Rotavirus trends and distribution of genotypes before and during COVID-19 pandemic era: Bangladesh, 2017-2021.

Rotavirus gastroenteritis is accountable for an estimated 128 500 deaths among children younger than 5 years worldwide, and the majority occur in low-income countries. Although the clinical trials of rotavirus vaccines in Bangladesh revealed a significant reduction of severe rotavirus disease by around 50%, the vaccines are not yet included in the routine immunization program. The present study was designed to provide data on rotavirus diarrhea with clinical profiles and genotypes before (2017-2019) and during the COVID-19 pandemic period (2020-2021). Fecal samples were collected from 2% of the diarrheal patients at icddr,b Dhaka hospital of all ages between January 2017 and December 2021 and were tested for VP6 rotavirus antigen using ELISA. The clinical manifestations such as fever, duration of diarrhea and hospitalization, number of stools, and dehydration and so on were collected from the surveillance database (n = 3127). Of the positive samples, 10% were randomly selected for genotyping using Sanger sequencing method. A total of 12 705 fecal samples were screened for rotavirus A antigen by enzyme immunoassay. Overall, 3369 (27%) were rotavirus antigen-positive, of whom children <2 years had the highest prevalence (88.6%). The risk of rotavirus A infection was 4.2 times higher in winter than in summer. Overall, G3P[8] was the most prominent genotype (45.3%), followed by G1P[8] (32.1%), G9P[8] (6.8%), and G2P[4] (6.1%). The other unusual combinations, such as G1P[4], G1P[6], G2P[6], G3P[4], G3P[6], and G9P[6], were also present. Genetic analysis on Bangladeshi strains revealed that the selection pressure (dN/dS) was estimated as <1. The number of hospital visits showed a 37% drop during the COVID-19 pandemic relative to the years before the pandemic. Conversely, there was a notable increase in the rate of rotavirus positivity during the pandemic (34%, p < 0.00) compared to the period before COVID-19 (23%). Among the various clinical symptoms, only the occurrence of watery stool significantly increased during the pandemic. The G2P[4] strain showed a sudden rise (19%) in 2020, which then declined in 2021. In the same year, G1P[8] was more prevalent than G3P[8] (40% vs. 38%, respectively). The remaining genotypes were negligible and did not exhibit much fluctuation. This study reveals that the rotavirus burden remained high during the COVID-19 prepandemic and pandemic in Bangladesh. Considering the lack of antigenic variations between the circulating and vaccine-targeted strains, integrating the vaccine into the national immunization program could reduce the prevalence of the disease, the number of hospitalizations, and the severity of cases.

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.

Anti-Ascaris IgE as a Risk Factor for Asthma Symptoms among 5-Year-Old Children in Rural Bangladesh with Even Decreased Ascaris Infection Prevalence.

BACKGROUND: Epidemiological studies have indicated that anti-Ascaris IgE enhances asthma and allergies under specific conditions although the association between them is still controversial. The association of anti-Ascaris IgE with increased asthma symptoms among children from a general population with a mild to moderate Ascaris infection prevalence was investigated. METHODS: A total of 126 children aged 5 years with wheezing during the previous year and 110 children who did not have wheezing were selected randomly from the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Serum levels of total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anti-cockroach IgEs were tested, and their risks for wheezing were analyzed. The wheezing children were then classified by hierarchical cluster analysis to investigate the contribution of anti-Ascaris IgE to wheezing. RESULTS: The anti-Ascaris IgE levels in wheezing and never-wheezing children were 1.07 and 0.65 UA/mL, and it contributed to 11% of wheezing in children. Anti-Ascaris IgE was significantly associated with wheezing (odds ratio [OR] per loge increment: 1.37 [95% CI: 1.01-1.87], p = 0.046). The ORs, which were adjusted for sex, parental asthma, pneumonia history, helminth infections, Haemophilus influenzae type B combination vaccination, antibiotic use during infancy, and total and specific IgE levels, increased even when only children with more specific symptoms of asthma were included in the analysis. Namely, the ORs for wheezing with sleep disturbance, four or more attacks, and wheezing with speech difficulties during the previous 1 year were OR = 1.44/loge increment [95% CI: 1.01-2.07], OR = 1.90/loge increment [95% CI: 1.11-3.25], and OR = 1.78/loge increment [95% CI: 1.01-3.14], respectively. CONCLUSIONS: The anti-Ascaris IgE levels in wheezing and never-wheezing children in the current study significantly decreased concurrently with Ascaris infection prevalence compared with their corresponding values in 2001. The contribution of anti-Ascaris IgE to wheezing also dropped from 26% in 2001 to 11% in the current study. Despite significant decreases in the levels and the seroprevalence and its contribution to wheezing, anti-Ascaris IgE remained significantly associated with increased risk of wheezing. Anti-Ascaris IgE significantly increased the risk of wheezing in a general population with a mild to moderate Ascaris infection prevalence, suggesting robustness as a risk factor and a possible dose-response relationship.

