BackgroundGut microbiota plays an important role in the growth of children. The gut of children with optimum growth is enriched in certain species, especially Bifidobacteria and Clostridia. ...Bifidobacteria and commensal Clostridia both contribute to formation of acidic stool, and an elevated faecal pH indicates reduction of these species in the gut. The purpose of the study was to investigate the association of faecal pH with childhood stunting.MethodsIn this cross-sectional study, 100 children with length-for-age Z score (LAZ) <−1 aged between 12 and 18 months were enrolled from the ongoing Bangladesh Environmental Enteric Dysfunction study conducted in Dhaka, Bangladesh. LAZ was measured by anthropometry and data on factors affecting linear growth were recorded. Faecal pH measurement was done using pH metre on freshly collected non-diarrhoeal faecal samples following standard procedure. Multiple quantile regression was done to quantify the relation between faecal pH and LAZ scores.ResultsThe mean LAZ and faecal pH of the children were −2.12±0.80 and 5.84±1.11, respectively. Pearson correlation analysis showed a statistically significant negative correlation between stool pH and the LAZ scores (p<0.01). After inclusion of other factors affecting linear growth into the regression model, a statistically significant inverse association was observed between faecal pH and LAZ score (p<0.01).ConclusionElevated faecal pH was found to have a significant association with stunted growth. As an indicator of gut microbiota status, faecal pH might have emerged as a possible indirect determinant of childhood stunting.Trial registration number NCT02812615
Background and objectiveSerological screening with a confirmation through biopsy has improved the understanding of coeliac disease (CD) epidemiology worldwide. Prevalence of CD in Bangladesh is not ...yet explored and therefore, we aimed to assess the seroprevalence of CD in slum-dwelling malnourished children and adults in Dhaka.MethodsSerum samples were collected from three different cohorts: stunted (length-for-age Z-scores (LAZ) <−2) and at risk of stunting children (LAZ <−1 to −2) and malnourished adults (body mass index <18.5 kg/m2). Samples from all the participants were assessed for anti-tissue transglutaminase antibody (tTG-IgA) and total serum IgA by ELISA. Positive tTG-IgA and randomly selected low IgA values were reconfirmed using anti-tTG-IgG and gliadin IgG ELISA. CD was diagnosed when second screening tests were found positive and the participants were further investigated by small bowel biopsy.ResultsA total of 818 participants (240 stunted, 272 at risk of stunting children and 306 malnourished adults) were enrolled in the study. Overall, anti-tTG-IgA was positive in 5/818 (0.6%; 95% CI 0.25% to 1.46%). Of the five positive cases, anti-tTG-IgG and gliadin IgG were found positive in only one participant. Duodenal biopsy of positive participant revealed characteristic lesions of CD. Randomly selected low IgA values were found negative in tTG-IgG and gliadin IgG for all the participants. No participant was found total IgA deficient.ConclusionThe incidence of coeliac autoimmunity is low in malnourished slum dwellers regardless of age in Bangladesh. It is important to investigate the nationwide prevalence to reveal the definite picture.
Shigella spp. constitutes some of the key pathogens responsible for the global burden of diarrhoeal disease. With over 164 million reported cases per annum, shigellosis accounts for 1.1 million ...deaths each year. Majority of these cases occur among the children of the developing nations and the emergence of multi-drug resistance Shigella strains in clinical isolates demands the development of better/new drugs against this pathogen. The genome of Shigella flexneri was extensively analyzed and found 4,362 proteins among which the functions of 674 proteins, termed as hypothetical proteins (HPs) had not been previously elucidated. Amino acid sequences of all these 674 HPs were studied and the functions of a total of 39 HPs have been assigned with high level of confidence. Here we have utilized a combination of the latest versions of databases to assign the precise function of HPs for which no experimental information is available. These HPs were found to belong to various classes of proteins such as enzymes, binding proteins, signal transducers, lipoprotein, transporters, virulence and other proteins. Evaluation of the performance of the various computational tools conducted using receiver operating characteristic curve analysis and a resoundingly high average accuracy of 93.6% were obtained. Our comprehensive analysis will help to gain greater understanding for the development of many novel potential therapeutic interventions to defeat Shigella infection.
