Publications by authors named "Subhasish Das"

66 Publications

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

Front Cell Infect Microbiol 2022 6;12:901324. Epub 2022 Jul 6.

Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

() 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 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 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 (β = 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 (β = 0.14; 95 percent CI = 0.01, 0.26; p-value=0.037) and negatively with neopterin (β = -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 (β = -0.12; 95% CI = -0.22, -0.03; p-value=0.011) and weight-for-age (β = -0.11; 95% CI = -0.22, -0.01; p-value=0.037). The study findings suggest that infection with certain pathotypes (EAEC and ETEC) influences gut health and EPEC is associated with linear growth and underweight in Bangladeshi children.
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http://dx.doi.org/10.3389/fcimb.2022.901324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299418PMC
July 2022

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

BMC Pediatr 2022 07 1;22(1):385. Epub 2022 Jul 1.

Nutrition and Clinical Services Division, icddr,b, Dhaka, 1212, Bangladesh.

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.
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http://dx.doi.org/10.1186/s12887-022-03436-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247958PMC
July 2022

Investigation of negative-ion resonances using a subspace-projected multiconfigurational electron propagator perturbed with a complex absorbing potential.

J Chem Phys 2022 Jun;156(22):224110

School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Argul, Odisha 752050, India.

The transient negative-ion resonances found in scattering experiments are important intermediates in many chemical processes. These metastable states correspond to the continuum part of the Hamiltonian of the projectile-target composite system. Usual bound-state electronic structure methods are not applicable for these. In this work, we develop a subspace-projection method in connection with an electron propagator (EP) defined in terms of a complete-active-space self-consistent-field initial state. The target Hamiltonian (Ĥ) is perturbed by a complex absorbing potential (CAP) for the analytical continuation of the spectrum of Ĥ to complex eigenvalues associated with the continuum states. The resonance is identified as a pole of the EP, which is stable with respect to variations in the strength of the CAP. The projection into a small subspace reduces the size of the complex matrices to be diagonalized, minimizes the computational cost, and affords some insight into the orbitals that are likely to play some role in the capture of the projectile. Two molecular (Πg2N and Π CO) and an atomic shaperesonance (P Be) are investigated using this method. The position and width of the resonances are in good agreement with the previously reported values.
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http://dx.doi.org/10.1063/5.0089912DOI Listing
June 2022

COVID-19 among staff and their family members of a healthcare research institution in Bangladesh between March 2020 and April 2021: a test-negative case-control study.

BMJ Open 2022 06 1;12(6):e058074. Epub 2022 Jun 1.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.

Objective: To identify factors associated with COVID-19 positivity among staff and their family members of icddr,b, a health research institute located in Bangladesh.

Setting: Dhaka, Bangladesh.

Participants: A total of 4295 symptomatic people were tested for SARS-CoV-2 by reverse-transcription PCR between 19 March 2020 and 15 April 2021. Multivariable logistic regression was done to identify the factors associated with COVID-19 positivity by contrasting test positives with test negatives.

Result: Forty-three per cent of the participants were tested positive for SARS-CoV-2. The median age was high in positive cases (37 years vs 34 years). Among the positive cases, 97% were recovered, 2.1% had reinfections, 24 died and 41 were active cases as of 15 April 2021. Multivariable regression analysis showed that age more than 60 years (adjusted OR (aOR)=2.1, 95% CI 1.3 to 3.3; p<0.05), blood group AB (aOR=1.5, 95% CI 1.1 to 2; p<0.05), fever (aOR=3.1, 95% CI 2.6 to 3.7; p<0.05), cough (aOR=1.3, 95% CI 1.1 to 1.6; p<0.05) and anosmia (aOR=2.7, 95% CI 1.3 to 5.7; p<0.05) were significantly associated with higher odds of being COVID-19 positive when compared with participants who were tested negative.

Conclusions: The study findings suggest that older age, fever, cough and anosmia were associated with COVID-19 among the study participants.
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http://dx.doi.org/10.1136/bmjopen-2021-058074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160595PMC
June 2022

Plasma Kynurenine to Tryptophan Ratio Is Not Associated with Undernutrition in Adults but Reduced after Nutrition Intervention: Results from a Community-Based Study in Bangladesh.

Nutrients 2022 Apr 20;14(9). Epub 2022 Apr 20.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh.

Infections and persistent immunological activation are linked to increased kynurenine (KYN) and the KYN-to-Tryptophan (TRP) or KT ratio and may be critical factors in undernutrition. We sought to determine the association between the KT ratio and adult malnutrition, as well as investigate if nutritional supplementation had any influence on the decrease of the KT ratio. A total of 525 undernourished adults aged 18-45 years were recruited and provided a nutrition intervention for 60 feeding days. TRP and KYN concentrations were determined from plasma samples using LC-MS/MS. At baseline, the median (interquartile range (IQR)) TRP, KYN and KT ratios were 24.1 (17.6, 34.3) µmol/L, 0.76 (0.53, 1.18) µmol/L and 30.9 (24.5, 41.7), respectively. Following intervention, the median (IQR) KYN and KT ratios were significantly reduced to 0.713 (0.46, 1.12) µmol/L and 27.5 (21.3, 35.8). The KT ratio was found to be inversely linked with adult BMI (coefficient: -0.09; 95% CI: -0.18, 0.004; -value = 0.06) but not statistically significant. Additionally, Plasma CRP was correlated positively, while LRP1 was inversely correlated with the KT ratio. Our data suggest that in Bangladeshi adults, the KT ratio is not related to the pathophysiology of malnutrition but correlated with inflammatory and anti-inflammatory biomarkers, and the ratio can be reduced by a nutrition intervention.
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http://dx.doi.org/10.3390/nu14091708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104876PMC
April 2022

Evaluation of seasonal dynamics of the surface water hydrochemistry using multivariate statistical techniques and aquatic macrophyte productivity in a mountainous lake, Northeast India.

Environ Sci Pollut Res Int 2022 May 13. Epub 2022 May 13.

Department of Statistics, Manipur University, Canchipur, Imphal, Manipur, 795003, India.

