Site-Specific Incidence Rate of \u3ci\u3eBlastocystis hominis\u3c/i\u3e and Its Association with Childhood Malnutrition: Findings from a Multi-Country Birth Cohort Study

In this study, we investigated the potential association between the burden of asymptomatic Blastocystis spp. (Blastocystis hominis) infection and nutritional status among children under 2 years of age using the data collected from 1,715 children from eight distinct geographic locations, including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. Childhood stunting, wasting, and underweight were the outcome variables, and B. hominis infection was the exposure variable of this present study. The presence of B. hominis in nondiarrheal stools was evaluated by TaqMan Array Cards. Site-specific incidence rates were estimated using Poisson regression, and multiple generalized estimating equation was used to assess the association between the B. hominis infection and nutritional status. The site-specific incidence rates of asymptomatic B. hominis infections per 100 child-months were higher in Tanzania, Peru, and South Africa when compared with the other study sites. Moreover, in terms of site-specific association, childhood stunting was significantly associated with asymptomatic B. hominis infection in Bangladesh (odds ratio [OR]: 1.62; 95% CI: 1.26–2.08), India (OR: 1.78; 95% CI: 1.46–2.16), Nepal (OR: 2.26; 95% CI: 1.60–3.21), Peru (OR: 1.47; 95% CI: 1.26–1.71), South Africa (OR: 1.57; 95% CI: 1.35–1.83), and Tanzania (OR: 2.46; 95% CI: 2.18–2.79) sites. Wasting was associated with B. hominis in the Brazil site only (OR: 3.19; 95% CI: 1.31–7.77). On the other hand, underweight was associated in the Bangladesh (OR: 1.89; 95% CI: 1.48–2.42), Brazil (OR: 4.41; 95% CI: 1.57–12.4), Nepal (OR: 2.25; 95% CI: 1.52–3.35), and Tanzania (OR: 1.68; 95% CI: 1.42–1.99) sites. Our analysis further reveals that the presence of additional pathogens may play a pathogenic role in children who have B. hominis infection

Preparation, GIAO NMR Calculations and Acidic Properties of Some Novel 4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives with Their Antioxidant Activities

Six novel 3-alkyl(aryl)-4-(p-nitrobenzoylamino)-4,5-dihydro-1H-1,2,4-triazol-5- ones (2a-f) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H- 1,2,4-triazol-5-ones (1a-f) with p-nitrobenzoyl chloride and characterized by elemental analyses and IR, 1H-NMR, 13C-NMR and UV spectral data. The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as acetone, isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide, and the half-neutralization potential values and the corresponding pKa values were determined for all cases. Thus, the effects of solvents and molecular structure upon acidity were investigated. In addition, isotropic 1H and 13C nuclear magnetic shielding constants of compounds 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound has been optimized using the 6-311G basis set. Theoretical values were compared to the experimental data. Furthermore, these new compounds and five recently reported 3-alkyl-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3a–c,e,f) were screened for their antioxidant activities

Proof-of-concept study of the efficacy of a microbiota-directed complementary food formulation (MDCF) for treating moderate acute malnutrition

BACKGROUND: Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between - 2 and - 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy growth. Here we describe the design controlled feeding study that tests whether MDCF-2 exhibits superior efficacy (ponderal growth, host biomarkers of a biological state) than a conventional Ready-to-use Supplementary Food (RUSF) in children with MAM over intervention period of 3 months. METHODS: Two separate cohorts of 12-18-month-old children will be enrolled: 124 with primary MAM, and 124 with MAM after having been treated for severe acute malnutrition (post-SAM MAM). We have established several field sites in an urban slum located in the Mirpur district of Dhaka, Bangladesh and at a rural site, Kurigram in the north of Bangladesh. The two groups of children receiving MDCF-2 and RUSF will be compared at baseline (pre-intervention), after 1 month, at the end of intervention (3 months), 1 month after cessation of intervention, and every 6 months thereafter for 4 years. DISCUSSION: This study will determine whether daily, controlled administration of MDCF-2 for 3 months provides superior improvements in weight gain, microbiota repair, and elevated levels of key plasma biomarkers/mediators of healthy growth compared to the control RUSF formulation. The pathogenesis of MAM is poorly defined and there are currently no WHO-approved treatments; results from the current study of children with primary MAM and post-SAM MAM will shed light on the effects of the gut microbiota on childhood growth/development and will provide a knowledge base that may help improve complementary feeding practices. TRIAL REGISTRATION: The primary MAM and post-SAM MAM trials are registered in Clintrials.gov (NCT04015999 and NCT04015986, registered on July 11, 2019, retrospectively registered)

Site-Specific Analysis of the Incidence Rate of Enterotoxigenic \u3ci\u3eEscherichia coli\u3c/i\u3e Infection Elucidates an Association with Childhood Stunting, Wasting, and Being Underweight: A Secondary Analysis of the MAL-ED Birth Cohort

Asymptomatic infection by fecal enteropathogens is a major contributor to childhood malnutrition. Here, we investigated the incidence rate of asymptomatic infection by enterotoxigenic Escherichia coli (ETEC) and assessed its association with childhood stunting, wasting, and being underweight among children under 2 years of age. The Malnutrition and Enteric Disease birth cohort study included 1,715 children who were followed from birth to 24 months of age from eight distinct geographic locations including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. The TaqMan array card assay was used to determine the presence of ETEC in the nondiarrheal stool samples collected from these children. Poisson regression was used to estimate the incidence rate, andmultiple generalized estimating equations with binomial family, logit link function, and exchangeable correlation were used to analyze the association between asymptomatic ETEC infection and anthropometric indicators such as stunting, wasting, and being underweight. The site-specific incidence rates of asymptomatic ETEC infections per 100 child-months were also higher at the study locations in Tanzania (54.81 [95% CI: 52.64, 57.07]) and Bangladesh (46.75 [95% CI: 44.75, 48.83]). In the Bangladesh, India, and Tanzania sites, the composite indicator of anthropometric failure was significantly associated with asymptomatic ETEC infection. Furthermore, a significant association between asymptomatic heat-stable toxin ETEC infections and childhood stunting, wasting, and being underweight was found in only the Bangladesh and Tanzania sites