Severe acute malnutrition (SAM) is a major public health concern among low- and middle-income countries, where the majority of the children encountering this acute form of malnutrition suffer from ...environmental enteric dysfunction (EED). However, evidence regarding the effects of L-carnitine supplementation on the rate of weight gain and EED biomarkers in malnourished children is limited.
We aimed to investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with SAM.
A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted at the Nutritional Rehabilitation Unit (NRU) of Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh. Children with SAM aged 9–24 mo were randomly assigned to receive commercial L-carnitine syrup (100 mg/kg/d) or placebo for 15 d in addition to standard of care. A total of 98 children with Weight-for-Length-z-score (WLZ) < −3 Standard deviation were enrolled between October 2021 and March 2023. Analyses were conducted on an intention-to-treat basis.
The primary outcome variable, “rate of weight gain,” was comparable between L-carnitine and placebo groups (2.09 ± 2.23 compared with 2.07 ± 2.70; P = 0.973), which was consistent even after adjusting for potential covariates (age, sex, Weight-for-Age z-score, asset index, and WASH practices) through linear regression ß: 0.37; 95% confidence interval (CI): −0.63,1.37; P = 0.465. The average hospital stay was ∼4 d. The results of adjusted median regression showed that following intervention, there was no significant difference in the EED biomarkers among the treatment arms; Myeloperoxidase (ng/mL) ß: −1342.29; 95% CI: −2817.35, 132.77; P = 0.074, Neopterin (nmol/L) ß: −153.33; 95% CI: −556.58, 249.91; P = 0.452, alpha-1-antitrypsin (mg/mL) ß: 0.05; 95% CI: −0.15, 0.25; P = 0.627. Initial L-carnitine (μmol/L) levels (median, interquartile range) for L-carnitine compared with placebo were 54.84 (36.0, 112.9) and 59.74 (45.7, 96.0), whereas levels after intervention were 102.05 (60.9, 182.1) and 105.02 (73.1, 203.7).
Although our study findings suggest that L-carnitine bears no additional effect on SAM, we recommend clinical trials with a longer duration of supplementation, possibly with other combinations of interventions, to investigate further into this topic of interest.
This trial was registered at clinicaltrials.gov as NCT05083637.
Introduction
: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the ...biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network (
www.chainnnetwork.org
) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach.
Methods and analysis
; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children.
Ethics and dissemination
. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases.
Trial registration
NCT03208725.
Adult undernutrition (BMI <18.5 kg/m2) is responsible for immune deficits, increased risk of disease burden, and higher rates of mortality. The prevalence of adult undernutrition in Bangladesh is ...substantial, but there have been few studies on the etiology of this condition for the inhabitants of urban slums.
The aim of this study was to identify the factors associated with undernutrition among slum-dwelling adults in Bangladesh.
A case-control study was conducted in the Bauniabadh area of Dhaka, Bangladesh. 270 adult participants (135 cases with a BMI <18.5 and 135 controls with a BMI between 18.5 and 24.9) aged 18–45 y were enrolled between October 2018 and January 2019. Sociodemographic variables, dietary diversity, micronutrient deficiencies, psychological symptoms, infection, and biomarkers of gut health were assessed to identify the factors associated with undernutrition using multivariable logistic regression analysis.
A higher number of siblings adjusted odds ratio (aOR): 1.39; 95% CI: 1.11, 1.77, increased self-reporting questionnaire-20 score (an instrument to screen mental health disorders and detect psychological symptoms) (aOR: 1.12; 95% CI: 1.04, 1.23), elevated fecal concentration of α-1 antitrypsin (aOR: 4.82; 95% CI: 1.01, 25.29), and anemia (aOR: 3.63; 95% CI: 1.62, 8.58) were positively associated with undernutrition in adults. Age (aOR: 0.90; 95% CI: 0.84, 0.96), dietary diversity score (aOR: 0.75; 95% CI: 0.56, 0.99), C-reactive protein (aOR: 0.82; 95% CI: 0.73, 0.92), Helicobacter pylori infection (aOR: 0.11; 95% CI: 0.05, 0.23), and always washing hands before eating or preparing foods (aOR: 0.33; 95% CI: 0.12, 0.87) were associated with reduced odds of undernutrition among the study population.
Our results indicate that undernutrition in slum-dwelling adults in Bangladesh is associated with numerous physiological and sociodemographic factors, including evidence of gastrointestinal inflammation and altered intestinal permeability.
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.
