Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants: a prospective cohort study

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. We measured maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. ORV shedding and seroconversion rates were significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk were negatively correlated with ORV response in India and Malawi, and this was mediated partly by a reduction in ORV replication. In the UK, ORV replication was not inhibited despite comparable maternal antibody levels. In both India and Malawi, pre-vaccination microbiota diversity was negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy

Unintentional injuries among children aged 1–5 years: understanding the burden, risk factors and severity in urban slums of southern India

Abstract Background Globally, 5.82 million deaths occurred among children under the age of five years in 2015 and injury specific mortality rate was 73 per 100,000 population. In India, injury specific mortality rate is around 2.1 per 1000 live births contributing to 4% of the total under 5 mortality rate. This study aims to estimate the burden and understand factors associated with unintentional injuries among children aged 1–5 years residing in urban slums of Vellore, southern India. We also attempted to assess the hazards posed by the living environment of these children and study their association with unintentional injury patterns. Methods This cross-sectional study was conducted in eight urban slums of Vellore, southern India and primary caregivers of children aged 1–5 years were interviewed with a questionnaire to obtain the details of injuries sustained in the past three months. Environmental hazard risk assessment was conducted at places frequented by these children and their scores calculated. Baseline prevalence and incidence rates of unintentional injuries were estimated. Multivariate logistic regression and poisson regression analysis were performed to examine factors associated with unintentional injuries and repeated injuries respectively. Association between environmental hazard risk and unintentional injuries was estimated. Results Prevalence of unintentional injuries was 39.1% (95% CI 35.4–42.9%) and incidence rate was 16.5 (95% CI 14.7–18.3) per 100 child months (N = 662). Bivariate analysis revealed that children of working mothers (OR 1.48; 1.01–2.18) and children from overcrowded families (OR 1.78; 1.22–2.60) had increased odds of sustaining unintentional injuries. Multivariate regression analysis revealed that children from overcrowded families had increased odds of sustaining unintentional injuries (AOR 1.66, 95% CI 1.14–2.41). Boys (IRR 1.33, 95% CI 1.07–1.66) and children from overcrowded families (IRR 1.50; 1.14–1.98) were at increased risk of having repeated injuries. There is an increase in incidence rate of injuries with an increased environmental hazard risk, although not statistically significant. Conclusions The burden of unintentional injuries was very high among study children when compared to studies in other urban slums in India. Environment plays an important role in the epidemiology of unintentional injuries; providing safe play environment and adequate supervision of children is important to reduce its burden

Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy

Association between maternal breastmilk microbiota composition and rotavirus vaccine response in African, Asian, and European infants: a prospective cohort study

Abstract Background Maternal breastmilk is a source of pre- and pro-biotics that impact neonatal gut microbiota colonisation. Since oral rotavirus vaccines (ORVs) are administered at a time when infants are often breastfed, breastmilk microbiota composition may have a direct or indirect influence on vaccine take and immunogenicity. Methods Using standardised methods across sites, we compared breastmilk microbiota composition in relation to geographic location and ORV response in cohorts prospectively followed up from birth to 18 weeks of age in India (n = 307), Malawi (n = 119), and the UK (n = 60). Results Breastmilk microbiota diversity was higher in India and Malawi than the UK across three longitudinal samples spanning weeks of life 1 to 13. Dominant taxa such as Streptococcus and Staphylococcus were consistent across cohorts; however, significant geographic differences were observed in the prevalence and abundance of common and rare genera throughout follow-up. No consistent associations were identified between breastmilk microbiota composition and ORV outcomes including seroconversion, post-dose 1 vaccine shedding, and/or post-vaccination rotavirus-specific IgA level. Conclusions Our findings suggest that breastmilk microbiota composition may not be a key factor in shaping trends in ORV response within or between countries. </jats:sec