The present work elucidates the effective application of multivariate statistics in understanding the probable relations between surface water hydrochemistry and aquatic macrophyte productivity and their underlying seasonal dynamics in a remote mountainous lake of northeast India. The result of hierarchical cluster analysis revealed three distinct clusters corresponding to the pre-monsoon (35.42%), post-monsoon (52.08%), and monsoon (12.50%) seasons. The factor analysis yielded three principal components suggesting the sediment flux, farming discharge, domestic waste, bacterial oxidation of sulfur compounds, and dissolution of plant matters associated with dissolved feldspar minerals as the influential factors. The lake hydrochemistry also varied significantly, both spatially and temporally implying geogenic weathering processes from rock-soil-water interactions. Overall, sixteen aquatic macrophytes were identified, and their monthly and daily net primary productivity varied considerably in different seasons. Regression analysis highlighted the effect of temperature, total dissolved solids, electrical conductivity, and turbidity on the seasonal fluctuations in macrophyte productivity. Overall, the study provides insights into seasonal variation in the lake water chemistry and highlights the role of statistical tools in understanding the fragile aquatic ecosystems over cost-, labor-, and time-intensive inventory studies.
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http://dx.doi.org/10.1007/s11356-022-20631-1DOI Listing
May 2022

Exploratory Analysis of Selected Components of the mTOR Pathway Reveals Potentially Crucial Associations with Childhood Malnutrition.

Nutrients 2022 Apr 12;14(8). Epub 2022 Apr 12.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh.

Dysregulations in the mammalian target of rapamycin (mTOR) pathway are associated with several human anomalies. We aimed to elucidate possible implications for potential aberrations in the mTOR pathway with childhood malnutrition. We analyzed the activity of phospho-mTORC1 and the expressions of several mTOR pathway genes, namely: , , , and from peripheral blood mononuclear cells isolated from venous blood of children suffering from different forms of malnutrition and compared them with those from healthy children. Significant reduction in the phosphorylation of mTORC1 was noted, as well as a decrease in expression of gene and increase in gene expression were observed between malnourished children in comparison to the healthy children. The deregulation in the activity of the and gene was significantly associated with all forms of childhood malnutrition. Our findings provide key insights into possible down-modulation in the overall activity of the mTOR pathway in childhood malnutrition. Further studies focusing on the analysis of a multitude of components involved in the mTOR pathway both at the gene and protein expression levels are required for conclusive evidence for the aforementioned proposition.
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http://dx.doi.org/10.3390/nu14081612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031007PMC
April 2022

Associations of Enteric Protein Loss, Vaccine Response, Micronutrient Deficiency, and Maternal Depressive Symptoms with Deviance in Childhood Linear Growth: Results from a Multicountry Birth Cohort Study.

Am J Trop Med Hyg 2022 Apr 11. Epub 2022 Apr 11.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

We identified the determinants of positive (children who had a birth weight < 2.5 kg and/or maternal height < 145 cm but were nonstunted at 24 months of age) and negative (children who had a birth weight ≥ 2.5 kg and maternal height ≥ 145 cm but were stunted at 24 months of age) deviance in childhood linear growth. We found that socioeconomic status (β = 1.54, P < 0.01), serum retinol (β = 0.05, P < 0.01), hemoglobin (β = 0.36, P < 0.01), length-for-age Z-score (LAZ) at birth (β = 0.47, P < 0.01), and tetanus vaccine titer (β = 0.182, P < 0.05) were positively and maternal depressive symptom (β = -0.05, P < 0.01), serum ferritin (β = -0.03, P < 0.01), male sex (β = -1.08, P < 0.01), and α1-antitrypsin (β = -0.81, P < 0.01) were negatively associated with positive deviance. Further, diarrhea episodes (β = 0.02, P < 0.01), male sex (β = 0.72, P < 0.01), and α1-antitrypsin (β = 0.67, P < 0.01) were positively and hemoglobin (β= -0.28, P < 0.01), soluble transferrin receptor level (β = -0.15, P < 0.01), and LAZ score at birth (β = -0.90, P < 0.01) were negatively associated with negative deviance. To summarize, enteric protein loss, micronutrient deficiency, vaccine responses and maternal depressive symptoms were associated with linear growth deviance in early childhood. In such a background, public health approaches aimed at reducing the risk of intestinal inflammation and altered gut permeability could prove fruitful in ensuring desired linear growth in children. In addition, maternal mental health issue should also be considered, especially for promoting better nutritional status in children in the context of linear growth deviance.
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http://dx.doi.org/10.4269/ajtmh.21-0403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209933PMC
April 2022

Sunlight, dietary habits, genetic polymorphisms and vitamin D deficiency in urban and rural infants of Bangladesh.

Sci Rep 2022 03 7;12(1):3623. Epub 2022 Mar 7.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

We conducted an observational study to assess the prevalence and risk factors of vitamin D deficiency in 12-24 months old children living in urban and rural Bangladesh. Serum 25-hydroxyvitamin D (free 25(OH)D) level, socio-demographic status, anthropometric status, dietary intake, exposure to sunlight and single nucleotide polymorphisms in vitamin-D pathway genes were measured in 208 children. Vitamin D deficiency (free 25(OH)D < 50 nmol/l) was reported in 47% of the children. Multivariable logistic regression model identified duration to sunlight exposure (regression coefficient, β =  - 0.01; 95% CI 0.00, - 0.02; p-value < 0.05), UV index (β =  - 0.36; 95% CI 0.00, - 0.02; p-value < 0.05) and breast-feeding (β =  - 1.15; 95% CI - 0.43, - 1.86; p-value < 0.05) to be negatively associated with vitamin D deficiency. We measured the role of single nucleotide polymorphisms in pathway genes (GC-rs7041 T > G, rs4588 C > A, CYP2R1-rs206793 A > G, CYP27B1-rs10877012 A > C and DHCR7-rs12785878 G > T) and found statistically significant differences in serum vitamin D levels between various genotypes. SNPs for CYP27B1 (CA & CC genotype) had statistically significant positive association (β = 1.61; 95% CI 2.79, 0.42; p-value < 0.05) and TT genotype of GC-rs7041 had negative association (β =  - 1.33; 95% CI - 0.02, - 2.64; p-value < 0.05) with vitamin-D deficiency in the surveyed children.
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http://dx.doi.org/10.1038/s41598-022-07661-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901932PMC
March 2022

Taking care of a diarrhea epidemic in an urban hospital in Bangladesh: Appraisal of putative causes, presentation, management, and deaths averted.

