Persistence of G10P[11] neonatal rotavirus infections in southern India

BACKGROUND: Neonatal rotavirus infections are predominantly caused by distinct genotypes restricted to this age-group and are mostly asymptomatic. METHOD: Stool samples from neonates admitted for >48 h in neonatal intensive care units (NICUs) in Vellore (2014–2015) and Chennai (2015–2016) in southern India, and from neonates born at hospitals in Vellore but not admitted to NICUs (2015–2016) were tested for rotavirus by ELISA and genotyped by hemi-nested RT-PCR. RESULTS: Of 791 neonates, 150 and 336 were recruited from Vellore and Chennai NICUs, and 305 were born in five hospitals in Vellore. Positivity rates in the three settings were 49.3% (74/150), 29.5% (99/336) and 54% (164/305), respectively. G10P[11] was the commonly identified genotype in 87.8% (65/74), 94.9% (94/99) and 98.2% (161/164) of the neonates in Vellore and Chennai NICUs, and those born at Vellore hospitals, respectively. Neonates delivered by lower segment cesarian section (LSCS) at Vellore hospitals, not admitted to NICUs, had a significantly higher odds of acquiring rotavirus infection compared to those delivered vaginally [p = 0.002, OR = 2.4 (1.4–4.3)]. CONCLUSIONS: This report demonstrates the persistence of G10P[11] strain in Vellore and Chennai, indicating widespread neonatal G10P[11] strain in southern India and their persistence over two decades, leading to interesting questions about strain stability

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

Exclusive breastfeeding practices and its determinants in Indian infants: findings from the National Family Health Surveys-4 and 5

Abstract Background The World Health Organization (WHO) recommends exclusive breastfeeding (EBF) in infants for the first 6 months of life. This analysis aims to estimate the proportion of Indian infants exclusively breastfed for the first 6 months using the National Family Health Surveys (NFHS)-4 and 5, and further, determine factors associated with EBF practices. Methods EBF for this analysis was defined as when infants received only breast milk and no complementary feeds (solid food, water, animal milk, baby formula, juice, and fortified food) in the last 24 h prior to the survey. The proportion of infants exclusively breastfed was plotted from birth to 6 months as per the age of children at the time of the survey, and this was computed for individual states, union territories, and overall, for India. Univariate and multivariable logistic regression analyses were performed to examine factors influencing EBF in Indian infants. Results The proportion of Indian infants exclusively breastfed for 6 months was 31.3% (1280/4095; 95% CI 29.9, 32.7) and 43% (1657/3853; 95% CI 41.4, 44.6) as per the NFHS-4 and 5 surveys, respectively. In NFHS-5, infants of scheduled tribes (aOR 1.5; 95% CI 1.2, 1.9) and mothers who delivered at public health facilities (aOR 1.3; 95% CI 1.1, 1.5) showed an increased odds of being exclusively breastfed at 6 months of life compared to their counterparts. Further, infants of mothers aged  50% of the population still not exclusively breastfeeding their infants for the WHO recommended duration of first 6 months. Behavioral studies dissecting the complex interplay of factors influencing EBF within the heterogenous Indian population can help plan interventions to promote and scale-up EBF in Indian infants

Hospitalization Rates and Direct Medical Costs for Fever in a Pediatric Cohort in South India

Primary data on causes and costs of hospitalization are necessary for costing and cost-effectiveness analysis. Data on incidence and causes of hospitalization and consequent expenses among Indian children are limited. A cohort of 6000 children aged 0.5-15 years residing in urban Vellore was followed for 3 years, under the Vellore Typhoid Study, 2016-2017, and later under the Surveillance for Enteric Fever project, 2017-2019. Data on hospitalization events and associated antibiotic use, and direct medical costs for fever-related hospitalization of study children were obtained from caregivers through weekly follow-up by study field workers. The incidence of hospitalization was 33 per 1000 child-years of observation. Children aged 0.5-5 years had the highest incidence of hospitalization. The top 5 infectious causes for hospitalization were acute undifferentiated fevers, respiratory tract infections, acute gastroenteritis, enteric fever, and dengue. The overall median cost of hospitalization for fever was 4243 (interquartile range, 2502-7215) Indian rupees (INR). An episode of dengue had a median cost of 5627 INR, followed by acute undifferentiated fevers and enteric fever with median costs of 3860 and 3507 INR, respectively. Hospitalization for fever is common in young children and impacts household finances in low-income Indian households

Increased bacterial taxonomic and functional diversity is associated with impaired rotavirus vaccine immunogenicity in infants from India and Malawi.

The immunogenicity and effectiveness of oral rotavirus vaccines (ORVs) against severe rotavirus-associated gastroenteritis are impaired in low- and middle-income countries (LMICs) where the burden of disease is highest. Determining risk factors for impaired ORV response may help identify strategies to enhance vaccine effectiveness. In this study, we use metagenomic sequencing to provide a high-resolution taxonomic analysis of stool samples collected at 6 weeks of age (coinciding with the first ORV dose) during a prospective study of ORV immunogenicity in India and Malawi. We then analyse the functional capacity of the developing microbiome in these cohorts. Microbiome composition differed significantly between countries, although functional capacity was more similar than taxonomic composition. Our results confirm previously reported findings that the developing microbiome is more diverse in taxonomic composition in ORV non-seroconverters compared with seroconverters, and we additionally demonstrate a similar pattern in functional capacity. Although taxonomic or functional feature abundances are poor predictors of ORV response, we show that skews in the direction of associations within these microbiome data can be used to identify consistent markers of ORV response across LMIC infant cohorts. We also highlight the systemic under-representation of reference genes from LMICs that limit functional annotation in our study (7% and 13% annotation at pathway and enzyme commission level, respectively). Overall, higher microbiome diversity in early life may act as marker for impaired ORV response in India and Malawi, whilst a holistic perspective of functional capacity may be hidden in the "dark matter" of the microbiome

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

ABSTRACTBackgroundMaternal 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.MethodsUsing 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).ResultsBreastmilk 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 asStreptococcusandStaphylococcuswere consistent across cohorts; however, significant geographic differences were observed in the prevalence and abundance of common and rare genera throughout follow-up. No significant 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.ConclusionsOur findings suggest that breastmilk microbiota composition may not be a key factor in shaping trends in ORV response within or between countries.</jats:sec

Factors Predicting Blood Culture Positivity in Children With Enteric Fever

Blood culture, despite low sensitivity, is the gold standard for enteric fever diagnosis. Understanding predictors of blood culture positivity may help design strategies to optimize enteric fever diagnosis. A cohort of 6760 children aged 0.5-15 years was followed for 3 years for enteric fever with blood cultures in an automated system, for fevers >3 days. Factors affecting test positivity in fevers and participant-level predictors for culture refusals were analyzed using regression models. Overall, 6097 suspected typhoid/paratyphoid fever (STF) episodes were reported, of which 5703 (93.5%) STFs had sampling for blood cultures, with 394 (6.5%) refusals. Salmonella enterica serovar Typhi/Paratyphi positivity was culture-confirmed in 3.8% (218/5703) of STF episodes. Older children (odds ratio [OR], 1.96 [95% CI, 1.39-2.77]), larger blood volume inoculated (OR, 2.82 [95% CI, 1.71-4.66]), higher temperatures during fever (OR, 3.77 [95% CI, 2.89-4.91]), and fevers diagnosed as suspected typhoid or acute undifferentiated fever (OR, 6.06 [95% CI, 3.11-11.78]) had a higher probability of culture positivity. Antibiotics before culture did not decrease culture positivity. Blood culture refusals were higher for children from wealthier households or with milder illness. Performing blood cultures in older children with fever, especially those fevers with toxic presentation and increasing blood volume for inoculation are strategies to improve enteric fever detection in surveillance settings

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