More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children ...with moderate acute malnutrition have perturbed development of their gut microbiota.
In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples.
A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment.
These findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the National Institutes of Health; ClinicalTrials.gov number, NCT04015999.).
The protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to the current vaccination or natural infection is a global concern. We aimed to investigate the rate of ...SARS-CoV-2 infection and its clinical features among infection-naïve, infected, vaccinated, and post-infection-vaccinated individuals. A cohort was designed among icddr,b staff registered for COVID-19 testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). Reinfection cases were confirmed by whole-genome sequencing. From 19 March 2020 to 31 March 2021, 1644 (mean age, 38.4 years and 57% male) participants were enrolled; where 1080 (65.7%) were tested negative and added to the negative cohort. The positive cohort included 750 positive patients (564 from baseline and 186 from negative cohort follow-up), of whom 27.6% were hospitalized and 2.5% died. Among hospitalized patients, 45.9% had severe to critical disease and 42.5% required oxygen support. Hypertension and diabetes mellitus were found significantly higher among the hospitalised patients compared to out-patients; risk ratio 1.3 and 1.6 respectively. The risk of infection among positive cohort was 80.2% lower than negative cohort (95% CI 72.6-85.7%; p < 0.001). Genome sequences showed that genetically distinct SARS-CoV-2 strains were responsible for reinfections. Naturally infected populations were less likely to be reinfected by SARS-CoV-2 than the infection-naïve and vaccinated individuals. Although, reinfected individuals did not suffer severe disease, a remarkable proportion of naturally infected or vaccinated individuals were (re)-infected by the emerging variants.
Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between ...the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.
Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the ...incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).
In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates.
Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r = -0.49; P = 0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED.
These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).
There is a lack of information highlighting the possible association between strain carrying genes of enteroaggregative Escherichia coli (EAEC) and environmental enteric dysfunction (EED) and on ...linear growth during childhood. Strain carrying genes of EAEC from stool samples collected from 1705 children enrolled in the MAL-ED birth cohort were detected by TaqMan Array Cards. We measured site-specific incidence rate by using Poisson regression models, identified the risk factors and estimated the associations of strain carrying genes of EAEC with the composite EED score and linear growth at 24 months of age. Overall highest incidence rate (43.3%) was found among children having infection with the aggR gene, which was the greatest in Tanzania (56.7%). Low maternal education, lack of improved floor, and ownership of domestic cattle were found to be risk factors for EAEC infection. In the multivariate models, after adjusting the potential covariates, strain carrying genes of EAEC showed strong positive associations with the EED scores and with poor linear growth at 24 months of age. Our analyses may lay the cornerstone for a prospective epidemiologic investigation for a potential vaccine development aimed at reducing the burden of EAEC infections and combat childhood malnutrition.
There is a lack of information highlighting the possible association between the genomic subtypes of enteropathogenic Escherichia coli (EPEC) on environmental enteric dysfunction (EED) and on linear ...growth during childhood. Genomic subtypes of EPEC from stool samples collected from 1705 children enrolled in the MAL-ED birth cohort were detected by TaqMan Array Cards. We measured site-specific incidence rate by using Poisson regression models, identified the risk factors and estimated the association of genomic subtypes of EPEC with the composite EED score and linear growth at 24 months of age. In general, the highest incidence rate (39%) was found among children having aEPEC infection, which was the greatest in Tanzania (54%). Exclusive breastfeeding and having an improved sanitation facility were found to be protective factors against EPEC infection. In the multivariate models, in overall effect after adjusting for the potential covariates aEPEC showed strong positive associations with the EED scores and tEPEC showed a positive association with poor linear growth at 24 months of age. Our analyses may lay the cornerstone for a prospective epidemiologic investigation for a potential vaccine development aimed at reducing the burden of EPEC infections and combat childhood malnutrition.
Globally more than 150 million children under age 5 years were stunted in 2018, primarily in low- and middle-income countries (LMICs), and the impact of early-onset, persistent stunting has not been ...well explored. To explore the association between early-onset persistent stunting in children and cognitive development at 5 years of age, and to identify the factors associated with early-onset stunting.
Children from the MAL-ED cohort study were followed from birth to 5 years of age in six LMICs. The Wechsler Preschool Primary Scales of Intelligence (WPPSI) was used to assess cognitive abilities (fluid reasoning) at 5 years and was adapted for each culture. Stunting was categorized as early-onset persistent (first stunted at 1-6 months and persisting at 60 months), early-onset recovered (first stunted at 1-6 months and not stunted at 60 months), late-onset persistent (first stunted at 7-24 months and persisting at 60 months), late-onset recovered (first stunted at 7-24 months and not stunted at 60 months), and never (never stunted). Mixed effects linear models were used to estimate the relationship between stunting status and cognitive development. Children with early-onset persistent stunting had significantly lower cognitive scores (-2.10 (95% CI: -3.85, -0.35)) compared with those who were never stunted. Transferrin receptor (TfR) was also negatively associated with cognitive development (-0.31 (95% CI: -0.49, -0.13)), while the HOME inventory, an index of quality of the home environment (0.46 (95% CI: 0.21, 0.72)) and socio-economic status (1.50 (95% CI: 1.03, 1.98)) were positively associated with cognitive development.