PLoS Negl Trop Dis 2021 11 15;15(11):e0009953. Epub 2021 Nov 15.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Background: In April 2018, a diarrhea epidemic broke out in Dhaka city and adjoining areas, which continued through May. The Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), a dedicated diarrheal disease hospital, had a large upsurge in patient visits during the epidemic. An enhanced understanding of the epidemiology of this epidemic may help health-related professionals better prepare for such events in the future. This study examined the microbial etiology and non-pathogen factors associated with diarrhea during the epidemic. The study also evaluated the patients' presentation and clinical course and estimated the potential mortality averted by treating patients during the epidemic.

Methodology/principal Findings: Data from the patients who were treated at Dhaka Hospital during the diarrhea epidemic between April 2 and May 12, 2018 and were enrolled into the Diarrheal Disease Surveillance System (DDSS) at icddr,b were compared with the DDSS-enrolled patients treated during the seasonally-matched periods in the flanking years using logistic regression. icddr,b Dhaka Hospital treated 29,212 diarrheal patients during the 2018 epidemic period (and 25,950 patients per comparison period on average). Vibrio cholerae was the most common pathogen isolated (7,946 patients; 27%) and associated with diarrhea during the epidemic (adjusted odds ratio [AOR] 1.5, 95% CI: 1.1-2.0). The interaction of Vibrio cholerae with ETEC (AOR 2.7, 95% CI: 1.3-5.9) or Campylobacter (AOR 2.4, 95% CI: 1.1-5.1) was associated with further increased odds of diarrhea during the epidemic. In children under five years old, rotavirus was the most common pathogen (2,029 patients; 26%). Those who were adolescents (AOR 2.0, 95% CI: 1.3-3.1) and young adults (AOR 1.9, 95% CI: 1.4-2.5) compared to children younger than five years, resided within a 10 km radius of Dhaka Hospital (AOR 1.6, 95% CI: 1.1-2.2) compared to those living outside 20 km, borrowed money or relied on aid to pay for the transport to the hospital (AOR 1.6, 95% CI: 1.2-2.0), used tap water (AOR 1.8, 95% CI: 1.4-2.4) for drinking compared to tubewell water, and disposed of the solid waste directly outside the house (AOR 4.0, 95% CI: 2.7-5.9) were more likely to present with diarrhea during the epidemic. During the epidemic, patients were more likely to present with severe dehydration (odds ratio [OR] 1.6, 95% CI: 1.3-2.0) and require inpatient admission (OR 2.5, 95% CI: 1.9-3.3), intravenous rehydration (OR 1.7, 95% CI: 1.4-2.1), and antibiotics (OR 2.2, 95% CI: 1.8-2.7). The in-hospital case fatality rate was low (13 patients; 0.04%), and the hospital averted between 12,523 and 17,265 deaths during the epidemic.

Conclusions/significance: Vibrio cholerae played the primary role in the 2018 diarrhea epidemic in Dhaka. Campylobacter, enterotoxigenic Escherichia coli, and rotavirus had a secondary role. Adolescents and adults, residents of the metropolitan area, and those who were relatively poor and lacked safe water, sanitation, and hygiene (WASH) practices comprised the most vulnerable groups. Despite the increased disease severity during the epidemic, the case fatality rate was less than 0.1%. icddr,b Dhaka Hospital saved as many as 17,265 lives during the epidemic.
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http://dx.doi.org/10.1371/journal.pntd.0009953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629377PMC
November 2021

Nutrition and Food Security in Bangladesh: Achievements, Challenges, and Impact of the COVID-19 Pandemic.

J Infect Dis 2021 Dec;224(Supplement_7):S901-S909

General Economics Division, Bangladesh Planning Commission, Government of Bangladesh, Dhaka, Bangladesh.

Background: Bangladesh has experienced remarkable transformation in demographic, health, and nutritional status of the population. The changes have exposed the population to a number of challenges, the detrimental effect of which on health and nutrition is likely to be increased by the coronavirus disease 2019 (COVID-19) pandemic. We provide an overview of health and nutritional challenges in Bangladesh in relation to demographic transition and the COVID-19 pandemic.

Methods: We identified and reviewed recent reports, published articles, and pertinent gray literature on nutrition and food security in Bangladesh to provide historical and contextual information.

Results: The review identifies the progress as well as existing burden regarding nutrition and food security in Bangladesh and highlights the challenges in the coming days in regard to population growth and the COVID-19 pandemic. The country is on track to reduce all forms of childhood undernutrition, while the proportion of nutrition-related noncommunicable diseases is rising owing to changes in dietary intake, low physical activity, and sedentary lifestyle.

Conclusions: Despite remarkable progress, health and nutritional status of the population in Bangladesh faces challenges, particularly in relation to demographic transition and compounded by the COVID-19 pandemic, which require concerted attention from policymakers as well as stakeholders.
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http://dx.doi.org/10.1093/infdis/jiab473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687095PMC
December 2021

Vibrio cholerae O139 persists in Dhaka, Bangladesh since 1993.

PLoS Negl Trop Dis 2021 09 2;15(9):e0009721. Epub 2021 Sep 2.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Background: After a multi-country Asian outbreak of cholera due to Vibrio cholerae serogroup O139 which started in 1992, it is rarely detected from any country in Asia and has not been detected from patients in Africa.

Methodology/principal Findings: We extracted surveillance data from the Dhaka and Matlab Hospitals of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) to review trends in isolation of Vibrio cholerae O139 in Bangladesh. Data from the Dhaka Hospital is a 2% sample of > 100,000 diarrhoeal patients treated annually. Data from the Matlab Hospital includes all diarrhoeal patients who hail from the villages included in the Matlab Health and Demographic Surveillance System. Vibrio cholerae O139 was first isolated in Dhaka in 1993 and had been isolated every year since then except for a gap between 2005 and 2008. An average of thirteen isolates was detected annually from the Dhaka Hospital during the last ten years, yielding an estimated 650 cases annually at this hospital. During the last ten years, cases due to serogroup O139 represented 0.47% of all cholera cases; the others being due to serogroup O1. No cases with serogroup O139 were identified at Matlab since 2006. Clinical signs and symptoms of cholera due to serogroup O139 were similar to cases due to serogroup O1 though more of the O139 cases were not dehydrated. Most isolates of O139 remained sensitive to tetracycline, ciprofloxacin, and azithromycin, but they became resistant to erythromycin starting in 2009.

Conclusions/significance: Cholera due to Vibrio cholerae serogroup O139 continues to cause typical cholera in Dhaka, Bangladesh.
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http://dx.doi.org/10.1371/journal.pntd.0009721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443037PMC
September 2021

Association of plasma low-density lipoprotein receptor-related protein-1 (LRP1) with undernutrition: a case-control study in Bangladeshi adults.

Biomarkers 2021 Nov 25;26(7):625-631. Epub 2021 Aug 25.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Purpose: Studies revealed that silencing of low-density lipoprotein receptor-related protein-1 (LRP1) expression can cause inhibition of adipogenesis in animal model and contribute to reduced body size. But there is no study that has explored the association of LRP1 with body mass index (BMI) of human adults. Therefore, the aim of this study was to investigate the relationship of LRP1 with undernutrition.

Methods: A total of 270 Bangladeshi slum-dwelling adults were enrolled as case control design. Their socio-economic, demographic, anthropometric and biomedical data were collected. Plasma LRP1, C-reactive protein (CRP), alpha-1 acid glycoprotein (AGP) and ferritin levels were measured by ELISA, haemoglobin by HemoCue and zinc by atomic absorption spectrometry.

Results: The median (IQR) values of plasma LRP1 were 1673.1 (1382.5-1886.2) ng/mL in healthy participants and 707.7 (588.6-839.9) ng/mL in undernourished participants, respectively. A strong positive correlation ( = 0.70,  < 0.05) between LRP1 and BMI was found. Multivariable logistic regression analysis revealed a positive association between low plasma LRP1 (Adj. OR = 0.98, CI = 0.98, 0.99 and  < 0.05) and undernutrition.

Conclusions: The study found that increased level of LRP1 is associated with increased BMI, whereas lower level is associated with low BMI.
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http://dx.doi.org/10.1080/1354750X.2021.1955974DOI Listing
November 2021

Association of lipocalin-2 and low-density lipoprotein receptor-related protein-1 (LRP1) with biomarkers of environmental enteric dysfunction (EED) among under 2 children in Bangladesh: results from a community-based intervention study.

BMJ Paediatr Open 2021 4;5(1):e001138. Epub 2021 Aug 4.

Nutrition and Clinical Services Division (NCSD), International Centre for Diarrhoeal Disease Research Bangladesh (icddr, b), Dhaka, Bangladesh.

Background: Environmental enteric dysfunction (EED) is thought to occur from persistent intestinal inflammation. Studies also revealed the association of lipocalin-2 (LCN2) and low-density lipoprotein receptor-related protein-1 (LRP1) with intestinal inflammation. Therefore, we intended to explore the relationship of LCN2 and LRP1 with gut inflammation and biomarkers of EED in Bangladeshi malnourished children.

Methods: A total of 222 children (length-for-age z-score (LAZ) <-1) aged 12-18 months were enrolled in this study in a cross-sectional manner. Among the participants, 115 were stunted (LAZ <-2) and 107 were at risk of being stunted (LAZ -1 to -2) children. Plasma and faecal biomarkers were measured using ELISA. Spearman's rank correlation was done to see the correlation among LCN2, LRP1 and biological biomarkers.

Results: LCN2 correlates positively with myeloperoxidase (r=0.19, p=0.005), neopterin (r=0.20, p=0.004), calprotectin (r=0.3, p=0.0001), Reg1B (r=0.20, p=0.003) and EED score (r=0.20, p=0.003). Whereas, LRP1 correlates negatively with myeloperoxidase (r = -0.18, p=0.006), neopterin (r = -0.30, p=0.0001), alpha-1-antitrypsin (r = -0.18, p=0.006), Reg1B (r=-0.2, p=0.003) and EED score (r = -0.29, p=0.0001).

Conclusions: Our findings imply that LCN2 might be a promising biomarker to predict gut inflammation and EED. Whereas, increased level of LRP1 may contribute to alleviating intestinal inflammation.
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http://dx.doi.org/10.1136/bmjpo-2021-001138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340289PMC
February 2022

Infection with Blastocystis spp. and its association with enteric infections and environmental enteric dysfunction among slum-dwelling malnourished adults in Bangladesh.

PLoS Negl Trop Dis 2021 08 18;15(8):e0009684. Epub 2021 Aug 18.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Background: Blastocystis spp. (Blastocystis) is a widely distributed gastrointestinal protist frequently reported in countries with tropical and sub-tropical climate. We sought to determine the factors associated with Blastocystis infection and investigate its role on biomarkers of intestinal health among slum-dwelling malnourished adults in Bangladesh.

Methodology: Total 524 malnourished adults with a body mass index ≤18.5 kg/m2 were included in this analysis. Presence of Blastocystis in feces was evaluated by TaqMan Array Card assays.

Principal Findings: Blastocystis was tested positive in 78.6% of the participants. Prevalence of infection with atypical strains of enteropathogenic Escherichia coli (aEPEC) (56% vs. 38%, p<0.001), and Trichuris trichiura (28% vs. 15%, p-value = 0.02) was significantly greater in adults with Blastocystis, while Giardia intestinalis was significantly lower (8% vs. 14%, p-value = 0.04) in Blastocystis positive adults. Malnourished adults who were living in households with high crowding index (aOR = 2.18; 95% CI = 1.11, 4.65; p-value = 0.03), and infected with aEPEC (aOR = 2.14; 95% CI = 1.35, 3.44; p-value = 0.001) and Trichuris trichiura (aOR = 1.97; 95% CI = 1.08, 3.77; p = 0.03) were more likely to be infected with Blastocystis. A significant negative relationship was observed between Blastocystis and fecal concentrations of alpha-1 antitrypsin (β = -0.1; 95% CI = -1.7, -0.1; p-value<0.001) and Reg1B (β = -3.6; 95% CI = -6.9, -3.0; p-value = 0.03).

Conclusions: The study findings suggest that the presence of Blastocystis in human intestine influences gut health and may have potential pathogenic role in presence of other pathogens.
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http://dx.doi.org/10.1371/journal.pntd.0009684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405003PMC
August 2021

Melding microbiome and nutritional science with early child development.

Nat Med 2021 09;27(9):1503-1506

The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.

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http://dx.doi.org/10.1038/s41591-021-01451-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713503PMC
September 2021

Influence of soil quality factors on capsaicin biosynthesis, pungency, yield, and produce quality of chili: An insight on Csy1, Pun1, and Pun1 signaling responses.

Plant Physiol Biochem 2021 Sep 16;166:427-436. Epub 2021 Jun 16.

Soil and Agro Bio-engineering Lab, Department of Environmental Science, Tezpur University, Tezpur, 784 028, India. Electronic address:

Hotness or pungency is the major trait of genetically diverse and economically valuable chili (Capsicum sp.) cultivars. However, little is known about the influence of soil characteristics on genetic regulation of pungency vis-à-vis capsaicin formation in endemic chilies. Hence, the present work was conducted by growing two endemic chili cultivars in two types (alluvial and lateritic) of soil. Capsaicin content, pungency, and capsaicin synthase activity were significantly greater in chilies grown in alluvial soil than in lateritic soil. Correspondingly, Csy1, the gene that encodes capsaicin synthase, was significantly upregulated in alluvial soil grown plants. Interestingly, upregulation of Pun1, the gene responsible for capsaicin accumulation in fruits, was more in lateritic soil than in alluvial soil; but pungency was inhibited in lateritic soil by the overexpression of Pun1, a recessive allele of Pun1 locus. Statistical analyses revealed that high organic C, microbial activity, and NPK status in alluvial soil were responsible for high pungency, capsaicin synthase activity, capsaicin accumulation, and suppression of Pun1. Fruit yield, dry matter, crude protein, titratable acidity, and soluble solids were also significantly high in chilies grown in alluvial soil. Therefore, we postulate that soil quality attributes play vital roles in genetic regulation of pungency, capsaicin biosynthesis, fruit yield, and produce quality of endemic chili cultivars.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.012DOI Listing
September 2021

A Microbiota-Directed Food Intervention for Undernourished Children.

N Engl J Med 2021 04 7;384(16):1517-1528. Epub 2021 Apr 7.

From the Edison Family Center for Genome Sciences and Systems Biology (R.Y.C., M.C.H., A.S.R., D.W., C.Z., V.S., K.A., M.F.M., M.J.B., J.I.G.), the Center for Gut Microbiome and Nutrition Research (R.Y.C., M.C.H., A.S.R., D.W., C.Z., V.S., K.A., M.F.M., M.J.B., J.I.G.), and the Department of Pathology and Immunology (M.C.H., A.S.R., D.W., M.J.B., J.I.G.), Washington University School of Medicine, St. Louis; and the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (I.M., S.D., M.M., N.N.N., M.M.I., S.H., M.A.A., M.U.Z., T.A.).

Background: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.

Methods: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples.

Results: A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment.

Conclusions: These findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the National Institutes of Health; ClinicalTrials.gov number, NCT04015999.).
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http://dx.doi.org/10.1056/NEJMoa2023294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993600PMC
April 2021

Changing trends in nutritional status of adolescent females: a cross-sectional study from urban and rural Bangladesh.

BMJ Open 2021 02 17;11(2):e044339. Epub 2021 Feb 17.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.

Objectives: Malnutrition remains a major problem among adolescents worldwide, but the types of nutritional problem impacting this group are changing significantly. This study aims to describe and analyse the trends in nutritional status and related epidemiological characteristics of 10 to 19 years old adolescent girls over time (2001 to 2018) in Bangladesh.

Methods: We extracted data from the Diarrhoeal Disease- Surveillance System of the International Centre for Diarrhoeal Disease Research Bangladesh. We performed χ test for trend to test for statistical significance of the changing trends of undernutrition and overnutrition among the study participants. Multivariable logistic regression model was fit to measure the strength of association, reported as adjusted OR (aOR) and corresponding 95% CIs.

Results: A total of 1224 and 628 adolescent females attended urban and rural treatment facilities, respectively, between 2001 and 2018. The proportion of stunting and thinness decreased substantially, whereas overweight has been observed to increase (1.7% to 7.4%, p<0.001) over the study period. Factors independently associated with stunting were illiteracy (aOR 2.39, 95% CI (1.68 to 3.39), p<0.001), monthly family income of less than US$100 (aOR 1.54, 95% CI (1.25 to 1.9), p<0.001) and family belonging to poorest wealth quintile (aOR 1.45, 95% CI (1.13 to 1.87), p=0.004). Younger participants (aOR 2.69, 95% CI (2.10 to 3.45), p<0.001), rural participants (aOR 1.71 95% CI (1.23 to 2.38), p<0.001), longer hospital stay (aOR 1.52, 95% CI (1.16 to 1.98), p=0.002) and monthly family income less than US$100 (aOR 1.44, 95% CI (1.09 to 1.89), p=0.009) were significantly associated with thinness. Conversely, overweight/obesity was associated with monthly family income more than US$100, duration of diarrhoea and rural participants.

Conclusion: Undernutrition in adolescent girls has decreased with time, but the burden of overweight has increased. Higher literacy and better wealth status were found to be associated with the improved nutritional status of the participants.
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http://dx.doi.org/10.1136/bmjopen-2020-044339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893671PMC
February 2021

Alterations in the histological features of the intestinal mucosa in malnourished adults of Bangladesh.

Sci Rep 2021 01 27;11(1):2355. Epub 2021 Jan 27.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68, Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.

