Protection of staff and families during COVID-19 pandemic: experience from a research institute in Bangladesh.

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), which contains the world's largest diarrheal disease hospital, established a service centre, including testing facilities, isolation unit, out-patient department, in-patient ward, and intensive care unit during COVID-19 pandemic. When the management of COVID-19 was challenging nationwide, icddr,b established this facility with the goal to provide COVID-related services to the staff and their relatives amidst the pandemic. Data related to this analysis were collected from April 2020 to December 2021. 1399 patients received treatment under this facility. Among them, 351 patients were treated at the out-patient facility, 98 at the isolation, and 197 at the in-patient ward. Among the admitted patients, survival was 86.29% (n = 170/197). Among the suspected patients, 17% (n = 103/606) were COVID-positive. Setting up an immediate COVID-19 management facility during the pandemic was challenging. It can be an example of how an organisation can adapt to any emergency and act accordingly.

Effects of L-Carnitine Supplementation on the Rate of Weight Gain and Biomarkers of Environmental Enteric Dysfunction in Children with Severe Acute Malnutrition: A Double-Blind Randomized Controlled Clinical Trial.

BACKGROUND: Severe acute malnutrition (SAM) is a major public health concern among low- and middle-income countries, where the majority of the children encountering this acute form of malnutrition suffer from environmental enteric dysfunction (EED). However, evidence regarding the effects of L-carnitine supplementation on the rate of weight gain and EED biomarkers in malnourished children is limited. OBJECTIVES: We aimed to investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with SAM. METHODS: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted at the Nutritional Rehabilitation Unit (NRU) of Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh. Children with SAM aged 9-24 mo were randomly assigned to receive commercial L-carnitine syrup (100 mg/kg/d) or placebo for 15 d in addition to standard of care. A total of 98 children with Weight-for-Length-z-score (WLZ) < -3 Standard deviation were enrolled between October 2021 and March 2023. Analyses were conducted on an intention-to-treat basis. RESULTS: The primary outcome variable, "rate of weight gain," was comparable between L-carnitine and placebo groups (2.09 ± 2.23 compared with 2.07 ± 2.70; P = 0.973), which was consistent even after adjusting for potential covariates (age, sex, Weight-for-Age z-score, asset index, and WASH practices) through linear regression [ß: 0.37; 95% confidence interval (CI): -0.63,1.37; P = 0.465]. The average hospital stay was ∼4 d. The results of adjusted median regression showed that following intervention, there was no significant difference in the EED biomarkers among the treatment arms; Myeloperoxidase (ng/mL) [ß: -1342.29; 95% CI: -2817.35, 132.77; P = 0.074], Neopterin (nmol/L) [ß: -153.33; 95% CI: -556.58, 249.91; P = 0.452], alpha-1-antitrypsin (mg/mL) [ß: 0.05; 95% CI: -0.15, 0.25; P = 0.627]. Initial L-carnitine (µmol/L) levels (median, interquartile range) for L-carnitine compared with placebo were 54.84 (36.0, 112.9) and 59.74 (45.7, 96.0), whereas levels after intervention were 102.05 (60.9, 182.1) and 105.02 (73.1, 203.7). CONCLUSIONS: Although our study findings suggest that L-carnitine bears no additional effect on SAM, we recommend clinical trials with a longer duration of supplementation, possibly with other combinations of interventions, to investigate further into this topic of interest. This trial was registered at clinicaltrials.gov as NCT05083637.

Inpatient Morbidity and Mortality of Severely Underweight Children Was Comparable to That of Severely Wasted Children in Dhaka, Bangladesh.

Both wasting and undernutrition are responsible for multiple morbidities and increased mortality in younger children hospitalized for acute illnesses. The question of whether children who are suffering from severe underweight are as vulnerable as children suffering from severe wasting needs to be researched further. We aimed to compare the morbidity and mortality of severely underweight but not severely wasted (SU-nSW) children with that of severely wasted (SW) children admitted to inpatient wards of a hospital. Data from 12,894 children aged < 5 years were collected using cross-sectional methods from Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh between March 2019 and December 2021. After exclusion of non-desired populations (N = 8,834), comparisons between SU-nSW (N = 1,876) and SW (N = 2,184) children were observed. The risk of morbidities and mortality among SU-nSW and SW children was analyzed after adjusting for age and sex. Inpatient morbidities were mostly similar among children with sepsis (adjusted odds ratio [aOR]: 0.90; 95% CI: 0.69, 1.19; P = 0.472) and convulsions (aOR: 0.84; 95% CI: 0.51, 1.37; P = 0.475). Dehydration (aOR: 0.71; 95% CI: 0.62, 0.81; P < 0.001) and hypokalemia (aOR: 0.58; 95% CI: 0.42, 0.79; P = 0.001) were more likely associated with SW children than with SU-nSW children. Pneumonia/severe pneumonia was more likely to affect SU-nSW children (aOR: 1.24; 95% CI: 1.02, 1.48; P = 0.018). Death was comparable between the two groups (aOR: 1.32; 95% CI: 0.70, 2.49; P = 0.386). This study underscores the importance of implementing present treatment guidelines for severe acute malnutrition in the facility-based management of severely underweight children as well.

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

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

Role of L-Carnitine supplementation on rate of weight gain and biomarkers of Environmental Enteric Dysfunction in children with severe acute malnutrition: A protocol for a double-blinded randomized controlled trial.

BACKGROUND: Severe acute malnutrition (SAM) and environmental enteric dysfunction (EED) are highly prevalent among children residing in resource-limited countries like Bangladesh. L-carnitine may play a role in improving the growth and ameliorating the EED among nutritionally vulnerable children. OBJECTIVE: To investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with severe acute malnutrition. METHODS: This study is a double-blinded, placebo-controlled, randomized clinical trial aiming to enroll diarrheal children with SAM between 9-24 months of both sexes attending the nutritional rehabilitation unit (NRU) of Dhaka Hospital of icddr,b. It is an ongoing trial including two arms where one arm receives L-carnitine supplementation, and the other arms receive a placebo for 15 days in addition to the existing standard treatment of SAM. The primary outcome is the rate of weight gain, and the secondary outcomes include duration of hospital stay and EED biomarkers. Outcomes are assessed at baseline and 15 days of post-intervention. We hypothesize that the L- carnitine supplementation for 15 days in children with SAM will improve the rate of weight gain and biomarkers of EED. TRIAL REGISTRATION: ClinicalTrials.gov # NCT05083637. Date of registration: October 19, 2021.

A qualitative assessment of facility readiness and barriers to the facility-based management of childhood severe acute malnutrition in the public healthcare settings in Bangladesh.

OBJECTIVE: To assess facility readiness and identify barriers to the facility-based management of childhood severe acute malnutrition (SAM) in public healthcare settings. DESIGN: Qualitative methods were applied to assess readiness and identify different perspectives on barriers to the facility-based management of children with SAM. Data collection was done using in-depth interviews, key informant interviews, exit interviews and pre-tested observation tools. SETTINGS: Two tertiary care and four district hospitals in Rangpur and Sylhet Divisions of Bangladesh. PARTICIPANTS: Healthcare professionals and caregivers of children with SAM. RESULTS: Anthropometric tools, glucometer, medicines, F-75, F-100 and national guidelines for facility-based management of childhood SAM were found unavailable in some of the hospitals. Sitting and sleeping arrangements for the caregivers were absent in all of the chosen facilities. We identified a combination of health system and contextual barriers that inhibited the facility-based management of SAM. The health system barriers include inadequate manpower, rapid turnover of staff, increased workload, lack of training and lack of adherence to management protocol. The major facility barriers were insufficient space and unavailability of required equipment, medicines and foods for hospitalised children with SAM. The reluctance of caregivers to complete the treatment regimen, their insufficient knowledge regarding proper feeding, increased number of attendants and poverty of parents were the principal contextual barriers. CONCLUSIONS: The study findings provide insights on barriers that are curbing the facility-based management of SAM and emphasise policy efforts to develop feasible interventions to reduce the barriers and ensure the preparedness of the facilities for effective service delivery.

Health Care Providers' Knowledge, Attitude, and Practice Regarding Facility-Based Management of Children With Severe Acute Malnutrition in Bangladesh.

BACKGROUND: Severe acute malnutrition (SAM) contributes to a substantial number of child deaths globally per year. The mortality rates can be lowered markedly if guideline-based management protocol is properly followed. However, case-fatality rates in resource-poor centers remain high even after introducing the guidelines. Perhaps, the lack of adequate knowledge leading to inappropriate management by the health care providers is responsible for such burden. OBJECTIVE: We aimed to evaluate health care providers' knowledge, attitude, and practice regarding the facility-based management of children with SAM in Bangladesh. METHODS: This was a qualitative study where data were collected cross-sectionally from 4 district and 2 tertiary care hospitals. Twenty-six semi-structured in-depth interviews were conducted among the doctors and nurses involved in inpatient care of SAM. Twenty-eight hours of observation were done in each facility to obtain information regarding the management practices. RESULTS: The doctors had substantial knowledge in managing children with SAM in the facilities. However, knowledge of nurses was found suboptimal when evaluated based on the national guideline. Both doctors and nurses demonstrated favorable attitude toward management of childhood SAM. Identification of SAM at the facilities was poor due to lack of practice in relation to anthropometric measurements. In addition, improper practices related to blood glucose testing, dehydration monitoring, essential micronutrient administration, and follow-up of children with SAM were observed. CONCLUSION: The study results underscore the importance of taking appropriate measures to enhance knowledge and ensure proper practice in relation to inpatient care of children with SAM according to the national guideline in Bangladesh.

