title: Early exposure of infants to natural rotavirus infection: a review of studies with human rotavirus vaccine RIX4414.
abstract: BACKGROUND
  Rotaviruses are the leading cause of severe acute gastroenteritis in children aged <5 years worldwide. A live attenuated human rotavirus vaccine, RIX4414 has been developed to reduce the global disease burden associated with rotavirus gastroenteritis. Serum anti-rotavirus immunoglobulin A (IgA) antibody measured in unvaccinated infants during clinical trials of RIX4414 reflects natural rotavirus exposure, and may inform the optimal timing for rotavirus vaccination.
  
  
  METHODS
  We reviewed phase II and III randomized, placebo-controlled clinical trials conducted by GlaxoSmithKline Vaccines, Wavre, Belgium between 2000 and 2008 which used the commercial formulation of RIX4414 lyophilized vaccine. We included trials for which demographic data and pre-dose-1 and post-last-dose anti-rotavirus IgA antibody status were available from placebo recipients.
  
  
  RESULTS
  Sixteen clinical trials met the inclusion criteria. The studies were conducted across Africa (N = 3), Asia (N = 4), Latin America (N = 4), Europe (N = 4) and North America (N = 1). Overall, 46,398 infants were enrolled and among these, 20,099 received placebo. The mean age at pre-dose-1 time point ranged from 6.4 - 12.2 weeks while the mean age at post-last-dose time point ranged from 13.5 - 19.6 weeks. The anti-RV IgA seropositivity rates at both time points were higher in less developed countries of Africa, Asia and Latin America (pre-dose-1: 2.1%-26.3%; post-last-dose: 6.3%-34.8%) when compared to more developed countries of Asia, Europe and North America (pre-dose-1: 0%-9.4%; post-last-dose: 0%-21.3%), indicating that rotavirus infections occurred at a younger age in these regions.
  
  
  CONCLUSIONS
  Exposure to rotavirus infection occurred early in life among infants in most geographical settings, especially in developing countries. These data emphasize the importance of timely rotavirus vaccination within the Expanded Program on Immunization schedule to maximize protection.
authors.forename: Nigel
authors.initials: N
authors.lastname: Cunliffe
authors.forename: Khalequ
authors.initials: K
authors.lastname: Zaman
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodrigo
authors.forename: Serge
authors.initials: S
authors.lastname: Debrus
authors.forename: Bernd
authors.initials: B
authors.lastname: Benninghoff
authors.forename: Suryakiran
authors.initials: S
authors.lastname: Pemmaraju Venkata
authors.forename: Htay-Htay
authors.initials: HH
authors.lastname: Han
mesh_terms: D000367:Age Factors; D000914:Antibodies, Viral / Q000097:blood*; D003906:Developing Countries; D005260:Female; D005759:Gastroenteritis / Q000517:prevention & control / Q000821:virology*; D006801:Humans; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000097:blood*; D007223:Infant; D008297:Male; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000517:prevention & control / Q000821:virology*; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated