Developments in the Treatment of Rotaviral Gastroenteritis

Oral Therapy with Immunoglobulins and Prospects for a Vaccine


Rotavirus is the most frequent agent of gastroenteritis in both industrialised and developing countries. It is responsible for a high number of deaths, hospitalisations and nosocomial infections. Besides rehydration, no specific therapy effective against the virus has so far been developed. However, immunotherapy involving oral administration of human serum immunoglobulin meets the criteria for ideal drug therapy for the following reasons: (a) commercially available immunoglobulin preparations have high neutralising antibody titres directed toward rotavirus; (b) the antibodies survive the gastric barrier and remain active throughout the intestine; (c) no adverse effects are associated with oral administration of immunoglobulin.

Preliminary studies have shown the efficacy of a single oral administration of immunoglobulin to children with severe and protracted rotaviral diarrhoea. Subsequently, a double-blind case- and placebo-controlled trial showed that immunotherapy was effective in decreasing the severity of symptoms and the duration of diarrhoea, viral excretion and hospital stay in children admitted with acute rotaviral gastroenteritis. The cost effectiveness of immunotherapy was also clearly proved. This therapy should therefore be considered for children admitted with rotaviral diarrhoea.

Because rotavirus is a large scale worldwide problem, attempts at making an effective vaccine are being pursued. Initial approaches were based on the use of high-passage attenuated rotavirus strains obtained from animals. Genetically engineered strains were also used. However, clinical trials have been only partially successful. The use of new tools available from molecular biology may help to overcome the problem of efficacy and duration of vaccine-induced immunity.


  1. 1.

    Prospects for immunizing against rotavirus. In: Institute of Medicine. New vaccine development: establishing priorities. Vol. 1. Diseases of importance in the United States. Washington DC: National Academy Press, 1985: 410–23

  2. 2.

    Prince DS, Astry C, Vonderfecht S, et al. Aerosol transmission of experimental rotavirus infection. Pediatr Infect Dis J 1986; 5: 218–22

    Article  CAS  Google Scholar 

  3. 3.

    Matson OM, Estes MK. Impact of rotavirus infection at a large pediatric hospital. J Infect Dis 1990; 162: 598–604

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Ho MS, Glass Rl, Pinsky PF, et al. Rotavirus as a cause of diarrheal morbidity and mortality in the United States. J Infect Dis 1988; 5: 1112–6

    Article  Google Scholar 

  5. 5.

    Communicable disease report: rotavirus surveillance, 1991. Public Health Laboratory Service Communicable Disease Report. Vol. 20. London: Public Health Laboratory Service, 1991: 1

  6. 6.

    Le Baron CW, Lew J, Glass R. 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: 783–8

    Google Scholar 

  7. 7.

    Soriano BH, Avendano P, O’Ryan M, et al. Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical study. Pediatrics 1991; 87: 18–27

    PubMed  Google Scholar 

  8. 8.

    Ogawa K, Ben RA, Pons E, et al. Volatile fatty acids, lactic acid, and pH in the stools of breast-fed and bottle-fed infants. J Pediatr Gastroenterol Nutr 1992; 15: 246–7

    Article  Google Scholar 

  9. 9.

    Duffy LC, Zielezny M, Riepenhoff-Talty D, et al. Effectiveness of Bifidobacterium bifidum in mediating the clinical course of murine rotavirus diarrhea. Pediatr Res 1994; 35: 690–5

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Isolauri E, Juntunen M, Rautanen T, et al. A human lactobacillus strain (Lactobacillus casei sp. strain GG) promotes recovery from acute diarrhea in children. Pediatrics 1991; 88: 90–7

    PubMed  CAS  Google Scholar 

  11. 11.

    Kaila M, Isolauri E, Soppi E, et al. Enhancement of the circulating antibody secreting cell response in human diarrhea by a human lactobacillus strain. Pediatr Res 1992; 32: 141–4

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Isolauri E, Majamaa H, Arvola T, et al. Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats. Gastroenterology 1993; 105: 1643–50

    PubMed  CAS  Google Scholar 

  13. 13.

    Majamaa H, Isolauri E, Saxelin M, et al. Lactic acid bacteria in rotavirus diarrhea. Microecol Ther. In press

  14. 14.