Impact of Haemophilus influenzae type b combination vaccination on asthma symptoms and pneumonia in 5-year-old children in rural Bangladesh: a longitudinal study and comparison with a previous cross-sectional study.

BACKGROUND: Although the prevalence of bronchial asthma has been increasing worldwide since the 1970's, the prevalence among 5-year-old children was significantly lower in 2016 than in 2001 in rural Bangladesh. We aimed to determine whether the Haemophilus influenzae type b (Hib) combination vaccination (without booster) started in 2009 contributed to this decrease. METHODS: A case-control study was conducted among 1658 randomly selected 5-year-old children from Matlab, Bangladesh. Data on wheezing were collected using the International Study of Asthma and Allergies in Childhood questionnaire. The vaccination data were collected from the records of the Matlab Health and Demographic Surveillance System, while data on pneumonia were obtained from the clinical records of Matlab Hospital. Adjusted odds ratios (aORs) were calculated for the risk for wheezing. The reduction rate was calculated to determine the impact of the vaccination on pneumonia history between the present study and our previous study conducted in 2001 by using the following formula: (percentage of pneumonia cases in 2001 - percentage of pneumonia cases in 2016)/(percentage of pneumonia cases in 2001) times 100 (%). RESULTS: Hib combination vaccination was a protecting factor against wheezing (aOR: 0.50; p = 0.010), while pneumonia at 1, 2, 3-4 years of age were risk factors for wheezing (aOR: 2.86, 3.19, 2.86; p = 0.046, 0.030, 0.030, respectively). The history of pneumonia was significantly lower in the 2016 study participants than those in 2001 both in the overall cohort and the wheezing group (paired t-test: p = 0.012, p < 0.001, respectively). Whereas the history of pneumonia decreased when the children grew older in the 2001 overall cohort, it peaked at the age of 2 years in 2016 wheezing group. The reduction rate decreased when children grew older in both the overall cohort and the wheezing group, however, it decreased faster in the wheezing group. CONCLUSIONS: Hib combination vaccination was a protective factor against wheezing in 0-year-old children. However, the effects of vaccination might have attenuated at the ages of 1-4 years, because no booster dose was administered. The addition of a booster dose might further decrease the prevalence of asthma and wheezing.

Gestational age data completeness, quality and validity in population-based surveys: EN-INDEPTH study.

BACKGROUND: Preterm birth (gestational age (GA) <37 weeks) is the leading cause of child mortality worldwide. However, GA is rarely assessed in population-based surveys, the major data source in low/middle-income countries. We examined the performance of new questions to measure GA in household surveys, a subset of which had linked early pregnancy ultrasound GA data. METHODS: The EN-INDEPTH population-based survey of 69,176 women was undertaken (2017-2018) in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda. We included questions regarding GA in months (GAm) for all women and GA in weeks (GAw) for a subset; we also asked if the baby was 'born before expected' to estimate preterm birth rates. Survey data were linked to surveillance data in two sites, and to ultrasound pregnancy dating at <24 weeks in one site. We assessed completeness and quality of reported GA. We examined the validity of estimated preterm birth rates by sensitivity and specificity, over/under-reporting of GAw in survey compared to ultrasound by multinomial logistic regression, and explored perceptions about GA and barriers and enablers to its reporting using focus group discussions (n = 29). RESULTS: GAm questions were almost universally answered, but heaping on 9 months resulted in underestimation of preterm birth rates. Preference for reporting GAw in even numbers was evident, resulting in heaping at 36 weeks; hence, over-estimating preterm birth rates, except in Matlab where the peak was at 38 weeks. Questions regarding 'born before expected' were answered but gave implausibly low preterm birth rates in most sites. Applying ultrasound as the gold standard in Matlab site, sensitivity of survey-GAw for detecting preterm birth (GAw <37) was 60% and specificity was 93%. Focus group findings suggest that women perceive GA to be important, but usually counted in months. Antenatal care attendance, women's education and health cards may improve reporting. CONCLUSIONS: This is the first published study assessing GA reporting in surveys, compared with the gold standard of ultrasound. Reporting GAw within 5 years' recall is feasible with high completeness, but accuracy is affected by heaping. Compared to ultrasound-GAw, results are reasonably specific, but sensitivity needs to be improved. We propose revised questions based on the study findings for further testing and validation in settings where pregnancy ultrasound data and/or last menstrual period dates/GA recorded in pregnancy are available. Specific training of interviewers is recommended.

Aflatoxin exposure was not associated with childhood stunting: results from a birth cohort study in a resource-poor setting of Dhaka, Bangladesh.

OBJECTIVE: Chronic aflatoxin exposure has been associated with childhood stunting (length-for-age/height-for-age < -2 sd), while data lacks for Bangladesh, a country with substantial burden of childhood stunting. This paper examined the association between aflatoxin exposure and childhood stunting in a slum setting of Dhaka city. DESIGN: In this MAL-ED aflatoxin birth cohort study, plasma samples were assayed for aflatoxin B1-lysine adduct (AFB1-lys) by MS at 7, 15, 24 and 36 months of age for 208, 196, 173 and 167 children to assess chronic aflatoxin exposure. Relationship between aflatoxin exposure and anthropometric measures was examined by mixed-effects logistic regression models. SETTING AND PARTICIPANTS: The study was conducted in Mirpur, Dhaka, where children were followed from birth to 36 months. RESULTS: Prevalence of stunting increased from 21 % at 7 months to 49 % at 36 months of age. Mean AFB1-lys concentrations at 7, 15, 24 and 36 months were 1·30 (range 0·09-5·79), 1·52 (range 0·06-6·35), 3·43 (range 0·15-65·60) and 3·70 (range 0·09-126·54) pg/mg albumin, respectively, and the percentage of children with detectable AFB1-lys was 10, 21, 18 and 62 %, respectively. No association was observed between aflatoxin exposure and stunting in multivariable analyses. Factors associated with childhood stunting were age, low birth weight, maternal height, stool myeloperoxidase and number of people sleeping in one room. CONCLUSIONS: A relatively lower exposure to aflatoxin may not influence the linear growth of children. This finding indicates a threshold level of exposure for linear growth deficit and further investigation in other areas where higher concentrations of aflatoxin exposure exist.

Effects of maternal exposure to biomass cooking fuel on birth size and body proportionality in full-term infants born by vaginal delivery.

It remains unclear whether and how maternal exposure to biomass fuel influences infant anthropometry or body proportionality at birth, which are linked to their survival, physical growth, and neurodevelopment. Therefore, this study seeks to explore the association between household-level exposure to biomass cooking fuels and infant size and body proportionality at birth among women in rural Bangladesh. A total of 909 women were derived from the Pregnancy Weight Gain study, which was conducted in Matlab, a rural area of Bangladesh. Infant's weight (g), length (cm), head circumference (cm), small for gestational age (SGAW), short for gestational age (SGAL), low head circumference for gestational age (SGAHC), ponderal index, and cephalization index at birth were the outcomes studied. Of the women, 721 (79.3%) were dependent on biomass fuel. Compared to infants born to mothers who used gas for cooking, those born to biomass users had lower weight (ß - 94.3, CI - 155.9, - 32.6), length (ß - 0.36, 95% CI - 0.68, - 0.04), head circumference (ß - 0.24, CI - 0.47, - 0.02) and higher cephalization index (ß 0.03, CI 0.01, 0.05) at birth. Maternal biomass exposure is more likely to lead to symmetric SGA, although there is evidence for some brain-sparing effects.

Prognostic accuracy of early warning scores for predicting serious illness and in-hospital mortality in patients with COVID-19.

A simple bedside triage tool is essential to stratify COVID-19 patients in the emergency department (ED). This study aimed to identify an early warning score (EWS) that could best predict the clinical outcomes in COVID-19 patients. Data were obtained from medical records of 219 laboratory-confirmed COVID-19 positive patients. We calculated 13 EWSs based on the admission characteristics of the patients. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of the scores in predicting serious illness and in-hospital mortality. The median patient age was 51 (38, 60) years, and 25 (11.4%) patients died. Among patients admitted with mild to moderate illness (n = 175), 61 (34.9%) developed serious illness. Modified National Early Warning Score (m-NEWS) (AUROC 0.766; 95% CI: 0.693, 0.839) and Rapid Emergency Medicine Score (REMS) (AUROC 0.890; 95% CI: 0.818, 0.962) demonstrated the highest AUROC point estimates in predicting serious illness and in-hospital mortality, respectively. Both m-NEWS and REMS demonstrated good accuracy in predicting both the outcomes. However, no significant difference was found between m-NEWS (p = 0.983) and REMS (p = 0.428) as well as some other EWSs regarding the AUROCs in predicting serious illness and in-hospital mortality. We propose m-NEWS could be used as a triage score to identify COVID-19 patients at risk of disease progression and death especially in resource-poor settings because it has been explicitly developed for risk stratification of COVID-19 patients in some countries like China and Italy. However, this tool needs to be validated by further large-scale prospective studies.

Effect of Gut Microbiota-Directed Complementary Food Supplementation on Fecal and Plasma Biomarkers of Gut Health and Environmental Enteric Dysfunction in Slum-Dwelling Children with Moderate Acute Malnutrition.

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.

Impacts of climate change on diarrhoeal disease hospitalisations: How does the global warming targets of 1.5-2°C affect Dhaka, Bangladesh?

Dhaka is one of the world's densely populated cities and faces significant public health challenges including high burden of diarrhoeal diseases. Climate change is intensifying existing environmental problems including urban heat island effect and poor water quality. While numerous epidemiological studies have linked meteorological factors to diarrhoeal diseases in Bangladesh, assessment of the impacts of future climate change on diarrhoeal diseases is scarce. We provide the assessment of climate change impacts on diarrhoeal disease in Dhaka and project future health risks under climate change scenarios. About 3 million acute diarrhoea cases presenting to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) during 1981-2010 were linked to daily temperature, rainfall and humidity and association investigated using time series adapted negative binomial regression models employing constrained distributed lag linear models. The findings were applied to climate projections to estimate future risks of diarrhoea under various global warming scenarios. There was a significantly raised risk of diarrhoea hospitalisation in all ages with daily mean temperature (RR: 3.4, 95% CI: 3.0-3.7) after controlling for the confounding effects of heavy rainfall, humidity, autocorrelations, day of the week effect, long-term time, and seasonal trends. Using the incidence rate ratio (IRR) of 1.034, temperature increases based on the global warming targets of 1.5-2°C could result in an increase of diarrhoea hospitalisations by 4.5-7.4% in all age groups by the 2100s. These effects were more pronounced among <5 children where the predicted temperature increases could raise diarrhoea hospitalisation by 5.7% - 9.4%. Diarrhoea hospitalisation will increase significantly in Dhaka even if the global warming targets adopted by the Paris Agreement is reached. This underscores the importance of preparing the city for management and prevention of diarrhoeal diseases.

Is heat wave a predictor of diarrhoea in Dhaka, Bangladesh? A time-series analysis in a South Asian tropical monsoon climate.

While numerous studies have assessed the association between temperature and diarrhoea in various locations, evidence of relationship between heat wave and diarrhoea is scarce. We defined elevated daily mean and maximum temperature over the 95th and 99th percentiles lasting for at least one day between March to October 1981-2010 as TAV95 and TAV99 and D95 and D99 heat wave, respectively. We investigated the association between heat wave and daily counts of hospitalisations for all-cause diarrhoea in Dhaka, Bangladesh using time series regression analysis employing constrained distributed lag-linear models. Effects were assessed for all ages and children aged under 5 years of age. Diarrhoea hospitalisation increased by 6.7% (95% CI: 4.6%- 8.9%), 8.3% (3.7-13.1), 7.0 (4.8-9.3) and 7.4 (3.1-11.9) in all ages on a TAV95, TAV99, D95 and D99 heat wave day, respectively. These effects were more pronounced for under-5 children with an increase of 13.9% (95% CI: 8.3-19.9), 24.2% (11.3-38.7), 17.0 (11.0-23.5) and 19.5 (7.7-32.6) in diarrhoea hospitalisations on a TAV95, TAV99, D95 and D99 heat wave day, respectively. At lags of 3 days, we noticed a negative association indicating a 'harvesting' effect. Our findings suggest that heat wave was a significant risk factor for diarrhoea hospitalisation in Dhaka. Further research is needed to elucidate the causal pathways and identify the preventive measures necessary to mitigate the impacts of heat waves on diarrhoea. Given that no heat wave definitions exist for Dhaka, these results may help to define heat waves for Dhaka and trigger public health interventions including heat alerts to prevent heat-related morbidity in Dhaka, Bangladesh.

Are young and older children with diarrhea presenting in the same way?

BACKGROUND: Diarrhoea is a global health problem. More than a quarter of diarrhoeal deaths occur among children less than five years. Different literatures analyzed presentation and outcomes of less than five diarrhoeal children. The world has made remarkable progress in reducing child mortality. So, older children are growing in number. Our aim was to identify clinical differentials and variations of pathogens among younger (less than five) and older (five to nine years) diarrhoeal children. METHOD: Data were extracted from the diarrhoeal disease surveillance system (DDSS) of Dhaka Hospital (urban site) and Matlab Hospital (rural site) of the International Centre for Diarrhoeal Disease Research, Bangladesh for the period of January 2012 to December 2021. Out of 28,781 and 12,499 surveillance patients in Dhaka and Matlab Hospital, 614 (2.13%) and 278 (2.22%) children were five to nine-years of age, respectively. Among under five children, 2456 from Dhaka hospital and 1112 from Matlab hospital were selected randomly for analysis (four times of five to nine years age children, 1:4). RESULTS: Vomiting, abdominal pain, and dehydrating diarrhoea were significantly higher in older children in comparison to children of less than five years age (p-value <0.05) after adjusting study site, gender, antibiotic use before hospitalization, diarrhoeal duration < 24 hours, intake of oral rehydration fluid at home, parental education, WASH practice and history of cough. Vibrio. cholerae, Salmonella, and Shigella were the common fecal pathogen observed among older children compared to under five after adjusting for age, gender and study site. CONCLUSION: Although percentage of admitted diarrhoeal children with five to nine years is less than under five years children but they presented with critical illness with different diarrhoeal pathogens. These observations may help clinicians to formulate better case management strategies for children of five to nine years that may reduce morbidity.

Development of machine learning models predicting mortality using routinely collected observational health data from 0-59 months old children admitted to an intensive care unit in Bangladesh: critical role of biochemistry and haematology data.

INTRODUCTION: Treatment in the intensive care unit (ICU) generates complex data where machine learning (ML) modelling could be beneficial. Using routine hospital data, we evaluated the ability of multiple ML models to predict inpatient mortality in a paediatric population in a low/middle-income country. METHOD: We retrospectively analysed hospital record data from 0-59 months old children admitted to the ICU of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. Five commonly used ML models- logistic regression, least absolute shrinkage and selection operator, elastic net, gradient boosting trees (GBT) and random forest (RF), were evaluated using the area under the receiver operating characteristic curve (AUROC). Top predictors were selected using RF mean decrease Gini scores as the feature importance values. RESULTS: Data from 5669 children was used and was reduced to 3505 patients (10% death, 90% survived) following missing data removal. The mean patient age was 10.8 months (SD=10.5). The top performing models based on the validation performance measured by mean 10-fold cross-validation AUROC on the training data set were RF and GBT. Hyperparameters were selected using cross-validation and then tested in an unseen test set. The models developed used demographic, anthropometric, clinical, biochemistry and haematological data for mortality prediction. We found RF consistently outperformed GBT and predicted the mortality with AUROC of ≥0.87 in the test set when three or more laboratory measurements were included. However, after the inclusion of a fourth laboratory measurement, very minor predictive gains (AUROC 0.87 vs 0.88) resulted. The best predictors were the biochemistry and haematological measurements, with the top predictors being total CO2, potassium, creatinine and total calcium. CONCLUSIONS: Mortality in children admitted to ICU can be predicted with high accuracy using RF ML models in a real-life data set using multiple laboratory measurements with the most important features primarily coming from patient biochemistry and haematology.

A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth.

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, ßtreatment 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).

Development and Acceptability of Shelf-Stable Microbiota Directed Complementary Food Formulations.

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 titleDevelopment and Acceptability of Shelf-Stable Microbiota-Directed Complementary FoodsPlain language summaryCountries around the world are making progress in fighting malnutrition, but it may be challenging to achieve the global nutrition targets for undernourished children by 2025 at the current rate. To address this problem, we need special types of food that can help children grow, develop properly, and sustain their growth. Children with moderate acute malnutrition have imbalanced gut bacteria. By providing them with the right nutrition, we can restore the healthy bacteria in their gut using a special food called microbiota-directed complementary food (MDCF). Currently, this food is made daily in the icddr, b established field kitchen, which follows standard production measures to control the quality of MDCF preparation, but we need to create stable prototypes that can be stored and used in different settings. This study was designed to develop shelf-stable new formulations in industrial settings and check their acceptability among children with moderate acute malnutrition. The shelf life of the food was extended using a sterilization method, and its microbiological safety was monitored for a year. The actual consumption and acceptability of these foods were evaluated and all these formulations were acceptable by the children and their mother. The children consumed all 4 food formulations in substantial quantities, with consumption rates exceeding 80% for each formulation. This study showed positive results in Bangladesh, but more research is needed to see if these formulations work well in other geographies and over longer periods.

Effects of probiotic and synbiotic supplementation on ponderal and linear growth in severely malnourished young infants in a randomized clinical trial.

Severe acute malnutrition (SAM) is a major global public health problem. We aimed to assess the effects of probiotic and synbiotic supplementation on rate of weight gain and change in length in young SAM infants. This study was substudy of a single-blind randomized clinical trial (NCT0366657). During nutritional rehabilitation, 67 <6 months old SAM infants were enrolled and randomized to receive either probiotic (Bifidobacterium. infantis EVC001) or synbiotic (B. infantis EVC001 + Lacto-N-neotetraose [LNnT]) or placebo (Lactose) for four weeks and were followed for four more weeks after supplementation. In multivariable linear regression model, the mean rate of weight gain in the probiotic arm compared to placebo was higher by 2.03 unit (P < 0.001), and 1.13 unit (P = 0.030) in the synbiotic arm. In linear mixed-effects model, mean WAZ was higher by 0.57 unit (P = 0.018) in probiotic arm compared to placebo. Although not statistically significant, delta length for age z score (LAZ) trended to be higher among children in probiotc (ß = 0.25) and synbiotic (ß = 0.26) arms compared to placebo in multivariable linear regression model. Our study describes that young SAM infants had a higher rate of weight gain when supplemented with probiotic alone, compared to their counterparts with either synbiotic or placebo.

Factors affecting the micronutrient status of adolescent girls living in complex agro-aquatic ecological zones of Bangladesh.

Inadequate intake of both macro and micronutrients is the major determinant of micronutrient deficiencies in adolescent girls. This study assessed multiple micronutrient status including vitamin D, iron, vitamin A, and urinary iodine concentration among adolescent girls through two seasonal cross-sectional surveys conducted during dry and wet seasons. Mixed-effects linear and logistic regression analysis were conducted to assess associations between micronutrient status, salinity and seasonality. The mean age of the girls was 14 years. Vitamin (OH)D insufficiency was significantly higher in freshwater areas in wet season compared to dry season (wet season: 58% and dry season: 30%, P < 0.001). In wet season, risk of vitamin (OH)D insufficiency was three times higher compared to dry season (AOR: 3.03, 95% CI 1.71, 5.37, P < 0.001). The odds of vitamin (OH)D insufficiency was 11 times higher in fresh water areas compared to high saline areas (AOR: 11.51, 95% CI 3.40, 38.93, P < 0.001). The girls had higher risk of iron deficiency in wet season. Despite the environment being enriched with micronutrient-contained aquatic food, adolescent girls in coastal areas experience different micronutrient deficiencies. The high prevalence of vitamin (OH)D insufficiency in freshwater locations and seasonal iron deficiency in high saline areas needs attention.

Determining clinical biomarkers to predict long-term SARS-CoV-2 antibody response among COVID-19 patients in Bangladesh.

Background: Information on antibody responses following SARS-CoV-2 infection, including the magnitude and duration of responses, is limited. In this analysis, we aimed to identify clinical biomarkers that can predict long-term antibody responses following natural SARS-CoV-2 infection. Methodology: In this prospective study, we enrolled 100 COVID-19 patients between November 2020 and February 2021 and followed them for 6 months. The association of clinical laboratory parameters on enrollment, including lactate dehydrogenase (LDH), neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), ferritin, procalcitonin (PCT), and D-dimer, with predicting the geometric mean (GM) concentration of SARS-CoV-2 receptor-binding domain (RBD)-specific IgG antibody at 3 and 6 months post-infection was assessed in multivariable linear regression models. Result: The mean ± SD age of patients in the cohort was 46.8 ± 14 years, and 58.8% were male. Data from 68 patients at 3 months follow-up and 55 patients at 6 months follow-up were analyzed. Over 90% of patients were seropositive against RBD-specific IgG till 6 months post-infection. At 3 months, for any 10% increase in absolute lymphocyte count and NLR, there was a 6.28% (95% CI: 9.68, -2.77) decrease and 4.93% (95% CI: 2.43, 7.50) increase, respectively, in GM of IgG concentration, while any 10% increase for LDH, CRP, ferritin, and procalcitonin was associated with a 10.63, 2.87, 2.54, and 3.11% increase in the GM of IgG concentration, respectively. Any 10% increase in LDH, CRP, and ferritin was similarly associated with an 11.28, 2.48, and 3.0% increase in GM of IgG concentration at 6 months post-infection. Conclusion: Several clinical biomarkers in the acute phase of SARS-CoV-2 infection are associated with enhanced IgG antibody response detected after 6 months of disease onset. The measurement of SARS-CoV-2 specific antibody responses requires improved techniques and is not feasible in all settings. Baseline clinical biomarkers can be a useful alternative as they can predict antibody response during the convalescence period. Individuals with an increased level of NLR, CRP, LDH, ferritin, and procalcitonin may benefit from the boosting effect of vaccines. Further analyses will determine whether biochemical parameters can predict RBD-specific IgG antibody responses at later time points and the association of neutralizing antibody responses.

Factors associated with dehydrating rotavirus diarrhea in children under five in Bangladesh: An urban-rural comparison.

INTRODUCTION: Rotavirus is the leading cause of dehydrating diarrhea in young children worldwide. This study aimed to identify the factors associated with dehydrating rotavirus diarrhea in children under five years of age in urban and rural Bangladesh. METHODS: The study analyzed data from 7,758 children under five who presented with rotavirus diarrhea to Dhaka (urban) and Matlab (rural) hospital of icddr,b during 2009-2018, and were enrolled in the Diarrheal Disease Surveillance System. Cases were defined as children having rotavirus isolated in stool specimens presented with dehydrating diarrhea. Controls were children infected with rotavirus have no dehydration. Multivariable logistic regression models were built to identify the factors associated with dehydrating diarrhea. RESULTS: Among the rotavirus-infected children, 1,784 (34%) in Dhaka and 160 (6%) in Matlab had diarrhea with some or severe dehydration. The female children and age group 24-59 months age was found to be at higher risk of dehydration compared to 6-11 months age. In the multivariable logistic regression model, maternal illiteracy, vomiting, the onset of diarrhea less than 24 hours prior to presenting to the hospital, monsoon months, stunting, and wasting were significantly associated with dehydrating rotavirus diarrhea among children aged 0-59 months in Dhaka. In Matlab, monthly income, duration less than 24 hours prior to attending the hospital, and wasting had an independent significant association with dehydrating rotavirus diarrhea episodes. CONCLUSIONS: Considering factors diversity, educating parents and proper counselling by health care personnel during diarrhea, could lessen the severity of dehydration and the number of hospital visits later on by eliminating the modifiable risk factors among the children, which needs further studies.