Small Intestine Bacterial Overgrowth is associated with increased Campylobacter and epithelial injury in duodenal biopsies of Bangladeshi children.

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10-6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter.

Effects of L-Carnitine Supplementation on the Rate of Weight Gain and Biomarkers of Environmental Enteric Dysfunction in Children with Severe Acute Malnutrition: A Double-Blind Randomized Controlled Clinical Trial.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Prevalence and factors associated with undernutrition and overnutrition among ever-married adolescent girls in Bangladesh: an analysis of national surveys from 2004 to 2017.

Nutritional impairment during adolescence may result in adverse physical and reproductive health outcomes. We investigated the prevalence and determined the factors associated with underweight and overweight/obesity among ever-married adolescent girls in Bangladesh. We used Bangladesh Demographic and Health Surveys data conducted in 2004, 2007, 2011, 2014, and 2017. A total of 7040 ever-married adolescent girls aged 15-19 years were included in this analysis. Prevalence of underweight (body mass index [BMI]<18.5 kg/m2) significantly decreased from 39.53% (95% CI = 36.71, 42.43) to 23.62% (95% CI = 21.35, 26.05) during 2004-2017 (p < 0.001). However, prevalence of overweight/obesity (BMI ≥ 23 kg/m2) significantly increased from 5.9% (95% CI = 4.67, 7.43) to 22.71% (95% CI = 20.39, 25.20) during the same period (p < 0.001). The girls with higher age (OR = 0.94, 95% CI = 0.90, 0.99, p = 0.023), higher level of education (OR = 0.60, 95% CI = 0.43, 0.83, p = 0.002), and richest wealth quintile (OR = 0.78, 95% CI = 0.62, 0.98, p = 0.035) had significantly lower risk of being underweight. Adolescent girls having more than one child (OR = 1.41, 95% CI = 1.15, 1.73, p = 0.001) were more likely to be underweight. Elderly adolescents with better economic status were more at risk of being overweight/obese (OR = 2.57, 95% CI = 1.86, 3.55, p < 0.001). Girls married to skilled/unskilled workers (OR = 0.58, 95% CI = 0.44, 0.77, p < 0.001) and persons involved in small businesses (OR = 0.66, 95% CI = 0.49, 0.89, p = 0.007) had lower risk of having a high BMI. Using contraceptive (OR = 0.8, 95% CI = 0.69, 0.94, p = 0.006) was negatively associated with overweight/obese. Although prevalence of undernutrition among ever-married adolescent girls is declining, the proportion of being overweight/obese is increasing in Bangladesh warranting effective strategies to improve adolescent nutrition.

Alteration of stool pH and its association with biomarkers of gut enteropathy among slum-dwelling women of reproductive age in Bangladesh.

BACKGROUND: Recent evidence suggests that measures of maternal gut enteropathy are associated with unfavorable fetal outcomes. It is, therefore, crucial to identify and treat the features of intestinal enteropathy among reproductive-age women living in areas where enteropathy is highly prevalent. However, there is a lack of non-invasive diagnostic tests to determine EED, making it difficult to identify the disease in field settings. In this study, we tested the potential of fecal pH as a biomarker of gut enteropathy and investigated its relationship with fecal biomarkers of intestinal enteropathy in reproductive-age women living in resource-limited environments. METHODS: Data on socio-demographic information, anthropometry, and biological samples were collected from 78 apparently healthy women aged between 20 and 27 years from November 2018 to December 2019. The association of stool pH with two fecal biomarkers of gut enteropathy (i.e., intestinal alkaline phosphatase [IAP] and fecal lipocalin-2 [LCN-2] was investigated using multiple linear regression models after adjusting for relevant covariates. RESULTS: In the adjusted models, alkaline stool pH (pH > 7.2) was found to be significantly associated with a decrease in the fecal IAP level by 1.05 unit (95% CI: -1.68, -0.42; p < 0.001) in the log scale, and acidic stool pH (pH < 6) was found to be significantly associated with an increase in the fecal LCN-2 level by 0.89 units (95% CI: 0.12, 1.67; p < 0.025) in the log scale. CONCLUSIONS: The study findings demonstrated an association of fecal pH with biomarkers of gut enteropathy indicating its applicability as a simple tool for understanding intestinal enteropathy among reproductive-age women living in resource-limited settings.

Nutritional status and dietary diversity of pregnant and nonpregnant reproductive-age Rohingya women.

There are no data on the nutritional status and dietary diversity of the pregnant and nonpregnant reproductive-age Rohingya women who have recently shifted to the Bhasan Char Relocation Camp located on an island in the Bay of Bengal. A cross-sectional survey was conducted in November-December, 2021 to assess the nutritional status and evaluate the dietary diversity of two vulnerable groups of the forcibly displaced Rohingya population: nonpregnant reproductive-age women and pregnant mothers. Multivariable logistic regression was applied to identify the factors associated with nutritional impairments. Overall, 7.6% of the nonpregnant reproductive-age women were underweight (Body Mass Index [BMI] < 18.5 kg/m2), and nearly one-third of them had a BMI ≥ 25 kg/m2. However, 26.7% of the pregnant mothers were undernourished (BMI < 20.0 kg/m2) and almost one-fourth of them were either overweight or obese (BMI ≥ 25.0 kg/m2). The prevalence of thinness (Mid Upper Arm Circumference [MUAC] < 23 cm) was 34.5% among pregnant mothers, and 10.1% of them were severely thin (MUAC < 21 cm). The mean (±SD) of the Women's Dietary Diversity Score (WDDS) was 3.3 (±1.1) for nonpregnant reproductive-age women and 3.7 (±1.3) for pregnant mothers enrolled in this study. Overall, 63.8% of the nonpregnant women of childbearing age and 46% of the pregnant mothers had a low WDDS (WDDS < 4). The WDDS was found to be protective against thinness among nonpregnant reproductive-age women (AOR = 0.61; 95% CI = 0.37, 0.93; p-value = .03) and low BMI in pregnant mothers (AOR = 0.71; 95% CI = 0.55, 0.91; p-value = .01). The results of this survey will assist in early recognition of the nutritional demands, and act as a guide to planning nutrition-based programs among Rohingya reproductive-age women relocated to the Bhasan Char Island.

Estimating the cost of illness of non-alcoholic fatty liver disease in Bangladesh.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is a growing concern, affecting about 45 million of the Bangladeshi population. There is a paucity of research on the economic burden of NAFLD. The study aims to estimate the cost of illness of NAFLD in Bangladesh. Methods: In this prospective, cross-sectional study, a total of 250 patients of NAFLD, non-alcoholic steatohepatitis (NASH), and NASH cirrhosis were included from public and private hospitals. Costs of hospitalization, physician fees, investigation costs, expenditures on medical procedures, drugs; and nonmedical costs such as transport expenses and other informal payments (tips) were estimated. Results: The overall cost per patient per evaluation was (16.90-46 942.00) USD. The cost in public and private hospitals was 384.76 and 1146.93 USD, respectively. The cost per patient of NAFLD was 157.91 (16.90-955.08) USD, and for NASH cirrhosis was 1783.80 (422.48-46 942) USD. The cost of illness increased to USD 281.18 for diabetics and 254.52 USD for hypertensive. If all the NAFLD patients are evaluated once in healthcare settings, the projected cost will be 7.11 billion USD. In NAFLD, cost for investigations, medicines, transportation, and consultation of physicians was 49.08%, 32.41%, 11.11%, and 6.67%, respectively. Conclusions: NAFLD is causing a huge economic burden to the healthcare system. The cost of illness is increased with NASH cirrhosis. Overall, this study provides valuable insights into the economic burden of NAFLD in Bangladesh and emphasizes the several ways of intervention to reduce the cost by preventive measures and accessible healthcare for affected individuals.

Success of health cell approach in improving knowledge, attitude and practice related to COVID-19: difference-in-differences analyses of a community-based quasi-experimental trial.

