Approximately one-third of children under the age of five are stunted in developing countries and many of them are micronutrient-deficient. We designed a comprehensive intervention package including ...egg/milk-based snacks to improve linear growth and dietary diversity among 6 to 12-month-old children in rural Bangladesh. In this 1-year community-based cluster randomized controlled longitudinal experiment, 412 mother-infant pairs were randomly assigned to receive either monthly food vouchers (for eggs, milk, semolina, sugar, and oil) to prepare egg and milk-based snacks for their children, along with multiple micronutrient powder (MNP), counseling on child feeding and handwashing, or regular government health communication alone (control; n = 206, treatment; n = 206). The trial was conducted in 12 clusters (small administrative units of sub-district). The primary inclusion criteria were ultra-poor households with limited resources and having children under 2-years-old. The primary and secondary outcomes were differences in children's length gain and dietary diversity. The effect of intervention on child growth was examined using a mixed effect linear regression model. Mean weight and length of the children did not significantly differ between groups at baseline. Around 90% of the children in both groups were breastfed. After receiving intervention for 12 months, LAZ score increased by 0.37 (CI 0.24, 0.51, p < 0.001) and risk of stunting reduced by 73% (OR: 0.27, CI 0.13, 0.58, p = 0.001). This comprehensive intervention package improved the growth and dietary diversity of children in extremely poor Bangladeshi households. A scaling-up of this intervention in contexts with limited resources should be taken into consideration.Trial registration: This trial registered retrospectively at ClinicalTrials.gov as NCT03641001, 21/8/2018.
Abstract The genomic diversity of 99 T4-like coliphages was investigated by sequencing an equimolar mixture with Illumina technology and screening them against different databases for horizontal gene ...transfer and undesired genes. A 9-phage cocktail was given to 15 healthy adults from Bangladesh at a dose of 3×109 and 3×107 plaque-forming units and placebo respectively. Phages were detected in 64% of the stool samples when subjects were treated with higher titer phage, compared to 30% and 28% with lower-titer phage and placebo, respectively. No Escherichia coli was present in initial stool samples, and no amplification of phage was observed. One percent of the administered oral phage was recovered from the feces. No adverse events were observed by self-report, clinical examination, or from laboratory tests for liver, kidney, and hematology function. No impact of oral phage was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool.
Antibiotic resistance is rising in important bacterial pathogens. Phage therapy (PT), the use of bacterial viruses infecting the pathogen in a species-specific way, is a potential alternative.
...T4-like coliphages or a commercial Russian coliphage product or placebo was orally given over 4days to Bangladeshi children hospitalized with acute bacterial diarrhea. Safety of oral phage was assessed clinically and by functional tests; coliphage and Escherichia coli titers and enteropathogens were determined in stool and quantitative diarrhea parameters (stool output, stool frequency) were measured. Stool microbiota was studied by 16S rRNA gene sequencing; the genomes of four fecal Streptococcus isolates were sequenced.
No adverse events attributable to oral phage application were observed (primary safety outcome). Fecal coliphage was increased in treated over control children, but the titers did not show substantial intestinal phage replication (secondary microbiology outcome). 60% of the children suffered from a microbiologically proven E. coli diarrhea; the most frequent diagnosis was ETEC infections. Bacterial co-pathogens were also detected. Half of the patients contained phage-susceptible E. coli colonies in the stool. E. coli represented less than 5% of fecal bacteria. Stool ETEC titers showed only a short-lived peak and were otherwise close to the replication threshold determined for T4 phage in vitro. An interim analysis after the enrollment of 120 patients showed no amelioration in quantitative diarrhea parameter by PT over standard care (tertiary clinical outcome). Stool microbiota was characterized by an overgrowth with Streptococcus belonging to the Streptococcus gallolyticus and Streptococcus salivarius species groups, their abundance correlated with quantitative diarrhea outcome, but genome sequencing did not identify virulence genes.
Oral coliphages showed a safe gut transit in children, but failed to achieve intestinal amplification and to improve diarrhea outcome, possibly due to insufficient phage coverage and too low E. coli pathogen titers requiring higher oral phage doses. More knowledge is needed on in vivo phage–bacterium interaction and the role of E. coli in childhood diarrhea for successful PT.
The study was supported by a grant from Nestlé Nutrition and Nestlé Health Science. The trial was registered with Identifier NCT00937274 at ClinicalTrials.gov.
•Coliphages given orally to children with bacterial diarrhea appeared in the stool, but did not improve clinical outcome.•In microbiologically diagnosed E. coli diarrhea, pathogen titers were close to the replication threshold of coliphages.•Acute bacterial diarrhea displayed a marked dysbiosis with fecal streptococci that stabilized with recovery from diarrhea.