There is paucity of knowledge on the histological features of the intestinal mucosa in malnourished adults of Bangladesh. The purpose of the study was to explore the histological features of the intestinal mucosa in malnourished adults of Bangladesh and to compare the findings with their well-nourished counterparts. 64 adults (37 malnourished with body mass index, BMI < 18.5 kg/m and 27 controls with BMI > 18.5 kg/m) from the Bangladesh Environmental Enteric Dysfunction (BEED) study, who underwent upper-gastrointestinal endoscopy, were selected for this study. With a view to address the association of environmental enteric dysfunction (EED) with malnutrition, upper-gastrointestinal endoscopy was performed and mucosal biopsies from the distal duodenum were studied for histopathology. Villous height, crypt depth, and presence of inflammatory infiltrates in lamina propria were investigated. Bivariate analysis was performed to quantify the relation between malnutrition and the histological features. About 95% adults, irrespective of nutritional status, were diagnosed to have chronic non-specific duodenitis on histopathology. Malnourished adults suffered significantly more from chronic active duodenitis compared to their well-nourished counterparts (p = 0.003). Malnourished adults also had significantly higher frequency of subtotal villous atrophy, crypt hyperplasia and marked cellular infiltration in the lamina propria than the healthy controls (p < 0.05).
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http://dx.doi.org/10.1038/s41598-021-82079-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840936PMC
January 2021

Introducing winter rice cropping by using non-saline tidal water influx in western basins of South 24 Parganas, India.

Sci Rep 2021 01 12;11(1):553. Epub 2021 Jan 12.

School of Water Resources Engineering, Jadavpur University, Kolkata, India.

A population exceeding 3.8 million people in the western region of 24-Parganas (South) is directly or indirectly reliant on agriculture as their primary source of livelihood. The agricultural trend shows a clear lack of multi-cropping with a drop of nearly 30% in rice cultivation during the winter season. Nearly 50% of the region is directly dependent on canals. The introduction of tidal water in the canal network provides an exceptionally economical and highly effective mode of irrigation water supply. The primary aim of the study was to identify the cartographic characteristics and channel hydraulics in the summer season. It was noted that the canals have a wide discharge range of 0.03-540.03 m/s, average evaporation loss of 9.07 mm/day with a seepage loss ranging from 0.04 to 6.36 m/s. The tidal water ingress quantity was calculated to be 4.17 Mm, 5.32 Mm, 1.88 Mm at Diamond Harbour sluice (Sl.), Kulpi Sl. and Kholakhali Sl. respectively. It was denoted that the augmentation of tidal backwater six times monthly would suffice the winter crop water requirement for the majority of the basins. This would result in the production of 172.13 kt which was previously 17.6 kt resulting in an increase of production by 878.01%. The per capita income would also be increased by nearly 978% for the season, resulting in the macro-socioeconomic upliftment of the region.
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http://dx.doi.org/10.1038/s41598-020-80797-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804003PMC
January 2021

Acute food insecurity and short-term coping strategies of urban and rural households of Bangladesh during the lockdown period of COVID-19 pandemic of 2020: report of a cross-sectional survey.

BMJ Open 2020 12 12;10(12):e043365. Epub 2020 Dec 12.

Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.

Introduction: We conducted a cross-sectional survey to assess the extent and to identify the determinants of food insecurity and coping strategies in urban and rural households of Bangladesh during the month-long, COVID-19 lockdown period.

Setting: Selected urban and rural areas of Bangladesh.

Participants: 106 urban and 106 rural households.

Outcome Variables And Method: Household food insecurity status and the types of coping strategies were the outcome variables for the analyses. Multinomial logistic regression analyses were done to identify the determinants.

Results: We found that around 90% of the households were suffering from different grades of food insecurity. Severe food insecurity was higher in urban (42%) than rural (15%) households. The rural households with mild/moderate food insecurity adopted either financial (27%) or both financial and food compromised (32%) coping strategies, but 61% of urban mild/moderate food insecure households applied both forms of coping strategies. Similarly, nearly 90% of severely food insecure households implemented both types of coping strategies. Living in poorest households was significantly associated (p value <0.05) with mild/moderate (regression coefficient, β: 15.13, 95% CI 14.43 to 15.82), and severe food insecurity (β: 16.28, 95% CI 15.58 to 16.97). The statistically significant (p <0.05) determinants of both food compromised and financial coping strategies were living in urban areas (β: 1.8, 95% CI 0.44 to 3.09), living in poorest (β: 2.7, 95% CI 1 to 4.45), poorer (β: 2.6, 95% CI 0.75 to 4.4) and even in the richer (β: 1.6, 95% CI 0.2 to 2.9) households and age of the respondent (β: 0.1, 95% CI 0.02 to 0.21).

Conclusion: Both urban and rural households suffered from moderate to severe food insecurity during the month-long lockdown period in Bangladesh. But, poorest, poorer and even the richer households adopted different coping strategies that might result in long-term economic and nutritional consequences.
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http://dx.doi.org/10.1136/bmjopen-2020-043365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735103PMC
December 2020

Plasma Kynurenine to Tryptophan Ratio Is Negatively Associated with Linear Growth of Children Living in a Slum of Bangladesh: Results from a Community-Based Intervention Study.

Am J Trop Med Hyg 2020 11 23;104(2):766-773. Epub 2020 Nov 23.

1Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Chronic exposure to infectious agents results in environmental enteric dysfunction-a significant contributor to childhood stunting. Low plasma tryptophan (TRP), increased kynurenine (KYN), and KYN-TRP (KT) ratio are associated with infections and chronic immune activation. We postulated that both these conditions are interlinked, and therefore aimed to identify the association between KT ratio and the linear growth of Bangladeshi children. A total of 480 stunted and at risk of being stunted children aged 12-18 months were enrolled and provided nutrition intervention for 90 days. Plasma samples were assessed using liquid chromatography tandem mass spectrometry to measure TRP and KYN concentrations. Multivariable linear regression with generalized estimating equations was applied to analyze association between the KT ratio and linear growth. Tryptophan, KYN, and KT ratio were significantly higher in stunted children than in children at risk of being stunted both at baseline and at the end of nutrition intervention. Following intervention, the median (interquartile range [IQR]) KYN concentration was significantly reduced from 4.6 (3.6, 5.4) µmol/L to 3.9 (0.3, 7.6) µmol/L, and median (IQR) KT ratio decreased from 104 (80.9, 131) to 92.8 (6.6, 247) in stunted children. We also found KT ratio to be negatively associated (coefficient = -0.7; 95% CI = -1.13, -0.26; P-value = 0.002) with linear growth. In addition, KYN and KT ratio were positively correlated with fecal neopterin and plasma C-reactive protein, whereas TRP was negatively correlated with both of these biomarkers and alpha-1-acid glycoprotein. Our findings imply that KT ratio is associated in the pathophysiology of stunting as well as with biomarkers of inflammation in Bangladeshi children.
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http://dx.doi.org/10.4269/ajtmh.20-0049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866305PMC
November 2020

Changes in Retinol Binding Protein 4 Level in Undernourished Children After a Nutrition Intervention Are Positively Associated With Mother's Weight but Negatively With Mother's Height, Intake of Whole Milk, and Markers of Systemic Inflammation: Results From a Community-Based Intervention Study.

