Open-label, randomised controlled trial found that a green banana mixed rice suji diet was most effective for persistent diarrhoea in children in Bangladesh.

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.

External validation of a mobile clinical decision support system for diarrhea etiology prediction in children: A multicenter study in Bangladesh and Mali.

Background: Diarrheal illness is a leading cause of antibiotic use for children in low- and middle-income countries. Determination of diarrhea etiology at the point-of-care without reliance on laboratory testing has the potential to reduce inappropriate antibiotic use. Methods: This prospective observational study aimed to develop and externally validate the accuracy of a mobile software application ('App') for the prediction of viral-only etiology of acute diarrhea in children 0-59 months in Bangladesh and Mali. The App used a previously derived and internally validated model consisting of patient-specific ('present patient') clinical variables (age, blood in stool, vomiting, breastfeeding status, and mid-upper arm circumference) as well as location-specific viral diarrhea seasonality curves. The performance of additional models using the 'present patient' data combined with other external data sources including location-specific climate, data, recent patient data, and historical population-based prevalence were also evaluated in secondary analysis. Diarrhea etiology was determined with TaqMan Array Card using episode-specific attributable fraction (AFe) >0.5. Results: Of 302 children with acute diarrhea enrolled, 199 had etiologies above the AFe threshold. Viral-only pathogens were detected in 22% of patients in Mali and 63% in Bangladesh. Rotavirus was the most common pathogen detected (16% Mali; 60% Bangladesh). The present patient+ viral seasonality model had an AUC of 0.754 (0.665-0.843) for the sites combined, with calibration-in-the-large α = -0.393 (-0.455--0.331) and calibration slope ß = 1.287 (1.207-1.367). By site, the present patient+ recent patient model performed best in Mali with an AUC of 0.783 (0.705-0.86); the present patient+ viral seasonality model performed best in Bangladesh with AUC 0.710 (0.595-0.825). Conclusions: The App accurately identified children with high likelihood of viral-only diarrhea etiology. Further studies to evaluate the App's potential use in diagnostic and antimicrobial stewardship are underway. Funding: Funding for this study was provided through grants from the Bill and Melinda GatesFoundation (OPP1198876) and the National Institute of Allergy and Infectious Diseases (R01AI135114). Several investigators were also partially supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116163). This investigation was also supported by the University of Utah Population Health Research (PHR) Foundation, with funding in part from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002538. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design, data collection, data analysis, interpretation of data, or in the writing or decision to submit the manuscript for publication.

Diarrhea is one of the most common illnesses among children worldwide. In low- and middle-income countries with limited health care resources, it can be deadly. Diarrhea can be caused by infections with viruses or bacteria. Antibiotics can treat bacterial infections, but they are not effective against viral infections. It can often be difficult to determine the cause of diarrhea. As a result, many clinicians just prescribe antibiotics. However, since diarrhea in young children is often due to viral infections, prescribing unnecessary antibiotics can cause children to have side effects without any benefit. Excessive use of antibiotics also contributes to the development of bacteria that are resistant to antibiotics, making infections harder to treat. Scientists are working to develop mobile health tools or 'apps' that may help clinicians identify the cause of diarrhea. Using computer algorithms to analyze information about the patient and seasonal infection patterns, the apps predict whether a bacterial or viral infection is the likely culprit. These tools may be particularly useful in low- or middle-income country settings, where clinicians have limited access to testing for bacteria or viruses. Garbern, Nelson et al. previously built an app to help distinguish cases of viral diarrhea in children in Mali and Bangladesh. Now, the researchers have put their app to the test in the real-world in a new group of patients to verify it works. In the experiments, nurses in Mali and Bangladesh used the app to predict whether a child with diarrhea had a viral or non-viral infection. The children's stool was then tested for viral or bacterial DNA to confirm whether the prediction was correct. The experiments showed the app accurately identified viral cases of diarrhea. The experiments also showed that customizing the app to local conditions may further improve its accuracy. For example, a version of the app that factored in seasonal virus transmission performed the best in Bangladesh, while a version that factored in data from recent patients in the past few weeks performed the best in Mali. Garbern and Nelson et al. are now testing whether their app could help reduce unnecessary use of antibiotics in children with diarrhea. If it does, it may help minimize antibiotic resistance and ensure more children get appropriate diarrhea care.

Association of Socio-Demographic and Climatic Factors with the Duration of Hospital Stay of Under-Five Children with Severe Pneumonia in Urban Bangladesh: An Observational Study.

Severe pneumonia is one of the leading contributors to morbidity and deaths among hospitalized under-five children. We aimed to assess the association of the socio-demographic characteristics of the patients and the climatic factors with the length of hospital stay (LoS) of under-five children with severe pneumonia managed at urban hospitals in Bangladesh. We extracted relevant data from a clinical trial, as well as collecting data on daily temperature, humidity, and rainfall from the Meteorological Department of Bangladesh for the entire study period (February 2016 to February 2019). We analyzed the data of 944 children with a generalized linear model using gamma distribution. The average duration of the hospitalization of the children was 5.4 ± 2.4 days. In the multivariate analysis using adjusted estimation of duration (beta; ß), extended LoS showed remarkably positive associations regarding three variables: the number of household family members (ß: 1.020, 95% confidence intervals (CI): 1.005-1.036, p = 0.010), humidity variation (ß: 1.040, 95% Cl: 1.029-1.052, p < 0.001), and rainfall variation (ß: 1.014, 95% Cl: 1.008-1.019), p < 0.001). There was also a significant negative association with LoS for children's age (ß: 0.996, 95% Cl: 0.994-0.999, p = 0.006), well-nourishment (ß: 0.936, 95% Cl: 0.881-0.994, p = 0.031), and average rainfall (ß: 0.980, 95% Cl: 0.973-0.987, p < 0.001). The results suggest that the LoS of children admitted to the urban hospitals of Bangladesh with severe pneumonia is associated with certain socio-demographic characteristics of patients, and the average rainfall with variation in humidity and rainfall.

Side Effects Following Administration of the First Dose of Oxford-AstraZeneca's Covishield Vaccine in Bangladesh: A Cross-Sectional Study.

In response to the raging COVID-19 pandemic, Bangladesh started its vaccine administration in early 2021; however, due to the rapid development and launch of the vaccines in the market, many people had concerns regarding the safety of these vaccines. The purpose of this study was to evaluate the side effects that were experienced by the Bangladeshi residents after receiving the first dose of the Oxford-AstraZeneca's Covishield vaccine (ChAdOx1nCoV-19). The study was conducted using both online and printed questionnaires and the data were analysed using SPSS. The results included the responses of 474 vaccine recipients from March-April 2021. Pain at the site of injection, fever, myalgia, fatigue and headache were the most commonly reported symptoms, and the overall side effects were found to be significantly more prevalent in the younger population (p ≤ 0.05). These findings were consistent with the results indicated by the clinical trial of ChAdOx1nCoV-19. Logistic regression analysis further revealed that compared to people aged 70 years or above, the incidence of reported side effects was significantly higher in people aged 18-30 years (odds ratio (OR) = 8.56), 31-40 years, (OR = 5.05), 41-50 years (OR = 4.08), 51-60 years (OR = 3.77) and 61-70 years (OR = 3.67). In addition, a significantly higher percentage of female participants suffered from post-vaccination side effects compared to males (OR = 1.51). It was concluded that the Covishield vaccine was well-tolerated among people of different age groups. Nevertheless, further long-term follow-up study with a larger sample size is warranted to establish the long-term safety of the COVID-19 vaccine.

Clinical Characteristics and Underlying Factors Related to Recovery from Severe Pneumonia in Under-Five Children with or without Malnutrition Treated at Health Care Facilities in Bangladesh.

Severe pneumonia with co-morbidity of malnutrition is one of the leading causes of death among children younger than five years of age. We aimed to compare the clinical features related to recovery from severe pneumonia in malnourished and well-nourished under-five children. A significantly lesser proportion of malnourished children compared to well-nourished recovered from rapid breathing (86.5% vs. 90.2%; p = 0.035), chest wall in-drawing (90.5% vs. 93.9%; p = 0.019), and fever (92.2% vs. 95.2%; p = 0.021) on day six after admission to health-care facilities. Malnourished children with severe pneumonia had significantly more rapid breathing (Adjusted Odds Ratio (AOR)) 1.636, 95% Confidence interval (CI) 1.150-2.328 p = 0.006), chest wall in-drawing (AOR 1.698, 95% CI 1.113-2.590, p = 0.014), and fever (AOR 1.700, 95% CI 1.066-2.710, p = 0.026) compared to those in well-nourished children. The study results suggested the lesser disappearance of clinical features among the malnourished children in Bangladesh underscores their vulnerability to severe pneumonia.

Vitamin D supplementation among Bangladeshi children under-five years of age hospitalised for severe pneumonia: A randomised placebo controlled trial.

INTRODUCTION: Vitamin D is important for its immunomodulatory role and there is an independent association between vitamin D deficiency and pneumonia. We assessed the effect of vitamin D supplementation on the outcome in children hospitalized for severe pneumonia. METHODS: This was a randomised, double blinded, placebo-controlled clinical trial in children aged >2-59 months with severe pneumonia attending Dhaka Hospital, icddr,b. Children received age-specific megadose of vitamin D3 (20,000IU: <6 months, 50,000 IU: 6-12 months, 100,000 IU:13-59 months) or placebo on first day and 10,000 IU as maintenance dose for next 4 days or until discharge (if discharged earlier) along with standard therapy. This trial is registered at ClinicalTrials.gov, number NCT02185196. FINDINGS: We enrolled 100 children in placebo group and 97 in vitamin D group. On admission, 50 (52%) and 49 (49%) of children in vitamin D and placebo groups, respectively were vitamin D deficient. Among children with a sufficient serum vitamin D level on admission, a lower trend for duration of resolution of severe pneumonia in hours [72(IQR:44-96)vs. 88(IQR:48-132);p = 0.07] and duration of hospital stay in days [4(IQR:3-5)vs.5(IQR:4-7);P = 0.09] was observed in vitamin D group compared to placebo. No beneficial effect was observed in vitamin D deficient group or irrespective of vitamin D status. CONCLUSION: Age-specific mega dose of vitamin D followed by a maintenance dose shown to have no statistical difference between the two intervention groups, however there was a trend of reduction of time to recovery from pneumonia and overall duration of hospital stay in under-five children with a sufficient serum vitamin D level on hospital admission.

Efficacy of a Green Banana-Mixed Diet in the Management of Persistent Diarrhea: Protocol for an Open-Labeled, Randomized Controlled Trial.

BACKGROUND: Diarrhea is the second-leading cause of death in children under 5 years of age. In low- and middle-income countries, 3%-20% of acute diarrheal episodes become persistent diarrhea (PD) (ie, duration ≥14 days), which results in 36%-56% of all diarrheal deaths. In Bangladesh, PD causes >25% of diarrhea-related deaths. Commensal gut microbiota dysbiosis is increasingly recognized in the pathogenesis of PD. Hospital-based management of PD requires a hospital stay, which increases the risk of infection and hospital costs. The higher cost of treatment and high case-fatality rates reiterate PD as an important public health problem. At the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), for the last two decades, a consensus-based guideline has been followed for PD. Observation has revealed that green banana helps in the resolution of diarrhea. However, no larger prospective study has been conducted to evaluate the efficacy of green banana in the management of PD among children older than 6 months of age. OBJECTIVE: Our objective is to assess the efficacy of full-strength rice suji (semolina) with and without green banana compared to three-quarter-strength rice suji in the management of PD in children aged 6-36 months at the Dhaka Hospital of the icddr,b. METHODS: This open-labeled, randomized controlled study aims to enroll a total of 145 children with PD who have not been improving on a diet of milk suji. Children will be randomized into three different diet-specific groups: full-strength rice suji containing green banana, full-strength rice suji alone, and three-quarter-strength rice suji. The primary outcome is the percentage of children who recovered from diarrhea by day 5. RESULTS: Recruitment and data collection began in December 2017 and were completed in November 2019. Results are expected by April 2020. CONCLUSIONS: This study is expected to provide insights into the incorporation of green banana into the dietary management of PD. This would be the first study to investigate the role of microbiota and metabolomics in the pathogenesis of PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03366740; https://clinicaltrials.gov/ct2/show/NCT03366740. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15759.

A phase I trial of WRSS1, a Shigella sonnei live oral vaccine in Bangladeshi adults and children.

Shigella sonnei live vaccine candidate, WRSS1, which was previously evaluated in US, Israeli and Thai volunteers, was administered orally to Bangladeshi adults and children to assess its safety, clinical tolerability and immunogenicity. In a randomized, placebo-controlled, dose-escalation, age-descending study, 39 adults (18-39 years) and 64 children (5-9 years) were enrolled. Each adult cohort (n = 13) received one dose of 3x104, or three doses of 3 × 105 or 3 × 106 colony forming unit (CFU) of WRSS1 (n = 10) or placebo (n = 3). Each child cohort (n = 16) received one dose of 3x103, or three doses of 3x104, 3x105, or 3 × 106 CFU WRSS1 (n = 12) or placebo (n = 4). WRSS1 elicited mostly mild and transient reactogenicity events in adults and children. In the 3 × 106 dose group, 50% of the adults shed the vaccine; no shedding was seen in children. At the highest dose, 100% of adults and 40% of children responded with a ≥ 4-fold increase of S. sonnei LPS-specific IgA antibody in lymphocyte supernatant (ALS). At the same dose, 63% of adults and 70% of children seroconverted with IgA to LPS, while in placebo, 33% of adults and 18% of children seroconverted. Both the vaccinees and placebos responded with fecal IgA to LPS, indicating persistent exposure to Shigella infections. In conclusion, WRSS1 was found safe up to 106 CFU dose and immunogenic in adults and children in Bangladesh. These data indicate that live, oral Shigella vaccine candidates, including WRSS1 can potentially be evaluated in toddlers and infants (<2 years of age), who comprise the target population in an endemic environment.

Prevalence, determinants and health care-seeking behavior of childhood acute respiratory tract infections in Bangladesh.

BACKGROUND: Acute respiratory infections (ARIs) are one of the leading causes of child mortality worldwide and contribute significant health burden for developing nations such as Bangladesh. Seeking care and prompt management is crucial to reduce disease severity and to prevent associated morbidity and mortality. OBJECTIVE: This study investigated the prevalence and care-seeking behaviors among under-five children in Bangladesh and identified factors associated with ARI prevalence and subsequent care-seeking behaviors. METHOD: The present study analyzed cross-sectional data from the 2014 Bangladesh Demographic Health Survey. Bivariate analysis was performed to estimate the prevalence of ARIs and associated care-seeking. Logistic regression analysis was used to determine the influencing socio-economic and demographic predictors. A p-value of <0.05 was considered as the level of significance. RESULT: Among 6,566 under-five children, 5.42% had experienced ARI symptoms, care being sought for 90% of affected children. Prevalence was significantly higher among children < 2 years old, and among males. Children from poorer and the poorest quintiles of households were 2.40 (95% CI = 1.12, 5.15) and 2.36 (95% CI = 1.06, 5.24) times more likely to suffer from ARIs compared to the wealthiest group. Seeking care was significantly higher among female children (AOR = 2.19, 95% CI = 0.94, 5.12). The likelihood of seeking care was less for children belonging to the poorest quintile compared to the richest (AOR = 0.03, 95% CI = 0.01, 0.55). Seeking care from untrained providers was 3.74 more likely among rural residents compared to urban (RRR = 3.74, 95% CI = 1.10, 12.77). CONCLUSION: ARIs continue to contribute high disease burden among under-five children in Bangladesh lacking of appropriate care-seeking behavior. Various factors, such as age and sex of the children, wealth index, the education of the mother, and household lifestyle factors were significantly associated with ARI prevalence and care-seeking behaviors. In addition to public-private actions to increase service accessibility for poorer households, equitable and efficient service distribution and interventions targeting households with low socio-economic status and lower education level, are recommended.

Clinical profile, antibiotic susceptibility pattern of bacterial isolates and factors associated with complications in culture-proven typhoid patients admitted to an urban hospital in Bangladesh.