OBJECTIVES: There remain hesitations and miscommunication regarding appropriate public health behaviours and conceptions related to COVID-19. We tested the effectiveness of the community-based health cell approach in improving knowledge, attitude and practice (KAP) related to COVID-19. SETTING: Households of the Bauniabadh slum area in Mirpur, Dhaka, Bangladesh. PARTICIPANTS: Household heads (HHs) and homemakers (HMs) of intervention (n=211) and comparison households (n=209). INTERVENTIONS: Behaviour change communication delivered at the community level in a quasi-experimental manner through small-scale community meetings and home visits. OUTCOME VARIABLES AND METHODS: The outcomes of interest were before-after mean and per cent changes in KAP scores. Data were collected from HHs and HMs before and after the intervention and difference-in-differences (DID) analysis technique was applied. RESULTS: We found statistically significant (p<0.05) before-after differences in the responses to the KAP questions made by the intervention groups. The DID models estimated the improvements in COVID-19-related KAP of HHs by 16.58 (95% CI: 14.05, 19.12), 20.92 (95% CI: 18.17, 23.67) and 28.45 (95% CI: 23.84, 33.07) per cent points, respectively. The DID estimates of KAP in HMs were 17.8 (95% CI: 15.09, 20.51), 22.33 (95% CI: 19.47, 25.19) and 28.06 (95% CI: 23.18, 32.93) per cent points, respectively. Overall, 20.91 (95% CI: 18.87, 22.94) and 21.81 (95% CI: 19.68, 23.94) per cent points of improvement were observed among HHs and HMs, respectively. The DID estimates of before-after mean changes in different KAP domains ranged from 2.24 to 2.68 units and the overall changes in KAP scores among HHs and HMs were 7.11 (95% CI: 6.42, 7.8) and 7.42 (95% CI: 6.69, 8.14) units. CONCLUSION: Scientifically valid information disseminated at the community level using the health cell approach could bring positive changes in KAP related to COVID-19.

Site-Specific Incidence Rate of Blastocystis hominis 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.

Nutritional and dietary diversity status of under-5 children and adolescent girls among forcibly displaced Myanmar nationals living in Bhasan Char relocation camp, Bangladesh: a cross-sectional survey.

OBJECTIVE: To generate baseline evidence regarding the nutritional and dietary diversity status of under-5 children and adolescent girls among forcibly displaced Myanmar nationals (FDMN) relocated to Bhasan Char relocation camp of Bangladesh. DESIGN: Cross-sectional survey. SETTING: Bhasan Char relocation camp, Bangladesh, 7 November 2021-12 November 2021. PARTICIPANTS: 299 under-5 children (both male and female) and 248 adolescent girls (11-17 years) were surveyed. OUTCOME MEASURES: Anthropometric indices and nutritional status of the study participants. RESULTS: Nearly 17% of the adolescent girls were suffering from severe thinness/thinness, while 5% were overweight/obese. Severe thinness was more prevalent (2% vs 3.9%) in older adolescents (15-17 years) than their younger counterparts (11-14 years). The prevalence of severe stunting and stunting in adolescents were 14% (95% CI 11.21 to 16.87%) and 29% (95% CI 25.93 to 31.59%), respectively. One-third of the surveyed under-5 children were severely (8.50% (95% CI 5.60 to 11.33%)) or moderately (23.08% (95% CI 20.24 to 25.90%)) stunted, 27% were either severely (4.43% (95% CI 1.60 to 7.27%)) or moderately (22.98% (95% CI 20.15 to 25.81%)) underweight and 12% were severely (1.21% (95% CI 0.00 to 4.04%)) or moderately (10.88% (95% CI 8.05 to 13.72%)) wasted. The prevalence of moderate and severe acute malnutrition in children was low. Surveyed adolescents took a mean of 3.10 (SD 1.03) of nine food groups and 25% (95% CI 22.97 to 28.64%) of under-5 children took minimum diversified diet. The survey respondents mostly consumed carbohydrate-based poorly diversified diets. Nutritional status of the participants did not show any statistically significant association to the dietary diversity status. CONCLUSION: A significant number of surveyed under-5 children and adolescent girls of relocated FDMN living in Bhasan Char of Bangladesh were suffering from thinness, stunting, underweight and wasting. Dietary diversity was poor among the surveyed population.