Association of human milk oligosaccharides and nutritional status of young infants among Bangladeshi mother-infant dyads.

Human milk oligosaccharides (HMOs) support the development of a healthy gut microbiome and the growth of infants. We aimed to determine the association of different HMOs with severe acute malnutrition (SAM) among Bangladeshi young infants. This study was nested within a single-blind, randomized, pilot clinical trial (NCT0366657). A total of 45 breastmilk samples from mothers of < 6 months old infants who had SAM (n = 26) or were non-malnourished (n = 19) and were analyzed for constituent HMOs. Of the infants with SAM, 14 (53.85%) had secretor mothers, and 11 (57.89%) of the non-malnourished infants had secretor mothers. A one-unit increase in the relative abundance of sialylated HMOs was associated with higher odds of SAM in age and sex adjusted model (aOR = 2.00, 90% CI 1.30, 3.06), in age, sex, and secretor status adjusted model (aOR = 1.96, 90% CI 1.29, 2.98), and also in age and sex adjusted model among non-secretor mothers (aOR = 2.86, 90% CI 1.07, 7.62). In adjusted models, there was no evidence of a statistically significant association between SAM and fucosylated or undecorated HMOs. Our study demonstrates that a higher relative abundance of sialylated HMOs in mothers' breastmilk may have a negative impact on young infants' nutritional status.

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

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: MTOR, TSC1, LAMTOR2, RPS6K1 and RICTOR 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 LAMTOR2 gene and increase in TSC1 gene expression were observed between malnourished children in comparison to the healthy children. The deregulation in the activity of the TSC1 and LAMTOR2 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.

Bifidobacterium infantis treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition.

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor-derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto-N-neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N-glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.

Use of TaqMan Array Cards to investigate the aetiological agents of diarrhoea among young infants with severe acute malnutrition.

OBJECTIVE: Studies involving less sensitive conventional microscopy and culture-based approaches have identified distinct differences in diarrhoeal aetiology in childhood malnutrition. Our study involved the use of an advanced molecular biology technique, the TaqMan Array Cards (TAC), to elucidate the diarrhoeal aetiology among young infants with severe acute malnutrition (SAM). METHOD: A total of 113 faecal samples was collected from SAM infants, aged 2-6 months, upon admission to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) with complications of diarrhoea and related comorbidities. We used TAC for the detection of 29 different diarrhoeal enteropathogens from a single faecal sample. For comparison, we also analysed 25 diarrhoeal samples from well-nourished infants of similar age. RESULTS: Higher odds of detection of all bacterial enteropathogens were associated with diarrhoea among SAM infants. In particular, the detection of Aeromonas sp (aOR: 25.7, p = 0.011), Campylobacter sp (aOR: 9.6, p < 0.01) and ETEC (aOR: 5.2, p = 0.022) was significantly associated with diarrhoea among SAM infants in comparison to well-nourished infants. 80% higher odds of detection of rotavirus and norovirus GII were associated with diarrhoea among well-nourished infants in comparison to SAM infants (aOR: 0.2, p < 0.05). CONCLUSION: Our study findings demonstrate a difference in diarrhoeal aetiology among SAM and well-nourished young infants, which may be useful in providing an evidence-based logic for possible revision of treatment guidelines for treatment of young diarrhoeal infants with SAM in the early management of the menace of antimicrobial resistance.

Antibiotic exposure among young infants suffering from diarrhoea in Bangladesh.

AIMS: Appropriate rehydration has always been significant in treating diarrhoeal diseases in children. Irrational antibiotic use among diarrhoeal children has remained a major public health concern. Information regarding antibiotic use in young infants suffering from diarrhoea is very limited and a unique aspect of research. We aimed to investigate the prevalence of antibiotic use in the community among 2-6 months infants with diarrhoeal illnesses and having different nutritional status. METHODS: We investigated a total of 5279 infants aged 2-6 months at Dhaka hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, between September 2018 and June 2019. Among them, 257 infants were suffering from severe acute malnutrition (SAM). History of taking antibiotics was ascertained by direct observation of a prescription by a physician, the bottle of antibiotic or asking the caregiver about the name of antibiotic or its price that is very close to the usual market price of an antibiotic. RESULTS: Overall, 52% of infants received antibiotics before hospital admission. Non-SAM infants had higher odds of receiving antibiotics (adjusted odds ratio [aOR] = 1.52, 95% confidence interval: 1.18, 1.97, P value = 0.003) compared to infants with SAM and use of antibiotics increased with age (aOR = 1.11, 95% confidence interval: 1.06, 1.17, P value<0.001). Commonly used antibiotics were azithromycin (13.3%), ciprofloxacin (7.7%), erythromycin (7.7%) and metronidazole (2.6%). The proportion of receiving ciprofloxacin was significantly lower in infants with SAM compared to their non-SAM counterparts (2.7% vs. 7.97%, P value = 0.004). CONCLUSIONS: The study underscores the excessive use of antibiotics among diarrhoeal infants, which is already a major public health concern in low- and middle-income countries.