Children living in the slums of Bangladesh face risks from unsafe food and water and stunted growth is common

Aim: This study investigated the microbial quality of food and water consumed by children in four slums in Dhaka, the capital of Bangladesh, together with the associated risk factors. Methods: This cross-sectional study took place from December 2015 to May 2016 and focused on 360 children under the age of five. We recorded household food security, namely adequate food for a healthy life, socio-economic and nutritional status, hygiene and feeding practices. Food and water samples were analysed. Results: We found that 63% of the children were malnourished and 58% were stunted. Yeast and moulds were detected in 86% of the food samples and coliforms in 73%. All the water samples were contaminated with faecal coliforms, yeasts and moulds and Staphylococcus. Food insecurity affected 83% of households. Children were twice as likely to be malnourished if they were born with a perceived low birth weight or their mothers did not wash their hands with soap after cleaning the child’s bottom following defecation. Exclusively breast-fed children were less likely to develop malnutrition. Conclusion: Children from the Dhaka slums were frequently stunted and malnourished and contaminated food and water was common. Integrated efforts are essential to create public awareness about hygiene

Developing shelf-stable Microbiota Directed Complementary Food (MDCF) prototypes for malnourished children: Study protocol for a randomized, single-blinded, clinical study

BACKGROUND: Childhood undernutrition is a major public health concern that needs special attention to achieve 2025 global nutrition targets. Moderate acute malnutrition (MAM), manifest as wasting (low weight-for-height), affects 33 million children under 5, yet there are currently no global guidelines for its treatment. We recently performed a randomized-controlled clinical study of a microbiota-directed complementary food formulation (MDCF-2) in 12-18-month-old Bangladeshi children with MAM. The results revealed that MDCF-2, freshly prepared each day, produced a significantly greater improvement in ponderal growth than a standard ready-to-use supplementary food (RUSF), an effect that is associated with repair of the disrupted gut microbial community development that occurs in children with MAM. To test the generalizability of these results in acutely malnourished children at other sites, there is a pressing need for a packaged, shelf-stable, organoleptically-acceptable formulation that is bioequivalent to MDCF-2. This report describes the protocol for a clinical study to evaluate candidate formulations designed to meet these criteria. METHODS: A randomized single-blind study will be conducted in 8-12-month-old Bangladeshi children with MAM to compare the efficacy of alternative shelf-stable MDCF prototypes versus the current MDCF-2 formulation that is produced fresh each day. V4-16S rDNA amplicon and shotgun sequencing datasets will be generated from faecal DNA samples collected from each child enrolled in each group prior to, during, and after treatment to determine the abundances of MDCF-2-responsive bacterial taxa. Efficacy will be assessed by quantifying the change in representation of MDCF-2-responsive gut bacterial taxa after 4-weeks of treatment with freshly prepared MDCF-2 compared to their changes in abundance after treatment with the prototype MDCFs. Equivalence will be defined as the absence of a statistically significant difference, after 4-weeks of treatment, in the representation of faecal bacterial taxa associated with the response to MDCF-2 in participants receiving a test MDCF. DISCUSSION: This trial aims to establish acceptability and equivalence with respect to microbiota repair, of scalable, shelf-stable formulations of MDCF-2 in 8-12-month-old Bangladeshi children with moderate acute malnutrition. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05094024). The trial has been registered before starting enrolment on 23 October 2021

Nutrition of Children and Women in Bangladesh: Trends and Directions for the Future

Although child and maternal malnutrition has been reduced in Bangladesh, the prevalence of underweight (weight-for-age z-score <-2) among children aged less than five years is still high (41%). Nearly one-third of women are undernourished with body mass index of <18.5 kg/m2. The prevalence of anaemia among young infants, adolescent girls, and pregnant women is still at unacceptable levels. Despite the successes in specific programmes, such as the Expanded Programme on Immunization and vitamin A supplementation, programmes for nutrition interventions are yet to be implemented at scale for reaching the entire population. Given the low annual rate of reduction in child undernutrition of 1.27 percentage points per year, it is unlikely that Bangladesh would be able to achieve the United Nations’ Millennium Development Goal to address undernutrition. This warrants that the policy-makers and programme managers think urgently about the ways to accelerate the progress. The Government, development partners, non-government organizations, and the academia have to work in concert to improve the coverage of basic and effective nutrition interventions, including exclusive breastfeeding, appropriate complementary feeding, supplementation of micronutrients to children, adolescent girls, pregnant and lactating women, management of severe acute malnutrition and deworming, and hygiene interventions, coupled with those that address more structural causes and indirectly improve nutrition. The entire health system needs to be revitalized to overcome the constraints that exist at the levels of policy, governance, and service-delivery, and also for the creation of demand for the services at the household level. In addition, management of nutrition in the aftermath of natural disasters and stabilization of prices of foods should also be prioritized

Use of antibiotics in children younger than two years in eight countries: A prospective cohort study

Objective: To describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics.Methods: Between 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers’ reports at twice-weekly visits over the children’s first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class.Findings: Over 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites.Conclusion: Repeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non-specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest