Ishita Mostafa

In coastal Bangladesh, climate-related hazards threaten health and primary healthcare (PHC) systems, already constrained by infrastructure, workforce, and energy gaps. Teknaf, a coastal sub-district of Cox’s Bazar, hosts part of the approximately 1.19 million Forcibly Displaced Myanmar Nationals (FDMNs) living in Cox’s Bazar District, adding pressure on PHC facilities. Terre des hommes (Tdh), Climate Action Accelerator (CAA), and icddr,b, with local stakeholders, developed Climate-Resilient and Environmentally Sustainable Healthcare (CRESH) solutions for thirteen PHC facilities in Teknaf. This protocol describes a RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance)-guided longitudinal, mixed-methods evaluation to assess implementation feasibility, acceptability, fidelity, adaptation, immediate outcomes, potential indicators of sustainment, and scale-up of CRESH solutions. The evaluation comprises pre–post facility surveys (13 facilities, approximately 35 staff per round), pre–post beneficiary surveys in three facility catchments (186 interviews per round), and initial and concurrent qualitative assessments (interviews, focus group discussions, and facility observations). Data collection runs from January to October 2026 within a 22-month project (March 2025–December 2026). Quantitative data will be analyzed with survey-design methods in Stata 17, and qualitative data by framework analysis. Without a comparison group and with a short implementation period, observed changes will be reported as changes following implementation rather than as effects caused by CRESH. Study findings will inform policy, effectiveness trials, and scale-up in Bangladesh and similar climate-vulnerable, displacement-affected settings.

Objective: This study used the trials of improved practices (TIPs) approach to explore complementary feeding practices among caregivers of children under two and assess the acceptance of new nutritional supplements by providing microbiota-directed supplementary food (MDSF), ready-to-use supplementary food (RUSF) and locally available food (LAF) among moderately malnourished children. Design: The study was conducted between May and October 2022 in preparation for a larger trial. The first phase focused on complementary feeding, hygiene, breast-feeding and responsive feeding practices using in-depth interviews and observations. The second phase involved counselling sessions and providing food supplements for forty-five participants. Follow-up visits evaluated acceptability and challenges faced during this period. Setting: Bauniabadh slum, Mirpur, Dhaka. Participants: Sixty-five children aged 6–24 months with moderate wasting and their caregivers. Results: Findings from IDI and observations revealed poor handwashing practices, with most caregivers washing only with water, and inconsistent use of soap. Only a minority boiled drinking water or cleaned utensils with soap. Responsive feeding practices were also limited, with frequent mobile phone use during feeding and lack of attention to the child. Among the three food interventions, LAF received the highest hedonic ratings across all sensory attributes, with a mean taste score of 5·7±1·4, compared with MDSF (4·8±1·9) and RUSF (4·7±1·6), although median consumption was similar across all supplements (75%). Conclusion: The TIPs approach identified context-specific caregiver behaviours and feeding preferences. These findings will guide the upcoming trial and assist policymakers and program planners in developing culturally tailored interventions to address childhood malnutrition in urban slums.

Objective: Intestinal Alkaline Phosphatase (IAP), expressed by enterocytes, maintains gut homeostasis by promoting commensal microbiota growth and limiting inflammation. Vitamin D strengthens intestinal barrier, and its deficiency is linked to various diseases. This study explores the relationship among IAP, vitamin D, and enteric pathogens in children. Methods: In the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development) study, 265 newborns were enrolled between February 2010 to February 2012, from Dhaka, Bangladesh. 15-month time point data was collected and analyses, where intestinal pathogens were identified by TaqMan Array Card assay, stool IAP and serum vitamin D level were determined by colorimetric assay and chemiluminescence immunoassay respectively. Multivariable linear regression was performed to determine the association between IAP, vitamin D and gut pathogens. A p-value of Campylobacter-pan Genome (p=0.047), Campylobacter jejuni (p=0.020) and Enterocytozoon bieneusi (p=0.023). Multivariable linear regression analysis revealed a significant and inverse association with the Adenovirus-pan genome (β= -2.00; 95% CI= -3.94, -0.07) and E. bieneusi (β= -3.03; 95% CI= -5.94, -0.11). Conclusion: IAP was inversely and significantly associated with Adenovirus-pan genome and E. bieneusi, a less-explored enteric pathogen, while its relationship with vitamin D was positive but not statistically significant. These findings suggest that IAP may play a protective role against specific enteric pathogens. What is already known on this topic: Intestinal Alkaline Phosphatase (IAP) plays a crucial role in maintenance of gut homeostasis by promoting beneficial microbiota and reducing intestinal inflammation. Vitamin D strengthens the intestinal barrier, and deficiency has been linked to increased risk of infections and various chronic diseases. While both IAP and vitamin D are important in gut health, evidence linking them with specific enteric pathogens in human, especially in children remains limited. What this study adds: This study demonstrates that IAP is inversely and significantly associated with Adenovirus-pan genome and Enterocytozoon bieneusi , a less-explored pathogen in children. It shows that although not statistically significant, IAP levels were positively related to vitamin D These findings provide novel evidence that IAP may play a protective role against specific viral and protozoan enteric infections. How this study might affect research, practice or policy: The results highlight IAP as a potential biomarker of intestinal defense and a candidate for future therapeutic or preventive interventions targeting childhood enteric infections. Insights into IAP–pathogen relationships could guide in the development of microbiome-based or nutritional strategies to reduce diarrheal disease burden, and support the inclusion of IAP as potential intervention in child health and nutrition research in low-resource settings.

Introduction: Environmental enteric dysfunction (EED), a subclinical intestinal disorder, is characterized by chronic fecal-oral exposure to entero-pathogens and could be diagnosed by measuring non-invasive biomarkers. Escherichia coli is the one of the key bacterial enteric pathogens that drives EED, but there is a lack of information on the E. coli pathotypes in relation to the biomarkers of EED in malnourished adults. Here, we intended to measure the possible association of these pathotypes with EED biomarkers and nutritional status of adults residing in a slum in Bangladesh.Method: Fecal samples were collected from 524 malnourished adults (BMI ≤18.5 kg/m²) living in a slum-setting in Dhaka from March 2016 to September 2019 and analyzed by TaqMan Array Card assays to evaluate the presence of E. coli pathotypes and other entero-pathogens. The multivariable linear regression model was used to assess the association.Results: In these malnourished adults, the most prevalent pathotype of E. coli was EAEC (61.7%) and the least prevalent was STEC (6.7%). The prevalence of atypical EPEC, ETEC and Shigella/EIEC were 52%, 48.9% and 45.1% respectively. The infection with atypical EPEC had significant positive association with levels of Myeloperoxidase (b = 0.38; 95% CI = 0.11, 0.65; p-value = 0.006). Similarly, a significantly higher concentration of alpha-1-antitrypsin (b = 0.13; 95% CI = 0.03, 0.22; p-value = 0.011) was found in the STEC-infected adults. However, no notable association was found between the E. coli pathotypes and nutritional status of these adult participants. Moreover, Plesiomonas infected adults were more likely to be infected with EAEC (p-value = 0.017), ETEC (p-value Giardia, Ascaris, Campylobacter, Salmonella, Enterocytozoon bieneusi, and Adenovirus.Discussion: The study results imply that there is an influence of particular E. coli pathotypes (EPEC and STEC) on intestinal inflammation and gut permeability of the malnourished Bangladeshi adults, but no association with nutritional status is found. Potential pathogenicity of the E. coli pathotypes is also observed when co-infection with other pathogens exists in these adults.

Globally, moderate wasting affects approximately 33 million children. Complex bidirectional interactions exist between wasting and infection in children. Children who experience both conditions have an increased risk of adverse outcomes including progression to severe wasting and mortality. Breaking the cycle between moderate wasting and infection could help improve growth and survival in these children. The NUTRIMAM trial will aim to investigate the efficacy of a 12-week regimen of three different nutritional interventions in at-risk young children (i.e., children who are moderately wasted and have one/more acute infections) on anthropometric recovery. Further, the study will explore whether recovery can be sustained with a post-intervention package that includes counseling and food vouchers. Sustaining anthropometric recovery beyond supplement administration will have important implications for programs. NUTRIMAM is a multi-country, multi-center individually randomized, open-label, trial in five countries including Bangladesh, India, Mali, Pakistan, and Tanzania. A total of 6360 moderately wasted children aged 6 to 24 months with acute illness will be enrolled at health centers. Children will be randomly allocated to receive one of three dietary supplements (locally available foods, ready-to-use supplementary foods, or microbiota-directed supplementary foods) for 12 weeks. Anthropometric recovery will be assessed over this period. Participants who recover will then be re-randomized to a post-recovery support intervention comprising either counseling and food vouchers or routine standard of care for recovered children for an additional 12 weeks to determine if this intervention facilitates sustained recovery at 24 weeks. Children who are moderately wasted and have an infection are at higher risk of adverse outcomes. There are very few clinical trials that have been performed among children with moderate wasting with infectious illnesses to investigate if it is possible to break the undernutrition–infection cycle and thereby reduce the risk of nutritional deterioration to severe wasting or mortality and decrease the risk of acute infections. The results of the trial are anticipated to fill important evidence gaps in feeding recommendations for moderately wasted children with acute illness as well as interventions to sustain anthropometric recovery in children beyond the period of the nutritional intervention. ISRCTN registry, ISRCTN53213318 . Registered on April 03, 2023.

Globally, severe acute malnutrition (SAM), defined as a weight-for-length z -score more than three SDs below a reference mean (WLZ < −3), affects 14 million children under 5 years of age. Complete anthropometric recovery after standard, short-term interventions is rare, with children often left with moderate acute malnutrition (MAM; WLZ −2 to −3). We conducted a randomized controlled trial (RCT) involving 12- to 18-month-old Bangladeshi children from urban and rural sites, who, after initial hospital-based treatment for SAM, received a 3-month intervention with a microbiome-directed complementary food (MDCF-2) or a calorically more dense, standard ready-to-use supplementary food (RUSF). The rate of WLZ improvement was significantly greater in MDCF-2–treated children ( P = 8.73 × 10 ⁻³ ), similar to our previous RCT of Bangladeshi children with MAM without antecedent SAM ( P = 0.032). A correlated meta-analysis of plasma levels of 4520 proteins in both RCTs revealed 215 positively associated with WLZ (largely representing musculoskeletal and central nervous system development) and 44 negatively associated (primarily related to immune activation). Moreover, the positively associated proteins were significantly enriched by MDCF-2 ( q = 1.1 × 10 ⁻⁶ ). Characterizing the abundances of 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome and how, during treatment for MAM, specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and anthropometric recovery. These results provide a rationale for further testing the generalizability of MDCF efficacy and for identifying biomarkers to define treatment responses.

Background: A randomized controlled trial in Bangladeshi children aged 12 to 18 months with moderate acute malnutrition found that dietary supplementation with the microbiota-directed complementary food (MDCF-2) significantly improved weight gain and repaired gut microbiota compared to the ready-to-use supplementary food. However, the MDCF-2 formulation was made daily from locally available ingredients and the need for a packaged, nutritionally compliant, and organoleptically acceptable MDCF-2 prototype was essential for future large-scale clinical studies. Objective: The study aimed to develop and assess the acceptability of 3 alternative foil-packaged formulations of MDCF-2 in comparison to current MDCF-2. Methods: Of the 3 packaged formulations, the Jumpstart version was provided in 2 sachets, the other 2 formulations were provided in a retort-stable foil pouch extended by sterilization, and microbiological growth was monitored over 10 months. The acceptability study included 40 children aged 8 to 12 months living in an urban slum in Dhaka, and the organoleptic properties were assessed using a 7-point hedonic scale. Results: In the 100 g distributed over the 2 sessions, children consumed 82.5 ± 7.84 g (mean ± SD) of kitchen-prepared MDCF-2, 85.4 ± 7.15 g of the “Jumpstart” MDCF-2 formulation, 85.4 ± 8.70 g of the MDCF-2 with green banana powder, and 86.2 ± 4.26 g of the MDCF-2 with sweet potato formulation. The “Jumpstart” MDCF-2 and MDCF-2 with sweet potato achieved the highest overall acceptability scores on the hedonic scale; although none of the shelf-stable formulations were significantly different from the kitchen-prepared MDCF-2. Conclusions: Packaged, shelf-stable prototypes of MDCF-2 exhibited comparable acceptability among Bangladeshi children aged 8 to 12 months to the original freshly prepared formulation. Plain language title: Development and Acceptability of Shelf-Stable Microbiota-Directed Complementary Foods

SUMMARY: Background: Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches. Methods: 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma. Findings: Children who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, β _{treatment group x study week} (95% CI) = 0.002 (0.001, 0.003); P =0.004]. They also had elevated fecal abundances of Agathobacter faecis , Blautia massiliensis , Lachnospira and Dialister , plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjusted P <0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention. Interpretation: MDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development. Funding: This work was supported by the BMGF (Grants OPP1134649/INV-000247). ClinicalTrials.gov identifier: NCT04015999

Dietary supplementation with a gut microbiota-directed complementary food (MDCF-2) significantly improved weight gain and repaired gut microbiota, as reported in a recent randomized controlled trial on Bangladeshi children with moderate acute malnutrition (MAM). Environmental enteric dysfunction (EED) is a small bowel disorder, and recent evidence shows that it is linked to growth failure in children. Therefore, we intended to investigate whether supplementation with MDCF-2 has any role in modifying gut health by changing the levels of biomarkers of EED and gut inflammation in children with MAM. We randomly assigned 124 children aged 12–18 months to one of two intervention diets, either MDCF-2 or ready-to-use supplementary food (RUSF). Approximately 50 g of the diet was administered in two feeding sessions daily for 12 weeks. Stool and plasma biomarkers were assessed to evaluate intestinal health. Results showed that the average change in citrulline concentration (µmol/L) significantly increased among children who consumed MDCF-2 compared to those who consumed RUSF (mean difference-in-differences: 123.10; 95% CI: 3.60, 242.61; p = 0.044). The research findings demonstrated that MDCF-2 might have a beneficial effect on improving the gastrointestinal health of malnourished children.

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.