Abstract
Background
Maternal breastmilk is a source of pre- and pro-biotics that impact neonatal gut microbiota colonization. Because 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 standardized methods across sites, we compared breastmilk microbiota composition in relation to geographic location and ORV response in cohorts prospectively followed from birth to 18 weeks of age in India (n = 307), Malawi (n = 119), and the United Kingdom (UK n = 60).
Results
Breastmilk microbiota diversity was higher in India and Malawi than the UK across 3 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, vaccine shedding after dose 1, and postvaccination rotavirus-specific immunoglobulin A 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.
Breastmilk microbiota composition differed significantly between cohorts in India, Malawi, and the UK. No consistent associations were identified between breastmilk microbiota composition and infant oral rotavirus vaccine response.
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.
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.
Rotavirus vaccines are playing a pivotal role in improving lives of infants and young children in low and middle-income countries (LMICs). Many of these countries have adopted the vaccine into their ...routine immunization, whereas others are considering introduction. This article provides an update on the impact of rotavirus vaccines in LMICs on morbidity and mortality in children aged less than 5 years, and their cost-effectiveness.
The WHO, in 2013, updated its recommendation to prioritize introduction of rotavirus vaccines in the routine immunization schedule, without age restrictions. Despite the decreased efficacy of the vaccines in LMICs, data from Sub-Saharan Africa have demonstrated a decrease in rotavirus-related morbidity, with some sites reporting an indirect protective effect on children age ineligible to receive the vaccine. Even with improvements in sanitation, nutritional status in children, and other health-related indices in LMICs, the use of rotavirus vaccines will play an important role in preventing rotavirus-related gastroenteritis. Economic models predict a reduction in economic burden because of rotavirus-related health costs, making vaccine introduction cost-effective in resource-constrained settings.
Increasing evidence from impact studies shows the significant impact of rotavirus vaccination on hospitalizations and economic burden because of rotavirus gastroenteritis in LMICs. Universal rotavirus vaccination is recommended, and introductions should be monitored by robust surveillance systems to measure effectiveness and impact.
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.
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.
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 < 20 years (aOR 0.5; 95% CI 0.4, 0.7), low birth weight infants (aOR 0.6; 95% CI 0.4, 0.8), and infants in whom breastfeeding was initiated one hour after birth (aOR 0.8; 95% CI 0.7, 0.9) showed a reduced odds of being exclusively breastfed at 6 months compared to their counterparts.
The overall EBF practice showed an increasing trend in the NFHS-5 compared to the NFHS-4 survey. However, a vast gap remains unaddressed in the Indian setting with > 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.
Delayed vaccination increases the susceptibility window for vaccine preventable diseases. Our analysis estimates the proportion of children between 10 and 23 months of age with delayed vaccination in ...India and the associated socio-demographic, maternal and child related factors.
We used individual level data from the National Family and Health Survey 4, conducted in 2015–2016. The primary outcome of the study was delayed vaccination for BCG, DPT- 1st dose and Measles. Delayed vaccination for each vaccine was defined as administration of the vaccine dose after 28 days of the minimum recommended age, as per the national immunization schedule in India. We estimated the proportion of children with delayed vaccination for each vaccine and used multivariable logistic regression to explore associated factors.
In the current analysis, 23.1%, 29.3% and 34.8% of children aged 10 to 23 months had delayed vaccination for BCG, DPT-1st dose and Measles respectively. Children from Muslim families (aOR 1.36 for BCG; aOR 1.45 for DPT-1; aOR 1.26 for Measles); birth weight < 2000 g (aOR 2.33 for BCG; aOR 1.53 for DPT-1; aOR 1.36 for Measles) had higher odds of delayed vaccination. Lower maternal education and belonging to a family from lower wealth quintile had higher odds of delayed vaccination. Children of mothers who had tetanus toxoid immunization during pregnancy had lower odds of delayed vaccination (aOR 0.69 for BCG; aOR 0.76 for DPT-1; aOR 0.78 for Measles).
The proportion of children with delayed vaccination is high in India. Vaccine timeliness should be a core indicator of the immunization program with greater focus on groups with higher chances of delayed vaccination i.e. home birth, low birth weight new-borns, poorer households, children of mothers with lower education and children from Muslim families.
•We estimated incidence of dengue in children in the community through active surveillance.•Annual incidence rate in fever of >3days was 49.5 per 1000 child years.•High dengue incidence in children ...warrants public health interventions.
Our main objective was to estimate population based dengue incidence estimates in children with fever >3 days.
