Natural Rotavirus Infection in an Indian Birth Cohort: How Much Protection Does It Give?

By Jennifer Zeis

Rotaviruses cause more than half a million deaths each year, and approximately 23 percent of these deaths occur in India. There are two vaccines available for use to prevent rotavirus gastroenteritis in infants and children: RotaTeq and Rotarix. But RotaTeq was introduced in India only earlier this year, and access to it is limited.
Oral vaccines are notorious for having a low efficacy rate in India. The oral trivalent polio vaccine, for example, has not provided long term protection there despite a high effectiveness in developed countries. Seroconversion interference by other enteroviruses is one known culprit, an issue that is compounded in India by high population density and low sanitation.
Earlier research has shown that two infections of rotavirus confer natural protection to children in Mexico against subsequent infections. Does this natural protection occur in India, where rotavirus has the highest mortality in the world?
To find out, Beryl Gladstone et al. recruited 452 children from Chinnallapuram, Ramanaickanpalayam, and Kasba, three contiguous slums in Vellore, India, between March 2002 and August 2003. Field workers visited each child’s house twice a week and obtained a stool sample every two weeks. During these visits the mothers were asked about their children’s health since the last visit. Descriptions of symptoms were recorded, as well as descriptions of illness among other members of the household.  All told, researchers made 121,005 home visits, they report in their study published in NEJM this week.
A blood sample was also collected at birth or during the first week of life and at least every 6 months for the 3 years of follow-up.  These samples were analyzed for antirotavirus IgA and IgG antibodies.  A diagnosis of rotavirus was made if the IgG antibody level rose by a factor of 4 or if IgA increased by a factor of 3.
Primary analyses were restricted to the 373 children who completed the full three years of follow-up. All surveillance and diarrheal stool samples – 26,902 in total, 91.8% of the scheduled collections – were screened for rotavirus using enzyme linked immunosorbent assay (ELISA).
If a test came back positive for rotavirus, it was screened again and then the strain was genotyped. Researchers genotyped 472 rotavirus strains. Infection with the most common type – G1P[8], which surfaced in 15.9% of infections – did not decrease the risk of overall or homotypic rotavirus infection or diarrhea.
These data provide a mixed result. Among the previously-reported Mexican cohort, three rotavirus infections resulted in complete protection against severe rotavirus, but among this Indian cohort, three infections provided 67% protection against rotavirus infection and 79% protection against moderate or severe diarrhea.
Researchers also found that reinfection rates were “much higher” than expected: 30% of all identified infections were primary, as compared with 52% and 81% in Mexico and Guinea-Bissau, respectively. Researchers found that rotavirus affected 53% of children by 6 months of age, a higher level at the same age than Mexico (34%) and Guinea-Bissau (26%).
The researchers conclude that early infection and frequent reinfection in this locale resulted in lower protection than has been reported elsewhere. They also comment that their study found no evidence of homotypic protection, even though the general belief is that protection from infections is initially homotypic and then broadens to heterotypic.
Lindsey Baden, MD, Deputy Editor at NEJM, notes “The findings in this report demonstrate the complex dynamics of rotaviruses in different parts of the world. Pubic health and vaccine deployment strategies will have to incorporate improvements in our understanding of rotavirus biology.”   
While the study by Gladstone et al. does not provide a simple answer to the future of rotavirus vaccination in India, it supplies data that may inform vaccination strategies in this and other resource-poor settings.
“Taken together,” the authors write, “these data indicate that rotavirus-vaccination strategies for India and similar settings may need to be modified by increasing the dose or number of doses of vaccine and considering earlier vaccination, such as neonatal or maternal immunization.”

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