Food Nutr Bull 2021 03 23;42(1):23-35. Epub 2020 Nov 23.

Nutrition and Clinical Services Division (NCSD), 56291International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b), Dhaka, Bangladesh.

Background: The changes of plasma retinol binding protein 4 (RBP4) level after a nutrition intervention can indicate the metabolic changes associated with the delivered intervention.

Objective: We investigated the changes in plasma RBP4 level among 12- to 18-month-old children after a nutrition intervention and measured its association with subcutaneous adiposity, maternal characteristics, and inflammation.

Methods: Data of 520 undernourished children (250 of them had length-for-age score [LAZ] <-1 to -2 and 270 had LAZ score <-2) were collected from the Bangladesh Environmental Enteric Dysfunction study conducted in Dhaka, Bangladesh. Multivariable linear regression and generalized estimation equations (GEE) modeling techniques were used to measure the association.

Results: At baseline, median RBP4 level was 19.9 mg/L (interquartile range [IQR]: 7.96), and at the end of the intervention, it was 20.6 mg/L (IQR: 9.06). Percentage changes in plasma RBP4 level were not significantly associated ( > .05) with the percentage changes in child's height, weight, and subcutaneous adiposity. But maternal height (regression coefficient, β = -1.62, = .002) and milk intake (β = -0.05, = .01) were negatively and maternal weight was positively associated (β = 0.56, = .03) with the changes in RBP4 levels. The GEE models revealed negative association of RBP4 levels with C-reactive protein (CRP; β = -0.14, < .05) and α-1-acid glycoprotein (AGP; β = -0.03, < .05).

Conclusion: Children whose mothers were taller experienced less increase in plasma RBP4 level, and children whose mothers had a higher weight experienced more increase in the RBP4 level from baseline. We have also found that CRP and AGP levels and intake of whole milk were negatively associated with the plasma RBP4 level.
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http://dx.doi.org/10.1177/0379572120973908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060731PMC
March 2021

Evaluating association of vaccine response to low serum zinc and vitamin D levels in children of a birth cohort study in Dhaka.

Vaccine 2021 01 27;39(1):59-67. Epub 2020 Oct 27.

Nutrition and Clinical Services Division, icddr,b, Dhaka, Bangladesh.

Background: Vaccine-preventable infectious diseases are often responsible for childhood morbidity and high rates of mortality. Immune response to the vaccine is associated with multiple factors in early childhood and measured by antibody titers. Among them, micronutrient deficiencies such as vitamin D and zinc deficiencies are the most important in resource-limited settings like Bangladesh.

Objective: We aimed to evaluate the association of vaccine response to low serum zinc and vitamin D levels in children.

Methods: We evaluated vaccine response for measles and poliovirus, tetanus and pertussis toxoid, and Ig A antibody levels to rotavirus by ELISA and serum vitamin D and zinc at 7 and 15 months in the MAL-ED birth cohort of the Bangladesh site. By using population-specific generalized estimating equations (GEE), the association between each explanatory variable and the binary outcome variable was examined longitudinally where the dependent variable was vaccine titers and the independent variables were low serum vitamin D and zinc levels.

Results: The GEE multivariable model identified a positive association between serum zinc level and tetanus vaccine titer (OR: 1.84; 95% CI: 1.07-3.17 and p value = 0.028) after adjusting for age, gender, birth weight, WAMI score, diarrhea, ALRI, exclusive breastfeeding, serum ferritin, serum retinol and undernutrition (stunting, wasting, underweight). No association was found between the rest of the vaccine titers with serum vitamin D and zinc level (p > 0.05).

Conclusion: In the MAL-ED birth cohort, where children were followed for five years, serum zinc level had a positive impact on tetanus vaccine titers.
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http://dx.doi.org/10.1016/j.vaccine.2020.10.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735373PMC
January 2021

Asymptomatic Duodenitis and Helicobacter pylori associated Dyspepsia in 2-Year-Old Chronic Malnourished Bangladeshi Slum-Dwelling Children: A Cross-Sectional Study.

J Trop Pediatr 2021 01;67(1)

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh.

Aim: There is insufficient knowledge on the * duodenal histology and Helicobacter pylori infection in malnourished Bangladeshi children. Therefore, we attempted to explore the prevalence of H. pylori infection and duodenal histopathology in 2-year-old chronic malnourished Bangladeshi slum-dwelling children and investigate their association with dyspeptic symptoms.

Methods: This cross-sectional study was conducted using the data of the Bangladesh Environmental Enteric Dysfunction study in an urban slum of Dhaka, Bangladesh. With a view to address the association of environmental enteric dysfunction (EED) with stunting, upper gastrointestinal endoscopy was performed on 54 chronic malnourished children {31 stunted [length-for-age Z-scores (LAZ) <-2] and 23 at risk of stunting (LAZ <-1 to -2)} aged between 12-24 months and the mucosal biopsies were subjected to histopathological examination after obtaining proper clinical history. Stool antigen for H. pylori (HpSA) was assessed to determine H. pylori status.

Results: In all, 83.3% (45/54) of the children had histopathological evidence of duodenitis. Chronic mild duodenitis was found to be the most prevalent form of duodenitis (53.7%) in the children. Only 8.9% (4/45) of the children with duodenitis had dyspepsia (p < 0.05). The 14.8% (8/54) of the children were found positive for H. pylori infection. Logistic regression analysis revealed children positive for HpSA had significant association with dyspepsia (OR 9.34; 95% CI 1.54-56.80).

Conclusions: The number of chronic malnourished children suffering from duodenitis was found to be very high. Majority of these children was asymptomatic. Children positive for HpSA had significant association with dyspeptic symptoms.
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http://dx.doi.org/10.1093/tropej/fmaa079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948384PMC
January 2021

Gender disparity in care-seeking behaviours and treatment outcomes for dehydrating diarrhoea among under-5 children admitted to a diarrhoeal disease hospital in Bangladesh: an analysis of hospital-based surveillance data.