OBJECTIVES: Typhoid fever is one of the major causes of morbidity and mortality in typhoid endemic countries like Bangladesh. However, data on the clinical and microbiological profile as well as factors associated with complications of typhoid in Bangladesh are scarce. We intended to characterise the clinical and microbiological profile of culture-proven typhoid fever and to identify factors associated with complications. METHODOLOGY: Retrospective analysis of clinical data from 431 patients with culture-confirmed typhoid fever admitted to Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh, between January 2010 and December 2014. Clinical and microbiological profiles of the patients including age, sex, and duration of illness prior to hospital admission, haematological parameters and the antimicrobial resistance profile of the infecting isolate, duration of hospital stay and defervescence time were examined by logistic regression to identify the factors associated with complications. RESULT: About one of three patients were children under 5 years, and 21.5% of them were severely malnourished. During hospitalisation, 17.4% patients developed complications; mainly encephalopathy (6.7%), ileus (6.5%) and pneumonia (3.5%). Among culture-positive cases, 28.3% isolates showed multidrug resistant (MDR) and more than 90% of isolates were resistant to nalidixic acid and had intermediate sensitivity to ciprofloxacin. Five isolates were resistant to azithromycin; all isolates were sensitive to cefixime and ceftriaxone. Complication was independently associated with duration of fever before admission (adjusted odds ratio: 0.85; 95% CI: 0.074-0.97; P < 0.05), thrombocytopenia on admission (AOR: 2.84; 95% CI: 01.06-7.57; P < 0.05), duration of hospital stay (AOR: 1.34; 95% CI: 1.15-1.57; P < 0.01) and defervescence time (AOR: 0.83; 95% CI: 0.70-0.99; P < 0.05). CONCLUSION: The high prevalence of typhoid fever among under-five children and complications among hospitalised patients are matters of concern. Sensitivity of Salmonella Typhi to ceftriaxone and cefixime was better than to other conventional antibiotics. Shorter duration of fever and thrombocytopenia on admission can be considered as early signs of complications.

The management of persistent diarrhoea at Dhaka Hospital of the International Centre for Diarrhoeal Disease and Research: a clinical chart review.

BACKGROUND: Persistent diarrhoea (PD) is poorly recognised and it requires proper assessment and early intervention to ensure effective treatment. The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) has been managing children with PD for more than two decades. This review focuses on different aspects of the management of PD in a hospital setting. AIM: To estimate the prevalence, socio-demographic and clinical characteristics, treatment outcome and hospital course in under-5 children with persistent diarrhoea (PD). METHODS: The hospital records of all children under 5 years admitted with PD to Dhaka Hospital of the International Centre for Diarrhoeal Disease Research between January 2012 and December 2013 were reviewed. Data were retrieved from the hospital's electronic database. RESULTS: Of 8638 children under 5 years of age admitted with diarrhoea, 551 (6.4%) had PD and one-third had developed PD during their hospital stay. The incidence of PD was highest (228, 41.4%) in summer (April-June). Half (51%) of the children with PD had dehydration on admission. Fifty-seven (10.3%) had never been breastfed, 138 (25.1%) were severely wasted and 21 (3.8%) had bipedal oedema. Following the steps of a dietary algorithm, 224 (40.6%) patients responded to a milk-based low-lactose diet, 235 (42.6%) to a lactose-, sucrose- and milk-free diet, 48 (8.7%) to a comminuted chicken and glucose-based diet, 41 (7.4%) to exclusive breastfeeding, and 3 (0.5%) required a partially hydrolysed, semi-elemental diet. Major stool pathogens were Campylobacter species (23/59, 39%), Salmonella (10/59, 16.9%) and Shigella (10/59, 16.9%). The overall recovery rate from PD was 95.6% (527/551) and the duration of treatment until resolution of diarrhoea was 6 (3-9) days. The case-fatality rate was 2% (11/551). CONCLUSION: Persistent diarrhoea remains an important public health problem in children under-5 in Bangladesh. Algorithm-based dietary management with simple clinical guidelines was effective in most cases. This treatment is appropriate in low-income settings where resources are limited.

Sex and Gender Differences in Acute Pediatric Diarrhea: A Secondary Analysis of the DHAKA Study.

Pediatric diarrheal disease is a significant source of morbidity and mortality in the developing world. While several studies have demonstrated an increased incidence of diarrheal illness in boys compared with girls in low- and middle-income countries (LMIC), the reasons for this difference are unclear. This secondary analysis of the dehydration: assessing kids accurately (DHAKA) derivation and validation studies included children aged <5 years old with acute diarrhea in Dhaka, Bangladesh. The dehydration status was established by percentage weight change with rehydration. Multivariable regression was used to compare percent dehydration, while controlling for differences in age and nutritional status. In this cohort, a total of 1396 children were analyzed; 785 were male (56.2%) and 611 were female (43.8%). Girls presenting with diarrhea were older than boys (median age 17 months vs. 15 months, p = 0.02) and had significantly more malnutrition than boys, even when controlled for age (mean 134.2 mm vs. 136.4 mm, p < 0.01). The mean percent dehydration did not differ between boys and girls after controlling for age and nutrition status (p = 0.25). Although girls did have higher rates of malnutrition than boys, measures of diarrhea severity were similar between the two groups, arguing against a cultural bias in care-seeking behavior that favors boys.