Antibiotic resistance of bacterial infections reached alarming levels. Phage therapy is a potential alternative antimicrobial. We demonstrated that two different oral phage preparations did not improve acute bacterial diarrhea in children from Bangladesh. We observed fecal excretion of the oral phage, but no major phage amplification in the gut. E. coli pathogen levels were low and the fecal microbiota showed a transient overgrowth with streptococci. Future phage trials should first verify the titer and association of the targeted pathogen with the disease.
Abstract Phage therapy has a long tradition in Eastern Europe, where preparations are comprised of complex phage cocktails whose compositions have not been described. We investigated the composition ...of a phage cocktail from the Russian pharmaceutical company Microgen targeting Escherichia coli / Proteus infections. Electron microscopy identified six phage types, with numerically T7-like phages dominating over T4-like phages. A metagenomic approach using taxonomical classification, reference mapping and de novo assembly identified 18 distinct phage types, including 7 genera of Podoviridae, 2 established and 2 proposed genera of Myoviridae, and 2 genera of Siphoviridae. De novo assembly yielded 7 contigs greater than 30 kb, including a 147-kb Myovirus genome and a 42-kb genome of a potentially new phage. Bioinformatic analysis did not reveal undesired genes and a small human volunteer trial did not associate adverse effects with oral phage exposure.
IntroductionEnvironmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of ...stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting.Methods and analysisThe BEED study is a community-based intervention where participants are recruited from three cohorts: stunted children aged 12–18 months (length for age Z-score (LAZ) <−2), at risk of stunting children aged 12–18 months (LAZ <−1 to −2) and malnourished adults aged 18–45 years (body mass index <18.5 kg/m2). After screening, participants eligible for study provide faecal, urine and plasma specimens to quantify the levels of candidate EED biomarkers before and after receiving a nutritional intervention. Participants who fail to respond to nutritional therapy are considered as the candidates for upper gastrointestinal endoscopy with biopsy. Histopathological scoring for EED will be performed on biopsies obtained from several locations within the proximal small intestine. Candidate EED biomarkers will be correlated with nutritional status, the results of histochemical and immunohistochemical analyses of epithelial and lamina propria cell populations, plus assessments of microbial community structure.Ethics and disseminationEthics approval was obtained in all participating institutes. Results of this study will be submitted for publication in peer-reviewed journals.Trial registration numberClinicalTrials.gov ID: NCT02812615. Registered on 21 June 2016.
Background
Although the Rome IV criteria are the most recent criteria to diagnose irritable bowel syndrome (IBS), their sensitivity has been shown to be low in Chinese and Western populations. There ...are scanty data comparing the Rome III and Rome IV criteria in diagnosis of IBS in the Indian and Bangladeshi populations where abdominal pain, an essential component of diagnosis of IBS by the Rome IV criteria, is less in frequency and of lower severity.
Methods
We analyzed the Indian and Bangladeshi data from the Rome Global Epidemiology Study to compare diagnostic sensitivity of the Rome III and Rome IV criteria for IBS, internal shifts in diagnostic categories of disorders of gut–brain interaction (DGBI), the severity of IBS diagnosed by the Rome III and Rome IV criteria, and consultation patterns in these populations.
Key Results
The Rome IV criteria were less sensitive than the Rome III criteria to diagnose IBS in these populations, and the subjects with Rome III IBS shifted internally to other DGBI when the Rome IV criteria were applied. Moreover, Rome IV IBS subjects had greater symptom severity than the Rome III IBS. A third of people fulfilling diagnostic criteria for IBS consulted doctors, and those diagnosed using Rome IV criteria, those with higher anxiety and depression symptom score, lower global physical health score, and greater IBS symptom severity score had greater correlation coefficients with doctors' consultation.
Conclusions and Inferences
The Rome IV diagnostic criteria for IBS are less sensitive than the Rome III criteria in Indian and Bangladesh communities. Application of the Rome IV criteria to people who meet the Rome III IBS criteria selects a subgroup of people with greater severity of symptoms, and hence, Rome IV IBS is more strongly associated with physician consultation. These findings may have important bearing in future iterations of the Rome criteria for a broader global applicability.
This study on Indian and Bangladeshi data from Rome Global Epidemiology Survey compared the Rome IV and III criteria to diagnose IBS, their clinical profile, and consultation behavior. Rome IV often missed Rome III‐ diagnosed IBS resulting in an internal diagnostic shift. As Rome IV selects out a subgroup with greater symptom severity, it may explain greater doctor consultations.