Environmental enteric dysfunction and small intestinal histomorphology of stunted children in Bangladesh.

There is lack of information on the histological characteristics of the intestinal mucosa in Bangladeshi children. Collection of intestinal biopsy samples and assessment of the histomorphological features is considered to be the traditional gold standard for diagnosis of environmental enteric dysfunction (EED). The purpose of the study was to evaluate the intestinal histological characteristics of stunted children aged between 12-18 months with possible EED. 110 children with chronic malnutrition (52 stunted with length-for-age Z score, LAZ<-2 and 58 at risk of stunting with LAZ <-1 to -2) from the Bangladesh Environmental Enteric Dysfunction (BEED) study protocol who underwent upper gastrointestinal (GI) endoscopy were selected for this study. To explore the association of EED with childhood stunting, upper GI endoscopy was done and the biopsy specimens were studied for histopathology. Villous height and crypt depth were measured and the presence and intensity of inflammatory infiltrates in the lamina propria was investigated. Bivariate analysis was performed to examine the relationship between stunting and histologic morphology. More than 90% children irrespective of nutritional status were diagnosed to have chronic non-specific duodenitis on histopathology. Half of the children from both groups had villous atrophy as well as crypt hyperplasia and lymphocytic infiltration was present in more than 90% children, irrespective of groups. However, no statistically significant difference was observed when compared between the groups. The prevalence of chronic non-specific duodenitis in Bangladeshi children, irrespective of nutritional status, was high. A significant number of these children had abnormal findings in intestinal histomorphology. Trial registration number: ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016. https://clinicaltrials.gov/ct2/results?cond=NCT02812615&term=&cntry=&state=&city=&dist.

Immune modulation by nutritional intervention in malnourished children: Identifying the phenotypic distribution and functional responses of peripheral blood mononuclear cells.

Malnourished children are susceptible to an increased risk of mortality owing to impaired immune functions. However, the underlying mechanism of altered immune functions and its interaction with malnutrition is poorly understood. This study investigates the immune function and evaluates the effect of a particular nutritional intervention on the immune cells of undernourished children. Stunted (LAZ <-2) and at-risk of being stunted (length-for-age Z-scores, LAZ <-1 to -2) children aged between 12 and 18 months were enrolled and were provided with the daily nutritional intervention of one egg and 150 mL cow's milk for 90 days. Peripheral blood mononuclear cells (PBMCs) were isolated at enrolment and upon completion of the intervention. Phenotypic profiles for CD3+ cells, CD4+ cells, CD8+ cells, NKT cells, and B cells were similar in both cohorts, both before and after the intervention. However, activated B cells (CD25+) were increased after nutritional intervention in the at-risk of being stunted cohort. Several pro-inflammatory cytokines, IL-6, IFN-γ, and TNF-α, were elevated in the stunted children following the nutritional intervention. The results of the study indicate that nutritional intervention may have a role on activated B cells (CD25+) s in children who are at-risk of being stunted and may alter the capacity of PBMC to produce inflammatory cytokines in stunted children.

Chronic Aflatoxin Exposure and Cognitive and Language Development in Young Children of Bangladesh: A Longitudinal Study.

Aflatoxin can cross the blood-brain barrier, damage brain tissues, and have the potential to harm the development of the human brain. Although dietary aflatoxin exposure is common in children, there is a paucity of data on aflatoxin exposure and child developmental outcomes. The child's cognitive, motor, and language functions were assessed using the Bayley Scales of Infant and Toddler Development-III or BSID-III at the same time points. Association between exposure to aflatoxin and subtests of BSID-III were examined using mixed-effect linear regression. Aflatoxin assays were performed on 194, 167, and 163 children at 15, 24, and 36 months of age, and chronic aflatoxin exposure was detected in 20.6%, 16.8%, and 60.7% of children, respectively. Multi-variable analyses showed that aflatoxin exposure was independently related to the children's cognitive score (ß: -0.69; 95% CI: -1.36, -0.02), receptive language score (ß: -0.90; 95% CI: -1.62, -0.17), and expressive language score (ß: -1.01; 95% CI: -1.96, -0.05). We did not observe any association between exposure to aflatoxin and the motor function of children. Chronic exposure to aflatoxin exposure was linked to reduced cognitive, expressive, and receptive language scores of the study children. Further research is needed in a different setting to confirm this novel finding.

