Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort

Beryl P Gladstone, Sasirekha Ramani, Indrani Mukhopadhya, Jayaprakash Muliyil, Rajiv Sarkar, Andrea M Rehman, Shabbar Jaffar, Miren Iturriza Gomara, James J Gray, David W G Brown, Ulrich Desselberger, Sue E Crawford, Jacob John, Sudhir Babji, Mary K Estes, Gagandeep Kang

Research output: Contribution to journalArticle

113 Citations (Scopus)

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.).

Original languageEnglish
Pages (from-to)337-346
Number of pages10
JournalThe New England Journal of Medicine
Volume365
Issue number4
DOIs
Publication statusPublished - 28 Jul 2011

Fingerprint

Rotavirus Infections
Parturition
Infection
Gastroenteritis
India
Rotavirus Vaccines
Poverty Areas
House Calls
Antibodies
Rotavirus
Mexico
Immunoglobulin A
Vaccines
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Polymerase Chain Reaction
Mortality
Serum

Keywords

  • Antibodies, Viral
  • Child, Preschool
  • Cohort Studies
  • Diarrhea
  • Feces
  • Female
  • Gastroenteritis
  • Humans
  • Immunoglobulin A
  • Immunoglobulin G
  • India
  • Infant, Newborn
  • Male
  • Recurrence
  • Rotavirus
  • Rotavirus Infections
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Gladstone, B. P., Ramani, S., Mukhopadhya, I., Muliyil, J., Sarkar, R., Rehman, A. M., ... Kang, G. (2011). Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort. The New England Journal of Medicine, 365(4), 337-346. https://doi.org/10.1056/NEJMoa1006261

Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort. / Gladstone, Beryl P; Ramani, Sasirekha; Mukhopadhya, Indrani; Muliyil, Jayaprakash; Sarkar, Rajiv; Rehman, Andrea M; Jaffar, Shabbar; Gomara, Miren Iturriza; Gray, James J; Brown, David W G; Desselberger, Ulrich; Crawford, Sue E; John, Jacob; Babji, Sudhir; Estes, Mary K; Kang, Gagandeep.

In: The New England Journal of Medicine, Vol. 365, No. 4, 28.07.2011, p. 337-346.

Research output: Contribution to journalArticle

Gladstone, BP, Ramani, S, Mukhopadhya, I, Muliyil, J, Sarkar, R, Rehman, AM, Jaffar, S, Gomara, MI, Gray, JJ, Brown, DWG, Desselberger, U, Crawford, SE, John, J, Babji, S, Estes, MK & Kang, G 2011, 'Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort', The New England Journal of Medicine, vol. 365, no. 4, pp. 337-346. https://doi.org/10.1056/NEJMoa1006261
Gladstone, Beryl P ; Ramani, Sasirekha ; Mukhopadhya, Indrani ; Muliyil, Jayaprakash ; Sarkar, Rajiv ; Rehman, Andrea M ; Jaffar, Shabbar ; Gomara, Miren Iturriza ; Gray, James J ; Brown, David W G ; Desselberger, Ulrich ; Crawford, Sue E ; John, Jacob ; Babji, Sudhir ; Estes, Mary K ; Kang, Gagandeep. / Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort. In: The New England Journal of Medicine. 2011 ; Vol. 365, No. 4. pp. 337-346.
@article{1775227f089a4187bd3ee6d075bb0e65,
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.).",
keywords = "Antibodies, Viral, Child, Preschool, Cohort Studies, Diarrhea, Feces, Female, Gastroenteritis, Humans, Immunoglobulin A, Immunoglobulin G, India, Infant, Newborn, Male, Recurrence, Rotavirus, Rotavirus Infections, Journal Article, Research Support, Non-U.S. Gov't",
author = "Gladstone, {Beryl P} and Sasirekha Ramani and Indrani Mukhopadhya and Jayaprakash Muliyil and Rajiv Sarkar and Rehman, {Andrea M} and Shabbar Jaffar and Gomara, {Miren Iturriza} and Gray, {James J} and Brown, {David W G} and Ulrich Desselberger and Crawford, {Sue E} and Jacob John and Sudhir Babji and Estes, {Mary K} and Gagandeep Kang",
year = "2011",
month = "7",
day = "28",
doi = "10.1056/NEJMoa1006261",
language = "English",
volume = "365",
pages = "337--346",
journal = "The New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "4",

}

TY - JOUR

T1 - Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort

AU - Gladstone, Beryl P

AU - Ramani, Sasirekha

AU - Mukhopadhya, Indrani

AU - Muliyil, Jayaprakash

AU - Sarkar, Rajiv

AU - Rehman, Andrea M

AU - Jaffar, Shabbar

AU - Gomara, Miren Iturriza

AU - Gray, James J

AU - Brown, David W G

AU - Desselberger, Ulrich

AU - Crawford, Sue E

AU - John, Jacob

AU - Babji, Sudhir

AU - Estes, Mary K

AU - Kang, Gagandeep

PY - 2011/7/28

Y1 - 2011/7/28

N2 - 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.).

AB - 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.).

KW - Antibodies, Viral

KW - Child, Preschool

KW - Cohort Studies

KW - Diarrhea

KW - Feces

KW - Female

KW - Gastroenteritis

KW - Humans

KW - Immunoglobulin A

KW - Immunoglobulin G

KW - India

KW - Infant, Newborn

KW - Male

KW - Recurrence

KW - Rotavirus

KW - Rotavirus Infections

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1056/NEJMoa1006261

DO - 10.1056/NEJMoa1006261

M3 - Article

VL - 365

SP - 337

EP - 346

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 4

ER -