The study used the ‘National Surveillance System for Enteric Fever in India’ (NSSEFI) cohort at the Vellore site. Children aged 6 months to 14 years from a peri-urban setting in Vellore were followed up for a year for the presence of fever. All children who had fever >3days were eligible for blood culture to diagnose typhoid. All children that presented with fever >3days on alternate days of the week were also tested for dengue. Dengue incidence estimates were then calculated.
There were 6648 children followed up with a cumulative observation period of 5800 child years. There were 11753 fever episodes with 3171 (27%) episodes lasting >3 days. Totally, 784 children with 868 episodes of fever were tested for Dengue. NS1 antigen or Dengue IgM or both were positive in 82 (9.4%) of those tested for Dengue. Dengue PCR was positive in 33/64 (51.6%) of the samples positive samples. The annual incidence rate of dengue was 49.5 per 1000 child years among children with fever >3 days.
There is high burden of dengue in peri-urban Vellore.
India has seen rapid unorganized urbanization in the past few decades. However, the burden of childhood diseases and malnutrition in such populations is difficult to quantify. The morbidity ...experience of children living in semi-urban slums of a southern Indian city is described.
A total of 176 children were recruited pre-weaning from four geographically adjacent, semi-urban slums located in the western outskirts of Vellore, Tamil Nadu for a study on water safety and enteric infections and received either bottled or municipal drinking water based on their area of residence. Children were visited weekly at home and had anthropometry measured monthly until their second birthday.
A total of 3932 episodes of illness were recorded during the follow-up period, resulting in an incidence of 12.5 illnesses/child-year, with more illness during infancy than in the second year of life. Respiratory, mostly upper respiratory infections, and gastrointestinal illnesses were most common. Approximately one-third of children were stunted at two years of age, and two-thirds had at least one episode of growth failure during the two years of follow up. No differences in morbidity were seen between children who received bottled and municipal water.
Our study found a high burden of childhood diseases and malnutrition among urban slum dwellers in southern India. Frequent illnesses may adversely impact children's health and development, besides placing an additional burden on families who need to seek healthcare and find resources to manage illness.
Cohort studies are pivotal in understanding the natural history, and to thereby determine the incidence of a disease. The conduct of large-scale community-based cohort studies is challenging with ...reference to money, manpower and time. Further, attrition inherent to cohort studies can affect the power, and thereby the study's validity. Our objective was to estimate the percentage of participant withdrawal and to subsequently understand reasons for the same in the Vellore Typhoid Surveillance (VTS) cohort.
VTS study, a prospective community-based pediatric cohort, was established in a semi-urban settlement of Vellore to estimate the incidence rate of typhoid fever. An active weekly surveillance identified children with fever, and blood cultures were performed for fevers of ≥3 days. Reasons for participant drop-out in the cohort were documented. Nine focus group discussions (FGD), each with 5 to 7 parents/primary caregivers of former as well current participants were conducted separately, to understand reasons for consent withdrawal as well as the good aspects of the study that the current participants perceived. A descriptive, as well as an interpretative account of the themes that emerged from the FGDs were done.
Of the 5639 children in the VTS cohort, 404 (7.2%) withdrew consent during the 12-month surveillance. Of these, 50% dropped out due to migration from study area; 18.1% as their parents were unhappy with the blood draws for blood culture; and 14.4% did not clearly put forth the reason for consent withdrawal. Being from an orthodox background, high socio-economic status and joint family were associated with a decision to drop-out. Frequent and voluminous blood draws, male field research assistants (FRA) making weekly home-visits, the perception that inquiring about fever made their child fall sick, and that the study clinic did not initiate antibiotics immediately, were the important themes that emerged from the FGDs conducted among drop-outs.
Our study showed that specific beliefs and behaviours within the community influenced the drop-out rate of the VTS cohort. Background characteristics and perceptions that exist, along with attrition data from previous cohort studies in the specific community are important to be considered while implementing large-scale cohort studies.
"I Lost My Beautiful Child" Sindhu, Kulandaipalayam Natarajan
The American journal of tropical medicine and hygiene,
10/2021, Letnik:
105, Številka:
4
Journal Article
Recenzirano
Odprti dostop
There exists an invisible blanket of factors beyond the walls of just the provision of healthcare and access to it. The existing intricate social behaviors, domestic violence that lingers silently, ...recalcitrant alcoholism in men, and the lack of education for large segments of the population are larger issues that are delicately interwoven into people’s lives and loom with animosity in poor communities. Our efforts as physicians must persist to better the lives of people holistically and not merely with reference to the bodily diseases in the community.
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