Maternal and child FUT2 and FUT3 status demonstrate relationship with gut health, body composition and growth of children in Bangladesh.

Fucosyltransferase 2 (FUT2) and 3 (FUT3) may influence host biological functions. We aim to assess the relationship between maternal and child FUT2 (Secretor) and FUT3 (Lewis) status with growth, body composition, gut health and histologic features in Bangladeshi children. We conducted a case-control study where secretor and Lewis status were ascertained from saliva samples of 408 mother-child dyads. Upper-arm fat area estimate (UFE) and total upper arm area (TUA) were found higher among children of Lewis negative mothers (p = 0.01 and p = 0.07, respectively). Changes in UFE after nutrition intervention were significantly greater among Lewis positive children than those of negative for Lewis (p = 0.05). Significant differences were observed for child UFE based on secretor and Lewis status of the mothers (p = 0.04). Lewis positive children had greater changes in WAZ (p = 0.07) and WLZ (p = 0.02) than Lewis negative children at the end of nutrition intervention. Fecal Reg1B was elevated in secretor positive children compared to their counterparts (p = 0.03). Lewis negative children had higher concentrations of MPO compared to Lewis positive children (p = 0.08). We also observed a higher frequency of subtotal villous atrophy among secretor negative and Lewis positive children (p = 0.09 and p = 0.01, respectively) than those of their counterparts. The findings provide insights for further studies to elucidate causal influences.

Association between Circulating Retinol Binding Protein 4, Body Mass Index, and Biomarkers of Environmental Enteric Dysfunction among Slum-Dwelling Lean Adults in Bangladesh.

The relationship of retinol binding protein 4 (RBP4) with biomarkers of intestinal health and gut integrity in adults is unknown. We sought to determine the correlation between plasma RBP4 level and BMI and investigate the relationship of circulating RBP4 concentration with biomarkers of environmental enteric dysfunction among lean adults (body mass index [BMI] < 25.0 kg/m2) in Bangladesh. Overall, 270 adults (135 undernourished with a BMI < 18.5 kg/m2 and 135 healthy controls with a BMI between 18.5 and 24.9 kg/m2) aged 18 to 45 years were evaluated. Multivariable linear regression was performed to test the association between RBP4 and fecal biomarkers of impaired gut health. RBP4 concentration was positively correlated (rho = 0.27, P < 0.001) with BMI and was significantly higher in healthy controls than undernourished adults (P < 0.001), in male than female (P < 0.001), and also in employed (P < 0.001), smokers (P = 0.048) and participants with low Self-Reporting Questionnaire (SRQ)-20 scores (an instrument to screen mental health disorders) (P = 0.049). Statistically significant negative correlations were observed between RBP4 and fecal biomarkers of gut enteropathy including myeloperoxidase (rho = -0.23, P < 0.001), neopterin (rho = -0.30, P < 0.001), and alpha-1 anti-trypsin (rho = -0.21, P < 0.001). Multivariable linear regression analysis showed that increased RBP4 concentration was associated with a significant reduction in fecal neopterin (coefficient = -0.95; 95% confidence interval: -1.44 to -0.45]; P < 0.001) after adjustment for age, sex, nutritional status at enrollment, education, dietary diversity score, SRQ-20 score, improved sanitation, household animal exposure, and alpha-1-acid glycoprotein. The study findings revealed an inverse relationship of plasma RBP4 concentration with fecal biomarkers of altered gut health among slum-dwelling lean adults in Bangladesh.

Role of L-Carnitine supplementation on rate of weight gain and biomarkers of Environmental Enteric Dysfunction in children with severe acute malnutrition: A protocol for a double-blinded randomized controlled trial.

