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.).

Figure 1. Incidence of Diarrhea and Rotavirus Infection Detected by Stool Testing Alone in the Birth Cohort

The two pyramids at the left show the numbers of deaths, hospitalizations, clinic visits, and diarrheal episodes in the recruited cohort of 452 children and in the cohort of 373 children who completed the 3-year follow-up, respectively; the values to the right of each pyramid are the ratios of the frequencies shown within the pyramid to the total number of diarrheal episodes. Two deaths that were not associated with diarrheal disease are not shown. The three pyramids at the right show the numbers of hospitalizations, clinic visits, diarrheal episodes, and rotavirus infections — and the corresponding ratios of these frequencies to the total number of rotavirus infections — according to the means of detection of rotavirus in stool specimens: positive finding on enzyme-linked immunosorbent assay (ELISA) or polymerase-chain-reaction (PCR) assay, the most sensitive definition; positive findings on ELISA and PCR assay, the most specific definition; or two positive findings on ELISA or one positive finding on PCR assay, the definition used here. These data do not include infections detected by means of serologic testing.

Figure 2. Vesikari Scores for Diarrheal Disease Severity in Consecutive Rotavirus Infections

Panel A shows scores between the first and second rotavirus infections in 196 children with at least two infections. Panel B shows scores between the second and third rotavirus infections in 149 children with at least three infections. An episode was classified as asymptomatic if the score was 0, mild if the score was between 1 and 10, moderate if the score was between 11 and 15, and severe if the score was between 16 and 20. The horizontal bars represent the mean score for each group (with the mean ±SD shown next to the bar).