Treatment outcome of children with persistent Diarrhoea admitted to an Urban Hospital, Dhaka during 2012-2013.

BACKGROUND: Despite availability of treatment guidelines, persistent diarrhoea (PD) has been a major contributor of diarrhoeal deaths in low and middle income countries. We evaluated the outcome of children under the age of 5 years who were treated for PD using management algorithm with locally available foods in a diarrhoeal disease hospital in Dhaka. METHODS: We extracted retrospective data from electronic database for all the under-five children admitted for PD in the Longer Stay Ward and Intensive Care Unit of the Dhaka hospital at icddr,b between 2012 and 2013. Descriptive analysis was done to explore available baseline socio-demographic, nutritional, and co-morbid statuses, pathogens from stool isolates, duration of treatment, use of antibiotics, duration of hospital stay and treatment success rates. We sought to investigate above mentioned descriptive features in addition to associated factors with time to recover from PD using survival analysis with Cox proportional hazard model. RESULTS: A total number of 426 children with a median age of 7.46 (inter-quartile range IQR; 5.39, 9.43) months were admitted for PD during the study period. Of these, 95% of children were recovered from PD and discharged from the hospital. The median duration of treatment response was 6 (IQR 4, 9) days. The case fatality rate was 1.17%. Multivariate analysis among the children of 6 months or less showed that the rate of recovery from PD was 57% lower in children with severe stunting compared to those without severe stunting (HR 0.43, 95% CI 0.22, 0.88, p < 0.05), 42% lower in children with severe wasting (HR 0.58, 95% CI 0.36, 0.95, p < 0.05), and 81% reduced in children who developed hospital acquired infection (HAI) compared to those without HAI (HR 0.19, 95% CI 0.06, 0.62, p < 0.05). Among the children who were more than 6 months old, age in months (HR 1.05, 95% CI 1.02, 1.09) and female gender (HR 1.41, 95% CI 1.09, 1.84) had better rates of recovery from PD (p < 0.05). Moreover, among children more than 6 months of age, HAI (HR 0.44, 95% CI 0.26, 0.75), and antibiotic use (HR 0.40, 95% CI 0.28, 0.56) were associated with impeded recovery rates from PD (p < 0.05). CONCLUSION: The treatment guideline for persistent diarrhoea patients followed at icddr,b Dhaka hospital was found to be successful and can be used in other treatment facilities of Bangladesh and other developing countries where any treatment algorithm for PD is unavailable. More emphasis is required to be given for the prevention of hospital acquired infection that may help to limit the use of antibiotic in order to enhance the recovery rate from PD.

Multi-drug resistant pathogenic bacteria in the gut of young children in Bangladesh.

BACKGROUND: The gut of human harbors diverse commensal microbiota performing an array of beneficial role for the hosts. In the present study, the major commensal gut bacteria isolated by culturing methods from 15 children of moderate income families, aged between 10 and 24 months, were studied for their response to different antibiotics, and the molecular basis of drug resistance. RESULTS: Of 122 bacterial colonies primarily selected from Luria-Bertani agar, bacterial genera confirmed by analytical profile index (API) 20E® system included Escherichia as the predominant (52%) organism, followed by Enterobacter (16%), Pseudomonas (12%), Klebsiella (6%), Pantoea (6%), Vibrio (3%), and Citrobacter (3%); while Aeromonas and Raoultella were identified as the infrequently occurring genera. An estimated 11 and 22% of the E. coli isolates carried virulence marker genes stx-2 and eae, respectively. Antimicrobial susceptibility assay revealed 78% of the gut bacteria to be multidrug resistant (MDR) with highest resistance to erythromycin (96%), followed by ampicillin (63%), tetracycline (59%), azithromycin (53%), sulfamethoxazole-trimethoprim (43%), cefixime (39%), and ceftriaxone (33%). PCR assay results revealed 56% of the gut bacteria to possess gene cassette Class 1 integron; while 8, 17.5 and 6% of the strains carried tetracycline resistance-related genes tetA, tetB, and tetD, respectively. The macrolide (erythromycin and azithromycin) resistance marker genes mphA, ereB, and ermB were found in 28, 3 and 5% of bacterial isolates, respectively; while 26, 12, 17, 32, 7, 4 and 3% of the MDR bacterial isolates carried the extended spectrum ß-lactamase (ESBL)-related genes e.g., blaTEM, blaSHV, blaCMY-9, blaCTX-M1, blaCTX-M2, blaCMY-2 and blaOXA respectively. Majority of the MDR gut bacteria harbored large plasmids [e.g., 140 MDa (43%), 105 MDa (30%), 90 MDa (14%)] carrying invasion and related antibiotic resistance marker genes. CONCLUSIONS: Our results suggest gut of young Bangladeshi children to be an important reservoir for multi-drug resistant pathogenic bacteria carrying ESBL related genes.

