title: Protective effect of natural rotavirus infection in an Indian birth cohort.
abstract: BACKGROUND
  More than 500,000 deaths are attributed to rotavirus gastroenteritis annually worldwide, with the highest mortality in India. Two successive, naturally occurring rotavirus infections have been shown to confer complete protection against moderate or severe gastroenteritis during subsequent infections in a birth cohort in Mexico. We studied the protective effect of rotavirus infection on subsequent infection and disease in a birth cohort in India (where the efficacy of oral vaccines in general has been lower than expected).
  
  
  METHODS
  We recruited children at birth in urban slums in Vellore; they were followed for 3 years after birth, with home visits twice weekly. Stool samples were collected every 2 weeks, as well as on alternate days during diarrheal episodes, and were tested by means of enzyme-linked immunosorbent assay and polymerase-chain-reaction assay. Serum samples were obtained every 6 months and evaluated for seroconversion, defined as an increase in the IgG antibody level by a factor of 4 or in the IgA antibody level by a factor of 3.
  
  
  RESULTS
  Of 452 recruited children, 373 completed 3 years of follow-up. Rotavirus infection generally occurred early in life, with 56% of children infected by 6 months of age. Levels of reinfection were high, with only approximately 30% of all infections identified being primary. Protection against moderate or severe disease increased with the order of infection but was only 79% after three infections. With G1P[8], the most common viral strain, there was no evidence of homotypic protection.
  
  
  CONCLUSIONS
  Early infection and frequent reinfection in a locale with high viral diversity resulted in lower protection than has been reported elsewhere, providing a possible explanation why rotavirus vaccines have had lower-than-expected efficacy in Asia and Africa. (Funded by the Wellcome Trust.).
authors.affiliation: Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
authors.forename: Beryl P
authors.initials: BP
authors.lastname: Gladstone
authors.forename: Sasirekha
authors.initials: S
authors.lastname: Ramani
authors.forename: Indrani
authors.initials: I
authors.lastname: Mukhopadhya
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Muliyil
authors.forename: Rajiv
authors.initials: R
authors.lastname: Sarkar
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Rehman
authors.forename: Shabbar
authors.initials: S
authors.lastname: Jaffar
authors.forename: Miren Iturriza
authors.initials: MI
authors.lastname: Gomara
authors.forename: James J
authors.initials: JJ
authors.lastname: Gray
authors.forename: David W G
authors.initials: DW
authors.lastname: Brown
authors.forename: Ulrich
authors.initials: U
authors.lastname: Desselberger
authors.forename: Sue E
authors.initials: SE
authors.lastname: Crawford
authors.forename: Jacob
authors.initials: J
authors.lastname: John
authors.forename: Sudhir
authors.initials: S
authors.lastname: Babji
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kang
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D015331:Cohort Studies; D003967:Diarrhea / Q000453:epidemiology / Q000517:prevention & control / Q000821:virology; D005243:Feces / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000401:mortality / Q000821:virology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007194:India; D007231:Infant, Newborn; D008297:Male; D012008:Recurrence; D012401:Rotavirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D012400:Rotavirus Infections / Q000150:complications / Q000276:immunology* / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G