    Pizarro JM, Pizarro JL, Fernandez J, et al. Effect of nucleotide analogues on rotavirus transcription and replication. Virology 1991; 184: 768–72

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Ludan AC. Current management of acute diarrhoeas: use and abuse of drug therapy. Drugs 1988; 36 Suppl. 4: 18–25

    PubMed  Article  Google Scholar 

  16. 16.

    Powell DW, Szanter KE. Non antibiotic therapy and pharmacotherapy of acute infectious diarrhea. Gastroenterol Clin North Am 1993; 22: 683–707

    PubMed  CAS  Google Scholar 

  17. 17.

    Bishop R, Lund J, Cipriani E, et al. Clinical, serological and intestinal immune responses to rotavirus infection of humans. Med Virol 1990; 9: 85–109

    Google Scholar 

  18. 18.

    Kapikian AZ, Chanock RM. Rotaviruses. In: Fields B, Knife DM, editors. Virology. 2nd ed. New York: Raven Press, 1990: 1353–404

    Google Scholar 

  19. 19.

    Matsui SM, Mackow ER, Greenberg HB. Molecular determinant of rotavirus neutralization and protection. Adv Virus Res 1989; 36: 181–214

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Capano G, Guandalini S, Guarino A, et al. Enteric infections, cow’s milk intolerance and parenteral infections in 118 consecutive cases of acute diarrhoea in children. Eur J Pediatr 1984; 142: 281–5

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Yolken RH, Wyatt RG, Zissis G, et al. Epidemiology of human rotavirus types 1 and 2 as studied by enzyme linked immunosorbent assay. N Engl J Med 1978; 299: 1156

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    LeBaron CW, Furutan NP, Lew JF, et al. Viral agents of gastroenteritis: public health importance and outbreak management. MMWR Morb Mortal Wkly Rep 1990; 5: 1–24

    Google Scholar 

  23. 23.

    Wenman WM, Hinde D, Felthan S, et al. Rotavirus infection in adults: results of a prospective family study. N Engl J Med 1979; 301: 303

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Offit PA, Clark HE Protection against rotavirus-induced gastroenteritis in a murine model by passively acquired gastrointestinal but not circulating antibodies. J Virol 1985; 54: 58–64

    PubMed  CAS  Google Scholar 

  25. 25.

    Snodgrass DR, Well RW. Rotavirus infection in lambs: studies on passive protection. Arch Virol 1976; 52: 201–5

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Woode GN, Bridges JC. Viral enteritis of calves. Vet Res 1975; 96: 85–8

    CAS  Google Scholar 

  27. 27.

    Totterdell BM, Chrystie IL, Banatvale JE. Cord blood and breast-milk antibodies in neonatal rotavirus infection. BMJ 1980; 280: 828–30

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Guarino A, Berni Canani R, Russo S, et al. Oral immunoglobulins for treatment of acute rotaviral gastroenteritis. Pediatrics 1994; 93: 12–6

    PubMed  CAS  Google Scholar 

  29. 29.

    Brussow H, Hilpert H, Walther I, et al. Bovine milk immunoglobulins for passive immunity to infantile rotavirus gastroenteritis. J Clin Microbiol 1987; 25: 982–6

    PubMed  CAS  Google Scholar 

  30. 30.

    Blum PM, Phelps DL, Ank BJ, et al. Survival of oral human immune serum globulin in the gastrointestinal tract of low birth weight infants. Pediatr Res 1981; 15: 1256–60

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    McClead RE, Gregory SA. Resistance of bovine colostral anti-cholera toxin antibody to in vitro and in vivo proteolysis. Infect Immun 1984; 44: 474–8

    PubMed  CAS  Google Scholar 

  32. 32.

    Petschow BW, Talbott RD. Reduction in virus-neutralizing activity of a bovine colostrum immunoglobulin concentrate by gastric acid and digestive enzymes. J Pediatr Gastroenterol Nutr 1994; 19: 228–35

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Losonsky GA, Johnson JP, Winkelstein JA, et al. Oral administration of human serum immunoglobulin in immunodeficient patients with viral gastroenteritis. J Clin Invest 1985; 76: 2362–7

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Saulsbury FT, Winkelstein JA, Yolken RH. Chronic rotavirus infection in immunodeficiency. J Pediatr 1980; 97: 61–5

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Guarino A, Spagnuolo MI, Russo S, et al. Etiology and risk factors of severe and protracted diarrhea. J Pediatr Gastroenterol Nutr 1995; 20: 173–8

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Guarino A, Guandalini S, Albano F, et al. Enteral immunoglobulins for treatment of protracted rotaviral diarrhea. Pediatr Infect Dis J 1991; 10: 612–4

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Casola A, Bruzzese E, Berni Canani R, et al. In vitro effect of immunoglobulins on rotavirus-enterocyte interaction. J Pediatr Gastroenterol Nutr 1994; 19: 335

    Article  Google Scholar 

  38. 38.

    Schiff RI. Transmission of viral infections through intravenous immune globulin. New Engl J Med 1994; 331: 1649–50

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Acquired immunodeficiency syndrome. WHO meeting and consultation on safety of blood and blood products. WHO Wkly Epidemiol Rec 1986; 18: 138–40

    Google Scholar 

  40. 40.

    Bernhisel-Broadbent J, Yolken RH, Sampson HA. Allergenicity of orally administered immunoglobulin preparations in food-allergic children. Pediatrics 1991; 87: 208–14

    PubMed  CAS  Google Scholar 

  41. 41.

    Snodgrass DR, Madely CR, Weels PW. Human rotavirus in lambs: infection and passive protection. Infect Immun 1977; 16: 268

    PubMed  CAS  Google Scholar 

  42. 42.

    Schaller JP, Saif LJ, Cordle CT, et al. Prevention of human rotavirus-induced diarrhea in gnotobiotic piglets using bovine antibody. J Infect Dis 1992; 165: 623–30

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Lecce JG, Leary HL, Clare DA, et al. Protection of agammaglobulinemic piglets from porcine rotavirus infection by antibody against simian rotavirus SA-11. J Clin Microbiol 1991; 29: 1382–6

    PubMed  CAS  Google Scholar 

  44. 44.

    Ebina T, Sato A, Umezu K, et al. Prevention of rotavirus infection by oral administration of cow colostrum containing anti-human-rotavirus antibody. Med Microbiol Immunol 1985; 174: 177–85

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Barnes GL, Doyle LW, Hewson PH, et al. A randomized trial of oral gammaglobulin in low-birth-weight infants infected with rotavirus. Lancet 1982; 1: 1371–3

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Davidson GP, Whyte PBD, Daniels E, et al. Passive immunization of children with bovine colostrum containing antibodies to human rotavirus. Lancet 1989; 2: 709–12

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Turner RB, Douglas KH. Passive immunization for prevention of rotavirus illness in healthy infants. Pediatr Infect Dis J 1993; 12: 718–22

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Brunser O, Espinoza J, Figueroa G, et al. Field trial of an infant formula containing anti-rotavirus and anti-Escherichia coli milk antibodies from hyperimmunized cows. J Pediatr Gastroenterol Nutr 1992; 15: 63–72

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Ford-Jones E, Mindorff C, Gold R, et al. The incidence of viral-associated diarrhea after admission to a pediatric hospital. Am J Epidemiol 1990; 131: 711–8

    PubMed  CAS  Google Scholar 

  50. 50.

    Crawley JMS, Bishop RF, Barnes GC. Rotavirus gastroenteritis in infants aged 0–6 months in Melbourne, Australia: implications for vaccination. J Paediatr Child Health 1993; 29: 219–21

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    Kim HW, Brandt CD, Kapikian AZ, et al. Human reovirus-like agent (HRVLA) infection: occurrence in adult contacts of pediatric patients with gastroenteritis. JAMA 1977; 238: 404–7

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Menon S, Santosham M, Reid R, et al. Rotavirus diarrhea in Apache children: a case control study. Int J Epidemiol 1990; 19: 715–21

    PubMed  Article  CAS  Google Scholar 

  53. 53.

    Flores J, Kapikian AZ. Vaccines against viral diarrhea. Bailliere’s Clin Gastroenterol 1990; 4: 675–93

    Article  CAS  Google Scholar 

  54. 54.