Diarrhoeal children with concurrent severe wasting and stunting compared to severe wasting or severe stunting.

OBJECTIVE: Children with both severe wasting and severe stunting (SWSS) represent an extreme form of malnutrition and are prone to develop severe infection. The study aims to demonstrate clinical features and aetiology of diarrhoea among children with SWSS compared to those with either severe wasting (SW) or severe stunting (SS), which may help in early identification of high-risk children. METHODS: Data were extracted from the database of the diarrhoeal disease surveillance system (DDSS) of Dhaka Hospital, icddr,b from 2008 to 2017. Among 14 403 under-five diarrhoeal children, 149 had concurrent SWSS (WLZ/WHZ ˂-3 with LAZ/HAZ ˂-3), 795 had SW (WLZ/WHZ ˂-3 but LAZ/HAZ ≥-3) alone, and 1000 had only SS (LAZ/HAZ ˂-3 but WLZ/WHZ ≥-3). RESULTS: In logistic regression analysis after adjusting for potential confounders, dehydrating diarrhoea and slum dwelling were independently associated with SWSS vs. SW (P < 0.05). When compared with SS, dehydration and maternal illiteracy were independently associated with SWSS (P < 0.05). In comparison with SW or SS, SWSS less often included infection with rotavirus (P < 0.05). Dehydration was independently associated with SW vs. SS after adjusting for potential confounders (P < 0.05). CONCLUSION: Children with SWSS more often presented with dehydrating diarrhoea (69%) than children who had either SW (55%) or SS (43%). However, SWSS patients less frequently presented with rotavirus-associated diarrhoeal illnesses. This result underscores the importance of early detection and prompt management of dehydrating diarrhoea in children with concomitant severe wasting and severe stunting to reduce morbidity and mortality in these children, especially in poor settings.

OBJECTIF: Les enfants souffrant à la fois d'émaciation sévère et de retard de croissance sévère (ESRCS) représentent une forme extrême de malnutrition et sont susceptibles de développer des infections graves. L'étude vise à démontrer les caractéristiques cliniques et l'étiologie de la diarrhée chez les enfants atteints d'ESRCS par rapport à ceux souffrant d'émaciation sévère ou de retard de croissance sévère, ce qui pourrait aider à identifier rapidement les enfants à haut risque. MÉTHODES: Les données ont été extraites de la base de données du système de surveillance des maladies diarrhéiques (SSMD) de l'hôpital de Dhaka, icddr,b de 2008 à 2017. Parmi les 14.403 enfants de moins de cinq ans atteints de diarrhée, 149 avaient une ESRCS concomitants (WLZ/WHZ ˂-3 avec LAZ/HAZ ˂-3), 795 avaient une ES seule (WLZ/WHZ ˂-3 mais LAZ/HAZ ≥-3) et 1000 avaient un RCS seul (LAZ/HAZ ˂-3 mais WLZ/WHZ ≥-3). RÉSULTATS: Dans l'analyse de régression logistique, après ajustement des facteurs de confusion potentiels, la diarrhée déshydratante et l'habitation dans les bidonvilles étaient associées indépendamment à l'ESRCS par rapport à l'ES (P < 0,05). Par rapport au RCS, la déshydratation et l'analphabétisme de la mère ont été associés indépendamment à l'ESRCS (P < 0,05). Par rapport à l'ES ou au RCS, l'ESRCS incluait moins souvent l'infection par un rotavirus (P < 0,05). La déshydratation a été associée indépendamment à l'ES comparé au RCS après ajustement pour les facteurs de confusion potentiels (P < 0,05). CONCLUSION: Les enfants ayant une ESRCS présentent plus souvent une diarrhée déshydratante (69%) que ceux ayant soit une ES (55%) ou un RCS (43%). Cependant, les enfants atteints d'ESRCS présentaient moins fréquemment des maladies diarrhéiques associées à un rotavirus. Ce résultat souligne l'importance d'une détection précoce et d'une prise en charge rapide de la diarrhée déshydratante chez les enfants présentant une émaciation et un retard de croissance sévères concomitants, afin de réduire la morbidité et la mortalité chez ces enfants, en particulier dans les milieux pauvres.