18:663.
- Saulsbury, FT, Winkelstein, JA, Yolken, RJ. Chronic rotavirus infection in immunodeficiency. J Pediatr 1980; 97:61.
- Yolken, RH, Bishop, CA, Townsend, TR, et al. Infectious gastroenteritis in bone-marrow-transplant recipients. N Engl J Med 1982; 306:1010.
- 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.
- Wood, DJ, David, TJ, Chrystie, IL, Totterdell, B. Chronic enteric virus infection in two T-cell immunodeficient children. J Med Virol 1988; 24:435.
- Gilger, MA, Matson, DO, Conner, ME, et al. Extraintestinal rotavirus infections in children with immunodeficiency. J Pediatr 1992; 120:912.
- Fitts, SW, Green, M, Reyes, J, et al. Clinical features of nosocomial rotavirus infection in pediatric liver transplant recipients. Clin Transplant 1995; 9:201.
- Gonzalez, 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.
- 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.
- 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.
- Konno, T, Suzuki, H, Katsuzawa, T, et al. Human rotavirus and intussusception. N Engl J Med 1977; 297:945.
- Konno, T, Suzuki, H, Katsuzawa, T, et al. Human rotavirus infection in infants and young children with intussusception. J Med Virol 1978; 2:265.
- Mulcahy, DL, Kamath, KR, deSilva, LM, et al. A 2-part study of the aetiological role of rotavirus in intussusception. J Med Virol 1982; 9:51.
- Nicolas, JC, Ingrand, D, Fortier, B, Bricout, F. A one year virological survey of acute intussusception in childhood. J Med Virol 1982; 9:267.
- Nakagomi, T. Rotavirus infection and intussusception: a view from retrospect. Microbiol Immunol 2000; 44:619.
- 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.
- 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.
- Takahashi, S, Oki, J, Miyamoto, A, et al. Encephalopathy associated with haemophagocytic lymphohistiocytosis following rotavirus infection. Eur J Pediatr 1999; 158:133.
- Riedel, F, Kroener, T, Stein, K, et al. Rotavirus infection and bradycardia-apnoea-episodes in the neonate. Eur J Pediatr 1996; 155:36.
- 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.
- Iyadurai, S, Troester, M, Harmala, J, Bodensteiner, J. Benign afebrile seizures in acute gastroenteritis: is rotavirus the culprit?. J Child Neurol 2007; 22:887.
- Hongou, K, Konishi, T, Yagi, S, et al. Rotavirus encephalitis mimicking afebrile benign convulsions in infants. Pediatr Neurol 1998; 18:354.
- Makino, M, Tanabe, Y, Shinozaki, K, et al. Haemorrhagic shock and encephalopathy associated with rotavirus infection. Acta Paediatr 1996; 85:632.
- 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.
- Sigurdsson, L, Flores, A, Putnam, PE, et al. Postviral gastroparesis: presentation, treatment, and outcome. J Pediatr 1997; 131:751.
- Guarinom, A, Spagnuolom, MI, Russom, S, et al. Etiology and risk factors of severe and protracted diarrhea. J Pediatr Gastroenterol Nutrit 1995; 20:173.
- Szajewska, H, Kantecki, M, Albrecht, P, Antoniewicz, J. Carbohydrate intolerance after acute gastroenteritis--a disappearing problem in Polish children. Acta Paediatr 1997; 86:347.
- Bhardwaj, A, Aggarwal, V, Chakravarty, A, Mittal, SK. Does Rota virus infection cause persistent diarrhoea in childhood?. Trop Gastroenterol 1996; 17:18.
- Cromien, JL, Himmelreich, CA, Glass, RI, et al. Evaluation of a new commercial enzyme immunoassay for rotavirus detection. J Clin Microbiol 1987; 25:2359.
- Hornsleth, A, Jankowski, M. Sensitive enzyme immunoassay for the rapid diagnosis of influenza A virus infections in clinical specimens. Res Virol 1990; 141:373.
- Thomas, EE, Puterman, ML, Kawano, E et. al. Evaluation of seven immunoassays for detection of rotavirus in pediatric stool samples. J Clin Microbiol 1988; 26:1189.
- Brandt, CD, Arndt, CW, Evans, GL, et al. Evaluation of a latex test for rotavirus detection. J Clin Microbiol 1987; 25:1800.
- Sanekata, T, Okada, H. Human rotavirus detection by agglutination of antibody-coated erythrocytes. J Clin Microbiol 1983; 17:1141.
- 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.
- Dennehy, PH, Gauntlett, DR, Tente, WE. Comparison of nine commercial immunoassays for the detection of rotavirus in fecal specimens. J Clin Microbiol 1988; 26:1630.
- Husain, M, Seth, P, Broor, S. Detection of group A rotavirus by reverse transcription and polymerase chain reaction in feces from children with acute gastroenteritis. Arch Virol 1995; 140:1225.
- Dimitrov, DH, Graham, DY, Estes, MK. Detection of rotaviruses by nucleic acid hybridization with cloned DNA of simian rotavirus SA11 genes. J Infect Dis 1985; 152:293.
- Flores, J, Purcell, RH, Perez, I, et al. A dot hybridization assay for detection of rotavirus. Lancet 1983; 1:222.
- Kasempimolporn, S, Lousririotchanul, S, Sinarachatanant, P, et al. Polyacrylamide gel electrophoresis and silver staining for detection of rotavirus in stools from diarrheic patients in Thailand. J Clin Microbiol 1988; 26:158.
- Pacini, DL, Brady, MT, Budde, CT, et al. Polyacrylamide gel electrophoresis of RNA compared with polyclonal- and monoclonal-antibody-based enzyme immunoassays for rotavirus. J Clin Microbiol 1988; 26:194.
- Sato, K, Inaba, Y, Shinozaki, T, et al. Isolation of human rotavirus in cell cultures. Arch Virol 1981; 69:155.
- Wyatt, RG, James, HDJ, Pittman, AL, et al. Direct isolation in cell culture of human rotaviruses and their characterization into four serotypes. J Clin Microbiol 1983; 18:310.
- Taniguchi, K, Urasawa, S, Urasawa, T. Electrophoretic analysis of RNA segments of human rotavirus cultivated in cell culture. J Gen Virol 1982; 60:171.
- Urasawa, T, Urasawa,S, Taniguchi, K. Sequential passages of human rotaviruses in MA-104 cells. Microbiol Immunol 1981; 25:1025.
- Urasawa, S, Urasawa, T, Taniguchi, K. Three human rotavirus serotypes demonstrated by plaque neutralization of isolated strains. Infect Immun 1982; 38:781.