    Kapikian AZ, Flores J, Midthun K, et al. Strategies for the development of a rotavirus vaccine against infantile diarrhea with an update on clinical trials of rotavirus vaccines. Adv Exp Med Biol 1989; 257: 67–89

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    Wyatt RG, Kapikian AZ, Greenberg HB, et al. Development of vaccines against rotavirus disease. Prog Food Nutr Sci 1983; 7: 189–92

    PubMed  CAS  Google Scholar 

  56. 56.

    Matson DO, O’Ryan ML, Herrera I, et al. Fecal antibody responses to symptomatic and asymptomatic rotavirus infection. J Infect Dis 1993; 167: 577–83

    PubMed  Article  CAS  Google Scholar 

  57. 57.

    Offit PA, Hoffenberg EJ, Pia ES, et al. Rotavirus specific helper T cell responses in newborns, infants, children, and adults. J Infect Dis 1992; 165: 1107–11

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Dharakul T, Labbe M, Cohen J, et al. Immunization with baculovirus-expressed recombinant rotavirus proteins VP1, VP4, VP6, and VP7 induces CD8+ T lymphocytes that mediate clearance of chronic rotavirus infection in SCID mice. J Virol 1991; 65: 5928–32

    PubMed  CAS  Google Scholar 

  59. 59.

    Beards GM, Desselberger U, Flewett TH. Temporal and geographical distributions of human rotavirus serotypes from 1983 to 1988. J Clin Microbiol 1989; 27: 2827–33

    PubMed  CAS  Google Scholar 

  60. 60.

    Anon. Puzzling diversity of rotaviruses [editorial]. Lancet 1990; 335: 573–5

  61. 61.

    Dunn SJ, Greenberg HB, Ward RL, et al. Serotyopic and genotyopic characterization of human serotype 10 rotaviruses from asymptomatic neonates. J Clin Microbiol 1993; 31: 165–9

    PubMed  CAS  Google Scholar 

  62. 62.

    Coulson BS. Typing of human rotavirus VP4 by an enzyme immunoassay using monoclonal antibodies. J Clin Microbiol 1993; 31: 1–8

    PubMed  CAS  Google Scholar 

  63. 63.

    Flores J, Perez Schael I, Gonzales M, et al. Protection against severe rotavirus diarrhoea by rhesus rotavirus vaccine in Venezuelan infants. Lancet 1987; 1: 882–4

    PubMed  Article  CAS  Google Scholar 

  64. 64.

    Bernstein DI, Smith VE, Sander DS, et al. Evaluation of WC3 rotavirus vaccine and correlates of protection in healthy infants. J Infect Dis 1990; 162: 1055–62

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Rennels MB, Losonsky GA, Yong AE, et al. An efficacy trial for the rhesus rotavirus vaccine in Maryland. Am J Dis Child 1990; 144: 601–4

    PubMed  CAS  Google Scholar 

  66. 66.

    Levine MM, Noriega F. Vaccines to prevent enteric infections. Bailliere’s Clin Gastroenterol 1993; 7: 501–17

    Article  CAS  Google Scholar 

  67. 67.

    Vesikari T. Clinical trials of oral rotavirus vaccines: the Finnish experience. Vaccine 1993; 11: 255–61

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Flores J, Perez-Schael I, Blanco M, et al. Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesusrotavirus-based quadrivalent vaccine. Lancet 1990; 2: 330–4

    Article  Google Scholar 

  69. 69.

    Streckert HJ, Brussow H, Werchaw H. A synthetic peptide corresponding to the cleavage region of VP3 from rotavirus SA 11 induces neutralizing antibodies. J Virol 1988; 62: 4265–9

    PubMed  CAS  Google Scholar 

  70. 70.

    Both GW, Lockett LJ, Janardhana V, et al. Protective immunity to rotavirus-induced diarrhoea is passively transferred to new-born mice from naive dams vaccinated with a single dose of a recombinant adenovirus expressing rotavirus VP7sc. Virology 1993; 193: 940–50

    PubMed  Article  CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Dr Alfredo Guarino.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Guarino, A., Canani, R.B. & Russo, S. Developments in the Treatment of Rotaviral Gastroenteritis. Clin. Immunother. 3, 476–484 (1995).

Download citation


  • Gastroenteritis
  • Bovine Colostrum
  • Rotaviral Gastroenteritis
  • Communicable Disease Report
  • High Neutralise Antibody Titre