Factors Associated with Klebsiella Bacteremia and Its Outcome in Under-Five Children Admitted with Diarrhea.

Although Klebsiella bacteremia in children is perceived to be associated with fatal consequences, data are scarce on those children presenting with diarrhea. We evaluated the factors associated with Klebsiella bacteremia in such children. In this retrospective chart analysis, data of all diarrheal children was retrieved from electronic medical record system (named as SHEBA) of Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), from January 1, 2010, to December 31, 2012, who had their blood culture done. This was a study having a case-control design where comparison of clinical and laboratory characteristics was done among children with Klebsiella bacteremia (cases = 30) and those without any bacteraemia (controls = 90). Controls were selected randomly. The cases more often had fatal outcome (p < 0.001). In logistic regression analysis, after adjusting for potential confounders such as young age, severe dehydration, severe wasting, abnormal mentation, hypotension, and fast breathing, the cases were independently associated with hospital-acquired infection and positive stool growth (for all, p < 0.05). The study highlights the importance of obtaining blood cultures in hospitalized children under five years old with diarrheal illness in the presence of either hospital-acquired infection or positive stool culture to have better outcome.

Efficacy of partially hydrolyzed guar gum (PHGG) supplemented modified oral rehydration solution in the treatment of severely malnourished children with watery diarrhoea: a randomised double-blind controlled trial.

OBJECTIVES: To examine whether PHGG added ORS reduce duration of diarrhoea, stool output and enhance weight gain. METHODS: In a double-blind controlled clinical trial, 126 malnourished children (weight for length/weight for age < -3 Z-score with or without pedal edema), aged 6 - 36 months with acute diarrhoea <7 days were studied in two treatment groups; 63 received modified WHO ORS (Na 75, K 40, Cl 87, citrate 7, glucose 90 mmol/L) with PHGG 15 g/L (study group); 63 received modified WHO ORS without PHGG (control). Other treatments were similar in both groups. The study protocol was approved by Ethics Committee of icddr,b; the study was carried out at the Dhaka Hospital. RESULTS: The mean duration of diarrhoea (h) was significantly shorter in children of the study group (Study vs. control, mean ± SD, 57 ± 31 vs. 75 ± 39, p = 0.01). Although there was a trend in stool weight reduction in children receiving ORS with PHGG (study vs. control, stool weight (g), mean ± SD; 1(st) 24 hour, 854.03 ± 532.15 vs. 949.11 ± 544.33, p = 0.32; 2(nd) 24 hour, 579.84 ± 466.01 vs. 761.26 ± 631.64, p = 0.069; 3(rd) 24 hour, 385.87 ± 454.09 vs. 495.73 ± 487.61, p = 0.196), especially in 2(nd) 24 h period, the difference was not statistically significant. The mean time (day) to attain weight for length 80% of NCHS median without edema was significantly shorter in the study group (study vs. control, mean ± SD, 4.5 ± 2.6 vs. 5.7 ± 2.8, p = 0.027). CONCLUSION: PHGG added to ORS substantially reduced duration of diarrhoea. It also enhanced weight gain. Further studies might substantiate to establish its beneficial effect. CLINICAL TRIAL REGISTRATION NUMBER: NCT01821586.

Metagenomic profile of gut microbiota in children during cholera and recovery.