Aim
Persistent diarrhoea continues for at least 14 days and kills more children than acute diarrhoea. We assessed whether rice suji, green banana mixed rice suji or 75% rice suji improved persistent ...diarrhoea in young children.
Methods
This open‐labelled randomised controlled trial was carried out between December 2017 and August 2019 at the Dhaka Hospital of icddr,b, Bangladesh, with 135 children aged 6–35 months with persistent diarrhoea. The children were randomly assigned to green banana mixed rice suji, rice suji or 75% rice suji, with 45 in each group. The primary outcome was the percentage who recovered from diarrhoea by day 5 using an intention‐to‐treat analysis.
Results
The children's median age was 8 months (interquartile range: 7–10 months). By day 5, the recovery rate was 58%, 31% and 58% for children in the green banana mixed rice suji, rice suji and 75% rice suji groups, respectively. The green banana mixed rice suji group had fewer relapses (7%) than the 75% rice suji group (24%). Enteroaggregative Escherichia coli, rotavirus, norovirus, Enteropathogenic Escherichia coli, astrovirus and Campylobacter were the major pathogens for persistent diarrhoea.
Conclusion
Green banana mixed rice suji was the most effective option for managing persistent diarrhoea in young children.
Postinfection irritable bowel syndrome (PI-IBS) and functional dyspepsia (PI-FD), though reported from the temperate countries, have not been studied in the tropics; PI-malabsorption syndrome (MAS), ...which mimics PI-IBS, is reported from the tropics. No report till date on PI-IBS excluded PI-MAS. We studied: (i) the frequency of continuing bowel dysfunction after acute gastroenteritis (AG), (ii) its predictors, and (iii) PI-MAS among patients with PI-IBS.
345 consecutive subjects each, with AG and age- and gender-matched healthy controls were followed up 3-monthly for 12 months using a translated-validated questionnaire and functional gastrointestinal disorders (FGIDs) were diagnosed by Rome III criteria. Symptom duration >3 months but <6 months was diagnosed as chronic bowel dysfunction (CBD) and dyspeptic symptoms, respectively. MAS was diagnosed if 2/3 tests (D-xylose H
breath test, Sudan III-stained stool microscopy, and duodenal histology) were abnormal. Fecal microbiological studies were performed in 245/345 (71%) patients.
AG patients more often developed PI-IBS and PI-FD than controls (16.5 vs. 2.6% and 7.4 vs. 0.6%, respectively; p<0.001). Presence of FD was a risk factor for PI-IBS and IBS for PI-FD. On multivariate analysis, dyspeptic symptoms, CBD, and weight loss were the risk factors for PI-FGIDs. The frequency of PI-IBS following Vibrio cholera and other bacterial infection was comparable. Malabsorption was present among 2/23 (9%) patients with PI-IBS.
FGIDs are common after AG; dyspeptic symptoms, CBD, and weight loss were risk factors for PI-FGIDs. Vibrio cholerae infection caused PI-FGID, which was never reported. About 9 % patients fulfilling the criteria for PI-IBS had PI-MAS.
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 less than or equal to18.5 kg/m.sup.2 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 (beta = -0.1; 95% CI = -1.7, -0.1; p-value<0.001) and Reg1B (beta = -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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is scarce data on energy expenditure in ill children with different degrees of malnutrition. This study aimed to determine resting energy expenditure (REE) trajectories in hospitalized ...malnourished children during and after hospitalization. We followed a cohort of children in Bangladesh and Malawi (2-23 months) with: no wasting (NW); moderate wasting (MW), severe wasting (SW), or edematous malnutrition (EM). REE was measured by indirect calorimetry at admission, discharge, 14-and-45-days post-discharge. 125 children (NW, n = 23; MW, n = 29; SW, n = 51; EM, n = 22), median age 9 (IQR 6, 14) months, provided 401 REE measurements. At admission, the REE of children with NW and MW was 67 (95% CI 58, 75) and 70 (95% CI 63, 76) kcal/kg/day, respectively, while REE in children with SW was higher, 79 kcal/kg/day (95% CI 74, 84, p = 0.018), than NW. REE in these groups was stable over time. In children with EM, REE increased from admission to discharge (65 kcal/kg/day, 95% CI 56, 73) to 79 (95% CI 72, 86, p = 0.0014) and was stable hereafter. Predictive equations underestimated REE in 92% of participants at all time points. Recommended feeding targets during the acute phase of illness in severely malnourished children exceeded REE. Acutely ill malnourished children are at risk of being overfed when implementing current international guidelines.
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