BACKGROUND: Severe acute malnutrition (SAM) and environmental enteric dysfunction (EED) are highly prevalent among children residing in resource-limited countries like Bangladesh. L-carnitine may play a role in improving the growth and ameliorating the EED among nutritionally vulnerable children. OBJECTIVE: To investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with severe acute malnutrition. METHODS: This study is a double-blinded, placebo-controlled, randomized clinical trial aiming to enroll diarrheal children with SAM between 9-24 months of both sexes attending the nutritional rehabilitation unit (NRU) of Dhaka Hospital of icddr,b. It is an ongoing trial including two arms where one arm receives L-carnitine supplementation, and the other arms receive a placebo for 15 days in addition to the existing standard treatment of SAM. The primary outcome is the rate of weight gain, and the secondary outcomes include duration of hospital stay and EED biomarkers. Outcomes are assessed at baseline and 15 days of post-intervention. We hypothesize that the L- carnitine supplementation for 15 days in children with SAM will improve the rate of weight gain and biomarkers of EED. TRIAL REGISTRATION: ClinicalTrials.gov # NCT05083637. Date of registration: October 19, 2021.

A qualitative assessment of facility readiness and barriers to the facility-based management of childhood severe acute malnutrition in the public healthcare settings in Bangladesh.

OBJECTIVE: To assess facility readiness and identify barriers to the facility-based management of childhood severe acute malnutrition (SAM) in public healthcare settings. DESIGN: Qualitative methods were applied to assess readiness and identify different perspectives on barriers to the facility-based management of children with SAM. Data collection was done using in-depth interviews, key informant interviews, exit interviews and pre-tested observation tools. SETTINGS: Two tertiary care and four district hospitals in Rangpur and Sylhet Divisions of Bangladesh. PARTICIPANTS: Healthcare professionals and caregivers of children with SAM. RESULTS: Anthropometric tools, glucometer, medicines, F-75, F-100 and national guidelines for facility-based management of childhood SAM were found unavailable in some of the hospitals. Sitting and sleeping arrangements for the caregivers were absent in all of the chosen facilities. We identified a combination of health system and contextual barriers that inhibited the facility-based management of SAM. The health system barriers include inadequate manpower, rapid turnover of staff, increased workload, lack of training and lack of adherence to management protocol. The major facility barriers were insufficient space and unavailability of required equipment, medicines and foods for hospitalised children with SAM. The reluctance of caregivers to complete the treatment regimen, their insufficient knowledge regarding proper feeding, increased number of attendants and poverty of parents were the principal contextual barriers. CONCLUSIONS: The study findings provide insights on barriers that are curbing the facility-based management of SAM and emphasise policy efforts to develop feasible interventions to reduce the barriers and ensure the preparedness of the facilities for effective service delivery.

Gut biomolecules (I-FABP, TFF3 and lipocalin-2) are associated with linear growth and biomarkers of environmental enteric dysfunction (EED) in Bangladeshi children.

In the current world, a major challenge to diagnose environmental enteric dysfunction (EED) is the lack of validated non-invasive biomarkers. Intestine derived molecules, including intestinal fatty acid binding protein (I-FABP), trefoil factor-3 (TFF3), lactoferrin, lipocalin-2 (LCN2), and mucin-2, have been reported as indicators of intestinal inflammation and gut health. Therefore, we aimed to investigate the levels of these bio-molecules as biomarkers of EED among under-2 children in Bangladesh. A total of 140 children were recruited in a case-control design. All the biomarkers were measured by ELISA. Spearman's rank correlation was performed to see the correlation between the biomarkers and the EED score. Moreover, multivariable linear regression was performed to investigate the association of biomarkers with length-for-age z-score (LAZ). TFF3 correlates positively with myeloperoxidase (r = 0.26, p < 0.05) and EED score (r = 0.17, p < 0.05). Likewise, LCN2 correlates positively with myeloperoxidase (r = 0.37, p < 0.05), neopterin (r = 0.33, p < 0.05) and EED score (r = 0.31, p < 0.05). Moreover, multivariable linear regression revealed a negative association of I-FABP with LAZ of the study participants. Our results imply that TFF3 and LCN2 might be promising biomarkers to diagnose intestinal inflammation and EED, while I-FABP is negatively associated with linear growth of Bangladeshi children.