Early-onset persistent stunting was associated with lower cognitive development in children at 5 years of age in this cohort of children.
The effectiveness of micronutrient powder (MNP) on the health outcome of children is yet to be proved. Although studies identified the barriers to the use of MNP the underlying factors related to the ...barriers to the use of MNP are still unexplored. We examined the underlying factors associated with the barriers reported by the caregivers of the children aged 6-59 months in Bangladesh.
We analyzed pooled data of 3, 634 caregiver-child dyads extracted from eight cross-sectional surveys. The surveys were conducted as part of an evaluation of the Maternal, Infant and Young Children Nutrition programme (phase 2) in Bangladesh. We performed univariate analysis to find the barriers reported by the caregivers of the children. We identified the underlying factors related to the reported barriers by performing multiple logistic regression analysis.
The mostly reported barrier was perceived lack of need for MNP among the caregivers of the children (39.9%), followed by lack of awareness of the product (21.7%) and cost of the product (18.1%). Caregivers of older children (adjusted odds ratio (aOR): 1.69; 95% CI: 1.43, 2.00) and caregivers who maintained good infant and young child feeding practices (aOR: 1.32; 95% CI: 1.12, 1.57) perceived more lack of need for MNP. Caregivers of the female children (aOR: 0.79; 95% CI: 0.63, 0.98) were less likely to report that their children disliked MNP compared to the caregivers of the male children.
Programmes intended to effectively promote MNP among the caregivers of children aged 6-59 months should carefully consider the factors that could underlie the barriers to the use of MNP.
The association between mother's education and the World Health Organization's (WHO's) eight Infant and Young Child Feeding (IYCF) core indicators has yet to be explored in South Asia (SA). This ...study aimed to explore the association between mother's education and the WHO's eight IYCF core indicators in SA. We analyzed data from the most recent nationally representative Demographic and Health Surveys of six South Asian Countries (SACs)-Afghanistan, Bangladesh, India, Maldives, Nepal, and Pakistan. We found significantly higher odds (adjusted odds ratio, AOR, 1.13 to 1.47) among mothers who completed secondary or higher education than among mothers with education levels below secondary for the following seven IYCF indicators: early initiation of breastfeeding (EIBF), exclusive breastfeeding under 6 months (EBF), the introduction of solid, semisolid or soft foods (ISSSF), minimum dietary diversity (MDD), minimum meal frequency (MMF), minimum acceptable diet (MAD), and consumption of iron-rich or iron-fortified foods (CIRF); the exception was for the indicator of continued breastfeeding at one year. Country-specific analyses revealed significantly higher odds in EIBF (AOR 1.14; 95% CI: 1.11, 1.18) and EBF (AOR 1.27; 95% CI: 1.19, 1.34) among mothers with secondary or higher education levels in India. In contrast, the odds were lower for EIBF in Bangladesh and for EBF in Pakistan among mothers with secondary or higher education levels. For country-specific analyses for complementary feeding indicators such as ISSSF, MDD, MMF, MAD, and CIRF, significantly higher odds (AOR, 1.15 to 2.34) were also observed among mothers with secondary or higher education levels. These findings demonstrate a strong positive association between mother's education and IYCF indicators. Strengthening national policies to educate women at least to the secondary level in SACs might be a cost-effective intervention for improving IYCF practices.
Urinary excretion of two orally-administered non-metabolizable sugars, lactulose and mannitol, is a valuable marker for evaluating intestinal permeability. Usually this test involves a time consuming ...procedure of about 5 hour's urine collection, which makes the test incompatible to some extent. As the results are expressed as the ratio of lactulose and mannitol recovered in urine within certain time, it may be possible to get similar result despite the reduced urine collection time of 2 hours. Moreover, different laboratories do the test by different methods, which make the results incomparable between laboratories. Here, we are also trying to find the correlation between results from most commonly used methods: HPAE-PAD and LC-MSMS. The lactulose: mannitol (LM) test was performed in a cohort of Bangladeshi infants considered at-risk for environmental enteropathy. 208 urine specimens from 104 (52 male and 52 female) infants were collected at 2 and 5 hours after LM solution administration and were tested for lactulose and mannitol by two different methods, one HPAE-PAD platform and another LC-MSMS platform. Median age of the children was 15.0 months (range 6.9 to 25.8 months) and their mean weight-for-age z-score was -0.92. A higher percentage of lactulose and mannitol recovery was found in 5 hours urine collection than in the corresponding 2 hours by both HPAE-PAD and LC-MSMS method, but when results were expressed as lactulose to mannitol ratio (LMR) there was no significant difference between 2 and 5 hours urine collection in both HPAE-PAD (P = 0.138) and LC-MSMS (P = 0.099) method. LMR based on 2 hours urine collection correlated well with LMR based on traditional 5 hours urine collection (Spearman's correlation coefficient 0.578 and 0.604 respectively for HPAE-PAD and LC-MSMS). In future, LM test to assess intestinal permeability in children can be simplified by shortening the urine collection time from 5 hours to 2 hours.
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