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Cohort studies, randomized trials, and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis (RVGE) in low- and middle-income countries. While susceptibility of children to rotavirus is known to vary within and between settings, implications for estimation of immune protection are not well understood. We sought to re-estimate naturally-acquired protection against rotavirus infection and RVGE, and to understand how differences in susceptibility among children impacted estimates. We re-analyzed data from studies conducted in Mexico City, Mexico and Vellore, India. Cumulatively, 573 rotavirus-unvaccinated children experienced 1418 rotavirus infections and 371 episodes of RVGE over 17,636 child-months. We developed a model that characterized susceptibility to rotavirus infection and RVGE among children, accounting for aspects of the natural history of rotavirus and differences in transmission rates between settings. We tested whether model-generated susceptibility measurements were associated with demographic and anthropometric factors, and with the severity of RVGE symptoms. We identified greater variation in susceptibility to rotavirus infection and RVGE in Vellore than in Mexico City. In both cohorts, susceptibility to rotavirus infection and RVGE were associated with male sex, lower birth weight, lower maternal education, and having fewer siblings; within Vellore, susceptibility was also associated with lower socioeconomic status. Children who were more susceptible to rotavirus also experienced higher rates of rotavirus-negative diarrhea, and higher risk of moderate-to-severe symptoms when experiencing RVGE. Simulations suggested that discrepant estimates of naturally-acquired immunity against RVGE can be attributed, in part, to between-setting differences in susceptibility of children, but result primarily from the interaction of transmission rates with age-dependent risk for infections to cause RVGE. We found that more children in Vellore than in Mexico City belong to a high-risk group for rotavirus infection and RVGE, and demonstrate that unmeasured individual- and age-dependent susceptibility may influence estimates of naturally-acquired immune protection against RVGE. [ABSTRACT FROM AUTHOR]

Background: Noroviruses are an important cause of gastroenteritis but little is known about disease and re-infection rates in community settings in Asia. Methods: Disease, re-infection rates, strain prevalence and genetic susceptibility to noroviruses were investigated in a birth cohort of 373 Indian children followed up for three years. Stool samples from 1856 diarrheal episodes and 147 vomiting only episodes were screened for norovirus by RT-PCR. Norovirus positivity was correlated with clinical data, secretor status and ABO blood group. Results: Of 1856 diarrheal episodes, 207 (11.2%) were associated with norovirus, of which 49(2.6%) were norovirus GI, 150(8.1%) norovirus GII, and 8 (0.4%) were mixed infections with both norovirus GI and GII. Of the 147 vomiting only episodes, 30 (20.4%) were positive for norovirus in stool, of which 7 (4.8%) were norovirus GI and 23 (15.6%) GII. At least a third of the children developed norovirus associated diarrhea, with the first episode at a median age of 5 and 8 months for norovirus GI and GII, respectively. Norovirus GI.3 and GII.4 were the predominant genotypes (40.3% and 53.0%) with strain diversity and change in the predominant sub-cluster over time observed among GII viruses. A second episode of norovirus gastroenteritis was documented in 44/174 (25.3%) ever-infected children. Children with the G428A homozygous mutation for inactivation of the FUT2 enzyme (se428se428) were at a significantly lower risk (48/190) of infection with norovirus (p = 0.01). Conclusions: This is the first report of norovirus documenting disease, re-infection and genetic susceptibility in an Asian birth cohort. The high incidence and apparent lack of genogroupII specific immunity indicate the need for careful studies on further characterization of strains, asymptomatic infection and shedding and immune response to further our understanding of norovirus infection and disease. [ABSTRACT FROM AUTHOR]

Background. Rotavirus gastroenteritis results in significant morbidity and mortality in Indian children. Although there are numerous studies on rotavirus diarrhea, there are few reports on antigenemia and extraintestinal presentations in these populations. Methods. Following screening for rotavirus antigen of stool samples from children with and without acute gastroenteritis with a commercial enzyme immunoassay (EIA), a total of 199 stool and serum sample pairs were identified for additional testing. All EIA-positive stool samples were genotyped, and viral load estimated by realtime reverse-transcriptase polymerase chain reaction (RT-PCR). Serum samples were tested for rotavirus antigen by an in-house EIA, and antigen was quantified by optical density. Scoring of disease severity was performed for all hospitalized children. Data on extra-intestinal presentations were collected if available. Results. Based on screening of stool samples by EIA, the study population could be divided into 3 groups, including 111 children with rotavirus diarrhea, 44 children with diarrhea and no rotavirus detected in stool specimens, and 44 children with asymptomatic rotavirus infection. Antigenemia was significantly higher among children with rotavirus diarrhea (50.4%) than among children with non-rotaviral diarrhea (16%) or asymptomatic infections (2.3%) ( ). P ! .001 Low copies of rotavirus were detected by RT-PCR in all 7 children with EIA-negative stool specimens and antigenemia. Presence and levels of rotavirus antigen in serum specimens correlated with stool viral load. Children with antigenemia had significantly more-severe disease but not more extraintestinal presentations than did children without antigenemia. Conclusions. Antigenemia occurs frequently in rotavirus infection and correlates with virus replication in the gut but not with extra-intestinal presentations. [ABSTRACT FROM AUTHOR]