Health Care Providers' Knowledge, Attitude, and Practice Regarding Facility-Based Management of Children With Severe Acute Malnutrition in Bangladesh.

BACKGROUND: Severe acute malnutrition (SAM) contributes to a substantial number of child deaths globally per year. The mortality rates can be lowered markedly if guideline-based management protocol is properly followed. However, case-fatality rates in resource-poor centers remain high even after introducing the guidelines. Perhaps, the lack of adequate knowledge leading to inappropriate management by the health care providers is responsible for such burden. OBJECTIVE: We aimed to evaluate health care providers' knowledge, attitude, and practice regarding the facility-based management of children with SAM in Bangladesh. METHODS: This was a qualitative study where data were collected cross-sectionally from 4 district and 2 tertiary care hospitals. Twenty-six semi-structured in-depth interviews were conducted among the doctors and nurses involved in inpatient care of SAM. Twenty-eight hours of observation were done in each facility to obtain information regarding the management practices. RESULTS: The doctors had substantial knowledge in managing children with SAM in the facilities. However, knowledge of nurses was found suboptimal when evaluated based on the national guideline. Both doctors and nurses demonstrated favorable attitude toward management of childhood SAM. Identification of SAM at the facilities was poor due to lack of practice in relation to anthropometric measurements. In addition, improper practices related to blood glucose testing, dehydration monitoring, essential micronutrient administration, and follow-up of children with SAM were observed. CONCLUSION: The study results underscore the importance of taking appropriate measures to enhance knowledge and ensure proper practice in relation to inpatient care of children with SAM according to the national guideline in Bangladesh.

Infection With Escherichia Coli Pathotypes Is Associated With Biomarkers of Gut Enteropathy and Nutritional Status Among Malnourished Children in Bangladesh.

Escherichia coli (E. coli) pathotypes are the most common cause of diarrhea, especially in developing countries. Environmental Enteric Dysfunction (EED) is presumed to be the result of infection with one or more pathotypes and can affect intestinal health and childhood growth. We sought to investigate the association of E. coli pathotypes infection with biomarkers of EED and nutritional status among slum-dwelling malnourished children in Bangladesh. This study comprised a total of 1050 stunted and at risk of stunting children. TaqMan Array Card assays were used to determine the presence of E. coli pathotypes in feces. Prevalence of infection with EAEC was highest (68.8%) in this cohort of children, followed by EPEC (55.9%), ETEC (44%), Shigella/EIEC (19.4%) and STEC (3.2%). The levels of myeloperoxidase and calprotectin were significantly higher in EAEC (P=0.02 and P=0.04), EPEC (P=0.02 and P=0.03) and Shigella/EIEC (P=0.05 and P=0.02) positive participants while, only calprotectin was significantly higher in ETEC (P=0.01) positive participants. Reg1B was significantly higher in participants with EAEC (P=0.004) while, neopterin levels were significantly lower in ETEC (P=0.003) and Shigella/EIEC (P=0.003) positive cases. A significant positive relationship was observed between EAEC and fecal levels of Reg1B (ß = 0.28; 95% CI = 0.12, 0.43; p-value<0.001). Besides, ETEC was found to be positively and significantly associated with the levels of calprotectin (ß = 0.14; 95 percent CI = 0.01, 0.26; p-value=0.037) and negatively with neopterin (ß = -0.16; 95% CI = -0.30, -0.02; p-value=0.021). On the other hand, infection with EPEC was found to be negatively associated with length-for-age (ß = -0.12; 95% CI = -0.22, -0.03; p-value=0.011) and weight-for-age (ß = -0.11; 95% CI = -0.22, -0.01; p-value=0.037). The study findings suggest that infection with certain E. coli pathotypes (EAEC and ETEC) influences gut health and EPEC is associated with linear growth and underweight in Bangladeshi children.

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.