BACKGROUND: The diverse bacterial communities colonizing the gut (gastrointestinal tract) of infants as commensal flora, which play an important role in nutrient absorption and determining the state of health, are known to alter due to diarrhea. METHOD: Bacterial community dynamics in children suffering from cholera and during recovery period were examined in the present study by employing metagenomic tool, followed by DNA sequencing and analysis. For this, bacterial community DNA was extracted from fecal samples of nine clinically confirmed cholera children (age 2-3 years) at day 0 (acute cholera), day 2 (antibiotic therapy), day 7 and, and day 28, and the variable region of 16S rRNA genes were amplified by universal primer PCR. RESULTS: 454 parallel sequencing of the amplified DNA followed by similarity search of the sequenced data against an rRNA database allowed us to identify V. cholerae, the cause of cholera, in all nine children at day 0, and as predominant species in six children, accounting for 35% of the total gut microbiota on an average in all the nine children. The relative abundance (mean ± sem %) of bacteria belonging to phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, was 55 ± 7, 18 ± 4, 13 ± 4, and 8 ± 4, respectively, at day 0, while these values were 12 ± 4, 43 ± 4, 33 ± 3, and 12 ± 2, respectively, at day 28. As antibiotic therapy began, V. cholerae count declined significantly (p< 0.001) and was found only in four children at day 2 and two children at day 7 with the relative abundance of 3.7% and 0.01%, respectively, which continued up to day 28 in the two children. Compared to acute cholera condition (day 0), the relative abundance of Escherichia coli, Enterococcus, and Veillonella increased at day 2 (antibiotic therapy) while Bifidobacterium, Bacteroides, and Ruminococcus decreased. CONCLUSION: Cholera results expulsion of major commensal bacteria of phyla Bacteroidetes, Firmicutes, and Actinobacteria, and increase of harmful Proteobacteria to colonize the gut during acute and convalescence states. The observed microbiota disruption might explain the prevalent malnutrition in children of Bangladesh where diarrheal diseases are endemic.

16S rRNA gene-targeted TTGE in determining diversity of gut microbiota during acute diarrhoea and convalescence.

The human gut microbiota play a vital role in health and nutrition but are greatly modified during severe diarrhoea due to purging and pathogenic colonization. To understand the extent of loss during and after diarrhoea, faecal samples collected from children (n=21) suffering from acute diarrhoea and from their healthy siblings (n=9) were analyzed by 16S rRNA gene-targeted universal primer polymerase chain reaction (PCR), followed by temporal temperature gradient gel electrophoresis (TTGE). The gut microbiota decreased significantly as indicated by the number of TTGE bands at day 0 of acute diarrhoea [patients vs healthy siblings: 11±0.9 vs 21.8±1.1 (mean ± standard error), p<0.01]. The number of bands showed a steady increase from day 1 to day 7; however, it remained significantly less than that in healthy siblings (15±0.9, p<0.01). These results suggest that appropriate therapeutic and post-diarrhoeal nutritional intervention might be beneficial for the early microbial restoration and recovery.

Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Treatment of shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of shigellosis in patients. METHODS: A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1ß [IL-1ß] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. RESULTS: Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1ß in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. CONCLUSION: Adjunct therapy with butyrate during shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00800930.

Gut microbiota of healthy and malnourished children in bangladesh.

Poor health and malnutrition in preschool children are longstanding problems in Bangladesh. Gut microbiota plays a tremendous role in nutrient absorption and determining the state of health. In this study, metagenomic tool was employed to assess the gut microbiota composition of healthy and malnourished children. DNA was extracted from fecal samples of seven healthy and seven malnourished children (n = 14; age 2-3 years) were analyzed for the variable region of 16S rRNA genes by universal primer PCR followed by high-throughput 454 parallel sequencing to identify the bacterial phyla and genera. Our results reveal that the healthy children had a significantly higher number of operational taxonomic unit in their gut than that of the malnourished children (healthy vs. malnourished: 546 vs. 310). In malnourished children, bacterial population of the phyla Proteobacteria and Bacteroidetes accounted for 46 and 18%, respectively. Conversely, in healthy children, Proteobacteria and Bacteroidetes accounted for 5% and 44, respectively (p < 0.001). In malnourished children, the phylum Proteobacteria included pathogenic genera, namely Klebsiella and Escherichia, which were 174-fold and 9-fold higher, respectively, than their healthy counterpart. The predominance of potentially pathogenic Proteobacteria and minimal level of Bacteroidetes as commensal microbiota might be associated to the ill health of malnourished children in Bangladesh.