BMJ Open 2020 09 3;10(9):e038730. Epub 2020 Sep 3.

Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.

Introduction: Despite economic development and augmented literacy rates, Bangladeshi households are still discriminating against girls when it comes to seeking medical care. We examined gender disparities in diarrhoeal disease severity and the treatment outcomes of under-5 children.

Setting: A tertiary level diarrhoeal disease hospital in Dhaka, Bangladesh.

Participants: 13 361 under-5 children admitted to the hospital between January 2008 and December 2017.

Outcome Variables And Methods: The primary outcome of interest was severity of diarrhoea, defined as 'dehydrating diarrhoea' or 'non-dehydrating diarrhoea'. Multivariable logistic regression analyses were performed to assess the association between 'gender' and admission to hospital for dehydrating diarrhoea.

Results: Data on 13 321 children under 5 years of age were analysed, of whom 61.5% were male and 38.5% were female. The mean (±SD) age of children with diarrhoea was 5.63 (±3.49) months. The median distance travelled to come to the hospital for admission was 10 miles (IQR: 6-25) and was significantly higher for boys (10 miles, IQR: 6-25) than girls (9.5 miles, IQR: 6-23) (p<0.001). Girls had 1.11 times higher odds (adjusted OR: 1.11, 95% CI 1.03 to 1.20, p=0.007) of presenting with dehydrating diarrhoea than boys at the time of hospital admission. Almost 20% of children received two or more medications during the period of hospital admission and this did not differ by gender. The median duration of hospital stay was 11 hours and was similar in both sexes. No gender-based disparity was observed in the management of diarrhoea and in the hospital outcome of children.

Conclusion: We found that girls were more likely to have dehydrating diarrhoea when they were presented to the Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. No gender-based disparity was observed in the hospital outcome of children.
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http://dx.doi.org/10.1136/bmjopen-2020-038730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473626PMC
September 2020

Duodenal Microbiota in Stunted Undernourished Children with Enteropathy.

N Engl J Med 2020 07;383(4):321-333

From the Edison Family Center for Genome Sciences and Systems Biology (R.Y.C., V.L.K., M.C.H., J.G., B.D.L., K.A., E.K., J.S.-B., M.J.B., J.I.G.), the Center for Gut Microbiome and Nutrition Research (R.Y.C., V.L.K., M.C.H., J.G., K.A., M.J.B., J.I.G.), and the Department of Pathology and Immunology (V.L.K., M.J.B., J.I.G.), Washington University School of Medicine, St. Louis; the International Center for Diarrhoeal Disease Research, Bangladesh (S.D., M.S.H., M.M., S.M.F., M.A.G., R.H., S.A.S., R.N.M., T.A.), the Department of Pathology, Dr. Sirajul Islam Medical College (S.M.K.N.B.), and Sheikh Russel National Gastroliver Institute and Hospital (M.M.R.), Dhaka, Bangladesh; the A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow (D.A.R., S.A.L.); and the Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (D.A.R., S.A.L., A.L.O.).

Background: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).

Methods: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy in 80 children who had biopsy-confirmed EED and available plasma and duodenal samples. We quantified the levels of 4077 plasma proteins and 2619 proteins in duodenal biopsy samples obtained from these children. The levels of bacterial strains in microbiota recovered from duodenal aspirate from each child were determined with the use of culture-independent methods. In addition, we obtained 21 plasma samples and 27 fecal samples from age-matched healthy children living in the same area. Young germ-free mice that had been fed a Bangladeshi diet were colonized with bacterial strains cultured from the duodenal aspirates.

Results: Of the bacterial strains that were obtained from the children, the absolute levels of a shared group of 14 taxa (which are not typically classified as enteropathogens) were negatively correlated with linear growth (length-for-age z score, r = -0.49; P = 0.003) and positively correlated with duodenal proteins involved in immunoinflammatory responses. The representation of these 14 duodenal taxa in fecal microbiota was significantly different from that in samples obtained from healthy children (P<0.001 by permutational multivariate analysis of variance). Enteropathy of the small intestine developed in gnotobiotic mice that had been colonized with cultured duodenal strains obtained from children with EED.

Conclusions: These results provide support for a causal relationship between growth stunting and components of the small intestinal microbiota and enteropathy and offer a rationale for developing therapies that target these microbial contributions to EED. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02812615.).
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http://dx.doi.org/10.1056/NEJMoa1916004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289524PMC
July 2020

Metal induced non-metallothionein protein in earthworm: A new pathway for cadmium detoxification in chloragogenous tissue.

J Hazard Mater 2021 01 1;401:123357. Epub 2020 Jul 1.

Soil and Agro Bio-engineering Lab, Department of Environmental Science, Tezpur University, Tezpur, 784028, India. Electronic address:

Earthworms neutralize toxic metals by a small (∼13 kDa) cysteine rich metal binding protein, metallothionein (MT). Although the rate of metal accumulation and MT expression does not correlate well, the reason behind such inconsistency has not yet been deciphered. The present investigation clearly demonstrates that expression of some non-MT metal induced proteins is responsible for such incongruity. Applying selective protein isolation techniques in fluorescence tagged cadmium exposed (135 mg/kg) earthworms we were able to purify a 150 kDa metal induced protein (MIP) among others. After 60 days of exposure cadmium accumulation in earthworm intestines was significant. Immunofluorescence staining followed by confocal microscopy exhibited that MIP accumulates ingested cadmium in the intestinal region and eventually deposits the metal in the chloragogenous tissue. We determined the N-terminal sequence of 15 amino acid residues and after bioinformatics analysis, it was concluded that MIP is most probably a glutamic acid rich, novel cadmium binding protein. To further validate the binding mechanism, we conducted paper chromatography and continuous variation experiments which evidenced that cadmium readily binds to glutamic acid. The present finding is the first in-vivo evidence of a non-metallothionein cadmium binding protein induced in the intestines of earthworm exposed to a cadmium rich environment.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123357DOI Listing
January 2021

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

Public Health Nutr 2021 08 3;24(11):3361-3370. Epub 2020 Jul 3.

Nutrition and Clinical Services Division, icddr,b, Dhaka1212, 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.
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http://dx.doi.org/10.1017/S1368980020001421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314919PMC
August 2021
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