Secretor status refers to the ability of an individual to secrete blood group antigens into body fluids and onto the different epithelial surfaces. Concurrent findings have demonstrated an ...association of the secretor status of children with susceptibility to a plethora of enteropathogens. We aimed to determine a possible association of secretor status of children with childhood enteropathy, an important causal factor for childhood growth failure. Participants of the Malnutrition and Enteric Disease (MAL-ED) birth cohort study from the Bangladesh site were enrolled along with their mothers. Saliva was analyzed for determining blood groups and secretor status of the children and their mothers by using an in-house ELISA. Approximately 59% of children and 65% of mothers were found to be secretor positive. Secretor-positive children were found to have a significantly positive association with alpha-1-antitrypsin (β-coefficient: 0.11, 95% CI: 0.07, 0.21,
P
< 0.01) and with environmental enteric dysfunction score (β-coefficient: 0.32, 95% CI: 0.29, 0.65,
P
= 0.05). However, despite a negative effect size, secretor-positive children did not show any statistical significance with length-for-age and weight-for-age
z
scores (LAZ and WAZ), respectively. Our findings indicate toward the genetic factor of secretor status of children being associated with childhood growth faltering, through increased susceptibility to distinct enteropathogens and the consequent development of enteric inflammation and enteropathy among children. However, these findings are only applicable in Bangladeshi settings and thus need to be validated in several other similar settings, to establish a possible relationship between the secretor status of children with enteropathy and resulting childhood growth failure.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) belongs to the coronaviridae family. In spite of several outbreaks in the very recent years, no vaccine against this deadly virus is developed ...yet. In this study, the receptor binding domain (RBD) of Spike (S) glycoprotein of MERS-CoV was analyzed through Computational Immunology approach to identify the antigenic determinants (epitopes). In order to do so, the sequences of S glycoprotein that belong to different geographical regions were aligned to observe the conservancy of MERS-CoV RBD. The immune parameters of this region were determined using different in silico tools and Immune Epitope Database (IEDB). Molecular docking study was also employed to check the affinity of the potential epitope towards the binding cleft of the specific HLA allele. The N-terminus RBD (S367-S606) of S glycoprotein was found to be conserved among all the available strains of MERS-CoV. Based on the lower IC50 value, a total of eight potential T-cell epitopes and 19 major histocompatibility complex (MHC) class-I alleles were identified for this conserved region. A 9-mer epitope CYSSLILDY displayed interactions with the maximum number of MHC class-I molecules and projected the highest peak in the B-cell antigenicity plot which concludes that it could be a better choice for designing an epitope based peptide vaccine against MERSCoV considering that it must undergo further in vitro and in vivo experiments. Moreover, in molecular docking study, this epitope was found to have a significant binding affinity of -8.5 kcal/mol towards the binding cleft of the HLA-C*12:03 molecule.
Objective
Studies involving less sensitive conventional microscopy and culture‐based approaches have identified distinct differences in diarrhoeal aetiology in childhood malnutrition. Our study ...involved the use of an advanced molecular biology technique, the TaqMan Array Cards (TAC), to elucidate the diarrhoeal aetiology among young infants with severe acute malnutrition (SAM).
Method
A total of 113 faecal samples was collected from SAM infants, aged 2–6 months, upon admission to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) with complications of diarrhoea and related comorbidities. We used TAC for the detection of 29 different diarrhoeal enteropathogens from a single faecal sample. For comparison, we also analysed 25 diarrhoeal samples from well‐nourished infants of similar age.
Results
Higher odds of detection of all bacterial enteropathogens were associated with diarrhoea among SAM infants. In particular, the detection of Aeromonas sp (aOR: 25.7, p = 0.011), Campylobacter sp (aOR: 9.6, p < 0.01) and ETEC (aOR: 5.2, p = 0.022) was significantly associated with diarrhoea among SAM infants in comparison to well‐nourished infants. 80% higher odds of detection of rotavirus and norovirus GII were associated with diarrhoea among well‐nourished infants in comparison to SAM infants (aOR: 0.2, p < 0.05).
Conclusion
Our study findings demonstrate a difference in diarrhoeal aetiology among SAM and well‐nourished young infants, which may be useful in providing an evidence‐based logic for possible revision of treatment guidelines for treatment of young diarrhoeal infants with SAM in the early management of the menace of antimicrobial resistance.
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